Common use of INFORMATION INCORPORATED BY REFERENCE Clause in Contracts

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to incorporate by reference into this prospectus supplement and the accompanying prospectus certain information we file with it, which means that we can disclose important information by referring you to those documents. The information incorporated by reference is considered to be a part of this prospectus supplement and the accompanying prospectus, and information that we file later with the SEC will automatically update and supersede information contained in this prospectus supplement and the accompanying prospectus. The following documents are incorporated by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including the portions of these documents that are furnished under Item 2.02 or Item 7.01 of a Current Report on Form 8-K, including any exhibits included with such Items): □ our annual report on Form 10‑K for the fiscal year ended December 31, 2018 filed with the SEC on March 15, 2019; □ the information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 2018; □ our quarterly report on Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 9, 2019; □ our current reports on Form 8-K filed with the SEC on January 7, 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 2019; and □ the description of our common stock contained in our registration statement on Form 8‑A12B, filed with the SEC on November 16, 2015 (File No. 001-37635), and all amendments or reports filed for the purpose of updating such description. We also incorporate by reference into this prospectus all documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus supplement and until the completion or termination of the offering contemplated hereby. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein or in a document incorporated or deemed to be incorporated by reference into this document will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained in this document or any other subsequently filed document that is deemed to be incorporated by reference into this document modifies or supersedes the statement. We make available, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may also obtain, free of charge, a copy of any of these documents (other than exhibits to these documents, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling us at the following address and telephone number: We may offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities pursuant to this prospectus, we will provide a prospectus supplement containing specific terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement also may add, update or change information contained in this prospectus. This prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price of our common stock was $6.55. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents incorporated by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information provided in the registration statement, this prospectus and in any prospectus supplement, including the information incorporated by reference. We have not authorized anyone to provide you with different information. You should not assume that the information in this prospectus or any supplement to this prospectus is accurate at any date other than the date indicated on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxx.

INFORMATION INCORPORATED BY REFERENCE. The SEC Securities and Exchange Commission allows us Cytogen to "incorporate by reference into this prospectus supplement reference" the information Cytogen files with the Securities and the accompanying prospectus certain information we file with itExchange Commission, which means that we Cytogen can disclose important information to you by referring you to those documents. The information incorporated by reference is considered to be a an important part of this prospectus supplement and the accompanying prospectus, and information that we file Cytogen files later with the SEC Securities and Exchange Commission will automatically update and supersede information contained in this prospectus supplement and the accompanying prospectusinformation. The following documents are incorporated Cytogen incorporates by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including the portions of these documents that are furnished under Item 2.02 or Item 7.01 of a Current Report on Form 8-K, including listed below and any exhibits included with such Items): □ our annual report on Form 10‑K for the fiscal year ended December 31, 2018 filed future filings made by Cytogen with the SEC on March 15, 2019; □ the information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 2018; □ our quarterly report on Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 9, 2019; □ our current reports on Form 8-K filed with the SEC on January 7, 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 Securities and May 9, 2019; and □ the description of our common stock contained in our registration statement on Form 8‑A12B, filed with the SEC on November 16, 2015 (File No. 001-37635), and all amendments or reports filed for the purpose of updating such description. We also incorporate by reference into this prospectus all documents (other than Current Reports furnished Exchange Commission under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Securities Exchange Act after of 1934, as amended, until the date filing of a post-effective amendment to this prospectus supplement and until the completion which indicates that all securities registered have been sold or termination which deregisters all securities then remaining unsold: o The description of the offering contemplated hereby. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on our common stock contained in each of Exhibit 3.1 to our Form 10-Q Quarterly Report for the quarter ended June 30, 2000 and Current Reports on Form 8-K. Any statement contained herein or in a document incorporated or deemed Exhibit 3 to be incorporated by reference into this document will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained in this document or any other subsequently filed document that is deemed to be incorporated by reference into this document modifies or supersedes the statement. We make available, free of charge, through our website our Annual Reports on Form 10-KQ Quarterly Report for the quarter ended June 30, Quarterly Reports on Form 10-Q, 1996; o The description of our Series C Junior Participating Preferred Stock contained in Exhibit 1 to our Current Reports Report on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may also obtain, free of charge, a copy of any of these documents (other than exhibits to these documents, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling us at the following address and telephone number: We may offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities pursuant to this prospectus, we will provide a prospectus supplement containing specific terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement also may add, update or change information contained in this prospectus. This prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price of our common stock was $6.55. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange CommissionCommission on June 24, 1998; o Cytogen's Annual Report on Form 10-K for the year ended December 31, 2000 filed with the Securities and Exchange Commission on March 30, 2001; o All other reports filed by Cytogen pursuant to Section 13(a) or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination 15(d) of the securities described Securities Exchange Act of 1934, as amended, since December 31, 2000; o The description of our common stock contained in our Registration Statement on Form 8-A; and o The description of our preferred stock contained in our Registration Statement on Form 8-A. Cytogen will provide to any person, including any beneficial owner of its securities, to whom this prospectus in one Prospectus is delivered, a copy of any or more offerings in amounts, at prices and on terms that we determine at the time all of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement information that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents has been incorporated by reference into in this prospectus as described below under the heading “Information Incorporated Prospectus but not delivered with this Prospectus. You may make such requests at no cost to you by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read writing or telephoning Cytogen at the SEC website following address or number: Cytogen Corporation 600 College Road East Princeton, New Xxxxxx 00000 Xxxxxxxxx: Xxxxxxx Xxxxxxx Telephone: (xxx.xxx.xxx609) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” 750-8220 You should rely only on the information incorpxxxxxx xx xxxxrence or provided in the registration statement, this prospectus and in Prospectus or any prospectus supplement, including the information incorporated by referenceProspectus Supplement. We have Cytogen has not authorized anyone else to provide you with different information. Cytogen is not making an offer of these securities in any state where the offer is not permitted. You should not assume that the information in this prospectus Prospectus or any supplement to this prospectus Prospectus Supplement is accurate at as of any date other than the date indicated on the cover page front of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distributionthose documents.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxx.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to “incorporate by reference into this prospectus supplement and reference” the accompanying prospectus certain information we file with it, them which means that we can disclose important information to you by referring you to those documentsdocuments instead of having to repeat the information in this prospectus supplement and the accompanying prospectus. The information incorporated by reference is considered to be a part of this prospectus supplement and the accompanying prospectus, and later information that we file later with the SEC will automatically update and supersede information this information. Any statement contained in a previously filed document incorporated by reference will be deemed to be modified or superseded for purposes of this prospectus to the extent that a statement contained in this prospectus supplement modifies or replaces that statement. We incorporate by reference the documents listed below and any future information filed (rather than furnished) with the SEC under Sections 13(a), 13(c), 14, or 15(d) of the Exchange Act between the date of this prospectus and the accompanying prospectus. The following documents termination of this offering, provided, however, that we are incorporated by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including the portions of these documents that are incorporating any information furnished under Item 2.02 or Item 7.01 of a Current Report any current report on Form 8-K, including any exhibits included with such Items): □ : • our annual report Annual Report on Form 10‑K 10-K for the fiscal year ended December 31, 2018 2020, filed with the SEC on March 151, 20192021; □ • the information contained in specifically incorporated by reference into our definitive proxy statement Annual Report on Form10-K for the year ended December 31, 2020, from our Definitive Proxy Statement on Schedule 14A for our 2019 Annual Meeting of Stockholders14A, filed with the SEC on April 2629, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 20182021; □ • our quarterly report Quarterly Report on Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 97, 20192021; □ • our current reports Current Report on Form 8-K filed with the SEC on January 7February 3 , 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 2019and February 18, 2021; and □ • the description of our common stock Common Stock contained in our registration statement Registration Statement on Form 8‑A12B8-A, filed with the SEC on November 16April 19, 2015 (File No. 001-37635)2010, and all including any amendments or reports filed for the purpose of updating such description. We These documents may also incorporate be accessed on our website xxxxx.xxxxxxx.xxx. Except as otherwise specifically incorporated by reference into in this prospectus all documents (other than Current Reports furnished under Item 2.02 supplement and the accompanying prospectus, information contained in, or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to Sections 13(a)accessible through, 13(c), 14 or 15(d) of the Exchange Act after the date our website is not a part of this prospectus supplement and until the completion or termination of the offering contemplated hereby. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein or in a document incorporated or deemed to be incorporated by reference into this document will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained in this document or any other subsequently filed document that is deemed to be incorporated by reference into this document modifies or supersedes the statementaccompanying prospectus. We make availablewill furnish without charge to you, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed upon written or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may also obtain, free of chargeoral request, a copy of any or all of these the documents (other than incorporated by reference, including exhibits to these documents, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling telephoning us at the following address and telephone numberaddress: Codexis, Inc. 000 Xxxxxxxxx Xxxxx Xxxxxxx Xxxx, Xxxxxxxxxx 00000 We may offer and sell the securities identified above from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000offerings. This prospectus provides you with a general description of the securities we may offersecurities. Each time we offer securities pursuant to this prospectusand sell securities, we will provide a supplement to this prospectus supplement containing that contains specific information about the offering and the amounts, prices and terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement may also may add, update or change information contained in this prospectusprospectus with respect to that offering. This You should carefully read this prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price supplement before you invest in any of our common stock was $6.55securities. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents incorporated by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information provided in the registration statement, this prospectus and in any prospectus supplement, including the information incorporated by reference. We have not authorized anyone to provide you with different information. You should not assume that the information in this prospectus or any supplement to this prospectus is accurate at any date other than the date indicated on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through one or more underwriters, initial dealers and agents, or directly to purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to timemethods. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of If any underwriters, initial purchasers, dealers or agents are involved in the sale of our any of the securities, their names and any related applicable purchase price, fee, commission or discount arrangementsarrangement between or among them will be set forth, or will be calculable from the information set forth, in the applicable prospectus supplement. See the sections of this prospectus entitled “About this Prospectus” and “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise or the context indicates otherwisefor more information. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe No securities may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug sold without delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our and the applicable prospectus supplement describing the method and terms of the offering of such securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxx.

