Contract analysis

Section 1.1 — Definitions. As used in this Agreement, the following terms shall have the meanings set forth below. Capitalized terms used but not defined in this Section 1.1 shall have the meanings ascribed to them elsewhere in this Agreement. "Additional Insured" means Veridian and each Participating Site Institution that is named as an additional insured under the Sponsor Insurance Policy, as more fully described i

ARTICLE II — SCOPE OF AGREEMENT

Section 2.1 — Purpose. Sponsor hereby engages Veridian and its Participating Sites, and Veridian hereby accepts such engagement, to conduct the CLARION trial at up to thirty-eight (38) Veridian Network sites located across fourteen (14) states within the United States, in accordance with the Protocol, GCP, all applicable laws and regulations, and the terms and conditions set forth in this Agreement. Veridian shall se

Section 2.2 — Protocol. The Study shall be conducted pursuant to Protocol PPC-4871-III (CLARION), as described in the Protocol Synopsis attached hereto as Exhibit A and incorporated herein by reference. The Protocol is designed as a Phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of penterafenib (PPC-4871) compared to placebo in adult subjects with advanced hepatocellu

Section 2.3 — Projected Timeline. The Parties anticipate the following projected timeline for the Study, subject to adjustment based on actual enrollment rates, regulatory requirements, and other factors: (a) Enrollment Period: Forty-two (42) months from the date of first patient in ("FPI"), with a target FPI date of August 14, 2023. (b) Follow-Up Period: Eighteen (18) months following the enrollment of the last Stud

Section 2.4 — Individual Site Agreements. Each Participating Site Institution shall, prior to initiating any Study activities, execute an Individual Site Agreement in substantially the form attached hereto as Exhibit C. Each Individual Site Agreement shall incorporate by reference the terms and conditions of this Agreement, identify the principal investigator designated for such site, specify the applicable IRB of re

Section 2.5 — Relationship to CRO Agreement. The Parties acknowledge that Sponsor has separately contracted with Meridian Contract Research Organization, Inc. under a Master Services Agreement dated January 15, 2023 (the "CRO Agreement") for the performance of certain monitoring, data management, pharmacovigilance, safety reporting, and biostatistics services in connection with the CLARION trial. Veridian and each Pa

Section 2.6 — Approved Subcontractors. Sponsor's approved subcontractors for the Study are listed in Exhibit K attached hereto and, as of the date hereof, include the following: (a) Meridian Contract Research Organization, Inc. — performing monitoring, data management, pharmacovigilance, safety reporting, and biostatistics services. (b) Pinnacle Data Solutions, Inc. — providing the electronic data capture ("EDC") pla

ARTICLE III — RESPONSIBILITIES OF SPONSOR

Section 3.1 — IND Maintenance. Sponsor shall maintain IND 157823 in good standing with the FDA throughout the term of the Study and shall bear sole responsibility for all regulatory submissions, amendments, annual reports, safety reports, and correspondence with the FDA and other regulatory authorities in connection with the IND and the Study. Sponsor shall promptly notify Veridian and the Global Principal Investigat

Section 3.2 — Supply of Investigational Product. Sponsor shall supply penterafenib (PPC-4871) and matching placebo in quantities sufficient for the conduct of the Study at all Participating Sites, at no cost to Veridian, any Participating Site, or any Study Subject. Sponsor shall be responsible for the manufacture, quality control, quality assurance, labeling, packaging, and distribution of the Investigational Produc

Section 3.3 — Protocol and Amendments. Sponsor shall provide the Protocol and any amendments thereto to Veridian and each Participating Site in a timely manner. Any Protocol amendment shall be communicated in writing to Veridian and all Participating Sites, and shall require applicable IRB approval prior to implementation at any Participating Site, except in circumstances where an immediate change is necessary to eli

Section 3.4 — Monitoring. Sponsor, through Meridian CRO, shall conduct monitoring visits at each Participating Site in accordance with ICH E6(R2) Guidelines and 21 C.F.R. Part 312. Monitoring activities shall include, without limitation, on-site monitoring, remote monitoring, centralized statistical monitoring, source data verification, review of informed consent documentation, verification of subject eligibility, an

Section 3.5 — Safety Reporting. Sponsor shall fulfill all IND safety reporting obligations under 21 C.F.R. § 312.32, including the submission of IND safety reports to the FDA. Fatal and life-threatening suspected adverse reactions shall be reported to the FDA as soon as possible but no later than seven (7) calendar days after Sponsor first receives the information ("7-day reports"), with a follow-up report submitted

Section 3.6 — Insurance. Sponsor shall obtain and maintain clinical trial liability insurance throughout the term of the Study and for the post-termination period specified in Article XI, with coverage limits and terms as set forth in Section 11.1 and Exhibit E. Sponsor shall name Veridian and each Participating Site Institution as additional insureds under the Sponsor Insurance Policy.

