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PROSPECTUS SUPPLEMENT SUMMARY. This summary highlights selected information contained elsewhere in this prospectus supplement, the accompanying prospectus and in the documents we incorporate by reference. This summary does not contain all of the information you should consider before making an investment decision. You should read this entire prospectus supplement and the accompanying prospectus carefully, especially the risks of investing in our common stock discussed under “Risk Factors” beginning on page S-7 of this prospectus supplement, the “Risk Factors” section of our most recent Annual Report on Form 10- K, as may be updated by our subsequent Quarterly Reports on Form 10-Q and other filings we make with the SEC, along with our consolidated financial statements and notes to those consolidated financial statements and the other information incorporated by reference in this prospectus supplement and the accompanying prospectus and in our filings with the SEC. Company Overview At Edgewise, patients are at the core of everything we do. We recognize that for patients with rare and debilitating diseases, every day without an effective treatment is a day too late and we are driven by this urgency to evolve disease knowledge with an aim to develop novel precision medicines for severe and rare disorders driven by muscle dysfunction. Our intimate knowledge of muscle biology and biophysics along with our ability to identify and design muscle specific precision small molecules have enabled us to rapidly advance our lead product candidate into clinical development while advancing our preclinical pipeline. From this foundation, we continue to build a leading, global biopharmaceutical company focused on rare diseases involving muscle in order to develop transformative precision medicines to treat and possibly cure these disorders. In less than five years, we have matured into a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of innovative treatments for severe, rare muscle disorders for which there is significant unmet medical need. Guided by our holistic drug discovery approach to targeting the muscle as an organ, we have combined our foundational expertise in muscle biology and small molecule engineering to build our proprietary, muscle-focused drug discovery platform. Our platform utilizes custom-built high throughput and translatable systems that measure integrated muscle function in whole organ extracts to identify small molecule precision medicines regulating key proteins in muscle tissue, initially focused on addressing rare neuromuscular and cardiac diseases. Since our inception in 2017, our precision medicine muscle platform has generated several programs to address a variety of muscle disorders. We are advancing one clinical-stage program and two preclinical programs. Our lead product candidate, EDG-5506, is an orally administered allosteric, selective, fast myofiber (type II) myosin small molecule inhibitor designed to address the root cause of dystrophinopathies including Duchenne muscular dystrophy (DMD) and Xxxxxx muscular dystrophy (BMD). Both of these disorders are rare and often debilitating diseases, and we estimate that in the United States there are approximately 12,000 to 15,000 DMD patients and 4,000 to 5,000 BMD patients. As a selective fast myosin inhibitor, EDG-5506 presents a novel mechanism of action designed to selectively limit injurious stress caused by lack of dystrophin by moderating fast skeletal muscle myosin force development and thereby compensating for the absence of functional dystrophin. Our preclinical data with EDG-5506 in animal models of muscular dystrophy demonstrated that selective regulation of fast (type II) myofiber contraction protected muscle from damage, reduced systemic fibrosis and improved measures of muscle function including strength and ability to engage in physical activities, which we believe may provide evidence of a disease modifying effect. A unique observation from our preclinical work is that EDG-5506 led to pronounced prevention of cardiac fibrosis. This is a highly relevant finding, particularly if replicated in clinical observations, since cardiac myopathy is a major driver of mortality in both DMD and BMD. EDG-5506 was evaluated in a Phase 1 clinical trial designed to assess the safety, tolerability and pharmacokinetics (PK) of EDG-5506 in adult healthy volunteers (HVs) (Phase 1a) and in adults with BMD (Phase 1b). Our Phase 1a data in HVs demonstrated that EDG-5506 was generally well-tolerated and amenable to daily dosing. Our Phase 1b data in BMD patients demonstrated proof of concept by showing a significant reduction in key biomarkers of muscle damage. We believe EDG-5506 has potential therapeutic utility as either a standalone or combination therapy for patients suffering from rare muscular dystrophies, if approved. We also intend to develop two other muscle-focused precision medicines. Our second program, EDG-5440, is a next generation myosin ATPase modulator designed to target skeletal muscle in a specific set of rare neuromuscular diseases. Our third program, EDG-002, focuses on identification of novel mechanism cardiac modulators. We are initially pursuing a new target for inherited hypertrophic cardiomyopathy (HCM) in addition to exploring the potential of this novel mechanism across other cardiac disorders. Our preliminary preclinical studies offer evidence that our EDG-002 program has the potential to yield molecules that could become a new therapeutic option for the treatment of HCM as well as other cardiac disorders. We anticipate candidate selection of a novel cardiac modulator for inherited hypertrophic cardiomyopathy from our EDG-002 cardiac muscle program in the second half of 2022. We believe our programs also offer substantial opportunities for us to expand into related rare diseases for which there are limited or no approved treatments. We are currently focusing on the development of EDG-5506 and anticipate advancing our preclinical programs into the next stage of development in the near term. While EDG-5440 and EDG-002 are important preclinical programs to us, we have not needed to devote significant financial resources to these programs to date since they are still in preclinical development and have not yet advanced into clinical trials. Corporate Information We were incorporated in Delaware in May 2017. Our principal executive offices are located at 0000 Xxxxxxxx Xxx., Xxxxxxx, Xxxxxxxx 00000. Our telephone number is 000-000-0000. Our website address is xxx.xxxxxxxxxx.xxx. Information contained on, or that can be accessed through, our website or any website is not incorporated by reference into this prospectus and should not be considered to be part of this prospectus unless expressly noted. We may use our website (xxx.xxxxxxxxxx.xxx), press releases, public conference calls, public webcasts, Twitter and LinkedIn as means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. We also make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC in accordance with the Securities Exchange Act of 1934, as amended (Exchange Act). These include our Annual Reports on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8- K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act. We make this information available on or through our website free of charge as soon as reasonably practicable after we electronically file the information with, or furnish it to, the SEC. The SEC also maintains a website that contains our SEC filings. The address for the SEC website is xxx.xxx.xxx. We use the Edgewise Therapeutics logo and other marks as trademarks in the United States and other countries. This prospectus contains references to our trademarks and service marks and to those belonging to other entities. Solely for convenience, trademarks and trade names referred to in this prospectus, including logos, artwork and other visual displays, may appear without the TM symbol, but such references are not intended to indicate in any way that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entity. THE OFFERING Common stock offered by us: Common stock to be outstanding after this offering: Shares of our common stock having an aggregate offering price of up to $125,000,000. Up to 12,886,597 shares, assuming the sale of $125,000,000 of shares of our common stock at a price of $9.70 per share, which was the closing price of our common stock on the Nasdaq Global Select Market on March 31, 2022. The actual number of shares issued will vary depending on the sales price under this offering. In addition, as there is no minimum offering amount required as a condition to close this offering, the actual number of shares that may be sold is not determinable at this time. See “Dilution” beginning on page S- 11 of this prospectus supplement.

