75N99223R0003 NITRO Q_A 29 June.pdf

75N99223R0003 NITRO BAA Questions and Answers

Questions and Answers 29 June:

The revisions to the BAA on 6/22/2023 include an upload of “the cost proposal spreadsheet (which serves the purpose of the SF-424A Budget Information form)”, we would like to confirm that this cost proposal spreadsheet is to be used for a Cooperative Agreement?

Please see Amendment 3, which provides for both the OT Cost Proposal Spreadsheet and the modified SF-424A Spreadsheet for Cooperative Agreements. Proposers requesting an OT should note the revised OT Spreadsheet provides for a higher threshold for providing supporting documentation for Other Direct Costs (as described in the amended BAA).

Cost proposal instructions in the BAA vs. cost proposal instructions on Materials-Supplies tab in the NITRO cost proposal spreadsheet. We would like confirmation that backup is only required on an entry with a unit cost over $5,000, but not required for an every entry as inferred in the BAA.

Please see Amendment 3 and also note both spreadsheets provide cells to address a justification and/or basis of estimate for all costs, not just ODCs. The requirement related to support for ODCs with an aggregate value of more than $10,000 is in addition to the basic requirement to provide a basis for the price/cost. While ARPA-H may request additional information/documentation to substantiate a proposed cost/price, the burden falls on the proposer to sufficiently support its proposed cost/price.

Proposers’ Day Frequently Asked Questions (FAQs) 15 June

NITRO SCIENCE QUESTIONS

Is systemic treatment for cartilage regeneration required or optional?

A systemic therapeutic for cartilage regeneration is required.

Can blood be collected from patients to for TA1 or TA2?

Please read BAA pages 7, 9, 15, 20-22. If the procurement of autologous sources is considered surgical, these approaches are not allowed for TA1 or TA2 therapeutics.

Does TA2 require development of both an intra-articular (IA) and a systemic (e.g., IV) therapeutic? Yes.

However, the two (2) therapeutics may be different; therapeutic(s) for IA and systemic delivery may be different.

a) What does systemic delivery in the context of TA2 mean? Therapeutic(s) are delivered to the whole body via oral, intravenous, or another systemic route of administration.

b) Can systemic mean simultaneous delivery into multiple joints? For TA2, multi-joint delivery must be via systemic administration. This does not mean repeated intra-articular injections.

c) Does the IV therapy need to be the same as the IA delivered therapy? No.

d) Following IA delivery of a bone therapeutic (TA1) and IA delivery of a cartilage therapeutic (TA2), can that be followed with something delivered systemically for cartilage? Yes. Proposers can use any combination of the IA bone therapeutic (TA1) with both developed IA and systemic cartilage therapeutics (TA2).

e) Can a bone therapeutic for TA1 be delivered systemically? No, as NITRO seeks targeted, subchondral bone therapeutics. The off-target effects of systemic bone formation, such as heterotopic ossification, are not solicited in this BAA.

Can a product for TA3 be both allogeneic and autogenous? Can a synthetic product be utilized?

Proposals for TA3 should develop both an allogeneic and autogenous implant. The allogeneic and autogenous implants must meet the specifications in the BAA (Page 23). If the product has any allogeneic components, it will need to accomplish the allogeneic specifications in the BAA. Synthetic products may be utilized in the development of the complete constructs for implantation, noting that no permanent fixation is listed as a metric in the BAA for TA3 proposals.

Do therapeutics need to be FDA approved before the end of the project?

No. Phase I clinical trials will be completed, however.

For large animal model can a focal (> critical size defect) be used or must OA be induced and treated?

The defect must be beyond a critical size defect and regenerate all stages of OA back to Grade 0. Please refer to the BAA for the specific language. Notably, the NITRO team will host the NITRO OA Model Symposium to help performers establish the ideal OA model to use in the Preclinical Phase.

Given the therapeutic is to be defined in NITRO Phase 1, what level of detail is needed to describe the large animal model work and the FDA Phase I Clinical Trial in NITRO Phase 2? Proposals should lay out a comprehensive response to the entirety of the program outlined in the BAA.

Does an arthroscope delivery satisfy TA3 requirements?

