AOI 15 QA.pdf

Area of Interest #15

Questions and Answers

Proposal Logistics - Deadline

Question Answer

1 You note that applications will be reviewed as they are received. Will awards be made on a rolling basis?

Yes. Proposals will be reviewed on a rolling basis as soon as they are received. Awards would be made upon successful negotiations which will also proceed on a rolling basis.

2 Will TechWatch meetings be prioritized for this AOI?

Yes. Tech Watch meetings will be prioritized and can begin the week of May 22.

3 Are there proposed dates for when additional information and/or awards to which companies will be made?

The BAA is open for submissions and proposals will be reviewed on a rolling basis. Timing will depend on reviews and negotiations.

4 About deadlines do we need white paper? when is the deadline for a white paper and for full proposal? September 25?

Please read the BAA language carefully. This area of interest is asking for full proposals and the deadline is September 25. However, proposals will be reviewed on a rolling basis.

5 In light of the limited availability of funds, is it advisable to submit proposals earlier than later?

If a company has a proposed approach that is responsive now, the BAA is open and we will review on a rolling basis. To the point of limited funding, it may be best to submit when ready and not wait until the deadline.

6 Are the go/no criteria to move from Base Period (Clinical Trial Planning) to Option 1 (Clinical Trial Execution)/Option 2 (Exploratory Endpoint Analyses) determined by BARDA or should it be proposed by offeror?

These should be proposed by the offeror.

7 Should potential offerors request Tech Watch meetings before submitting proposals?

Yes. It would be advisable to request a Tech Watch meeting and we will try to complete as many as possible during the week of May 22. Please note however, that potential offerors must have submitted a response to the recent RFI for next-generation COVID vaccines, which remains open until May 26, to be eligible for a Tech Watch.

Potential Funding Timelines

8 When will monies be distributed? Any funding is dependent on proposal submission and reviews.

9 Timing for BARDA to make contract decisions, and expected timing to initiate the first Phase 2b trial

This is dependent on proposal receipt, reviews, and potential negotiations on the pre-award side and then technical readiness post-award. But on the pre-award side, we intend to move as quickly as possible.

10 For AOI#15, will there be a future opportunity for companies in late pre-clinical stage (i.e., based on RFI scope)?

We cannot guarantee that future opportunities will be available for candidates that are currently in preclinical development. That would be subject to any future funding.

11 Will NextGen be given the same priority and urgency as Operation Warp Speed.

This Area of Interest is a high priority for BARDA, but unlike Operation Warp Speed, does not include other investments at risk such as manufacturing activities.

12 What is the expected turnaround time for proposal review

We will review as quickly as possible upon receipt but do not have specific turnaround times.

13 What is the timing to start clinical trials in relationship to funding? Is there adequate funding in advance of study start?

As noted in the BAA language, the base period will cover trial planning activities and option 1 would support trial execution.

14 The Biden administration has set-aside $5B for Next Gen Covid19, will these be the only funds allotted for this topic of interest in the BAA?

It should be noted that Project Next Gen is more than just this BAA AOI. We cannot assume any follow-on funding at this time.

Potential Contractual Mechanisms

15 Has it been determined which type of contract vehicle will be used and whenever an OTA will be considered?

The type of contract would be discussed during any negotiations with potential offerors.

16 Are contractors who worked under the ATI/MCDC program eligible?

Yes. There are no restrictions on eligibility from that perspective.

17 How many awards are intended? The number of awards will depend on timing of proposal receipt and costs/potential award. But we do expect multiple awards.

18 Are there any restrictions in terms of non-US territory applicants?

There are no restrictions on location of applicant.

19 Can one submit more than one application?

There is nothing that prevents the submission of multiple proposals, but I would recommend engaging through a Tech Watch.

20 USG used other transactions authority (OTA) for COVID19 related contracts during the PHE, does BARDA expect to use this mechanism again for topic of interest #15 – Next Gen Covid19 vaccines?

No decisions have been made on contractual mechanisms and would be subject to negotiations.

21 Is SAM Vendor registration mandatory for submitting a proposal?

Registration in SAM.gov is required for submission of a Full Proposal.

