A06B_Attachment_H_ARPA-H_SBP_Government_Answered_Questions.pdf

Attachment H: ARPA-H Small Business Program Solicitation #4 Government Answered Questions Document

General Questions

Q1. The SBIR solicitation states that it’s required to use the Solution Summary Template provided with the BAA, however I am unable to find the template.

Answer:

The Solution Summary template is available on SAM.gov as Attachment G.

Q2. If a proposal includes multiple collaborating organizations like as required for STTR

(e.g., a small business and a university), should a single Foreign Disclosure form be submitted for the entire proposal, or is a separate Foreign Disclosure form required from each participating organization?

Answer:

No, just the small business submitting the proposal.

Q3. Do you recommend including references?

Answer:

References are not required as part of this solicitation, however proposers submitting full proposal packages at Stage 2 will have the opportunity to provide supporting documentation as they deem necessary.

Q4. Should the references page be included in the 4-page limit, or is it considered an extra page in addition to the 4 pages?

Answer:

References are not counted in the 4 page limit.

Q5. What is the recommended total project duration for Fast Track application?

Answer:

A Phase I contract is typically ≤12 months and a Phase II contract is typically 24 – 36 months, but this varies with individual projects and technologies. You can find anticipated timelines for each topic under Section 8 of the BAA.

Q6. Should the team members and capabilities be introduced in the solution summary submission?

Answer:

Include information as needed to establish technical merit and novelty. The Key Personnel

Worksheet is a requirement of Stage 2 and not required at solution summary submission.

Q7. How does the Government define a "Partner Organization" for purposes of this solicitation? Does the term include all organizations with which an offeror has a business relationship, or only those organizations participating in or supporting the proposed effort?

Answer:

Partner organizations are those that are participating in the proposed projects.

Q8. If the majority owner of the small business applying is in the process of getting their green card (is married to a US citizen) and will likely have it before the Sept deadline, are they eligible for an SBIR/STTR award?

Answer:

Yes.

Q9. Within solution summary, how detailed or specific do we need to be on patient population, claims, and decision?

Answer:

The solution summary should be specific about the patient population and claims that are made about the technology and what will be accomplished.

Q10. Are the recording and slides available from Proposers’ Day?

Answer:

The Proposers’ Day recording can be found here: https://youtu.be/SRnKQGQDiwI

Q11. For a Fast Track proposal, should the Solution Summary consist of a single four-page document that addresses both Phase I and Phase II activities, milestones, and objectives, or should proposers submit separate four-page Solution Summaries for each phase?

Answer:

Fast Track proposals are allowed 1 additional page in their Solution Summary specifically to detail their Commercialization Plan Statement, bringing the maximum length to 5-pages.

Proposers for Fast Track projects should not submit multiple Solution Summaries.

Q12. For STTR proposals, may more than one research institution participate in the proposed effort? If so, how should the required research institution performance percentage be allocated among multiple participating research institutions?

https://youtu.be/SRnKQGQDiwI

More than one research institution may participate. The research institution that originated the technology being developed must have a 30% share of the workload. If the technology was originated by multiple institutions, a single research institution must still have a ≥30% share of the work.

Q13: What distinguishes a Phase I proposal from a Phase II proposal under this solicitation? Specifically, what level of technical maturity and validation is expected for each phase, what criteria determine eligibility for Direct to Phase II, and what types of datasets (e.g., longitudinal clinical data) are expected to support a Phase II proposal? If awarded a Phase I project, may an offeror subsequently apply for Phase II upon successful completion of Phase I?

Answer:

All Phase I recipients are eligible to submit a Phase II proposal during the last quarter of their performance. However, it is not guaranteed that the Phase II proposal will be funded. Phase

Is are intended to develop a proof of concept that addresses that demonstrates the feasibility of the approach, while Phase II builds a functional prototype. The supporting data needed is project and topic specific.

Q14. Does the July 10 submission deadline apply to the Solution Summary or the full proposal?

Answer:

The July 10 deadline applies to the Stage 1 Solution Summary. This is being extended to

July 17, 2026 at 11:59am Eastern time, as part of Amendment 01 of the BAA. The deadline for Stage 2 proposal materials will be announced separately when encourage and discourage notifications are released.

Q15. What is the submission process for Phase I, Phase II, and Fast Track proposals?

Answer:

All proposal types follow the same two-stage submission process. However, Phase II and Fast

Track proposals require additional documentation, as described in the solicitation. Please see

BAA Sections 3, 4, and 5 for further information.

Q16. What are the submission deadlines?

Answer:

The Solution Summary submission deadline is July 17 at 11:59 a.m. Eastern Time.

Proposers should always refer to the solicitation and official amendments for current deadlines.

Q17. Will additional SBIR/STTR topics be released?

Yes. ARPA-H anticipates releasing additional topics in the future. The timing has not yet been determined. Future announcements will be communicated through ARPA-H channels and

SAM.gov.

Q18. May a proposer submit proposals to more than one topic?

Answer:

Yes. Proposers may submit proposals to multiple topics, provided each proposal is distinct and responsive to the specific topic requirements. Duplicate proposals submitted to multiple topics will not be reviewed and will be considered non-conforming.

