HHS-NIH-NIAID-BAA2025-1.pdf

Issuing Office: Office of Acquisitions, DEA, NIAID, NIH

5601 Fishers Lane, MSC 9821, Bethesda, MD 20892-9821

Issuing Contracting Officer: Swee L. Teo

Email: teosl@niaid.nih.gov

Phone: (240)-669-5173

This solicitation contains opportunities to submit a proposal under the following distinct Research Areas, which are identified below:

RESEARCH

AREA

TITLE PAGE

NO.

PROPOSALS DUE*

Development of Candidate

Therapeutics, Vaccines, and In Vitro

Diagnostics for Antimicrobial-Resistant

(AMR) Bacterial or Fungal Pathogens

February 21, 2025

Development of Direct Acting

Antivirals (DAA) for Viral Families of

Pandemic Potential

January 21, 2025

* Proposals must be received before 3:00 PM Eastern Daylight Time on the date specified herein. Please see the Proposal Submission Instructions (Section 4.3.2.1) for more information. For planning purposes, the

Government requests potential Offerors to submit a Notice of Intent. Please see Notice of Intent (Section

4.3.2.1.4) for more information.

Offers will be valid for 240 days unless a different period is specified by the Offeror on the Attachment entitled, "Proposal Summary and Data Record, NIH 2043”.

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2026 Division of Microbiology & Infectious Diseases (DMID)

Omnibus Broad Agency Announcement (BAA):

Development of Medical Countermeasures for Biodefense and

Emerging Infectious Diseases

No. HHS-NIH-NIAID-BAA2025-1

Solicitation Issue Date: November 22, 2024 mailto:teosl@niaid.nih.gov

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2026 DMID Omnibus Broad Agency Announcement

No. HHS-NIH-NIAID-BAA2025-1

TABLE OF CONTENTS

SECTION 1 – Broad Agency Announcement Information…………………………………………………….p. 4

SECTION 2 – Contracting Officer Point of Contact……………………………….………..…………….........p. 4

SECTION 3 – Research Areas and Technical Objectives……………………………….……..…..…………...p. 4

3.1 – Division of Microbiology and Infectious Diseases (DMID) Background………………….………p. 4

3.2 – Funding and Award Information………………………………...………...………………..………p. 5

3.3 – Research Areas

3.3.1 – Research Area 001: Development of Candidate Therapeutics, Vaccines and In Vitro

Diagnostics for Antimicrobial-Resistant (AMR) Bacterial or Fungal Pathogens…………….p. 6

3.3.1.1 – Topic A: Therapeutics for AMR Bacterial or Fungal Pathogens……………...p. 6

3.3.1.2 – Topic B: Vaccines for AMR Bacterial Pathogens……………………………..p. 9

3.3.1.3 – Topic C: In Vitro Diagnostics for Fungal Pathogens…………………………...p. 11

3.3.2 – Research Area 002: Development of Direct Acting Antivirals (DAA) for Viral

Families of Pandemic Potential ………………………….…………………………………...p. 12

3.4 – Research Areas 001 (Topics A and B) and 002: Additional Technical Proposal Instructions.........p. 16

3.5 – Research Areas 001 (Topics A and B) and 002: Reporting Requirements and Deliverables …….p. 19

3.6 – Research Area 001 (Topic C): Additional Technical Proposal Instructions ..…………………….p. 25

3.7 – Research Area 001 (Topic C): Reporting Requirements and Deliverables………………………p. 28

SECTION 4 – Instructions, Conditions, and Notice to Offerors……………………………………………….p. 30

4.1 – General Instructions to Offerors …………………………………………………………………...p. 30

4.2 – General Information………………………………………………………………………………p. 33

4.3 – Instructions to Offerors…………………………………………………………………………...p. 35

4.3.1 – General Information…………………………...………………...………...……...........p. 35

4.3.2 – Technical Proposal Instructions …………………………………………….…….…....p. 40

4.3.3 – Business Proposal Instructions……………………………………………………………p. 73

SECTION 5 – Special Contract Requirements………………………………………………………………....p. 88

SECTION 6 – Evaluation Factors for Award...……………………………………………………………….p. 117

SECTION 7 – Definitions…………………….……………………………………………………………….p. 124

SECTION 8 – Attachments…………………...……………………………………………………………….p. 125

SECTION 1. - BROAD AGENCY ANNOUNCEMENT INFORMATION

You are invited to submit a proposal in accordance with the requirements of this BROAD AGENCY

ANNOUNCEMENT (BAA). The BAA is governed by Federal Acquisition Regulation (FAR) 6.102 and further described in FAR 35.016 as well as the National Institutes of Health (NIH) Policy Manual, Manual Chapter

6035, Broad Agency Announcements. A BAA may be used as a solicitation mechanism for basic and applied research directed toward advancing the state-of-the-art or increasing knowledge or understanding and that part of development not related to the development of a specific system or hardware procurement. BAAs are general in nature, identifying areas of research interest, and shall only be used when meaningful proposals with varying technical/scientific approaches can be reasonably anticipated.