22 Could you provide clarification on when and to whom the Invitation Letter referenced in the Cost Proposal section should be addressed?

An invitation letter would be sent from BARDA to offerors who submitted a white paper that advances to the full proposal stage. See Attachment 10 of the BARDA BAA for the BARDA BAA Process Flow Chart.

23 What degree of cost sharing will be required?

Offerors should propose a plan.

24 Re: AOI #15 minimum criteria #5 and Key Tenant #2: It is noted in AOI #15 that USG will identify and fund central laboratories for primary endpoint assays and key immune assays. Please confirm that these costs should not be included within the Cost Proposal? Alternatively, if required to include immunogenicity analyses within the budget, are the central laboratories determined by USG available to provide budgets to each offeror?

Correct. These costs do not need to be included.

However, offerors are free to propose supplemental analyses.

25 BARDA appears to have engaged their Clinical Services network for similar activities. Are product sponsors free to engage with members of BARDA’s Clinical Services network for activities to be proposed under the Broad Agency Announcement?

Yes. Partners under the Clinical Services Network are free to assess and consider opportunities directly with potential sponsors for next-generation vaccine development under the Broad Agency Announcement.

Technical – BAA Scope

26 We have a product that goes into the air that stops the transfer of COVID or ANY airborne pathogen, acceptable?

The BAA is specifically soliciting research for Phase 2b clinical studies for vaccines against COVID-19.

27 What is your priority for oral RNA vaccines delivering anti-COVID-19 mucosal immunity?

Mucosal administration, to include oral delivery, is a priority as noted in the BAA language.

28 Is the agency interested in non-traditional vaccine projects (e.g., either mucosal vaccine of innate immune modulators)

Mucosal administration is one of the priority areas, however, as noted in the BAA, candidates must be sufficiently mature to be poised for Phase 2b studies.

29 Will you fund vaccine Platform development?

No. This Area of Interest has a specific focus of a Phase 2b clinical trial.

30 Is there an interest brining novel drug that are currently being developed for COVID and related respiratory/lung functions?

No. This Area of Interest has a specific focus of a Phase 2b clinical trial for vaccines.

31 Are you looking for innovative, multi-omic and adaptable diagnostics technologies as a shield for future pandemics?

No. This Area of Interest has a specific focus of a Phase 2b clinical trial for vaccines.

32 Why was the decision made to not consider support for Phase 1/2 research for next-gen covid-19 vaccines?

This area of interest is specific for Phase 2b studies.

For any Phase ½ studies, product sponsors should engage with our NIAID partners at this time.

33 What volumes does HHS intend to "stockpile" for these mAb therapies?

This area of interest has a specific focus on Phase 2b clinical studies for vaccines and stockpiling is not being considered.

34 How should organizations prioritize existing vaccine assets (Phase 2b ready) versus improved vaccines (not Phase 2b ready)?

This area of interest has a specific focus on Phase 2b clinical studies for vaccines. It is a company's decision on how they would priority assets that are Phase 2b-ready versus improved candidates that are less mature.

35 Does clinical supply have to be manufactured domestically?

There are no requirements for location of manufacturing under this area of interest.

36 Can the IND be submitted during the base period?

Yes. IND can be submitted during the base period.

However, it is expected that a pre-IND meeting with FDA will have been held prior to proposal submission.

37 RE #15: Would having an IND and clinical trials outside of the US be acceptable to fulfill requirements 1 and 2?

Previous clinical trials outside of the US may be acceptable as long as the candidate vaccine is ready for Phase 2b clinical trial.

38 Is Clinical trial Phase III allowed? No. The BAA language is specific in support of a Phase 2b trial aligned with the synopsis attached to Amendment 42 of the BAA.

39 How will BARDA support the development and commercialization of promising innovations at smaller (e.g., startup) companies?

The scope of this area of interest is limited to phase 2b studies. Offerors should not assume continued support for further development and commercialization.