Q19. What is the period of performance?

Answer:

The period of performance depends on the type of award (Phase I, Phase II, or Fast Track) and will be negotiated prior to award. Proposers should refer to Section 1.1 of the solicitation for additional information.

Q20. Is SAM registration required?

Answer:

Yes. Proposers must maintain an active SAM registration and Unique Entity Identifier (UEI) in accordance with the solicitation requirements before an award can be made. Because registration and renewal can require several weeks, proposers are strongly encouraged to begin the process as early as possible.

Q21. If multiple small businesses will collaborate on a proposal, which organization should serve as the prime contractor?

Answer:

Proposers should ensure that the proposed prime contractor satisfies all eligibility requirements identified in Section 2 of the solicitation. Teaming arrangements must comply with all applicable SBIR/STTR eligibility requirements.

Q22. Are solo founders eligible to apply?

Answer:

Eligibility is governed by the requirements set forth in Section 2 of the solicitation. There is no minimum company size requirement, but Team is an evaluation factor. Proposers should review the eligibility and certification requirements to determine whether their proposed organization satisfies the applicable criteria.

Q23. How can an offeror merge ARPA-H Solutions accounts associated with different organizations or email addresses?

Proposers may submit a support ticket through the "Ask a Question" function on the ARPA-H

Solutions website and select the option related to the Solutions Site Support. ARPA-H technical support can assist with merging accounts.

Q24. What intellectual property and data rights apply?

Answer:

SBIR data rights are governed by the applicable SBIR Data Rights clauses. Additional intellectual property considerations, where applicable, will be negotiated prior to award.

Q25. Who can attend Proposers’ Day? Do you need to be affiliated with a university?

Answer:

Anyone is welcome to attend Proposers' Day to learn more about ARPA-H's SBIR/STTR

Program. Please refer to the BAA posted on sam.gov for the eligibility requirements listed in

Section 2 for submission of a Solution Summary.

Q26. Could you please clarify whether Solution Summaries should be submitted via email or ARPA-H web https://solutions.arpa-h.gov, and if not, to which address? I would also appreciate any additional guidance regarding formatting or submission requirements beyond those outlined in the solicitation materials.

Answer:

Solution Summaries will be submitted via the ARPA-H Solutions Site https://solutions.arpa-h.gov. Solution Summaries and Proposals submitted via email will not be evaluated.

Q27. Could you provide additional guidance regarding formatting or submission requirements beyond those outlined in the solicitation materials.

Answer:

Requirements for the Solution Summary Phase can be found in Section 4.2 Documents required at submission in the solicitation. Templates for these required documents are linked in the solicitation as well as on sam.gov

Q38. What if our project does not appear to align directly with any of the anticipated topics outlined in the solicitation?

Answer:

The Small Business Program will periodically be releasing new research topics. If your project does not align with current topics, please continue to check the ARPA-H Small Business

Program page (https://arpa-h.gov/explore-funding/sbir) as new topics will be periodically released. You can also sign up for the ARPA-H Vitals newsletter, which will announce the release of any additional topics. We encourage you to also monitor SAM.gov for any updates.

Q29. Is an SBIR submission by a small business acceptable as prime, or does ARPA-H expect a clinical system or other 501(c)(3) as prime with the small business as subcontractor?

Answer:

Please refer to Section 2, Eligibility and Certifications to ensure the prime applicant for your solution meets all the necessary requirements.

Q30. For a Fast-Track submission, where is the most appropriate section to include preliminary data, given that a Feasibility Statement is not required?

Answer:

The Solution Summary.

Q31. In the "Relevance of the Proposed Technology" section, should the discussion focus primarily on alignment with the specific program objectives and focus areas, or should it also address broader relevance to other ARPA-H mission areas and ISOs?

Answer:

For this SBIR/STTR opportunity, focus on the specific topic and its objectives.

Q32. What is the expected Technology Readiness Level (TRL) at the start of Phase I for responsive proposals?

Answer:

There is no set rule regarding TRL thresholds.

Q33. How should proposers distinguish between subawardees, consultants, contract service providers, and teaming partners when identifying project participants in the proposal?

Answer:

For purposes of this solicitation, ARPA-H applies the same definitions used by the National

Institutes of Health (NIH). Organizations providing contract services (e.g., contract research organizations (CROs) performing fee-for-service work) are not considered teaming partners solely by virtue of providing those services. However, consultants are considered subawardees for purposes of proposal submission and should be identified accordingly.

Proposers should identify project participants consistent with the solicitation requirements and applicable NIH definitions. https://seed.nih.gov/faqs#11782

Q34. If a proposal builds upon work that is currently supported by other funding sources, what level of differentiation is expected between the proposed ARPA-H effort and the existing funded work?

https://seed.nih.gov/faqs#11782

The proposed ARPA-H effort must be clearly differentiated from work supported by other funding sources. ARPA-H funding may not be used to duplicate activities that are already funded. Proposers should clearly describe the unique scope of work to be performed under the proposed ARPA-H award and demonstrate that the proposed effort is non-duplicative.

Q35. What is the date of Proposers’ Day?

