B-SAFE_QA_v2.docx

HR001124S0032

Questions and Answers

B-SAFE

Updated 7/26/2024 General Questions

1. Is a DARPA representative available for a call to discuss our proposed approach?

The best way to receive feedback on an approach is through the submission of a proposal abstract by July 15, 2024, 4:00 PM EST. Most answers to questions can be found in the BAA, which describes the program and program requirements in detail. If you cannot find the answer to your question in the BAA, please e-mail your question to B-SAFE@darpa.mil. Please be aware that your question and its answer may be published on this FAQ, after the question has been revised (if necessary) to remove any proprietary details. If needed, please mark any portion of your question as proprietary to avoid unintentional publication.

2. Will the Industry Day slides be posted online?

Briefing materials that were presented by DARPA at the B-SAFE Industry Day will be made available on the DARPA Opportunities webpage: http://www.darpa.mil/work-with-us/opportunities

3. Are International Universities eligible to participate as collaborators in response to the BAA? What about non-US organizations?

Yes. Per the BAA, all responsible sources capable of satisfying the Government’s needs may submit a proposal that shall be considered by DARPA. Non-U.S. organizations and/or individuals 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.

4. Are Government entities or Federally Funded Research and Development Centers (FFRDCs) eligible to participate as collaborators in response to the BAA?

Federally Funded Research and Development Corporations (FFRDCs) and Government entities interested in participating in the B-SAFE program or proposing to this BAA should first contact the Agency Point of Contact (POC) at B-SAFE@darpa.mil prior to the Abstract due date to discuss eligibility. Complete information regarding eligibility can be found at Proposer Instructions and General Terms and Conditions.

5. Do I need to submit an abstract? What is the advantage of submitting an abstract?

Yes, abstracts are required to submit a full proposal. DARPA will provide written and/or verbal feedback for each abstract submitted. DARPA will provide feedback regarding technical approach and will highlight components for proposers where additional information or clarification should be provided in the full proposal to meet the requirements of the BAA and vision of the program. Feedback will also be provided to encourage or discourage submission of a full proposal to the B-SAFE solicitation based on the proposal’s alignment with the program vision and technical innovation.

6. When is the expected award date?

Winter 2024.

7. How many awards are expected under B-SAFE, and what is the total budget available for the B-SAFE program?

While there are no predetermined or expected number of awards under B-SAFE, at this time, multiple awards are expected. Proposers should propose ambitious, yet achievable projects, and outline costs that are commensurate with what is required to achieve project goals and meet the program requirements. DARPA has not predetermined award amounts. Typically, BTO programs of this size and scope have budgets that range from $5-10M over 2-3 years. Proposers are required to provide a well‐justified budget that covers the scope of the proposed work with tasks described and budgets requested necessary to meet the B-SAFE program objectives. Budgets will be examined in detail for appropriateness. If the proposal is selected for award, a government contract officer will negotiate the terms of the contract. During this negotiation, every aspect of the statement of work and cost proposal will be reviewed. Please ensure that all of the instructions in HR001124S0032 are followed. This will enable the government contract office to expedite negotiations.

8. To allow enough time to make proposal revisions once questions have been fully answered (such as Universities that will need additional time for administrative approval processes), would DARPA be willing to extend the proposal due date by one week?

While DARPA appreciates the technical and administrative burden of proposal submission, there is no extension of the proposal due date anticipated at this time. Please check sam.gov for any updates.

Teaming Questions

9. Is there a limit on team size? Is there a recommended team size? Can DARPA assist with team formation?

No. It is the responsibility of proposers to assemble a team that can effectively address all technical and programmatic requirements of the program. DARPA will not provide any recommendations on team size, makeup, etc.

10. Does DARPA expect us to have a project coordinator or manager?

Yes. Each team is expected to include one project coordinator or manager to ensure effective communication and task management amongst team members and with DARPA.