Section 3.7 — Regulatory Compliance. Sponsor shall comply with all applicable laws, rules, and regulations in connection with the conduct of the Study, including without limitation: (a) 21 C.F.R. Parts 11 (Electronic Records; Electronic Signatures), 50 (Protection of Human Subjects), 54 (Financial Disclosure by Clinical Investigators), 56 (Institutional Review Boards), and 312 (Investigational New Drug Application);

ARTICLE IV — RESPONSIBILITIES OF VERIDIAN AND PARTICIPATING SITES

Section 4.1 — Site Activation. Veridian shall use commercially reasonable efforts to activate each of the thirty-eight (38) Participating Sites listed on Schedule 1 in a timely manner consistent with the projected timeline set forth in Section 2.3. Site activation shall include, without limitation, the execution of Individual Site Agreements, obtainment of IRB approval, completion of site feasibility and qualificatio

Section 4.2 — Conduct of Study. Each Participating Site shall conduct the Study in strict accordance with the Protocol, GCP, all applicable federal, state, and local laws and regulations, and the terms and conditions of this Agreement and the applicable Individual Site Agreement. Each Participating Site shall use its best efforts to enroll Study Subjects in accordance with the enrollment targets and timelines establi

Section 4.3 — Qualified Investigators. Veridian shall ensure that each Participating Site designates a qualified principal investigator who meets the requirements of 21 C.F.R. § 312.53 and who is appropriately trained and experienced in the conduct of clinical research in oncology. The Global Principal Investigator for the CLARION trial shall be Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone

Section 4.4 — IRB Approval. Each Participating Site must obtain and maintain IRB approval for the Protocol, the informed consent document, and all other study-related documents prior to enrolling any Study Subject. The lead sites — Graystone University Medical Center and Lakemont Medical Center — shall obtain approval from their respective individual institutional review boards. Graystone University Medical Center sh

Section 4.5 — Informed Consent. Each Participating Site shall obtain informed consent from each Study Subject prior to the conduct of any study-related procedures, in accordance with 21 C.F.R. Part 50, ICH E6(R2) Guidelines, and applicable IRB requirements. The informed consent document shall be approved by the applicable IRB and shall include all required elements set forth in 21 C.F.R. § 50.25, including a descript

Section 4.6 — Safety Reporting by Sites. Each Participating Site shall report all Serious Adverse Events to Sponsor and Meridian CRO within twenty-four (24) hours of the Investigator first becoming aware of such event, using the forms and procedures specified in Exhibit J attached hereto. Each Participating Site shall also report all Adverse Events, protocol deviations, and other safety-related information in accorda

Section 4.7 — Data Collection and Recording. Each Participating Site shall enter all Study data into the EDC system provided by Pinnacle Data Solutions, Inc. in a timely, accurate, and complete manner, in accordance with the Protocol, the EDC data entry guidelines, and applicable data management plans. Source documents shall be created and maintained at each Participating Site for all Study activities and shall be av

Section 4.8 — Site Staff Qualifications. Each Participating Site shall ensure that all Site Staff involved in the conduct of the Study are adequately trained, qualified, and experienced to perform their assigned Study-related duties. Each Participating Site shall maintain documentation of Site Staff training, including Protocol-specific training, GCP training, EDC training, and any other training required by Sponsor

Section 4.9 — Cooperation with Monitoring. Each Participating Site shall provide reasonable access to monitors from Meridian CRO for the conduct of on-site monitoring visits, including access to Study Subjects (subject to applicable consent and privacy requirements), source documents, case report forms, the Investigational Product and accountability records, laboratory records, and all other Study-related documents a

Section 4.10 — Regulatory Filings. Each Investigator shall complete and maintain a current FDA Form 1572 (Statement of Investigator) and shall file financial disclosure certifications in accordance with 21 C.F.R. Part 54. Each Investigator shall promptly notify Sponsor and Veridian of any changes to the information provided on the Form 1572 or in the financial disclosure certification. Each Participating Site shall a

Section 4.11 — HIPAA Compliance. Each Participating Site shall comply with all applicable requirements of HIPAA and the HITECH Act, including the Privacy Rule and the Security Rule, in connection with the collection, use, disclosure, and protection of protected health information ("PHI") of Study Subjects. Each Participating Site shall obtain appropriate research authorizations from Study Subjects for the use and dis

Section 4.12 — Anti-Kickback and Sunshine Act Compliance. Veridian and each Participating Site represent and warrant that all payments received under this Agreement reflect fair market value for the services rendered and are consistent with applicable Anti-Kickback Statute safe harbors, including without limitation the personal services and management contracts safe harbor set forth at 42 C.F.R. § 1001.952(d). Veridi