40 Is there interest in advancing microneedle patch candidates? To my knowledge, no current candidates meet the AOI criteria

Microneedle patch candidates are generally of interest. However, this specific AOI would only be applicable if the candidate is ready for a Phase 2b study

41 Can we develop a second-generation vaccine without animal data available?

The AOI is specific for Phase 2b studies only.

42 What constitutes phase 2b trial-ready vaccines? How many months from onset of Phase 2b is suitable?

The expectation is that there will be adequate safety and immunogenicity data to support progression into a large-size efficacy study; having safety and immunogenicity data from 6 months post-vaccination would put candidates in good position to be Phase 2b-ready. The expectation is the onset of the Phase 2b would be within 6 months of proposal submission.

43 We don't have Phase 1 data yet available of our COVID vaccine. Is it required to have this available before we submit our ideas?

Without out Phase 1 data, it may be difficult to provide a response where a Phase 2b study could be initiated within 6 months of proposal submission.

However, potential offerors are free to request Tech Watches and we would plan on including our NIAID partners in case there is interest from their perspective.

44 Can discovery phase vaccines apply? A discovery phase vaccine would not be responsive to the AOI.

45 How will building manufacturing capability and capacity be addressed?

Manufacturing capability and capacity will not be addressed under this AOI.

46 How can company that has next-gen Covid-19 vaccine in earlier stages of development leverage AOI#15 program opportunity?

AOI 15 is specific to support Phase 2b studies and may not be applicable to earlier stage technologies.

At this time, we would suggest engaging the NIAID team if interested in earlier stage clinical support.

47 By phase 2b ready do you mean that development should have already completed a successful phase 1 trial?

Generally speaking, that would be a good benchmark. However, depending on a sponsor’s existing plans, if they are in a phase 1/2 design for example, there may be expedited paths. But having safety and immunogenicity from 6-month time points in clinical studies would be important to evaluation of the candidate. The most important thing is that any sponsor must be able to present a defensible plan that would get them to Phase 2b starts within 6 months of proposal submission.

48 Does the Phase IIa results impact the funding opportunity?

If an offeror already has Phase 2a data, they would likely be in position to meet the timeline requirements. But they would need to meet the other requirements as well.

49 Can BARDA fund a run up phase 1 for establishing safety for adding another antigen?

No. That is outside the scope of this BAA and we would recommend engaging our NIAID partners.

50 If a potential offeror already had a SARS- CoV-2 vaccine with demonstrated increased breadth and/or duration and had a study planned that would measure these elements, would this fulfill the minimum requirements for submission?

The candidate would have to meet the criteria laid out in the BAA but in theory yes as long as it is mucosally delivered, spike plus non-spike antigens, and/or a multi-RBD approach. However, any proposed plan would have to align with the protocol synopsis provided in the BAA.

51 Will BARDA accept a Phase 3 study to be performed in the requisite time as fulfilling the minimum requirement? If a phase 3 study can be started within 6 months of award would that be acceptable?

The AOI specifically asks for a Phase 2b study. That phase 2b study must be aligned with the synopsis provided in the BAA.

52 Would BARDA accept a Phase 2/3 study to start within a year of award as fulfilling the minimum requirements?

No. That does not meet the requirement of a Phase 2b within 6 months of proposal submission. Offerors should also note that this AOI is specifically requesting proposals that align with the synopsis provided in the BAA.

53 Is there any flexibility in the timeline regarding the requirement that the Phase IIb trial starts no later than 6 months after proposal submission? According to the revised Amendment 42, the minimum criteria is specified as “Program must have an active or complete Phase 1 clinical trial, with unblinded safety and immunogenicity data to support” and “Program must have available sufficient clinical trial material to support the proposed Phase 2b study no later than 6 months after proposal submission”. Given these requirements, is it possible for companies that have previously submitted a response to BARDA’s RFI and that are likely to be only entering Phase 1 in Q4 2023 to still be eligible for funding?

There is currently no flexibility in the requirements.

However, we are partnering with NIAID in this effort and would suggest engaging with NIAID for earlier stage programs.

54 Does the scope of funding pertain solely to clinical trials, or does it also cover associated CMC (manufacturing) costs?

Please see the BAA language, this only supports a Phase 2b study.

