THRIVE Frequently Asked Questions (FAQs)

PGM in THRIVE stands for Precision Genetic Medicine.

THRIVE is disease agnostic. THRIVE encourages solutions that can address multiple gene variants, clusters of mutations, or categories of rare diseases with a single approach. THRIVE also encourages solutions for small populations with the highest unmet medical needs currently not addressed by industry.

THRIVE is age agnostic. THRIVE understands that strategic timing of genetic intervention is critical to meaningfully slow progression, direct regression, or even prevent disease. To that point, THRIVE encourages solutions designed and poised to make transformative impacts, and requires strong rationale behind a team’s portfolio strategy. Ethical considerations, risks and mitigations should be clearly stated. Of note, THRIVE challenges teams to address mutations that cause severe conditions in neonatal or pediatric populations and mimic adult conditions with similar genetic profiles.

THRIVE is organ agnostic. THRIVE encourages solutions that are flexible for use in multiple organs. THRIVE aims to overcomes the current technical limitations such as imprecision, inconsistency, and uncontrollability. Solutions capable of selectively bypassing more easily targeted organs such as the liver will be considered more compelling.

A THRIVE platform has two components: 1) “cargo,” or tools needed to correct genomes, and 2) “delivery,” or tools that preferentially shepherd cargo to disease relevant cells in the body. Any cargo–delivery platform design may be proposed. Platforms should enable future iteration of precision genetic medicines (PGMs).

THRIVE encourages teams to incorporate tunability into their solutions, e.g. inhibitory and activating small molecules, bio-responsive delivery vehicles, optogenetic molecules, temperature, focused ultrasound, focused magnetic charges, and epigenetic regulators. Inclusion of expression modulators in proposed solutions will be reviewed more favorably.

Ex-vivo approaches and supplemental transgene solutions are out of scope for THRIVE.

THRIVE discourages the use of AAV delivery, as the program envisions a future of distributed, automated, cell-free manufacturing for all PGMs. However, THRIVE recognizes that AAV may be strategically leveraged to de-risk otherwise untested therapeutic cargo and to initiate solutions for THRIVE Modules 2 and 3.

THRIVE aims to work with regulatory agencies including the FDA on behalf of all performer teams through an inter-government agency collaboration to accelerate regulatory innovation, informed by the science.

Yes. THRIVE acknowledges that some modular platform components have achieved clinical or regulatory acceptance. Their strategic inclusion must be justified within the context of the ISO requirements.

Yes. At the time of submission, proposers must propose how they will meet all objective criteria and metrics for each module. Solutions that do not address all three modules will be marked as non-compliant and will not be reviewed.

The THRIVE team has developed program objectives, metrics and point system with the intention of bounding the scope of effort while affording maximum flexibility, creativity, and innovation of proposed solutions to the goals. However, we are open to other approaches that would define success for each module provided convincing rationale supports their inclusion.

Yes. THRIVE aims to make publicly available a dynamic and robust library of tools, assays, standards, and references available for future developers. THRIVE expects its performers to contribute its data outputs to an open-source database.

No. Submitting a Solution Summary is a pre-requisite for submitting a Full Proposal. The THRIVE team will review Solution Summaries and either encourage or discourage the teams for submitting a Full Proposal.

THRIVE will only make awards to “teams” and not prime contractors who intend to establish prime/sub relationships. THRIVE requires a Program Team Lead (PTL) to be designated by the proposing team. The resulting OT will be executed by ARPA-H and the PTL. The PTL is expected to not only serve as the main point of contact and coordinator of the team, but also to oversee and direct the project design, implementation, co-ordination and reporting of the results per contractual obligations.

Proposals identified for award negotiation will result in Other Transaction (OT) Agreements. OTs are commercial-like contractual arrangements. Specific terms and conditions will be negotiated for each OT. An OT terms and conditions template will be provided if selected for award negotiations.

To incentivize stakeholders from academia, industry, and private and PAG-led ventures to develop customized, branded solutions, ARPA-H will cost-share the program over five years at the following rates: 100% in the first year, 80% in the second year, 60% in the third year, 40% in the fourth year, and 20% in the fifth year. ARPA-H requires all teams to submit a cost-sharing strategy.