Answer:

Registration for Proposers' Day closed on June 9, 2026 and Proposers' Day took place on

June 11, 2026.

Q36. Could you provide additional guidance regarding formatting or submission requirements beyond those outlined in the solicitation materials.

Answer:

Requirements for the Solution Summary Phase can be found in Section 4.2 Documents required at submission in the solicitation. Templates for these required documents are linked in the solicitation as well as on sam.gov

Q37. For SBIR or STTR proposals, does ARPA-H require the Primary Investigator to meet the greater than 50 percent employment threshold with the small business at the time of proposal submission, or is it acceptable for the PI to meet this requirement by the time of award?

Answer:

The Principal Investigator must be primarily employed (>50%) by the small business at the time of award and throughout the duration of the project. At proposal submission, the PI does not have to already meet the >50% employment requirement, however you are expected to demonstrate a credible plan that they will by award. For STTR awards, the PI may be employed by the research institution partner.

Q38. Do proposers need to have their own lab capabilities, or are partnerships between digital health companies and clinical or research organizations acceptable?

Answer:

Not all work needs to be done in-house. Partnerships or contracted work are acceptable provided that the relationship and budget meet criteria for the funding mechanism.

Q39. Our focus has the potential for high impact but is not addressed in any ARPA-H solicitation. Could program initiatives be made less specific in order to encompass a wider solution set?

The Small Business Program will be releasing new topics throughout the year. If your project does not align with current topics, please continue to check the ARPA-H Small Business

Program page (https://arpa-h.gov/explore-funding/sbir) as new topics will be periodically released. We encourage you to also monitor SAM.gov for any updates.

Contracting & Budget Questions

Q1. How does Phase I transition to Phase II?

Answer:

For Fast Track awards, both phases are incorporated into a single award and continuation decisions are based on successful completion of Phase I milestones. ARPA-H will typically choose whether to exercise the option activating Phase II during the last quarter of Phase I performance. For standalone Phase I awards, progression to Phase II is determined through discussions with the Program Manager and will depend on technical progress, funding availability, and Government interest in continued development. All Phase I performers are permitted to submit a Phase II proposal prior to the end of their Phase I, but there is no guarantee that it will be funded.

Q2. Should we include a rough order of magnitude budget in the solution summary?

Answer:

This will be collected by the ARPA-H Solutions Site.

Q3. For the Stage 1 Solution Summary, is entry of the total proposed budget sufficient, or should proposers also include a budget breakdown (e.g., by milestone, objective, or task) within the submission? If additional budget detail is recommended, what level of detail should be provided?

Answer:

When submitting the Solution Summary, the Solutions Site will require proposers to input a

Rough order Magnitude (ROM) cost estimate (the total award amount sought). If there are complex teaming arrangements, then it may be helpful to address how funds will be distributed amongst the companies composing the team in the Solution Summary.

Q4. Is there a possibility that if we apply for a Phase II but do not meet the requirements that we can get relegated to a Phase I?

Answer:

No.

Q5. Are SBIR/STTR awards issued as Other Transactions (OTAs)?

OTAs will not be issued for topics 1 through 7.

Q6. When will awards be made?

Answer:

Awards are anticipated to be made during Fiscal Year 2027. Specific award dates will be announced at a later time.

Q7. How does the HHS nine-proposal submission limit apply to this solicitation?

Answer:

The nine-proposal limit applies to Stage 2 proposals only. Stage 1 Solution Summaries do not count toward the submission limit. Phase I and Phase II proposals are counted as separate submissions.

Q8. What indirect cost rate should be used if our institution does not have a federally negotiated rate?

Answer:

We are asking proposers to provide a fully burdened labor rates. Proposers can provide indirect costs; however, the Government reserves the right to request substantiating information regarding cost.

Q9. Is the money disbursed after a milestone is achieved i.e. the submitting company will have to incur the charges upfront and then ARPA-H will disburse the funds after a milestone is completed? Or is it like NIH when grant monies are disbursed on a monthly basis.

Answer:

Typically, we divide the overall cost of the project into even quarterly payments to give performers regular cashflow, and the first payment milestone is the ‘kickoff,’ which occurs within the first 30 days of contract execution. If there are substantial upfront costs that must be incurred to begin technical work, that information should be provided to the Small

Business Team for consideration. Currently, monthly payments are not permitted.

Q10. For the SBIR Funding Agreement Certification, what contract or solicitation number should be referenced?

75N99226SN106

Topic 1 (Development of an annual test to inform women about their future fertility) Questions

Q1. Is use of the NIH All of Us Research Program required for this solicitation?

Answer:

No. Use of the NIH All of Us Research Program is optional.proposers

Q2. If additional technical data are generated after the Solution Summary submission deadline, may applicants update their submission?

Answer:

No. Solution Summaries cannot be updated after the submission deadline. If a proposer submits a Stage 2 proposal, additional technical data generated prior to the Stage 2 submission deadline may be incorporated into the full proposal.

Q3. Are AI-based imaging approaches responsive to Topic 1?

Answer:

AI-enabled image analysis and image processing approaches may be responsive, provided the imaging modality is non-invasive, scalable, and suitable for deployment in the intended clinical setting (e.g., primary care or home use), consistent with the solicitation requirements.