This BAA contains two (2) distinct Research Areas 001 and 002. For Research Area 001, there are three (3) separate Topics – A, B, and C. For Research Area 001, Offerors may submit a proposal in response to Topics

A, B, and/or C. Offerors may submit a proposal in response to one or both Research Areas contained herein.

Offers submitted in response to this BAA must present separate detailed technical and business proposals designed to meet the Technical Objectives described for each Research Area and/or Topic proposed. The Statement of Work (SOW), including the specific technical requirements and performance specifications, is developed and proposed by the Offeror, not the Government.

Proposals are NOT evaluated against each other since they are not submitted in accordance with a common

SOW issued by the Government. Instead, Research and Technical Objectives are provided in the BAA that describe individual Research Areas in which the Government is interested. Proposals received in response to the BAA are evaluated in accordance with the Evaluation Factors for Award specified in Section 6. The

Government reserves the right to conduct discussions about all, some, one, or none of the proposals received in response to this BAA. If discussions are conducted, the National Institute of Allergy and Infectious Diseases

(NIAID) reserves the right to suggest modifying, adding, or deleting milestones, decision points, research plans, processes, schedules, budgets, or products. The Government also reserves the right to make awards without discussions. Additionally, the Government reserves the right to accept proposals in their entirety or to select only portions of proposals for award. Multiple awards are anticipated. The selection for award under this BAA will be based upon the evaluation factors, agency priorities, and the availability of funds.

SECTION 2. - CONTRACTING OFFICER POINT OF CONTACT

This BAA contains Research Areas issued by the Division of Microbiology and Infectious Diseases (DMID) within NIAID. The Contracting Officer (CO) point of contact for questions is identified below.

Point of Contact:

Swee L. Teo

Contracting Officer

Email: teosl@niaid.nih.gov

Tel: 240-669-5173

SECTION 3. - RESEARCH AREAS AND TECHNICAL OBJECTIVES

3.1 – DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES (DMID) BACKGROUND

NIAID, one of 27 institutes of the NIH, an agency within the Department of Health and Human Services

(DHHS); conducts and supports research to understand, treat, and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives. Through a variety of research grants and contracts, NIAID’s DMID specifically supports extramural research to develop new medical countermeasures (MCMs) against potential agents of bioterrorism, drug-resistant pathogens, and emerging and re-emerging infectious diseases. This research addresses goals articulated in a number of mailto:teosl@niaid.nih.gov important biodefense and public health strategies, such as The 2022 National Biodefense Strategy and

Implementation Plan (https://www.whitehouse.gov/wp-content/uploads/2022/10/National-Biodefense-

Strategy-and-Implementation-Plan-Final.pdf ), NIAID’s Pandemic Preparedness Plan

(https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf), The World Health

Organization (WHO) R&D Blueprint for epidemics (https://www.who.int/blueprint/priority-diseases/en/), as well as prioritized pathogens to prevent and control antimicrobial resistance by both

WHO (https://www.who.int/publications/i/item/9789240093461) and the Centers for Disease Control and Prevention (CDC) (https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html)

In support of the goals articulated in the above strategies, NIAID intends to use this BAA to advance the research and development of promising candidate therapeutics, vaccines, and diagnostics for biodefense and emerging infectious diseases in each of two (2) Research Areas described in Section 3.3 below.

3.2 – FUNDING AND AWARD INFORMATION

Contract funding for therapeutic and vaccine development will support candidate testing, manufacturing, preclinical or nonclinical toxicology testing, and early clinical studies, which may include Phase I clinical trials; within funding and under special circumstances, platform trials that allow simultaneous comparison of multiple interventions groups against a single control group or a trial that includes sequential stages are permitted. Contract funding for diagnostics will support phases of in vitro diagnostic (IVD) product development from late-stage feasibility research through planning and design, development, up to and including final clinical validation. Contracts resulting from this BAA shall not reimburse costs incurred in connection with work performed outside the contract’s period of performance. Costs incurred before the contract’s effective date or after its completion date are unallowable and cannot be charged to the contract.

For both Research Areas, the total duration of a proposed contract 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 the technical objectives. The total performance period comprising the combined Base Requirement, and any

Options, if proposed by an Offeror, shall not exceed an estimated 5 years. If applicable, clinical trial activities are encouraged to start as soon as possible and be completed within the 5-year period. Revisions to the completion date will be considered by the Government during contract performance.

Research Area 001: For FY 26, NIAID estimates up to $8.5 million for the award of 1-2 cost reimbursement type base contracts in Research Area 001. The estimated FY 26 funding is for the non-severable Base Requirement (direct and indirect costs combined) only. If options are proposed by an

Offeror, they will be evaluated in accordance with Section 6 of the BAA. The number of awarded contracts will depend on the number of technically meritorious proposals, agency priorities, and availability of funds.

For Research Area 001, awards are anticipated to be made in or around May 2026. At the discretion of the

Government, awards may be streamlined to meet agency needs.

Research Area 002: For FY 26, NIAID estimates up to $20 million for the award of 3-4 cost reimbursement type base contracts in Research Area 002. The estimated FY 26 funding is for the non-severable Base Requirement (direct and indirect costs combined) only. If options are proposed by an

Offeror, they will be evaluated in accordance with Section 6 of the BAA. The number of awarded contracts will depend on the number of technically meritorious proposals, agency priorities and availability of funds.