55 Does BARDA have any long-term funding plan beyond the phase IIb? Upon successful completion of phase IIb clinical trial, would the Awardee become eligible

Please see the BAA language, this only supports a Phase 2b study.

for phase III clinical trial funding and/or regulatory activities?

56 Is there an expectation that contracts awarded under AOI#15 will result in future stockpile procurement opportunities and/or pandemic readiness?

No. That is not an expectation.

57 When does BARDA anticipate the start of the Phase 2b study?

Offerors should propose a realistic plan. If a realistic plan does not involve initiation within 6 months of proposal submission it will not be responsive.

58 Who will hold the IND for the Phase 2b study?

Any awardees under the BAA will be expected to hold the IND. Per the AOI, a US IND is expected.

59 BARDA core services (e.g., animal study network, flexible manufacturing facilities) are available for use. Are these core services contracted separately after award is approved, or should any requirement for these services be included in the full proposal submission?

Generally speaking, yes, but offerors should not necessarily plan on it being part of their proposed program.

60 Re: AOI #15 minimum criteria #4:

Depending on the expected timeline between proposal submission and award, having clinical trial material available takes time – will BARDA absorb the time after final award decisions are made or is there a process whereby multiple parties could be funded to start manufacturing before final award decisions are made?

No. The expectation is that any offerors will have material available.

Criteria

61 Future Inhaling focus? Mucosal administration is one of the three priority types of candidates noted in the BAA language.

62 Is there an opportunity for addressing the monovalent virus that emerges or solely multivalent & whether 2 or 3 RBD's which ones?

Any proposals must focus on candidates that hit one of the three main categories noted: mucosal administration, spike plus non-spike antigens, or multi-RBD. A monovalent approach would have to be either mucosal or spike/non-spike.

63 Is there a definition to what a spike protein and at least one additional non-spike SARSCoV-2 antigen is?

Any non-spike antigen of SARS-CoV-2 would be acceptable (nucleocapsid, membrane, or envelope for example)

64 How flexible is BARDA regarding the timing of 2b readiness?

This is not flexible. The BAA language notes within 6 months of proposal submission.

65 Do the 6 listed criteria a MUST for the proposal to be deemed responsive to the

BAA?

Yes. The 6 criteria are a must, although submission of a US IND during the base period would be allowable as long as the Phase 2b could start within 6 months of proposal submission.

66 Is BARDA interested to work with companies with alternative vaccine technologies other than mRNA?

Yes. This area of interest is open to any platform as long as the vaccine candidate meets one or more of the aspects included in the BAA, the product is Phase 2b-ready and meets the other requirements described in the BAA.

67 Our sublingual technology contributes to mucosal immunity. Does BARDA have interest in sublingual Covid vaccine development?

Sublingual would count as mucosal administration.

That would be responsive if the candidate is Phase 2b ready.

68 Would an intramuscular vaccine candidate which drives strong mucosal responses be in scope?

No. Unless it meets one of the other categories (spike + non-spike antigen or multi-RBD), that would not be responsive.

69 Will we have a solution that is NOT a shot?

Mucosally administered vaccines are one of the categories in terms of types of vaccine. These would not require a needle.

70 Can the requirement to use mucosal administration be replaced with the ability to induce mucosal immune response?

No. The requirements set forth are mucosal administration, spike plus non-spike antigens, or multi-RBD based approaches. If an approach does not use mucosal administration, it must fall into one of the other two categories.

71 The minimum requirements appear largely focused on awarding those vaccines that have increased breadth and duration of response. If a company had a vaccine that provided either greater breadth or greater response duration, would this fulfill the requirements, even if they did not use the exact methods described in the AOI #15 minimum requirements (i.e., more than 2 SARS- CoV-2 strains, etc.)?

No. Any candidate must meet the minimum criteria being one of the three categories noted in the AOI.

72 Will BARDA consider single antigen vaccines?

Single antigen vaccines will only be considered if delivered mucosally per the AOI language.

Trial Design

73 What consideration should be given for Phase 2b design in the context of potentially updated bivalent mRNA vaccine this Fall?