PROSPECTUS SUPPLEMENT SUMMARY. This summary description about us, our business and this offering highlights selected information contained elsewhere in this prospectus supplement, the accompanying supplement or incorporated in this prospectus and in the documents we incorporate supplement by reference. This summary does not contain all of the information you should consider before deciding to invest in our common stock. You should carefully read this entire prospectus supplement, the accompanying base prospectus and any free writing prospectus with respect to this offering filed by us with the SEC, including each of the documents incorporated herein or therein by reference, before making an investment decision. You Investors should read this entire prospectus supplement and carefully consider the accompanying prospectus carefully, especially the risks of investing in our common stock discussed information set forth under “Risk Factors” beginning on page S-7 of this prospectus supplement, S-6 and in the “Risk Factors” section of our most recent Annual Report on Form 10- K, as may be updated by our subsequent Quarterly Reports on Form 10-Q and other filings we make with the SEC, along with our consolidated financial statements and notes to those consolidated financial statements and the other information documents incorporated by reference in into this prospectus supplement and or the accompanying prospectus and in our filings with the SECbase prospectus. Company Overview At Edgewise, patients We are at the core of everything we do. We recognize that leader in pharmaceutically-produced transdermal cannabinoid therapies for patients with rare and debilitating diseases, every day without an effective treatment is a day too late and we are driven by this urgency to evolve disease knowledge with an aim to develop novel precision medicines for severe and near-rare disorders driven by muscle dysfunction. Our intimate knowledge of muscle biology and biophysics along with our ability to identify and design muscle specific precision small molecules have enabled us to rapidly advance our lead product candidate into clinical development while advancing our preclinical pipeline. From this foundation, we continue to build a leading, global biopharmaceutical company focused on rare diseases involving muscle in order to develop transformative precision medicines to treat and possibly cure these disorders. In less than five years, we have matured into a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of innovative treatments for severe, rare muscle disorders for which there is significant unmet medical need. Guided by our holistic drug discovery approach to targeting the muscle as an organ, we have combined our foundational expertise in muscle biology and small molecule engineering to build our proprietary, muscle-focused drug discovery platform. Our platform utilizes custom-built high throughput and translatable systems that measure integrated muscle function in whole organ extracts to identify small molecule precision medicines regulating key proteins in muscle tissue, initially focused on addressing rare neuromuscular and cardiac diseases. Since our inception in 2017, our precision medicine muscle platform has generated several programs to address a variety of muscle neuropsychiatric disorders. We are advancing one clinical-stage program committed to improving the lives of patients and two preclinical programs. Our lead product candidatetheir families living with severe, EDG-5506chronic health conditions including Fragile X syndrome, is an orally administered allostericor FXS, selectiveautism spectrum disorder, fast myofiber (type II) myosin small molecule inhibitor designed to address the root cause or ASD, 22q11.2 deletion syndrome, or 22q, and a heterogeneous group of dystrophinopathies including Duchenne muscular dystrophy (DMD) and Xxxxxx muscular dystrophy (BMD). Both of these disorders are rare and often debilitating diseasesultra-rare epilepsies known as developmental and epileptic encephalopathies, or DEE. Cannabinoids are a class of compounds derived from Cannabis plants. The two primary cannabinoids contained in Cannabis are cannabidiol and we estimate Tetrahydrocannabinol, or THC. Clinical and preclinical data suggest that cannabidiol has positive effects on treating behavioral symptoms of FXS, ASD, 22q and seizures in patients with epilepsy. We are currently developing Zygel, the United States there first and only pharmaceutically-produced cannabidiol formulated as a permeation-enhanced gel for transdermal delivery, which is patent protected through 2030. Five additional patents expiring in 2038 are approximately 12,000 directed to 15,000 DMD patients methods of use relating to Zygel, including methods of treating FXS and 4,000 ASD. In preclinical animal studies, Xxxxx’s permeation enhancer increased delivery of cannabidiol through the layers of the skin and into the circulatory system. These preclinical studies suggest increased bioavailability, consistent plasma levels and the avoidance of first-pass liver metabolism of cannabidiol when delivered transdermally. In addition, an in vitro study published in Cannabis and Cannabinoid Research in April 2016 demonstrated that cannabidiol is degraded to 5,000 BMD patientsTHC (the major psychoactive cannabinoid in Cannabis) in an acidic environment such as the stomach. As a selective fast myosin inhibitorresult, EDG-5506 presents we believe such degradation may lead to increased psychoactive effects if cannabidiol is delivered orally. These effects may be avoided with the transdermal delivery of Zygel, which maintains cannabidiol in a novel mechanism neutral pH. Zygel is being developed as a clear gel with once- or twice-daily dosing and is targeting treatment of action behavioral symptoms of FXS, ASD and 22q and the reduction of seizures in patients with DEE syndromes. We have been granted orphan drug designations from United States Food and Drug Administration, or FDA, for the use of cannabidiol for the treatment of FXS and for the treatment of 22q. In May 2019, we received Fast Track designation from the FDA for treatment of behavioral symptoms associated with FXS. The FDA’s Fast Track program is designed to selectively limit injurious stress caused facilitate the development of drugs intended to treat serious conditions and fill unmet medical needs and can lead to expedited review by lack the FDA in order to get new important drugs to the patient earlier. Our clinical program for Zygel includes clinical trials evaluating Zygel in the treatment of dystrophin behavioral symptoms of FXS, ASD and 22q and the reduction of seizures and the treatment of associated symptoms in patients with DEE syndromes. As of May 2021, the Zygel safety database across all clinical studies conducted by moderating fast skeletal muscle myosin force development us includes data from 906 volunteers and thereby compensating patients. Across these clinical studies, Zygel has been well-tolerated and consistent with previously reported data. CONNECT-FX Trial (FXS) In June 2020, we announced results of our pivotal CONNECT-FX clinical trial, a multi-national randomized, double-blind, placebo-controlled, 14- week study designed to assess the efficacy and safety of Zygel in children and adolescents ages three through 17 years who have full mutation of the FMR1 gene. While Xxxxx did not achieve statistical significance versus placebo in the primary endpoint of improvement in the Social Avoidance subscale of the Aberrant Behavior Checklist – Community FXS (ABC-CFXS), a pre-planned ad hoc analysis of the most severely