Contract analysis

ARTICLE 1 — DEFINITIONS As used in this Agreement, the following terms shall have the meanings set forth below. Capitalized terms used but not defined in any particular provision of this Agreement shall have the meanings ascribed to them elsewhere in this Agreement or in the Exhibits and Schedules attached hereto.

Section 1.1 "Adverse Event" or "AE" means any untoward medical occurrence in a Subject who is administered the Investigational Product or placebo, which does not necessarily have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the Investigational Product

Section 1.2 "Agreement" means this Master Clinical Trial Agreement, together with all Exhibits and Schedules attached hereto and incorporated herein by reference, as the same may be amended, supplemented, or modified from time to time in accordance with the provisions hereof.

Section 1.3 "Applicable Law" means all federal, state, and local laws, statutes, regulations, rules, ordinances, orders, decrees, judgments, and governmental requirements applicable to the conduct of the Study or the performance of the Parties' obligations hereunder, including without limitation: (a) the Federal Food, Drug, and Cosmetic Act, as amended (21 U.S.C. § 301 et seq.); (b) FDA regulations at 21 C.F.R. Parts

Section 1.4 "Approved Subcontractors" means those third-party service providers engaged by Sponsor or Site Network in connection with the Study that have been approved by both Parties and are listed on Exhibit K attached hereto, which as of the Effective Date include: (a) Meridian Contract Research Organization, Inc., a Delaware corporation ("Meridian CRO" or "CRO"), providing monitoring, data management, safety repo

Section 1.5 "Briarcliff Policy" means the clinical trial liability insurance policy issued by Briarcliff Mutual Insurance Company to Sponsor, bearing Policy No. BM-CTL-2023-04182, as more particularly described in Article 10 and Exhibit E hereof.

Section 1.6 "Budget" means the budget and payment schedule attached hereto as Exhibit B, setting forth the detailed breakdown of all compensation payable under this Agreement, as the same may be amended from time to time in accordance with the provisions hereof.

Section 1.7 "Central IRB" means the Veridian Central Institutional Review Board, a centralized institutional review board operated by Site Network for the purpose of providing IRB review and oversight for Participating Sites within the Site Network that are located outside the Commonwealth of Pennsylvania and that elect to rely on the Central IRB pursuant to an IRB Authorization Agreement.

Section 1.8 "Closing Date" means the date on which all Conditions Precedent set forth in Article 4 have been satisfied or waived in writing by the Party entitled to the benefit thereof.

Section 1.9 "Conditions Precedent" means the conditions to closing set forth in Section 4.1 of this Agreement.

Section 1.10 "Confidential Information" has the meaning set forth in Section 15.1 of this Agreement.

Section 1.11 "CRO" means Meridian Contract Research Organization, Inc., the contract research organization engaged by Sponsor as an Approved Subcontractor to provide monitoring, data management, safety reporting, biostatistical, and related services in connection with the Study.

Section 1.12 "Data" or "Study Data" means all clinical trial data, information, and results generated, collected, recorded, or produced in connection with the Study, including without limitation all case report form data, electronic data capture records, source data verifications, laboratory data, imaging data, pharmacokinetic and pharmacodynamic data, biomarker data, adverse event reports, safety data, statistical a

Section 1.13 "DSMB" means the independent Data Safety Monitoring Board established by Sponsor to monitor Subject safety during the conduct of the Study.

Section 1.14 "EDC" means the electronic data capture platform provided by Pinnacle Data Solutions, Inc. for the collection, storage, and management of Study Data in accordance with 21 C.F.R. Part 11.

Section 1.15 "Effective Date" means the date first written above in the preamble to this Agreement, which shall be the date on which all Conditions Precedent have been satisfied in accordance with Article 4.

Section 1.16 "FDA" means the United States Food and Drug Administration, or any successor agency thereto.

Section 1.17 "GCP" means Good Clinical Practice as defined in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline E6(R2), as amended from time to time.

Section 1.18 "IND" means Investigational New Drug Application No. IND 157823, filed by Sponsor with the FDA for the Investigational Product, as amended or supplemented from time to time.

Section 1.19 "Individual Site Agreement" means the joinder agreement, substantially in the form attached hereto as Exhibit C, to be executed by each Participating Site as a condition to that Participating Site's participation in the Study, pursuant to which such Participating Site agrees to be bound by the applicable terms and conditions of this Agreement.

Section 1.20 "Investigational Product" means penterafenib (PPC-4871), the oral multi-kinase inhibitor that is the subject of the Study, and the matching placebo, in each case as supplied by Sponsor in accordance with the Protocol and this Agreement.

Section 1.21 "Investigator" means, with respect to each Participating Site, the principal investigator, co-principal investigators, and sub-investigators designated by Site Network and approved by Sponsor to conduct the Study at such Participating Site, each of whom shall have executed an FDA Form 1572 and an Investigator Undertaking in the form attached hereto as Exhibit I.

Section 1.22 "Investigator Grant" means the grants for academic publication support payable to Investigators in accordance with the Budget, as more particularly described in Section 3.5 of this Agreement.

