Treating Hereditary Rare Diseases With In Vivo Precision Genetic Medicines (THRIVE)

Amendment / Modification

This document is Amendment No. 4 to the Innovative Solutions Opening (ISO) for Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE). It updates key dates and provides further details on the program.

• Dates: The posting date is listed as November 14, 2025. Specific deadlines for Solution Summary, PowerPoint presentation, and Full Proposal submissions are provided.
• Program Details: The amendment includes updated information on the program's purpose, structure (Modules 1, 2, and 3), and specific requirements for performers.
• Submission Process: Details regarding the submission process, including Solution Summary, PowerPoint presentation, and Full Proposal submissions, are elaborated upon.
• Evaluation Criteria: The criteria for proposal review remain consistent.
• Policy Requirements: Various policy requirements, including OCI, IP, and research security, are reiterated and potentially updated.

This amendment impacts various sections of the original solicitation, including dates, submission processes, and potentially policy requirements. Refer to the full amendment document for specific section-by-section changes.

Potential bidders should review the updated dates and any revised requirements to ensure timely and compliant submissions. The core objectives and evaluation criteria of the THRIVE program remain the focus.

Amendment / Modification

This document is Amendment No. 4 to the Innovative Solutions Opening (ISO) for Treating Hereditary Rare diseases with In Vivo precision genetic medicines (THRIVE).

This amendment does not appear to modify specific sections of the original solicitation but rather serves as an update to the document, indicated by the "Amendment No. 4" and the date "November 14, 2025".

No specific impact on submission deadlines or requirements is detailed in this amendment document itself, beyond updating the record with Amendment No. 4.

Amendment / Modification

This document is Amendment No. 1 to the Innovative Solutions Opening (ISO) for Treating Hereditary Rare diseases with In Vivo precision genetic medicines (THRIVE).

This amendment does not appear to modify specific sections of the original solicitation but rather serves as an update or addition to the initial announcement.

No changes to proposal deadlines or submission requirements are indicated in this amendment. The original posting date was September 25, 2025, with a proposal due date of December 19, 2025.

Amendment / Modification

This document is Amendment No. 1 to the Innovative Solutions Opening (ISO) for Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE), Solicitation Number ARPA-H-SOL-25-122.

Key updates include:

• Posting Date: The posting date has been updated to September 25, 2025.
• Q&A Deadline: The deadline for questions and answers is now October 24, 2025.
• Proposers' Day Recording Release: The recording will be released on September 25, 2025.
• Lightning Talks and Sidebars: These virtual sessions are scheduled for October 02, 2025.
• Solution Summary Due Date: The deadline for Solution Summary submissions is October 31, 2025, at 11:59 PM ET.
• Full Proposal Due Date: The deadline for Full Proposal submissions is December 19, 2025, at 11:59 PM ET.

This amendment updates the dates and deadlines associated with the solicitation. Specific sections detailing these dates include the "Dates" under "INNOVATIVE SOLUTIONS OPENING SUMMARY INFORMATION" and "Solution Summary and Full Proposal Submission Deadlines" under "SUBMISSION PROCESS."

Potential bidders should note the revised submission deadlines for Solution Summaries and Full Proposals. All other aspects of the original solicitation remain in effect unless otherwise specified in this amendment.

Questions & Answers / Clarifications

This document provides Frequently Asked Questions (FAQs) to offer timely information about the THRIVE program and its application process, responding to inquiries from potential performers.

• What is a THRIVE PGM? A Precision Genetic Medicine (PGM) is an intervention designed to address root causes at the genetic level, potentially slowing, reversing, or preventing disease. Modalities can vary, and higher-risk modular components may receive more points than those already proven.
• Disease and Population Agnosticism: THRIVE is disease and age agnostic, encouraging solutions for multiple gene variants, rare diseases, and any age group (perinatal to adult). Solutions for small populations with high unmet needs are encouraged.
• Technology Agnosticism: THRIVE is technology agnostic, aiming to build and validate platforms that can create genetic medicines. Teams are expected to propose a portfolio of at least two PGMs across at least two PGM platforms.
• Evaluation of Risk: Proposals will be evaluated holistically, with a focus on collective capabilities. Less clinically demonstrated platforms or components will be weighted more heavily than those already proven.
• Scope of Work: Solutions must address all three modules of the THRIVE program. Non-compliant solutions will not be reviewed.
• Cost-Sharing: ARPA-H will cost-share the program over five years, with decreasing government contribution each year. Teams must submit a cost-sharing strategy, with cash contributions preferred over in-kind.
• Teaming: Teaming is required, encouraging diverse organizational types (academic, industry, non-profits, patient advocacy groups). Teams must address all modules, and there is no limit to the number of organizations per team. International collaboration is encouraged.

This FAQ clarifies key aspects of the THRIVE program, including the definition of PGMs, scope of work, technology and disease focus, evaluation criteria, teaming requirements, and cost-sharing. Potential bidders should use this information to refine their proposals and ensure compliance with all program requirements, particularly the need to address all three modules.

Solicitation / RFP / RFQ

This solicitation, ARPA-H-SOL-25-122, is an Innovative Solutions Opening (ISO) for the "Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines" (THRIVE) program. The goal is to accelerate the development and availability of precision genetic medicines (PGMs) for rare diseases (RDs) by supporting innovative research and integrated platforms. ARPA-H seeks to address the significant unmet medical needs in RD populations, where nearly 95% lack approved therapies, and to reduce the substantial financial burden of RDs on taxpayers. The program aims to transform the healthcare paradigm from chronic treatments to one-time curative interventions.