Q4. May existing fertility biomarkers be combined with novel biomarkers or analytical methods?

Answer:

Existing biomarkers may be incorporated into a proposed solution; however, proposals should clearly identify the novel component that meaningfully advances current practice. The

Government is seeking innovations that provide new clinically useful information beyond existing biomarker combinations or analytical approaches.

Q4. May IVF patient populations be used to identify or validate fertility biomarkers?

Answer:

IVF populations may be appropriate for biomarker discovery or validation. However, proposers should demonstrate that the resulting diagnostic approach can ultimately be generalized to the broader intended patient population.

Q5. Is long-term clinical validation required during Phase I?

Answer:

No. Phase I is intended to establish proof of concept. Proposers may use existing datasets or retrospective analyses to demonstrate feasibility. Long-term prospective validation is not expected during Phase I and may be addressed during subsequent development phases.

Q6. Does the desired fertility prediction test need to predict fertility only in the near term?

Answer:

The objective is to provide women with clinically meaningful information regarding future fertility potential sufficiently early to support informed reproductive decision-making.

Proposers should propose an approach that provides actionable predictive information consistent with the goals of the solicitation.

Q7. If applying only for Phase I, should the Solution Summary address Phase II activities?

Answer:

The Solution Summary should address the phase for which the offeror is applying. Proposers applying only for Phase I should focus on Phase I objectives. Fast Track and Phase II proposals should address the applicable phase requirements described in the solicitation.

Q8. Does the desired turnaround time require that testing be performed at the point of care?

Answer:

Testing performed at time of care is not required. Centralized laboratory processing is acceptable. The referenced processing time applies to the analytical process itself and does not preclude specimen shipment to a laboratory or multiplexed testing approaches where appropriate.

Q9. Are direct-to-consumer diagnostic approaches responsive to Topic 1?

Answer:

Direct-to-consumer diagnostic approaches are not responsive to Topic 1. The Government intends for the technology to support clinical care within the healthcare delivery system and to follow an appropriate regulatory pathway. The objective is to facilitate use within routine healthcare settings, including primary care, rather than direct-to-consumer deployment.

Q10. May a proposal include both physician-directed and direct-to-consumer deployment pathways?

Answer:

For purposes of this solicitation, the proposed technology should be developed for integration into the clinical care pathway and regulatory framework described in the solicitation. While proposers may pursue additional commercialization pathways independently, proposals submitted under this solicitation should focus on the intended clinical implementation.

Q11. How strictly will sensitivity and specificity targets be evaluated?

The Government recognizes that these are ambitious technical goals and understands the inherent technical risk associated with achieving them. Proposers should propose aggressive but realistic performance objectives. During project execution, performers are expected to communicate technical challenges and work collaboratively with the Government to address them while maintaining progress toward program objectives.

Q12. Does the Target Product Profile describe the desired commercial end product or the expected deliverable at the end of the award?

Answer:

The Target Product Profile describes the intended commercial end product. The solicitation separately identifies the technical milestones and deliverables expected by the conclusion of each project phase.

Q13. Are non-biomarker specific tests in scope for this topic?

Answer:

Non-biomarker specific tests are not within scope for this topic.

Q14. 1) What is the proposal funding ceiling? 2) Do you have any government contracted medical diagnostic companies that we can work with? 3) is this a phase I or phase II of SBIR STTR, or cover both?

Answer:

1) Proposal funding ceiling is dependent on what phase is awarded Phase 1 has a ceiling of

$600k and Phase II has a ceiling of $3.5M. Refer to Section 1.1 Program Phases in the solicitation for additional information. 2) We do not have specific companies in which we ask performers to work with. 3) To determine which Phases are anticipated to be award per topic, please refer to the specific research topic of interest in the solicitation section 8. Those details are listed in a table at the top of each research topic.

Q15. Is ARPA H looking only for solutions that discover new biological biomarkers, or are approaches that combine existing biomarkers with AI, predictive modeling, and digital health platforms also acceptable?

Answer:

This topic is focused on discovery of novel biomarkers, either imaging, device, or biologic.

Approaches that combine biomarkers with modeling, AI, and other digital platforms would be acceptable, but the solution cannot rely solely on these tools. Competitive proposals will have solutions that are applicable regardless of availability of patient history.

Q16. How important does ARPA H consider AI and machine learning models that bring together multiple types of data, such as hormone levels, behavioral inputs, and long term health records, for fertility prediction?

Answer:

This topic is particularly interested in novel biomarkers (device, imaging, or biologic) that can inform women about their fertility. AI and modeling combining multiple data types can be part of the solution. Solutions should consider the intended care setting described in the solicitation and ability to be used by patients without robust medical histories.

Q17. Is the goal to create a clinical diagnostic tool, or would ARPA H also support solutions that provide patient friendly insights through digital platforms to help with fertility planning?

Answer:

Per the solicitation, the topic is focused on tools and biomarkers via biospecimen collection, imaging, or device diagnostics, that are evidence-based to support the Target Product Profile defined. Solutions that are focused on patient education or inferred decision making are unlikely to be competitive.

