Treating Hereditary Rare Diseases With In Vivo Precision Genetic Medicines (THRIVE) ARPA-H-SOL-25-122

The Advanced Research Projects Agency for Health (ARPA-H) Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program envisions a future where patients can opt for one-time therapeutic interventions designed to slow, reverse, or cure disease, harnessing revolutionary technologies and a rapidly evolving understanding of the genetic underpinnings of the biological processes that lead to disease. Interested parties are invited to review the attached THRIVE Innovative Solutions Opening (ISO) ARPA-H -SOL-25-122. For detailed information regarding Proposers' Day review Special Notice (SN) ARPA-H-SN-25-131. Solution summaries are due October 31, 2025, 11:59 PM ET. For more information about THRIVE, please visit:https://arpa-h.gov/explore-funding/programs/thrive

Amendment 2: Changes to the ISO The purpose of this amendment is to amend the THRIVE ISO. An updated version of the ISO and an updated version of the ISO with tracked changes are included as attachments. Changes to the ISO include: Cost share is now strongly encouraged instead of mandatory. Multi-party teaming arrangements are no longer required. ARPA-H's involvement with regulatory facilitation has been clarified. Please review the amended ISO for all changes. ---------------------------------------------------------------------------------------------------------------- Amendment 1: Added the Frequently Asked Questions (FAQ) to the list of attachments. ---------------------------------------------------------------------------------------------------------------- The Advanced Research Projects Agency for Health (ARPA-H) Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program envisions a future where patients can opt for one-time therapeutic interventions designed to slow, reverse, or cure disease, harnessing revolutionary technologies and a rapidly evolving understanding of the genetic underpinnings of the biological processes that lead to disease. Interested parties are invited to review the attached THRIVE Innovative Solutions Opening (ISO) ARPA-H -SOL-25-122. For detailed information regarding Proposers' Day review Special Notice (SN) ARPA-H-SN-25-131. Solution summaries are due October 31, 2025, 11:59 PM ET. For more information about THRIVE, please visit:https://arpa-h.gov/explore-funding/programs/thrive

Amendment 3: Team Organization and Capabilities Section The purpose of this amendment is to clarify that the following information, requested in the Teaming Organization and Capabilities section of the Solution Summary, may be included in the Table for Key Personnel: Provide the name, position, and institution of each key team member and describe in 1-2 sentences the skills and experience they bring to the team. If included in the Table for Key Personnel, this information will not count towards the (3) page Solution Summary page limit, however, the Table for Key Personnel must still not exceed (1) page in length. In addition, the Q&A deadline is extended to October 30, 2025 at 11:59PM ET. ---------------------------------------------------------------------------------------------------------------- Amendment 2: Changes to the ISO The purpose of this amendment is to amend the THRIVE ISO. An updated version of the ISO and an updated version of the ISO with tracked changes are included as attachments. Changes to the ISO include: Cost share is now strongly encouraged instead of mandatory. Multi-party teaming arrangements are no longer required. ARPA-H's involvement with regulatory facilitation has been clarified. Please review the amended ISO for all changes. ---------------------------------------------------------------------------------------------------------------- Amendment 1: Added the Frequently Asked Questions (FAQ) to the list of attachments. ---------------------------------------------------------------------------------------------------------------- The Advanced Research Projects Agency for Health (ARPA-H) Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program envisions a future where patients can opt for one-time therapeutic interventions designed to slow, reverse, or cure disease, harnessing revolutionary technologies and a rapidly evolving understanding of the genetic underpinnings of the biological processes that lead to disease. Interested parties are invited to review the attached THRIVE Innovative Solutions Opening (ISO) ARPA-H -SOL-25-122. For detailed information regarding Proposers' Day review Special Notice (SN) ARPA-H-SN-25-131. Solution summaries are due October 31, 2025, 11:59 PM ET. For more information about THRIVE, please visit:https://arpa-h.gov/explore-funding/programs/thrive