For Research Area 002, awards are anticipated to be made in or around November 2025. At the discretion of the Government, awards may be streamlined to meet agency needs.

3.3 – RESEARCH AREAS

https://www.whitehouse.gov/wp-content/uploads/2022/10/National-Biodefense-Strategy-and-Implementation-Plan-Final.pdf https://www.whitehouse.gov/wp-content/uploads/2022/10/National-Biodefense-Strategy-and-Implementation-Plan-Final.pdf https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf https://www.who.int/blueprint/priority-diseases/en/ https://www.who.int/blueprint/priority-diseases/en/ https://www.who.int/publications/i/item/9789240093461 https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html

For Research Area 001, Offerors may submit a proposal in response to Topics A, B, and/or C. Offers must present separate detailed technical and business proposals designed to meet the Technical Objectives described for each Topic proposed.

3.3.1.1 – Topic A: Therapeutics for AMR Bacterial or Fungal Pathogens

3.3.1.1.1 - Technical Objectives

The objective of Topic A is to develop new therapeutic products against severe infections and/or drug-resistant strains of the following bacterial and fungal pathogens:

a. Pseudomonas aeruginosa, and/or Acinetobacter baumannii; OR

b. Candida auris, Cryptococcus spp., Aspergillus fumigatus, and/or Mucorales.

Important notice to Offerors: For this Topic, “therapeutic” activity refers to the cure of disease, by elimination or substantial reduction of infective pathogens, by administration of a pharmaceutical agent after symptoms of disease are clinically observable.

An antimicrobial therapeutic candidate refers to an advanced lead series, optimized leads, or product candidate, that is a new chemical entity and either a small molecule (e.g., natural products, nucleosides, or peptides of </= 40 amino acids), monoclonal antibody or a nanobody conjugate/fusion product, or a bacteriophage product. The following are not included: proteins, other biological entities, and conjugates of such entities (except monoclonal antibodies, nanobodies and bacteriophages).

3.3.1.1.2 – Technical Approach

This Topic will support lead optimization, pre-clinical Investigational New Drug (IND) enabling studies, and clinical Phase I trials of lead candidates with demonstrated therapeutic activities. For some pathogens, the development of a therapeutic product under the U.S. Food and Drug Administration’s

(FDA) Animal Rule will be supported. The scope of support differs depending on the developmental/

‘entry’ stage of the project being proposed, as outlined below:

Entry Point of the Proposal Desired End Point

Lead Optimization Selection of pre-clinical candidate(s) and completion of non-Good Laboratory Practice

(non-GLP) IND enabling activities with non-

Good Manufacturing Practice (non-GMP) manufacturing (3 years period of performance)

Pre-Clinical Candidate Completion of GLP IND enabling activities, GMP manufacturing and Phase I clinical trial (3-

5 years period of performance)

Clinical Candidate Completion of Phase I clinical trial (3 years period of performance)

3.3.1- Research Area 001 – Development of Candidate Therapeutics, Vaccines and In Vitro Diagnostics for Antimicrobial-Resistant (AMR)

Bacterial or Fungal Pathogens

Proposals that include Lead Optimization are expected to select a single pre-clinical candidate therapeutic by the end of the base period and complete non-GLP IND-enabling activities (non-GMP manufacturing) within 3 years of performance. Lead optimization activities must be performed within the base period. Projects that include lead optimization must not include a Phase I clinical trial.

Proposals that do not include Lead Optimization are expected to complete preclinical studies and evaluation in a Phase I clinical trial within the 3-5 years proposed period of performance. A clinical trial may be proposed only if a clinical candidate is identified at the time of contract award. The Government will consider any revision to the Phase I completion date beyond the 3 years during contract performance.

Proposals only seeking support for Phase I clinical trial conduct will also be considered if successful completion of all required IND-enabling studies is demonstrated.

Description of Activities within Each Development Stage:

Lead Optimization

• Optimizing a lead series by generation of new analogs with improved indicators of potency, safety, pharmacokinetics, and physiochemical properties compatible with the Target Product Profile (TPP).

• Conducting non-GLP in vivo toxicology aligned with the TPP.

• Conducting in vivo efficacy determination in animal models of diseases consistent with 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.

Pre-Clinical (IND Enabling) Studies

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

• Conducting non-GLP and 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 of the drug substance (DS) and drug product (DP).

• Manufacturing and stability testing of non-GMP and GMP-compliant DS and DP.

• 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 FDA.

Phase I Studies

• Conducting Phase I clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article.

3.3.1.1.3 - Additional Requirements

1. Stage-appropriate data must be provided. For proposals that include Lead Optimization, stage-appropriate data demonstrates achievement or near-achievement of lead (i.e., preclinical candidates) selection criteria by exemplars of the proposed lead series. For all other proposals, a single entity, the proposed preclinical candidate, or clinical candidate (i.e., drug substance or product) to be developed under the contract, must demonstrate achievement or potential to achieve all minimally acceptable criteria of the TPP.

