Contract analysis

1. Protocol Title Cadence-3: A Prospective, Single-Arm, Open-Label Feasibility Study of the ThornValve MV-200 System for Transcatheter Mitral Valve Repair in Patients with Moderate-to-Severe Mitral Regurgitation The Cadence-3 Trial represents the third in a planned sequence of investigator-initiated feasibility studies designed to evaluate the safety, technical feasibility, and preliminary clinical performance of the

2. Protocol Identifiers The following identifiers have been assigned to the Cadence-3 Trial: All correspondence relating to this study, whether directed to the Sponsor, the Institution, the FDA, or any regulatory body, should reference the applicable identifiers listed above to ensure accurate identification and tracking of study-related communications.

3. Sponsor Name: Thornwick Medical Research Institute, Inc. Address: 280 Longmeadow Drive, Cambridge, MA 02139 Entity Type: Massachusetts nonprofit corporation organized under Section 501(c)(3) of the Internal Revenue Code. Thornwick Medical Research Institute, Inc. is a mission-driven research organization dedicated to the development and clinical translation of novel cardiovascular technologies. The Sponsor assumes

4. Investigational Site Institution: Hargrove University Medical Center, Inc. Address: 1400 Sterling Heights Boulevard, New Haven, CT 06510 Entity Type: Connecticut nonprofit corporation, academically affiliated with Hargrove University. Hargrove University Medical Center operates as a tertiary care academic medical center and serves as the primary teaching hospital for the Hargrove University School of Medicine. Stu

5. Principal Investigator and Sub-Investigator 5.1 Principal Investigator Name: Dr. Julian M. Castañeda, M.D., FACC Title: Professor of Cardiovascular Medicine, Hargrove University School of Medicine; Director, Structural Heart Interventions Program, Hargrove University Medical Center Qualifications: Dr. Castañeda is a board-certified interventional cardiologist with over 18 years of experience in transcatheter valve

6. Investigational Device Device Name: ThornValve MV-200 System Device Type: Transcatheter Mitral Valve Repair Device Description: The ThornValve MV-200 System is a proprietary transcatheter mitral valve repair system developed by Thornwick Medical Research Institute, Inc. The system consists of a catheter-based delivery platform designed for percutaneous, transseptal repair of the mitral valve in patients with clini

7. Study Design The design of the Cadence-3 Trial is summarized as follows: The single-arm, open-label design is appropriate for the feasibility stage of the device development program. The primary purpose of the Cadence-3 Trial is to establish the initial safety profile and technical performance of the ThornValve MV-200 System in a carefully selected patient population, rather than to demonstrate comparative effecti

8. Study Objectives 8.1 Primary Objective The primary objective of the Cadence-3 Trial is to evaluate the safety and technical feasibility of the ThornValve MV-200 System for transcatheter mitral valve repair in patients with moderate-to-severe mitral regurgitation. This objective encompasses both an assessment of the acute and short-term safety of the device implantation procedure and an evaluation of the ability of

9. Study Population 9.1 Planned Enrollment The Cadence-3 Trial plans to enroll a total of 45 evaluable subjects at Hargrove University Medical Center. An evaluable subject is defined as a subject who provides informed consent, meets all eligibility criteria, and in whom the ThornValve MV-200 System implantation procedure is attempted. To account for potential screen failures and early withdrawals, the site may screen

1. Age ≥ 18 years at the time of informed consent.

2. Moderate-to-severe (3+) or severe (4+) mitral regurgitation, as confirmed by an independent echocardiographic core laboratory based on standardized echocardiographic grading criteria (integrative assessment per American Society of Echocardiography guidelines).