The expectation is that the Phase 2b study design would incorporate the use of active comparators that are licensed/authorized for use at the time of initiation of the study.

74 Please discuss pathway for obtaining comparator for study in current US market.

As stated in the BAA, the Program must include plans for access to comparator (i.e., licensed product) thus Potential offerors are expected to source comparator on their own.

75 Is there interest to support vaccine solutions that are specific tailored for pediatrics?

The Phase 2b trial is expected to be conducted in adults, however, the results may inform futher development in the pediatric population.

76 What temperature will the vaccines be stored at? Will BARDA be seeking a bio storage partner also?

Potential offerors should have a plan for storage consistent with the needs for a phase 2b study as described.

77 We have developed a home blood collection device with a very low COGS -would this support decentralized clinical studies?

It would be the offeror’s responsibility to propose any approach that might include decentralized studies.

78 Will BARDA accept real-world access to licensed comparator vaccines via pharmacies, health dept.

The trial design should include plans for an active comparison to licensed or authorized product.

79 Please highlight the plans and support for COVID prevention trials in patients with Autoimmune conditions.

We would expect that that would be part of plans proposed by potential offerors as needed.

80 Can BARDA assist in obtaining comparator licensed product

No. As of right now, offerors must provide a plan to secure their own comparator.

81 Will the Phase 2b address the role of pre-existing immunity?

There are no specific requirements to address different types of pre-existing immunity, but offerors are free to propose plans to do so as long as plans are consistent with the synopsis included in the BAA.

82 Does BARDA expect awardees to address the role of pre-existing immunity and enroll subjects vaccinated with different platforms?

Offerors are free to propose study designs in line with the synopsis, but no specific focus on various previous vaccinations is expected.

83 Does BARDA have a preferred list of viruses that next-generation vaccines should cover both VOC and other coronavirus clades?

Offerors should use FDA guidance. Central immune assays will be part of the program.

84 Is BARDA looking to use the relative efficacy study to identify new Correlates of Protection? (i.e., non-neutralizing effector functions)

Potentially yes, however offerors can propose supplemental analyses.

85 Considering the Phase 2b protocol synopsis provided includes evaluation of efficacy, which SARS-CoV-2 variant S protein will be required to be used as the mucosal vaccine antigen?

That is incumbent on the potential offeror to propose.

86 Is BARDA interested in United States Phase 2b trial data only, or would BARDA support a trial conducted in multiple countries which includes the United States?

Yes. BARDA would consider international sites.

87 Does BARDA require single-dose vials, or would BARDA accept a multi-dose vial presentation for the proposed Phase 2b trial?

The offeror may propose what is best for their candidate.

88 Does BARDA wish to include the VRBPAC supported strain/variants that is expected in Jun'23 as part of the proposed trial?

There are no firm requirements so offerors may propose their antigen choice, however, it may be best to align with FDA guidance.

89 Re: AOI #15 minimum criteria #6: Does BARDA have a preference for the comparator used in the Phase 2b trial (e.g., SpikeVax vs COMIRNATY)?

No.

90 As noted in the synopsis, population considerations will be made to ensure representation of older adults (>65 years old), individuals at high risk for severe COVID-19, and racially and ethnically diverse populations in the Phase 2b study. What does BARDA consider to be “appropriate representation” for these groups?

See FDA guidance.

91 Does BARDA recommend a centralized diagnosis for the clinical efficacy endpoint?

Yes. Labs can be discussed during negotiations.

92 Considering populational hybrid immunity and lower overall incidence rates of COVID-19, there is a possibility accrual for the number of cases is not met within one season. As a mitigation measure, should two seasons be planned for?

That is acceptable if the offeror's opinion is that it will be needed.

93 What is BARDA’s recommended procedure for asymptomatic COVID-19 infection surveillance?

That is up to the offeror to propose.

94 What is the expected subset of study subjects that will have cellular immunity analyses (e.g., ELISpot)?

The offerors may propose a number for that subset.

95 Does BARDA recommend including cardiac assessments at baseline?

That is up to the offeror to propose as long as it aligns with any expectations from FDA.