impacted patients in the trial, as defined by patients having at least 90% methylation (“highly methylated”) of the impacted FMR1 gene, demonstrated that those patients receiving Zygel achieved statistical significance in the primary endpoint of improvement at 12 weeks of treatment in the Social Avoidance subscale of the ABC-CFXS compared to placebo. RECONNECT Trial (FXS) In May 2021, following guidance received from the FDA regarding the regulatory path forward for Zygel, we announced that we will be conducting a pivotal, multi-national, confirmatory Phase 3 trial of Zygel in patients with FXS. The trial, which will be called RECONNECT (A Randomized, Double-Blind, Placebo-Controlled, Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome), is designed to evaluate the efficacy and safety of Zygel in children and adolescents with FXS. We believe that the results, if positive, from RECONNECT will be sufficient to support the submission of a New Drug Application for Zygel in patients with FXS. The RECONNECT trial will be an 18-week trial which will enroll approximately 200 children and adolescents of which approximately 160 patients will have complete (100%) methylation of their FMR1 gene and approximately 40 patients will have partial methylation of their FMR1 gene. The primary endpoint for the absence trial will be the change in the Aberrant Behavior Checklist-Community FXS Specific (ABC-CFXS) Social Avoidance subscale in patients who have complete methylation of functional dystrophintheir FMR1 gene. Our preclinical data with EDG-5506 in animal models All patients, including the cohort of muscular dystrophy demonstrated that selective regulation of fast (type II) myofiber contraction protected muscle from damagepartially methylated patients, reduced systemic fibrosis and improved measures of muscle function including strength and ability to engage in physical activities, which we believe may provide evidence of a disease modifying effect. A unique observation from our preclinical work is that EDG-5506 led to pronounced prevention of cardiac fibrosis. This is a highly relevant finding, particularly if replicated in clinical observations, since cardiac myopathy is a major driver of mortality in both DMD and BMD. EDG-5506 was evaluated will be included in a key secondary endpoint analysis. We expect to initiate the RECONNECT trial in the third quarter of 2021. All patients will be eligible to enroll in our ongoing open-label extension after completing dosing in this clinical trial. Phase 1 2 BRIGHT Trial (ASD) In May 2020, we reported positive top-line results of the Phase 2 BRIGHT clinical trial, a 14-week, open-label clinical trial designed to assess the safety, tolerability and pharmacokinetics (PK) efficacy of EDG-5506 in adult healthy volunteers (HVs) (Phase 1a) and in adults with BMD (Phase 1b). Our Phase 1a data in HVs demonstrated that EDG-5506 was generally well-tolerated and amenable to daily dosing. Our Phase 1b data in BMD patients demonstrated proof of concept by showing a significant reduction in key biomarkers of muscle damage. We believe EDG-5506 has potential therapeutic utility as either a standalone or combination therapy for patients suffering from rare muscular dystrophies, if approved. We also intend to develop two other muscle-focused precision medicines. Our second program, EDG-5440, is a next generation myosin ATPase modulator designed to target skeletal muscle in a specific set of rare neuromuscular diseases. Our third program, EDG-002, focuses on identification of novel mechanism cardiac modulators. We are initially pursuing a new target for inherited hypertrophic cardiomyopathy (HCM) in addition to exploring the potential of this novel mechanism across other cardiac disorders. Our preliminary preclinical studies offer evidence that our EDG-002 program has the potential to yield molecules that could become a new therapeutic option Zygel for the treatment of HCM as well as pediatric and adolescent patients with ASD. Patients treated with Zygel demonstrated statistically significant improvement at week 14 compared to baseline for each ABC-C subscale (Irritability, Inappropriate Speech, Stereotypy, Social Withdrawal, and Hyperactivity). The results of the other cardiac disorders. We anticipate candidate selection of a novel cardiac modulator for inherited hypertrophic cardiomyopathy from our EDG-002 cardiac muscle program efficacy assessments were consistent with the results demonstrated in the second ABC-C. We expect to discuss a path forward with the FDA in the first half of 2022. We believe our programs also offer substantial opportunities for us to expand into related rare diseases for which there are limited or no approved treatments. We are currently focusing on the development of EDG-5506 and anticipate advancing our preclinical programs into the next stage of development in the near term. While EDG-5440 and EDG-002 are important preclinical programs to us, we have not needed to devote significant financial resources to these programs to date since they are still in preclinical development and have not yet advanced into clinical trials. Corporate Information We were incorporated in Delaware in May 2017. Our principal executive offices are located at 0000 Xxxxxxxx Xxx2021., Xxxxxxx, Xxxxxxxx 00000. Our telephone number is 000-000-0000. Our website address is xxx.xxxxxxxxxx.xxx. Information contained on, or that can be accessed through, our website or any website is not incorporated by reference into this prospectus and should not be considered to be part of this prospectus unless expressly noted. We may use our website (xxx.xxxxxxxxxx.xxx), press releases, public conference calls, public webcasts, Twitter and LinkedIn as means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. We also make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC in accordance with the Securities Exchange Act of 1934, as amended (Exchange Act). These include our Annual Reports on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8- K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act. We make this information available on or through our website free of charge as soon as reasonably practicable after we electronically file the information with, or furnish it to, the SEC. The SEC also maintains a website that contains our SEC filings. The address for the SEC website is xxx.xxx.xxx. We use the Edgewise Therapeutics logo and other marks as trademarks in the United States and other countries. This prospectus contains references to our trademarks and service marks and to those belonging to other entities. Solely for convenience, trademarks and trade names referred to in this prospectus, including logos, artwork and other visual displays, may appear without the TM symbol, but such references are not intended to indicate in any way that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entity. THE OFFERING Common stock offered by us: Common stock to be outstanding after this offering: Shares of our common stock having an aggregate offering price of up to $125,000,000. Up to 12,886,597 shares, assuming the sale of $125,000,000 of shares of our common stock at a price of $9.70 per share, which was the closing price of our common stock on the Nasdaq Global Select Market on March 31, 2022. The actual number of shares issued will vary depending on the sales price under this offering. In addition, as there is no minimum offering amount required as a condition to close this offering, the actual number of shares that may be sold is not determinable at this time. See “Dilution” beginning on page S- 11 of this prospectus supplement.

