CALDERWOOD & HARKNESS LLP One Post Office Square, Suite 4100 Boston, Massachusetts 02109
Telephone: (617) 884-7000 Facsimile: (617) 884-7001 www.calderwoodharkness.com
February 28, 2026
VIA EMAIL AND FedEx
Rebecca S. Norcross, Esq. Partner, Life Sciences & Academic Medicine Group Pemberton, Yates & Caldwell LLP 55 Church Street, Suite 1200 New Haven, CT 06510
Re: Clinical Trial Agreement between Thornwick Medical Research Institute, Inc. and Hargrove University Medical Center, Inc. — CADENCE-3 Trial (ThornValve MV-200 System) Our Matter No.: 1029-00001
Dear Ms. Norcross:
As you know, this firm represents Thornwick Medical Research Institute, Inc. ("TMRI") in connection with the negotiation and execution of the Clinical Trial Agreement (the "CTA") with Hargrove University Medical Center, Inc. ("HUMC") for the CADENCE-3 investigator-initiated feasibility trial of the ThornValve MV-200 System (Transcatheter Mitral Valve Repair Device). We are pleased to report that we have reached the execution stage following the constructive and thorough negotiation process between the parties. Enclosed herewith for your review and execution are four (4) signature copies of the execution version of the CTA, each incorporating the final negotiated terms as reflected in the parties' exchanges culminating in HUMC's comments on the third draft of the CTA received by our office on February 26, 2026. The execution version incorporates all agreed-upon revisions from that final round of comments without further modification.
The enclosed documents consist of four (4) original counterpart signature copies of the Clinical Trial Agreement, dated as of March 2, 2026 (the "Effective Date"). Each counterpart is a complete copy of the agreement and includes the following:
(a) The body of the CTA, reflecting all final negotiated terms agreed to by the parties, including, without limitation, the provisions regarding indemnification obligations (Article IX), intellectual property ownership and licensing (Article X), and publication rights (Article XI), each of which was the subject of extensive discussion between the parties and their respective counsel;
(b) Exhibit A — Study Budget, reflecting the total agreement value of Six Million Dollars ($6,000,000.00), inclusive of all direct and indirect costs, milestone payments, and the institutional overhead rate as agreed between the parties; and
(c) Exhibit B — Protocol Synopsis for the CADENCE-3 Trial, referencing ClinicalTrials.gov Identifier NCT06198234, FDA Investigational Device Exemption ("IDE") Number G260012, and Institutional Review Board Protocol No. HUMC-IRB-2025-0847.
Please note that TMRI's authorized signatory, Dr. Ansel R. Varnham, M.D., Ph.D., President and Chief Executive Officer, has duly executed each of the four (4) counterpart signature copies on behalf of TMRI in accordance with TMRI's organizational authorization requirements.
We respectfully request that Dr. Priya Anand-Kessler, M.D., MBA, President and Chief Executive Officer of HUMC, execute each of the four (4) counterpart signature copies on behalf of Hargrove University Medical Center, Inc. Upon execution by Dr. Anand-Kessler, we kindly ask that two (2) fully executed originals be returned to Calderwood & Harkness LLP at the address set forth above for TMRI's records. The remaining two (2) fully executed originals should be retained by HUMC for its own files. We would like to emphasize that the target execution date of March 2, 2026 is of critical importance to the parties' mutual objectives. Timely execution on or before that date is necessary to support TMRI's IDE supplement filing with the United States Food and Drug Administration ("FDA"), which is currently targeted for March 15, 2026. Any delay in execution could have downstream consequences for the regulatory timeline, including the estimated first patient enrollment date of April 7, 2026, which date is itself dependent upon timely FDA review and acceptance of the IDE supplement. We therefore respectfully request your assistance in facilitating prompt execution and return of the counterpart originals.
