Industry Partner Foundation for the National Institutes of Health

1. What are some specific examples of public-private partnerships that the Foundation for the National Institutes of Health (FNIH) has formed to support the mission of the National Institutes of Health (NIH)?

FNIH has a 25+ year history in forming and facilitating Public-Private Partnerships (PPPs) to support the NIH’s mission. Some of these are individual PPPs, like the Partnership for Accelerating Cancer Therapies, which is focused on speeding the development of immune-based oncology treatments through the identification and use of biomarkers, and the Accelerating COVID-19 Therapeutic Interventions and Vaccines program, which formed in 2020 to develop a research strategy for prioritizing and speeding development of the most promising COVID-19 vaccines and therapeutics. Others are collections of PPPs, like the Accelerating Medicines Partnership^® (AMP^®) Program, which initially focused on data harmonization and target validation in a number of individual disease areas and has since expanded to multiple disease classifications and broader research applications through seven distinct partnerships.

2. Can you provide more information about the Bespoke Gene Therapy Consortium (BGTC) and its goals in streamlining adeno-associated virus (AAV) manufacturing and regulatory frameworks?

The BGTC was formed in 2021 as the sixth scientific area under the AMP program with the goal of making AAV gene therapies more accessible to patients with rare diseases. The consortium was designed to develop and demonstrate a defined and repeatable pathway that ultimately hundreds or thousands of AAV gene therapies might be able to follow. BGTC is using a portfolio of clinical indications as test cases for streamlining manufacturing analytics, standardizing sets of pre-clinical testing protocols, and creating regulatory templates that are intended to accelerate the development of future AAV gene therapies to the IND submission and first-in-human clinical trials.

3. How does the FNIH select which therapeutic areas and diseases to focus on in its Accelerating Medicines Partnership (AMP) programs?

The AMP program is overseen by an Executive Committee (EC) comprised of senior leadership from the NIH and Industry. The AMP EC is responsible for the review and approval of new projects, which could be in any therapeutic area where there is an alignment of interests and expertise between the NIH and industry. All AMP projects share three common principles – shared governance and funding from the public and private sectors, a commitment to rapid and broad dissemination of research results, and a focus in the pre-competitive space so that the entire field benefits from the work of the projects. New AMP projects are first reviewed as a defined concept, and then a full PPP is designed over the course of 6-12 months.

4. What are some of the achievements and milestones that have been reached through the AMP programs?

Since its establishment in 2014 in three initial disease areas, the AMP program has grown to encompass 10 individual projects which collectively involve 16 NIH Institutes and Centers and over 70 private sector partners from for-profit and non-profit organizations. Over $830M has been invested by the NIH and the private sector in the program and several more projects are in development, which speaks to the strength and success of the AMP model for PPPs. Many of the AMP programs have a strong focus on multi-omics datasets and in some cases provided the first and/or most comprehensive harmonization of multiple large datasets and the analytic tools needed to probe the data for druggable targets and predictive markers. For example, the AMP Type 2 Diabetes portal is the largest repository of its kind of summary level data from T2D and complications cohorts, and is being further expanded through both the AMP Common Metabolic Diseases effort as well as community data from non-AMP sources. AMPs have also developed research tools and protocols that help advance the entire field, such as single-cell RNA-Seq for specific cell and tissue types, and synovial biopsy techniques that are now standard in research and clinical uses. Future efforts are expected to advance various diagnostic and prognostic biomarkers and improve precision medicine approaches through better patient stratification.

5. How does the FNIH collaborate with industry partners and nonprofit organizations in the AMP programs?

The FNIH has three roles in the AMP program, each of which requires collaboration with industry partners and nonprofit organizations. First, the FNIH is instrumental in the design of the PPP: over the course of 6-12 months the FNIH leads a group of stakeholders in defining the goals of the PPP, the specific steps needed to accomplish the goals, and the resources needed for success. This effort culminates in a Research Plan for a multi-year partnership reflecting the extensive inputs from the NIH Institutes and the industry and non-profit stakeholders. Second, the FNIH is responsible for securing the private sector funding commitments to the project, through financial or in-kind contributions towards the research goals – without these relationships no PPP would be successful. Finally, once the PPP launches, the FNIH provides expert project management throughout the life of the partnership to ensure that the goals are met, and the subject matter expertise of the industry partners and the nonprofit organizations is instrumental to achieving the research outcomes.

6. Could you elaborate on the challenges faced in developing gene and cell therapies, particularly in scaling manufacturing for vector-based gene therapies?

Manufacturing is one of the biggest hurdles in bringing AAV gene therapies forward, both due to the high costs as well as the technology requirements. In addition to the clinical portfolio, the BGTC is also funding several research projects aimed at improving vector generation and therapeutic gene expression of the transgene. Increasing the efficiency of various steps of the manufacturing process could potentially bring down costs and make scaling more feasible. Likewise, improving the level of gene expression in a patient could have ramifications not only for manufacturing, where achieving a therapeutic level of gene expression with a smaller viral load could increase the number of doses produced in a given batch, but also potentially improve the safety profile by reducing the risk of side effects associated with high viral loads.