Q18. Would ARPA H consider proposals that use existing datasets and known biomarkers along with advanced analytics, or is the focus mainly on discovering entirely new biomarkers?

Answer:

This topic is focused on discovery of novel biomarkers, either imaging, device, or biologic.

Approaches that combine biomarkers with modeling, AI, and other digital platforms would be acceptable, but the solution cannot rely solely on these tools. Competitive proposals will have solutions that are applicable regardless of availability of patient history.

Q19. What level of clinical validation is expected in Phase I, especially for solutions based on predictive modeling or software rather than traditional lab tests?

Answer:

ARPA-H does not specify the level of clinical validation required, this will vary by project and topic.

Q20. How is ARPA H thinking about accessibility, affordability, and user experience for an annual fertility test, particularly for making it practical for widespread use?

Answer:

Please refer to the target product profile and requirements in the solicitation which addresses these points.

Q21. Does ARPA H expect the solution to integrate with existing healthcare systems, and how important is compatibility with electronic health records and digital health platforms?

Answer:

Please refer to the target product profile and requirements in the solicitation which addresses these points.

Topic 2 (Versatile Bioadhesives) Questions Q1. Reversible Topic 2 description in the BAA document (item 2 in technical areas supported, in-scope) mentions reversibility. Could you elaborate on what you mean by that? Do you mean that the bioadhesive should be designed so that there is a way for it to become non-adhesive beyond through degradation? Or does degradation imply reversibility?

Answer:

The bioadhesive should be degraded without any side effects or toxicity.

Q2. Our technology is suitable for a broad range of tissue and organ applications.

Could you provide some guidelines on how we should prioritize which applications we include in the proposal? Are there any high priority tissues and organs ARPA-H is primarily interested in? We have selected the following: blood vessel, lung, skin, sternum, GI, nerve, solid organs, heart, trauma, and hernia repair. We are down-selecting from this list and would be interested in getting some feedback on any specific applications that ARPA-H is highly interested in.

Answer:

ARPA-H does not have a preference on priority of types of tissues or organs. The above listed types are just examples.

Q3. The information session topic 2 slide stated local drug delivery for chemo as a desirable application. Controlled drug release of chemo drugs is a very different application than surgical bioadhesives. Our technology is very suitable for this application, so we are wondering how important this application is for ARPA-H and if we should prioritize it and include it in our proposal.

Chemotherapy is just an example, we are requesting proposals where the bioadhesives can be a drug delivery depot.

Topic 3 (Universal Platform for Living Adaptive Toxin-removal) Questions

Q1. I am reading the call for summaries for SBIRs and one in particular would possibly be a good match; however, the write-up isn't clear. Do you have more information on ARPA-H 03 - Universal Platform for Living Adaptive Toxin-removal (UNI-PLAT)?

Answer:

Proposers’ Day already occurred on June 11, 2026. A recording of the Proposers' Day can be at https://youtu.be/SRnKQGQDiwI

Q2. I'm interested in attending the proposers' day with particular focus on ARPA-H 03

UNI-PLAT. I realize my special considerations note didn't save. I'm a co-founder of a stealth biotech building a microfluidic platform to enable end-to-end lab-in-the-loop antibody discovery. This platform would be reprogrammable to automate all the steps in relevant antibody assays. We are very early, and I can understand that this proposer's day is limited, but I would love to join and learn more.

Answer:

Proposers’ Day occurred on June 11, 2026. A recording of the Proposers' Day can be found at https://youtu.be/SRnKQGQDiwI

Q3. What is the scope for designing a reprogrammable and “universal chassis”?

Answer:

Engineered bacterial strains under UNI‑PLAT should be readily reprogrammable across multiple toxin types as described in the solicitation. The intent is that core elements, such as delivery approach, genome engineering methods, and shared assays for chassis stability, metabolic flux, and functional performance will remain consistent across different toxin‑removal applications.

While some toxin‑specific assays will naturally be required, proposers should design their platforms so that expanding to new targets does not require rebuilding the chassis from scratch or identifying entirely new genomic integration sites for each function. Ideally, teams will demonstrate a “plug‑and‑play” architecture: modular pathways or genetic components that can be inserted, swapped, or tuned with minimal redesign. UNI-PLAT seeks to create a platform technology that supports diverse detoxification modules without major re-engineering.

Q4. The solicitation calls for multi-toxin removal capabilities across two-categories of toxin elimination targets. Can proposers target two chemical sub-types within one category?

Answer:

Proposers may target two toxins within the same category only if the selected toxins are structurally distinct in a way that results in meaningfully different chemical behavior or degradation requirements. Selection of closely related variants that do not sufficiently test the flexibility of the platform will not be considered. The goal is to develop a platform that has breadth for toxin elimination rather than closely related variants of the same molecule.

Proposers are strongly encouraged provide a clear scientific justification with supporting evidence (e.g., prior data or literature) explaining why their chosen toxin pair represents a compelling demonstration of platform breadth. This includes showing that the engineered strain must leverage distinct pathways or mechanisms, rather than minor variants of the same biochemical process. All proposed elimination or degradation pathways must be safe, without generating toxic intermediates or byproducts; potential byproducts should be identified and addressed in the proposal.

