THRIVE Frequently Asked Questions (FAQs)

A THRIVE PGM is a Precision Genetic Medicine. A PGM is ideally, but not limited to, one-time interventions designed to slow, reverse, or prevent suffering from disease by addressing the root causes at the genetic level. A PGM can be any modality. Note that PGMs composed of higher risk modular components that have yet been proven from a technical, clinical, or regulatory perspective will be awarded more points than modalities that have previously demonstrated some degree of success. Teams are encouraged to pursue PGM platforms of varying degrees of difficulty to successfully innovate all Modules and earn enough points to meet milestones and avoid down-selection.

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 suffering from disease. Perinatal, pediatric, or other age groups are within scope. Ethical considerations, risks and mitigations should be clearly stated. Of note, THRIVE challenges teams to address mutations that cause severe conditions in young populations that mimic adult conditions with similar genetic profiles.

No.

THRIVE is organ agnostic. THRIVE encourages solutions that are flexible for use in multiple organs. THRIVE aims to overcome current technical limitations such as immunotoxicity, 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 typically 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 be considered distinct “engines” that could enable future iteration customizable PGMs with minor changes, eg. gRNA sequences for base editors.

THRIVE is technology agnostic. THRIVE aims to build and validate various platforms that serve as engines that can create many more genetic medicines for rare and other types of diseases. Teams may propose any novel and innovative platforms and provide rationale for the overall portfolio strategy. All performer teams are expected to strategize a portfolio of >2 PGMs in each of >2 PGM platforms. THRIVE encourages engineered or cell-free approaches; however, teams may propose viral vectors (e.g., AAV) as part of a larger portfolio strategy to address all modules in THRIVE. Teams should strategize an optimal portfolio that can realistically accomplish the goals set out in the THRIVE program. Please consult the THRIVE points system included in the ISO when strategizing a portfolio.

A team’s proposal will be evaluated holistically, with a focus on the collective capabilities and potential of each team to successfully collaborate and innovate across all three modules. Previously successful platforms or modular components will be weighted less heavily than those platforms or modular components that have not yet been clinically demonstrated. Teams are highly encouraged to strive for moonshots and spaceshots. Strategies that include less technically risky platforms to launch Module 2 and 3 are encouraged.

THRIVE is not solely a gene editing program. Rather, THRIVE is an all-encompassing challenge for teams to leverage technologies and modalities at all risk levels to establish a viable, sustainable, and scalable ecosystem of regulation, reimbursement, access, and partnership across academia, industry, and non-profits virtually networked to enable all patients in the future to be treated as the unique individuals we are, regardless of where we are.

Teams should propose realistic, end-to-end strategies that cover all modules 1-3 (including clinical trial readiness and community deployment), with complex, multi-party teaming including patient advocacy groups (PAGs), data and manufacturing partners, and satellite sites. Success is defined by progressing platforms toward approval and patients, not just proof-of-concept studies.

The THRIVE program rewards performers points on an ongoing basis based on meeting metrics establish for the minimal, moonshot, and spaceshot goals. Low scoring teams may be downselected over the course of the program.  The team’s overall strategy should account for the potential to collect points for each of its innovations across all modules.

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. Other innovations are welcome. Inclusion of expression modulators in proposed solutions will be reviewed more favorably. Teams should strategize a balanced portfolio of low and high-risk approaches to successfully progress platforms developed in Module 1 through Modules 2 and 3.

• Ex-vivo approaches are out of scope.
• AAV-mediated supplemental transgene solutions are only in scope if they are strategically included as part of a bigger portfolio strategy to address all modules in the THRIVE program. AAV-costs will be supported up to 20%.

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. THRIVE will also need to work with regulatory agencies outside of the U.S. We intend to be a catalyst to surpass current timelines meaningfully. Proposers are also encouraged to develop clinical trial and regulatory strategies to bring innovations to building a new regulatory pathway for these novel PGMs for all future sponsors to leverage.

PGMs can be at any stage of development.

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. THRIVE encourages all proposing teams to start all modules in parallel, and therefore, teams may choose to start Modules 2 and 3 with previously proven platforms or PGM components. Teams should consult the metrics points awarding system when developing their overall portfolio strategy to ensure they are optimizing the team’s ability to stay competitive throughout the course of the program. Teams may risk down-selection based on points compared with other teams.

Although THRIVE aims to create one-time treatments for multiple diseases, solutions that include repetitive administration are not excluded (e.g., ASO, siRNA, etc.). We will evaluate the entire portfolio strategy as a whole. Teams are encouraged to review the points system created in THRIVE to develop their portfolio strategies.

Yes. At the time of submission, proposers must propose how they will meet all objective criteria and metrics for each module. 

Note: 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. If performers propose milestones that are relevant for the platform technologies and PGMs that are proposed, clear rationale and justification are requested.

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 to accelerate the developments of PGMs during and after THRIVE. Proposers are encouraged to develop a data strategy within their teams to address the goals of the program. Additionally, proposers are encouraged to propose solutions to create a federated way for data created to be leveraged for future PGM sponsors.

Yes. The intent of THRIVE is to accelerate the development of platforms and PGMs during THRIVE and after the performance period of THRIVE.

Teams are required to demonstrate that their path to market is viable, that they have addressed any potential IP obstacles that could hinder commercialization, and how they intend to overcome them. We look forward to reviewing all creative and innovative commercialization and IP solutions proposed with the goal of creating affordable cures available to all rare disease patients and other patients affected by genetic disorders. Teams are encouraged to have cost-share partners that are interested in co-designing a future state of the industry that rewards solutions for small populations of patients, down to N=1.

Yes. THRIVE encourages international collaboration as rare diseases are global, and the future of precision medicine can be applied to all.

