SECOND DRAFT — FOR DISCUSSION PURPOSES ONLY
MASTER CLINICAL TRIAL AGREEMENT
May 19, 2023
Second Draft — Prepared by Calderwood & Harkness LLP on behalf of Sponsor
Circulated to: Whitmore, Jansen & Callahan LLP, counsel to Veridian Health Research Network, Inc.
Calderwood & Harkness Matter No. 1018-00004
This draft reflects Sponsor's responses to Site Network's initial markup dated April 28, 2023, and incorporates the Indemnification Term Sheet exchanged May 5, 2023. Bracketed provisions indicate open issues requiring further discussion.
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MASTER CLINICAL TRIAL AGREEMENT
This Master Clinical Trial Agreement (this "MCTA" or this "Agreement") is entered into as of [\\\\\\\_], 2023 (the "Effective Date"), by and between:
PENTERRA PHARMACEUTICALS CORP., a corporation organized and existing under the laws of the State of Delaware, with its principal offices located at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540 (hereinafter referred to as "Sponsor" or "Penterra");
and
VERIDIAN HEALTH RESEARCH NETWORK, INC., a corporation organized and existing under the laws of the State of Delaware and recognized as a tax-exempt organization under Section 501(c)(3) of the Internal Revenue Code, with its principal offices located at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104 (hereinafter referred to as "Site Network" or "Veridian").
Sponsor and Site Network are each individually referred to herein as a "Party" and collectively as the "Parties."
RECITALS
WHEREAS, Sponsor is the holder of Investigational New Drug Application No. IND 157823, filed with the United States Food and Drug Administration (the "FDA"), for the investigational product penterafenib (PPC-4871), an oral multi-kinase inhibitor being developed for use in the treatment of advanced hepatocellular carcinoma and related oncology indications;
WHEREAS, the FDA authorized the IND filed by Sponsor in October 2021, and Sponsor has since completed a Phase II clinical trial, the results of which were reported in January 2023 and demonstrated a thirty-eight percent (38%) objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC), thereby supporting advancement of the investigational product into a pivotal Phase III clinical trial;
WHEREAS, Sponsor desires to conduct a Phase III, randomized, double-blind, placebo-controlled clinical trial designated as Protocol PPC-4871-III, titled "CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology" (ClinicalTrials.gov Identifier: NCT05928174) (the "Study" or the "Trial"), for the purpose of evaluating the efficacy and safety of penterafenib in patients with advanced hepatocellular carcinoma who have received prior systemic therapy;
WHEREAS, Site Network operates a network of thirty-eight (38) academic medical centers and affiliated research institutions across fourteen (14) states throughout the United States, with an annual research volume of approximately $1.4 billion in sponsored research, and possesses the institutional capabilities, qualified personnel, patient populations, and infrastructure necessary to support the conduct of the Study;
WHEREAS, Sponsor desires to engage Site Network and its member institutions to serve as clinical trial sites for the Study, and Site Network desires to participate in the Study and to coordinate participation of its member institutions, subject to the terms and conditions set forth herein;
WHEREAS, Sponsor has separately engaged Meridian Contract Research Organization, Inc. ("Meridian CRO"), a contract research organization with offices at 9200 Corporate Boulevard, Raleigh, North Carolina 27615, to provide monitoring, data management, safety reporting, and biostatistics services for the Study pursuant to a Master Services Agreement between Sponsor and Meridian CRO dated January 15, 2023 (the "CRO Agreement");
WHEREAS, the Parties intend this Agreement to serve as the master agreement governing the overall relationship between Sponsor and Site Network with respect to the Study, with each participating Site Network member institution executing an Individual Site Agreement substantially in the form attached hereto as Exhibit C, which shall incorporate the terms of this MCTA by reference and set forth the site-specific obligations, budgets, and personnel for each participating institution; and
NOW, THEREFORE, in consideration of the mutual covenants and agreements set forth herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows:
ARTICLE 1 — DEFINITIONS
As used in this Agreement, the following capitalized terms shall have the meanings set forth below. Capitalized terms used but not otherwise defined in this Article 1 shall have the meanings ascribed to them elsewhere in this Agreement.
1.1 "Adverse Event" or "AE" means any untoward medical occurrence in a Subject who has been administered the Investigational Product, whether or not such occurrence has a causal relationship with the Investigational Product. 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.
1.2 "Aggregate Cap" has the meaning set forth in Article 10 (Indemnification) of this Agreement.
1.3 "Applicable Law" means all applicable federal, state, and local laws, statutes, rules, regulations, ordinances, guidelines, and orders, including without limitation the Federal Food, Drug, and Cosmetic Act (21 U.S.C. §§ 301 et seq.), the regulations promulgated by the FDA at 21 C.F.R. Parts 11, 50, 54, 56, and 312, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ("ICH") Guideline for Good Clinical Practice E6(R2), the Health Insurance Portability and Accountability Act of 1996, as amended, and the regulations promulgated thereunder at 45 C.F.R. Parts 160 and 164 ("HIPAA"), the Anti-Kickback Statute (42 U.S.C. § 1320a-7b), the False Claims Act (31 U.S.C. §§ 3729–3733), and the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h), in each case as amended from time to time during the term of this Agreement.
1.4 "CRO" means Meridian Contract Research Organization, Inc., a Delaware corporation with offices at 9200 Corporate Boulevard, Raleigh, North Carolina 27615, engaged by Sponsor under the CRO Agreement to provide monitoring, data management, safety reporting, biostatistical analysis, and related services in connection with the Study.
1.5 "Central Laboratory" means Northbridge Bioanalytical Laboratories, Inc., located at 2900 Commerce Way, Baltimore, Maryland 21224, which has been designated by Sponsor to provide central laboratory services, including pharmacokinetic/pharmacodynamic (PK/PD) analyses, biomarker analyses, and safety laboratory testing for the Study.
1.6 "Confidential Information" has the meaning set forth in Article 12 of this Agreement.
1.7 "EDC Platform" means the electronic data capture system provided by Pinnacle Data Solutions, Inc., located at 6000 Clearwater Drive, San Diego, California 92121, which shall be used by all Sites for the electronic capture, transmission, and management of Study Data in connection with the conduct of the Study.
1.8 "Effective Date" means the date first written above in the preamble of this Agreement.