7. Can you explain the open nomination process used to identify diseases for inclusion in the BGTC's pilot clinical program?

Because the BGTC ultimately was focused on the development process rather than on any specific disease or disease area, we turned to the clinical research and patient communities to help us identify diseases that would be good candidates for the clinical program, with a strong focus on indications that were as close as possible to being ready for a first-in-human clinical trial as well as indications that currently had no commercial interest. The first step in the process involved a simple nomination form that captured information about the disease or disorder, the patient population, and the body of work that had already been completed. All diseases were required to be a rare disease (meeting the US definition of fewer than 200,000 patients) and involve a single gene that could be packaged within an AAV vector. Other prior research factors that were considered included demonstrated transgene functionality, an established disease model, and any prior natural history, dose-finding, or other studies. An established contact registry and/or patient advocacy group for the disease or disorder was a strong factor in the review as well. Based on subject matter experts’ evaluation, the 14 strongest candidates were selected from an initial list of 62 submissions, and clinical trial proposals were requested. The submissions were reviewed by both our Pre-Clinical and Clinical sub-teams, and final selections were made based on the review criteria and availability of funds, with an eye to ensuring diversity in the total patient population represented by the disease portfolio as well as program diversity such as multiple AAV serotypes and routes of administration across the portfolio.

8. What are some of the potential benefits and impacts of the BGTC's work on rare diseases and gene therapies?

While we hope that the consortium has eight successful clinical trials and successfully treats 50-60 patients across the clinical portfolio, the benefits are not just for these eight diseases but for any future gene therapy that follows in our footsteps. We hope that the “playbook” produced by the consortium with our streamlined manufacturing and preclinical testing protocols and our regulatory templates enables many more gene therapies to proceed faster and more cheaply than the current process.

9. How does the FNIH envision the future of gene therapy development and the potential for standardized regulatory paths and reference materials?

There is a significant effort to move away from one-off approaches to AAV gene therapies, especially for rare diseases. In addition to the BGTC other projects are underway that also aim to provide more standard approaches to AAV gene therapy development. At the National Center for Advancing Translational Therapeutics (NCATS), the Platform Vector Gene Therapy pilot seeks to demonstrate a true platform approach for the AAV vector itself, standardizing every aspect of four selected clinical trials (two organic acidemias and two congenital myasthenic syndromes) except for the target gene. They will use the same manufacturer and manufacturing process, the same AAV serotype, the same route of administration and the same clinical site for all four trials. NCATS is also leading the NIH’s Somatic Cell Gene Editing program which is aiming to improve gene editing approaches to therapies. Complementary efforts are being done across the field, including a collaboration between the National Institute of Standards and Technology (NIST), its Manufacturing USA^® institute the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) and United States Pharmacopeia (USP) to develop standards and analytical methods for AAV manufacturing. Future PPP efforts led by the FNIH could potentially seek to address other gene therapy delivery technologies or platform-based manufacturing approaches.

10. Is there anything that you would like to promote to our readers? (Any upcoming initiatives / webinars, conferences etc.)

The BGTC will be providing a progress update at the ASGCT Policy Summit being held in Washington, DC on September 18-19, 2023, and will be distributing its second anniversary newsletter to the consortium’s mailing list in late October. The AMP Program will be holding a scientific symposium in conjunction with its 10^th anniversary on February 5-6, 2024.

Dr. Courtney Silverthorn is an Associate Vice President for Science Partnerships at the Foundation for the National Institutes of Health (FNIH). With extensive experience in public-private partnerships and federal technology transfer policy, she serves as the Director of the Accelerating Medicines Partnership® (AMP®) program and is responsible for new business development in platform approaches to therapeutics and the program’s Bespoke Gene Therapy Consortium, a multi-year public-private partnership to advance manufacturing and regulatory frameworks for gene therapy treatments for rare diseases.

Prior to joining the FNIH, Courtney held several positions in the Technology Partnerships Office at the National Institute of Standards and Technology (NIST), including serving as the Acting Director of the office from 2020 to 2021. During her time at NIST, she led technology transfer activities at the agency and was central to the interagency Lab-to-Market initiative. Her interagency policy coordination efforts included serving as a Co-Chair of the National Science and Technology Council’s Lab-to-Market subcommittee and developing and implementing findings from NIST’s Return on Investment Initiative. She also served as a Senior Policy Advisor to the Office of Science and Technology Policy, supporting both Lab-to-Market and Citizen Science, and executed hundreds of technology transfer partnerships at the National Cancer Institute and the Frederick National Laboratory for Cancer Research.

Dr. Silverthorn earned a Ph.D. in Pharmacology from The Johns Hopkins University School of Medicine, a M.S. in Leadership from Washington University in St. Louis, and a B.S. in Biochemistry and Molecular Biology from Sweet Briar College. She has also earned certificates in Biotechnology Enterprise from Johns Hopkins and in Policy Strategy from the Brookings Institution.