It is up to the proposing team to propose what they think is reasonable. PGMs costing greater than one million dollars are unlikely to be deemed affordable by most payers. Different solutions will have different costs, which is also dependent on whether these are one-time or multiple intervention strategies. Team strategies around IP licensing, royalties, etc., are encouraged for each platform developed. A goal of THRIVE is to innovate viable, sustainable, and scalable platform engines and an ecosystem to support a robust industry and serve millions more patients worldwide.

Yes, proposing teams must identify their intended collaborative expert and satellite centers at the time of Solution Summary submission, as each team is required to have a strategy to innovate across all three modules at that time.

Teams are expected to include the names and contacts and summary strategy of who and how Modules 2 and 3 will be addressed in their overall strategies in their Solution Summaries. Formal commitments and letters will be required during contract negotiations, should a team’s proposal progress to that stage.

No. Submitting a Solution Summary is a pre-requisite for submitting a Full Proposal. The THRIVE team will review all Solution Summaries and invite select ones to submit Full Proposals.

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. 

Note: We recommend the PTL to submit solicitation documents on behalf of the proposing team.

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, including piloting PGM centers, 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 required to submit a ROM in the Solution Summary. We are not expecting verification documents until the Full Proposal stage.

There are two (2) types of cost-sharing: Cash Contributions or In-Kind Contributions. Cash contributions are the preferred method of fulfilling the performer’s cost-share; however, the Government will consider in-kind contributions that directly support the proposed solution. Please review the THRIVE ISO for additional examples of cost-share for each type.

Government funded equipment, materials and supplies shall not be proposed as cost share contributions.

NIH resources are Government funded and shall not be counted toward cost share.

An NIH funded consortium serving as a sub-performer may NOT use its funding to match funds.

It is up to the team members to work amongst their proposing team to develop an optimal budgeting strategy. ARPA-H will not determine for a team how much cost-share each team member must contribute to the overall team cost share amount. Cost share is meant to set up a seamless transition into the real world.

Program Team Leads (PTLs) should only submit one solution summary, since the ISO dictates that PTLs may only submit one proposal as the PTL. However, PTLs and other team members may participate in multiple Teams under separate submissions.

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. Proposers may review recently awarded projects and programs to understand the range of budgets that have been approved.

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 driving collaborators through 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.

Note: Proposing teams are required to address all three modules in their submission to the THRIVE ISO.

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.

Yes, that is the goal.

Yes. We intend to make the recordings available (link opens in new window) to the THRIVE community.

THRIVE is designed to incentivize currently siloed academic, industrial, and non-profit entities to work in real world collaboration free of commercial constraints and aligned on a joint mission – to catalyze a viable, scalable, and sustainable future of individualized, precision medicine for all. 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 especially for small, currently commercially unviable populations 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 the stated goals and technical metrics and to successfully realize the spirit the overall THRIVE program.

There is no minimum or maximum number of organizations that can be on one proposing team. However, the proposing team must address all modules in the THRIVE program in one submission.

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.

The rare disease community understands that catalytic transformation will take collaboration across fences, walls, and moats. Patients are driven by their deeply immersive lived experiences and bring essential real-world perspectives. Some have even demonstrated success in corralling and leading cutting edge scientific and clinical expertise towards innovative solutions. After all, they are the ones who viscerally understand the urgency and rigor required to literally save their own children and families from fateful diagnoses.

To address the goals within the THRIVE program, including innovation of a new ecosystem tailored for a future with ubiquitous use of PGMs, we expect organizations to form teams that cross boundaries. THRIVE believes collaborative public and private entities can together realize a new ecosystem that will change the paradigm of medicine and re-align financial incentives to optimize cost, pricing, and access. Though organizations are not required to be part of any team to submit to THRIVE, all modules must be addressed in the submission. THRIVE does not expect any single entity to be able to address all of the challenges posed.

It is permissible to join as many proposals as you would like within each team submission. 

Performers will not be paid multiple times through different awards for the same work performed.

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.

There is no limit.

There are many organizations with interests to build clinics around the globe. These organizations may be academic or private hospital systems, government ministries of health, patient advocacy groups, philanthropy groups, global foundations, and others. These partners may come from the U.S. or outside the U.S. Expert centers may have existing relationships to other clinics and partners who can also be brought into THRIVE. We recommend all organizations interested in being a part of a THRIVE performing team to submit a teaming profile to be discovered by all interested parties.

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. 

No, formal letters of intents are only required at the Full Proposal submission stage.

The team will elect one member (organization) preferably PTL 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.

It is up to the proposing team to decide how a team should be structured and who should be assigned as the PTL. The PTL can be a scientist, physician, clinician, patient, or someone else within the team. Though it may be advantageous for a PTL to have program management and/or a background in industry, it is ultimately up to the team to determine who is best to lead the team. The teaming arrangements are likely to be a result of the capabilities and expertise of the participants and organizations in the team. The THRIVE Team will not determine the structure or assign the PTL for the team. However, ARPA-H will establish privity of contract between all team members and will have access to interact with all team members during the performance period. 

No. It is up to the proposing team to decide how a team should be structured. ARPA-H will establish privity of contract between all team members and will have access to interact with all team members during the performance period. ARPA-H will be making one payment to the team, and it is up to the PTL to distribute those payments to all other team members.

It is up to the proposing team to decide how a team should be structured and what are required by each team member. ARPA-H will establish privity of contract between all team members and will have access to interact with all team members during the performance period.

It is up to the proposing team to decide how a team should be structured and what are required by each team member. ARPA-H will establish privity of contract between all team members and will have access to interact with all team members during the performance period.

We will look to you to propose how you plan to incentivize this post-THRIVE.