96 Does BARDA recommend futility analysis as per DSMB charter?

That is up to the offeror to propose.

97 Titers vs T-cells for durability of protection?

Durability of protection assessments will be based on clinical efficacy. Additionally, correlates of protection analyses will include assessments of both cellular and humoral immunity.

Live Q&A

98 Is this RFP only for vaccines or pharmaceuticals that are currently in ready for Phase2?

The Area of Interest 15 is only for vaccines, and only for Phase 2b clinical studies.

99 Pharmaceuticals (small molecules) not antibodies

This area is only for vaccines.

100 is the agency only interested in mRNA vaccine technologies?

No. We are open to any platform as long as it meets the criteria noted in the BAA.

What is the total award $ amount?

It is incumbent on the offeror to provide proposed costs.

Where on sam.gov will the questions answered on this webinar be available?

Thank you for your question, we plan to share the answers to all questions answered under on the BARDA BAA page:

https://sam.gov/opp/6f989eb9c421422788a4c3a91 33917f0/view

103 I am curious about the timing of the end of this fiscal year and the successful selection, negotiation, and award of money. Does the timing require an award to be made before the end of September? Thanks.

There is currently no firm requirement, but budgets are always subject to changes from year to year.

Will BARDA have provided written responses to questions?

Thank you for your question, we plan to share the answers to all questions answered under on the BARDA BAA page:

https://sam.gov/opp/6f989eb9c421422788a4c3a91 33917f0/view

105 If a company can enter phase 2b in 1H2024, will BARDA consider extending timeline for a mucosal vaccine in pre-clinical stage, beyond 6-month requirement as stated in BAA?

No. As of now the timeline is not flexible.

Will you be seeking cold storage for vaccines upon completion?

It is incumbent on the offeror to propose any storage needed in alignment with the clinical trial.

There are no requirements for purchase or storage of vaccine under this announcement.

107 Where should we go to find information about the BARDA's interest in small molecules as COVID/ lung function therapeutics?

Please check with FASTxBAA@hhs.gov.

If we are interested in a Phase 1, can you please provide contacts for NIAID engagement?

Please engage through our Tech Watch program.

However, Tech Watches are currently only being granted if you have submitted a response to the previously posted request for information (SAM.gov).

109 You just mentioned Ph2b 6mo from “award” but I thought the BAA stated 6mo from submission for the Ph2b. Can you please clarify?

Apologies, we mis-spoke. The requirement is 6 months from proposal submission.

110 For clarity, will you please confirm the envisioned duration of the POP of the base period, and when expected to begin/complete the base -- is it a 6-month POP starting at the time of contract award? The BAA states be

Offerors should propose a realistic and defensible schedule for the base and options, with clear go/no go criteria.

https://sam.gov/opp/6f989eb9c421422788a4c3a9133917f0/view https://sam.gov/opp/6f989eb9c421422788a4c3a9133917f0/view https://sam.gov/opp/6f989eb9c421422788a4c3a9133917f0/view https://sam.gov/opp/6f989eb9c421422788a4c3a9133917f0/view https://sam.gov/opp/53668acd172e4440a096362247bcea73/view ready for the Phase 2b trial "within 6 months of proposal submission," which is a little bit confusing.

111 Why is BARDA limiting the demonstration of breadth and duration as including spike + non-spike proteins and having a multi-RBD approach?

The criteria for this area of interest were put in place due to the technical team’s assessment that these approaches may be most likely to result in improved performance.

112 The two mRNA companies have made it clear that they will not share vaccine for comparator studies on numerous occasions. Distributors are also HIGHLY reticent to sell mRNA vaccines. If BARDA will not get involved how will awardees secure comparator vaccines?

As of right now, we are asking offerors to propose a plan to source. We acknowledge that the situation is difficult at the moment, however, the expectation is that vaccine comparators will be more readily accessible upon commercialization this fall.

113 My company has never applied for government funding before. Do you recommend any consultants or 3rd party firms who can help us navigate this process and prepare proposals to ensure we get it right the first time?