Amendment 4: PowerPoint presentation The purpose of this amendment is to add a virtual PowerPoint presentation to the evaluation process. This additional step requires submission of PowerPoint presentation slides, a Gantt chart, and an optional appendix in PDF format. For full details, please see the revised ISO, with changes identified in red font, attached to this amendment. Please note, the deadline for the PowerPoint presentation submission is December 22, 2025 at 3:00PM E.T. The virtual PowerPoint presentations are expected to be held from January 5th to January 16th, 2026. ---------------------------------------------------------------------------------------------------------------- Amendment 3: Team Organization and Capabilities Section The purpose of this amendment is to clarify that the following information, requested in the Teaming Organization and Capabilities section of the Solution Summary, may be included in the Table for Key Personnel: Provide the name, position, and institution of each key team member and describe in 1-2 sentences the skills and experience they bring to the team. If included in the Table for Key Personnel, this information will not count towards the (3) page Solution Summary page limit, however, the Table for Key Personnel must still not exceed (1) page in length. In addition, the Q&A deadline is extended to October 30, 2025 at 11:59PM ET. ---------------------------------------------------------------------------------------------------------------- Amendment 2: Changes to the ISO The purpose of this amendment is to amend the THRIVE ISO. An updated version of the ISO and an updated version of the ISO with tracked changes are included as attachments. Changes to the ISO include: Cost share is now strongly encouraged instead of mandatory. Multi-party teaming arrangements are no longer required. ARPA-H's involvement with regulatory facilitation has been clarified. Please review the amended ISO for all changes. ---------------------------------------------------------------------------------------------------------------- Amendment 1: Added the Frequently Asked Questions (FAQ) to the list of attachments. ---------------------------------------------------------------------------------------------------------------- The Advanced Research Projects Agency for Health (ARPA-H) Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program envisions a future where patients can opt for one-time therapeutic interventions designed to slow, reverse, or cure disease, harnessing revolutionary technologies and a rapidly evolving understanding of the genetic underpinnings of the biological processes that lead to disease. Interested parties are invited to review the attached THRIVE Innovative Solutions Opening (ISO) ARPA-H -SOL-25-122. For detailed information regarding Proposers' Day review Special Notice (SN) ARPA-H-SN-25-131. Solution summaries are due October 31, 2025, 11:59 PM ET. For more information about THRIVE, please visit:https://arpa-h.gov/explore-funding/programs/thrive

Amendment 5: PowerPoint presentation template The purpose of this amendment is to provide the template for the PowerPoint presentation. Please see the Attachments section for the template. Amendment 4: PowerPoint presentation The purpose of this amendment is to add a virtual PowerPoint presentation to the evaluation process. This additional step requires submission of PowerPoint presentation slides, a Gantt chart, and an optional appendix in PDF format. For full details, please see the revised ISO, with changes identified in red font, attached to this amendment. Please note, the deadline for the PowerPoint presentation submission is December 22, 2025 at 3:00PM E.T. The virtual PowerPoint presentations are expected to be held from January 5th to January 16th, 2026. ---------------------------------------------------------------------------------------------------------------- Amendment 3: Team Organization and Capabilities Section The purpose of this amendment is to clarify that the following information, requested in the Teaming Organization and Capabilities section of the Solution Summary, may be included in the Table for Key Personnel: Provide the name, position, and institution of each key team member and describe in 1-2 sentences the skills and experience they bring to the team. If included in the Table for Key Personnel, this information will not count towards the (3) page Solution Summary page limit, however, the Table for Key Personnel must still not exceed (1) page in length. In addition, the Q&A deadline is extended to October 30, 2025 at 11:59PM ET. ---------------------------------------------------------------------------------------------------------------- Amendment 2: Changes to the ISO The purpose of this amendment is to amend the THRIVE ISO. An updated version of the ISO and an updated version of the ISO with tracked changes are included as attachments. Changes to the ISO include: Cost share is now strongly encouraged instead of mandatory. Multi-party teaming arrangements are no longer required. ARPA-H's involvement with regulatory facilitation has been clarified. Please review the amended ISO for all changes. ---------------------------------------------------------------------------------------------------------------- Amendment 1: Added the Frequently Asked Questions (FAQ) to the list of attachments. ---------------------------------------------------------------------------------------------------------------- The Advanced Research Projects Agency for Health (ARPA-H) Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program envisions a future where patients can opt for one-time therapeutic interventions designed to slow, reverse, or cure disease, harnessing revolutionary technologies and a rapidly evolving understanding of the genetic underpinnings of the biological processes that lead to disease. Interested parties are invited to review the attached THRIVE Innovative Solutions Opening (ISO) ARPA-H -SOL-25-122. For detailed information regarding Proposers' Day review Special Notice (SN) ARPA-H-SN-25-131. Solution summaries are due October 31, 2025, 11:59 PM ET. For more information about THRIVE, please visit:https://arpa-h.gov/explore-funding/programs/thrive

