Funding opportunities
Heart-derived cells in hydrogel for cardiac regeneration
Funding Type:
Disease Team Therapy Planning I
Grant Number:
DR2-05401
Funds Committed:
$110,000
Funding Recommendations:
Recommended
Public Abstract:
This project seeks to develop [REDACTED], an engineered tissue product consisting of cells derived from a donor heart embedded in a biological material called a hydrogel. We are hoping to treat patients with recent heart attacks (myocardial infarction, or MI) and weak hearts. In such patients, [REDACTED] is designed to replace scar tissue with healthy working heart muscle, thereby enhancing the function of the injured heart. Post-MI patients who are left with weak scarred hearts number in the millions in the USA; best current therapy slows disease progression but does not reverse injury. Unlike existing treatments, which forestall but do not prevent the progression to overt heart failure, the proposed therapy is potentially curative. [REDACTED] will be manufactured by [REDACTED], in collaboration with [REDACTED], which makes the biomaterial of choice. We will perform extensive preclinical experiments to optimize formulation and dosing, and to demonstrate the safety and efficacy of [REDACTED], delivered by minimally-invasive injection catheter methods, in reducing scar size and improving function in pigs with post-MI dysfunction. Additional preclinical studies will establish clinical-grade product manufacturing, quality control and release criteria. The project will culminate in a clinical trial in patients with recent MI and weak hearts, to assess safety and efficacy (by quantification of myocardial scar size, function and perfusion, and quantification of major adverse cardiovascular events).
Statement of Benefit to California:
The present project stands to benefit both the public health as well as the economy of the state of California. This project seeks to develop [REDACTED], an engineered tissue product consisting of cells derived from a donor heart embedded in a biological material called a hydrogel. We are hoping to treat patients with recent heart attacks (myocardial infarction, or MI) and weak hearts. In such patients, [REDACTED] is designed to replace scar tissue with healthy working heart muscle, thereby enhancing the function of the injured heart. Post-MI patients who are left with weak scarred hearts number in the millions in the USA, and in tens of thousands in California; best current therapy slows disease progression but does not reverse injury. Unlike existing treatments, which forestall but do not prevent the progression to overt heart failure, the proposed therapy is potentially curative. [REDACTED] will be manufactured by [REDACTED], in collaboration with [REDACTED], which makes the biomaterial of choice. We will perform extensive preclinical experiments to optimize formulation and dosing, and to demonstrate the safety and efficacy of [REDACTED], delivered by minimally-invasive injection catheter methods, in reducing scar size and improving function in pigs with post-MI dysfunction. Additional preclinical studies will establish clinical-grade product manufacturing, quality control and release criteria. The project will culminate in a clinical trial in patients with recent MI and weak hearts, to assess safety and efficacy (by quantification of myocardial scar size, function and perfusion, and quantification of major adverse cardiovascular events). The net result will be benefit to Californians both in terms of a new product that stands to decrease premature morbidity and mortality from heart disease, as well as by expanding employment and the economic tax base of two California companies.
Review Summary:
Executive Summary
Project Synopsis
This application describes the development of a cell therapy to repair hearts damaged by myocardial infarction (MI) through Phase II clinical trials. The combination therapy consists of allogeneic cardiac derived cells embedded in a hydrogel matrix (HCDC) to promote cell retention at the site of direct cardiac injection. In year one of the award, the applicants plan to optimize their formulation, dosage and delivery protocol, perform investigational new drug (IND)-enabling studies with optimized HCDC in a relevant preclinical model and establish standard operating procedures for GMP manufacturing. An IND submission and approval is planned in the second year of the award, followed by Phase I safety trials in year 3 and randomized, controlled Phase II clinical trials in year 4.
Significance and Impact
- The proposed therapy addresses a clear unmet medical need and could have major impact if it successfully regenerates myocardium in failing hearts.
- A reviewer noted that the proposed therapy represents an incremental improvement to related, simpler therapies currently in clinical development. In order to have meaningful impact, this more complex preparation would need to significantly outperform these competing approaches.
Project Rationale and Feasibility
- Overall, reviewers found the application lacked adequate critical details. For example, it did not adequately describe the status of the master cell bank nor did it report how this cell bank was sourced, generated and characterized. Without such key information, reviewers were unable to accurately assess the feasibility of achieving the programs goals.
- Reviewers noted that much of the key preliminary data in relevant preclinical models was not directly relevant to the proposal, as it was derived using autologous cells, while the application focused on the use of allogeneic cells. In particular, reviewers were not convinced that allogeneic HCDC would induce the same response as autologous cardiac derived cells.
- Concern was also expressed regarding the potential immunogenicity of HCDC, which was not adequately addressed in the proposal.
- Reviewers highlighted the complexity of the proposed product and noted that all three components (cells, hydrogel, delivery technology) remain experimental. The FDA may therefore require additional safety studies. Further, benefit from hydrogel alone could confound the ability to determine efficacy of the cell component.
- While IND-enabling studies were appropriate, reviewers questioned whether the proposed timeline was adequate for enrollment, completion and follow up of both Phase I and Phase II clinical trials.
PI and Planning Leader
- The PI is an interventional cardiologist who has contributed to the field of cell based cardiac repair and has applicable experience running clinical trials. S/he has assembled a team with appropriate regulatory and statistical expertise.
- The planning leader has managed relevant clinical programs, but the experience or this individual in managing PI’s and coordinating industry relationships was unclear from the application.
Programmatic review:
- This application scored below the initial scientific merit funding line, no programmatic reason to fund the application was proposed, and the GWG voted to place the application in Tier 3, Not Recommended for Funding.
Conflicts:
