Amendment_2_-_Q&A_-_Research_Areas_001_and_002.pdf

Amendment #2

Solicitation HHS-NIH-NIAID-BAA2018

AMENDMENT TWO (2)

OFFICE OF ACQUISITONS

National Institute of Allergy and Infectious Diseases (NIAID) 5601 Fishers Lane, Room 3D32, MSC 9821 Rockville, MD 20852

Solicitation Number: HHS-NIH-NIAID-BAA2018

Date of Solicitation Issuance: 06/01/2018

Date of Amendment No.1 Issuance: 07/03/2018

Date of Amendment No.2 Issuance: 07/03/2018

Number of Pages: 6

Issued By:

George W. Kennedy, Contracting Officer Email: kennedyg@mail.nih.gov Phone: 240-669-5170

Points of Contact:

Division of Microbiology and Infectious Diseases (DMID)

Research Area 001: Development of Broad Spectrum Therapeutic Products for Biodefense, Anti-microbial Resistant Infections and Emerging Infectious Diseases;

Research Area 002: Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases

George Kennedy, Contracting Officer Phone: (240) 669-5170; Email: kennedyg@mail.nih.gov

Julie Rodriguez, Contract Specialist Phone: (301) 761-7735; Email: julie.rodriguez@nih.gov

The hour and date specified for receipt of Offers remains unchanged.

Offerors must acknowledge receipt of the amendment by Amendment number(s) and date of the amendment. Include a statement of acknowledgement in your proposal submission. Failure of acknowledgement may result in rejection of your offer.

Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full force and effect.

mailto:kennedyg@mail.nih.gov mailto:kennedyg@mail.nih.gov mailto:julie.rodriguez@nih.gov

PURPOSE OF SOLICITATION AMENDMENT

The purpose of this amendment is to provide responses to questions received regarding Research Areas 001 and 002 of this solicitation.

SOLICITATION QUESTIONS AND RESPONSES

This section provides the Government’s responses to questions received regarding this solicitation. The responses are offered for information only and do not modify or become part of this solicitation.

Additional amendments will be provided as needed to address further questions and their related responses.

RESEARCH AREAS 001 and 002 QUESTIONS

The Government’s responses to questions received regarding Research Areas 001 and 002 are as follows:

Question 1: Do the base and options have to run in consecutive one-year periods?

Answer 1: Base and options need not be proposed as consecutive one-year periods. The activities in each period of performance (base and individual options) should be functionally related.

The milestone criteria for beginning each option should reflect achievements of the critical path milestones. In proposing performance periods for the base and each option, the Offeror should make a reasonable estimate of the time in months that would be needed to complete the activities under the base and each option. Please also refer to Section 3.1.3.3, which provides a description of the Workplan, applicable to Research Areas 001 and 002.

Question 2: While a full development program will be proposed, is it possible for Offeror to execute some studies or certain activities at their own expense and outside of a contract?

Answer 2: If awarded a contract, only the scope of work and activities detailed therein will be governed by the contract.

Please also note Section 4.3.3.1 of the solicitation, which allows Offerors to propose cost sharing under this solicitation. Cost sharing is a cost-reimbursement contract in which the Government and the Offeror negotiate the share of the project costs eligible for reimbursement under the contract. A cost-sharing contract may be used when the contractor agrees to absorb a portion of the costs, in the expectation of substantial compensating benefits. The contractor receives no fee and is reimbursed only for the negotiated portion of its allowable costs.

Question 3: We have multiple ongoing projects that align well with this announcement. Are we allowed to submit multiple proposals?

Answer 3: Offerors can submit more than one proposal.

Question 4: Are projects that have utilized NIAID preclinical services eligible for further development though this announcement?

Answer 4: Offerors can apply for this solicitation while support is provided by NIAID or other government agencies via grants, contracts, and services. NIAID and Offeror will negotiate the statement of work that removes tasks and activities completed on the candidate therapeutics since proposal submission and to remove overlap with studies performed under other grants and contracts issued by the government.

Question 5: Is the BAA open to non-U.S. organizations?

Answer 5: This Announcement is being solicited using full and open competition; thus non-US organizations may apply as long as they are not one of the prohibited sources identified in

FAR 25.7.