1.9 "GCP" or "Good Clinical Practice" means the standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected, as set forth in the ICH Guideline for Good Clinical Practice E6(R2) and 21 C.F.R. Part 312.
1.10 "Global Principal Investigator" means Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, 1200 University Avenue, Philadelphia, Pennsylvania 19104, who shall serve as the overall principal investigator for the Study, or such other individual as may be designated in accordance with Section 5.1 of this Agreement.
1.11 "IND" means Investigational New Drug Application No. IND 157823, filed with the FDA by Sponsor for penterafenib (PPC-4871) and maintained in good standing by Sponsor throughout the term of this Agreement.
1.12 "Individual Site Agreement" means the form of joinder and site-specific agreement attached hereto as Exhibit C, to be executed by each participating Veridian Network member institution, which shall incorporate the terms and conditions of this MCTA by reference and set forth site-specific details including investigator identification, institutional approvals, site-specific budgets, and other site-level obligations.
1.13 "Institutional Review Board" or "IRB" means the duly constituted ethics committee or institutional review board having jurisdiction over each Site's conduct of the Study, including the Graystone University Institutional Review Board (IRB Registration No. IRB00012847) and the Veridian Central IRB, each of which shall be organized and operated in accordance with 21 C.F.R. Part 56 and applicable federal and state law.
1.14 "Investigational Product" means penterafenib (PPC-4871), an oral multi-kinase inhibitor, and matching placebo, each as manufactured, labeled, packaged, and supplied by Sponsor for use in the Study in accordance with the Protocol.
1.15 "Investigator" means each principal investigator, co-principal investigator, and sub-investigator at a participating Site who is identified on the applicable FDA Form 1572 (Statement of Investigator) for such Site and who is responsible for the conduct of the Study at that Site or a portion thereof.
1.16 "Participating Site" or "Site" means each Veridian Network member institution that has executed an Individual Site Agreement and has been activated by Sponsor for participation in the Study, as identified in Schedule 1 hereto, as may be amended from time to time.
1.17 "Per-Patient Fee" means the amount of Fifty-Two Thousand Dollars ($52,000) per enrolled Subject, payable in milestones as set forth in Section 6.3 of this Agreement and as further detailed in the Budget and Payment Schedule attached as Exhibit B.
1.18 "Protocol" means Protocol PPC-4871-III (CLARION), including the protocol synopsis attached as Exhibit A and all protocol amendments approved by Sponsor and the applicable IRBs, as such Protocol may be amended from time to time during the conduct of the Study.
1.19 "Serious Adverse Event" or "SAE" means any adverse event occurring at any dose that results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or any other important medical event that, based upon appropriate medical judgment, may jeopardize the Subject and may require medical or surgical intervention to prevent one of the foregoing outcomes, as defined in 21 C.F.R. § 312.32.
1.20 "Study Data" means all data generated, collected, or derived during the conduct of the Study, including without limitation data entered into the EDC Platform, case report forms (whether electronic or paper-based), source data, laboratory data from the Central Laboratory and local laboratories, biomarker data, pharmacokinetic and pharmacodynamic data, imaging data, patient-reported outcome data, safety data, and all analyses, reports, compilations, and databases derived therefrom.
1.21 "Subject" means an individual who has provided informed consent and has been enrolled in the Study as a participant in accordance with the Protocol, applicable IRB requirements, and Applicable Law.
1.22 "Subject Injury" means any physical injury, illness, or adverse health consequence to a Subject that is causally related to, or reasonably attributable to, the Subject's participation in the Study, including but not limited to injuries resulting from the administration of the Investigational Product, study procedures performed pursuant to the Protocol, or any medical intervention conducted as part of the Study.
ARTICLE 2 — SCOPE OF AGREEMENT
2.1 Purpose. Sponsor hereby engages Site Network to coordinate and facilitate the participation of its member institutions as clinical trial sites for the conduct of Protocol PPC-4871-III (CLARION), and Site Network hereby accepts such engagement, subject to the terms and conditions set forth in this Agreement. Site Network shall serve as the central administrative and coordinating entity for its member institutions' participation in the Study.
2.2 Study Description. The Study is a Phase III, randomized, double-blind, placebo-controlled, multi-center clinical trial of penterafenib (PPC-4871) versus matching placebo in patients with advanced hepatocellular carcinoma who have received at least one prior line of systemic therapy. The Study is designed to evaluate the superiority of penterafenib over placebo with respect to the primary efficacy endpoint and key secondary endpoints described in this Article 2 and in the Protocol.
2.3 Planned Enrollment. The Study is designed to enroll a total of approximately one thousand two hundred (1,200) Subjects across all participating Sites, who shall be randomized in a 2:1 ratio, with approximately eight hundred (800) Subjects assigned to the penterafenib arm and approximately four hundred (400) Subjects assigned to the placebo arm. Enrollment targets for individual Sites shall be set forth in the applicable Individual Site Agreements and may be adjusted by Sponsor in consultation with Site Network based on enrollment performance.
2.4 Number of Sites. The Study shall be conducted at thirty-eight (38) Veridian Network member institution Sites located across fourteen (14) states, as set forth in Schedule 1 attached hereto. Sponsor reserves the right, in consultation with Site Network, to add or remove Sites based on enrollment performance, site readiness, or other operational considerations, subject to the terms of the applicable Individual Site Agreement.
2.5 Projected Timeline. The projected timeline for the Study is as follows:
(a) Enrollment Period: Approximately forty-two (42) months, with a target first-patient-in date of August 14, 2023, and a projected last-patient-in date of February 2027.
(b) Follow-Up Period: Approximately eighteen (18) months of post-treatment follow-up following the close of enrollment.
(c) Total Study Duration: Approximately sixty (60) months from first patient enrolled to projected study completion, with projected study completion estimated as August 2028.
(d) Individual Site Activation: Each Site shall be activated upon completion of all regulatory, IRB, and contractual requirements as set forth in this Agreement and the applicable Individual Site Agreement.
The foregoing timelines are estimates and projections only and are subject to adjustment based on enrollment rates, regulatory developments, and other factors. Sponsor shall provide Site Network with periodic updates regarding any material changes to the projected timeline.