In addition to the executed counterparts, we request that HUMC provide, on or before the execution date of March 2, 2026, a certificate of insurance issued by Pinnacle Mutual Insurance Company evidencing HUMC's professional liability coverage currently maintained under Policy No. PML-HU-2025-4471. The certificate should reflect professional liability coverage limits of not less than Five Million Dollars ($5,000,000.00) per occurrence and Fifteen Million Dollars ($15,000,000.00) in the aggregate, consistent with the insurance requirements set forth in Section 9.4 of the CTA. We further request that the certificate of insurance name Thornwick Medical Research Institute, Inc. as an additional insured with respect to HUMC's activities arising out of or related to the CADENCE-3 Trial, as contemplated by the CTA. For its part, TMRI will separately provide to HUMC a certificate of insurance issued by Commonwealth Specialty Underwriters, Inc. under Policy No. CTL-2025-08843, naming Hargrove University Medical Center, Inc. as an additional insured with respect to the CADENCE-3 Trial. That certificate will be delivered to your office and to HUMC's Office of Research Administration under separate cover on or about the execution date.
For completeness, we note that TMRI anticipates receipt of the following additional closing deliverables from HUMC at or around the time of execution, each of which has been discussed between the parties during the course of negotiation:
(i) A copy of the Institutional Review Board approval letter (Protocol No. HUMC-IRB-2025-0847, dated December 18, 2025) for inclusion in the closing binder and for submission to the FDA in connection with TMRI's IDE supplement filing;
(ii) The Principal Investigator conflict of interest disclosure from Dr. Julian M. Castañeda, M.D., FACC, in his capacity as the designated Principal Investigator for the CADENCE-3 Trial at HUMC, as required under Section 5.3 of the CTA and applicable federal regulations (42 C.F.R. Part 50, Subpart F; 45 C.F.R. Part 94);
(iii) Confirmation of HUMC's Institutional Federalwide Assurance ("FWA") maintained with the Office for Human Research Protections, United States Department of Health and Human Services, as required under Section 5.1(c) of the CTA; and
(iv) Wire transfer instructions for HUMC's designated account for receipt of the upfront institutional activation fee of Three Hundred Thousand Dollars ($300,000.00) payable by TMRI within ten (10) business days following the Effective Date, as set forth in Exhibit A, Section I.A of the Study Budget.
As Ms. Norcross is aware, a comprehensive closing checklist enumerating all deliverables required from both parties at or around execution has been prepared and was provided separately to your office by email on February 25, 2026. We would be pleased to provide an updated version of the checklist upon request.
On behalf of TMRI and the Calderwood & Harkness team, I would like to express our sincere appreciation for the constructive and collegial nature of the negotiations between the parties and between counsel. The professionalism and responsiveness demonstrated by you and your colleague, Daniel F. Huang, Esq., throughout the negotiation process contributed significantly to the efficient resolution of the remaining open issues and to the timely completion of the execution version of the CTA. We look forward to continuing to work cooperatively with Pemberton, Yates & Caldwell as the CADENCE-3 Trial progresses.
Should you have any questions regarding the enclosed documents, the execution process, or any of the closing deliverables referenced herein, please do not hesitate to contact me directly, or Joel Strauss, Responsible Partner on this matter, at your convenience. I can be reached at (617) 884-7246 or by email at caiken@calderwoodharkness.com.
Very truly yours,
CALDERWOOD & HARKNESS LLP
By: ________
Christopher Aiken Associate, Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP One Post Office Square, Suite 4100 Boston, Massachusetts 02109 Tel: (617) 884-7246
Email: caiken@calderwoodharkness.com
Enclosures (4)
Four (4) counterpart signature copies of the Clinical Trial Agreement between Thornwick Medical Research Institute, Inc. and Hargrove University Medical Center, Inc. (CADENCE-3 Trial), dated as of March 2, 2026, each including Exhibit A (Study Budget) and Exhibit B (Protocol Synopsis)
cc:
Marcus D. Pruitt, J.D., General Counsel, Thornwick Medical Research Institute, Inc. Dr. Elaine K. Sutherland, M.D., Vice President of Clinical Development, Thornwick Medical Research Institute, Inc. Joel Strauss, Esq., Calderwood & Harkness LLP Amy Whitfield, Esq., Calderwood & Harkness LLP Leonard B. Ostrowski, Ph.D., Senior Vice President for Research Administration, Hargrove University Medical Center, Inc. Daniel F. Huang, Esq., Pemberton, Yates & Caldwell LLP