No, unless you can perform an allogeneic and autogenous joint replacement that meets all the metrics in the BAA for TA3 using the arthroscopic approach. An arthroscopic approach alone is not sufficient to meet all these requirements. An arthroscopic approach is, however, a valid approach for TA1 and TA2. Please reference the metrics for the program in the BAA for further information on potential approaches.

For TA3 for the patient-specific implant, would NITRO be open to a semi-custom system in which a catalog of multiple shapes and sizes are readily available for use; or must it be fully designed for each patient?

Yes, if it meets 100% of the metrics in the BAA. In general, the NITRO team does not have a preference related to specific technologies under development. If the product fits the metrics of the BAA, it will be considered.

a) For the Total Knee Arthroplasty (TKA) allograft with the technical requirements still be met if the product is off the shelf available within 24 hours? The custom TKA allograft must be manufactured in less than 24 hours, this includes any planning to get the allograft fully manufactured and ready for implantation. Please refer to the BAA for each of the specific metrics related to TA3.

b) For TKA autograft with the program allow the graft to be designed before the 30-day manufacturing timeline? The custom TKA autograft must be manufactured in less than 30 days, this includes any planning to get the autograft fully manufactured and ready for implantation. Please refer to the BAA for each of the specific metrics related to TA3.

c) I can make a strong scientific argument that an allogeneic cell source taking >24 hours < 30 days could provide a more robust osteochondral construct for the patient. For example, custom implant manufacturer and allogenic cell culture- is this allowed for TA3? The allograft must be manufactured within less than 24 hours for TA3.

Can an off-the-shelf cell product be used for TA1 and or TA2?

Yes, if it meets 100% of the metrics in the BAA.

Single vs. multi-joint approach; what happens if one therapeutic does better than the others during the program?

At this stage, the performer team will have conversations with the NITRO team about the best path forward.

Can you repurpose an FDA-approved drug?

Yes, if it meets 100% of the metrics in the BAA.

If a therapeutic has hit clinical stage, do we still need to start at the beginning of Phase 1 of the NITRO program?

Yes. To the best of our knowledge, we are not aware of a current potential therapeutic that meets the metrics of the Phase I clinical testing that are required by the BAA. Unless the proposed therapeutic meets these metrics, performers must begin the program at the appropriate stage in which all metrics are to be met.

Phase 1 Clinical Trial- does a sport injury patient make the cut?

Phase 1 Clinical Trials will follow FDA rules and regulations. The patient population will be a diverse cohort described in the BAA metrics. The BAA does not exclude patients with different pathologies of OA.

NITRO STRUCTURE QUESTIONS

Is ARPA-H looking for proposals with technical solutions that are well-developed, likely already in NITRO Phase 2?

ARPA-H cautions proposers from making assumptions outside of the information provided in the BAA. For instance, while the program timeline indicates a 24-month discovery phase, aggressive timelines like this are standard for ARPA-H. ARPA-H is not looking for any specific technology or proposals and encourages performers to feel free to submit all technical solutions they believe can accomplish the program metrics even if they aren’t “well-developed” at this time. ARPA-H welcomes compliant abstracts/proposals with technical solutions that meet the metrics outlined in the BAA. Proposals will be evaluated against the evaluation criteria provided in the BAA and will not be evaluated against each other. All potential performers will start the program at NITRO Phase 1 regardless of current technical progress in clinical trials; all performers must meet all metrics in the BAA.

Will abstracts receive feedback in addition to or beyond “encourage” or “discourage” submission?

No. Please see the BAA for further details on abstract review criteria.

The BAA and on the Proposers’ Day deck states that 20% of participants in clinical trials should be Native American / Alaskan Native however I believe only about 1% of the US population is NA/AN. Given that, are these numbers for Clinical Trial Equity going to be followed and enforced?

Yes. The ARPA-H NITRO team is in consultation with experts and a revision may occur in the future, however, we are committed to equity and believe the NITRO Clinical Trials should be no exception.

Must the Equity Officer be part of the proposer’s institution?

No, a subcontractor billed to the award is acceptable.

Will the program staff be suggesting groups team up based on the abstracts?

No. Teaming is at the discretion of proposers.