Proposers are also allowed to develop technical plans beyond the minimum required for

UNI-PLAT both in the context such as number of targets or advancing the multiplexing capabilities.

Q5. What if there is no FDA action level or clinically defined luminal/gut concentration for my toxin of interest?

Many toxins lack established FDA action levels or have limited human exposure and toxicokinetic data. In these cases, proposers may:

• Identify and justify a scientifically grounded benchmark (e.g., values from toxicology literature, WHO/EFSA guidelines, occupational/environmental exposure limits, or modeled dietary intake).

• Explain how the chosen benchmark relates to relevant human exposure scenarios as they relate to the UNI-PLAT topic outlined in the solicitation.

• Provide a rationale for why reducing the toxin to that level would be protective for human health based on the best available evidence.

Topic 4 (Breaking Ground: The First Curative, Durable, Non-Surgical Therapy for Endometriosis) Questions

Q1. Is use of the NIH All of Us Research Program required for this solicitation?

Use of the NIH All of Us Research Program is entirely optional. It is offered as a potential research resource for proposers but will not affect the evaluation of proposals.

Q2. What constitutes a "non-invasive" approach?

Answer:

The solicitation intentionally allows flexibility in defining non-invasive approaches. At a minimum, the Government does not envision approaches requiring an operating room procedure. Proposers should propose and justify an approach consistent with the objectives of the solicitation.

Q3. If additional technical data are generated after the Solution Summary submission deadline, may applicants update their submission?

Answer:

Solution Summaries cannot be updated after the submission deadline. If an offeror is encouraged to submit a Stage 2 proposal, additional technical data generated prior to the

Stage 2 submission deadline may be incorporated into the full proposal.

Q4. Are biologics and other therapeutic modalities acceptable, or is the topic limited to traditional pharmaceuticals?

Answer:

The Government is technology agnostic. Pharmaceutical drugs, biologics, cell therapies, and other therapeutic modalities are all within scope, provided the proposed approach satisfies the objectives and requirements of the solicitation.

Q5. Is reduction in lesion size the only acceptable efficacy metric?

Answer:

The Government recognizes that lesion size may not always directly correlate with clinical benefit. Proposers may propose alternative efficacy metrics where supported by a compelling scientific rationale and appropriate evidence. However, proposals should clearly explain and justify any departure from the example performance metrics provided in the solicitation.

Q6. If applying only for Phase I, should the Solution Summary address Phase II activities?

Answer:

The Solution Summary should address the phase for which the offeror is applying. Proposers applying only for Phase I should focus on Phase I objectives. Fast Track and Phase II proposals should address the applicable phase requirements described in the solicitation.

Q7. Is prior endometriosis-specific preliminary data required for Topic 4?

Endometriosis-specific preliminary data is not a requirement of Topic 04.Proposals should provide a scientifically sound rationale explaining why the proposed therapeutic approach is expected to be effective for endometriosis. While prior endometriosis-specific data may strengthen a proposal, a well-supported mechanistic rationale may also be appropriate.

Q8. Is expertise specific to women's health or endometriosis expected on the project team?

Answer:

The Government strongly encourages teams to include appropriate expertise in women's health and endometriosis. Although technologies from other disease areas may be applicable, subject matter expertise will strengthen the scientific rationale and increase confidence in the proposed development approach.

Q9. May a proposal include both physician-directed and direct-to-consumer deployment pathways?

Answer:

For purposes of this solicitation, the proposed technology should be developed for integration into the clinical care pathway and regulatory framework described in the solicitation. While proposers may pursue additional commercialization pathways independently, proposals submitted under this solicitation should focus on the intended clinical implementation.

Q10. May existing drugs be repurposed using novel delivery methods?

Answer:

Repurposed drugs with innovative delivery approaches are within scope. However, the

Government anticipates significant competition and will evaluate proposals based on the evaluation criteria in Section 5 of the BAA.

Q11. How strictly will sensitivity and specificity targets be evaluated?

Answer:

The Government recognizes that these are ambitious technical goals and understands the inherent technical risk associated with achieving them. Proposers should propose aggressive but realistic performance objectives. During project execution, performers are expected to communicate technical challenges and work collaboratively with the Government to address them while maintaining progress toward program objectives.

Q12. Does the Target Product Profile describe the desired commercial end product or the expected deliverable at the end of the award?

The Target Product Profile describes the intended commercial end product. The solicitation separately identifies the technical milestones and deliverables expected by the conclusion of each project phase.

Q13. Is Direct-to-Phase II permitted under Topic 04? If so, what level of prior preclinical evidence—such as target validation, mechanism-of-action data, or in vivo efficacy in disease-relevant models—is expected to satisfy the Phase I feasibility threshold?

Answer:

Direct to phase II is allowed and you would just need to show that you have sufficient evidence demonstrating the proof of concept.

Q14. Could ARPA-H clarify the intended scope of “non-invasive” under Topic 04?

Specifically, would a therapeutic delivered via routine parenteral administration, such as subcutaneous or intravenous injection, and not requiring surgical intervention or implantation, be consistent with the topic’s intent? Or is the topic limited to needle-free routes such as oral or transdermal administration?