11. Is it preferable if teams are co-located?

There is no preference for co-located teams, however, multi-PI and multi-institute teams should indicate how they plan to manage efforts that are distributed.

12. Do teams need to be finalized prior to submitting an abstract?

No. However, proposers must finalize teams prior to submitting the full proposal.

13. Can a team member be an employee at a government organization (CDC, NIH, etc)?

Yes. There is no restriction on including team members from government agencies as subcontractors. However, if a proposal includes a government agency as the prime contractor, the agency must provide authority to compete with industry in its BAA proposal submission or must submit its proposal directly to the DARPA Program Manager in lieu of submitting the proposal directly to the BAA.

14. Can a performer team be on multiple proposals/awards?

Yes. Teams can be subcontractors on multiple proposals. If chosen for multiple awards, a clear path will be established for ensuring no conflicts are present between the efforts. Proposers who are subcontractors on multiple teams should be cognizant of the distribution of the level of effort across multiple awards and will be required to ensure that DARPA is only charged once for any potential duplicate efforts.

15. Does DARPA do active “matchmaking” between synergistic entities?

DARPA does not provide any teaming services. Proposers are responsible for building appropriate teams.

Programmatic Questions

16. How should a proposer determine an appropriate budget?

Cost realism is an important evaluation criterion for proposers to address. Proposers must provide a realistic estimate of the costs (e.g. staff, resources, equipment) necessary to successfully complete milestones and deliverables.

17. Is in-kind support from PI teams acceptable?

Yes. This type of support (e.g., HHMI PI salary) is acceptable, but must be defined and justified in the proposal.

18. Is there a limit to how much a subcontractor can receive in funds?

No. All budgets should be realistic and represent costs associated with the tasks assigned to each subcontractor. Depending on the award vehicle, limitations on pass-through charges may apply (e.g., FAR 52.215-23).

19. Will the program accept grant proposals?

No. DARPA does not intend to award grants under the B-SAFE program. B-SAFE awards may include cooperative agreements, procurement contracts, or other transactions.

20. Is cost sharing specific to the funding directly applicable to proposed work? Or can previous and continued internal investments into the technology maturation be considered as cost sharing?

Previous investments are not considered appropriate cost sharing. Continued internal investment by the performer team that is directly applicable to the proposed work may be applicable, however, that continued investment must be concurrent with the period of performance of a potential award. Cost sharing by the performer team should be explicitly defined/specified within the cost proposal and the source of the cost share (e.g., internal R&D funding, venture capital, etc.) should be clearly identified.

21. Can we include in our budget funds to support the preparation of publications?

Yes, funds can be included in the proposed budget to support the preparation of publications. Like any Other Direct Cost, these costs need to be fully justified and supported, and will be a part of the evaluation of the cost proposal.

Program Schedule and Timeline Questions

22. Do I have to stick to the program structure/timeline outlined in the BAA? How rigid is the schedule?

Yes, key technical areas, milestones and timelines as outlined in the BAA should be maintained in the proposed efforts.

23. Is progression from Phase I to Phase II to Phase III purely milestone based? Or is it also constrained by budget?

Progression from Phase I to Phase II to Phase III is dependent on multiple factors, including technical progress demonstrated by teams and the available budget for the program.

24. Since this is a multi-year program, will there be more opportunities to apply for funding throughout the program’s lifecycle?

No, this will be the only open call for proposals for the B-SAFE program.

25. How does DARPA adjust contracting “on the fly” within a very restrictive SOW? What happens when a new discovery or insight suggests a direction that deviates from the SOW?

Contracting modifications can be made by the Contracting Officer if there is a significant change in scope or schedule based on the technical progress.

26. Does the timing of the capability demonstrations (especially in TA2) exclude any time needed for DNA synthesis?

The capability demonstrations at Months 10, 20, and 30 are intended to be performed in those months and are inclusive of all steps needed to demonstrate the proposed capability. The notional metrics in the BAA are intended to guide proposers and are not prescriptive. Proposers should fully describe their proposed metrics, including time to result, and what components are required for the capability demonstration.