Will PATIO or the XIR resources be available to help match proposers to potential EOs?

While the PATIO resources – which includes the XIR resources – will be available to performers in the program at the discretion of the NITRO team, proposers must find and provide their own EO(s) for their performer teams.

These EOs need to be indicated in the proposals for ARPA-H review and approval.

Timelines for clinical trials are aggressive- Will ARPA-H collaborate with clinical sites to facilitate and accelerate trials?

The ARPA-H model is inherently fast-paced and fuels innovation at an accelerated rate. While ARPA-H may collaborate with clinical sites, we expect performers to move at the pace of the program in order to succeed.

More information will be provided to performers once the program begins.

Can a team change after phase 1 based on results? What would the process be?

Teaming changes may be allowed at ARPA-H’s discretion and in response to new or different needs arising from the program’s progress. However, requests would be dealt with on a case-by-case basis.

Will we be penalized for not partnering if we believe our group can do it all?

No. If you believe you and/or your team can accomplish all program metrics, there is no requirement to team with other entities. While we believe teaming will be important to succeed, teaming is at your discretion.

Clinical follow-up period: FDA generally mandates 2-year follow up; 5-year data for CMS; we're looking at 12-month reliability which is longer than most 5-year data requirement for CMS any chance to relax it/encourage acceptance prior to that to encourage funding?

The NITRO timelines will remain as written in the BAA to revolutionize the field.

Regulatory involvement/guidance: the type of therapeutic/species of therapeutic can determine what's 'regulatory possible'- will ARPA-H help brainstorm finding the right FDA venue?

Yes. At the discretion of the NITRO team, ARPA-H and PATIO will help performer teams find the appropriate regulatory routes with the FDA or EMA.

With an aggressive timeline, are you evaluating the feasibility and timeline?

No. The timeline is aggressive and set at the same benchmark for all proposers. The full proposals will be evaluated based on the criteria stated in the BAA.

Does my research apply broadly to and fit within the scope of the NITRO Technical Areas 1, 2, and/or 3?

The NITRO project team is unable to discuss concepts that a potential applicant is considering submitting to the BAA. We will evaluate and provide feedback on technical concepts once they have been officially submitted. The NITRO program anticipates that teaming will be necessary to accomplish our program goals and metrics. You can find more information about teaming on the NITRO teaming page, here: https://arpa-h.gov/engage/programs/nitro/teaming/. Additionally, the NITRO program anticipates considering a broad spectrum of applications across a range of development phases. The specifics about the NITRO program can be found in the BAA.

The NITRO BAA can be found here https://sam.gov/opp/0d6d0844c8c949f39819badf44197a98/view. Please be sure to review the posting in it its entirety, including all the attachments at the bottom of the page. The submission process and other questions should all be answered by reviewing these materials.

Is attendance at Proposers’ Day required for submission of an Abstract or Full Proposal?

https://sam.gov/opp/0d6d0844c8c949f39819badf44197a98/view

Participation in the NITRO Proposers’ Day is not a requirement for submission of an abstract, full proposal, or selection for funding.

Are Lightning Talks and Sidebars limited to in-person participants for Proposers’ Day?

Lightning Talks and Sidebar conversations are not limited to in-person participants; virtual participants were also selected.

Is there a limit for in-person registrants and virtual registrants for Proposers’ Day?

The in-person registration is limited to 2 individuals per institutional department, and 130 maximum in-person attendees. The virtual registration is not limited based on institutional department, and the maximum number of attendees is 3000.

I am confirmed for the in-person and virtual Proposers’ Day, what should I expect throughout the day regarding travel plans and watching the event virtually?

Proposers’ Day will be a full day of events with opening presentations from ARPA-H Directors to presentations on the specifics about the NITRO BAA from the Program Manager and Acquisitions.

The Proposers’ Day complete Schedule will be released no later than 6/14/23 to all confirmed registrants. At this time, please note the event will take place on Thursday, June 15, 2023, from 8:30AM to 6:00PM CDT.

If selected for a timeslot to present at Proposers’ Day, registrants will be notified no later than 6/14/23.