2. In addition to proposal requirements in Sections 3.4 and 4 of this solicitation, proposals submitted to this Topic must include the following additional criteria and supporting data:

a. For non-bacteriophage products:

1. Complete chemical structure of the most advanced lead, preclinical, and clinical candidate, or, in the case of monoclonal antibody - or nanobody conjugates/fusion, a precise description of the product candidate composition. The proposal is confidential and the composition of matter pertaining to the proposal must be disclosed in the proposal.

2. Monoclonal antibody and nanobody conjugate/fusion production, purification, and release assay data. The purity and size of the nanobody product as detected; e.g., by

SDS-PAGE, size exclusion chromatography, etc.

3. Complete chemical structures or compositions for all entities for which experimental data is provided.

4. A Medicinal Chemistry Plan or a Protein Engineering Plan, to be executed in the base period of performance if Lead Optimization for small molecule- and monoclonal antibody, nanobody conjugate/fusion product, respectively, if applicable.

5. In vitro efficacy against the pathogenic target or targets identified in the TPP. In vitro efficacy against animal-adapted pathogens is acceptable with reasonable justification;

however, the proposal should include planned studies against clinically relevant pathogens identified in the TPP.

6. In vitro assessment of absorption, distribution, metabolism, excretion, and toxicity

(ADMET).

7. Therapeutic efficacy in an animal model of disease is relevant to the indication identified in the TPP. Efficacy testing must include studies where the first dose occurs after the challenge.

8. In vivo toxicology using a dosing route and regimen consistent with the TPP.

9. In vivo PK in a relevant species with a dosing route and regimen consistent with the

TPP.

b. For bacteriophage products:

1. Must be relevant to the indication identified in the TPP. Efficacy testing must include dosing after the challenge.

2. A full discussion on the characterization of the phage or phage cocktail product including, but not limited to, specificity, spectrum, complete phage sequence(s) and sequences of engineered genes, and confirmation of absence of deleterious genes,

3. Potential for toxicology requirements if the phage or phage cocktail product contains engineered genes.

4. Other relevant data on product purity, toxicity, tissue, distribution, PK, etc.

Offerors responding to this Topic, collectively with the proposed subcontractors and consultants, where applicable, must have documented expertise in drug discovery and development, including demonstrated knowledge of regulatory guidelines, and submission processes for candidate products directed against emerging infectious diseases.

3.3.1.1.4 - Contracts awarded under this Topic 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:

a. Basic research, including target validation, high throughput screening, mechanism elucidation, lead series discovery, hit-to-lead optimization, and in vitro assay development.

b. Development of a product that is prophylactic, post-exposure prophylactic, or otherwise not therapeutic.

c. Development of only backup candidates.

d. Development of a product from a known class that does not demonstrate, through data provided in the proposal, distinct and medically impactful differentiation from leading examples of the class.

e. Development of a product that is derived from, substantially similar to, or identical to an entity that has ever been part of a commercially available human consumable product in any jurisdiction worldwide. Such products include, but are not limited to, homeopathic remedies, traditional medicines, supplements, foodstuffs, tinctures, extracts, and sham treatments (placebos).

f. Development of a product that is derived from, substantially similar to, or identical to an entity that has ever entered a Phase III clinical trial or has been approved for human or veterinary use in any jurisdiction worldwide. Such products include, but are not limited to, combinations not containing a novel agent, prodrugs, alternate salt forms, crystal forms, formulations, dosing regimens, or clinical indications.

g. Development of a product that functions as a topical antiseptic.

h. Development of a product derived from serum.

i. Development of a device as the product or as a component of a product (such as a diagnostic or drug delivery device). Use of an existing device that does not require development is allowed.

j. Development of a product that is a probiotic, or a prebiotic, or which exerts its therapeutic effect by modification of, or interaction with, non-pathogenic commensal organisms (such as the intestinal microbiome).

k. Research involving human fetal tissue.

l. Development of therapeutic products for pathogens other than Pseudomonas aeruginosa, and/or

Acinetobacter baumannii; OR Candida auris, Cryptococcus spp., Aspergillus fumigatus, and/or

Mucorales.

3.3.1.2 – Topic B: Vaccines for AMR Bacterial Pathogens

3.3.1.2.1 – Technical Objectives

The objective of Topic B is to protect human health and well-being by advancing vaccine candidates for the following ESKAPE bacterial pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.

These opportunistic ESKAPE pathogens have been shown to acquire resistance determinants, resulting in antibiotic resistant infections. The development of vaccines against these microorganisms is critical, since vaccines reduce the need to use antimicrobials and antibiotics, and therefore, reduce the threat of antibiotic resistance.

3.3.1.2.2 – Technical Approach

Offerors may propose a vaccine against a single or multiple ESKAPE pathogens. NIAID reserves the right to negotiate vaccines for a single indication, multiple indications, and/or combined indications, balancing the faster, straightforward development and regulatory path of a single indication with flexibility and preparedness against multiple pathogens.

