Common use of Lead Optimization Clause in Contracts

Lead Optimization. The Research Committee will update the Research Plan to provide for the accelerated lead optimization of the selected Committed Compound Sets with Committed Targets in the Collaboration, subject to Steering Committee approval. The Research Plan will set project priorities and define success criteria for a GLP Toxicology Candidate. As described in the Collaboration Plan, in a typical project the parties will iteratively develop and test Analog Compounds based on Committed Compounds. The parties will determine whether a proposed Analog Compound is an Available Compound before synthesis, and only Available Compounds will proceed to synthesis and testing in the Collaboration. The Analog Compounds developed by the parties shall automatically become Committed Compounds under this Agreement and, therefore, the Committed Compound Set for the Committed Target will likely expand as a result of the lead optimization efforts. At the discretion of the Research Committee, the parties may also use such Analog Compounds in primary screens against other ACADIA Targets. The parties anticipate that lead optimization of Committed Compounds will occur in two stages: ---------------------- CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE SUCH OMISSIONS. (i) In the first stage, the parties will develop Analog Compounds as combinatorial libraries to explore the promise of the Committed Compound Set for the Committed Target. The parties will test these Analog Compounds for various properties determined by the Research Committee to predict whether the Committed Compound Set may eventually meet the defined success criteria for a GLP Toxicology Candidate. The parties will decide whether to proceed to stage two for a given Committed Compound Set within [*****] (ii) In the second stage, the parties intend to concentrate their efforts on developing [*****] and [*****] corresponding Committed Compound Set(s) to identify a GLP Toxicology Candidate, with [*****] from the first stage. The parties shall maintain a level of effort determined by the Research Committee for the [*****] The Research Committee may release Committed Targets and the corresponding Committed Compound Set(s) that are no longer of interest to the Collaboration or which are no longer the subject of the active efforts by the parties, as determined by the Research Committee and subject to Steering Committee approval, in which case the allocation provisions of Section 9.6. shall apply. Lead optimization activities will continue with respect to a Committed Target until the Research Committee and Steering Committee decide to stop further efforts. The parties anticipate that lead optimization activities will continue with respect to a Committed Target until the parties (i) develop an acceptable GLP Toxicology Candidate, (ii) determine that they are unlikely to develop an acceptable GLP Toxicology Candidate, or (iii) decide to seek commercialization of the Committed Compound Set(s) and Committed Target as described below.

Lead Optimization. The Research Committee will update the Research Plan to provide for the accelerated lead optimization of the selected Committed Compound Sets with Committed Targets in the Collaboration, subject to Steering Committee approval. The Research Plan will set project priorities and define success criteria for a GLP Toxicology Candidate. As described in the Collaboration Plan, in a typical project the parties will iteratively develop and test Analog Compounds based on Committed Compounds. The parties will determine whether a proposed Analog Compound is an Available Compound before synthesis, and only Available Compounds will proceed to synthesis and testing in the Collaboration. The Analog Compounds developed by the parties shall automatically become Committed Compounds under this Agreement and, therefore, the Committed Compound Set for the Committed Target will likely expand as a result of the lead optimization efforts. At the discretion of the Research Committee, the parties may also use such Analog Compounds in primary screens against other ACADIA Targets. The parties anticipate that lead optimization of Committed Compounds will occur in two stages: ---------------------- CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE SUCH OMISSIONS.: (i) In the first stage, the parties will develop Analog Compounds as combinatorial libraries to explore the promise of the Committed Compound Set for the Committed Target. The parties will test these Analog Compounds for various properties determined by the Research Committee to predict whether the Committed Compound Set may eventually meet the defined success criteria for a GLP Toxicology Candidate. The parties will decide whether to proceed to stage two for a given Committed Compound Set within [*****]. (ii) In the second stage, the parties intend to concentrate their efforts on developing [*****] and [*****] corresponding Committed Compound Set(s) to identify a GLP Toxicology Candidate, with [*****] from the first stage. The parties shall maintain a level of effort determined by the Research Committee for the [*****] ]. The Research Committee may release Committed Targets and the corresponding Committed Compound Set(s) that are no longer of interest to the Collaboration or which are no longer the subject of the active efforts by the parties, as determined by the Research Committee and subject to Steering Committee approval, in which case the allocation provisions of Section 9.6. shall apply. Lead optimization activities will continue with respect to a Committed Target until the Research Committee and Steering Committee decide to stop further efforts. The parties anticipate that lead optimization activities will continue with respect to a Committed Target until the parties (i) develop an acceptable GLP Toxicology Candidate, (ii) determine that they are unlikely to develop an acceptable GLP Toxicology Candidate, or (iii) decide to seek commercialization of the Committed Compound Set(s) and Committed Target as described below.)