2.6 Primary Endpoint. The primary efficacy endpoint of the Study is overall survival (OS), defined as the time from randomization to death from any cause.
2.7 Key Secondary Endpoints. The key secondary endpoints of the Study include:
(a) Progression-free survival (PFS), defined as the time from randomization to documented disease progression (per RECIST v1.1 criteria) or death from any cause, whichever occurs first;
(b) Objective response rate (ORR), defined as the proportion of Subjects achieving a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 criteria;
(c) Duration of response (DOR), defined as the time from the first documented response (CR or PR) to documented disease progression or death from any cause.
Additional secondary and exploratory endpoints are described in the Protocol and Protocol Synopsis.
2.8 Protocol Synopsis. A synopsis of Protocol PPC-4871-III (CLARION) is attached hereto as Exhibit A and incorporated herein by reference. In the event of any conflict between the Protocol Synopsis and the full Protocol, the full Protocol shall control.
2.9 Individual Site Agreements. Each member institution of the Veridian Network that participates in the Study shall execute an Individual Site Agreement substantially in the form attached hereto as Exhibit C. Each Individual Site Agreement shall incorporate the terms and conditions of this MCTA by reference and shall set forth site-specific details, including the identity of the Site's principal investigator and sub-investigators, institutional IRB information, site-specific regulatory approvals, local budget considerations, and any site-specific modifications or addenda approved by both Parties. No member institution shall commence Study activities until it has executed an Individual Site Agreement and satisfied all activation requirements set forth therein and in this MCTA.
ARTICLE 3 — RESPONSIBILITIES OF SPONSOR
3.1 Protocol Development. Sponsor shall be responsible for the design, development, and finalization of the Protocol, including all protocol amendments. Sponsor shall provide Site Network and each Site with the current version of the Protocol and all amendments thereto in a timely manner. Sponsor shall consult with the Global Principal Investigator regarding substantive protocol amendments and shall consider feedback from Site Network and participating Investigators, provided that final authority over the Protocol shall reside with Sponsor.
3.2 IND Maintenance. Sponsor shall maintain IND 157823 in good standing with the FDA throughout the duration of the Study, including the timely submission of all required IND annual reports, safety reports, protocol amendments, and other filings required under 21 C.F.R. Part 312. Sponsor shall promptly notify Site Network of any FDA clinical hold, partial clinical hold, or other regulatory action affecting the IND that may impact the conduct of the Study at any Site.
3.3 Supply of Investigational Product. Sponsor shall manufacture or cause to be manufactured the Investigational Product (penterafenib and matching placebo) in accordance with current Good Manufacturing Practice (cGMP) requirements, and shall supply each Site with sufficient quantities of the Investigational Product at no cost to Site Network or any Site. All Investigational Product shall be properly labeled in accordance with 21 C.F.R. § 312.6 and applicable FDA requirements. Sponsor shall be responsible for the distribution and shipment of the Investigational Product to each Site, including chain-of-custody documentation, temperature monitoring, and compliance with all applicable storage and handling requirements specified in the Protocol and the Investigator's Brochure.
3.4 CRO Oversight. Sponsor shall manage its relationship with Meridian CRO (9200 Corporate Boulevard, Raleigh, North Carolina 27615) pursuant to the CRO Agreement and shall ensure that Meridian CRO performs its obligations in compliance with the Protocol, GCP, and all Applicable Law. Sponsor shall remain ultimately responsible for the quality and integrity of all activities delegated to Meridian CRO. Sponsor shall promptly inform Site Network of any material changes to the scope of Meridian CRO's services or any replacement of Meridian CRO as the contract research organization for the Study.
3.5 EDC Platform. Sponsor shall provide access to the EDC Platform operated by Pinnacle Data Solutions, Inc. (6000 Clearwater Drive, San Diego, California 92121) for electronic data capture at all Sites. Sponsor shall be responsible for the configuration, validation, and maintenance of the EDC Platform in compliance with 21 C.F.R. Part 11 requirements. Sponsor shall provide each Site with user credentials, training, and technical support necessary for the Sites to enter Study Data into the EDC Platform.
3.6 Central Laboratory. Sponsor shall arrange and maintain central laboratory services through the Central Laboratory (Northbridge Bioanalytical Laboratories, Inc., 2900 Commerce Way, Baltimore, Maryland 21224) for pharmacokinetic/pharmacodynamic analyses, biomarker analyses, and safety laboratory testing as specified in the Protocol. Sponsor shall be responsible for the shipment of laboratory kits to Sites, the logistics of specimen collection and transport, and the integration of central laboratory data into the Study database.
3.7 Regulatory Filings. Sponsor shall be responsible for all regulatory filings and safety reporting obligations with respect to the IND, including but not limited to: (a) seven (7)-calendar-day reporting to the FDA of any unexpected fatal or life-threatening suspected adverse reaction, as required by 21 C.F.R. § 312.32(c)(2); (b) fifteen (15)-calendar-day reporting to the FDA of all other IND safety reports, as required by 21 C.F.R. § 312.32(c)(1); and (c) distribution of IND safety reports to all participating Investigators and IRBs as required by 21 C.F.R. § 312.32(c)(3).
3.8 Training. Prior to the activation of each Site, Sponsor shall provide comprehensive training to Investigators and site staff on the Protocol, GCP requirements, the EDC Platform, the Investigational Product (including dosing, administration, storage, handling, accountability, and return/destruction procedures), safety reporting procedures (as further described in Exhibit J), and all other study-specific procedures. Sponsor shall also provide supplemental training as needed in connection with protocol amendments or other changes to study procedures.
3.9 Monitoring. Sponsor, through Meridian CRO, shall conduct site monitoring visits in accordance with the monitoring plan established for the Study, including site initiation visits, periodic monitoring visits (at intervals specified in the monitoring plan), and site close-out visits. Monitoring visits shall be conducted in accordance with GCP and ICH E6(R2) requirements and shall include, at a minimum, source data verification, review of informed consent documentation, Investigational Product accountability, and review of SAE reporting. Sites shall provide Sponsor and Meridian CRO with reasonable access to study records, source documents, and facilities during monitoring visits.
3.10 Insurance. Sponsor shall obtain and maintain, at its own expense, clinical trial liability insurance in accordance with the requirements set forth in Article 11 and Exhibit E of this Agreement.
