Common use of IND-Enabling Toxicology Study Design Clause in Contracts

IND-Enabling Toxicology Study Design. The Parties have agreed upon a high- level outline of a pre-clinical toxicology plan as of the Effective Date, and will finalize such plan at the first meeting of the JSC. The JSC will propose and agree upon a pre-clinical toxicology plan for die Development Candidate (“IND- Enabling Toxicology Plan”) no later than [***]. If the JSC is unable to agree on the IND-Enabling Toxicology Plan within the time period set forth in this Section 3.6.1, then either Party may refer the matter to the Senior Representatives for resolution. If the Senior Representatives cannot agree on the IND-Enabling Toxicology Plan within [***] after the matter is so referred, then Ionis will have final decision-making authority with respect to [***], provided that Ionis’ decision is consistent with the choices Ionis makes for its other similar programs, and Praxis will have final decision-making authority with respect to [***]. Promptly after the Parties agree upon the IND- Enabling Toxicology Plan, Praxis will notify the JSC of the name of the contract manufacturing organization (“CMO”) Praxis intends to use for the supply of the API and finished drug product to be used in the IND-Enabling Toxicology Study and provide to the JSC a draft statement of work for the manufacture of such supply. Praxis will, at its own expense, deliver API and finished drug product to Ionis or Ionis’ designee for the IND-Enabling Toxicology Study contemplated in the IND-Enabling Toxicology Plan and will endeavor to make such delivery no later than [***]. Praxis will enter into an agreement with CONFIDENTIAL such CMO for the production of the API and finished drug product to be used in the IND-Enabling Toxicology Study, and, if applicable, shall have reserved a manufacturing slot with such CMO for such production (and pay any reservation fees, if applicable), no later than [***]. Ionis will conduct the IND-Enabling Toxicology Study in accordance with the IND-Enabling Toxicology Plan. Ionis will provide the Draft Report for the IND-Enabling Toxicology Study to the JSC and to Praxis promptly following Completion of such study.

IND-Enabling Toxicology Study Design. The Parties Biogen shall have agreed upon a high- level outline of a pre-clinical toxicology plan as the right to make the final decision regarding which and how many of the Effective Dateproposed lead Development Candidate or Related Program Compounds for any Collaboration Program are to be advanced into IND-Enabling Toxicology Studies as Development Candidates, subject to the Parties agreeing upon the Toxicology Strategy under Section 1.8.3(c), and will finalize such plan at the first meeting requirements of the JSCthis Section 1.8.4(a). The JSC will propose and agree upon a pre-clinical toxicology plan for die Development Candidate (“IND- Enabling Toxicology Plan”) no later than [***]. If the JSC is unable Subject to agree on the IND-Enabling Toxicology Plan Study Completion Date and the Option Deadline, Biogen shall have the right to make the final decision regarding the timing and the order in which to conduct the IND-Enabling Toxicology Studies for Development Candidates. For clarity, Biogen may designate additional Development Candidates at a later date if Biogen wishes to conduct IND-Enabling Toxicology Studies on additional Compounds. The applicable Neurology JDC shall agree upon the study design and any amendments to the Toxicology Strategy for each IND-Enabling Toxicology Study for each Development Candidate (which study design will be in the form of a draft study protocol for the relevant in vivo studies to be conducted under the Toxicology Strategy) at least [***] days prior to the anticipated first dosing of the first animal in such IND-Enabling Toxicology Study. Notwithstanding the foregoing, if the Neurology JDC cannot agree upon a study design for an IND-Enabling Toxicology Study or any amendment to a Toxicology Strategy within the applicable time period as set forth in this Section 3.6.11.8.4(a), then either Party may refer the matter to the Senior Representatives CSC for resolution. If the Senior Representatives CSC cannot agree on the study design for an IND-Enabling Toxicology Plan Study or any amendment to a Toxicology Strategy within [***] days after the matter is so referred, as applicable, then Ionis Biogen will have final decision-making authority with respect to any such IND-Enabling Toxicology Study design or such Toxicology Strategy amendment, provided that Biogen shall exercise its final decision-making authority by the date that is [***] Business Days following the earlier of (i) the CSC’s determination that it is unable to agree, or (ii) the expiration of the [***], provided that Ionis’ decision is consistent with the choices Ionis makes for its other similar programs, and Praxis will have final decision-making authority with respect to [***]. Promptly after the Parties agree upon the IND- Enabling Toxicology Plan, Praxis will notify the JSC of the name of the contract manufacturing organization (“CMO”) Praxis intends to use -day period allowed for the supply of the API and finished drug product CSC to be used in the IND-Enabling Toxicology Study and provide agree pursuant to the JSC a draft statement of work for the manufacture of such supplyforegoing sentence. Praxis will, at its own expense, deliver API and finished drug product to Ionis or Ionis’ designee for the IND-Enabling Toxicology Study contemplated in the IND-Enabling Toxicology Plan and will endeavor to make such delivery no later than [***]. Praxis will enter into an agreement with CONFIDENTIAL such CMO for the production of the API and finished drug product to be used in the IND-Enabling Toxicology Study, and, if applicable, shall have reserved a manufacturing slot with such CMO for such production (and pay any reservation fees, if applicable), no later than [***]. Ionis Biogen will conduct the IND-Enabling Toxicology Study Studies under the applicable Toxicology Strategy and study design. Notwithstanding the foregoing, (A) Ionis shall have the right to elect, by providing written notice in accordance with the applicable Development Candidate Data Package for a Collaboration Program pursuant to Section 1.8.3(e), to conduct the IND-Enabling Toxicology Plan. Ionis will provide Studies for any [***] Compounds that are included in the Draft Report Development Candidate Data Package for the such Collaboration Program that Biogen elects to designate as Development Candidates and advance to IND-Enabling Toxicology Study Studies, and (B) if the Parties agree through the Neurology JDC, then Ionis may conduct IND-Enabling Toxicology Studies for any other Development Candidate for which Ionis provided a notice of interest in the applicable Development Candidate Data Package, in each case of (A) and (B), at [***] and in accordance with Sections 1.8.4(c) and 1.8.4(d). In conducting any IND-Enabling Toxicology Studies under this Section 1.8.4 for those categories of IND-Enabling Toxicology Studies listed on Schedule 1.8.4(a), the Parties will not use a CRO to conduct any such IND-Enabling Toxicology Studies that is not either (i) an “Approved CRO” listed on Schedule 1.8.4(a) with respect to the JSC applicable category of IND-Enabling Toxicology Studies, or (ii) approved in writing by the other Party, such approval not to be unreasonably withheld, conditioned or delayed. If the members of the Neurology JDC unanimously agree, then the Parties may add or remove CROs to or from the “Approved CRO” list and categories of IND-Enabling Toxicology Studies by adding such updated list of Approved CROs to Praxis promptly following Completion the minutes of the Neurology JDC meeting at which such studychanges were discussed.