PROSPECTUS SUPPLEMENT SUMMARY. This summary highlights certain information about us and selected information contained elsewhere in or incorporated by reference into this prospectus supplement, the accompanying prospectus and in the documents we incorporate by reference. This summary is not complete and does not contain all of the information that you should consider before making an investment decision. You should read this entire prospectus supplement and the accompanying prospectus carefully, especially the risks of investing deciding to invest in our common stock discussed under “Risk Factors” beginning on page S-7 stock. For a more complete understanding of our Company, we encourage you to read and consider carefully the more detailed information in this prospectus supplement, including the “Risk Factors” section of our most recent Annual Report on Form 10- K, as may be updated by our subsequent Quarterly Reports on Form 10-Q and other filings we make with the SEC, along with our consolidated financial statements and notes to those consolidated financial statements and the other information incorporated by reference in this prospectus supplement and the accompanying information under the heading “Risk Factors” in this prospectus and in our filings with the SECsupplement, before making an investment decision. Company Overview At Edgewise, patients We are at the core of everything we do. We recognize that for patients with rare and debilitating diseases, every day without an effective treatment is a day too late and we are driven by this urgency to evolve disease knowledge with an aim to develop novel precision medicines for severe and rare disorders driven by muscle dysfunction. Our intimate knowledge of muscle biology and biophysics along with our ability to identify and design muscle specific precision small molecules have enabled us to rapidly advance our lead product candidate into clinical development while advancing our preclinical pipeline. From this foundation, we continue to build a leading, global biopharmaceutical company focused on rare diseases involving muscle in order to develop transformative precision medicines to treat and possibly cure these disorders. In less than five years, we have matured into a clinical-stage biopharmaceutical pharmaceutical company focused on the discovery, development and commercialization of innovative treatments and differentiated prescription therapeutics for severe, rare muscle disorders for which there is significant unmet medical need. Guided by debilitating skin diseases with a focus on our holistic drug discovery approach to targeting the muscle as an organ, we have combined our foundational expertise in muscle biology and small molecule engineering to build our proprietary, muscle-focused drug discovery platform. Our platform utilizes custom-built high throughput and translatable systems that measure integrated muscle function in whole organ extracts to identify small molecule precision medicines regulating key proteins in muscle tissue, initially focused on addressing rare neuromuscular and cardiac diseases. Since our inception in 2017, our precision medicine muscle platform has generated several programs to address a variety of muscle disorders. We are advancing one clinical-stage program and two preclinical programs. Our lead product candidate, EDG-5506, is an orally administered allosteric, selective, fast myofiber (type II) myosin small molecule inhibitor designed to address the root cause of dystrophinopathies including Duchenne muscular dystrophy (DMD) and Xxxxxx muscular dystrophy (BMD). Both of these disorders are rare and often debilitating diseases, and we estimate that in the United States there are approximately 12,000 to 15,000 DMD patients and 4,000 to 5,000 BMD patients. As a selective fast myosin inhibitor, EDG-5506 presents a novel mechanism of action designed to selectively limit injurious stress caused by lack of dystrophin by moderating fast skeletal muscle myosin force development and thereby compensating for the absence of functional dystrophin. Our preclinical data with EDG-5506 in animal models of muscular dystrophy demonstrated that selective regulation of fast (type II) myofiber contraction protected muscle from damage, reduced systemic fibrosis and improved measures of muscle function including strength and ability to engage in physical activities, which we believe may provide evidence of a disease modifying effect. A unique observation from our preclinical work is that EDG-5506 led to pronounced prevention of cardiac fibrosis. This is a highly relevant finding, particularly if replicated in clinical observations, since cardiac myopathy is a major driver of mortality in both DMD and BMD. EDG-5506 was evaluated in a Phase 1 clinical trial designed to assess the safety, tolerability and pharmacokinetics (PK) of EDG-5506 in adult healthy volunteers (HVs) (Phase 1a) and in adults with BMD (Phase 1b). Our Phase 1a data in HVs demonstrated that EDG-5506 was generally well-tolerated and amenable to daily dosing. Our Phase 1b data in BMD patients demonstrated proof of concept by showing a significant reduction in key biomarkers of muscle damage. We believe EDG-5506 has potential therapeutic utility as either a standalone or combination therapy for patients suffering from rare muscular dystrophies, if approved. We also intend to develop two other muscle-focused precision medicines. Our second program, EDG-5440, is a next generation myosin ATPase modulator designed to target skeletal muscle in a specific set of rare neuromuscular diseases. Our third program, EDG-002, focuses on identification of novel mechanism cardiac modulators. We are initially pursuing a new target for inherited hypertrophic cardiomyopathy (HCM) in addition to exploring the potential of this novel mechanism across other cardiac disorders. Our preliminary preclinical studies offer evidence that our EDG-002 program has the potential to yield molecules that could become a new therapeutic option asset for the treatment of HCM hyperhidrosis. Our executive management team and board of directors bring extensive experience in product development and global commercialization, having served in leadership roles at large global pharmaceutical companies and biotechs that have developed and/or launched successful products, including several that were first-in-class and/or achieved iconic status, such as well as other cardiac disordersCialis®, Taltz®, Gemzar®, Prozac®, Cymbalta®, and Juvederm®. Our pivotal Phase 3 clinical-stage investigational product candidate, sofpironium bromide, is a new chemical entity that belongs to a class of medications called anticholinergics. Anticholinergics block the action of acetylcholine, a chemical that transmits signals within the nervous system that are responsible for a range of bodily functions, including activation of the sweat glands. Sofpironium bromide was retrometabolically designed. Retrometabolic drugs are designed to exert their action locally and are potentially rapidly metabolized to a less active form once absorbed into the blood. This proposed mechanism of action may allow for potentially highly effective doses to be used while limiting systemic side effects. We anticipate candidate selection intend to develop sofpironium bromide as a potential best-in-class, self-administered, once daily, topical therapy for the treatment of primary axillary (underarm) hyperhidrosis. Hyperhidrosis is a novel cardiac modulator life-altering condition of sweating beyond what is physiologically necessary for inherited hypertrophic cardiomyopathy thermoregulation of the body. It is believed to be caused by an overactive cholinergic response of the sweat glands and affects an estimated 15.3 million, or 4.8%, of the U.S. population. According to a 2016 update on the prevalence and severity of hyperhidrosis in the U.S. by Xxxxxxxxx et al., axillary hyperhidrosis, which is the targeted first potential indication for sofpironium bromide, is the most common occurrence of hyperhidrosis, affecting approximately 65% of patients, or an estimated 10 million individuals, in the U.S. We are currently developing sofpironium bromide in the U.S. for the treatment of primary axillary hyperhidrosis. In the fourth quarter of 2020, we initiated the pivotal Phase 3 program for sofpironium bromide, which is comprised of two pivotal Phase 3 clinical trials (Cardigan I and II) to evaluate the safety and efficacy of sofpironium bromide