3.11 Payment. Sponsor shall make payments to Site Network and each participating Site in accordance with the Budget and Payment Schedule set forth in Exhibit B and as further described in Article 6 of this Agreement. Payments shall be made within forty-five (45) days following Sponsor's receipt of a proper and complete invoice submitted through Veridian's centralized invoicing system.
3.12 Approved Subcontractors. Sponsor's approved subcontractors for the Study are listed in Exhibit K and include: (a) Meridian Contract Research Organization, Inc. (monitoring, data management, safety reporting, and biostatistics); (b) Pinnacle Data Solutions, Inc. (EDC Platform); and (c) Northbridge Bioanalytical Laboratories, Inc. (central laboratory services). Sponsor shall ensure that each approved subcontractor is bound by obligations of confidentiality and data protection consistent with the requirements of this Agreement.
3.13 Regulatory Counsel. Sponsor has engaged the law firm of Castleton & Hargrove LLP, located at 1100 Connecticut Avenue NW, Suite 900, Washington, DC 20036, for FDA regulatory strategy in connection with the Investigational Product and the Study. Dr. Priya Sundaram, Esq. serves as lead regulatory counsel at Castleton & Hargrove LLP. Site Network acknowledges and agrees that communications between Sponsor and Castleton & Hargrove LLP regarding regulatory strategy are subject to the attorney-client privilege and are not required to be disclosed to Site Network.
ARTICLE 4 — RESPONSIBILITIES OF SITE NETWORK
4.1 Site Coordination. Veridian shall coordinate and oversee the participation of its thirty-eight (38) member institutions in the Study, shall facilitate the execution of Individual Site Agreements by each member institution, and shall serve as the central administrative point of contact between Sponsor and the participating Sites. Veridian shall designate a Network Study Director to serve as the primary liaison with Sponsor and Meridian CRO for Study-related operational matters. Veridian's coordination responsibilities shall include, without limitation, assisting Sites with regulatory and IRB submissions, facilitating site activation processes, supporting enrollment tracking, coordinating centralized invoicing, and communicating protocol amendments and other Study-related information to Sites.
4.2 Investigator Identification and Oversight. Site Network shall ensure that each participating Site identifies qualified Investigators with appropriate training, experience, and expertise to conduct the Study in accordance with the Protocol, GCP, and Applicable Law. The Global Principal Investigator for the Study shall be Dr. Catherine Aldridge, M.D., Ph.D., of Graystone University Medical Center, 1200 University Avenue, Philadelphia, Pennsylvania 19104. The Co-Principal Investigator for the Study shall be Dr. Howard Matsuoka, M.D., of Lakemont Medical Center, 4400 North Michigan Drive, Chicago, Illinois 60611. Each site-level principal investigator shall be identified in the applicable Individual Site Agreement and shall be subject to Sponsor's approval prior to site activation.
4.3 IRB Approvals. Site Network shall ensure that each participating Site obtains and maintains approval from its applicable Institutional Review Board prior to the enrollment of any Subject at that Site and throughout the duration of the Site's participation in the Study. Graystone University Medical Center shall obtain and maintain approval from the Graystone University Institutional Review Board (IRB Registration No. IRB00012847). Non-Pennsylvania Sites within the Veridian Network may, at their election and subject to Sponsor's approval, rely upon the Veridian Central IRB for review and approval of the Protocol and informed consent documents, pursuant to an IRB Authorization Agreement executed between the relying institution and the Veridian Central IRB in accordance with applicable regulations. Each Site shall be responsible for timely submission of all required continuing reviews, amendments, reportable events, and other IRB communications.
4.4 Protocol Compliance. Each participating Site shall conduct the Study in strict accordance with the Protocol, GCP, ICH E6(R2) guidelines, and all Applicable Law. Any deviation from the Protocol shall be documented and reported to Sponsor and Meridian CRO in accordance with the procedures set forth in the Protocol and in Exhibit J. Deviations that are made to protect the immediate safety of a Subject shall be reported to Sponsor and the applicable IRB as soon as practicable but no later than forty-eight (48) hours following the deviation.
4.5 Informed Consent. Each Site shall obtain and document written informed consent from each Subject prior to the Subject's participation in any study-related activities, in accordance with 21 C.F.R. Part 50, applicable IRB requirements, and Applicable Law. The informed consent form shall be the form approved by the applicable IRB and shall include all elements required under 21 C.F.R. § 50.25. Sites shall ensure that each Subject is provided with adequate time and opportunity to consider participation and that no coercion or undue influence is exerted upon any prospective Subject.
4.6 Safety Reporting. Each Site shall report all Serious Adverse Events to Sponsor and Meridian CRO within twenty-four (24) hours of the Site's awareness of the event, in accordance with the Safety Reporting Procedures set forth in Exhibit J. Reports shall be submitted using the SAE reporting forms and communication channels specified in Exhibit J. Sites shall also report all Adverse Events and other safety information as required by the Protocol, including follow-up reports until resolution or stabilization of the event.
4.7 Data Entry and Source Documentation. Each Site shall enter Study Data into the EDC Platform accurately, completely, and in a timely manner in accordance with the timelines specified in the Protocol and the data management plan. Sites shall maintain complete and accurate source documents for all Study Data entered into the EDC Platform, and shall make such source documents available for review during monitoring visits, audits, and regulatory inspections.
4.8 Record Retention. Each Site shall retain all source documents, study records, regulatory files, IRB correspondence, informed consent forms, and other documentation related to the Study for a minimum period of fifteen (15) years following the completion or termination of the Study, or for such longer period as may be required by Applicable Law, institutional policy, or Sponsor's written instructions, whichever is longest. No study records shall be destroyed without prior written authorization from Sponsor.
4.9 Form FDA 1572. Each Investigator at each participating Site shall complete and maintain a current FDA Form 1572 (Statement of Investigator) in accordance with 21 C.F.R. § 312.53. The initial Form 1572 for each Investigator shall be submitted to Sponsor prior to site activation, and updated Form 1572s shall be submitted promptly upon any change in the information previously provided, including changes to sub-investigators, facilities, or IRB information.