(https://www.acquisition.gov/sites/default/files/current/far/html/Subpart%2025_7.html)

Question 6: Is the expectation that the proposed clinical trials will be conducted in the US, or is it possible to conduct the trials (according to FDA regulations) outside the US?

Answer 6: The same full and open principal applies with regard to the clinical sites: the solicitation is considered full and open competition; thus non-US organizations may be included in a proposal as long as they are not a prohibited sources identified in FAR 25.7. Please also refer to Sections 4 and 5 of the solicitation for important information regarding Human Subjects, Human Research, and Clinical Trials.

Question 7: Could you please clarify whether the $15.5M mentioned in the BAA are going to be split between two or more proposals or does this funding level apply to each proposal? Are these $15.5M the total funds over 4-5 years or funds for year 1 only?

Answer 7: The $15.5 million is the estimated total available for the non-severable base work across all contracts (direct and indirect costs combined), across Research Areas 001 and 002.

Please note, the base period is not limited to twelve months. The total duration of a proposed contract should be consistent with the nature and complexity of the offeror’s proposed research. The total performance period comprised of the base and any options proposed by an Offeror should not exceed five (5) years.

Question 8: The BAA seems to exclude consideration of proposals if they do not have in vivo data. For Filovirus, which is one of the priority areas, there are very few animal models available and they are not widely accessible. If we have a validated MOA for a therapeutic and detailed knowledge of why the antiviral work, will the BAA support validation in pre-clinical animals, which are part of the animal rule path, to support the endpoint of an IND?

Answer 8: As noted in section 3.1.2.1.2, among the four characteristics listed: (• Demonstrated feasibility of manufacturing; • In vitro and in vivo evidence of efficacy; • In vitro and in vivo evidence of acceptable preliminary pharmacokinetic, safety and toxicology; and • Sufficient characterization to allow the development of a draft target product profile), therapeutic candidates or lead series must show in vitro and in vivo evidence of efficacy in order to be eligible. Additional animal efficacy studies may be supported under a contract on specific therapeutic candidate(s); however, the development of animal model(s) as a resource to evaluate the therapeutic product is not supported by this BAA.

https://www.acquisition.gov/sites/default/files/current/far/html/Subpart%2025_7.html

Question 9: Could you please advise whether it would be preferable to submit proposal which covers both MDR Gram-negatives and select agents, or whether focusing on MDR Gram-negatives would be preferable?

Answer 9: Due to the competitive nature of this solicitation, we are unable to provide guidance regarding preference. As noted in technical objectives 3.1.2.1.2, proposals for the development of broad-spectrum therapeutics are encouraged, as well as candidate therapeutics or lead series with a limited spectrum that target high-priority pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern are eligible as proposed candidates/products or lead series.

Question 10: Must product candidates address: (1) a bacterial pathogen on the CDC or WHO list and at least one identified; (2) only needs to address at least one identified select agent; (3) or only needs to address a pathogen on the CDC or WHO list?

Answer 10: As noted in section 3.1.2.1.3, Technical Approach under Antibacterial Therapeutics, candidate therapeutics or lead series that are eligible for this solicitation if they address one or more pathogens only in item A, the drug-resistant bacteria listed in the 2013 CDC Antibiotic Resistance Threats in the United States report or in the WHO Priority Pathogens List for R&D of New Antibiotics. Similarly, candidate therapeutics or lead series are eligible if they address one or more pathogens only in item B, the select bacterial agents. NIAID encourages broad spectrum therapeutics, and in this solicitation, Offerors have the ability to address pathogens in both items A and B.

Question 11: The BAA states that development of serum derived products under Research Area

001 will not be considered; does this include plasma derived hyperimmune products?

Answer 11: Plasma derived hyperimmune products are not eligible under this solicitation.

Question 12: Can one apply for the above contract for compounds active against drug resistant

Mycobacterium Tuberculosis?

Answer 12: While NIAID encourages broad spectrum candidate therapeutics or lead series, candidates that are active against one or more pathogens that are identified in the 2013 CDC Antibiotic Resistance Threats in the United States report or in the WHO Priority Pathogens List for R&D of New Antibiotics are eligible.

Question 13: Does phage potentially qualify as an approach for “Development of Therapeutic

Products for Biodefense, AMR, etc” per the NIAID BAA? The way I read it, it does, but just wanted to confirm.