Section 1.23 "IRB" means an Institutional Review Board established and operating in accordance with 21 C.F.R. Part 56 and applicable federal and state requirements, including the Graystone University Institutional Review Board (IRB Registration: IRB00012847) and the Veridian Central IRB.

Section 1.24 "Losses" means any and all claims, demands, actions, causes of action, suits, proceedings, investigations, losses, damages, liabilities, judgments, settlements, penalties, fines, costs, and expenses (including reasonable attorneys' fees, expert witness fees, and costs of litigation or arbitration), whether known or unknown, direct or indirect.

Section 1.25 "Network Coordination Fee" means the administrative and coordination fee payable to Veridian central office in consideration of the management, coordination, and oversight services provided by Veridian in connection with the Study across all Participating Sites, as set forth in Section 3.6 and the Budget.

Section 1.26 "Participating Site" or "Site" means each academic medical center, hospital, or affiliated research institution within the Veridian Health Research Network that is identified on Schedule 1 attached hereto and that has executed an Individual Site Agreement in the form of Exhibit C, thereby agreeing to conduct the Study at such institution in accordance with the terms of this Agreement.

Section 1.27 "Party" means either Sponsor or Site Network, as the context requires, and "Parties" means both Sponsor and Site Network.

Section 1.28 "Per-Patient Fee" means the fee of Fifty-Two Thousand Dollars ($52,000) per Subject, payable in milestone-based installments as set forth in Section 3.2 and the Budget.

Section 1.29 "Principal Investigator" or "PI" means the Global Principal Investigator for the Study, Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, or such replacement as may be designated by Site Network and approved in writing by Sponsor.

Section 1.30 "Protocol" means Protocol PPC-4871-III, the clinical trial protocol for the CLARION trial, as summarized in Exhibit A attached hereto, together with any amendments thereto approved by the Parties and the applicable IRB(s) in accordance with this Agreement.

Section 1.31 "Regulatory Authority" means the FDA and any other federal, state, local, or foreign governmental authority, agency, commission, or body with jurisdiction over the conduct of the Study, the Investigational Product, or the activities of the Parties under this Agreement.

Section 1.32 "SAE" means a Serious Adverse Event, defined as any Adverse Event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is a medically important event that may jeopardize the Subject or may require medical or surgical intervention

Section 1.33 "Safety Report" means any safety report required to be submitted to the FDA under 21 C.F.R. § 312.32, including seven (7)-day reports for fatal or life-threatening unexpected suspected adverse reactions and fifteen (15)-day reports for all other reportable safety events.

Section 1.34 "Signing Date" means the date on which this Agreement is executed by duly authorized representatives of both Parties, which date may precede the Effective Date.

Section 1.35 "Site Maintenance Fee" means the annual maintenance fee of Forty Thousand Dollars ($40,000) per Participating Site per year, payable in accordance with Section 3.4 of this Agreement.

Section 1.36 "Start-Up Fee" means the site start-up fee of Seventy-Five Thousand Dollars ($75,000) per Participating Site, payable in accordance with Section 3.3 of this Agreement.

Section 1.37 "Study" means the Phase III, randomized, double-blind, placebo-controlled clinical trial of penterafenib (PPC-4871) in subjects with advanced hepatocellular carcinoma, conducted under the Protocol at the Participating Sites pursuant to the terms of this Agreement.

Section 1.38 "Subject" means an individual human participant who has been enrolled in the Study in accordance with the Protocol and applicable informed consent requirements.

Section 1.39 "Subject Injury" means any physical injury, illness, adverse health consequence, or exacerbation of a pre-existing condition suffered by a Subject that arises out of or in connection with the Subject's participation in the Study, including without limitation any injury caused by the administration of the Investigational Product or any study procedure required by the Protocol.

Section 1.40 "Term" means the period commencing on the Effective Date and continuing until the termination or expiration of this Agreement in accordance with Article 13.

ARTICLE 2 — SCOPE OF WORK AND STUDY CONDUCT

Section 2.1 — Engagement; Study Overview. (a) Sponsor hereby engages Site Network, and Site Network hereby accepts such engagement, to conduct the Study at the Participating Sites in accordance with the Protocol, this Agreement, GCP, and all Applicable Law. Site Network shall use commercially reasonable efforts to perform all Study activities in a timely, professional, and competent manner and in accordance with the

Section 2.2 — Participating Sites. (a) The Study shall be conducted at up to thirty-eight (38) Participating Sites located across fourteen (14) states within the United States, as identified on Schedule 1 attached hereto. The Parties anticipate that all thirty-eight (38) Sites will be activated during the first twelve (12) months following the Effective Date, subject to the timely satisfaction of all regulatory and i

Section 2.3 — Principal Investigator and Co-Principal Investigator. (a) The Global Principal Investigator for the Study shall be Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center. Dr. Aldridge shall serve as the primary scientific leader of the Study and shall be responsible for overseeing the overall scientific conduct of the Study across all Participating Sites, inclu