Encouraged are vaccine strategies utilizing technology platforms that ideally elicit a rapid onset of immunity following a single dose, provide a durable immune response, and are readily adaptable to other pathogens. Vaccine technologies that lessen logistical requirements, bypass supply chain limitations and/or cold chain requirements, are readily scalable, and elicit mucosal immunity (when appropriate) are of specific interest. These vaccine technologies and platforms may include, but are not limited to, novel adjuvant vaccine formulations and/or delivery platforms, nucleic acid-based technologies, viral vectors, and nanoparticle or virus-like particle (VLP) approaches.

The scope of this vaccine Topic covers the advancement of a promising lead candidate from pre-clinical testing through IND submission to the FDA, as well as Phase I clinical trial conduct.

For the purpose of this solicitation, the definition of a lead vaccine candidate is a candidate in which the antigen(s), adjuvant (if applicable), vaccine platform (e.g., mRNA, viral vector, subunit, etc.), and delivery route have been selected and are clinically relevant (i.e., intended for the final clinical product), for which proof-of-concept immunogenicity in relevant animal model(s) has already been demonstrated.

NIAID will prioritize technically acceptable proposals based on programmatic need, maturity of the candidate product, and risk/benefit assessment. The scope of work awarded will depend on the developmental stage of the clinically relevant lead vaccine candidate as demonstrated by the background and existing preliminary data provided in the proposal, such as:

1. Background on disease indication, gaps in corresponding medical countermeasure pipeline (if applicable)

2. Justification/rationale for antigen selection, immunogen design and/or platform selection including any seroepidemiology or efficacy data

3. Nonclinical immunogenicity data for the lead vaccine candidate

4. Evidence of proof-of-concept efficacy data in a relevant animal model and any other non-clinical efficacy studies, if available

5. Description of the current manufacturing processes sufficient to produce research grade material that could be scalable/amenable to current Good Manufacturing Practice (cGMP) production with targeted process development, or

6. Description of current cGMP production processes if known, including product characterization, assay development, formulation, and stability

7. Description of any existing well-characterized, quality-controlled assays, including potency assay(s)

8. Any IND-enabling toxicology study results

9. Any clinical data available for the lead candidate (antigen, adjuvant) and/or platform

Proposals must provide experimental plans on the lead vaccine candidate for the following:

1. A TPP and Product Development Plan (PDP) for the candidate product, including nonclinical, manufacturing, and regulatory activities to be undertaken

2. Non-clinical immunogenicity and efficacy studies and IND-enabling toxicology studies to support IND submission

3. Manufacture, release, and stability studies of research and cGMP Master Banks

4. Process development, manufacture, release, and stability studies of engineering and cGMP lots of product

5. Development of all assays (including potency) and reagents needed to support IND submission

6. Regulatory activities required to support proposed IND submission

7. Development, submission, and sponsorship of an IND/combination product application, including compliance with all regulatory requirements.

8. Phase I clinical trial synopsis/plan

Offerors responding to this Topic, collectively with the proposed subcontractors and consultants where applicable, must have documented expertise in vaccine development, including demonstrated knowledge of regulatory guidelines and submission processes for candidate products directed against emerging infectious diseases identified in the Technical Objectives.

3.3.1.2.3 - Contracts awarded under this Topic will NOT support the following activities. Proposals

a. Basic research and discovery of new series/candidates/products

b. Development of devices or diagnostics in the absence of a companion product

c. Development of therapeutics

d. Monoclonal antibodies, including those intended for prophylactic use

e. Trained immunity: vaccine candidates that do not elicit an antigen-specific adaptive immune response and that are unlikely to elicit a memory immune response that persists beyond 28 days

f. Vaccine candidates against pathogens other than ESKAPE bacterial pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species

3.3.1.3 – Topic C: In Vitro Diagnostics for AMR Fungal Pathogens

3.3.1.3.1 Technical Objectives

The objective of Topic C is to develop innovative platform technologies to speed the identification of infection from among a broad panel of fungi and to profile the phenotypic antifungal susceptibility. This emphasis aligns with NIAID’s goal of addressing persistent challenges in adequate clinical management associated with mycological infections and alleviating the burden of antifungal resistance.

Offerors may propose a multiplexed fungal species identification (ID) platform or a comprehensive antifungal susceptibility testing (AFST) platform or a platform that accomplishes a combination of both diagnostic functions. Proposed assay solutions may be on established, FDA-cleared systems or on de novo test systems that are currently in development and have not previously gone through regulatory clearance. Overall, Offerors are encouraged to submit proposals for innovative solutions that significantly improve existing capabilities for direct-from-blood or other biofluid detection and identification of fungal infection with phenotypic AFST.

Innovations in product development might include, but are not limited to:

• Faster sample prep methods leading to faster test turnaround times of < 1 hour for ID

• Faster, more comprehensive fungal-drug combination testing for antifungal susceptibility

• Highly multiplexed fungal identification capability, including broad genera and/or species differentiation, and associated resistance characterization

• Novel diagnostic approaches, including breath-based methods

• Higher sample testing throughput

• Analytical sensitivity approaching 1 CFU/mL, resulting in lower input volumes of whole blood or other specimen type

Funding preference will be given to diagnostic solutions that significantly expand beyond current fungal

IVD capabilities.