Answer:

Per the drafted solicitation, "Solutions that are in scope include therapy that does not require surgery and can be administered non-invasively to the body (e.g., oral, topical, intravenous, subcutaneous, etc.).”

Q15. Can you provide details on how to apply and details about ARPA-H 04 objectives and qualifications?

Answer:

Details on how to apply (Section 4 Submissions) for an ARPA-H Small Business award and who can apply (Section 2 Eligibility & Certifications) for them can be found in the solicitation.

Q16. Topic 4 excludes invasive surgical procedures and seeks non-surgical therapies for endometriosis. Would ARPA-H consider a non-surgical, clinician-administered intraperitoneal delivery approach to be in scope if the approach is designed to make intraperitoneal injection feasible for qualified non-surgeon healthcare professionals and does not require laparoscopy, open surgery, operating-room access, general anesthesia, or imaging guidance? Specifically, would an office-based or outpatient intraperitoneal injection route for local delivery of a therapeutic product be considered responsive to Topic 4, or would ARPA-H consider any needle- or catheter-based intraperitoneal access to be an out-of-scope invasive surgical procedure?

Answer:

Local delivery of a therapeutic that could be performed by a general provider may be considered in scope assuming the solution met all requirements outlined in the solicitation.

However such a delivery solution may not be competitive if it requires a trained provider or procedure to place the delivery mechanisms.

Topic 5 (ARPA-H Lineage Topic) Questions

Q1. Who is eligible for an ARPA-H Lineage Topic award?

Answer:

Prior ARPA-H primary awardees, subawardees, entities commercializing Intellectual Property

(IP) developed using ARPA-H funding (e.g. a startup spun-out of an academic lab), ARPA-H challenge finalists and those who have received co-funding from ARPA-H.

Q2. How do we figure out if we can/should apply for Topic 5: ARPA-H Lineage Topic and be in scope. Our team is currently part of a program that is anticipated to be awarded under another ARPA-H program.

Answer:

Lineage Topic is intended for Research & Development (R&D) that enables the commercialization and transition of IP/capabilities that result from ARPA-H funded programs and projects. You are only eligible if you’re commercializing R&D that was developed via

ARPA-H funding.

Q3. Is there a list of lineage topics?

Answer:

There is only one lineage topic, but it applies broadly to technologies resulting from all

ARPA-H funded efforts.

Q4. What type of ARPA-H R&D effort is eligible for SBIR Topic 5: ARPA-H Lineage

Topic? For example, are finalists in AIxCC, which ARPA-H was a partner in, eligible?

Answer:

Prior ARPA-H primary awardees, subawardees, entities commercializing IP developed using

ARPA-H funding (e.g. a startup spun-out of an academic lab), ARPA-H challenge finalists and those who have received co-funding from ARPA-H.

Topic 6 (Rapid Comprehensive Diagnostic Test for Multi-System Autoimmune Disease)

Questions

Q1. Is the intent for the proposed test to function primarily as a screening test or as a diagnostic test? What is the intended clinical workflow following a positive result?

The objective is to develop a diagnostic capability that can be readily ordered in a primary care or other frontline healthcare setting when a patient presents with symptoms suggestive of autoimmune disease. The desired test should be inexpensive, rapidly deployable, and provide actionable information that enables timely referral to the appropriate specialist before significant multi-organ disease progression occurs. The intent is to reduce delays associated with current diagnostic pathways and facilitate earlier intervention.

Q2. What biological sample types, organs, biomarkers, or tissue compartments are required?

Answer:

The Government is intentionally non-prescriptive regarding the biological specimen, biomarkers, or analytical approach. Proposers should propose the sampling strategy and biological compartment that best supports their technical approach and demonstrate why it is appropriate for achieving the program objectives. Proposals should clearly justify how the selected approach supports early identification of multisystem autoimmune disease within the intended healthcare delivery setting.

Q3. What technologies are within scope, and what technology readiness level (TRL) is expected for Phase I and Phase II?

Answer:

The Government does limit specific TRLs for Phase I and Phase II projects. Proposers should propose realistic technical milestones that rapidly mature the technology, demonstrating progression toward a deployable prototype. By the conclusion of Phase II, the expectation is a mature prototype positioned for regulatory advancement and commercialization.

Milestones should be front-loaded and measurable to demonstrate early technical progress.

Q4. Are laboratory-developed tests or CLIA-certified laboratory workflows within scope?

Answer:

Yes, laboratory-developed tests or CLIA-certified laboratory workflows are within scope.

Solutions utilizing centralized laboratory infrastructure may be appropriate provided they can deliver clinically useful turnaround times and support deployment at the intended scale.

Solutions capable of providing same-day or rapid results are preferred. Proposers should clearly describe the operational workflow, including specimen transport, processing, and reporting timelines.

Q5. Is point-of-care testing preferred over centralized laboratory testing?

The Government prefers solutions that minimize burden on patients and healthcare providers. Point-of-care testing performed in a physician's office is desirable; however, centralized laboratory approaches are also acceptable if they provide timely results and fit within an efficient clinical workflow. Proposers should justify the proposed deployment model.