INFORMATION INCORPORATED BY REFERENCE. The rules of the SEC allows allow us to incorporate by reference into in this prospectus supplement and the accompanying prospectus certain information in other documents that we file with it, which means that we can disclose important information to you by referring you to those documentsdocuments that we have filed separately with the SEC. The You should read the information incorporated by reference because it is considered to be a an important part of this prospectus supplement and supplement. We hereby incorporate by reference the accompanying prospectus, and following information that we file later with the SEC will automatically update and supersede information contained in or documents into this prospectus supplement and the accompanying prospectus. The following documents are incorporated by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including the portions of these documents that are furnished under Item 2.02 or Item 7.01 of a Current supplement: ● our Annual Report on Form 810-K, including any exhibits included with such Items): □ our annual report on Form 10‑K K for the fiscal year ended December 31, 2018 2020, filed with the SEC on March 15, 2019; □ the information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 20182021; □ ● our quarterly report Quarterly Report on Form 10-Q for the three months quarter ended March 31, 2019 2021, filed with the SEC on May 917, 20192021; □ our current reports ● the Current Reports on Form 8-K filed with the SEC Commission on January 7March 26, 2019 (two filings)2021, June 3, 2021, June 22, 2021 and July 2, 2021; January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 2019; and □ ● the description of our common stock contained as set forth in our registration statement filed on Form 8‑A12B8-A under the Exchange Act on May 8, 1984, as amended by: ● the description of our common stock as set forth in Exhibit 4.4 to the Annual Report on Form 10-K for the year ended December 31, 2020, filed on March 26, 2021; and ● the description of our Series 1 Preferred as set forth in the Current Report on Form 8-K filed with the SEC Commission on November 16March 9, 2015 (File No2020. 001-37635), and all amendments Any information in any of the foregoing documents will automatically be deemed to be modified or reports superseded to the extent that information in this prospectus or in a later filed for the purpose of updating document that is incorporated or deemed to be incorporated herein by reference modifies or replaces such descriptioninformation. We also incorporate by reference into this prospectus all documents any future filings (other than Current Reports current reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us made with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after Act, until the date termination of the offering as to which this prospectus supplement relates. Information in such future filings updates and supplements the information provided in this prospectus supplement and until the completion or termination of accompanying prospectus. Any statements in any such future filings will automatically be deemed to modify and supersede any information in any document we previously filed with the offering contemplated hereby. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein or in a document SEC that is incorporated or deemed to be incorporated herein by reference into this document will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained statements in this document or any other subsequently the later filed document that is deemed to be incorporated by reference into this document modifies modify or supersedes the statement. We make available, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file replace such material with, or furnish it to, the SECearlier statements. You may also obtain, free of charge, obtain a copy of any of these documents (other than exhibits to these documentsfilings, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) without charge, by writing or calling us at the following address at: CADIz INC. By this prospectus and telephone number: We an accompanying prospectus supplement, we may offer and sell from time to time our shares offer and sell, in one or more offerings, up to $205,000,000 in any combination of common stockdebt securities, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or depositary shares, warrants, subscription rights and units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the these securities. We will provide you with more specific terms of these securities we may offer. Each time we offer securities pursuant in one or more supplements to this prospectus, we will provide a . Any prospectus supplement containing specific terms of the particular offering together with may also add, update, or change information contained in this prospectus. You should read this prospectus and the applicable prospectus supplement or issuer free writing prospectus relating to a particular offering, as well as the documents incorporated or deemed to be incorporated by reference in this prospectus, carefully before you invest invest. We may offer these securities from time to time in any amounts, at prices and on other terms to be determined at the time of the offering. We may offer and sell these securities to or through underwriters, dealers or agents, or directly to investors, or through a combination of these methods, on a continuous or delayed basis. The supplements to this prospectus will provide the specific terms of the plan of distribution. See the sections of this prospectus entitled “About this Prospectus” and “Plan of Distribution” beginning of pages 1 and 20, respectively, for more information. No securities may be sold without delivery of this prospectus and the applicable prospectus supplement describing the method and terms of the offering of such securities. The prospectus supplement price to the public of such securities and the net proceeds we expect to receive from such sale will also may add, update or change information contained be set forth in this prospectus. This prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Nasdaq Global Market under the symbol “AXSM.” CDZI”. On November 30June 15, 20162021, the closing price of our common stock as reported by the Nasdaq Global Market was $6.5513.17 per share. We may sell will provide information in any applicable prospectus supplement regarding the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale listing of securities to you, and other than shares of our common stock on any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securitiessecurities exchange. ABOUT THIS PROSPECTUS 1 THE COMPANY 3 AXSOME THERAPEUTICS, INC 3 SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 2 Corporate Information 3 About Cadiz 3 USE OF PROCEEDS 5 RISK FACTORS 4 General 5 DESCRIPTION OF DEBT SECURITIES 5 Consolidation, Merger or Sale 7 Conversion or Exchange Rights 7 Modifications of Indenture; Waiver 8 Events of Default under the Indenture 7 Form, Exchange and Transfer 9 Discharge 9 Payment and Paying Agents 10 Information Concerning the Trustee 10 Subordination of Subordinated Debt Securities 10 Governing Law 10 General 11 DESCRIPTION OF CAPITAL STOCK 5 11 Series 1 Preferred Stock 11 Common Stock 11 Indemnification of Directors and Officers 14 Future Class or Series of Preferred Stock 13 Anti-Takeover Effects of Delaware Law and Certain Provisions of our Charter Documents 14 Exchange Listing 14 General 16 DESCRIPTION OF DEPOSITARY SHARES 16 Withdrawal of Preferred Stock 17 Dividends and Other Distributions 16 Voting Deposited Preferred Stock 17 Redemption, Conversion and Exchange of Preferred Stock 17 Charges of Preferred Stock Depositary; Taxes and Other Governmental Charges 18 Amendment and Termination of the Deposit Agreement 18 Miscellaneous 18 Resignation and Removal of Depositary 18 Exercise of Warrants 19 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 19 DESCRIPTION OF UNITS 18 20 DESCRIPTION OF SUBSCRIPTION RIGHTS 20 General 21 PLAN OF DISTRIBUTION 19 20 Dealers 22 Underwriters and Agents 21 Institutional Purchasers 22 Direct Sales 22 Market-Making, Stabilization and Other Transactions 23 Indemnification; Other Relationships 22 EXPERTS 23 LEGAL MATTERS 20 EXPERTS 20 23 INFORMATION INCORPORATED BY REFERENCE 24 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 23 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the “Commission” or the “SEC, ,” using a the “shelf” registration process. Under this the shelf registration process, using this prospectus, together with a prospectus supplement, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000offerings. This prospectus provides you with a general description of the securities we that may offerbe offered. Each time we offer sell securities under pursuant to this registration statement prospectus, we will provide a prospectus supplement that describes will contain specific information about the terms of the relevant offeringsecurities being offered. A prospectus supplement may include a discussion of any risk factors or other special considerations applicable to those securities or to us. The prospectus supplement may also may addadd to, update or change information contained in this prospectusprospectus and, accordingly, to the extent inconsistent, the information in this prospectus will be superseded by the information in the prospectus supplement. Before making an investment decision, you You should read carefully both this prospectus, any applicable prospectus supplement and any prospectus supplement together with related issuer free writing prospectus, as well as the documents additional information incorporated by reference into in this prospectus as described below under the heading “Where You Can Find More Information” and “Information Incorporated by Reference.” The registration statement that contains this or in any applicable prospectus supplement and any related issuer free writing prospectus, including before making an investment in our securities. This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of the documents referred to herein have been filed, or will be filed or incorporated by reference as exhibits to the registration statement of which this prospectus is a part, and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, you may obtain copies of those documents as discussed described below under the heading “Where You Can Find More Information.” You should may rely only on the information provided contained or incorporated by reference in this prospectus. Neither we nor any other person has authorized anyone to provide any information other than that contained or incorporated by reference in this prospectus, any accompanying prospectus supplement or in any free writing prospectus prepared by or on behalf of us or to which we have referred you. We take no responsibility for, and can provide no assurance as to the reliability of, any other information that others may give you. Neither this prospectus nor any accompanying prospectus supplement nor any free writing prospectus prepared by or on behalf of us or to which we have referred you constitutes an offer to sell nor a solicitation of an offer to buy any securities other than those registered by this prospectus, or an offer to sell or a solicitation of an offer to buy securities where an offer or solicitation would be unlawful. This prospectus does not contain all of the information included in the registration statement, this prospectus and in any prospectus supplement, including . For a more complete understanding of the information incorporated by reference. We have not authorized anyone to provide you with different information. You should not assume that the information in this prospectus or any supplement to this prospectus is accurate at any date other than the date indicated on the cover page offering of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth you should refer to the names of any underwritersregistration statement, initial purchasersincluding its exhibits. Unless the context otherwise requires, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distribution.” The terms “Axsomewe,” the “Companyus,” “our,” “usCadiz,” and “we,the Company” as used in this prospectus, refer to Axsome Therapeutics, Cadiz Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxxDelaware corporation.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to incorporate by reference into this This prospectus supplement and the accompanying prospectus certain are part of a registration statement that we have filed with the SEC. The SEC allows us to “incorporate by reference” the information that we file with it, which means that we can disclose important information to you by referring you to those documents. The information incorporated by reference is considered to be a part of this prospectus supplement and the accompanying prospectus, and information that prospectus from the date we file later with the SEC will automatically update and supersede information contained in this prospectus supplement and the accompanying prospectusthat document. The following Any documents are incorporated by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including the portions of these documents that are furnished under Item 2.02 or Item 7.01 of a Current Report on Form 8-K, including any exhibits included with such Items): □ our annual report on Form 10‑K for the fiscal year ended December 31, 2018 filed with the SEC on March 15, 2019; □ the information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 2018; □ our quarterly report on Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 9, 2019; □ our current reports on Form 8-K filed with the SEC on January 7, 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 2019; and □ the description of our common stock contained in our registration statement on Form 8‑A12B, filed with the SEC on November 16, 2015 (File No. 001-37635), and all amendments or reports filed for the purpose of updating such description. We also incorporate by reference into this prospectus all documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to under Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act with the SEC (including those portions of our Definitive Proxy Statement on Schedule 14A, as filed with the SEC, specifically incorporated by reference in our Annual Report on Form 10-K or amendments thereto); after the date of this prospectus supplement and until before the completion or termination of date that the offering contemplated herebyof shares by means of this prospectus supplement and accompanying prospectus is terminated will automatically update and, where applicable, supersede any information contained or incorporated by reference in this prospectus supplement and accompanying prospectus. These We incorporate by reference into this prospectus supplement and the accompanying prospectus the following documents include periodic reportsor information filed with the SEC (other than, such in each case, documents or information deemed to have been furnished and not filed in accordance with SEC rules): · Our Annual Report on Form 10-K for the year ended December 31, 2020 filed with the SEC on March 8, 2021, as amended by Amendment No. 1 to our Annual Reports Report on Form 10-K, Quarterly Reports as filed with the SEC on March 29, 2021 (including those portions of our Definitive Proxy Statement on Schedule 14A, as filed with the SEC, specifically incorporated by reference in our Annual Report on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein K or in a document incorporated or deemed to be incorporated by reference into this document will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained in this document or any other subsequently filed document that is deemed to be incorporated by reference into this document modifies or supersedes the statement. We make available, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, amendments thereto); · Our Current Reports on Form 8-K filed with the SEC on February 9, 2021, February 12, 2021, March 9, 2021 and amendments March 24, 2021; and · the description of our capital stock contained in our Information Statement, filed as Exhibit 99.1 to those reports filed or furnished pursuant Amendment No. 4 to Section 13(aour Registration Statement on Form 10 (File No. 001-36876), 13(c)filed on June 9, 14 2015, including any amendment or 15(d) report filed for the purpose of updating such description. We will provide without charge to each person, including any beneficial owner, to whom this prospectus supplement and the Exchange Act as soon as reasonably practicable after we electronically file such material withaccompanying prospectus are delivered, upon his or furnish it to, the SEC. You may also obtain, free of chargeher written or oral request, a copy of any of these or all documents (other than referred to above that have been or may be incorporated by reference into this prospectus supplement and the accompanying prospectus, excluding exhibits to these documents, those documents unless the exhibits they are specifically incorporated by reference into these those documents. You may request those documents or referred to in this prospectus) from us by writing or calling contacting us at the following address address: We are currently subject to the information requirements of the Exchange Act, and telephone number: in accordance therewith file periodic reports, proxy statements and other information with the SEC. Our filings with the SEC are available to the public from the SEC’s website at xxx.xxx.xxx. In addition, our common stock is listed on the NYSE, and our reports and other information can be inspected at the offices of the NYSE, 00 Xxxxx Xxxxxx, Xxx Xxxx, Xxx Xxxx 00000. We maintain a website at xxx.xxxxxxx.xxx. The information on our website is not part of or incorporated by reference in this prospectus supplement or the accompanying prospectus. Prospectus We may offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000150,000,000 or the equivalent amount in other currencies or currency units. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities pursuant to this prospectus, we We will provide a prospectus supplement containing the specific terms of the particular offering together with securities to be offered in one or more supplements to this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any our securities. The prospectus supplement also may add, update or change information contained in this prospectus. This prospectus may not be used to offer and sell our securities unless accompanied by a prospectus supplement describing the applicable prospectus supplement. Our common stock is listed on method and terms of the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price offering of our common stock was $6.55those securities. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In additionOur common stock is listed on the New York Stock Exchange under the symbol “BW” and our 8.125% senior notes due 2026 are listed under the New York Stock Exchange under the symbol “BWSN”. None of the other securities that we may offer under this prospectus are currently publicly traded. On March 8, 2021, the underwritersclosing price of our common stock was $6.76 per share and the closing price of our 8.125% senior notes due 2026 was $25.64 per Note. The date of this prospectus is , if any, may over-allot a portion 2021. Table of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 Contents Page This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of sell the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with up to an aggregate initial offering price of up to $150,000,000150,000,000 or the equivalent amount in other currencies or currency units. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement sell securities, we will provide a prospectus supplement that describes will contain specific information about the terms of that offering. For a more complete understanding of the relevant offeringoffering of the securities, you should refer to the registration statement of which this prospectus forms a part, including its exhibits. The prospectus supplement may also may add, update or change information contained in this prospectus. Before making an investment decision, you You should read carefully both this prospectus and any prospectus supplement together with the documents incorporated by reference into this prospectus as described below additional information referenced under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading headings “Where You Can Find More Information” and “Information We Incorporate By Reference.” You should rely only on the information provided in the registration statement, this prospectus and in any prospectus supplement, including the information incorporated by reference. We have not authorized anyone to provide you with different informationinformation from the information contained or incorporated by reference in this prospectus and in any prospectus supplement or free writing prospectus that we may provide you. You should not assume that the information contained in this prospectus, any prospectus supplement, any document incorporated by reference or any supplement to this free writing prospectus is accurate at as of any date date, other than the date indicated mentioned on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of deliverydocuments. We are not making an offer offers to sell the securities in any jurisdiction where the in which an offer or sale solicitation is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole authorized or in part any proposed purchase of our securitieswhich the person making such offer or solicitation is not qualified to do so or to anyone to whom it is unlawful to make an offer or solicitation. An applicable Unless we otherwise state or the context otherwise indicates, all references in this prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See to “Plan of Distribution.” The terms “AxsomeB&W,” the “Company,” “us,” “our,” “us” and or “we,” as used in this prospectusor similar references, refer to Axsome Therapeuticsmean Xxxxxxx & Xxxxxx Enterprises, Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxx.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to incorporate by reference information into this prospectus supplement and the accompanying prospectus certain information we file with it, which document. This means that we can disclose important information to you by referring you to those documentsanother document filed separately with the SEC. The information incorporated by reference is considered to be a an important part of this prospectus supplement and the accompanying prospectus, and information that we file later with the SEC will automatically update and supersede information contained this information. We incorporate by reference the documents listed below and any future filings made with the SEC under Sections 13(a), 13(c), 14, or 15(d) of the Exchange Act made subsequent to the date of this prospectus until the termination of the offering of the securities described in this prospectus supplement and the accompanying prospectus. The following documents are incorporated by reference into this document (other than the portions of these documents deemed to be information in such filings that was “furnished,” or not deemed to be under applicable SEC rules, rather than “filed,” including ”). We incorporate by reference the portions of these following documents or information that are furnished under Item 2.02 or Item 7.01 of a Current Report on Form 8-K, including any exhibits included we have filed with such Items): □ the SEC: • our annual report on Form 10‑K 10-K for the fiscal year ended December 31, 2018 filed with the SEC on March 15, 2019; □ the information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 2018; □ our quarterly report on Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 9March 18, 20192020; □ • our current reports on Form 8-K filed with the SEC on January 7onFebruary 10, 2019 2020, February 18, 2020, March 18, 2020 and April 3, 2020 (two filingsin each case, except for information contained therein which is furnished rather than filed); January 8, 2019; January • our definitive proxy statement on Schedule 14A filed with the SEC on March 30, 2019; February 62020, 2019; March 4as amended on April 3, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 20192020; and □ • the description of our common stock contained in our registration statement on Form 8‑A12B, onForm S-8 filed with the SEC on November 16September 10, 2015 (File No. 001-37635)2019, and all amendments including any amendment or reports report filed for the purpose of updating such description. We also incorporate by reference into this prospectus all documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus supplement and until the completion or termination of the offering contemplated hereby. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein in this prospectus or contained in a document incorporated or deemed to be incorporated by reference into this document prospectus will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained in this document prospectus or any other subsequently filed supplement to this prospectus, or document that is deemed to be incorporated by reference into this document prospectus, modifies or supersedes the statement. We make available, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. statement You may also obtain, free of charge, request a copy of any of these documents (other than exhibits to these documentsfilings at no cost, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling telephoning us at the following address and telephone numberaddress: We may offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities pursuant to this prospectus, we will provide a prospectus supplement containing specific terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement also may add, update or change information contained in this prospectus. This prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price of our common stock was $6.55. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents incorporated by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information incorporated by reference or provided in the registration statement, this prospectus and or in any prospectus supplement, including the information incorporated by reference. We have not authorized anyone else to provide you with different or additional information. An offer of these securities is not being made in any jurisdiction where the offer or sale is not permitted. You should not assume that the information in this prospectus or any prospectus supplement to this prospectus is accurate at as of any date other than the date indicated on the cover page front of these documents those documents. This prospectus is part of a registration statement we filed with the SEC. This prospectus does not contain all of the information set forth in the registration statement and the exhibits to the registration statement. For further information with respect to us and the securities we are offering under this prospectus, we refer you to the registration statement and the exhibits and schedules filed as a part of the registration statement. You should rely only on the information contained in this prospectus or the filing date of any document incorporated by reference, regardless of its time of deliveryreference in this prospectus. We have not authorized anyone else to provide you with different information. We are not making an offer to sell the of these securities in any jurisdiction state where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination You should not assume that the information in this prospectus is accurate as of any date other than the date on the front page of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise regardless of the time of delivery of this prospectus or any sale of the context indicates otherwisesecurities offered by this prospectus. We are a clinical stage biopharmaceutical company developing novel therapies for file annual, quarterly and current reports, proxy statements and other information with the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequateSEC. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we SEC filings are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers the public from commercial document retrieval services and improve over the lives Internet at the SEC’s website at xxxx://xxx.xxx.xxx. Copies of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed certain information filed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range us with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We SEC are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained also available on our website at xxx.xxxxxxxxxxx.xxx. Information contained in or accessible through our website does not constitute a part of this prospectus and is not incorporated by reference into in this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxx.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us We have elected to incorporate certain information by reference into this prospectus supplement and the accompanying prospectus certain information we file with itprospectus. By incorporating by reference, which means that we can disclose important information to you by referring you to those documentsother documents we have filed or will file with the SEC. The information incorporated by reference is considered deemed to be a part of this prospectus supplement and the accompanying prospectus, and except for information incorporated by reference that we file later with the SEC will automatically update and supersede is superseded by information contained in this prospectus supplement and the accompanying prospectus. The following documents are This means that you must look at all of the SEC filings that we incorporate by reference to determine if any statements in the prospectus or any document previously incorporated by reference into have been modified or superseded. We incorporate by reference the documents listed below and any future information filed (rather than furnished) with the SEC under Sections 13(a), 13(c), 14, or 15(d) of the Exchange Act between the date of this document (other than prospectus and the portions termination of these documents deemed to be “furnished” or this offering, provided, however, that we are not deemed to be “filed,” including the portions of these documents that are incorporating any information furnished under Item 2.02 or Item 7.01 of a Current Report any current report on Form 8-K, including any exhibits included with such Items): □ our annual report : • Our Annual Report on Form 10‑K 10-K for the fiscal year ended December 31, 2018 2021 filed with the SEC on March 15, 2019; □ the information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 20182022; □ our quarterly report • Our Quarterly Report on Form 10-Q for the three months quarterly period ended March 31, 2019 2022, filed with the SEC on May 9onMay 16, 20192022; □ our current reports • Our Current Report on Form 8-K filed with the SEC on January 7, 2019 (two filings); January March 8, 2019; January 302022, 2019; February 6as amended on March 21, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 20192022; and □ the • The description of our common stock the Common Stock contained in our registration statement the Company’s Registration Statement on Form 8‑A12B, 8-A filed with the SEC Commission on November 16October 29, 2015 2020 (File No. 001-3763539676), and all amendments or reports together with any amendment thereto filed with the Commission for the purpose of updating such description. We also incorporate You may obtain copies of these documents on the website maintained by the SEC athttp://xxx.xxx.xxx, or from us without charge (other than exhibits to such documents, unless such exhibits are specifically incorporated by reference into this prospectus all documents (other than Current Reports furnished under Item 2.02 such documents) by writing us at Inhibikase Therapeutics, Inc., 0000 Xxxxxxxxx Xxxxxxx XX, Xxxxx 0000, Xxxxxxx, XX 00000 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus supplement and until the completion or termination of the offering contemplated herebyvisiting our website at xxxx://xxx.xxxxxxxxxx.xxx. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein or in a document incorporated or deemed to be incorporated by reference into in this document will prospectus shall be deemed to be modified or superseded for the purposes of the document this prospectus to the extent that a statement contained herein, any prospectus supplement or in this document or any other subsequently filed document which also is or deemed to be incorporated by reference herein modifies or supersedes that statement. Any statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this prospectus. We may offer and sell, from time to time in one or more offerings, up to $100,000,000.00 of our common stock, preferred stock, debt securities, warrants and rights, or any combination of these securities, and/or units consisting of one or more of these securities. We may also offer common stock or preferred stock upon conversion of debt securities and common stock upon conversion of preferred stock. All of the securities listed above may be sold separately or as units with other securities. This prospectus describes some of the general terms that may apply to these securities. When we decide to sell a particular class or series of securities, we will provide specific terms of the offered securities in one or more prospectus supplements. We may also authorize one or more free writing prospectuses to be provided to you in connection with these offerings. The prospectus supplement, and any documents incorporated by reference, may also add, update or change information contained in or incorporated by reference into this prospectus. However, no prospectus supplement shall offer a security that is not registered and described in this prospectus at the time of its effectiveness. You should read this prospectus and any prospectus supplement, as well as the documents incorporated by reference or deemed to be incorporated by reference into this document modifies or supersedes the statement. We make available, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may also obtain, free of charge, a copy of any of these documents (other than exhibits to these documents, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling us at the following address and telephone number: We may offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities pursuant to this prospectus, we will provide a and any free writing prospectus supplement containing specific terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement also may add, update or change information contained in this prospectusinvest. This prospectus may not be used to offer and or sell our securities unless accompanied by a prospectus supplement relating to the applicable prospectus supplementoffered securities. Our common stock is listed on the NASDAQ The Nasdaq Capital Market under the symbol “AXSMIKT.” On November 30Each prospectus supplement will contain information, 2016where applicable, as to our listing on any securities exchange of the closing securities covered by the prospectus supplement. The aggregate market value of our outstanding common stock held by non-affiliates was $26,753,591 based on 25,177,051 shares of outstanding common stock, of which 5,359,576 shares are held by affiliates, and a price of $1.35 per share, which was the last reported sale price of our common stock was as quoted on The Nasdaq Capital Market on January 26, 2022. Pursuant to General Instruction I.B.6 of Form S-3, in no event will we sell securities registered in a public primary offering with a value exceeding more than one-third of our public float (the market value of our common stock held by our non-affiliates) in any 12 calendar month period so long as our public float remains below $6.5575.0 million. We have not offered any securities pursuant to General Instruction I.B.6 of Form S-3 during the prior 12 calendar month period that ends on and includes the date of this prospectus. As of January 26, 2022, one-third of our public float is equal to approximately $8,900,000. These securities may sell the securities be sold by us directly to investorspurchasers, through dealers or agents, or to or through underwriters, or through a combination of these methods. See “Plan of Distribution” in this prospectus. We may also describe the plan of distribution for any particular offering of our securities in a prospectus supplement. If any agents, underwriters or dealersdealers are involved in the sale of any securities in respect of which this prospectus is being delivered, we will disclose their names and also to other purchasers or through agentsthe nature of our arrangements with them in a prospectus supplement. The names of net proceeds we expect to receive from any underwriters or agents that are such sale will also be included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In additionAn investment in our securities involves a high degree of risk. See the sections entitled “ Risk Factors” in our most recent Annual Report on Form 10-K, in any Quarterly Report on Form 10-Q and in any Current Report on Form 8-K, as well as in any prospectus supplement or free writing prospectus related to these specific offerings. We may amend or supplement this prospectus from time to time by filing amendments or supplements as required or related free writing prospectuses. You should read the underwriters, entire prospectus and any amendments or supplements carefully before you make your investment decision. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if any, may over-allot this prospectus is truthful or complete. Any representation to the contrary is a portion of the securitiescriminal offense. ABOUT THIS PROSPECTUS 1 PROSPECTUS SUMMARY 2 THE OFFERING 3 AXSOME THERAPEUTICS, INC 3 OUR COMPANY 4 RISK FACTORS 6 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 7 USE OF PROCEEDS 5 DESCRIPTION 10 DIVIDEND POLICY 11 DESCRIPTIONS OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT THE SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 WE MAY OFFER 12 PLAN OF DISTRIBUTION 19 31 LEGAL MATTERS 20 34 EXPERTS 20 34 WHERE YOU CAN FIND MORE INFORMATION 21 34 INFORMATION INCORPORATED BY REFERENCE 21 34 This prospectus is part of a registration statement Registration Statement that we filed with the Securities and Exchange Commission, or the Commission (“SEC, ”) using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus having a maximum aggregate offering price of $100,000,000.00 in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offerofferings. Each time we offer securities under this registration statement securities, we will provide prepare and file with the SEC a prospectus supplement or information that is incorporated by reference into this prospectus that describes the specific amounts, prices and terms of the relevant offeringsecurities we offer. We may also authorize one or more free writing prospectuses to be provided to you that may contain material information relating to these offerings and securities. The prospectus supplement also may add, update or change information contained in this prospectus or the documents incorporated herein by reference. You should read carefully this prospectus, any applicable prospectus supplement and any related free writing prospectus together with additional information described below under the caption “Where You Can Find More Information.” This prospectus does not contain all the information provided in the Registration Statement we filed with the SEC. Before making an investment decisionFor further information about us or our securities offered hereby, you should read carefully both this prospectus and any prospectus supplement together with refer to that Registration Statement, which you can obtain from the documents incorporated by reference into this prospectus SEC as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information provided contained or incorporated by reference in the registration statementthis prospectus, this prospectus and in any prospectus supplement, including the information incorporated by referencesupplement and any related free writing prospectus. We have not authorized anyone any other person to provide you with different information. You If anyone provides you with different or inconsistent information, you should not assume that the information in this prospectus or any supplement to this rely on it. This prospectus is accurate at any date other than the date indicated on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities securities, and it is not soliciting an offer to buy securities, in any jurisdiction where the offer or sale is not permitted. You should assume that the information appearing in this prospectus, any prospectus supplement, any related free writing prospectus as well as information we have previously filed with the SEC and incorporated by reference, is accurate as of the date of those documents only. Our business, financial condition, results of operations and prospects may have changed since those dates. This prospectus incorporates by reference, and any prospectus supplement or free writing prospectus may contain and incorporate by reference, market data and industry statistics and forecasts that are based on independent industry publications and other publicly available information. Although we believe these sources are reliable, we do not guarantee the accuracy or completeness of this information and we have not independently verified this information. Although we are not aware of any misstatements regarding the market and industry data presented in this prospectus and the documents incorporated herein by reference, these estimates involve risks and uncertainties and are subject to change based on various factors, including those discussed under the heading “Risk Factors” contained in this prospectus, the applicable prospectus supplement and any applicable free writing prospectus, and under similar headings in other documents that are incorporated by reference into this prospectus. Accordingly, investors should not place undue reliance on this information. We may sell our securities to through underwriters or dealers, through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a any combination of any of these methods of sale, as designated from time to timemethods. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable The prospectus supplement, which we will provide prepare and file with the SEC each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers agents or agents others involved in the sale of our securities, and any related applicable fee, commission or discount arrangementsarrangements with them. See “Plan of Distribution.” The terms “Axsome,” In this prospectus, unless otherwise indicated, the “CompanyRegistrant,” “ourour company,” “we,” “us” and or “we,our” as used in this prospectus, refer to Axsome Inhibikase Therapeutics, Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid Delaware corporation and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxxconsolidated subsidiaries.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to incorporate We are incorporating by reference into this prospectus supplement and the accompanying prospectus certain information that we file with itthe SEC, which means that we can disclose are disclosing important information to you by referring you to those documents. The information incorporated by reference is considered deemed to be a part of this prospectus supplement and the accompanying prospectus, and except for information incorporated by reference that we file later with the SEC will automatically update and supersede is superseded by information contained in this prospectus supplement and the accompanying prospectus. The following documents are This means that you must look at all of the SEC filings that we incorporate by reference to determine if any statements in this prospectus supplement, the accompanying prospectus or any document previously incorporated by reference into this document (other than have been modified or superseded. This prospectus supplement incorporates by reference the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including set forth below that we have previously filed with the portions of these documents that are furnished under Item 2.02 or Item 7.01 of a Current SEC: • our Annual Report on Form 810-K, including any exhibits included with such Items): □ our annual report on Form 10‑K for the fiscal year ended December 31, 2018 filed with the SEC on March 15, 2019; □ the information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 20182019; □ • our quarterly report Quarterly Report on Form 10-Q for the three months quarter ended March 31, 2020; • our Definitive Proxy Statement on Schedule 14A relating to our 2019 Annual Meeting of Stockholders, filed with the SEC on May 9November 1, 2019; □ • our current reports Current Reports on Form 8-K filed with the SEC on January 7March 10, 2019 (two filings); January 8, 2019; January 30, 2019; February 2020 and July 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 20192020; and □ • the description of our common stock contained in Exhibit 4.17 to our registration statement Annual Report on Form 8‑A12B, filed with the SEC on November 16, 2015 (File No. 00110-37635), and all amendments or reports filed K for the purpose fiscal year ended December 31, 2019. Any information in any of updating the foregoing documents will automatically be deemed to be modified or superseded to the extent that information in this prospectus supplement or in a later filed document that is incorporated or deemed to be incorporated herein by reference modifies or replaces such descriptioninformation. We also incorporate by reference into this prospectus all documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with we subsequently file in the SEC future pursuant to Sections Section 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus supplement and until the completion or termination of the offering contemplated herebyoffering. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein K (except, in any such case, the portions furnished and not filed pursuant to Item 2.02, Item 7.01 or in otherwise), as well as any proxy statements. We will provide to each person, including any beneficial owner, to whom a document incorporated prospectus supplement and accompanying prospectus are delivered, without charge upon written or deemed to be oral request, a copy of any or all of the documents that are incorporated by reference into this document will be deemed to be modified or superseded for purposes of prospectus supplement and the document to accompanying prospectus but not delivered with the extent that a statement contained in this document or any other subsequently filed document that is deemed to be incorporated by reference into this document modifies or supersedes the statement. We make availableprospectus supplement and accompanying prospectus, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may also obtain, free of charge, a copy of any of these documents (other than including exhibits to these documents, unless the exhibits which are specifically incorporated by reference into such documents. You may request a copy of these documents or referred to in this prospectus) filings at no cost, by writing to or calling telephoning us at the following address and telephone numberaddress: We may offer and sell from time to time our shares offer and sell up to $125,000,000 of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt warrants to purchase common stock or preferred stock or any combination of the foregoing, either individually or in units, at prices and on terms described in one or more supplements to this prospectus. We may also offer securities as may be issuable upon conversion, redemption, repurchase, exchange or unitsexercise of any securities registered hereunder, including any applicable anti-dilution provisions. This prospectus provides the general terms of the securities we may offer and the general manner in which these securities will be offered. Each time we offer to sell securities, we will provide specific terms related to such offers in a supplement to this prospectus. The prospectus supplements may also add, update or change information contained in this prospectus. Before you invest, you should carefully read this prospectus and the applicable prospectus supplement, as well the documents incorporated by referenced in this prospectus. This prospectus may not be used to consummate a sale of securities unless accompanied by the applicable prospectus supplement. Our common stock is currently listed on the Nasdaq Capital Market under the symbol “BPTH.” On May 14, 2019, the last reported sales price per share of our common stock on the Nasdaq Capital Market was $18.00. We will sell these securities directly, through agents, dealers or underwriters as units that include designated from time to time, or through a combination of these methods. For additional information on the methods of sale, you should refer to the section titled “Plan of Distribution” in this prospectus. If any agents, dealers or underwriters are involved in the sale of these securities, the applicable prospectus supplement will set forth the names of the agents, dealers or underwriters and any applicable fees, commissions or discounts. We The price to the public of such securities and the net proceeds that we expect to receive from such sale will also be set forth in a supplement to this prospectus. ABOUT THIS PROSPECTUS ii PROSPECTUS SUMMARY 1 USE OF PROCEEDS 6 RISK FACTORS 4 SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS 5 DESCRIPTION OF WARRANTS 10 DESCRIPTION OF CAPITAL STOCK 7 LEGAL OWNERSHIP OF SECURITIES 13 DESCRIPTION OF UNITS 12 LEGAL MATTERS 18 PLAN OF DISTRIBUTION 16 WHERE YOU CAN FIND MORE INFORMATION 18 EXPERTS 18 INFORMATION INCORPORATED BY REFERENCE 18 This prospectus is part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission (the “SEC”) using a “shelf” registration process. Under this shelf registration statement process, we may from time to time sell common stock, preferred stock, warrants to purchase common stock or preferred stock or any combination of these securities the foregoing, either individually or in units, in one or more offerings with an aggregate initial offering price of up to an offering amount of $150,000,000125,000,000. This prospectus provides you with a general description of the securities we may offeroffer and the general manner in which these securities will be offered. Each time we offer securities pursuant to this prospectushereunder, we will provide a prospectus supplement containing specific terms of the particular related to such offering together with in a supplement to this prospectus. You should The prospectus supplements may add, update or change any of the information contained in this prospectus or in the documents that we have incorporated by reference into this prospectus. We urge you to read carefully this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement also may addsupplement, update or change information contained in this prospectus. This prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price of our common stock was $6.55. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents information incorporated herein by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading sections titled “Where You Can Find More Information.” and “Information Incorporated by Reference” below. If there is any inconsistency between the information in this prospectus and any prospectus supplement, you should rely on the information contained in that prospectus supplement. You should rely only on the information we have provided or incorporated by reference in the registration statement, this prospectus and in any the applicable prospectus supplement, including the information incorporated by reference. We have not authorized anyone to provide you with different information. No dealer, salesperson or other person is authorized to give any information or to represent anything not contained in this prospectus or the applicable prospectus supplement. You must not rely on any unauthorized information or representation. This prospectus or any applicable supplement to this prospectus do not constitute an offer to sell or the solicitation of an offer to buy any securities other than the registered securities to which they relate, nor do this prospectus or any applicable supplement to this prospectus constitute an offer to sell or the solicitation of an offer to buy securities in any jurisdiction to any person to whom it is unlawful to make such offer or solicitation in such jurisdiction. You should not assume that the information in this prospectus or any supplement to this prospectus is accurate at any date other than only as of the date indicated on the cover page front of these documents or the filing document and that any information we have incorporated by reference is accurate only as of the date of any the document incorporated by reference. Our business, regardless financial condition, results of its time operations and prospects may have changed since those dates. This prospectus contains summaries of deliverycertain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. We All of the summaries are not making an offer qualified in their entirety by the actual documents. Copies of some of the documents referred to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securitiesherein have been filed, will set forth be filed or will be incorporated by reference as exhibits to the names registration statement of any underwriters, initial purchasers, dealers or agents involved in the sale of our securitieswhich this prospectus is a part, and any related fee, commission or discount arrangements. See you may obtain copies of those documents as described below under the section titled “Plan of DistributionWhere You Can Find More Information.” The terms Unless the context requires otherwise, references in this prospectus to “Axsome,” the “Companywe,” “our,” “us,” “the Company” and “we,Bio-Path” as used in this prospectus, refer to Axsome TherapeuticsBio-Path Holdings, Inc. and its wholly-owned subsidiary. Bio-Path Holdings, Inc.’s wholly-owned subsidiary, Bio-Path, Inc., unless we state otherwise or the context indicates otherwise. is sometimes referred to herein as “Bio-Path Subsidiary.” We are a clinical and preclinical stage biopharmaceutical oncology focused RNAi nanoparticle drug development company developing utilizing a novel therapies technology that achieves systemic delivery for target specific protein inhibition for any gene product that is over-expressed in disease. Our drug delivery and antisense technology, called DNAbilize®, is a platform that uses P-ethoxy, which is a deoxyribonucleic acid (DNA) backbone modification that is intended to protect the management DNA from destruction by the body’s enzymes when circulating in vivo, incorporated inside of central nervous systema neutral charged lipid bilayer. We believe this combination allows for high efficiency loading of antisense DNA into non-toxic, cell-membrane-like structures for delivery of the antisense drug substance into cells. In vivo, the DNAbilize® delivered antisense drug substances are systemically distributed throughout the body to allow for reduction or CNSelimination of target proteins in blood diseases and solid tumors. Through testing in numerous animal studies and treatment in over 70 patients, disorders the Company’s DNAbilize® drug candidates have demonstrated an excellent safety profile. DNAbilize® is a registered trademark of the Company. Using DNAbilize® as a platform for which there are limited treatment options. By focusing on this therapeutic areadrug development and manufacturing, we are addressing significant and growing markets where current treatment options are limited or inadequatecurrently have three antisense drug candidates in development to treat at least five different cancer disease indications. Our product candidate portfolio includes two late stage candidateslead drug candidate, AXS‑02 prexigebersen (pronounced prex” i je ber’ sen), is in the efficacy portion of a Phase 2 clinical trial for acute myeloid leukemia (AML) in combination with low-dose cytarabine (LDAC) and AXS‑05in combination with decitabine. On March 6, 2019, we announced intended amendments to this Phase 2 clinical trial to, among other things, add prexigebersen in combination with decitabine for myelodysplastic syndrome and close prexigebersen in combination with LDAC. In addition, preclinical efficacy studies are underway for triple combination prexigebersen, decitabine and Venclexta in AML. Prexigebersen is also being studied in the safety portion of a Phase 2a clinical trial for chronic myeloid leukemia in combination with dasatinib. Prexigebersen was shown to enhance chemotherapy efficacy in preclinical solid tumor models, such as ovarian cancer, and we intend to file an Investigational New Drug (IND) application for prexigebersen in solid tumors in 2019. Our second drug candidate, Liposomal Bcl-2 (“BP1002”), targets the protein Bcl-2, which we are developing is responsible for multiple indicationsdriving cell survival in up to 60% of all cancers. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 studyare currently preparing an IND application for BP1002 after completing additional IND enabling studies. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan intend to initiate a Phase 2/3 1 clinical trial of BP1002 in agitation in refractory/relapsed lymphoma and chronic lymphocytic leukemia patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops once we receive approval from the U.S. Food and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disordersDrug Administration (FDA). Our first product third drug candidate, AXS‑02 Liposomal Stat3 (disodium zoledronate tetrahydrate“BP1003”), targets the Stat3 protein and is currently in preclinical development as a potentially first-in-class, oral, targetedpotential treatment of pancreatic cancer, non-opioid therapeutic small cell lung cancer (NSCLC) and AML. Preclinical models have shown BP1003 to inhibit cell viability and STAT3 protein expression in NSCLC and AML cell lines. Further, BP1003 successfully penetrated pancreatic tumors and significantly enhanced the efficacy of gemcitabine, a treatment for chronic painpatients with advanced pancreatic cancer, in a pancreatic patient derived tumor model. AXS‑02 Our lead indication for BP1003 is a potent inhibitor pancreatic cancer due to the severity of osteoclaststhis disease and the lack of effective, which are bone remodeling cells that break down bone tissuelife-extending treatments. We are initially developing AXS‑02 intend to complete IND enabling studies of BP1003 in 2019 and to file an IND application for a Phase 1 clinical trial of BP1003 for the treatment of pain solid tumors, including pancreatic cancer in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, 2020. Our DNAbilize® technology-based products are available for out-licensing or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdownpartnering. We intend to seek U.S. Food apply our drug delivery technology template to new disease-causing protein targets as a means to develop new nanoparticle antisense RNAi drug candidates. We have a new product identification template in place to define a process of scientific, preclinical, commercial and Drug Administrationintellectual property evaluation of potential new drug candidates for inclusion into our drug product development pipeline. As we expand, we will look at indications where a systemic delivery is needed and antisense RNAi nanoparticles can be used to slow, reverse or FDAcure a disease, approval either alone or in combination with another drug. On July 19, 2017, we announced that the United States Patent and Trademark Office issued a notice of allowance for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for claims related to DNAbilize®, including its use in the treatment of CRPScancers, autoimmune diseases and infectious diseases. Our second product candidateWe have certain intellectual property as the basis for our current drug products in clinical development, AXS‑05specifically prexigebersen, is an innovative fixed-dose combination of dextromethorphan, or DM, BP1002 and bupropionBP1003. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD RNAi antisense nanoparticle drug candidates based on our own patented technology to treat cancer and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as autoimmune disorders where targeting a single agent. AXS‑05 uses bupropion protein may be advantageous and result in reduced patient adverse effects as a novel drug delivery method compared to inhibit DM metabolism small molecule inhibitors with off-target and increase its bioavailabilitynon-specific effects. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration composition of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 matter and method of use intellectual property for the treatment design and manufacture of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxxantisense RNAi nanoparticle drug products.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to incorporate by reference into this prospectus supplement and the accompanying prospectus certain information we file with itthem, which means that we can disclose important information to you by referring you to those documents. The information incorporated by reference is considered to be a part of this prospectus supplement and the accompanying prospectussupplement, and later information that we file later filed with the SEC will automatically update and supersede information contained in this prospectus supplement and the accompanying prospectusinformation. The following documents are incorporated We incorporate by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including listed below that we have previously filed with the portions of these documents SEC, except that are information furnished under Item 2.02 or Item 7.01 of a our Current Report Reports on Form 8-KK or any other filing where we indicate that such information is being furnished and not filed under the Exchange Act, including any exhibits included with such Items): □ is not deemed to be filed and not incorporated by reference herein: ● our annual report Annual Report on Form 10‑K 10-K for the fiscal year ended December 31, 2018 2020 as filed with the SEC on February 11, 2021, and amended on March 1510, 20192021; □ the information contained in ● our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 2018; □ our quarterly report Quarterly Report on Form 10-Q for the three months fiscal quarters ended March 31, 2019 2021 (as filed with the SEC on May 913, 20192021); □ ● our current reports Current Reports on Form 8-K filed with the SEC on January 7, 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; 2021, January 19, 2021, January 20, 2021, January 22, 2021, March 271, 2019; April 152021, 2019; May 624, 2019 2021, and May 928, 20192021; and □ ● the description of our common stock contained in our the registration statement on Form 8‑A12B8-A as filed with the SEC on February 28, 2005,as updated by Exhibit 4.1 to our Form 10-K for the year ended 2020, filed with the SEC on November 16February 11, 2015 (File No. 001-37635)2021, and all amendments or reports filed for the purpose of updating such descriptionamended on March 10, 2021. We also incorporate by reference into this prospectus all supplement additional documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us we may file with the SEC pursuant to under Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus supplement and until prior to the completion or termination of the offering contemplated herebyoffering, including all such documents we may file with the SEC after the date of the initial registration statement and prior to the effectiveness of the registration statement, but excluding any information deemed furnished and not filed with the SEC. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement statements contained herein or in a previously filed document incorporated or deemed to be incorporated by reference into this document will be prospectus supplement is deemed to be modified or superseded for purposes of the document this prospectus supplement to the extent that a statement contained in this document prospectus supplement, or any other in a subsequently filed document that is deemed to be also incorporated by reference into this document herein, modifies or supersedes the that statement. We make availableThis prospectus supplement may contain information that updates, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments modifies or is contrary to those reports filed information in one or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) more of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SECdocuments incorporated by reference in this prospectus supplement. You may also obtainshould rely only on the information incorporated by reference or provided in this prospectus supplement. We have not authorized anyone else to provide you with different information. You should not assume that the information in this prospectus supplement is accurate as of any date other than the date of this prospectus supplement or the date of the documents incorporated by reference in this prospectus supplement. We will provide to each person, free of chargeincluding any beneficial owner, to whom this prospectus supplement is delivered, upon written or oral request, at no cost to the requester, a copy of any and all of these documents (other than exhibits to these documents, unless the exhibits are specifically information that is incorporated by reference into these documents or referred to in this prospectusprospectus supplement. You may request a copy of these filings, at no cost to you, by telephoning us at (000) 000-0000 or by writing or calling us at the following address and telephone numberaddress: You may also access the documents incorporated by reference in this prospectus supplement through our website at xxx.xxxxx.xxx. The reference to our website is an inactive textual reference only and, except for the specific incorporated documents listed above, no information available on or through our website shall be deemed to be incorporated in this prospectus supplement, the accompanying prospectus or the registration statement of which it forms a part. We may offer and sell up to $75,000,000 in the aggregate of any combination of the securities identified above from time to time our shares in one or more offerings. This prospectus provides you with a general description of common stockthe securities. Each time we offer and sell securities, shares we will provide a supplement to this prospectus that contains specific information about the offering and the amounts, prices and terms of preferred stockthe securities. The supplement may also add, warrants, debt securities update or change information contained in this prospectus with respect to that offering. You should carefully read this prospectus and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include the applicable prospectus supplement and any related free writing prospectus before you invest in any of these our securities. We may offer and sell the securities described in this prospectus and any prospectus supplement to or through one or more underwriters, dealers and agents, or directly to purchasers, or through a combination of these methods. If any underwriters, dealers or agents are involved in the sale of any of the securities, their names and any applicable purchase price, fee, commission or discount arrangement between or among them will be set forth, or will be calculable from the information set forth, in the applicable prospectus supplement. See the sections of this prospectus entitled “About this Prospectus” and “Plan of Distribution” for more information. No securities may be sold without delivery of this prospectus and the applicable prospectus supplement describing the method and terms of the offering of such securities. Our common stock is listed on the NYSE American LLC under the symbol “INUV.” The last reported sale price of our common stock on February 10, 2021 was $1.84 per share. The aggregate market value of our outstanding common stock held by non-affiliates is $197,790,564.48 based on 118,513,403 shares of common stock outstanding, of which 107,494,872 shares are held by non-affiliates, and a per share value of $1.84 based on the closing price of our common stock on the NYSE American on February 10, 2021. ABOUT THIS PROSPECTUS 3 AVAILABLE INFORMATION 3 OUR COMPANY 4 RISK FACTORS 4 CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS 5 USE OF PROCEEDS 5 DIVIDEND POLICY 5 DESCRIPTION OF CAPITAL STOCK 6 DESCRIPTION OF WARRANTS 7 DESCRIPTION OF UNITS 8 LEGAL OWNERSHIP OF SECURITIES 8 PLAN OF DISTRIBUTION 11 LEGAL MATTERS 12 EXPERTS 12 INFORMATION INCORPORATED BY REFERENCE 12 You should rely only on the information we have provided or incorporated by reference in this prospectus or in any prospectus supplement. We have not authorized anyone to provide you with information different from that contained or incorporated by reference in this prospectus or in any prospectus supplement. This prospectus and any prospectus supplement is an offer to sell only the securities offered hereby, but only under circumstances and in jurisdictions where it is lawful to do so. You should assume that the information contained in this prospectus and in any prospectus supplement is accurate only as of their respective dates and that any information we have incorporated by reference is accurate only as of the date of the document incorporated by reference, regardless of the time of delivery of this prospectus or any prospective supplement or any sale of securities. The registration statement, including the exhibits and the documents incorporated herein by reference, can be read on the website of the Securities and Exchange Commission, or “SEC,” or on our corporate website at xxx.xxxxx.xxx as set forth in this prospectus under the heading “Available Information.” This prospectus is part of a registration statement on Form S-3 that we filed with the SEC utilizing a “shelf” registration, or continuous offering, process. Under the shelf registration process, we may issue and sell any combination of these the securities described in this prospectus in one or more offerings with an aggregate initial a maximum offering price of up to $150,000,00075,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer sell securities pursuant to under this prospectusshelf registration, we will provide a prospectus supplement containing that will contain certain specific information about the terms of that offering, including a description of any risks related to the particular offering together with offering, if those terms and risks are not described in this prospectus. You should read this prospectus and the applicable A prospectus supplement carefully before you invest in any securities. The prospectus supplement may also may add, update or change information contained in this prospectus. This If there is any inconsistency between the information in this prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed , you should rely on the NASDAQ Capital Market under information in the symbol “AXSM.” On November 30, 2016, the closing price of our common stock was $6.55. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a The registration statement that we filed with the Securities and Exchange Commission, or SEC includes exhibits that provide more details on the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained matters discussed in this prospectus. Before making an investment decision, you You should read carefully both this prospectus and any the related exhibits filed with the SEC and the accompanying prospectus supplement together with the documents incorporated by reference into this prospectus as additional information described below under the heading headings “Available Information” and “Information Incorporated by Reference.” The registration statement that contains before investing in any of the securities offered. Neither we, nor any agent, underwriter or dealer has authorized any person to give any information or to make any representation other than those contained or incorporated by reference in this prospectus, including the exhibits any applicable prospectus supplement or any related free writing prospectus prepared by or on behalf of us or to the registration statement and the information incorporated by referencewhich we have referred you. This prospectus, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information provided in the registration statement, any applicable supplement to this prospectus and or any related free writing prospectus does not constitute an offer to sell or the solicitation of an offer to buy any securities other than the registered securities to which they relate, nor does this prospectus, any applicable supplement to this prospectus or any related free writing prospectus constitute an offer to sell or the solicitation of an offer to buy securities in any prospectus supplement, including the information incorporated by reference. We have not authorized anyone jurisdiction to provide you with different informationany person to whom it is unlawful to make such offer or solicitation in such jurisdiction. You should not assume that the information contained in this prospectus, any applicable prospectus supplement or any supplement to this related free writing prospectus is accurate at on any date other than subsequent to the date indicated set forth on the cover page front of these documents the document or that any information we have incorporated by reference is correct on any date subsequent to the filing date of any the document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in even though this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise any applicable prospectus supplement or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous systemany related free writing prospectus is delivered, or CNSsecurities are sold, disorders on a later date. This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for which there complete information. All of the summaries are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 qualified in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed their entirety by the mechanisms actual documents. Copies of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment some of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a resultdocuments referred to herein have been filed, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive will be filed or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not will be incorporated by reference into as exhibits to the registration statement of which this prospectusprospectus is a part, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also may obtain copies of these filings by visiting those documents as described below under the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxxsection entitled “Available Information.”

INFORMATION INCORPORATED BY REFERENCE. We file annual, quarterly and other reports, proxy statements and other information with the SEC. The SEC allows us to incorporate by reference into this prospectus supplement and the accompanying prospectus certain information we file with itthem, which means that we can disclose important information to you by referring you to those documents. The information incorporated by reference is considered to be a part of this prospectus supplement and the accompanying prospectussupplement, and later information that we file later filed with the SEC will automatically update and supersede information contained in this prospectus supplement and the accompanying prospectusinformation. The following documents are incorporated We incorporate by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including listed below that we have previously filed with the portions of these documents SEC, except that are information furnished under Item 2.02 or Item 7.01 of a our Current Report Reports on Form 8-KK or any other filing where we indicate that such information is being furnished and not filed under the Exchange Act, including any exhibits included with such Items): □ is not deemed to be filed and not incorporated by reference herein: ● our annual report Annual Report on Form 10‑K 10-K for the fiscal year ended December 31, 2018 2020 as filed with the SEC on March 15February 11, 20192021; □ the information contained in ● our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 2018; □ our quarterly report on Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 9, 2019; □ our current reports Current Reports on Form 8-K as filed with the SEC on January 7, 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 272021, 2019; April 15January 19, 2019; May 62021, 2019 January 20, 2021, and May 9January 22, 20192021; and □ ● the description of our common stock contained in our the registration statement on Form 8‑A12B, 8-A as filed with the SEC on November 16February 28, 2015 (File No. 001-37635), and all amendments or reports filed for the purpose of updating such description2005. We also incorporate by reference into this prospectus all supplement additional documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us we may file with the SEC pursuant to under Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus supplement and until prior to the completion or termination of the offering contemplated herebyoffering, including all such documents we may file with the SEC after the date of the initial registration statement and prior to the effectiveness of the registration statement, but excluding any information deemed furnished and not filed with the SEC. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement statements contained herein or in a previously filed document incorporated or deemed to be incorporated by reference into this document will be prospectus supplement is deemed to be modified or superseded for purposes of the document this prospectus supplement to the extent that a statement contained in this document prospectus supplement, or any other in a subsequently filed document that is deemed to be also incorporated by reference into this document herein, modifies or supersedes the that statement. We make availableThis prospectus may contain information that updates, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments modifies or is contrary to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may also obtain, free of charge, a copy of any of these documents (other than exhibits to these documents, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling us at the following address and telephone number: We may offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities information in one or more offerings with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities pursuant to this prospectus, we will provide a prospectus supplement containing specific terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement also may add, update or change information contained in this prospectus. This prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price of our common stock was $6.55. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents incorporated by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains in this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information incorporated by reference or provided in the registration statement, this prospectus and in any prospectus supplement, including the information incorporated by referenceprospectus. We have not authorized anyone else to provide you with different information. You should not assume that the information in this prospectus or any supplement to this prospectus is accurate at as of any date other than the date indicated on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or the date of the documents incorporated by reference in deciding whether this prospectus. We will provide to purchase our securities. Our filings with the SEC are posted on our website each person, including any beneficial owner, to whom this prospectus is delivered, upon written or oral request, at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish no cost to the SECrequester, a copy of any and all of the information that is incorporated by reference in this prospectus. The public can also obtain copies We will provide to each person, including any beneficial owner, to whom this prospectus supplement is delivered, upon written or oral request, at no cost to the requester, a copy of any and all of the information that is incorporated by reference in this prospectus supplement. You may request a copy of these filings filings, at no cost to you, by visiting the SEC’s Public Reference Room telephoning us at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, (000) 000-0000 or by calling writing us at the SEC at 1‑800‑SEC‑0330 or following address: You may also access the documents incorporated by accessing reference in this prospectus supplement on the SEC’s website xxxxx.xxx.xxx or through our website at xxx.xxx.xxxxxx.xxxxx.xxx. The reference to our website is an inactive textual reference only and, except for the specific incorporated documents listed above, no information available on or through our website shall be deemed to be incorporated in this prospectus supplement, the accompanying prospectus or the registration statement of which it forms a part.