Lead Optimization. The Research Committee will update the Research Plan to provide for the accelerated lead optimization of the selected Committed Compound Sets with Committed Targets in the Collaboration, subject to Steering Committee approval. The Research Plan will set project priorities and define success criteria for a GLP Toxicology Candidate. As described in the Collaboration Plan, in a typical project the parties will iteratively develop and test Analog Compounds based on Committed Compounds. The parties will determine whether a proposed Analog Compound is an Available Compound before synthesis, and only Available Compounds will proceed to synthesis and testing in the Collaboration. The Analog Compounds developed by the parties shall automatically become Committed Compounds under this Agreement and, therefore, the Committed Compound Set for the Committed Target will likely expand as a result of the lead optimization efforts. At the discretion of the Research Committee, the parties may also use such Analog Compounds in primary screens against other ACADIA Targets. The parties anticipate that lead optimization of Committed Compounds will occur in two stages: ---------------------- CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE SUCH OMISSIONS.: (i) In the first stage, the parties will develop Analog Compounds as combinatorial libraries to explore the promise of the Committed Compound Set for the Committed Target. The parties will test these Analog Compounds for various properties determined by the Research Committee to predict whether the Committed Compound Set may eventually meet the defined success criteria for a GLP Toxicology Candidate. The parties will decide whether to proceed to stage two for a given Committed Compound Set within [*****]. (ii) In the second stage, the parties intend to concentrate their efforts on developing [*****] * and [*****] * corresponding Committed Compound Set(s) to identify a GLP Toxicology Candidate, with [*****] * from the first stage. The parties shall maintain a level of effort determined by the Research Committee for the [*****] . The Research Committee may release Committed Targets and the corresponding Committed Compound Set(s) that are no longer of interest to the Collaboration or which are no longer the subject of the active efforts by the parties, as determined by the Research Committee and subject to Steering Committee approval, in which case the allocation provisions of Section 9.6. shall apply. Lead optimization activities will continue with respect to a Committed Target until the Research Committee and Steering Committee decide to stop further efforts. The parties anticipate that lead optimization activities will continue with respect to a Committed Target until the parties (i) develop an acceptable GLP Toxicology Candidate, (ii) determine that they are unlikely to develop an acceptable GLP Toxicology Candidate, or (iii) decide to seek commercialization of the Committed Compound Set(s) and Committed Target as described below.

Lead Optimization. The Research Committee will update in consideration of the Research Plan rights and licenses granted by ChemBridge to provide CBL under this Agreement, CBL agrees to collaborate with ChemBridge on two (2) Optimization Projects, wherein ChemBridge shall have the responsibility for providing the accelerated chemistry components of the project and CBL shall have the responsibility for providing the pharmacological/biochemical components of the project, each party to bear the full costs of its responsibilities. CBL shall have the responsibility to present for consideration by ChemBridge all its data on “Confirmed Hits” that have a reasonable possibility of becoming lead optimization compounds that arise from its research activities, whether or not such activities are conducted with a Collaborator. ChemBridge shall then have 90 days to determine whether it wishes to select the Confirmed Hit as one of its two Optimization Projects. ChemBridge shall receive a 50% ownership of the Confirmed Hit and all derivative compounds produced during the course of the selected Committed Compound Sets with Committed Targets in the Collaboration, subject to Steering Committee approval. The Research Plan will set project priorities and define success criteria for a GLP Toxicology Candidate. As described in the Collaboration Plan, in a typical project the parties will iteratively develop and test Analog Compounds based on Committed Compounds. The parties will determine whether a proposed Analog Compound is an Available Compound before synthesis, and only Available Compounds will proceed to synthesis and testing in the Collaboration. The Analog Compounds developed by the parties shall automatically become Committed Compounds under this Agreement and, therefore, the Committed Compound Set for the Committed Target will likely expand as a result of the lead optimization efforts. At the discretion of the Research Committee, the parties may also use such Analog Compounds in primary screens against other ACADIA Targets. The parties anticipate that lead optimization of Committed Compounds will occur in two stages: ---------------------- CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE SUCH OMISSIONS. (i) In the first stage, the parties will develop Analog Compounds as combinatorial libraries to explore the promise of the Committed Compound Set for the Committed Target. The parties will test these Analog Compounds for various properties determined by the Research Committee to predict whether the Committed Compound Set may eventually meet the defined success criteria for a GLP Toxicology Candidate. The parties will decide whether to proceed to stage two for a given Committed Compound Set within [*****] (ii) In the second stage, the parties intend to concentrate their efforts on developing [*****] and [*****] corresponding Committed Compound Set(s) to identify a GLP Toxicology Candidate, with [*****] from the first stageOptimization Projects. The parties shall maintain a level of effort determined by jointly determine