Priority Pathogens

The diagnostic test system must detect analytes from at least one, and preferably several, of the following agents and markers:

• Candida spp. and associated resistance markers

• Aspergillus fumigatus and associated resistance markers

• Coccidioides spp.

• Mucorales

3.3.1.3.2 – Technical Approach

Offerors should demonstrate through existing data and concept studies how their solution has the potential to impact the clinical management of fungal infections. Offerors should present sufficient and convincing proof-of-concept data that the proposed diagnostic method can detect the targeted pathogen analyte (i.e., from the list of agents and/or markers indicated as priority pathogens), preferably from a relevant clinical matrix (e.g., blood, urine, respiratory or skin swab, cerebrospinal fluid, or bronchoalveolar lavage).

Offerors responding to this Topic, collectively with their proposed subcontractors and consultants, where applicable, should have documented or proposed access to all reagents, facilities, and capabilities required to perform the proposed development work, such as antibodies or recombinant proteins, pathogen isolates, clinical samples, and biocontainment facilities. They should also have documented or planned expertise in all areas of product development to justify their capability to advance the development and validation of a candidate diagnostic through FDA clearance and commercial launch.

3.3.1.3.3 - Contracts awarded under this Topic will NOT support the following activities. Proposals

a. Development of a diagnostic ID or AFST that does not include at least one of the above-listed agents in the Priority Pathogens section: Candida spp., Aspergillus fumigatus, Coccidioides spp., and/or Mucorales.

b. Development of a diagnostic ID from a positive blood culture or isolate (growth plate).

c. Development of a diagnostic ID test that relies solely on host-response markers (antibodies, other proteins, or RNA).

d. Development of diagnostic ID test that will only be validated using surrogate organisms.

3.3.2 - Research Area 002 – Development of Direct Acting Antivirals

(DAA) for Viral Families of Pandemic Potential

3.3.2.1 - Technical Objectives

The coronavirus disease 2019 (COVID-19) pandemic has emphasized the need for a robust MCM development program, to include viruses of pandemic potential. To this end, NIAID published a pandemic preparedness plan (https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf plan.pdf) that supports the American Pandemic Preparedness Plan (APPP or AP3)

(https://www.whitehouse.gov/wp- content/uploads/2021/09/American-Pandemic-Preparedness-

Transforming-Our-Capabilities-Final-For- Web.pdf). The response to the COVID-19 pandemic built upon prior research and development by advancing antivirals that had been discovered and/or clinically tested against other viruses. Therefore, advancing more candidate antivirals through Phase I should accelerate future outbreak or pandemic responses. To address this need, this Research Area aims to develop safe and effective antivirals to combat viruses of pandemic potential, as well as to build sustainable platforms for targeted drug discovery and the development of a robust pipeline of candidates. Proposals MUST focus on antivirals that:

• Directly modify viral target function (not through the modulation of the host responses); AND

• Act by reducing viral burden in early stages of disease; AND

• Act against viruses of pandemic potential (i.e., Bunyaviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthopoxviridae, Paramyxoviridae, Picornaviridae, and Togaviridae); AND

• Are new chemical entities limited to small molecules (e.g., natural products, nucleosides, or peptides of </= 40 amino acids) and nanobody conjugates/fusion products that are directly acting on viral targets and functions (not through the modulation of the host responses); AND

• Have safety profiles and suitable routes of administration for broad outpatient use.

Proposed products are not required to be narrow-spectrum and may include other pathogens in their spectrum of activity, provided one of the listed pathogens is in the list above.

Important notice to Offerors: Research Area 002 only supports the development of therapeutic products. “Therapeutic” activity for this solicitation refers to the elimination or substantial reduction of infective pathogens by administration of a pharmaceutical agent after viral challenge.

Proposals are encouraged for the development of broad-spectrum small molecules or nanobody conjugate/fusion products, with activity against more than one member of a viral family or multiple viral families of pandemic potential listed below. Limited spectrum therapeutic candidates that target pandemic pathogens for which limited standard clinical treatment exists, or for which drug resistance poses a significant public health concern are eligible. “Pan-coronavirus” activity requires demonstrated in vivo efficacy against clinical strains of SARS-CoV-2 variants and MERS-CoV.

A “therapeutic” candidate refers to an advanced lead series, optimized leads, or product candidate, that is a new chemical entity and either a small molecule (e.g., natural products, nucleosides, or peptides of

</= 40 amino acids) or nanobody conjugate/fusion product. The following are not included: proteins, monoclonal antibodies, other biological entities, and conjugates of such entities.