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us Under the Securities Act of 1933, the Company has filed with the Securities and Exchange Commission ("SEC") a registration statement (the "Registration Statement") relating to incorporate the Contracts offered by reference into this prospectus. This prospectus supplement and the accompanying prospectus certain information we file with it, which means that we can disclose important information by referring you to those documents. The information incorporated by reference is considered to be has been filed as a part of this prospectus supplement the Registration Statement and does not contain all of the information set forth in the Registration Statement and the accompanying prospectus, exhibits and reference is hereby made to such Registration Statement and exhibits for further information that we file later with relating to the SEC will automatically update and supersede information contained in this prospectus supplement Company and the accompanying prospectusContracts. The following documents are incorporated by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including the portions of these documents that are furnished under Item 2.02 or Item 7.01 of a Current Report on Form 8-K, including any exhibits included with such Items): □ our Company's annual report on Form 10‑K for the fiscal year ended December 31, 2018 10-K was filed with the SEC on March 1530, 2019; □ the 2015 via XXXXX File No. 033-03094. The Form 10-K contains information contained in our definitive proxy statement on Schedule 14A for our 2019 Annual Meeting of Stockholders, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year period ended December 31, 2018; □ our quarterly report on 2014, about the Company, including consolidated audited financial statements for the Company's latest fiscal year. The Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 9, 2019; □ our current reports on Form 8-K filed with the SEC on January 7, 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 2019; and □ the description of our common stock contained in our registration statement on Form 8‑A12B, filed with the SEC on November 16, 2015 (File No. 001-37635), and all amendments or reports filed for the purpose of updating such description. We also incorporate is incorporated by reference into this prospectus xxxxxxxxxx.Xx addition, all documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are subsequently filed by us with the SEC Company pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Securities Exchange Act after of 1934, as amended ("Exchange Act") prior to the date of this prospectus supplement and until the completion or termination of the offering contemplated hereby. These documents include periodic reportsoffering, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein or in a document incorporated or deemed to be are also incorporated by reference into this document will be prospectus. We are not incorporating by reference, in any case, any documents or information deemed to be modified or superseded for purposes have been furnished and not filed in accordance with SEC rules. There have been no material changes in the Company's affairs which have occurred since the end of the document to latest fiscal year for which audited consolidated financial statements were included in the extent that a statement contained in this document or any other subsequently filed document that is deemed to be incorporated by reference into this document modifies or supersedes the statement. We make available, free of charge, through our website our Annual Reports on latest Form 10-K, Quarterly Reports on K or which have not been described in a Form 10-Q, Current Reports on Q or Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of by the Company under the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it toAct. If requested, the SEC. You may also obtainCompany will furnish, free of without charge, a copy of any of these documents (other than exhibits to these documents, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling us at the following address and telephone number: We may offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description all of the securities we may offer. Each time we offer securities pursuant to this prospectus, we will provide a prospectus supplement containing specific terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement also may add, update reports or change information contained in this prospectus. This prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price of our common stock was $6.55. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents documents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents incorporated by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information provided in the registration statement, this prospectus and in any prospectus supplement, including the information incorporated by reference. We have not authorized anyone to provide you with different information. You should not assume that the information in this prospectus or any supplement to this prospectus is accurate at any date other than the date indicated on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus. You may direct Your requests to the Company at, 00000 Xxxxx Xxxxxxxxx Xxxxx Xxxx, Xxxxxxxxx, XX, 00000. The telephone number 0-000-000-0000. You may also access the incorporated reports and you should not consider other documents at xxx.xxxxxxx.xxx. The Company files periodic reports as required under the Exchange Act (including Form 10-K, 10-Q and 8-K). You may also read and copy any information contained on, or materials that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings the Company files with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s 's Public Reference Room at 000 X Xxxxxx XXXxxxxx, Xxxxxxxxxx X.X., Xxxxxxxxxx, XX 00000, or . The public may obtain information on the operation of the Public Reference Room by calling the SEC at 1‑800‑SEC‑0330 or by accessing 0-000-XXX-0000. The SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC’s website SEC at xxx.xxx.xxxxxxx://xxx.xxx.xxx.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to “incorporate by reference into this prospectus supplement and reference” the accompanying prospectus certain information we file with it, them which means that we can disclose important information to you by referring you to those documentsdocuments instead of having to repeat the information in this prospectus supplement and the accompanying prospectus. The information incorporated by reference is considered to be a part of this prospectus supplement and the accompanying prospectus, and later information that we file later with the SEC will automatically update and supersede information this information. Any statement contained in a previously filed document incorporated by reference will be deemed to be modified or superseded for purposes of this prospectus to the extent that a statement contained in this prospectus supplement modifies or replaces that statement. We incorporate by reference the documents listed below and any future information filed (rather than furnished) with the SEC under Sections 13(a), 13(c), 14, or 15(d) of the Exchange Act between the date of this prospectus and the accompanying prospectus. The following documents termination of this offering, provided, however, that we are incorporated by reference into this document (other than the portions of these documents deemed to be “furnished” or not deemed to be “filed,” including the portions of these documents that are incorporating any information furnished under Item 2.02 or Item 7.01 of a Current Report any current report on Form 8-K, including any exhibits included with such Items): □ : ∎ our annual report Annual Report on Form 10‑K F orm 10-K for the fiscal year ended December 31, 2018 2019, filed with the SEC on March 15February 27, 20192020; □ ∎ the information contained in specifically incorporated by reference into our definitive proxy statement Annual Report on Schedule 14A F orm 10-K for the year ended December 31, 2018, from our 2019 Annual Meeting of StockholdersDefinitive Proxy Statement on S chedule 14A, filed with the SEC on April 26, 2019, to the extent incorporated by reference in Part III of the Form 10 K for the fiscal year ended December 31, 2018; □ ∎ our quarterly report Current Report on Form 10-Q for the three months ended March 31, 2019 filed with the SEC on May 9, 2019; □ our current reports on Form F orm 8-K filed with the SEC on January 7February 20, 2019 (two filings); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 20192020; and □ ∎ the description of our common stock contained in our registration statement on Form 8‑A12B, F orm 8-A filed with the SEC on November 16October 6, 2015 (File No. 001-37635)2015, and all including any amendments or reports filed for the purpose of updating such description. We also incorporate by reference into this prospectus all documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us with the SEC pursuant to Sections 13(a)for the purposes of updating this description. These documents may also be accessed on our website at xxx.xxxxxx.xxx. Except as otherwise specifically incorporated by reference in this prospectus supplement and the accompanying prospectus, 13(c)information contained in, 14 or 15(d) of the Exchange Act after the date accessible through, our website is not a part of this prospectus supplement and until the completion or termination of the offering contemplated hereby. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement contained herein or in a document incorporated or deemed to be incorporated by reference into this document will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained in this document or any other subsequently filed document that is deemed to be incorporated by reference into this document modifies or supersedes the statementaccompanying prospectus. We make availablewill furnish without charge to you, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed upon written or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may also obtain, free of chargeoral request, a copy of any or all of these the documents (other than incorporated by reference, including exhibits to these documents, unless the exhibits are specifically incorporated by reference into these documents or referred to in this prospectus) by writing or calling telephoning us at the following address and telephone numberaddress: We may offer and sell up to $250,000,000 in the aggregate of the securities identified above from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities or units, as well as units that include any of these securities. We may sell any combination of these securities in one or more offerings with an aggregate initial offering price of up to $150,000,000offerings. This prospectus provides you with a general description of the securities we may offersecurities. Each time we offer securities pursuant to this prospectusand sell securities, we will provide a supplement to this prospectus supplement containing that contains specific information about the offering and the amounts, prices and terms of the particular offering together with this prospectus. You should read this prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement may also may add, update or change information contained in this prospectusprospectus with respect to that offering. This You should carefully read this prospectus may not be used to offer and sell securities unless accompanied by the applicable prospectus supplement. Our common stock is listed on the NASDAQ Capital Market under the symbol “AXSM.” On November 30, 2016, the closing price supplement before you invest in any of our common stock was $6.55securities. We may sell the securities directly to investors, or to or through underwriters or dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, the underwriters, if any, may over-allot a portion of the securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICS, INC 3 FORWARD-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell from time to time any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement we will provide a prospectus supplement that describes the terms of the relevant offering. The prospectus supplement also may add, update or change information contained in this prospectus. Before making an investment decision, you should read carefully both this prospectus and any prospectus supplement together with the documents incorporated by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this prospectus, including the exhibits to the registration statement and the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading “Where You Can Find More Information.” You should rely only on the information provided in the registration statement, this prospectus and in any prospectus supplement, including the information incorporated by reference. We have not authorized anyone to provide you with different information. You should not assume that the information in this prospectus or any supplement to this prospectus is accurate at any date other than the date indicated on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through one or more underwriters, initial dealers and agents, or directly to purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to timemethods. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of If any underwriters, initial purchasers, dealers or agents are involved in the sale of our any of the securities, their names and any related applicable purchase price, fee, commission or discount arrangementsarrangement between or among them will be set forth, or will be calculable from the information set forth, in the applicable prospectus supplement. See the sections of this prospectus entitled “About this Prospectus” and “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise or the context indicates otherwisefor more information. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe No securities may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug sold without delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our and the applicable prospectus supplement describing the method and terms of the offering of such securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxx.

INFORMATION INCORPORATED BY REFERENCE. The SEC allows us to incorporate by reference into this prospectus supplement and the accompanying prospectus certain information we file with it, which means that we can disclose important information to you by referring you to those documentsanother document that we have filed separately with the SEC. The information incorporated by reference is considered deemed to be a part of this prospectus supplement and the accompanying prospectussupplement, and subsequent information that we file later with the SEC will automatically update and supersede that information. You should read the information incorporated by reference because it is an important part of this prospectus supplement. Any statement contained in a previously filed document incorporated by reference will be deemed to be modified or superseded for purposes of this prospectus supplement to the extent that a statement contained in this prospectus supplement and the accompanying prospectusmodifies or replaces that statement. The following documents are incorporated We incorporate by reference into this document the following information or documents that we have filed with the SEC (other than the excluding those portions of these documents deemed to be “furnished” or any Form 8-K that are not deemed to be “filed,” including pursuant to the portions General Instructions of these documents that are furnished under Item 2.02 or Item 7.01 of a Current Report on Form 8-K, including any exhibits included with such Items): □ • our annual report Annual Report on Form 10‑K 10-K for the fiscal year ended December 31, 2018 2021 filed with the SEC on March 151, 20192022; □ • the information contained specifically incorporated by reference in our Annual Report on Form 10-K for the year ended December 31, 2021, from our definitive proxy statement on Schedule 14A for relating to our 2019 Annual Meeting 2022 annual meeting of Stockholdersstockholders, filed with the SEC on April 2629, 2019, 2022; • the description of our common stock contained in Exhibit 4.7 to the extent incorporated by reference in Part III of the our Annual Report on Form 10 10-K for the fiscal year ended December 31, 20182021, filed with the SEC on March 1, 2022, including any amendment or report filed for the purpose of updating such description; □ • our quarterly report Quarterly Report on Form 10-Q for the three months ended March 31, 2019 2022 filed with the SEC on May 910, 20192022; □ and • our current reports Current Reports on Form 8-K filed with the SEC on January 712, 2019 2022 (two filingsexcluding information furnished thereunder); January 8, 2019; January 30, 2019; February 6, 2019; March 4, 2019; March 6, 2019; March 14, 2019; March 27, 2019; April 15, 2019; May 6, 2019 and May 9, 2019; and □ the description of our common stock contained in our registration statement on Form 8‑A12B, filed with the SEC on November 