Registrants notified with selected timeslots will not need to upload slides at the time of Proposers’ Day (the ARPA-H team will handle all slides during the event to maintain schedule given time constraints). Registrants selected for a timeslot for a Sidebar conversation on Proposers’ Day were notified on 6/9/23.

Due to the enormous interest in sidebars, ARPA-H will be scheduling additional sidebars on 6/20/23. ARPA-H will provide additional scheduling information to those who previously requested the sidebars in their registration for Proposers’ Day; information will be sent no later than 6/19/20. No additional requests for sidebars will be accepted.

Can you meet with me to discuss the NITRO program?

The NITRO project team is unable to accommodate individual requests for calls or meetings to discuss concepts that a potential applicant is considering submitting to the BAA. We will evaluate and provide feedback on technical concepts once they have been officially submitted. Sidebar conversations serve as the opportunity to meet with the NITRO team to discuss your concepts and to answer any BAA specific questions.

Is there a limit on the level of funding and are there mandatory requirements for the cost proposal?

The BAA does not include a funding limit for individual awards. Abstracts will be evaluated based on the criteria laid out in the solicitation, to develop novel techniques for the regeneration and reconstruction of intra-articular (IA) cartilage and subchondral (SC) bone, the two key tissue types in a joint, in osteoarthritis (OA) patients, and the cost realism of such development.

There is no statutory requirement for cost sharing under any OTs negotiated by ARPA-H. ARPA-H will consider proposals for cost sharing from Proposers. Ultimately award terms and conditions will be determined for each project considering all elements of the projects (e.g., Fixed support, Expenditure with cost share or Expenditure based with no cost share). Please refer to the solicitation for all the details:

ELIGIBILITY QUESTIONS

Are there any limitations on collaborating with international entities?

Please see paragraph 3.1.2. Other Applicants of the BAA regarding international entities.

Will you fund or allow work outside the US such as clinical trials?

NITRO strongly prefers that clinical trials be performed in the US, however, trials in other countries will be considered on a case-by-case basis at ARPA-H's discretion. Additionally, foreign sub-awardees will be considered on a case-by-case basis at ARPA-H's discretion. Please see Section 3.1.2. “Other Applicants” of the BAA for requirements for foreign entity participation on ARPA-H awards.

How do we collaborate without NDAs?

NDAs may be used at the proposer’s/performer's discretion.

Regarding qualifying for NITRO- are there restrictions to the funding we receive, who owns the company?

Receiving funding from someone else does not necessarily disqualify you. Majority ownership through a private enterprise is acceptable, but all situations will be assessed by ARPA-H at the proposal review stage with a determination made on a case-by-case basis.

I’m an OA patient, how can I get involved with the NITRO program?

ARPA-H does not conduct its own research. Instead, the agency funds research organizations such as universities and medical centers to conduct such work. If you have an interest in volunteering for studies, you could look for volunteer opportunities at hospitals, universities, or research institutions near you. For example, the National Institutes of Health maintains a webpage with information on volunteering: https://clinicaltrials.gov/. Thank you again for your interest, and we encourage you to stay up to date on the current state of the program at https://arpa-h.gov/engage/programs/nitro/.

Who is allowed to submit for Abstracts and Full proposals? Young Investigators? Industry? Academia?

We welcome investigators at all stages in both academia and industry. The NITRO program anticipates teaming will be necessary to accomplish our program goals and metrics. You can find more information about teaming on the NITRO teaming page, here: https://arpa-h.gov/engage/programs/nitro/teaming/.

APPLICATION AND SUBMISSION QUESTIONS

When will abstract feedback be provided to proposers?

ARPA-H estimates abstract feedback, limited to encouraging or discouraging submission of a full proposal, will be provided by 6 July.

Can an entity propose through multiple proposals?

An entity may only submit a single proposal as the prime awardee. An entity may propose in multiple proposers’ teams as a sub-awardee/subcontractor. If an entity, proposed as a sub-awardee, is part of multiple successful teams (i.e., award recipients), the Government may establish Associate Contractor Agreements (ACAs) with the applicable prime awardees. The requirement for an ACA will be dependent on the types of services/supplies provided by the sub-awardee; and the specific terms and conditions will be negotiated for each award.