Antivirals must act against infection caused by at least one of the viral families (with example viruses) below:

• Bunyaviridae (e.g., Lassa, Junin, Rift Valley Fever Virus, Andes, Sin Nombre, LaCrosse, California Encephalitis, Crimean Congo Hemorrhagic Fever)

• Coronaviridae (e.g., SARS-CoV-2, MERS-CoV)

• Filoviruses (e.g., Ebola, Sudan, Marburg)

• Flaviviruses (e.g., Dengue, Zika, West Nile)

• Orthopoxviridae (e.g., mpox, pan-orthopox)

• Paramyxoviridae (e.g., Nipah, Hendra)

• Picornaviridae (e.g., EV-D68, EV-A71)

• Togaviridae (e.g., Chikungunya, EEE, VEE, WEE) https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf https://www.whitehouse.gov/wp-content/uploads/2021/09/American-Pandemic-Preparedness-Transforming-Our-Capabilities-Final-For-Web.pdf https://www.whitehouse.gov/wp-content/uploads/2021/09/American-Pandemic-Preparedness-Transforming-Our-Capabilities-Final-For-Web.pdf https://www.whitehouse.gov/wp-content/uploads/2021/09/American-Pandemic-Preparedness-Transforming-Our-Capabilities-Final-For-Web.pdf https://www.whitehouse.gov/wp-content/uploads/2021/09/American-Pandemic-Preparedness-Transforming-Our-Capabilities-Final-For-Web.pdf

3.3.2.2 - Technical Approach

Research Area 002 will support lead optimization, pre-clinical (IND enabling) studies, and/or Phase I clinical trials. The scope of support differs depending on the proposed project stage, as outlined below.

Proposed products are not required to be narrow-spectrum and may include other pathogens in their spectrum of activity, provided one of the listed pathogens is in the primary indication of the proposed

TPP. Product development under the FDA’s Animal Rule (21 CFR 314 subpart I) will be supported if appropriate to the proposed pathogen target.

Entry Point of the Proposal Desired End Point

Lead Optimization Selection of pre-clinical candidate(s) and completion of non-GLP IND enabling activities with non-GMP manufacturing (3 years period of performance)

Pre-Clinical Candidate Completion of GLP IND enabling activities, GMP manufacturing and Phase I clinical trial (3-

5 years period of performance)

Clinical Candidate Completion of Phase I clinical trial (3 years period of performance)

Proposals that include Lead Optimization are expected to select a single pre-clinical candidate therapeutic by the end of the base period and complete non-GLP IND-enabling activities (non-GMP manufacturing) within 3 years of performance. Lead Optimization must be performed only in the base period, if proposed. Proposals that include Lead Optimization must not include a clinical trial.

Proposals that do not include Lead Optimization are expected to complete preclinical studies and evaluation in a Phase I clinical trial within the 3-5 years proposed period of performance. A clinical trial may be proposed only if a clinical candidate is identified at the time of contract award. The Government will consider any revision to the Phase I completion date beyond the 3 years during contract

Proposals only seeking support for Phase I clinical trial conduct will also be considered if successful completion of all required IND-enabling studies is demonstrated.

Description of Activities within Each Development Stage:

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-GLP in vivo toxicology aligned with the TPP.

• Conducting in vivo efficacy determination in animal models of diseases consistent with the TPP.

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

• Selecting a preclinical candidate and initiating IND-enabling studies, not including GMP manufacturing of DP.

Pre-Clinical (IND Enabling) Studies

• Demonstrating acceptable 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 of

DS and DP.

• Manufacturing and stability testing of non-GMP and GMP-compliant DS and DP.

• 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 application to the FDA.

Phase I Studies. Conducting Phase I clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article.

3.3.2.3 – Additional Requirements

1. Stage-appropriate data must be provided. For proposals that include Lead Optimization, stage-appropriate data demonstrates achievement or near-achievement of preclinical candidate selection criteria by exemplars of the proposed lead series. For all other proposals, a single entity, the proposed preclinical candidate, or product to be developed under the contract, must demonstrate achievement or potential to achieve all minimally acceptable criteria of the TPP.

2. In addition to proposal requirements in Sections 3.4 and 4 of this solicitation, proposals submitted to this Research Area must include the following additional criteria and supporting data:

• Complete chemical structure of the most advanced lead or preclinical candidate or, in the case of nanobodies, a precise description of the product candidate composition, particularly for a cocktail product. The proposal is confidential and the composition of matter pertaining to the proposal must be disclosed in the proposal.

• Complete chemical structures or compositions for all entities for which experimental data is provided.

• A Medicinal Chemistry Plan or a Protein Engineering Plan to be executed in the base period of performance if Lead Optimization for small molecule and nanobody conjugate/fusion product, respectively, if applicable.

• Nanobody conjugate/fusion production, purification, and release assay data. The purity and size of the nanobody product as detected e.g. by SDS-PAGE, size exclusion chromatography, etc.

• In vitro efficacy and mode of action characterization against the pathogenic target or targets identified in the TPP. The antiviral characterization using animal-adapted pathogens is acceptable with reasonable justification; however, the proposal should include planned studies against clinically relevant pathogens identified in the TPP.

• In vitro assessment of ADMET.

• Therapeutic efficacy in an animal model of infection is relevant to the indication identified in the TPP. Efficacy testing must include a study where the first dose occurs after the challenge.

• In vivo toxicology using a dosing route and regimen consistent with the TPP.

• In vivo PK in a relevant species with a dosing route and regimen consistent with the TPP.

Offerors responding to this Research Area, collectively with the proposed subcontractors and consultants where applicable, must have documented expertise in drug discovery and development, including demonstrated knowledge of regulatory guidelines, and submission processes for candidate products.