Admittedly the process for submitting a full proposal is intensive and having someone consult you the first time isn’t a bad idea. However, we can’t recommend specific consultants.

Can you please repeat the deadline for scheduling a Tech Watch for AOI 15 if a response to the RFI was submitted?

If you have submitted a response to the RFI, there is no firm deadline to submit a Tech Watch request.

Sooner is better but there is no firm deadline at the moment.

115 The minimum requirements seem to be very specific/targeted. Can you speak to why this is the case? Also, can you speak to the potential for a future AOI to be less restrictive?

The minimum requirements are targeted for Phase 2b clinical studies. Future AOI’s may include other activities but that cannot be guaranteed.

116 Double blinding is requested. Would this include mock IM shot for the mucosal vaccine arm and mock intranasal dosing for the active comparator arm?

Yes, our initial thought is that those mock vaccinations may be advisable, however, offerors are free to propose alternatives as they see fit.

When will you be posting the recording of this webinar?

Thank you for your question, we will not be sharing the recording, we do plan to share the answers to all questions answered under on the BARDA BAA page:

https://sam.gov/opp/6f989eb9c421422788a4c3a91 33917f0/view

118 Yes, written responses would be nice. Written responses will be posted.

119 Will BARDA consider extending the RFI date given that submission to that is a reissuement for submission under the

BAA?

As of right now, the RFI deadline is May 26. Please reach out to the contacts noted in the RFI if you would like to request an extension.

120 If you used for example a 33-microgram dose in your prior Phase 1 trial can use multi RBD's to that total up to 33 micrograms.

That seems reasonable but it would be expected that any such strategies are also discussed with the

FDA.

121 Would a challenge study be an acceptable way to assess efficacy in a phase 2B?

No. Any proposed Phase 2b’s must align with the synopsis included in amendment 42 of the BAA.

Is the vaccine manufactured outside the US eligible for phase 2b grant?

Yes. As manufacturing is not part of the scope, we are not putting any constraints on location at which vaccine was manufactured.

123 Is it correct that BARDA does not consider this Ph2b as registrational trial?

That is correct.

124 Has BARDA selected the immune response assays, beyond neuts, and vendors that are qualified?

Yes. That can be discussed during Tech Watches and or negotiations.

Is there a plan for a successful Phase2a trial run through NIAID to transition to a 2b with BARDA?

There are no guarantees of that flow, but we are open to successful Phase 2a trials run through NIAID coming into the Phase 2b program, assuming an appropriate proposal is submitted.

126 Will the offeror or BARDA own right of reference to the data?

That will be subject to any negotiations.

127 Please give us an update as to where the present vaccines stand and what area needs improvements?

The minimum criteria note the types of vaccines that would be responsive.

128 Did you say that CMC activities are not covered for funding under base period activities

CMC activities are not covered under this AOI.

129 Assuming a study enrolling10,000 subjects, how quickly should offerors propose to fully enroll the study?

Offerors should propose a realistic plan and timeline to enroll subjects.

130 Is an application eligible if the vaccine consists of one full-length spike antigen and one RBD only antigen?

Per the definition noted in the AOI, candidates should be mucosally delivered, contain spike plus a non-spike antigen, and/or consist of multiple RBDs.

131 Where should we go to find information about the BARDA's interest in small molecules as COVID/ lung function therapeutics?

Please check first with FASTxBAA@hhs.gov

132 Would a challenge study be accepted under the BAA?

No. Any clinical studies should align with the synopsis provided in amendment 42 of the BAA.

133 For clinical trial design - should there be comparison of viral load between investigational vaccine and comparator in those that are diagnosed with COVID? should duration of symptoms be compared with comparator group?

There’s no firm requirement, but in general that is something offerors may propose.

mailto:FASTxBAA@hhs.gov

134 Does NIAID have part of the $5 billion Next Gen Funding for earlier stage COVID vaccines?

This Q&A is focused on AOI 15 under the BARDA

BAA.

What is the scope of NextGen Covid-19 vaccine? New variants, bivalent, multivalent SARS-Cov-2?