ARTICLE V — PRINCIPAL INVESTIGATOR

Section 5.1 — Global Principal Investigator. Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, 1200 University Avenue, Philadelphia, Pennsylvania 19104, shall serve as the Global Principal Investigator for the CLARION trial. In this capacity, Dr. Aldridge shall be responsible for providing overall scientific leadership and medical oversight for the Study across all Par

Section 5.2 — Co-Principal Investigator. Dr. Howard Matsuoka, M.D., Associate Professor of Hepatology & Oncology at Lakemont Medical Center, 4400 North Michigan Drive, Chicago, Illinois 60611, shall serve as the Co-Principal Investigator for the CLARION trial. In this capacity, Dr. Matsuoka shall support Dr. Aldridge in the scientific oversight and coordination of the Study, serve as a co-chair of the publications co

Section 5.3 — Investigator Obligations. Each Investigator, including the Global Principal Investigator and the Co-Principal Investigator, shall comply with the Protocol, GCP, all applicable federal, state, and local laws and regulations, and the Investigator Undertaking attached hereto as Exhibit I. Each Investigator shall assume personal responsibility for the conduct of the Study at his or her Participating Site an

Section 5.4 — Replacement of Investigators. Replacement of a principal investigator at any Participating Site requires the prior written approval of Sponsor, which approval shall not be unreasonably withheld, conditioned, or delayed. In the event that a principal investigator at a Participating Site becomes unable or unwilling to continue serving in such capacity, or is removed for cause, Veridian shall promptly noti

Section 6.1 — Enrollment Target. The planned enrollment target for the Study is one thousand two hundred (1,200) Study Subjects across all Participating Sites. The Parties shall work together in good faith to achieve this enrollment target within the forty-two (42) month enrollment period specified in Section 2.3. Enrollment targets for individual Participating Sites shall be established by Sponsor in consultation wi

Section 6.2 — Randomization. Study Subjects who meet all inclusion criteria and none of the exclusion criteria set forth in the Protocol shall be randomized in a 2:1 ratio, with eight hundred (800) subjects assigned to the penterafenib (PPC-4871) treatment arm and four hundred (400) subjects assigned to the placebo control arm. Randomization shall be performed using the interactive response technology ("IRT") system

Section 6.3 — Enrollment Period. The enrollment period for the Study shall be forty-two (42) months from the date of FPI. The Parties may extend the enrollment period by mutual written agreement if enrollment targets are not met within the initial forty-two (42) month period, subject to regulatory and budgetary considerations.

Section 6.4 — Inclusion/Exclusion Criteria. Study Subjects shall be enrolled only if they meet all inclusion criteria and none of the exclusion criteria as set forth in the Protocol (Exhibit A). Each Participating Site shall be responsible for verifying subject eligibility prior to randomization.

Section 6.5 — Subject Screening. Each Participating Site shall follow the Protocol-specified screening procedures to assess the eligibility of potential Study Subjects. Per-Patient Fees shall begin to accrue at the time of randomization in accordance with the milestone payment structure set forth in Section 7.3(b). Screening failures shall not be subject to Per-Patient Fees, but reasonable and documented screening co

ARTICLE VII — BUDGET AND PAYMENT

Section 7.1 — Total Deal Value. The total value of this Agreement across all Participating Sites over the projected life of the Study is Eighty Million Dollars ($80,000,000) (the "Total Deal Value"). This figure represents the maximum aggregate amount payable under this Agreement and encompasses all components set forth in Section 7.2 below. The Total Deal Value may be increased only by mutual written agreement of th

Section 7.2 — Budget Components. The Total Deal Value is comprised of the following components: (a) Per-Patient Site Fees: Fifty-Two Thousand Dollars ($52,000) per Study Subject multiplied by one thousand two hundred (1,200) planned subjects, for a total of Sixty-Two Million Four Hundred Thousand Dollars ($62,400,000). (b) Start-Up Fees: Seventy-Five Thousand Dollars ($75,000) per Participating Site multiplied by thi

Section 7.3 — Payment Schedule. Payments under this Agreement shall be made in accordance with the following schedule: (a) Start-Up Fees: Fifty percent (50%) of the Start-Up Fee (Thirty-Seven Thousand Five Hundred Dollars ($37,500)) per Participating Site shall be payable upon site activation, defined as the date on which the applicable Individual Site Agreement has been fully executed, IRB approval has been obtained

Section 7.4 — Payment Terms. All amounts due under this Agreement shall be payable Net forty-five (45) calendar days from the date of Sponsor's receipt of a proper and complete invoice submitted by Veridian in accordance with Section 7.5. Payments shall be made in United States Dollars by wire transfer of immediately available funds to the bank account designated by Veridian in writing. Late payments shall bear inter