4.10 Financial Disclosure. Each Investigator shall complete a Financial Disclosure Certification in accordance with 21 C.F.R. Part 54, using the template attached as Exhibit I or such other form as may be provided by Sponsor. Financial disclosure certifications shall be submitted to Sponsor prior to site activation and shall be updated annually during the conduct of the Study and for one (1) year following the completion of the Study. Site Network shall ensure that all Investigators are informed of their obligations under the financial disclosure regulations and shall assist in the collection and submission of financial disclosure certifications to Sponsor.
4.11 Regulatory Compliance. Site Network represents and warrants that it, each participating Site, and each Investigator shall comply with all Applicable Law in the conduct of the Study, including without limitation the Anti-Kickback Statute (42 U.S.C. § 1320a-7b), the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h), and HIPAA (45 C.F.R. Parts 160 and 164). Detailed representations and covenants regarding regulatory compliance are set forth in Exhibit H.
4.12 Insurance. Veridian and each participating Site shall obtain and maintain insurance coverage as set forth in Article 11 and Exhibit E of this Agreement.
4.13 Notification of Debarment. Site Network shall notify Sponsor in writing immediately, and in no event more than five (5) business days, after becoming aware that any Investigator, sub-investigator, or site staff member involved in the conduct of the Study has been debarred, suspended, proposed for debarment, or otherwise excluded under 21 U.S.C. § 335a (the Generic Drug Enforcement Act), or has been listed on the Office of Inspector General's List of Excluded Individuals/Entities or the General Services Administration's System for Award Management exclusion list. Upon receipt of such notification, Sponsor shall have the right to require the immediate removal of the affected individual from any Study-related activities.
ARTICLE 5 — PRINCIPAL INVESTIGATOR OBLIGATIONS
5.1 Global Principal Investigator. Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology, Graystone University Medical Center, 1200 University Avenue, Philadelphia, Pennsylvania 19104, shall serve as the Global Principal Investigator for the Study. Dr. Aldridge shall be responsible for overall scientific and medical oversight of the Study across all participating Sites, including coordination of multi-center analyses, oversight of data quality and subject safety across the network, and coordination of multi-center publications in accordance with Article 13. Replacement of the Global Principal Investigator shall require the prior written consent of Sponsor, such consent not to be unreasonably withheld, conditioned, or delayed. In the event that Dr. Aldridge becomes unable or unwilling to serve as Global Principal Investigator, Site Network shall propose a replacement candidate of comparable qualifications and experience within thirty (30) days, subject to Sponsor's written approval.
5.2 Co-Principal Investigator. Dr. Howard Matsuoka, M.D., Lakemont Medical Center, 4400 North Michigan Drive, Chicago, Illinois 60611, shall serve as Co-Principal Investigator for the Study. Dr. Matsuoka shall support the Global Principal Investigator in the scientific and medical oversight of the Study, with particular responsibility for coordinating Study activities at Midwest and Western Region Sites within the Veridian Network, as designated by the Global Principal Investigator. Replacement of the Co-Principal Investigator shall be subject to the same procedures as set forth in Section 5.1 above.
5.3 Investigator Undertaking. Each Investigator (including each site-level principal investigator, co-principal investigator, and sub-investigator) shall execute an Investigator Undertaking substantially in the form attached hereto as Exhibit I, acknowledging and agreeing to comply with the Protocol, GCP, Applicable Law, and the terms of this Agreement and the applicable Individual Site Agreement. Investigator Undertakings shall be submitted to Sponsor prior to the activation of the applicable Site and shall be maintained in the regulatory files for each Site.
5.4 [Investigator Personal Liability — Open Issue.]
[Note: The scope of Investigator personal liability versus institutional liability remains an open issue between the Parties. Veridian's position, as set forth in its initial markup dated April 28, 2023, is that Investigators should bear no personal liability under this Agreement or any Individual Site Agreement except in cases of gross negligence or willful misconduct, and that any indemnification obligations of Site Indemnitees under Article 10 should flow to the institution rather than the individual Investigator. Sponsor acknowledges Veridian's position but reserves the right to address individual Investigator carve-outs from the indemnification framework, particularly in cases involving individual Investigator misconduct, unauthorized protocol deviations, or individual fraud. The Parties intend to address this issue in the next round of negotiations and in Veridian's second markup.]
ARTICLE 6 — BUDGET AND PAYMENT
6.1 Total Deal Value. The total projected value of payments under this Agreement across all Veridian Network Sites over the projected life of the Study is Eighty Million Dollars ($80,000,000), subject to adjustment based on actual enrollment, the number of activated Sites, and other variables as set forth in this Article 6 and the Budget and Payment Schedule attached as Exhibit B.
6.2 Budget Breakdown. The total projected budget for the Study, as further detailed in Exhibit B, is comprised of the following categories:
(a) Per-Patient Site Fees: Fifty-Two Thousand Dollars ($52,000) per enrolled Subject multiplied by one thousand two hundred (1,200) projected Subjects, for a total projected per-patient site fee expenditure of Sixty-Two Million Four Hundred Thousand Dollars ($62,400,000).
(b) Start-Up Fees: Seventy-Five Thousand Dollars ($75,000) per Site multiplied by thirty-eight (38) Sites, for a total start-up fee expenditure of Two Million Eight Hundred Fifty Thousand Dollars ($2,850,000).
(c) Annual Site Maintenance Fees: Forty Thousand Dollars ($40,000) per Site per year multiplied by thirty-eight (38) Sites over an average of three and one-half (3.5) years per Site, for a total projected annual site maintenance fee expenditure of Five Million Three Hundred Twenty Thousand Dollars ($5,320,000).
(d) Investigator Grants (Publication and Academic Support): One Million Five Hundred Thousand Dollars ($1,500,000), allocated to support publication activities, academic presentations, and related scholarly work by Investigators in connection with the Study results, subject to the terms of Article 13.
(e) Network Coordination/Administrative Fee to Veridian Central: Four Million Two Hundred Thousand Dollars ($4,200,000), payable to Veridian in its capacity as the central coordinating and administrative entity for the Study, as further described in Section 6.5 below.
(f) Technology/EDC Integration Costs (Pinnacle Data Solutions): One Million Two Hundred Thirty Thousand Dollars ($1,230,000), representing costs associated with the configuration, integration, validation, training, and ongoing support of the EDC Platform at all participating Sites.
