Questions and Answers 10 July 2017.docx

NOTE: All references to the companies must be removed before this is posted to grants.gov.

Questions are reproduced exactly how they were submitted.

1. After reading over the Funding Announcementand creating the proposal I notice there is no place built in grants.gov to include the Key Personnel accept the budget.. Also, thereis no instruction regarding where the curriculum vitae/biosketch shouldbe uploaded for Key Personnel. Although, there is a Qualificationssection in Attachment 1 (30 page limit), is this where Key Personnel andbiosketches should be included? Please advise.

A: Key Personnel should be included in the Technical Volume, under “Technical/Management Approach” (Please see page 2 of the Application Instructions (AI)).

Curriculum vitae/biosketchs are to be included in the Technical Volume and do not count towards the thirty page limit. Please see page 1 of the AI: “The page limit for the Technical Volume is 30 Pages (Excluding Resumes or Curriculum Vitae (CVs) and FWA)”.

2. We found the following announcement on grants.gov < Caution-http://grants.gov > : Caution-https://www.grants.gov/web/grants/view-opportunity.html?oppId=294860 < Caution-https://www.grants.gov/web/grants/view-opportunity.html?oppId=294860 > but we have difficulty locating the full announcement. Your assistance in locating the full text of the announcement would be greatly appreciated.

A. The funding opportunity can be located at:

https://www.grants.gov/web/grants/search-grants.html?keywords=N62645-PA-17-1

3. The program announcement specifically states “Research activities under this cooperative agreement will take place primarily within IDD-NMRC laboratories.” Is this to be interpreted that one of the primary intents of this funding opportunity is to manage the hiring of personnel; procurement of supplies, materials, and equipment; administer sub-contracts; and perform other managerial and administrative duties that are to be performed within the walls of the DoD facility? Or is this to be interpreted that this funding opportunity expects that research collaborations be performed directly with each of respective laboratories (i.e., scientific collaboration with the scientists)?

A: The awardee will be expected to support both functions listed above. The personnel hired will work collaboratively with their Government counterparts to support the research outlined in the PA.

4. Is the grantee expected to serve as an administrative infrastructure subcontracting to scientific institutions at the behest of IDD-NMRC or to act as the scientific partner?

A: Please refer to the answer for question 3.

5. Would an application be considered competitive if it did not respond to all of the specific collaborative efforts listed in the summary of responsibilities section? For example, an application addressed all areas except it did not respond with specific expertise to “identify biomarkers predictive of clinical outcomes in skin and soft tissue infections”. Will it still be responsive?

A: The applicant must be able to collaborate with the Government and support all areas covered in the PA. Applications that do not identify the ability to support all areas mentioned in the PA, will be considered non- responsive.

6. Can there be guidance for the assumptions that need to be made for the application (including pre-clinical and clinical trials that are alluded to in the summary of responsibilities section)? Any specific guidance on study parameters (number of animals/subjects, time periods for the trials, specimen collection times, objectives/endpoint, etc.) will allow for more precise descriptions, budget estimates, and budget justification--facilitating peer and programmatic review. In addition, the application must be realistic in what they propose can be accomplished within 18 months. Some example issues are summarized below:

A: The collaborative input desired by the applicant relates to pre-clinical studies and clinical trials that are currently ongoing or that will be launched during the 18 month period. For new studies (animal and human), study parameters are difficult to determine at this time given that much of the study design for future studies will hinge on results of ongoing work. The proposal should indicate the expertise of the applicants’ staff in planning, developing, writing proposals/protocols, submitting protocols for scientific and ethical review, conducting pre-clinical and clinical studies, analyzing the data, and writing reports/manuscripts for publication.

a. For pre-clinical animal studies in support of a vaccine candidate’s IND, should the application propose formal toxicology studies? Should the applicant justify the number of animals, the number of experiments, number of replicates and timepoints?

A: The application should not propose formal toxicology studies at this time but rather provide collaborative input to planning future toxicology studies based on input from pre-IND meetings with the FDA. For toxicology studies that have already been planned, the applicant should expect to provide collaborative input into executing these studies and interpreting data.

b. As part of anticipating the advanced development of study products, should the application describe the expertise for supporting the generation and successful submission of INDs, including the ongoing reporting required to support active INDs?