Amendment 6: Revised PowerPoint presentation template and Cost Proposal Spreadsheet Template The purpose of this amendment is to provide a revised version of the PowerPoint template for the presentation. Changes are indicated in red (see Slide Nos. 7, 8, and 10). Proposers are instructed to use this version of the template when creating a PowerPoint for the presentation. In addition, the amendment includes the cost proposal spreadsheet template for the proposal submission. As a reminder, cost proposal spreadsheets are not due until full proposals are due (February 5, 2026 by 03:00PM ET). Amendment 5: PowerPoint presentation template The purpose of this amendment is to provide the template for the PowerPoint presentation. Please see the Attachments section for the template. Amendment 4: PowerPoint presentation The purpose of this amendment is to add a virtual PowerPoint presentation to the evaluation process. This additional step requires submission of PowerPoint presentation slides, a Gantt chart, and an optional appendix in PDF format. For full details, please see the revised ISO, with changes identified in red font, attached to this amendment. Please note, the deadline for the PowerPoint presentation submission is December 22, 2025 at 3:00PM E.T. The virtual PowerPoint presentations are expected to be held from January 5th to January 16th, 2026. ---------------------------------------------------------------------------------------------------------------- Amendment 3: Team Organization and Capabilities Section The purpose of this amendment is to clarify that the following information, requested in the Teaming Organization and Capabilities section of the Solution Summary, may be included in the Table for Key Personnel: Provide the name, position, and institution of each key team member and describe in 1-2 sentences the skills and experience they bring to the team. If included in the Table for Key Personnel, this information will not count towards the (3) page Solution Summary page limit, however, the Table for Key Personnel must still not exceed (1) page in length. In addition, the Q&A deadline is extended to October 30, 2025 at 11:59PM ET. ---------------------------------------------------------------------------------------------------------------- Amendment 2: Changes to the ISO The purpose of this amendment is to amend the THRIVE ISO. An updated version of the ISO and an updated version of the ISO with tracked changes are included as attachments. Changes to the ISO include: Cost share is now strongly encouraged instead of mandatory. Multi-party teaming arrangements are no longer required. ARPA-H's involvement with regulatory facilitation has been clarified. Please review the amended ISO for all changes. ---------------------------------------------------------------------------------------------------------------- Amendment 1: Added the Frequently Asked Questions (FAQ) to the list of attachments. ---------------------------------------------------------------------------------------------------------------- The Advanced Research Projects Agency for Health (ARPA-H) Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program envisions a future where patients can opt for one-time therapeutic interventions designed to slow, reverse, or cure disease, harnessing revolutionary technologies and a rapidly evolving understanding of the genetic underpinnings of the biological processes that lead to disease. Interested parties are invited to review the attached THRIVE Innovative Solutions Opening (ISO) ARPA-H -SOL-25-122. For detailed information regarding Proposers' Day review Special Notice (SN) ARPA-H-SN-25-131. Solution summaries are due October 31, 2025, 11:59 PM ET. For more information about THRIVE, please visit:https://arpa-h.gov/explore-funding/programs/thrive