(g) Contingency/Change Order Reserve: Two Million Five Hundred Thousand Dollars ($2,500,000), reserved for unanticipated costs, protocol amendments requiring additional procedures, change orders, and other contingencies, which shall be accessible only upon mutual written agreement of the Parties.
6.3 Payment Milestones for Per-Patient Fees. The Per-Patient Fee of Fifty-Two Thousand Dollars ($52,000) per enrolled Subject shall be paid in four (4) equal milestone installments as follows, reflecting the agreed position from the Indemnification Term Sheet exchanged May 5, 2023, and Sponsor's response to Veridian's initial request for front-loaded payment milestones:
(i) Twenty-five percent (25%) ($13,000) upon randomization of the Subject;
(ii) Twenty-five percent (25%) ($13,000) upon completion of the Subject's Week 12 assessment visit;
(iii) Twenty-five percent (25%) ($13,000) upon completion of the Subject's Week 24 assessment visit;
(iv) Twenty-five percent (25%) ($13,000) upon the Subject's completion of the Study (i.e., the final study visit) or upon the Subject's early discontinuation from the Study, subject to completion of all required end-of-study data collection procedures.
For each milestone, payment shall be triggered upon the Site's entry into the EDC Platform of the data confirming the applicable milestone event and Sponsor's or Meridian CRO's verification of such data during routine monitoring.
6.4 Start-Up Fee Payment. The Start-Up Fee of Seventy-Five Thousand Dollars ($75,000) per Site shall be payable in two (2) installments:
(a) Fifty percent (50%) (Thirty-Seven Thousand Five Hundred Dollars ($37,500)) upon site activation, defined as the date on which the Site has satisfied all regulatory, IRB, contractual, and logistical requirements for participation in the Study as confirmed by Sponsor in writing; and
(b) Fifty percent (50%) (Thirty-Seven Thousand Five Hundred Dollars ($37,500)) upon the first Subject enrolled (i.e., randomized) at that Site.
6.5 Network Coordination Fee. The Network Coordination/Administrative Fee of Four Million Two Hundred Thousand Dollars ($4,200,000) shall be payable to Veridian in quarterly installments of Three Hundred Thousand Dollars ($300,000) each, over fourteen (14) consecutive quarters, commencing on the first calendar quarter following the Effective Date. Such payments shall compensate Veridian for its central coordination, administrative oversight, and management services rendered in connection with the Study across all participating Sites.
6.6 Site Maintenance Fees. Annual site maintenance fees of Forty Thousand Dollars ($40,000) per Site per year shall be paid annually in advance on each anniversary of the applicable Site's activation date, for so long as such Site remains active and participating in the Study. Site maintenance fees shall cover routine ongoing costs of maintaining the Site's readiness and participation in the Study, including research coordinator support, regulatory file maintenance, IRB continuing review submissions, and site infrastructure.
6.7 Investigator Grants. Investigator grants for publication and academic support shall be disbursed upon the acceptance for publication of manuscripts in peer-reviewed journals or acceptance of presentations at scientific conferences, subject to the prior review and approval process set forth in Article 13 (Publication Rights). The amount of each individual grant shall be determined in accordance with Exhibit B and shall reflect fair market value for the academic and scholarly effort involved.
6.8 Payment Terms. All payments under this Agreement shall be made within forty-five (45) days (Net 45) from Sponsor's receipt of a proper, complete, and undisputed invoice. Payments shall be made in United States Dollars by wire transfer or ACH electronic funds transfer to the bank account designated by Veridian or the applicable Site in writing.
6.9 Invoicing Procedures. Each participating Site shall submit invoices through Veridian's centralized invoicing system. Veridian shall compile, review, and transmit invoices from all Sites to Sponsor on a monthly or quarterly basis, as mutually agreed. All invoices shall reference Protocol PPC-4871-III, the applicable site number, the Subject identification number (where applicable for per-patient milestone payments), and the specific milestone or fee category to which the invoice relates. Incomplete or improperly submitted invoices shall be returned to Veridian for correction and resubmission, and the payment period shall not commence until a proper invoice is received.
6.10 Fair Market Value. The Parties represent and warrant that all payments under this Agreement, including per-patient fees, start-up fees, site maintenance fees, investigator grants, network coordination fees, and all other forms of compensation, reflect the fair market value of the services rendered and items provided, have been negotiated at arm's length, and are not intended to, and shall not, directly or indirectly, serve as an inducement or reward for referrals of patients, prescriptions, or other business, in each case in compliance with the Anti-Kickback Statute (42 U.S.C. § 1320a-7b) and the applicable safe harbor regulations at 42 C.F.R. § 1001.952.
6.11 Taxes. Each Party shall be solely responsible for all taxes, assessments, and other governmental charges imposed upon it as a result of this Agreement, including income taxes, franchise taxes, and other applicable taxes. Sponsor shall withhold amounts from payments under this Agreement only to the extent required by Applicable Law and shall promptly notify Site Network of any withholding obligation. Veridian's Employer Identification Number (EIN) is 23-4178205.
ARTICLE 7 — REGULATORY COMPLIANCE
7.1 Applicable Regulations. The Study shall be conducted in compliance with all Applicable Law, including without limitation the Federal Food, Drug, and Cosmetic Act, the regulations promulgated thereunder at 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), the ICH E6(R2) Guideline for Good Clinical Practice, and HIPAA (45 C.F.R. Parts 160 and 164). Each Party shall remain informed of changes in Applicable Law and shall adjust its procedures as necessary to maintain compliance throughout the term of the Study.
7.2 Anti-Kickback Statute. The Parties represent and warrant that all compensation payable under this MCTA and each Individual Site Agreement is consistent with the fair market value of the services rendered and is structured to satisfy the personal services and management contracts safe harbor under 42 C.F.R. § 1001.952(d). Specifically, each arrangement under this Agreement: (a) is set out in writing and signed by the Parties; (b) specifies the services to be provided; (c) covers all of the services provided by Site Network and the participating Sites in exchange for the compensation; (d) sets forth the aggregate compensation to be paid over the term of the agreement, which compensation has been set in advance, is consistent with fair market value, and is not determined in a manner that takes into account the volume or value of any referrals or business otherwise generated between the Parties; and (e) involves services that do not involve the counseling or promotion of a business arrangement or other activity that violates any federal or state law. The Parties shall cooperate to ensure ongoing compliance with the Anti-Kickback Statute and applicable safe harbors.