Section 2.4 — Protocol Compliance. (a) All Study activities at each Participating Site shall be conducted in strict compliance with the Protocol, GCP, and all Applicable Law. Site Network shall ensure that all Investigators, sub-investigators, study coordinators, and other site personnel involved in the conduct of the Study are trained on and comply with the Protocol and all applicable regulatory requirements. (b) No

Section 2.5 — Regulatory Approvals and IRB Oversight. (a) No Subject shall be enrolled at any Participating Site until that Site has obtained written approval (or favorable opinion) from the applicable IRB for the Protocol, the informed consent form, and all other study-specific documents requiring IRB review, and until all other regulatory and institutional approvals necessary for the conduct of the Study at that Si

Section 2.6 — Investigational Product Supply. (a) Sponsor shall supply the Investigational Product, including penterafenib (PPC-4871) and matching placebo, to each Participating Site at no cost to Site Network or any Participating Site. The Investigational Product shall be manufactured in accordance with current Good Manufacturing Practice ("cGMP") regulations and shall be labeled and packaged in accordance with the

Section 2.7 — Approved Subcontractors. (a) Sponsor has engaged the Approved Subcontractors listed on Exhibit K to perform certain Study-related services in support of the Study. Site Network acknowledges and agrees that the Approved Subcontractors shall perform their respective services in accordance with their agreements with Sponsor and that Site Network shall cooperate fully with all Approved Subcontractors in the

Section 2.8 — Record Keeping. (a) Each Participating Site shall maintain complete, accurate, and legible source documents and study records for each Subject enrolled in the Study, including without limitation medical records, laboratory reports, imaging reports, case report forms (whether electronic or paper), drug accountability records, informed consent documents, and all other documents and records required by the

ARTICLE 3 — COMPENSATION AND PAYMENT

Section 3.1 — Total Compensation. (a) The total compensation payable by Sponsor to Site Network under this Agreement shall not exceed Eighty Million Dollars ($80,000,000) over the projected life of the Study (the "Total Compensation"), subject to adjustment only as expressly provided in this Agreement, including through the change order process set forth in Section 3.8. The Total Compensation is inclusive of all per-

Section 3.2 — Per-Patient Site Fees. (a) Sponsor shall pay Site Network a Per-Patient Fee of Fifty-Two Thousand Dollars ($52,000) per Subject for each Subject enrolled in the Study from screening through study completion (or early termination of such Subject's participation). Based on the planned enrollment of one thousand two hundred (1,200) Subjects, the total estimated per-patient site fees under this Agreement ar

Section 3.3 — Start-Up Fees. (a) Sponsor shall pay Site Network a Start-Up Fee of Seventy-Five Thousand Dollars ($75,000) for each Participating Site, for an estimated total of Two Million Eight Hundred Fifty Thousand Dollars ($2,850,000) across all thirty-eight (38) Participating Sites. The Start-Up Fee is intended to compensate each Participating Site for the costs associated with site activation, including regulat

Section 3.4 — Annual Site Maintenance Fees. (a) Sponsor shall pay Site Network an annual Site Maintenance Fee of Forty Thousand Dollars ($40,000) per Participating Site per year, for an estimated total of Five Million Three Hundred Twenty Thousand Dollars ($5,320,000) over the projected life of the Study (based on an average active participation period of approximately three and one-half (3.5) years per Site across t

Section 3.5 — Investigator Grants. (a) Sponsor shall provide Investigator Grants in the aggregate amount of One Million Five Hundred Thousand Dollars ($1,500,000) to support academic publication efforts by Investigators in connection with the Study. Investigator Grants are intended to support the preparation, submission, and publication of manuscripts reporting Study results in peer-reviewed scientific and medical jo

Section 3.6 — Network Coordination Fee. (a) In consideration of the centralized management, coordination, and administrative oversight services provided by Veridian's central office in connection with the Study, Sponsor shall pay Site Network a Network Coordination Fee in the aggregate amount of Four Million Two Hundred Thousand Dollars ($4,200,000). The Network Coordination Fee covers Veridian's costs of centralized

Section 3.7 — Technology / EDC Integration Costs. (a) Sponsor shall pay Site Network a fixed amount of One Million Two Hundred Thirty Thousand Dollars ($1,230,000) for the integration of the Pinnacle Data Solutions, Inc. EDC platform across all Participating Sites, including the costs of system configuration, user account setup, site-level training, data validation programming, and ongoing technical support during th

Section 3.8 — Contingency / Change Order Reserve. (a) The Parties have established a contingency and change order reserve fund in the amount of Two Million Five Hundred Thousand Dollars ($2,500,000) (the "Reserve Fund") to cover unanticipated costs, Protocol amendments, additional study procedures, changes in the number of Participating Sites, or other modifications to the scope of work that may arise during the cour

Section 3.9 — Invoicing and Payment Terms. (a) Site Network shall submit invoices to Sponsor upon the achievement of the applicable payment milestones set forth in this Article 3 and the Budget, accompanied by supporting documentation reasonably sufficient to demonstrate that the applicable milestone has been achieved. Invoices shall be submitted in the form and manner reasonably specified by Sponsor from time to tim