Section 7.5 — Invoicing. Veridian shall submit invoices on behalf of itself and the Participating Sites on a monthly basis, or at such other intervals as may be agreed upon by the Parties. Each invoice shall set forth in reasonable detail the services performed, the milestones achieved, the amounts due by component, and such other information as Sponsor may reasonably request. Invoices shall be directed to: Penterra

Section 7.6 — Taxes. Each Party shall be responsible for the payment of its own taxes, including without limitation federal, state, and local income taxes, franchise taxes, and employment taxes. The Parties acknowledge Veridian's status as a tax-exempt organization under Section 501(c)(3) of the Internal Revenue Code. Sponsor shall have no obligation to withhold or remit taxes on payments made to Veridian, provided t

Section 7.7 — Contingency Reserve. The Contingency/Change Order Reserve of Two Million Five Hundred Thousand Dollars ($2,500,000) shall be available for unanticipated costs, including without limitation costs arising from Protocol amendments, additional study procedures, regulatory requirements, extended enrollment periods, or other changes to the Study scope. Use of the Contingency Reserve shall require the prior wr

Section 7.8 — Fair Market Value. The Parties represent and warrant that all payments under this Agreement have been determined through arm's-length negotiation and reflect the fair market value of the services to be rendered and the costs to be incurred in connection with the Study. No payment under this Agreement is intended to induce or reward the referral of Study Subjects, patients, or healthcare services, or to

Section 7.9 — Detailed Budget. The detailed line-item budget and payment schedule for the Study is set forth in Exhibit B attached hereto and incorporated herein by reference. In the event of any conflict between the provisions of this Article VII and the terms of Exhibit B, the provisions of this Article VII shall control.

ARTICLE VIII — INDEMNIFICATION

Section 8.1 — Sponsor Indemnification of Site Network, Sites, and Investigators. Penterra shall indemnify, defend, and hold harmless Veridian, each Participating Site Institution, each Investigator, each sub-investigator, and each member of Site Staff (collectively, the "Site Indemnitees"), and their respective officers, directors, trustees, employees, agents, successors, and assigns, from and against any and all cla

Section 8.2 — Carve-Outs from Sponsor Indemnification. Notwithstanding anything to the contrary in Section 8.1, Sponsor's indemnification obligations under Section 8.1 shall not apply to the extent, and only to the extent, that Losses arise from or are attributable to: (i) the negligence, gross negligence, or willful misconduct of a Participating Site, any Investigator, any sub-investigator, or any member of Site Sta

Section 8.3 — Subject Medical Care Costs. In addition to its indemnification obligations under Section 8.1, Sponsor shall cover the reasonable and customary medical costs for the treatment of study-related injuries sustained by Study Subjects that are not covered by such Study Subject's own health insurance, health plan, or other third-party payor. Sponsor's obligation under this Section 8.3 shall be subject to the f

Section 8.4 — Medically Necessary Protocol Deviations. Liability for Losses arising from a Medically Necessary Protocol Deviation undertaken by an Investigator in good faith and in the exercise of his or her reasonable medical judgment for the immediate safety, rights, or welfare of a Study Subject shall remain with Sponsor under Section 8.1(a), provided that the following conditions are satisfied: (a) The Investigat

Section 8.5 — Site Network/Investigator Indemnification of Sponsor. Veridian and each Participating Site Institution shall, severally and not jointly, indemnify, defend, and hold harmless Sponsor and its officers, directors, employees, agents, Affiliates, successors, and assigns from and against any and all Losses arising out of or in connection with: (a) the negligence, gross negligence, or willful misconduct of Sit

Section 8.6 — Cap on Site Indemnification. The indemnification obligations of Veridian and each Participating Site Institution under Section 8.5 shall be subject to the following limitations: (a) Per-Site, Per-Occurrence Cap: The maximum liability of any individual Participating Site Institution under Section 8.5 shall not exceed Five Million Dollars ($5,000,000) per occurrence. (b) Aggregate Cap: The maximum aggrega

Section 8.7 — Notice of Claims. The indemnified party shall provide written notice to the indemnifying party within thirty (30) calendar days of becoming aware of any claim, demand, action, suit, or proceeding for which indemnification is sought under this Article VIII, specifying in reasonable detail the nature and basis of such claim and the amount of Losses claimed or estimated. Failure to provide timely notice un

Section 8.8 — Defense and Settlement. Upon receipt of a notice of claim under Section 8.7, the indemnifying party shall have the right, but not the obligation, to assume and control the defense of any indemnified claim, using legal counsel of its choosing that is reasonably acceptable to the indemnified party. If the indemnifying party elects to assume the defense, the indemnified party shall cooperate fully with the