A: Yes, submission of INDs and fulfilling reporting requirements is a key part of NMRC-IDD’s product development activities.

c. For clinical studies, should the application propose a number of phase 1 and phase 2 studies for each theoretical candidate (knowing that it is unrealistic that all studies can be completed within 18 months)?

A: Yes, the applicant should feel free to propose phase 1 and phase 2 studies in support of moving current vaccine products and countermeasures toward licensure. This should be done with the expectation that such proposed studies and study designs are subject to change based on collaborative input from NMRC investigators and based the results of ongoing clinical studies.

d. Would it be correct to assume that inpatient studies (e.g., for close monitoring of safety, for performing challenge studies for preliminary efficacy, etc.) are anticipated as an attractive capability of the application?

A: Being able to conduct/support inpatient studies is a desired capability. The clinical testing of vaccines and other countermeasures often involves challenge (controlled human infection) with live laboratory-derived or wild type organisms that may require inpatient observation and monitoring of study subjects.

e. For the determination of biomarkers and immune mechanisms of protection (in either animal models or humans), should the application propose to use traditional flow cytometry, mass cytometry (e.g., CyTOF or Helios), or other preferred measures (e.g., gut homing markers for antigen-specific ASC for candidate Shigella or ETEC vaccines)?

A: Determination of biomarkers and immune mechanisms of protection is a desired outcome of our clinical and pre-clinical studies. The applicants’ suggestions are welcomed regarding the most efficient and effective way to meet the desired outcomes. Final decisions regarding methods used will be derived from collaborative discussions with the applicant.

f. Should we assume that the laboratory studies (microbiology, immunology, etc) will be performed at NMRC facilities or we can include in the application studies that will be performed at our institution and/or in the facilities of our subcontractors?

A: It is anticipated that most of the work will be conducted in NMRC-IDD laboratories. However, laboratory studies can also be performed at the applicant’s facilities if the procedures and instrumentation used to conduct the studies and analyze data generated from the studies meet NMRC standards.

g. Will synopses or summaries of the various trials/experimental studies be acceptable for back-up information to justify the budgets? Will that count toward the 30-page or can this be part of the budget justification? Is there a page limit for the budget justification?

A: Yes, synopses or summaries of various trials/experimental studies is acceptable as back-up information. Page limitations apply.

7. Are studies of the stool microbiome and transcriptome (e.g., from patients with CJ infection) and the sequencing of CJ isolates considered “molecular biology” studies? Otherwise, what molecular biology study capabilities are envisioned or desired?

A: Molecular biology studies would indeed potentially include microbiome, transcriptome characterization of the host and pathogen in the setting of infection. In addition, genome sequencing capability would likely be called upon as well. These would constitute the bulk of molecular biology work in support of CJ.

8. The development of a humanized mouse model appears to be a significant capability for the application to demonstrate, but what is the pathogen(s) or disease(s) of interest? There are many potential humanized mouse models, each tailored according to each pathogen or disease of interest.

A: NMRC-IDD is pursuing the use of the DRAG and DRAGA mouse models to study immunological responses and the pathogenesis of infection due to malaria, dengue, and rickettsial species.

9. Will references be counted toward the 30-page maximum in the technical application? Alternatively, will the statement that “references upon request” be acceptable?

A: References fall under the same category as Resumes or Curriculum Vitae (CVs). As such they do not count toward the page limit. Please see the answer to question one.

10. Will NIH-style biosketches or curriculum vitae (CVs) be acceptable as part of the technical application and will those count toward the 30-page maximum? Alternatively, please provide instructions on how these supporting documents may be appended to the application.

A: Yes, NIH-style biosketches or curriculum vitae (CVs) are acceptable. For the remainder of the question please refer to the answer to question 1.

11. Will an Administrative Core and other Cores (e.g., Immunology Core, Genomics or ‘Omics Core, Regulatory and Quality Management Core, etc.) be acceptable? These would be programmatic units within the applicant’s existing infrastructure that are intended to straddle across the different projects and has the potential for more efficient cost-sharing.

A: We encourage the applicant to propose whatever they feel is the best structure to promote optimal administrative performance and economic efficiency.

12. Can evaluation priorities be provided?

A: Evaluation priorities are provided in the PA, beginning on page 8 under “IV. EVALUATION INFORMATION.”