gel, 15% compared to vehicle (placebo) in approximately 350 subjects (per trial) aged nine years or older with primary axillary hyperhidrosis in the U.S. We expect to report topline results from our EDG-002 cardiac muscle the pivotal Phase 3 program in the second half fourth quarter of 20222021. If successful, the results from these studies are expected to form the basis of a prospective new drug application in the U.S. with the U.S. Food and Drug Administration for the treatment of primary axillary hyperhidrosis. Our Corporate Information Our corporate headquarters are located in Boulder, Colorado, where we occupy facilities totaling approximately 3,038 square feet under a lease agreement that expires in October 2021 and includes two additional three-year renewal options. We believe use our programs also offer substantial opportunities current facilities primarily for us to expand into related rare diseases for which there are limited or no approved treatments. We are currently focusing on the development of EDG-5506 research and anticipate advancing our preclinical programs into the next stage of development in the near term. While EDG-5440 and EDG-002 are important preclinical programs to us, we have not needed to devote significant financial resources to these programs to date since they are still in preclinical development and have not yet advanced into clinical trials. Corporate Information We were incorporated in Delaware in May 2017. Our principal executive offices are located at 0000 Xxxxxxxx Xxx., Xxxxxxx, Xxxxxxxx 00000general and administrative personnel. Our telephone number is (000-) 000-0000. Our , and our website address is xxx.xxxxxxxxxx.xxxxxxxx://xxx.xxxxxxxxxxx.xxx. Information contained on, or that can be accessed through, on our website or any website is not a part of this prospectus supplement or the accompanying prospectus, you should not consider information contained on our website in deciding whether to purchase our securities and the inclusion of our website address in this prospectus supplement and the accompanying prospectus is an inactive textual reference only. This prospectus supplement and the accompanying prospectus, including the documents incorporated by reference into this prospectus supplement and should not be considered to be part of this prospectus unless expressly noted. We may use our website (xxx.xxxxxxxxxx.xxx)the accompanying prospectus, press releases, public conference calls, public webcasts, Twitter and LinkedIn as means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. We also make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC in accordance with the Securities Exchange Act of 1934, as amended (Exchange Act). These include our Annual Reports on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8- K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act. We make this information available on or through our website free of charge as soon as reasonably practicable after we electronically file the information with, or furnish it to, the SEC. The SEC also maintains a website that contains our SEC filings. The address for the SEC website is xxx.xxx.xxx. We use the Edgewise Therapeutics logo and other marks as trademarks in the United States and other countries. This prospectus contains contain references to our trademarks and service marks and to those trademarks belonging to other entities. Solely for convenience, trademarks and trade names referred to in this prospectus supplement and the accompanying prospectus, including the documents incorporated by reference into this prospectus supplement and the accompanying prospectus, including logos, artwork artwork, and other visual displays, may appear without the ® or TM symbolsymbols, but such references are not intended to indicate indicate, in any way way, that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other entitiescompanies’ trade names, names or trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entitycompany. THE OFFERING Common stock offered by us: Common stock to be outstanding after this offering: us Shares of our common stock having an aggregate offering price of up to $125,000,00050.0 million. Up Manner of offering “At the market offering” that may be made from time to 12,886,597 sharestime through the Agents, assuming as our sales agents. See “Plan of Distribution” in this prospectus supplement for a more complete description of the sale manner of $125,000,000 offering. Use of shares proceeds We intend to use the net proceeds of our common stock at a price of $9.70 per sharethis offering, if any, for general corporate purposes, which was may include, but not be limited to, working capital, capital expenditures, the closing price repayment or refinancing of our common stock on indebtedness and other investments or business development opportunities. See “Use of Proceeds” in this prospectus supplement for a more complete description of the Nasdaq Global Select Market on March 31, 2022. The actual number intended use of shares issued will vary depending on the sales price under proceeds from this offering. In addition, as there is no minimum offering amount required as a condition to close this offering, Risk factors Investing in our securities involves significant risks. Please read the actual number of shares that may be sold is not determinable at this time. See information contained in or incorporated by reference under the heading “DilutionRisk Factors” beginning on page S- 11 S-5 of this prospectus supplement., and under similar headings in other documents filed after the date hereof and incorporated by reference into this prospectus supplement and the accompanying prospectus. Nasdaq Capital Market symbol BBI

PROSPECTUS SUPPLEMENT SUMMARY. This summary highlights certain information about this offering and selected information contained elsewhere in or incorporated by reference into this prospectus supplement, supplement and the accompanying prospectus and in the documents we incorporate by referenceprospectus. This summary is not complete and does not contain all of the information that you should consider before making an investment decisiondeciding whether to invest in our shares of common stock. You should carefully read this entire prospectus supplement and accompanying prospectus, including the accompanying prospectus carefullyinformation incorporated herein and therein, especially the risks of investing in our common stock discussed under “Risk Factors” beginning on page S-7 of this prospectus supplement, including the “Risk Factors” section of our most recent Annual Report on Form 10- K, as may be updated by our subsequent Quarterly Reports on Form 10-Q and other filings we make with the SEC, along with our consolidated financial statements and notes to those consolidated financial statements and the other information incorporated by reference contained in this prospectus supplement and the accompanying other documents incorporated by reference into this prospectus and in our filings with supplement. Overview Relmada Therapeutics, Inc. (“Relmada,” the SEC. Company Overview At Edgewise, patients are at the core of everything we do. We recognize that for patients with rare and debilitating diseases, every day without an effective treatment “Company,” “we,” “us” or “our”) is a day too late and we are driven by this urgency to evolve disease knowledge with an aim to develop novel precision medicines for severe and rare disorders driven by muscle dysfunction. Our intimate knowledge of muscle biology and biophysics along with our ability to identify and design muscle specific precision small molecules have enabled us to rapidly advance our lead product candidate into clinical development while advancing our preclinical pipeline. From this foundation, we continue to build a leading, global biopharmaceutical company focused on rare diseases involving muscle in order to develop transformative precision medicines to treat and possibly cure these disorders. In less than five years, we have matured into a clinical-stage biopharmaceutical biotechnology company focused on the discoverydevelopment of d- methadone (“dextromethadone” or “REL-1017”), development and commercialization an N-methyl-D-aspartate (“NMDA”) receptor antagonist. d-methadone is a new chemical entity (“NCE”) that potentially addresses areas of innovative treatments for severe, rare muscle disorders for which there is significant high unmet medical needneed in the treatment of