• Development of at least two PGM platforms, each demonstrating at least two PGMs targeting specific RD use cases.

• Focus on novel PGM designs capable of addressing multiple variants within a gene, clusters of mutations, or diseases with common genetic pathways.

• Emphasis on integrated technology innovation, combining therapeutic cargo (e.g., gene editors, gene insertions) with precise in vivo delivery tools (e.g., nanoparticles).

• Acceleration of regulatory pathways for PGMs and platform evaluations.

• Piloting the viability and scalability of treatments through clinical trials at expert centers and virtually networked satellite clinics.

• Establishment of a publicly accessible data platform for AI-assisted iteration and growth of the PGM industry.

• Solutions must address cost of goods, manufacturability, and product quality.

• Proposals must not involve human embryos, fetal tissue, or human-animal chimeras.

• Adeno-associated virus (AAV)-mediated gene therapies involving the addition or supplementation of a functional copy of a defective gene are discouraged.

• Potential Award Instruments: Other Transaction Agreements (OT).

• Program Duration: Five (5) years.

• Anticipated Awards: Multiple awards.

• Two-step submission process: Solution Summary (3 pages max) followed by Full Proposal.

• Key Deadlines:

  • Solution Summary Due Date: October 31, 2025
  • Full Proposal Due Date: December 19, 2025

• Evaluation Criteria (in descending order of importance):

  1. Technical Merit
  2. Potential Contribution and Relevance to the ARPA-H Mission
  3. Proposer’s Capabilities and/or Related Experience
  4. Cost Realism

• Open to all responsible sources: universities, non-profit organizations, small businesses, and other than small businesses.

• Federally Funded Research and Development Centers (FFRDCs) and other Government entities are generally prohibited from participating as team members.

• Non-U.S. entities are eligible but must comply with applicable regulations; collaboration with domestic U.S. entities is encouraged.

• All proposers must have an active registration in SAM.gov.

• Cost sharing is required, with ARPA-H funding decreasing over the five years.

• Teams are required to execute a Multi-Party Teaming Agreement (MPTA) prior to award.

• Proposals must include a full-time Project Manager/Integrator (PMI).

Solicitation / RFP / RFQ

This solicitation, "Innovative Solutions Opening (ISO) for Treating Hereditary Rare diseases with In Vivo precision genetic medicines (THRIVE)," issued by ARPA-H's Health Science Futures Office, aims to accelerate better health outcomes by advancing innovative research for society's most challenging health problems. It seeks to develop groundbreaking ways to tackle health-related challenges through high-potential, high-impact biomedical and health research, specifically focusing on rare diseases (RDs) with unmet medical needs. The program intends to negotiate multiple Other Transaction (OT) Agreements.

• Development of multiple Precision Genetic Medicine (PGM) platforms and at least two PGMs per platform.

• Focus on addressing multiple variants within a gene, clusters of mutations, or diseases with common genetic pathways.

• Emphasis on innovative PGM designs, including but not limited to, CRISPR-based technologies, antisense oligonucleotides (ASOs), and other precision editing tools.

• Development of targeted, preferential cell-specific delivery tools with broad cargo carrying capacity.

• Incorporation of tunability in solutions (e.g., inhibitory/activating small molecules, optogenetics).

• Non-clinical testing for safety, off-target effects, toxicity, and efficacy in human cells/tissues/organoids.

• Pilot viability of platforms and patient access through interventional PGM centers and virtually networked satellite clinics.

• Establishment of a publicly accessible data platform for AI-assisted iteration.

• Potential Award Instruments: Other Transaction Agreements (OT).

• Period of Performance: Five (5) years.

• Cost Sharing: Required and must be added to the proposal. ARPA-H funding decreases over the five years (100% Year 1, 80% Year 2, 60% Year 3, 40% Year 4, 20% Year 5).

• Anticipated Awards: Multiple awards.

• Two-step submission process: Solution Summary followed by Full Proposal.

• Key Deadlines:

  • Q&A Deadline: October 24, 2025
  • Solution Summary Due Date: October 31, 2025
  • Proposal Due Date: December 19, 2025

• Evaluation Criteria (in descending order of importance):

  1. Technical Merit
  2. Potential Contribution and Relevance to the ARPA-H Mission
  3. Proposer's Capabilities and/or Related Experience
  4. Cost Realism

• Eligible Proposers: Universities, non-profit organizations, small businesses, and other than small businesses are eligible and encouraged.

• Geographically dispersed teams are encouraged.

• Prohibition of Performer Participation from Federally Funded Research and Development Centers (FFRDCs) and Other Government entities.

• Non-U.S. entities may participate if they comply with applicable regulations, but collaboration with domestic U.S. entities is encouraged.

• Proposals must be submitted by teams, not prime contractors with sub-prime relationships.

• A Multi-Party Teaming Agreement (MPTA) is required prior to award.

• Specific guidance on Intellectual Property (IP) strategy, commercialization, and cost sharing is provided.

• THRIVE discourages the use of AAV delivery and supplemental transgene expression solutions, but may support up to 20% of AAV costs if used as part of a de-risking strategy.