Technical Area Questions

27. Technical Area 1: Is the goal to inhibit the full range of Cas9 and Cas12 or ALL DNA editors of ANY kind?

Inhibition of Cas9 and Cas12 molecules is a requirement of the B-SAFE program. Additional DNA editors are encouraged but not required.

28. Is inhibition of both Cas9 and Cas12 required?

Inhibition of both Cas9 and Cas12 is required, however, it is not a requirement that the same molecule inhibit both.

29. What does “potency” (% inhibition) mean relative to the dose of the inhibitor?

The lower the dose of inhibitor required, the more preferred that solution would be.

30. What would be some example CONOPS for the gene editor inhibitors and how might those CONOPS impact choice of inhibition approach?

The B-SAFE program is a fundamental tool building program which seeks the most broadly applicable approaches.

31. Are the performance metrics (e.g., potency, broad-spectrum) per each Cas or in combination of Cas9 and Cas 12?

The performance metrics are both per each Cas and in combination. The metrics for 99% inhibition of Cas9 and 99% inhibition of Cas12 combine for the total number of inhibitors to achieve this level of inhibition.

32. Do you have to achieve the metrics with a single inhibitor? Or is a cocktail of inhibitors within scope as long as it meets the metrics?

A cocktail approach of inhibitors is within scope as long as the total number of inhibitors meets the metrics.

33. Are the metrics for the total number of inhibitors or candidate inhibitors per Cas or total? For example, TA1 <6 inhibitors for Cas9 and a separate <6 inhibitors for Cas12 (<12 total) or is it <6 inhibitors total?

The B-SAFE program aims to find the fewest number of inhibitors to inhibit the broadest spectrum of editors. In the example above, the preferred solution would be <6 inhibitors total.

34. Is a combination of mechanisms within scope? Or do we need to commit to a single mechanism for all inhibitors?

A combination of mechanisms is within scope.

35. Should demonstrations of inhibition be in vitro or in vivo? If in vivo, is there interest in prokaryotic, eukaryotic, vertebrate, or other contexts?

Approaches that include animal subjects or human subjects research are not in scope. Cell-based demonstrations of prokaryotic, eukaryotic, vertebrate, and others are encouraged as long as the work is not in animal or human subjects.

36. Is delivery a concern? For example, should we scope out inhibitor delivery to prokaryotic vs mammalian vs other cells? What about organisms?

Delivery in cellular contexts is within scope of the B-SAFE program. The types of cells and breadth of cellular contexts will be determined by the capabilities of the proposer. Animal or human subjects research is not in scope of the B-SAFE program.

37. To what extent do we need to demonstrate scalability vs a plan to scale?

Demonstration of scalability is not a primary focus of the B-SAFE program. These considerations should be articulated in relation to the small scale-up exercise at the end of Phase III and the technology transfer package.

38. To what extent do we need to have plans for or demonstrate manufacturability or fieldability?

These are not required elements of the B-SAFE program, however, the simpler the process of manufacturing the better.

39. Will the novel GE target in CD3 be restricted to any particular class, e.g., a Cas, or more broadly, an RNA-guided GE?

The novel GE target in CD3 will be determined by the Government team based on the progress made by the selected proposer over the period of performance. As each team may have a unique approach, the pressure test in CD3 may be unique for each selected performing team.

40. How much information will we get about the novel GE target in CD3, beyond its sequence? If it is an RNA-guided GE, will the PAM and gRNA, or the target, sequences be shared?

Minimal information will be provided in CD3 to simulate inhibition of a novel GE.

Technology Transition

41. For technology transition at the end of the program, to whom would B-SAFE technology transition?

Technology transition will be to US Government stakeholders (e.g., DoD) for further test and evaluation purposes.