central nervous system (“CNS”) diseases and other disorders. Guided by our holistic drug discovery approach to targeting NMDA receptors are present in many parts of the muscle central nervous system and play important roles in regulating neuronal activity. We believe that dextromethadone acting as an organ, we NMDA receptor antagonist can have combined our foundational expertise potential applications in muscle biology a number of disease indications which mitigates risk and small molecule engineering to build our proprietary, muscle-focused drug discovery platform. Our platform utilizes custom-built high throughput and translatable systems that measure integrated muscle function in whole organ extracts to identify small molecule precision medicines regulating key proteins in muscle tissue, initially focused on addressing rare neuromuscular and cardiac diseases. Since our inception in 2017, our precision medicine muscle platform has generated several programs to address a variety of muscle disorders. We are advancing one clinical-stage program and two preclinical programsoffers significant upside. Our lead product candidate, EDG-5506d-methadone, is an orally administered allostericNCE being developed as a rapidly acting, selective, fast myofiber (type II) myosin small molecule inhibitor designed to address the root cause of dystrophinopathies including Duchenne muscular dystrophy (DMD) and Xxxxxx muscular dystrophy (BMD). Both of these disorders are rare and often debilitating diseases, and we estimate that in the United States there are approximately 12,000 to 15,000 DMD patients and 4,000 to 5,000 BMD patients. As a selective fast myosin inhibitor, EDG-5506 presents a novel mechanism of action designed to selectively limit injurious stress caused by lack of dystrophin by moderating fast skeletal muscle myosin force development and thereby compensating sustained effect oral agent for the absence treatment of functional dystrophindepression and other potential indications. Our preclinical We have previously completed Phase 1 single and multiple ascending dose studies and on October 15, 2019 we reported top-line data with EDG-5506 in animal models of muscular dystrophy demonstrated that selective regulation of fast (type II) myofiber contraction protected muscle from damage, reduced systemic fibrosis and improved measures of muscle function including strength and ability to engage in physical activities, which we believe may provide evidence of a disease modifying effect. A unique observation from our preclinical work is that EDG-5506 led to pronounced prevention of cardiac fibrosisstudy REL- 1017-202. This is was a highly relevant findingdouble-blind, particularly if replicated in clinical observations, since cardiac myopathy is a major driver of mortality in both DMD and BMD. EDG-5506 was evaluated in a placebo-controlled Phase 1 2 clinical trial designed to assess evaluating the safety, tolerability and pharmacokinetics efficacy of two oral doses of REL-1017, 25 mg once a day and 50 mg once a day, as an adjunctive treatment in patients with major depressive disorder (PK“MDD”) who experienced an inadequate response to 1 to 3 adequate antidepressant treatments with an antidepressant medication. In the REL-1017-202 study, 62 subjects, average age 49.2 years, with an average Xxxxxxxx Depression Rating Scale score of EDG-5506 in adult healthy volunteers 25.3 and an average Xxxxxxxxxx- Xxxxxx Depression Rating Scale (HVs“MADRS”) score of 34.0 (Phase 1a) and in adults with BMD (Phase 1bsevere depression), were randomized. Our Phase 1a data in HVs demonstrated that EDG-5506 was generally well-tolerated and amenable Other demographic characteristics were balanced across all arms. After an initial screening period, subjects were randomized to daily dosing. Our Phase 1b data in BMD patients demonstrated proof one of concept by showing a significant reduction in key biomarkers of muscle damage. We believe EDG-5506 has potential therapeutic utility as either a standalone three arms: placebo, REL-1017 25 mg or combination therapy for patients suffering from rare muscular dystrophiesREL-1017 50 mg, if approved. We also intend to develop two other muscle-focused precision medicines. Our second program, EDG-5440, is a next generation myosin ATPase modulator designed to target skeletal muscle in a specific set of rare neuromuscular diseases. Our third program, EDG-002, focuses on identification of novel mechanism cardiac modulators. We are initially pursuing a new target for inherited hypertrophic cardiomyopathy (HCM) in addition to exploring the potential of this novel mechanism across other cardiac disordersstable background antidepressant therapy. Our preliminary preclinical studies offer evidence that our EDG-002 program has the potential to yield molecules that could become a new therapeutic option for the treatment of HCM as well as other cardiac disorders. We anticipate candidate selection of a novel cardiac modulator for inherited hypertrophic cardiomyopathy from our EDG-002 cardiac muscle program Subjects in the second half REL-1017 treatment arms received one loading dose of 2022either 75 mg (25 mg arm) or 100 mg (50 mg arm) of REL-1017. Subjects were treated inpatient for 7 days and discharged home at Day 9. They returned for follow-up visits at Day 14 and Day 21. Efficacy was measured on Days 2, 4 and 7 in the dosing period and on Day 14, one week after treatment discontinuation. 61 subjects received all treatment doses and were included in the per-protocol population (PPP) treatment analysis; 57 subjects completed all visits. All 62 randomized subjects were part of the intention-to-treat (ITT) analysis. No differences were observed between the ITT and PPP analyses and results. Key findings: We believe our programs also offer substantial opportunities for us observed that subjects in both the REL-1017 25 mg and 50 mg treatment groups experienced statistically significant improvement on all efficacy measures tested as compared to expand into related rare diseases for which there are limited or no approved treatmentssubjects in the placebo group, including: the MADRS; the Clinical Global Impression – Severity (CGI-S) scale; the Clinical Global Impression – Improvement (CGI-I) scale; and the Symptoms of Depression Questionnaire (SDQ). We are currently focusing Improvements on the development MADRS endpoint appeared on Day 4 in both REL-1017 dose groups and continued through Day 7 and Day 14, seven days after treatment discontinuation, with P values< 0.03 and large effect sizes (a measure of EDG-5506 quantifying the difference between two groups), ranging from 0.7 to 1.0. Similar findings emerged from the CGI-S and anticipate advancing our preclinical programs into CGI-I scales. LS = Least Squares; d = Xxxxx’x effect size The study also confirmed the next stage favorable tolerability profile of development REL-1017, which was also observed in the near termPhase 1 studies. While EDG-5440 Subjects experienced mild and EDG-002 are important preclinical programs to usmoderate adverse events (AEs), we have not needed to devote and no serious adverse events, without significant financial resources to these programs to date since they are still differences between placebo and treatment groups. The AEs observed in preclinical development the Phase 2 clinical study were of the same nature as those observed in the Phase 1 clinical studies in d-Methadone, and have not yet advanced into clinical trialsthere was no evidence of either treatment induced psychotomimetic and dissociative AEs or withdrawal signs and symptoms upon treatment discontinuation. Corporate Information We were incorporated in Delaware in May 2017. Our principal executive offices are located at 0000 Xxxxxxxx Xxx.000 Xxxxx Xxxxxx, Xxxxxxx00xx Xxxxx, Xxxxxxxx 00000. Our Xxx Xxxx, XX 00000 and our telephone number is +0-000-000-0000. Our website address is xxx.xxxxxxxxxx.xxxxxx.xxxxxxx.xxx. Information The information contained on, therein or that can connected thereto shall not be accessed through, deemed to be incorporated into this prospectus or the registration statement of which it forms a part. The information on our website or any website is not part of this prospectus. For additional information about us, please refer to other documents we have filed with the SEC and that are incorporated by reference into this prospectus and should not be considered to be part of this prospectus unless expressly noted. We may use our