HHS-NIH-NIAID-BAA2023-1 - Amendment Three.pdf

HHS-NIH-NIAID-BAA2023-1

Page 1 of 7 Amendment Three (3)

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2023 DMID Omnibus Broad Agency Announcement (BAA):

No. HHS-NIH-NIAID-BAA2023-1

Solicitation Amendment Three (3)

Issuing Office: OFFICE OF ACQUISITIONS

National Institute of Allergy and Infectious Diseases (NIAID)

5601 Fishers Lane, Room 3D38, MSC 9821

Bethesda, MD 20892-9821

Solicitation Number: HHS-NIH-NIAID-BAA2023-1

Date of Solicitation Issuance: January 11, 2023

Date of Amendment Three Issuance February 6, 2023

Number of Pages: Seven (7)

Proposal Due Dates: The hour and date specified for receipt of offers for each

Research Area remains unchanged:

RESEARCH

AREA

TITLE PROPOSALS DUE*

Development of Vaccine Candidates for

Biodefense and Emerging Infectious

Diseases

April 11, 2023

Development of Therapeutic Candidates for Biodefense, Antimicrobial Resistant

(AMR) Infections and Emerging

Infectious Diseases

The Antiviral Program for Pandemics

(APP): Development of Antivirals for

Specific RNA Viral Families of

Pandemic Potential

March 13, 2023

Development of In Vitro Diagnostics for

Biodefense, Antimicrobial Resistant

Infections (AMR), and Emerging

Infectious Diseases

* Proposals must be received before 3:00 PM Eastern Time on the date specified herein.

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Contracting Office Points of Contact:

Primary Contact:

Swee L. Teo, Contracting Officer

Email: teosl@niaid.nih.gov

Phone: 240-669-5173

Secondary Contact:

Ebony Taylor, Contract Specialist

Email: ebony.taylor@nih.gov

Phone: 240-292-0668

Offerors MUST acknowledge receipt of the amendment by Amendment number(s) and date of the amendment. Failure to receive your acknowledgment of this amendment may result in the rejection of your proposal.

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

PURPOSE OF AMENDMENT THREE (3)

The purpose of Amendment Three (3) is to:

I. Revise Section 3.3.3.2 – Technical Approach (page 13) of Research Area 003.

II. Provide the NIAID’s response to questions received regarding the solicitation. The responses are offered for information only and do not modify or become part of this solicitation. Additional amendments may be provided as needed to address further questions and their related responses.

I. REVISIONS TO HHS-NIH-NIAID-BAA2023-1 (highlighted in red):

Research Area 003 - Antiviral Program for Pandemics (APP): Development of Antivirals for

RNA Viral Families of Pandemic Potential

Section 3.3.3.2 – Technical Approach:

Research Area 003 will support lead optimization, pre-clinical (IND enabling) studies and clinical trials that include Phase 1 or Phase 2 studies or confirmatory trials of no greater than 120 subjects.

The scope of support differs depending on the stage of the project being proposed, as outlined below.

Development Activities in-scope for Research Area 003:

Lead Optimization

• Optimizing a lead series by generation of new analogs with improved indicators of potency, safety, pharmacokinetics, and physiochemical properties compatible with the

TPP

• Conducting non-Good Laboratory Practices (non-GLP) in vivo toxicology aligned with the TPP

• Conducting in vivo efficacy determination in animal models of diseases consistent with mailto:teosl@niaid.nih.gov mailto:ebony.taylor@nih.gov

Page 3 of 7 Amendment Three (3) the TPP

• Conducting experiments to identify pharmacokinetic/pharmacodynamic (PK/PD) relationships and define efficacious exposure targets for further pre-clinical and clinical studies

• Selecting a preclinical candidate and initiating IND-enabling studies

• Lead Optimization must be performed in the base period if proposed

Pre-Clinical (IND Enabling) Studies

• Demonstrating acceptable absorption, distribution, metabolism, and excretion (ADME) characteristics in non-GLP animal studies as necessary for IND filing

• Conducting GLP and non-GLP non-clinical studies for toxicology, pharmacology, and immunogenicity (as appropriate)

• Continuing development of animal models for determining efficacy and defining PK/PD relationships for further preclinical and clinical studies

• Developing a scalable and reproducible manufacturing process amenable to GMP

• Manufacturing non-GMP and GMP-compliant drug substance and drug product

• Developing in-process assays and analytical methods for product characterization and release, including assessments of potency, purity, identity, strength, sterility, and quality as appropriate

• Preparing and submitting an IND to the U.S. Food and Drug Administration (FDA)

Phase 1 Studies

• Conducting Phase 1 clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article in healthy volunteers

Phase 2 Studies

• Conducting Phase 2 clinical trials(s) to determine safety, pharmacokinetics, and efficacy of the clinical test article in patients. Phase 2 trial designs shall be no greater than 120 subjects

Proposals that do not include Lead Optimization are expected to complete evaluation in a Phase 1 or Phase 2 clinical trial within the 5-year proposed period of performance. Phase 1 and Phase 2 clinical trial completion is defined as completion of a Final Clinical Study Report following

International Conference on Harmonization (ICH) Guidelines on Structure and Content of Clinical

Study Reports E3 (https://www.fda.gov/media/71271/download).