3. Symptomatic mitral regurgitation (NYHA Functional Class II, III, or IV) despite optimal medical therapy, as determined by the treating heart team. Optimal medical therapy is defined as maximal tolerated doses of guideline-directed medical therapy for heart failure, including, as appropriate, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (or angiotensin receptor-neprilysin

4. Suitable mitral valve anatomy for transcatheter repair with the ThornValve MV-200 System, as assessed by pre-procedural transesophageal echocardiography (TEE) and/or cardiac computed tomography (CT), evaluated in accordance with the anatomic eligibility criteria set forth in the full Protocol (Version 3.0).

5. The subject (or the subject's legally authorized representative, where applicable under state law) provides written informed consent to participate in the study in accordance with 21 CFR Part 50 and the informed consent procedures approved by the HUMC IRB.

6. The subject is a candidate for the study procedure in the opinion of the local heart team, which must include at a minimum one interventional cardiologist and one cardiac surgeon. 9.3 Key Exclusion Criteria A subject who meets any of the following exclusion criteria will not be eligible for enrollment in the Cadence-3 Trial:

1. Prior mitral valve surgery (including surgical repair, surgical replacement, or any prior open surgical intervention on the mitral valve) or prior transcatheter mitral valve intervention (including any prior transcatheter repair or replacement device implantation).

2. Severe mitral annular calcification, as determined by pre-procedural imaging (TEE and/or cardiac CT), that in the judgment of the heart team precludes safe and effective deployment of the ThornValve MV-200 System.

3. Active endocarditis or other active systemic infection at the time of screening or at any time prior to the planned procedure.

4. Severe, uncompensated heart failure requiring inotropic support, mechanical circulatory support (e.g., intra-aortic balloon pump, percutaneous ventricular assist device, or extracorporeal membrane oxygenation), or hospitalization for acute decompensated heart failure within 7 days prior to the planned procedure.

5. Life expectancy of less than 12 months due to non-cardiac comorbidities, as assessed by the Principal Investigator in consultation with the heart team.

6. Known hypersensitivity or allergy to any material used in the manufacture of the ThornValve MV-200 System, including but not limited to nickel, titanium, polyester, or other device component materials, as identified in the Investigator's Brochure.

7. Current participation in another investigational device or investigational drug clinical trial that, in the opinion of the Principal Investigator, may confound study results or interfere with the subject's participation in the Cadence-3 Trial. Participation in observational registries or post-market surveillance studies is not exclusionary.

8. Pregnancy at the time of screening or planned pregnancy during the study period (from enrollment through the 24-month follow-up visit). Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to the index procedure.

9. Inability or unwillingness to comply with the study follow-up requirements, including all scheduled follow-up visits through 24 months post-procedure, as determined by the Principal Investigator. Additional inclusion and exclusion criteria are specified in the full Protocol (Version 3.0), which is maintained on file with the Sponsor and the Institution and is incorporated by reference into the Clinical Trial Agree

10. Study Endpoints 10.1 Primary Safety Endpoint The primary safety endpoint of the Cadence-3 Trial is the rate of major adverse events (MAEs) occurring within 30 days post-procedure. The 30-day MAE rate is defined as a composite of the following events: (a) All-cause death; (b) Stroke (ischemic or hemorrhagic), as adjudicated by the Clinical Events Committee; (c) Device embolization (defined as migration of the impl

11. Study Procedures and Schedule of Assessments 11.1 Screening / Baseline (Pre-Procedure) The screening and baseline assessment period begins with the provision of written informed consent and continues through the day of the index procedure. The following assessments will be performed during the screening and baseline period: • Provision and documentation of written informed consent • Comprehensive medical history

12. Data Safety Monitoring Board (DSMB) DSMB Chair: Dr. Garrett P. Lindholm, M.D., Ph.D., Professor of Biostatistics and Cardiology, Ellsworth University, Chicago, Illinois. Constitution: The independent Data Safety Monitoring Board for the Cadence-3 Trial was formally constituted in November 2025 by the Sponsor, in consultation with the Principal Investigator. The DSMB operates under a separate, written DSMB Charter