website (xxx.xxxxxxxxxx.xxx), press releases, public conference calls, public webcasts, Twitter and LinkedIn as means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. We also make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC in accordance with the Securities Exchange Act of 1934prospectus, as amended (Exchange Act). These include our Annual Reports on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8- K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) listed under the heading “Incorporation of the Exchange Act. We make this information available on or through our website free of charge as soon as reasonably practicable after we electronically file the information with, or furnish it to, the SEC. The SEC also maintains a website that contains our SEC filings. The address for the SEC website is xxx.xxx.xxx. We use the Edgewise Therapeutics logo and other marks as trademarks in the United States and other countries. This prospectus contains references to our trademarks and service marks and to those belonging to other entities. Solely for convenience, trademarks and trade names referred to in this prospectus, including logos, artwork and other visual displays, may appear without the TM symbol, but such references are not intended to indicate in any way that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entity. Certain Information by Reference.” THE OFFERING Common stock offered by us: Common stock to be outstanding after this offering: us Shares of our common stock having an aggregate offering price of up to $125,000,00075,000,000. Common stock to be outstanding after this offering Up to 12,886,597 shares16,771,276 shares of common stock (as more fully described in the notes following this table), assuming the sale sales of $125,000,000 of 1,830,608 shares of our common stock in this offering at a an offering price of $9.70 40.97 per share, which was the closing last reported sale price of our common stock on the Nasdaq Global Select Market on March 31May 13, 20222020. The actual number of shares issued will vary depending on the sales price under this offering. In addition, as there is no minimum offering amount required as a condition to close this Plan of Distribution “At the market offering, the actual number of shares ” that may be sold is not determinable at this timemade from time to time through our sales agent, Jefferies. See the section entitled Use of Proceeds We intend to use the net proceeds from this offering for working capital and general corporate purposes, which includes, without limitation, clinical studies required to gain regulatory approvals, implementation of adequate systems and controls to allow for regulatory approvals, further development of our product candidates, investing in or acquiring companies that are synergistic with or complimentary to our technologies, licensing activities related to our current and future product candidates and working capital, the development of emerging technologies, investing in or acquiring companies that are developing emerging technologies, licensing activities, or the acquisition of other businesses. See the section titled “DilutionUse of Proceeds” on page S-6 of this prospectus supplement. Risk Factors See “Risk Factors” beginning on page S- 11 S-4 of this prospectus supplementsupplement and in the documents incorporated by reference herein for a discussion of factors you should consider carefully before investing in our common stock. Nasdaq symbol “RLMD” The number of shares of our common stock to be outstanding after this offering is based on 14,940,668 shares of our common stock outstanding as of March 31, 2020, and excludes: ● 834,719 shares of our common stock issuable upon the exercise of stock options outstanding at March 31, 2020, at a weighted average exercise price of $9.61 per share; ● 3,160,715 shares of our common stock issuable upon the exercise of warrants outstanding at March 31, 2020, at a weighted average exercise price of $6.79 per share (of which warrants to purchase approximately 177,700 shares have been exercised since March 31, 2020, and such shares are outstanding); and ● 1,155,086 additional shares of our common stock available for future issuance as of March 31, 2020, under our 2014 Stock Option and Equity Incentive Plan.

PROSPECTUS SUPPLEMENT SUMMARY. This summary highlights selected information contained elsewhere in this prospectus supplement, the accompanying prospectus or incorporated by reference herein and in the documents we incorporate by reference. This summary does not contain all of the information that you should need to consider before in making an your investment decision. You should carefully read this the entire prospectus supplement and the accompanying prospectus carefullyprospectus, especially including the risks of investing in our common stock securities discussed under the heading “Risk Factors” beginning on page S-7 of contained in this prospectus supplement, the “Risk Factors” section of our most recent Annual Report on Form 10- K, as may be updated by our subsequent Quarterly Reports on Form 10-Q and other filings we make with the SEC, along with our consolidated financial statements and notes to those consolidated financial statements and the other information incorporated by reference in this prospectus supplement and the accompanying prospectus and in our filings with the SEC. Company Overview At Edgewise, patients are at the core of everything we do. We recognize that for patients with rare and debilitating diseases, every day without an effective treatment is a day too late and we are driven by this urgency to evolve disease knowledge with an aim to develop novel precision medicines for severe and rare disorders driven by muscle dysfunction. Our intimate knowledge of muscle biology and biophysics along with our ability to identify and design muscle specific precision small molecules have enabled us to rapidly advance our lead product candidate into clinical development while advancing our preclinical pipeline. From this foundation, we continue to build a leading, global biopharmaceutical company focused on rare diseases involving muscle in order to develop transformative precision medicines to treat and possibly cure these disorders. In less than five years, we have matured into a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of innovative treatments for severe, rare muscle disorders for which there is significant unmet medical need. Guided by our holistic drug discovery approach to targeting the muscle as an organ, we have combined our foundational expertise in muscle biology and small molecule engineering to build our proprietary, muscle-focused drug discovery platform. Our platform utilizes custom-built high throughput and translatable systems that measure integrated muscle function in whole organ extracts to identify small molecule precision medicines regulating key proteins in muscle tissue, initially focused on addressing rare neuromuscular and cardiac diseases. Since our inception in 2017, our precision medicine muscle platform has generated several programs to address a variety of muscle disorders. We are advancing one clinical-stage program and two preclinical programs. Our lead product candidate, EDG-5506, is an orally administered allosteric, selective, fast myofiber (type II) myosin small molecule inhibitor designed to address the root cause of dystrophinopathies including Duchenne muscular dystrophy (DMD) and Xxxxxx muscular dystrophy (BMD). Both of these disorders are rare and often debilitating diseasesany related free writing prospectus, and we estimate that under similar headings in the United States there other documents that are approximately 12,000 to 15,000 DMD patients and 4,000 to 5,000 BMD patients. As a selective fast myosin inhibitor, EDG-5506 presents a novel mechanism of action designed to selectively limit injurious stress caused by lack of dystrophin by moderating fast skeletal muscle myosin force development and thereby compensating for the absence of functional dystrophin. Our preclinical data with EDG-5506 in animal models of muscular dystrophy demonstrated that selective regulation of fast (type II) myofiber contraction protected muscle from damage, reduced systemic fibrosis and improved measures of muscle function including strength and ability to engage in physical activities, which we believe may provide evidence of a disease modifying effect. A unique observation from our preclinical work