which, if any, compounds emerging from the Research Committee Optimization Projects should be taken into further development. For such compounds as the parties agree should be taken into further development, ChemBridge shall be responsible for the [*****] The Research Committee may release Committed Targets chemistry, and CBL shall be responsible for the corresponding Committed Compound Set(s) that are no longer of interest to pharmacology/biochemistry necessary for the Collaboration or which are no longer continued development. For later development functions, such as toxicology, formulation, pharmacoeconomics, pilot scale manufacturing, clinical trials and all regulatory and commercial activities, the subject of parties shall share equally in the active efforts cost. Patent costs and related legal expenses shall be borne equally by the parties, as determined by the Research Committee and subject to Steering Committee approval, in which case the allocation provisions of Section 9.6. shall apply. Lead optimization activities will continue with respect to a Committed Target until the Research Committee and Steering Committee decide to stop further efforts. The parties anticipate that lead optimization activities will continue with respect to a Committed Target until shall jointly manage the parties (i) develop an acceptable GLP Toxicology Candidate, (ii) determine that they are unlikely to develop an acceptable GLP Toxicology Candidate, or (iii) decide to seek development and commercialization of any compound arising from an Optimization Project. CBL will have the Committed Compound Set(s) right to define the moment of out-licensing of any compound arising from an Optimization Project and Committed Target as described belowthe terms and conditions of such out-licensing, if the parties, after reasonable discussion and consultation with each other, are not able to agree on these matters. During the course of an Optimization Project, either party may elect at any time not to proceed with the project. If one party elects not to proceed with the project, then the other party shall have the right to purchase the rights of the other at fair market value, lithe parties are unable to agree on a fair market value, then such shall be determined by binding arbitration.

Lead Optimization. The Research Committee will update the Research Plan to provide for the accelerated lead optimization of the selected Committed qualified Collaboration Compound Sets with Committed or Collaboration Compounds and the corresponding Collaboration Targets (or, if the GTC Target is unknown, the anti-infective activity identified in the Collaborationrelevant assay), subject to Steering Committee approval. The Research Plan will set project priorities and define success criteria for a GLP Toxicology Candidate. As described in the Collaboration Plan, in a typical project the parties Parties will iteratively develop and test Analog Compounds based on Committed Collaboration Compounds. The parties Parties will determine whether a proposed Analog Compound is an Available Compound before synthesis, and only Available Compounds will proceed to synthesis and testing in the Collaboration. The Analog Compounds developed by the parties Parties shall automatically become Committed Collaboration Compounds under this Agreement and, therefore, the Committed Collaboration Compound Set for the Committed Collaboration Target will likely expand as a result of the lead optimization efforts. At the discretion of the Research Committee, the parties Parties may also use such Analog Compounds in primary screens against other ACADIA TargetsGTC Targets or assays, as described in Section 3.4. The parties anticipate that lead optimization of Committed Compounds will occur in two stages: ---------------------- CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE SUCH OMISSIONS. (i) In the first stage, the parties will develop Analog Compounds as combinatorial libraries to explore the promise of the Committed Compound Set for the Committed Target. The parties will test these Analog Compounds for various properties determined by the Research Committee to predict whether the Committed Compound Set may eventually meet the defined success criteria for a GLP Toxicology Candidate. The parties will decide whether to proceed to stage two for a given Committed Compound Set within [*****] (ii) In the second stage, the parties intend to concentrate their efforts on developing [*****] and [*****] corresponding Committed Compound Set(s) to identify a GLP Toxicology Candidate, with [*****] from the first stage. The parties shall maintain a level of effort determined by the Research Committee for the [*****] The Research Committee may release Committed from the scope of the Collaboration any Collaboration Compounds, Collaboration Compound Sets, and Collaboration Targets and the corresponding Committed Compound Set(s) that are no longer of interest to the Collaboration or which are no longer the subject of the active efforts by the partiesCollaboration, as determined by the Research Committee and subject to Steering Committee approval; provided, however that the same shall continue to be subject to the rights of the Parties as set forth in which case the allocation provisions of Section 9.69.5. shall applybelow. Lead optimization activities will continue with respect to in a Committed Target project until the Research Committee recommends that further efforts be stopped and the Steering Committee decide to stop further effortsaccepts such recommendation. The parties Parties anticipate that lead optimization activities will continue with respect to in a Committed Target project until the parties Parties (i) develop an acceptable GLP Toxicology Candidate, (ii) determine that they are unlikely to develop an acceptable GLP Toxicology CandidateCandidate and cease development activities with respect thereto, or (iii) decide to seek commercialization of the Committed Compound Set(s) and Committed Target Collaboration Work Product as described belowin Section 3.9 herein.