This Q&A is focused on AOI15 under the BARDA BAA and the general categories of vaccine are noted as mucosal, spike plus non-spike antigens, and/or multi-RBD.

136 Is the RFI response due by May 26th?

Are there options if we cannot make that date? How can I access the RFI?

You can find the RFI here, https://sam.gov/opp/6f989eb9c421422788a4c3a91 33917f0/view

137 This Phase IIb trial is an event-driven study to reach 255 events based on a 3% cumulative incidence over 12 months. What happens if the study does not accrue 255 events over 12 months? Are there any plans to extend the study duration?

The offerors should propose plans that would speak to the potential need to extend.

138 You mentioned using existing FDA guidance to help guide companies with phase 2b design. How will BARDA be engaging with FDA to ensure guidance is up to date for next-gen vaccines?

It is incumbent on potential offerors to engage with FDA as needed on specific guidance.

139 In the synopsis, the efficacy analyses section discusses calculating VE defined against placebo but there is no placebo in this study. Please explain.

Apologies, VE would be calculated against the comparator which is noted as a licensed/authorized boost and not placebo.

140 I'm still a little unclear how to propose the Base timeline. Should we propose a 6-month Base period for planning activities as outlined in the BAA, and then execution of the Phase 2b study to begin in Option 1 starting at completion of Base upon meeting go/no go criteria? In other words that would allow 6 months, during the Base period, to set up for executing the actual study?

To request a TechWatch meeting, visit https://medicalcountermeasures.gov/request-barda-techwatch-meeting/

141 You mentioned using existing FDA guidance to help guide companies with phase 2b design. How will BARDA be engaging with FDA to ensure guidance is up to date for next-gen vaccines? Will there be efforts to expand regulatory capacity provided to next gen vaccine review as was done for the original COVID vaccines during Operation Warp Speed?

The BAA lays out the expectations for the Phase 2b design. It is incumbent on potential offerors to engage with FDA as needed on specific guidance for their individual product. We cannot speak to regulatory capacity.

https://sam.gov/opp/6f989eb9c421422788a4c3a9133917f0/view https://sam.gov/opp/6f989eb9c421422788a4c3a9133917f0/view https://medicalcountermeasures.gov/request-barda-techwatch-meeting/ https://medicalcountermeasures.gov/request-barda-techwatch-meeting/

How can we get a transcript or recording of this meeting?

Thank you for your question, we plan to share the answers to all questions answered under on the BARDA BAA page:

https://sam.gov/opp/6f989eb9c421422788a4c3a91 33917f0/view

143 The TechWatch meeting we received stated that all companies who received TechWatch meetings did meet the minimum criteria but that is not consistent with your answers on this call. Can you confirm that if we received a TechWatch invite BARDA determined we meet minimum criteria?

Tech Watch meetings are shared with our NIAID colleagues. If you were granted a meeting, you have at least met the criteria of having submitted an RFI response and having a platform that the broader team wished to discuss. Depending on maturity the Tech Watch may be more relevant for BARDA or NIAID but it does not necessarily mean it meets the BAA criteria at this time.

144 It is clear that BARDA is seeking additional work on the vaccine it means that area of improvements is needed.

The AOI notes the general categories of vaccine that are of interest.

What are those?

The AOI notes the general categories of vaccine that are of interest.

Will offerors get only one chance for the TechWatch meeting? If possible and required by offerors, could NIAID join the TechWatch meeting?

NIAID will be in attendance. There are no restrictions in terms of only having one chance.

Often, we will hold an initial Tech Watch and can have follow up meetings if needed to clarify or get updates on data.

Did you indicate where we can get a recording or transcript of the meeting?

Thank you for your question, we plan to share the answers to all questions answered under on the BARDA BAA page:

https://sam.gov/opp/6f989eb9c421422788a4c3a91 33917f0/view

148 Can you say must be ready for PH IIB within 6 months of award again?

Apologies, that should be ready within 6 months of proposal submission.

149 Could you share how NIAID is involved?

is there an open RFI held by NIAID?

thanks for any guidance.

NIAID will be involved in any Tech Watches, and per the language in the RFI, RFI responses are being shared with the NIAID team.