7.3 Physician Payments Sunshine Act / Open Payments. Sponsor shall report all payments and other transfers of value made to Investigators, physician-investigators, and applicable institutions (including teaching hospitals) as required by the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h) and the implementing regulations at 42 C.F.R. Part 403, Subpart I. Sites and Investigators shall cooperate with Sponsor's tracking and reporting procedures, including providing accurate National Provider Identifier (NPI) numbers, contact information, and other data reasonably necessary for Sponsor to comply with its Sunshine Act reporting obligations.
7.4 Financial Disclosure (21 C.F.R. Part 54). Each Investigator shall disclose to Sponsor any financial interests in Penterra Pharmaceuticals Corp. or the Investigational Product, including but not limited to equity interests, significant payments, proprietary interests in the Investigational Product, and significant equity interests in a publicly held company, as defined in 21 C.F.R. Part 54. A template Financial Disclosure Certification form is attached to this Agreement as part of Exhibit I. Investigator financial disclosures shall be updated annually and upon any change in financial interests during the Study and for one (1) year following the completion of the Study.
7.5 Debarment/Exclusion. Each Party represents and warrants that, as of the Effective Date, neither the Party itself, nor any of its officers, directors, employees, Investigators, sub-investigators, or key personnel involved in the conduct of the Study, has been debarred, suspended, proposed for debarment, declared ineligible, or voluntarily excluded from participation in any federal healthcare program or from any federal procurement or non-procurement program, or is listed on the FDA's Debarment List pursuant to 21 U.S.C. § 335a, the OIG List of Excluded Individuals/Entities, or the GSA's System for Award Management exclusion list. Each Party shall promptly notify the other Party in writing, in accordance with Section 4.13 of this Agreement, upon becoming aware of any change in the foregoing status with respect to any such individual or entity.
7.6 Regulatory Inspections. Both Parties shall cooperate fully with inspections, audits, and other regulatory activities conducted by the FDA or other regulatory authorities having jurisdiction over the Study. Sites shall permit Sponsor, Meridian CRO, and applicable regulatory authorities access to all study records, source documents, facilities, and personnel involved in the conduct of the Study, at reasonable times and upon reasonable notice (except that regulatory authority inspections may occur without advance notice). Sites shall promptly notify Sponsor of any FDA inspection or other regulatory authority inspection of the Site related to the Study, and shall provide Sponsor with copies of any FDA Form 483 observations or inspection reports related to the Study within five (5) business days of receipt.
7.7 Detailed Regulatory Representations. Detailed representations and covenants regarding regulatory compliance are set forth in Exhibit H, which is incorporated herein by reference.
ARTICLE 8 — STUDY DATA OWNERSHIP AND DATA MANAGEMENT
8.1 Ownership of Study Data. Sponsor shall retain exclusive ownership of all Study Data, including but not limited to all data entered into the EDC Platform, case report forms (whether electronic or paper-based), electronic data, biomarker data, pharmacokinetic and pharmacodynamic data, imaging data, patient-reported outcome data, safety and adverse event data, laboratory data from the Central Laboratory and local laboratories, and all analyses, reports, compilations, statistical outputs, and databases derived therefrom. Site Network and each participating Site hereby assign and agree to assign to Sponsor all right, title, and interest in and to all Study Data, to the extent not already owned by Sponsor, effective upon creation thereof. Notwithstanding the foregoing, source documents created and maintained by Sites in the ordinary course of patient care (e.g., medical records) shall remain the property of the applicable Site or institution, subject to Sponsor's access rights as set forth in this Agreement.
8.2 EDC Platform. All Study Data shall be entered into the EDC Platform provided by Pinnacle Data Solutions, Inc. Each Site shall ensure that Study Data is entered accurately, completely, and within the timelines specified in the Protocol and the data management plan. Sites shall use only authorized user credentials for access to the EDC Platform and shall comply with all security and access-control procedures established by Sponsor and Pinnacle Data Solutions. Electronic records entered into the EDC Platform shall comply with the requirements of 21 C.F.R. Part 11 regarding electronic records and electronic signatures.
8.3 Central Laboratory Data. Laboratory results, including PK/PD, biomarker, and safety laboratory data, generated by Northbridge Bioanalytical Laboratories, Inc. shall be transmitted electronically to the Study database and integrated under Sponsor's direction. Sponsor shall be responsible for the quality control and data reconciliation of central laboratory data with corresponding clinical data entered by Sites.
8.4 Source Documents. Each Site shall create and maintain complete, accurate, and legible source documents for all Study Data entered into the EDC Platform. Source documents shall include, but not be limited to, hospital medical records, clinic charts, laboratory reports, imaging reports, pharmacy dispensing records, electronic patient diaries, and any other records from which Study Data is derived. Sponsor and Meridian CRO shall have direct access to all source documents for the purpose of source data verification, monitoring, auditing, and regulatory inspection, and Sites shall facilitate such access upon reasonable request.
8.5 Data Transfer. Upon the completion or termination of the Study (or upon the termination of an individual Site's participation), each Site shall transfer to Sponsor all Study Data in the format and medium specified by Sponsor, including electronic data exports from the EDC Platform and copies of any paper-based source documents as reasonably requested by Sponsor. Such transfer shall be completed within sixty (60) days following the close-out of the Site or completion of the Study, as applicable.
8.6 Record Retention. Each Site shall retain all source documents, study records, and regulatory files related to the Study for a minimum period of fifteen (15) years following the completion or termination of the Study, or for such longer period as may be required by Applicable Law, regulatory authority guidance, or Sponsor's written instructions, whichever is longest. In no event shall a Site destroy any study records without providing Sponsor with at least ninety (90) days' prior written notice and an opportunity to request transfer of such records to Sponsor.