13. How will the agenda of activities be set?

A: Please refer to Page 1 of the PA, specifically “6. Funding Decision Date”. The government plans to make a funding decision by: August 10, 2017.

14. Should the 18-month base period be broken out into two budget periods based on fiscal year, or should the budget be submitted as one 18 month budget period?

A: The budget should be submitted as a single 18 month budget period.

15. Please advise if a salary cap should be applied for this Program Announcement?

A: There are no salary caps in place for this Program Announcement.

16. Should applicants include CVs for all personnel designated as senior/key?

A: Yes.

17. When we propose a vendor on a fee-for-service basis, the vendor is not classified as a subaward and a detailed subaward budget is not included. Please advise if this is acceptable and if, in lieu of a subaward budget, a vendor quote should be included with the application.

A: Under the specific circumstances described above, this is acceptable.

18. For planning and budgeting purposes is a November 1, 2017 start date reasonable, given the project is not anticipated to begin less than 3 months after the application deadline?

A: The anticipated period of performance will start in September of 2017.

19. Would the process of securing necessary clearances described on page 2 of the Program Announcement be initiated upon award or is the applicant expected to have security clearances in place now?

A. Candidates must have an existing favorable adjudication of the results of the background investigation.

20. Technical volume page limit:

A: Please refer to page one of the AI specifically, “The page limit for the Technical Volume is 30 Pages (Excluding Resumes or Curriculum Vitae (CVs) and FWA).”

21. Can the cover page be excluded from the page limit?

A: Yes.

22. Can the table of contents be excluded from the page limit?

A: Yes.

23. Although an acronym list isn't required, if we provide one, can the acronym list be excluded from page limit and be submitted as an attachment?

A: Yes.

24. Can the reference list be excluded from the page limit and be provided as an attachment?

A: Please see the answer to question 9.

25. Can the current and pending support be excluded from the technical page limit and provided as an attachment?

With 10 items required for each support item, this could quickly become 1/3 of the technical page limit.

A: No.

26. I am writing to enquire about Funding Opportunity N62645-PA-17-1, "Research and Development of Protective Vaccines and Other Countermeasures Against Infectious Disease Agents of Military Importance."

Applicant X intends to submit an application for this grant with a focus on using bacteriophage to treat MDR ESKAPE pathogens. We have the ability to source extramural resources (Contract Research Organizations, etc) for animal and human studies, if it would be of value to our NMRC collaborators. However, we would be happy to use intramural resources as well (or exclusively). Whatever will best meet the needs of the NMLC/NMRC and Applicant X in achieving the objectives of the grant in a timely and quality manner. What is the best way to determine the current needs of the NMRC are in this regard, in advance of submitting the grant application?

A: The needs of NMRC are outlined in the PA.

27. In re-reading the grant and submission instructions it is not clear whether the collaboration would require cooperation in all 4 key areas of the grant (vaccines and phage therapy), or whether a company specialized in one of these areas can apply to assist only on goals related to one of these areas (e.g., bacteriophage). We actually have a DOD grant using phage to treat traveler's diarrhea; my objective for this grant would have been to provide support for item 4, advancing the use of bacteriophage in treating multi-drug resistant bacteria, though this could be expanded to include traveler's diarrhea as well if it would be appropriate to do so in this grant.

Discovery, research, preclinical and clinical development, and regulatory approval of phage are highly specialized and we are not focused on vaccine development. Does this make this grant inappropriate for us?

A: Please refer to the answer to question 5.

28. Our research proposal is to develop novel therapeutics against multidrug-resistant bacteria (wound infection). It would not include bacteriophage. Would that be acceptable?

A: Please refer to the answer to question 5.

29. It is not clear to me what the role of IDD-NMRC would be in the implementation of the proposal. Will we have to send our research team to the IDD-NMRC Laboratories for the implementation of the project? Do certain aspects of the project have to be executed at the IDD-NMRC Laboratories?

A: Please see the answer to question 6.f.

30. Can we include multiple collaborators in the proposal?

A: Yes.

31. In this RFP, I found the proposed research priorities (copied below) seem to focus more on vaccine development though other countermeasures are mentioned, and more on clinical development (late stages of research/development). Are you still interested in the basic drug discovery research which is being carried out in my lab? Or are there any better fitted RFP available?

A: Please see the answers to questions 5 and 26. No other program announcements are out at this time.