is that EDG-5506 led to pronounced prevention of cardiac fibrosis. This is a highly relevant finding, particularly if replicated in clinical observations, since cardiac myopathy is a major driver of mortality in both DMD and BMD. EDG-5506 was evaluated in a Phase 1 clinical trial designed to assess the safety, tolerability and pharmacokinetics (PK) of EDG-5506 in adult healthy volunteers (HVs) (Phase 1a) and in adults with BMD (Phase 1b). Our Phase 1a data in HVs demonstrated that EDG-5506 was generally well-tolerated and amenable to daily dosing. Our Phase 1b data in BMD patients demonstrated proof of concept by showing a significant reduction in key biomarkers of muscle damage. We believe EDG-5506 has potential therapeutic utility as either a standalone or combination therapy for patients suffering from rare muscular dystrophies, if approved. We also intend to develop two other muscle-focused precision medicines. Our second program, EDG-5440, is a next generation myosin ATPase modulator designed to target skeletal muscle in a specific set of rare neuromuscular diseases. Our third program, EDG-002, focuses on identification of novel mechanism cardiac modulators. We are initially pursuing a new target for inherited hypertrophic cardiomyopathy (HCM) in addition to exploring the potential of this novel mechanism across other cardiac disorders. Our preliminary preclinical studies offer evidence that our EDG-002 program has the potential to yield molecules that could become a new therapeutic option for the treatment of HCM as well as other cardiac disorders. We anticipate candidate selection of a novel cardiac modulator for inherited hypertrophic cardiomyopathy from our EDG-002 cardiac muscle program in the second half of 2022. We believe our programs also offer substantial opportunities for us to expand into related rare diseases for which there are limited or no approved treatments. We are currently focusing on the development of EDG-5506 and anticipate advancing our preclinical programs into the next stage of development in the near term. While EDG-5440 and EDG-002 are important preclinical programs to us, we have not needed to devote significant financial resources to these programs to date since they are still in preclinical development and have not yet advanced into clinical trials. Corporate Information We were incorporated in Delaware in May 2017. Our principal executive offices are located at 0000 Xxxxxxxx Xxx., Xxxxxxx, Xxxxxxxx 00000. Our telephone number is 000-000-0000. Our website address is xxx.xxxxxxxxxx.xxx. Information contained on, or that can be accessed through, our website or any website is not incorporated by reference into this prospectus and supplement. You should not be considered to be part of this prospectus unless expressly noted. We may use our website (xxx.xxxxxxxxxx.xxx), press releases, public conference calls, public webcasts, Twitter and LinkedIn as means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. We also make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC in accordance with the Securities Exchange Act of 1934, as amended (Exchange Act). These include our Annual Reports on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8- K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act. We make this information available on or through our website free of charge as soon as reasonably practicable after we electronically file carefully read the information with, or furnish it to, the SEC. The SEC also maintains a website that contains our SEC filings. The address for the SEC website is xxx.xxx.xxx. We use the Edgewise Therapeutics logo and other marks as trademarks in the United States and other countries. This prospectus contains references to our trademarks and service marks and to those belonging to other entities. Solely for convenience, trademarks and trade names referred to in this prospectus, including logos, artwork and other visual displays, may appear without the TM symbol, but such references are not intended to indicate in any way that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other entities’ trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entity. THE OFFERING Common stock offered incorporated by us: Common stock to be outstanding after this offering: Shares of our common stock having an aggregate offering price of up to $125,000,000. Up to 12,886,597 shares, assuming the sale of $125,000,000 of shares of our common stock at a price of $9.70 per share, which was the closing price of our common stock on the Nasdaq Global Select Market on March 31, 2022. The actual number of shares issued will vary depending on the sales price under this offering. In addition, as there is no minimum offering amount required as a condition to close this offering, the actual number of shares that may be sold is not determinable at this time. See “Dilution” beginning on page S- 11 of reference into this prospectus supplement, including our financial statements and related notes, and the exhibits to the registration statement of which this prospectus supplement is a part, before making your investment decision. OCUPHIRE PHARMA, INC. Overview Ocuphire is a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of several eye disorders. Ocuphire’s pipeline currently includes two small molecule product candidates targeting front and back of the eye indications. Its lead product candidate, Nyxol® Eye Drops (“Nyxol”), is a once-daily eye drop formulation of phentolamine mesylate designed to reduce pupil diameter and improve visual acuity. As a result, Nyxol can potentially be used for the treatment of multiple indications such as dim light or night vision disturbances (“NVD”), pharmacologically- induced mydriasis (which refers to the use of pharmacological agents to dilate the pupil for office-based eye exams) and presbyopia (a gradual, age-related loss of the eyes’ ability to focus on nearby objects). Ocuphire management believes this multiple indication potential represents a significant market opportunity. Nyxol has been studied across three Phase 1 and four Phase 2 trials totaling over 230 patients and has demonstrated promising clinical data for use in multiple ophthalmic indications. Ocuphire initiated a Phase 3 trial for the treatment of NVD in the fourth quarter of 2020, a Phase 3 trial for reversal of pharmacologically-induced mydriasis (“RM”) in the fourth quarter of 2020, and initiated a Phase 2 trial in combination with low dose pilocarpine for presbyopia, in the first quarter of 2021. Ocuphire expects top-line results to read out as early as the first quarter of 2021 and throughout the remainder of 2021, and, assuming successful and timely completion of further trials, anticipates submitting a new drug application (“NDA”) to the U.S. Food and Drug Administration (“FDA”) in early 2023 under the 505(b)(2) pathway. Ocuphire’s second product candidate, APX3330, is a twice-a-day oral tablet designed to target multiple pathways relevant to retinal and choroidal (the vascular layer of the eye) vascular diseases such as diabetic retinopathy (“DR”) and diabetic macular edema (“DME”) which, if left untreated, can result in permanent visual acuity loss and eventual blindness. DR is a disease resulting from diabetes in which chronically elevated blood sugar levels cause progressive damage to blood vessels in the retina. DME is a severe form of DR which involves leakage of protein and fluid into the macula, the central portion of the retina, causing swelling and damage. Prior to Ocuphire’s in-licensing of the product candidate, APX3330 had been studied by third parties in six Phase 1 and five Phase 2 trials totaling over 440 patients for inflammatory and oncology indications, and had demonstrated promising evidence of tolerability, pharmacokinetics, durability, and target engagement. Ocuphire plans to initiate a Phase 2 trial for APX3330 in the first quarter of 2021 for the treatment of patients with DR, including moderately severe non-proliferative DR (“NPDR”) and mild proliferative DR (“PDR”), as well as patients with DME without loss of central vision. Ocuphire has also in- licensed APX2009 and APX2014, which are additional second-generation product candidates and analogs of APX3330. As part of its strategy, Ocuphire will continue to explore opportunities to acquire additional ophthalmic assets and to seek strategic partners for late-stage development, regulatory preparation and commercialization of drugs in key global markets.