13. Data Management and Biostatistical Analysis Contract Research Organization (CRO): Meridian Clinical Sciences, Inc. 900 Weston Parkway, Suite 400 Cary, NC 27513 CRO Contact: Victoria Reeves, Vice President, Cardiovascular Programs Telephone: (919) 555-7800 Email: vreeves@meridiancs.com Scope of CRO Services: Meridian Clinical Sciences, Inc. has been engaged by the Sponsor to provide comprehensive data management a

14. Regulatory Considerations The ThornValve MV-200 System is an investigational device that has not been approved or cleared by the United States Food and Drug Administration for commercial distribution. The device is authorized for use in the Cadence-3 Trial exclusively under FDA Investigational Device Exemption (IDE) Number G260012, in accordance with the requirements of 21 CFR Part 812. The Cadence-3 Trial protoc

15. Informed Consent Written informed consent will be obtained from each subject (or, where applicable under Connecticut state law, the subject's legally authorized representative) prior to the performance of any study-specific procedures, including screening assessments. The informed consent process will be conducted in accordance with 21 CFR Part 50 (Protection of Human Subjects), the requirements of the HUMC IRB,

16. Adverse Event Reporting and Safety Monitoring All adverse events (AEs) and serious adverse events (SAEs) will be systematically collected, documented, assessed, and reported from the time of the ThornValve MV-200 System implantation procedure through the completion of the 24-month follow-up period for each subject. The Principal Investigator and study staff will assess each adverse event for severity, seriousness

17. Study Duration and Key Milestones The following table summarizes the estimated key milestones and timeline for the Cadence-3 Trial: The enrollment period is estimated to be approximately 15 months (April 2026 through June 2027), during which 45 evaluable subjects will be enrolled at an anticipated rate of approximately 3 subjects per month. Each subject will be followed for 24 months from the date of device impla

18. Sample Size Justification The Cadence-3 Trial is a feasibility study, and the sample size of 45 evaluable subjects has been selected to provide adequate preliminary safety and performance data to inform the design of a future pivotal trial, rather than to achieve definitive statistical hypothesis testing. The sample size of 45 subjects provides the following statistical properties: (a) Safety estimation: With 45

19. Study Committees and Oversight The following committees and oversight bodies will provide governance and monitoring for the Cadence-3 Trial: Sponsor Oversight: Thornwick Medical Research Institute, Inc., through its Vice President of Clinical Development, Dr. Elaine K. Sutherland, will provide overall sponsor oversight of the Cadence-3 Trial. Sponsor oversight responsibilities include, but are not limited to, mon

20. Confidentiality and Data Protection All subject data collected during the Cadence-3 Trial will be handled in strict accordance with the requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA), as amended, the HIPAA Privacy Rule (45 CFR Parts 160 and 164), applicable Connecticut state privacy laws, and the institutional policies of Hargrove University Medical Center governing the us

21. Publication and Dissemination of Results Publication and dissemination of the results of the Cadence-3 Trial are governed by the publication rights provisions set forth in the Clinical Trial Agreement dated March 2, 2026, between Thornwick Medical Research Institute, Inc. and Hargrove University Medical Center, Inc. The Principal Investigator and the Institution agree to comply with the publication review, author

22. Protocol Amendments Any modifications to this Protocol — whether substantive or administrative — require written approval from the Sponsor (through its Vice President of Clinical Development or designee) and the Hargrove University Medical Center Institutional Review Board prior to implementation at the study site, except as provided below. Amendments that affect the scientific basis of the study, the study desig

23. References to Agreement Exhibits and Related Documents This Protocol Synopsis is attached as Exhibit B to, and is incorporated by reference into, the Clinical Trial Agreement by and between Thornwick Medical Research Institute, Inc. and Hargrove University Medical Center, Inc., dated March 2, 2026 (the "Agreement"). All capitalized terms used but not defined in this Protocol Synopsis shall have the meanings ascri