3.3.2.4 – 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:

a. Development of a product not in the scope of the Research Area 2 description.

b. Development of a biological product such as protein, monoclonal antibody, and their conjugates

(except nanobody-based products).

c. Basic Research includes target validation, high throughput screening, mechanism elucidation, lead series discovery, hit-to-lead optimization, and in vitro assay development.

d. Development of a product that is prophylactic or otherwise not “therapeutic” as defined in section

3.3.2.1.

e. Development of a product from a known class that does not demonstrate, through data provided in the proposal, distinct and medically impactful differentiation from leading examples of the class.

f. Development of a product that is derived from, substantially similar or identical to, an entity that has ever been part of a commercially available human consumable product in any jurisdiction worldwide. Such products include, but are not limited to, homeopathic remedies, traditional medicines, supplements, foodstuffs, tinctures, extracts, and sham treatments (placebos).

g. Development of a product that is derived from, substantially similar to, or identical to an entity that has ever entered a Phase III clinical trial or has been approved for human or veterinary use in any jurisdiction worldwide. Such products include, but are not limited to, combinations not containing a novel agent, prodrugs, alternate salt forms, crystal forms, formulations, dosing regimens, or clinical indications.

h. Development of a product that functions as a topical antiseptic.

i. Development of a product derived from serum.

j. Development of a device as the product or as a component of a product (such as a diagnostic or drug delivery device). Use of an existing device that does not require development is allowed.

k. Development of a product that is a probiotic or prebiotic or which exerts its therapeutic effect by modification of, or interaction with, non-pathogenic commensal organisms (such as the intestinal microbiome).

l. Development of a product using monoclonal antibodies.

m. Development of only backup candidates.

n. Research involving human fetal tissue.

3.4 – RESEARCH AREAS 001 (Topics A and B) AND 002 - ADDITIONAL TECHNICAL

PROPOSAL INSTRUCTIONS

The following information supplements Section 4 – Instructions, Conditions, and Notices to Offerors of this solicitation, and should be used for preparing proposals in response to Research Area 001 (Topics A and B) and 002. Separate and distinct proposals must be submitted for each Research Area and/or Topic to which you are proposing.

3.4.1 - CLINICAL TRIAL PROTOCOL DEVELOPMENT AND IMPLEMENTATION

Human subjects research may be carried out under this contract with the approval of DMID. A clinical trial can be conducted within the U.S. and/or globally. If successful, clearance by the State Department must be obtained prior to awarding a foreign contract, a foreign subcontract, or a domestic contract with a foreign component.

Describe experience in the conduct of human subjects research and clinical trials in accordance with DMID, NIAID, and NIH policies and guidelines and provide a statement acknowledging willingness to conduct clinical research according to these policies and in accordance with applicable International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and FDA regulations and guidance. NIH policy is published at https://grants.nih.gov/policy/clinical-trials.htm; NIAID policy can be found at https://www.niaid.nih.gov/research/niaid-clinical-research-standards; DMID forms and policies are at https://www.niaid.nih.gov/research/dmid-clinical-research-policies. A synopsis of Instructions for the Conduct of Contractor-Held IND Clinical Trials Performed under a Contract can be found here

(https://www.niaid.nih.gov/sites/default/files/baaclinical.pdf). Upon completion of protocol development, DMID will determine if the Offeror will hold the IND and conduct the clinical trial, using the form “Request to Sponsor an IND/IDE for a DMID-Funded Clinical Trial.” The form will be included as an attachment to the contract award.

Provide a Protocol Synopsis for each proposed clinical trial, including a brief description of the following:

• Study objectives and endpoints

• Human subjects protections

• Provisions for data monitoring and safety reports

• Draft inclusion/exclusion criteria and recruitment, and retention of study participants

• Planned enrollment by racial and ethnic categories and sex

• Summary of statistical approaches

• Platform trials proposed must include details about the interventions to be included. Platform trials must contain sufficient detail to assess the totality of planned interventions and overall study size.

Document experience of the Offeror and any proposed subcontractor(s) and consultant(s) with designing early phase clinical trials, executing early phase clinical trials and managing early phase clinical trials in compliance with regulatory requirements and GCP.

Provide a plan that specifies at which points in the SOW it will be critical to engage in communications with the FDA and the means by which NIAID will be kept apprised of such communications.

3.4.2 - REGULATORY COMPLIANCE, QUALITY CONTROL & ASSURANCE, AND

DATA MANAGEMENT

• Describe the data management and quality control systems/procedures that will be used for all studies and procedures in accordance with 21 Code of Federal Regulations (CFR) 11.

• Describe the statistical design and analysis resources that will be used to support contract activities.

• Provide a plan to develop and maintain quality assurance documentation to support adherence to FDA regulatory standards and guidance.

• Document experience of the Offeror and any proposed subcontractors and consultants experience with performing regulated studies in accordance with FDA regulations and guidance, including GLP, cGMP, and/or GCP guidelines as appropriate to their proposed SOW.

• Provide an audit history and audit plan to determine when audits need to be performed, timely scheduling of audits, performance of audits, and responding to audit reports.

• Additional NIAID audits may be performed on nonclinical studies for products anticipating market approval under the FDA Animal Rule.

3.4.3 -…