II. GOVERNMENT’S RESPONSES TO QUESTIONS RECEIVED REGARDING THIS

SOLICITATION AREA AS FOLLOWS:

Please note, in the questions/responses below, specific organizational names have been removed or replaced where possible as well as other minor adjustments.

A. General Questions applicable to all Research Areas:

https://www.fda.gov/media/71271/download

Page 4 of 7 Amendment Three (3)

Question 1: Are offerors based at foreign organization eligible to submit a proposal for this solicitation, or is it only open to those based in the United States?

Response: This BAA is being solicited using full and open competition. All offerors, including foreign organizations, not otherwise prohibited by law are eligible to respond.

B. RESEARCH AREA 001

Question 1: Research Are 002 (therapeutics) covers C. difficile (CDC antibiotic resistance pathogen list). I would like to know whether Research Area 001 (vaccine development) covers C.

difficile?

Response: No, C. difficile would be non-responsive to Research Area 001 (Vaccine

Development). Please refer to Section 3.3.1.3 - Contracts awarded under this Research Area will

NOT support the following activities; proposals containing any of these activities will be excluded from peer review and will not be considered further for award: bullet point 5: Vaccines against bacterial pathogens. C. difficile is a bacterial pathogen and is therefore NOT supported under Research area 001.

C. RESEARCH AREA 002

Question 1: We are proposing possible interactions around our molecules for (i) influenza A virus (IAV) that is approaching IND readiness stage and (ii) BKV at lead optimization stage. Can both trials be included in a single application, with the understanding that release of the funds for the Phase 2a trial would be conditional upon successful completion of Phase 1?

Response: Since each molecule is distinct and at a different stage, each shall be submitted as a separate proposal. See Section 1 (page 4) of the BAA. If an offeror submits more than one proposal for a Research Area(s), the offeror should assure that the principal investigator, and all other personnel proposed, shall not be committed on federal grants and contracts for more than a total of 100% of their time. If the situation arises where it is determined that a proposed employee is committed for more than 100% of his or her time, the government will require action on the part of the offeror to correct the time commitment. See Section 4.3.2.2, Section 7 (page 50) of the BAA.

Question 1a: If separate applications are required, can these be separated in time, with the Phase

2a application submitted once Phase 1 is successful? That is, does NIAID envision multiple future dates at which applications can be submitted?

Response: For each proposal, an offeror may propose option(s) for each non-severable task. For example, an offeror may propose “IND Submission” for the Base Period and “Phase 1 Clinical

Trial” as an Option. When the prerequisite for an Option is met and at the discretion of the

Government, an Option may be exercised. Note that options are not required to follow sequentially from the Base period or a previous Option. Rather, each option should reflect a logically coherent set of tasks whose requirement is defined by certain prerequisites having been met during contract execution. It is possible for multiple Options and/or the Base period to be concurrent depending on the proposed design of the development program. See Section 4.3.2.2

(page 45) of the BAA. Nonetheless, the total performance period comprised of combined Base

Period and all Options proposed by an offeror shall not exceed five (5) years. See Section 3.2

(page 6) of the BAA.

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“Non-severable” means work resulting in a final product or end-item and for which benefit is received only when the project is complete, such as process development activities resulting in a product development report or efficacy studies sufficient to submit for regulatory approval of a candidate to enter clinical trials.

Question 1b: Should the BKV studies be filed in a separate application from the influenza studies, or can they be included in a single application?

Response: See response to Question 1 above.

Question 1c: If they should be separated, do both need to be submitted for the April deadline, or will there be a later date at which one could submit one of the applications?

Response: All proposals for Research Areas 001, 002, and 004 are due on April 11, 2023, 3:00pm Eastern Time.

Question 2: On page 6 of the program announcement, the sum of $12.8 million is mentioned. Do we understand correctly that this is the TOTAL appropriation that is intended to cover all approved applications in Research Areas 001, 002 and 004? Or is this the maximal size award that any individual enterprise may receive?

Response: The NIAID estimates a budget of up to $12.8 million to be divided among the non-severable Base periods only for all contract awards for Research Areas 001, 002, and 004, depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds. See Section 3.2 (page 6) of the BAA.