Q6. Are home-based diagnostic tests within scope?

Answer:

Home-based testing is within scope. However, proposers should demonstrate how such an approach would appropriately integrate with physician oversight and clinical decision-making. Because the objective is to facilitate referral and management by qualified healthcare providers, proposals should clearly describe how home testing would support those objectives.

Q7. Does the Government seek detection of specific autoimmune diseases or broader multisystem autoimmune involvement?

Answer:

The primary objective is early identification of multisystem autoimmune disease, particularly in patients whose initial symptoms may not clearly indicate widespread disease involvement.

Proposals focused on improving early detection of patients who would otherwise experience delayed diagnosis are of greatest interest. Solutions addressing diseases that are already readily identified using existing diagnostic pathways remain responsive if they provide meaningful improvements in accessibility, cost, speed, or overall clinical utility.

Q8. Are adaptive immune repertoire technologies (e.g., B-cell receptor, T-cell receptor, or antigen repertoire approaches) within scope?

Answer:

Such technologies may be appropriate if they contribute to identifying multisystem autoimmune disease and support improved clinical management. Technologies focused solely on characterizing immune repertoires without providing information that advances early identification of multisystem disease or informs subsequent clinical management may be less responsive to the objectives of this topic.

Q9. Is the desired diagnostic expected to identify organ-specific manifestations in addition to detecting autoimmune disease?

Answer:

Yes. The Government is interested in diagnostics that provide clinically actionable information regarding potential multisystem involvement and help direct patients toward appropriate specialty care before significant disease progression occurs. The greater the ability to support targeted clinical decision-making, the more responsive the proposed solution is likely to be.

Q10. May proposals utilize a staged diagnostic strategy in which an initial low-cost screening test is followed by a more comprehensive secondary test?

Answer:

Yes. A staged diagnostic workflow may be appropriate if the initial test provides clinically meaningful information that supports referral or further evaluation and the overall approach demonstrates improved patient outcomes, cost-effectiveness, and earlier diagnosis compared to current practice. Proposers should clearly justify the proposed workflow.

Q11. Are AI and machine learning approaches within scope?

Answer:

Yes, AI and machine learning approaches are within scope. Artificial intelligence and machine learning approaches are encouraged where they improve diagnostic accuracy, reduce cost, shorten turnaround time, reduce uncertainty, or otherwise improve clinical utility. AI may be integrated with biomarker measurements or other diagnostic modalities as appropriate.

Q12. Are AI-based approaches that do not rely on biospecimens responsive to this topic?

Answer:

The Government is open to non-traditional diagnostic approaches provided they address the objectives of early identification of clinically relevant multisystem autoimmune disease and clearly demonstrate how they achieve those objectives within the intended healthcare setting.

Q13. Does the Government require a specific analytical modality or biomarker technology?

Answer:

The Government is technology agnostic. Proposers should propose the analytical approach best suited to meeting the program objectives and clearly justify its scientific basis, technical feasibility, and clinical utility.

Q14. Are platform devices that utilize disposable consumable tests within scope? Does the $1,500 cost target include the capital equipment?

Platform-based approaches are within scope. The approximate $1,500 target applies to the consumable test. Capital equipment that is reusable may be considered separately. However, proposals requiring expensive new instrumentation that is not commonly available within existing clinical workflows may be less responsive than approaches that leverage existing diagnostic infrastructure or minimize additional capital investment.

Q15. What patient population is the Government primarily interested in?

Answer:

The focus is on patients presenting in frontline healthcare settings with early or seemingly nonspecific symptoms that may represent multisystem autoimmune disease. The objective is to identify patients who would otherwise experience delayed diagnosis and referral through current clinical practice.

Q16. Is a diagnostic capable of rapidly ruling out autoimmune disease also responsive?

Answer:

Proposals should demonstrate meaningful clinical value, such as improving speed, accessibility, cost, or diagnostic decision-making compared with current practice. Proposers should clearly explain how the proposed approach advances the state of the art and supports improved patient management.

Q17. Would technologies developed primarily for Alzheimer's disease, oncology, or other non-autoimmune indications be responsive if they could be adapted for autoimmune disease?

Answer:

This topic is focused specifically on autoimmune disease. Technologies developed primarily for other disease areas generally would not be responsive unless the proposed effort directly addresses the objectives of this topic. Proposers

Q18. Should proposers apply through this solicitation or through the ARPA-H Open

BAA/ISO if their development timeline exceeds the Phase II schedule?

Answer:

Proposers should propose only work that can realistically be accomplished within the applicable phase of this solicitation.

Q19. What level of maturity is expected for Direct to Phase II proposals?

Answer:

Direct to Phase II proposals should already possess sufficient technical maturity such that the

Phase I feasibility objectives have effectively been demonstrated. Proposers should provide evidence supporting readiness to proceed directly into Phase II development.

Q20. May nonprofit research organizations participate?

Nonprofits may not propose as a prime proposer. However, nonprofit organizations may participate as members of a teaming arrangement, provided the overall proposal satisfies the eligibility requirements of the SBIR…