16, 2015 2022 (File No. 001-37635excluding information furnished thereunder), and all amendments or reports filed for the purpose of updating such descriptionMarch 25, 2022. We also incorporate by reference into this prospectus all supplement additional documents (other than Current Reports furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items) that are filed by us we may file with the SEC pursuant to under Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus supplement and until prior to the completion or termination of the offering contemplated herebyoffering, but excluding any information deemed furnished and not filed with the SEC. These documents include periodic reports, such as Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Any statement statements contained herein or in a previously filed document incorporated or deemed to be incorporated by reference into this document will be prospectus supplement is deemed to be modified or superseded for purposes of the document this prospectus supplement to the extent that a statement contained in this document prospectus supplement, or any other in a subsequently filed document that is deemed to be also incorporated by reference into this document herein, modifies or supersedes the that statement. We make availableThis prospectus supplement may contain information that updates, free of charge, through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments modifies or is contrary to those reports filed information in one or furnished pursuant to Section 13(a), 13(c), 14 or 15(d) more of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SECdocuments incorporated by reference in this prospectus supplement. You may also obtainshould rely only on the information incorporated by reference or provided in this prospectus supplement. We have not authorized anyone else to provide you with different information. You should not assume that the information in this prospectus supplement is accurate as of any date other than the date of this prospectus supplement or the date of the documents incorporated by reference in this prospectus supplement. We will provide to each person, free of chargeincluding any beneficial owner, to whom this prospectus supplement is delivered, upon written or oral request, at no cost to the requester, a copy of any and all of these documents (the information that is incorporated by reference in this prospectus supplement, but not delivered with the prospectus supplement, other than exhibits to these documents, such documents unless the such exhibits are specifically incorporated by reference into these the documents or referred to that this prospectus supplement incorporates. Requests for such documents should be directed to: You may also access the documents incorporated by reference in this prospectus) by writing prospectus supplement through our website at xxxxx://xxx.xxxxxxxxxxx.xxx. Except for the specific incorporated documents listed above, no information available on or calling us at through our website shall be deemed to be incorporated in this prospectus supplement or the following registration statement of which it forms a part. Inclusion of our website address and telephone number: in this prospectus supplement is an inactive textual reference only. ImmunityBio, Inc. may offer, from time to time, We may from time to time, in one or more offerings, offer and sell from time to time our shares of common stock, shares of preferred stock, warrants, debt securities and rights to purchase common stock, preferred stock, debt securities securities, warrants to purchase common stock, preferred stock or unitsdebt securities, as well as units that include any of these securities. We may sell or any combination of these securities in the foregoing, either individually or as units comprised of one or more offerings with an aggregate initial offering price of up to $150,000,000the other securities. This prospectus provides you with a general description of the securities we may offer. Each time we offer This prospectus may not be used to sell securities pursuant unless accompanied by a prospectus supplement, which will describe the method and the terms of the offering. We will provide you with the specific amount, price and terms of the applicable offered securities in one or more supplements to this prospectus, we will provide a . We may also authorize one or more free writing prospectuses to be provided to you in connection with these offerings. A prospectus supplement containing specific terms of the particular offering together with this prospectus. You should read this and any free writing prospectus and the applicable prospectus supplement carefully before you invest in any securities. The prospectus supplement may also may add, update or change information contained in this prospectus with respect to that offering. You should read this prospectus. This prospectus may not , the information and documents incorporated, or deemed to be used to offer incorporated, by reference in this prospectus, and sell securities unless accompanied by the any applicable prospectus supplementsupplement and any related free writing prospectus carefully before you purchase any of our securities offered hereby. Our common stock is listed on the NASDAQ Capital Nasdaq Global Select Market under the symbol “AXSMIBRX.” On November 30February 24, 20162022, the closing last reported sale price of our common stock on the Nasdaq Global Select Market was $6.557.04 per share. We There is currently no market for the other securities we may sell offer. Investing in our securities involves risks. Please carefully read the securities directly to investorsinformation under the headings “Risk Factors” beginning on page 6 of this prospectus and in any similar section contained in or incorporated by reference herein, including, without limitation, our Annual Report on Form 10-K filed with the SEC on March 1, 2022, or in the applicable prospectus supplement before you invest in our securities. These securities may be offered and sold to or through underwriters one or more underwriters, dealers and agents, or directly to purchasers, or through a combination of these methods. If underwriters, dealers, and also to other purchasers or through agents. The names of any underwriters or agents that are included used to sell the securities, we will name them and describe their compensation in a sale of securities to you, and any applicable commissions or discounts, will be stated in an accompanying prospectus supplement. In addition, See the underwriters, if any, sections of this prospectus entitled “About this Prospectus” and “Plan of Distribution” for more information. No securities may over-allot a portion be sold without delivery of this prospectus and the applicable prospectus supplement describing the method and terms of the offering of such securities. ABOUT THIS PROSPECTUS 3 AXSOME THERAPEUTICSThe date of this prospectus is May 18, INC 3 FORWARD2022. TABLE OF CONTENTS Page Forward-LOOKING STATEMENTS 4 RISK FACTORS 4 RATIO OF EARNINGS TO FIXED CHARGES AND PREFERRED STOCK DIVIDEND REQUIREMENTS 5 USE OF PROCEEDS 5 DESCRIPTION OF CAPITAL STOCK 5 DESCRIPTION OF WARRANTS 8 DESCRIPTION OF DEBT SECURITIES 10 DESCRIPTION OF RIGHTS 17 DESCRIPTION OF UNITS 18 PLAN OF DISTRIBUTION 19 LEGAL MATTERS 20 EXPERTS 20 WHERE YOU CAN FIND MORE INFORMATION 21 INFORMATION INCORPORATED BY REFERENCE 21 Looking Statements 6 Dividend Policy 7 Legal Matters 23 This prospectus is part of a registration statement on Form S-3 that we filed with the U.S. Securities and Exchange Commission, or the SEC, using a “shelf” registration process. Under this shelf registration process, we may offer and sell may, from time to time time, offer or sell any combination of the securities described in this prospectus in one or more offerings in amounts, at prices and on terms that we determine at the time of the offering, with an aggregate initial offering price of up to $150,000,000offerings. This prospectus provides you with a general description of the securities we may offer. Each time we offer securities under this registration statement sell securities, we will provide a prospectus supplement that describes will contain specific information about the terms of the relevant that offering. We may also authorize one or more free writing prospectuses to be provided to you that may contain material information relating to these offerings. The prospectus supplement or any related free writing prospectus may also may addadd to, update or change information contained in this prospectusprospectus and, accordingly, to the extent inconsistent, information in this prospectus is superseded by the information in the prospectus supplement. Before making an investment decisionEach prospectus supplement will provide the amount, price, terms and plan of distribution relating to the securities to be sold pursuant to such prospectus supplement. For additional information on the methods of sale, you should refer to the section entitled “Plan of Distribution” in this prospectus. No person has been authorized to give any information or make any representations in connection with this offering other than those contained or incorporated by reference in this prospectus, any accompanying prospectus supplement and any related issuer free writing prospectus in connection with the offering described herein and therein. We and any agent, underwriter or dealer take no responsibility for, and can provide no assurance as to the reliability of, any other information others may give you. Neither this prospectus nor any prospectus supplement nor any related issuer free writing prospectus shall constitute an offer to sell or a solicitation of an offer to buy offered securities in any jurisdiction in which it is unlawful for such person to make such an offering or solicitation. This prospectus does not contain all of the information included in the registration statement. For a more complete understanding of the offering of the securities, you should refer to the registration statement, including its exhibits. Statements contained in this prospectus about the provisions or contents of any agreement or other document are not necessarily complete. If the SEC’s rules and regulations require that an agreement or document be filed as an exhibit to the registration statement, please see that agreement or document for a complete description of these matters. You should read carefully both this the entire prospectus and any prospectus supplement together with and any related issuer free writing prospectus, as well as the documents incorporated by reference into this prospectus as described below under the heading “Information Incorporated by Reference.” The registration statement that contains this or any prospectus supplement or any related issuer free writing prospectus, including the exhibits to the registration statement before making an investment decision. You should also read and carefully consider the information incorporated by reference, provides additional information about us and our securities. That registration statement can be read at in the SEC website (xxx.xxx.xxx) or at the SEC public reference room, as discussed below under the heading documents we have referred you to in “Where You Can Find More Information” and “Incorporation of Certain Information by Reference.” You should rely only on Neither the delivery of this prospectus or any prospectus supplement or any issuer free writing prospectus nor any sale made hereunder shall under any circumstances imply that the information provided in the registration statement, this prospectus and contained or incorporated by reference herein or in any prospectus supplementsupplement or issuer free writing prospectus is correct as of any date subsequent to the date hereof or of such prospectus supplement or issuer free writing prospectus, including the information incorporated by reference. We have not authorized anyone to provide you with different informationas applicable. You should not assume that the information appearing in this prospectus, any prospectus supplement or any document incorporated by reference is accurate only as of the date of the applicable documents, regardless of the time of delivery of this prospectus or any supplement to this prospectus is accurate at any date other than the date indicated on the cover page of these documents or the filing date of any document incorporated by reference, regardless of its time of delivery. We are not making an offer to sell the securities in any jurisdiction where the offer or sale is not permitted. We may sell our securities to or through underwriters, initial purchasers, dealers or agents, directly to purchasers or through a combination of any of these methods of sale, as designated from time to time. We and our agents reserve the sole right to accept or reject in whole or in part any proposed purchase of our securities. An applicable prospectus supplement, which we will provide each time we offer the securities, will set forth the names of any underwriters, initial purchasers, dealers or agents involved in the sale of our securities, and any related fee, commission or discount arrangements. See “Plan of Distribution.” The terms “Axsome,” the “Company,” “our,” “us” and “we,” as used in this prospectus, refer to Axsome Therapeutics, Inc., unless we state otherwise or the context indicates otherwise. We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late stage candidates, AXS‑02 and AXS‑05, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE‑1 study, and a Phase 3 trial with AXS‑02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST‑1 study. We have also initiated a Phase 3 trial with AXS‑05 in treatment resistant depression, or TRD, which we refer to as the STRIDE‑1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders. Our first product candidate, AXS‑02 (disodium zoledronate tetrahydrate), is a potentially first-in-class, oral, targeted, non-opioid therapeutic for chronic pain. AXS‑02 is a potent inhibitor of osteoclasts, which are bone remodeling cells that break down bone tissue. We are initially developing AXS‑02 for the treatment of pain in the following three conditions: CRPS; knee OA associated with BMLs; and chronic low back pain, or CLBP, associated with type 1 or mixed type 1 and type 2 Xxxxx changes, or MCs. These conditions exhibit target lesions or specific pathology that we believe may be addressed by the mechanisms of action of AXS‑02, such as inhibition of osteoclast activity. These mechanisms may result in a reduction of pain in these conditions. We have successfully completed a Phase 1 trial of AXS‑02 to characterize the pharmacokinetics of zoledronic acid and its effects on markers of bone resorption after oral administration of AXS‑02. The results of our Phase 1 trial demonstrated that oral administration of AXS‑02 tablets resulted in rapid absorption of zoledronic acid, which is the active molecule in AXS‑02 and the free acid form of disodium zoledronate tetrahydrate, and substantial suppression of bone resorption markers, which are proteins indicative of bone tissue breakdown. We intend to seek U.S. Food and Drug Administration, or FDA, approval for AXS‑02 utilizing the 505(b)(2) regulatory development pathway. AXS‑02 has been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CRPS. Our second product candidate, AXS‑05, is an innovative fixed-dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway. We have one active program, AXS‑06, in preclinical development. We are developing AXS‑06 for the treatment of chronic pain disorders. Our principal executive offices are located at 00 Xxxxxxxx, 0xx Xxxxx, Xxx Xxxx, Xxx Xxxx 00000, and our telephone number is (212) 332‑3241. Our website address is xxx.xxxxxx.xxx. The information contained on our website is not incorporated by reference into this prospectus, and you should not consider any information contained on, or that can be accessed through, our website as part of this prospectus or in deciding whether to purchase our securities. Our filings with the SEC are posted on our website at xxx.xxxxxx.xxx. The information found on our website is not part business, financial condition, results of this or any other report we file with or furnish to the SEC. The public can also obtain copies of these filings by visiting the SEC’s Public Reference Room at 000 X Xxxxxx XX, Xxxxxxxxxx XX 00000, or by calling the SEC at 1‑800‑SEC‑0330 or by accessing the SEC’s website at xxx.xxx.xxxoperations and prospects may have changed since that date.