Question 3: If we were to submit a multi-PI plan targeting both vaccine development and antiviral drug development for RNA viruses, would the March 13th submission date apply for the antivirals and the April 11th submission date apply for the vaccines? How would this timing be worked out?

Response: Offerors may submit a proposal in response to one, or more, of the Research Areas contained in the BAA. See Section 1 (page 4) of the BAA. If you are proposing a vaccine development and an antiviral drug development, you must submit a proposal for Research Area

001 and a proposal for Research Area 003. The proposals due dates for RA 001 and RA 003 are

April 11, 2023, 3:00pm ET and March 13, 2023, 3:00pm ET, respectively. See page 1 and Section

4.3.2.1.1 (page 43) of the BAA.

An offeror may propose multiple principal investigators. See Section 4.3.2.2, Section 7 (page 48) of the BAA for details.

D. RESEARCH AREA 003

Question 1: Our question relates to eligibility for a proposal that would include preclinical studies (primarily toxicology), the preparation and submission of a new IND, and a clinical Phase

1 study for a candidate therapeutic treatment comprised of a combination or co-formulation of two small molecules. The profile for both small molecules and the combination/co-formulated product are compatible with the required product profile in Section 3.3.3.1 and i) act on a viral target (distinct mechanisms of action), ii) are compatible with oral dosing, iii) exhibit favorable in vitro and in vivo activities (and synergistic or additive activities in vitro and in vivo) against a

Page 6 of 7 Amendment Three (3) number the listed viruses of pandemic potential for which limited treatments exist, and existing independent preclinical and clinical data (INDs and Phase 1 data) would be available to facilitate and guide the new IND filing. Given that one of the small molecule agents is a novel agent that is not identical to any entity or part of any commercially available human consumable product, or approved for any human or veterinary use in any jurisdiction worldwide and has never been in a

Phase 3 clinical trial (addressing criteria 6 and 7 in Section 3.3.3.4), and neither have been approved in the US for any purpose, would our proposal be eligible for submission and funding?

Response: Yes, provided the proposal meets all criteria for Research Area 003

Question 2: Are nanobodies acceptable biotherapeutics that can be considered under research area 003.

Response: Yes.

E. RESEARCH AREA 004

Question 1: How long can the Base Period be?

Response: The total duration of the Base Period should be consistent with the nature and complexity of the offeror’s proposed research and may vary depending on the scope of the project and technical objectives. Further, for purposes of scheduling, Base and Option periods may overlap with development phases of a project’s product development. In proposing performance periods for the Base and each Option, an offeror should make reasonable estimate of the time in months needed to complete the activities under the Base and each Option. The total performance period comprising the combined Base Period and all Options proposed by an offeror shall not exceed five (5) years. See Section 3.2 (page 6) of the BAA.

Question 2: Is this solicitation open to Small Businesses without negotiated or audited indirect rates? It feels like a very detailed/heavy proposal lift but our technology is a 'direct hit' in terms of what the solicitation is calling for.

Response: This BAA is being solicited using full and open competition. All offerors, including small businesses, not otherwise prohibited by law are eligible to respond. Offerors are not required to have a negotiated indirect rate agreement or audited indirect rates in order to submit a proposal in response to this solicitation. However, an organization receiving an award will be required to negotiate an indirect rate agreement with their cognizant federal agency after contract award if an established indirect rate agreement is not already in place. Offerors who have negotiated rates with a cognizant federal agency must use their approved rates when preparing their project budgets.

Question 3: Does the budget of $12.8m for the anticipated 5-6 projects under Research Areas

001, 002, and 004 mean we should budget $2-2.5m annually for the Base Period, or is that budget amount meant to cover the entirety of the Base Period e.g. a two year Base Period would mean closer to $1-2m/year?

Response: The NIAID estimates a budget of up to $12.8 million to be divided among the non-severable Base periods only for all contract awards for Research Areas 001, 002, and 004, depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds. The total duration of the Base Period should be consistent with the

Page 7 of 7 Amendment Three (3) nature and complexity of the offeror’s proposed research and may vary depending on the scope of the project and technical objectives. See Section 3.2 (page 6) of the BAA.

For “non-severable” definition, please see response to Question 1a. under Research Area 002.

Question 4: Our company has a COVID/Flu diagnostic product. We would like to understand if

RSV inclusion in a COVID/Flu diagnostic test would be considered within the scope of “novel coronaviruses” mentioned in the Research Area 004 of the BAA?

Response: RSV inclusion in a COVID/Flu diagnostic test would be deemed out of scope, as RSV

(Paramyxoviridae) is not considered a novel coronavirus (Coronoaviridae), and therefore is not on the list of in-scope pathogen targets. See Sections 3.3.4.2 and 3.3.4.4 (pages 17-18) of the

BAA.