Can a Principal Investigator (PIs) propose under multiple abstracts/proposals?

https://clinicaltrials.gov/ https://arpa-h.gov/engage/programs/nitro/ https://arpa-h.gov/engage/programs/nitro/teaming/

While PIs can only be on one prime award, PIs are not limited to the number of subawards given that the level of effort meets the needs of each subaward. PIs should consider their level of effort across numerous assets and expect the NITRO program to take a significant level of effort.

Can we submit with a couple of different teams using our platform technology?

You may be the Sub-Awardee on multiple proposals. You may only be the Prime Awardee on one proposal.

What’s the budget range?

Please provide realistic, justifiable, comprehensive and reasonable budgets that demonstrate how you will accomplish the metrics of your selected program structure (e.g., Option A, Option B, Option C).

I’ve run into an issue with Abstract or Proposal submission. Can the NITRO team help?

Please email NITRO@arpa-h.gov with more specific information about the issue and a team member will get back to you to resolve the issue.

What is the difference between an Abstract and a Full Proposal?

Please refer to the information on the solicitation for the NITRO BAA here:

https://sam.gov/opp/0d6d0844c8c949f39819badf44197a98/view. Abstracts are limited to 6-pages to pitch the idea to the NITRO team. While not required, abstracts are intended to be an option for potential performers to receive a recommendation from ARPA-H (i.e., recommendation to submit or not submit a full proposal) prior to investing the effort required to submit a full proposal. Full Proposals are limited to 40-pages.

How do we choose which funding pathway to request? What is the reason that a proposer should select co-op agreement versus OTA?

We recommend you work within your institution/entity to establish the best funding pathway for proposer-agnostic necessities. ARPA-H will not provide guidance on which funding pathway to select; it is up to the proposer to select and make that decision. However, award type will be negotiable and will ultimately be at ARPA-H's decision.

Who owns the IP?

IP rights will be part of award negotiations between the proposer and ARPA-H. Note, there are more flexibilities regarding IP under other transactions than under financial assistance regulations.

Are multiple PIs allowed?

Yes, but only one PI may be the Prime Awardee. Similarly, an individual can only be a Prime Awardee once but can be Sub-awardee on multiple proposals.

When will my teaming information be posted on the teaming page, and can I change the teaming information after the initial submission?

The teaming information is reviewed and posted on a rolling basis. Submission of teaming information does not guarantee that the information will be posted on the NITRO Teaming Page. The NITRO team reviews the team profiles based on the completeness, relevance, and acceptability of the submitted information. Incomplete, non-relevant, and non-acceptable submissions will not be posted on the teaming page. If you wish to change your teaming information, please email NITRO@arpa-h.gov with the requested changes.

What is the timeline from abstract submission to invitation for full proposal?

mailto:NITRO@arpa-h.gov mailto:NITRO@arpa-h.gov

There will be no invitation for full proposal. Abstracts are welcomed but not required. Regardless of abstract feedback, any potential proposer who believes he/she/they are able to accomplish the program metrics may submit a full proposal by July 28th at 5:00pm ET. Please refer to the information on the solicitation for the NITRO BAA here: https://sam.gov/opp/0d6d0844c8c949f39819badf44197a98/view.

Is a university, as an institution, limited to submitting one (1) proposal as a prime awardee?

A university, as an institution, is not limited to submitting one (1) proposal as a prime awardee. A department within an institution (e.g., a university) is limited to submitting one (1) proposal as a prime awardee.

a) If so, would the limitation apply to submission of abstracts or invited full proposals? The limitation will only apply to full proposals, not abstracts.

b) Or for universities, should the term proposer be understood in reference to individual PIs, and thus multiple PIs at the same university could submit in parallel on behalf of independent teams? Multiple PIs from different departments at the same institution may submit separate Abstracts or Full Proposals given that there is no overlap between the applications. Multiple PIs from the same department can submit an Abstract to the NITRO BAA; however, only one (1) Full Proposal will be considered from each department. It is possible that multiple Full Proposals could be accepted from different departments in the same institution, yet the teams must not overlap.

Are cover letters limited to one page? Are there margin formatting restrictions?

Please see the BAA for specific guidance related to these and other formatting questions.