Answer 13: Yes

Question 14: Is Leishmania an eligible EID for this solicitation (despite not being listed)? The compound is safe, FDA approved and effective against multiple infections, but is it ok if the proposal just focuses on investigating the mechanism on a single disease?

Can the study be successful if it is a mouse study, or is a human component (clinical trials or tests on human cells) required? If the drug is not directly killing the pathogen but rather acting on the host somehow leading to decreased pathogen burdens, can the study be used to determine how the compound is acting on the host leading to decreased parasite counts and disease?

Answer 14: Candidate therapeutics that solely target Leishmania are not eligible under this solicitation. Offerors should propose studies and activities in their submissions that are needed to develop and advance candidate therapeutics or lead series. Due to the competitive nature of the solicitation, NIAID is unable to provide guidance on specific proposed approach.

Question 15: Would a new proposal for a candidate therapeutic previously funded by NIAID be acceptable?

Answer 15: Offerors may submit a new proposal for candidate therapeutics or lead series that is currently being supported via ongoing grants and contracts. Prior to awarding a contract, NIAID and the Offeror would negotiate a statement of work that removes tasks and activities completed on the candidate therapeutics since proposal submission, and to remove overlap with studies performed under other grants and contracts issued by the Government.

Question 16: Would a CMC heavy proposal be competitive, or would NIAID prefer to see a more blended range of activities (CMC, Biology, Clinical, Safety/Tox, PK/PD)?

Answer 16: Due to the competitive nature of the solicitation, NIAID is unable to provide guidance on specific proposed approach.

Question 17: Would an agent with limited Biodefense activity, but strong AMR activity be competitive?

Answer 17: A description of the solicited products under this Research Area is listed in Section

3.1.2.1.2 “Technical Objectives” of the BAA. Due to the competitive nature of the solicitation, NIAID is unable to provide guidance on specific proposed approach.

Question 18: Would an 18-month PoP be competitive to reviewers? Is it permissible to propose an accelerated project, that includes only activities encompassing a base period?

Answer 18: Offerors should propose activities that best fit its timelines and goals. It is permissible that a proposal include only a base period. Due to the competitive nature of the solicitation, NIAID is unable to provide guidance on specific proposed approach.

Question 19: Is developing more efficacious new analogs of FDA-approved host-targeted drugs, with structure modifications and/or combination of drugs which would alter the structure of the FDA-approved drugs, thus requiring FDA approval again, to treat infections caused by multi-antibiotic resistant pathogens of high public health significance considered non-responsive to this solicitation?

Answer 19: New analogs of FDA-approved drugs are eligible, if the candidate therapeutics or lead series exhibit all four characteristics that are listed in Section 3.1.2.1.2 “Technical Objectives” of the BAA: - Demonstrated feasibility of manufacturing, - In vitro and in vivo evidence of efficacy, - In vitro and in vivo evidence of acceptable preliminary pharmacokinetic, safety and toxicology, - Sufficient characterization to allow the development of a draft target product profile.

Combination of drugs is eligible under this BAA, if at least one component is a new molecular entity that is not an approved drug and exhibits all four characteristics listed above.

Question 20: We have a project funded through another source which will end soon with FIH

SAD and MAD studies. Are we eligible to apply for Phase 1 special PK studies followed by Phase 2 for this project?

Answer 20: As noted in the solicitation in Section 3.1.2.1.2, Offerors can submit proposals that include Phase 1, Phase 1/2 and/or Phase 2 clinical trial for candidate product. Phase 3 trials are not supported under this Research Area.

Question 21: Can NIAID clarify the following language in Section 3.1.2.1.2 of Research Area 001:

Research Area 001 will support the progression of candidate therapeutics or lead series through the product development pipeline toward IND submission and early phase clinical studies and development, which includes Phase I and Phase II. To that end, therapeutic candidates or lead series must show all of the following characteristics:

• Demonstrated feasibility of manufacturing;

• In vitro and in vivo evidence of efficacy;

• In vitro and in vivo evidence of acceptable preliminary pharmacokinetic, safety and toxicology; and

• Sufficient characterization to allow the development of a draft target product profile.

Does this mean that an Offeror must have all of those stages complete prior of submission, or does this mean that these are stages an awardee will have to complete if funded?

Answer 21: Candidate therapeutics or lead series must demonstrate all four characteristics to be eligible and proposals should describe these characteristics of candidate therapeutics or lead series.