Amendment 7: Changes to the ISO The purpose of this amendment is to amend the THRIVE ISO. An updated version of the ISO, with changes in red font, is included as an attachment to this amendment. Changes to the ISO include: Clarified the inclusion and application of indirect rates as part of the encouraged cost share (see Section 2.5.1). Replaced 2.5.2 "Post-THRIVE IP licensing and PGM Pricing" with 2.5.2 "Public disclosure of regulatory interactions." Changed the quarterly reporting requirement to a a bi-annual reporting requirement (see Section 5.6). Added due dates for the Volume I, Technical and Management Proposal, and Volume II, Cost Proposal to Appendix B (but please note that the due dates have not changed). Clarified that Volume III, Administrative and Policy Requirements Submission, does not need to be submitted unless a proposer is invited to negotiate an award. Clarified that the Volume I, Section J, Schedule and Milestones Milestone Payment Schedule does not need to be submitted unless a proposer is invited to negotiate an award. Revised the information requested in Volume I, Section A "Executive Summary." Removed Volume, Section B "Solution Fit with Thrive." Added Volume I, Section C "Regulatory Innovation Plan." Replaced Volume I, Section F "Commercialization Plan" with Section F "Sustainable Deployment Model." Revised Volume I, Section G "Statement of Work" and Section H "Schedule and Milestones." Clarified that the Volume I, Section K "Data Management and Sharing Plan" does not need to be submitted unless a proposer is invited to negotiate an award. Revised Volume II, Cost Proposal Spreadsheet. Revised Appendix C: Target Product Profile. Please carefully review the amended ISO for all changes. In addition, a Statement of Work template and a Milestone Payment Schedule template are included as attachments to the amendment. As applicable, please use these templates for Volume I, Section G and H. Amendment 6: Revised PowerPoint presentation template and Cost Proposal Spreadsheet Template The purpose of this amendment is to provide a revised version of the PowerPoint template for the presentation. Changes are indicated in red (see Slide Nos. 7, 8, and 10). Proposers are instructed to use this version of the template when creating a PowerPoint for the presentation. In addition, the amendment includes the cost proposal spreadsheet template for the proposal submission. As a reminder, cost proposal spreadsheets are not due until full proposals are due (February 5, 2026 by 03:00PM ET). Amendment 5: PowerPoint presentation template The purpose of this amendment is to provide the template for the PowerPoint presentation. Please see the Attachments section for the template. Amendment 4: PowerPoint presentation The purpose of this amendment is to add a virtual PowerPoint presentation to the evaluation process. This additional step requires submission of PowerPoint presentation slides, a Gantt chart, and an optional appendix in PDF format. For full details, please see the revised ISO, with changes identified in red font, attached to this amendment. Please note, the deadline for the PowerPoint presentation submission is December 22, 2025 at 3:00PM E.T. The virtual PowerPoint presentations are expected to be held from January 5th to January 16th, 2026. ---------------------------------------------------------------------------------------------------------------- Amendment 3: Team Organization and Capabilities Section The purpose of this amendment is to clarify that the following information, requested in the Teaming Organization and Capabilities section of the Solution Summary, may be included in the Table for Key Personnel: Provide the name, position, and institution of each key team member and describe in 1-2 sentences the skills and experience they bring to the team. If included in the Table for Key Personnel, this information will not count towards the (3) page Solution Summary page limit, however, the Table for Key Personnel must still not exceed (1) page in length. In addition, the Q&A deadline is extended to October 30, 2025 at 11:59PM ET. ---------------------------------------------------------------------------------------------------------------- Amendment 2: Changes to the ISO The purpose of this amendment is to amend the THRIVE ISO. An updated version of the ISO and an updated version of the ISO with tracked changes are included as attachments. Changes to the ISO include: Cost share is now strongly encouraged instead of mandatory. Multi-party teaming arrangements are no longer required. ARPA-H's involvement with regulatory facilitation has been clarified. Please review the amended ISO for all changes. ---------------------------------------------------------------------------------------------------------------- Amendment 1: Added the Frequently Asked Questions (FAQ) to the list of attachments. ---------------------------------------------------------------------------------------------------------------- The Advanced Research Projects Agency for Health (ARPA-H) Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program envisions a future where patients can opt for one-time therapeutic interventions designed to slow, reverse, or cure disease, harnessing revolutionary technologies and a rapidly evolving understanding of the genetic underpinnings of the biological processes that lead to disease. Interested parties are invited to review the attached THRIVE Innovative Solutions Opening (ISO) ARPA-H -SOL-25-122. For detailed information regarding Proposers' Day review Special Notice (SN) ARPA-H-SN-25-131. Solution summaries are due October 31, 2025, 11:59 PM ET. For more information about THRIVE, please visit:https://arpa-h.gov/explore-funding/programs/thrive