8.7 HIPAA Compliance. All sharing, transmission, and use of protected health information (as defined under HIPAA) between the Parties and their respective agents and subcontractors shall comply with the requirements of HIPAA, including the Privacy Rule (45 C.F.R. Part 164, Subpart E) and the Security Rule (45 C.F.R. Part 164, Subpart C). Each Site shall obtain valid research authorizations from Subjects or applicable waivers of authorization from the IRB, as required under 45 C.F.R. § 164.508 or § 164.512(i), prior to disclosing protected health information to Sponsor, Meridian CRO, or any other authorized recipient. All disclosures of protected health information shall comply with the minimum necessary standard set forth in 45 C.F.R. § 164.502(b). De-identified data shall be prepared in accordance with the standards set forth in 45 C.F.R. § 164.514(a)–(c). A detailed framework for data protection and HIPAA compliance is set forth in Exhibit F.
ARTICLE 9 — INTELLECTUAL PROPERTY
9.1 Pre-Existing intellectual Property. Each Party retains all right, title, and interest in and to its pre-existing intellectual property, including all patents, patent applications, copyrights, trade secrets, know-how, and other proprietary rights that were owned or controlled by such Party prior to the Effective Date or that are developed by such Party independently of, and without use of, the other Party's Confidential Information or resources. No license or other right to either Party's pre-existing intellectual property is granted under this Agreement except as expressly set forth herein.
9.2 Study Inventions. Inventions, discoveries, improvements, and know-how (whether or not patentable) that are conceived or first reduced to practice during the conduct of the Study shall be allocated as follows:
(a) Sponsor Sole Inventions: Inventions conceived solely by employees, agents, or contractors of Sponsor shall be the sole property of Sponsor.
(b) Site Network/Investigator Sole Inventions: Inventions conceived solely by Investigators, site staff, or other personnel of Site Network or the applicable participating institution shall be the property of [Site Network/applicable institution — this provision remains subject to negotiation; the Parties have not yet reached agreement on the ownership of sole inventions conceived by Site Network/Investigator personnel, and the Parties intend to address this issue in the IP Side Letter referenced in Section 9.3 below].
(c) Joint Inventions: Inventions conceived jointly by personnel of Sponsor (or its agents) and personnel of Site Network (or its member institutions) shall be jointly owned by the Parties and shall be governed by the IP Side Letter referenced in Section 9.3 below, which shall address joint ownership arrangements, licensing rights, patent prosecution and maintenance responsibilities, and commercialization rights.
9.3 IP Side Letter. The Parties shall negotiate and execute a separate intellectual Property Side Letter concurrently with, or promptly following the execution of, this MCTA, which shall set forth detailed terms governing the ownership, licensing, patent prosecution, and commercialization of inventions arising from the Study, including joint inventions. Until such IP Side Letter is executed, any disputes regarding intellectual property rights shall be resolved in accordance with Article 15 (Governing Law and Dispute Resolution) of this Agreement.
9.4 No License Grant. Except as expressly set forth in this Agreement, neither Party grants to the other Party any license, right, or interest, whether express or implied, in or to any patents, patent applications, copyrights, trademarks, trade secrets, know-how, or other intellectual property rights owned or controlled by such Party. Each Party expressly reserves all rights not expressly granted herein.
9.5 Detailed Provisions. Detailed provisions regarding intellectual property rights, including background IP, foreground IP, licensing, and publication-related IP matters, are set forth in Exhibit G, which is incorporated herein by reference.
ARTICLE 10 — INDEMNIFICATION
This Article 10 incorporates the terms of the Indemnification Term Sheet exchanged between the Parties on May 5, 2023, and reflects Sponsor's responses to Site Network's initial markup of the indemnification provisions dated April 28, 2023.
10.1 Sponsor Indemnification of Site Network and Investigators.
(a) Penterra shall indemnify, defend, and hold harmless Veridian, each participating Site institution, each Investigator, sub-investigator, and site staff member, and their respective officers, directors, trustees, employees, agents, successors, and assigns (collectively, the "Site Indemnitees"), from and against any and all claims, demands, actions, suits, proceedings, losses, damages, liabilities, costs, and expenses (including reasonable attorneys' fees and court costs) (collectively, "Losses") arising from or in connection with:
(i) Subject Injury caused by the Investigational Product when the Investigational Product has been stored, handled, and administered in accordance with the Protocol, the Investigator's Brochure, and Sponsor's written instructions;
(ii) Any defect in the Investigational Product, whether a manufacturing defect, design defect, labeling defect, or any other product-related defect, regardless of whether the defect was known or should have been known by Sponsor at the time of supply;
(iii) Any breach by Sponsor of any of its representations, warranties, obligations, or covenants under this Agreement or under the Protocol;
(iv) The negligence, recklessness, or willful misconduct of Sponsor or any of its employees, officers, agents, or contractors (including Meridian CRO and other approved subcontractors) in connection with the Study.
(b) The indemnification obligation of Sponsor under Section 10.1(a)(ii) with respect to defects in the Investigational Product shall be uncapped and shall not be subject to any per-occurrence, per-Subject, or aggregate limitation.
10.2 Carve-Outs from Sponsor Indemnification. Notwithstanding the provisions of Section 10.1, Sponsor's indemnification obligations under this Agreement shall not apply to the extent that the Losses for which indemnification is sought arise from or are attributable to:
(i) The negligence, recklessness, or willful misconduct of any Site Indemnitee, including any Investigator or site staff member, in connection with the conduct of the Study;
(ii) Any deviation from the Protocol by any Site, Investigator, or site staff member that was not authorized by Sponsor in writing or that was not required for the immediate safety or well-being of a Subject (subject to the provisions of Section 10.7 below);
(iii) Any breach by Site Network, any participating Site, any Investigator, or any site staff member of any of their respective representations, warranties, obligations, or covenants under this Agreement, any Individual Site Agreement, or Applicable Law.
In the event that Losses arise from a combination of causes, some of which are indemnifiable by Sponsor under Section 10.1 and others of which fall within the carve-outs set forth in this Section 10.2, the Losses shall be allocated between the Parties based on their respective degrees of fault, as determined by mutual agreement or, failing agreement, by the dispute resolution procedures set forth in Article 15.
10.3 Subject Medical Care Costs.
(a) In addition to the indemnification obligations set forth in Section 10.1, Sponsor shall cover the reasonable and customary medical costs incurred for the treatment of study-related injuries suffered by Subjects that are not covered by the Subject's own health insurance or other applicable third-party coverage. Sponsor's obligation to cover such medical costs shall be limited to injuries that are causally related to the Subject's participation in the Study and that arise from