Please note that proposals that front-load costs to maximize ARPA-H’s total funding contributions or proposals that inflate costs to minimize actual cost-share contributions may be determined non-selectable for award. Cost-share contributions must be proportionally expended throughout the five years – that is, the performer must contribute 0% of costs in the first year, 20% in the second year, 40% in the third year, 60% in the fourth year, and 80% in the fifth year. Performers must determine their own cost-sharing strategy as a part of formal teaming agreement.

Proposers are encouraged to propose a realistic, justifiable, comprehensive, and reasonable budget that aligns with the proposed solution. The proposed budget should align with the technical scope. No budget ceiling has been established.

We are not able to provide budgetary details for THRIVE or a target number for your budget.

ARPA-H discourages strategies such as using only junior staff or proposing only low-risk ideas to cut costs.

No. Individual modules do not have timeline requirements or restrictions. Rather, individual PGM development metrics include time goals, i.e. minimum, moonshot and spaceshot. Furthermore, performer teams are required to address all three modules within the 5-year performance period. To achieve this goal, THRIVE encourages teams to perform across all three modules in parallel and to initiate all portfolio platforms at program kick-off.

Yes. THRIVE requires patient voices to lead as part of a leadership trio with scientists and clinicians to solve the mission of THRIVE. To that end, THRIVE encourages scientifically minded patient advocacy groups (PAGs) experienced in novel drug development, patient registries, digital tools, data applications, patient outcomes, and others to propose to THRIVE. PAGs are encouraged to seek collaborators through their own networks and to sign up on THRIVE’s teaming webpage.

Yes, proposers may submit a similar Solution Summary to the THRIVE ISO for consideration, even if the proposer has already submitted to an ARPA-H Mission Office ISO. However, the offeror must disclose that a similar Solution Summary was submitted to the Mission Office ISO to ensure transparency and avoid any duplication of effort.

It is recommended for the PTL to register for a Unique Entity ID on behalf of the newly formed team on https://sam.gov/entity-registration as soon as possible. Registration can take up to 14 business days to become active. However, existing UEI numbers of entities part of the team can also be used.

It is expected that proposals will require cross functional, multidisciplinary teams with a combination of expertise and capabilities needed to achieve the goals of all three Modules. ARPA-H encourages proposer teams to encompass a variety of organizational types (e.g., commercial organizations, academic institutions, patient advocacy organizations, etc.) to ensure expertise and capabilities requirements are fulfilled, future commercialization is optimized, and adherence to project timelines is managed. The THRIVE team has provided recommendations on the expertise and capabilities needed in a team in the ISO. However, the THRIVE team will not require any number of individuals for any given expertise or capability. The purpose of this process is to successfully bring together the highest performing teams to meet all the technical metrics and to successfully achieve the medical breakthroughs for THRIVE.

Parties interested in seeking teaming partners should submit a one-page profile with their contact information, a brief description of their technical capabilities, and the desired expertise from other teams, as applicable at the THRIVE Teaming Profile Form. Interested parties are highly encouraged to submit them well ahead of Solution Summaries closing date to identify potential teaming partners in a timely manner. While we cannot make introductions for you, we encourage you to use our teaming website since all teaming profiles will be made available on the THRIVE program webpage for all prospective proposers to find the contact information for potential teammates.

It is permissible to join as many proposals as you would like within each team submission. While there is statutory language that may suggest ARPA-H is limited in the number of awards it may make to one entity, there are circumstances in which ARPA-H may make more than three awards to a particular person or organization.

Yes. ARPA-H acknowledges that many rare disease efforts and organizations also exist outside the United States. Non-U.S. entities may participate to the extent that such participants comply with any necessary nondisclosure agreements, security regulations, export control laws, and other governing statutes applicable under the circumstances. Please review the Program Solicitation, specifically the section on Eligibility Information, for additional details.

Team members will be required to execute a Multi-Party Teaming Agreement (MPTA) with all members of their team to outline the terms and conditions of their established relationship, as parties to the resultant OT. ARPA-H is not a party to MPTAs, but the OT will require that the MPTA terms and conditions to comply with the minimum expectations set forth in Appendix D in the ISO. The MPTA will be required to be executed prior to award.

The team will elect one member (organization) to act as their “agent” to submit on behalf of the team to the government. The lead member (agent) will submit invoices in the Payment Management System (PMS), receive payments (through the entity’s EIN) on behalf of the entire team, and will then distribute funds to the team accordingly. Each team member does not submit invoices to the government directly. The Government expects MPTAs will outline the resulting distribution of funds to applicable team members.