Lead Optimization. The Research Committee will update the Research Plan to provide for the accelerated lead optimization Upon designation of the selected Committed at least one Lead Compound Sets with Committed Targets in the Collaboration, subject to Steering Committee approval. The Research Plan will set project priorities and define success criteria for a GLP Toxicology Candidate. As described in the Collaboration Plan, in a typical project the parties will iteratively develop and test Analog Compounds based on Committed Compounds. The parties will determine whether a proposed Analog Compound is an Available Compound before synthesis, and only Available Compounds will proceed to synthesis and testing in the Collaboration. The Analog Compounds developed by the parties shall automatically become Committed Compounds under this Agreement and, therefore, the Committed Compound Set for the Committed Target will likely expand as a result of the lead optimization efforts. At the discretion of the Research Committee, the parties may also use such Analog Compounds in primary screens against other ACADIA Targets. The parties anticipate that lead optimization of Committed Compounds will occur in two stages: ---------------------- CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE SUCH OMISSIONS. (i) In the first stage, the parties will develop Analog Compounds as combinatorial libraries to explore the promise of the Committed Compound Set for the Committed Target. The parties will test these Analog Compounds for various properties determined by the Research Committee to predict whether the Committed Compound Set may eventually meet the defined success criteria for a GLP Toxicology Candidate. The parties will decide whether to proceed to stage two for a given Committed Compound Set within Target, the Parties will determine which Party shall primarily conduct Lead Optimization. The selected Party, in consultation with the other Party, shall conduct a Lead Optimization program consisting of medicinal chemistry synthesis of analogs of the Lead Compound(s) and testing of these analogs in a series of assays to determine efficacy, selectivity and pharmaceutical properties, as set forth in the Research Plan. Additional pharmacological studies of analogs may also be performed by the selected Party, as set forth in the Research Plan. The JRC shall review the results of the assays, determine which Lead Compound(s) should be designated as IND Candidates, and submit its recommendations to the JMC for written approval. No more than [*****] (ii) In ] days after the second stageJRC’s recommendation is presented to the JMC, the parties intend to concentrate their efforts on developing [*****] and [*****] corresponding Committed Compound Set(sJMC shall determine in writing under Section 2.3(c)(ii) to identify a GLP Toxicology Candidate, with [*****] from the first stagewhether such Lead Compound(s) merit designation as IND Candidates. The parties shall maintain a level of effort determined by the Research Committee for After the [****] day period following the end of the Collaboration Term, if CVT does not take an exclusive license to Collaboration Compounds which are Active against a particular Target pursuant to Section 4.6, then such Collaboration Compounds shall be deemed Non-Collaboration Compounds, and PTC shall have the right to screen such Non-Collaboration Compounds and to develop and commercialize products incorporating such Non-Collaboration Compounds with no royalty or milestone obligations to CVT for such products under this Agreement. If, prior to the [*] The Research Committee may release Committed Targets and day following the corresponding Committed Compound Set(s) that are no longer end of interest to the Collaboration or which are no longer Term, CVT exercises its right to obtain an exclusive license pursuant to Section 4.6 to Collaboration Compounds identified as Active against such Target in the subject of the active efforts applicable Lead Optimization program (as documented by the partiesJMC pursuant to Section 2.3(c)(iii)), as determined by the Research Committee and then such Collaboration Compounds shall be subject to Steering Committee approval, CVT’s license pursuant to Section 4.6 for so long as such license remains in which case effect. [*] Certain information on this page has been redacted and filed separately with the allocation provisions of Section 9.6Securities and Exchange Commission. shall apply. Lead optimization activities will continue Confidential treatment has been requested with respect to a Committed Target until the Research Committee and Steering Committee decide to stop further efforts. The parties anticipate that lead optimization activities will continue with respect to a Committed Target until the parties (i) develop an acceptable GLP Toxicology Candidate, (ii) determine that they are unlikely to develop an acceptable GLP Toxicology Candidate, or (iii) decide to seek commercialization of the Committed Compound Set(s) and Committed Target as described belowomitted portions.