HHS-NIH-NIAID-BAA-2024-1pdf.pdf

Issuing Office:

Issuing Contracting Officer:

Office of Acquisitions, DEA, NIAID, NIH 5601 Fishers Lane, Room 3D38, MSC 9821, Bethesda, MD 20892-9821

Alexandra J. Buck, JD Email: NIAID_DMIDOmnibusBAAQuestions@nih.gov

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*

001 Vaccine Candidates 5 March 12, 2024

002 Therapeutic Candidates 8 March 12, 2024

003 In Vitro Diagnostics 12 March 12, 2024

* 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)

2024 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-BAA2024-1

Solicitation Issue Date: December 13, 2023

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2024 DMID Omnibus Broad Agency Announcement

No. HHS-NIH-NIAID-BAA2024-1

TABLE OF CONTENTS

SECTION 1 – Broad Agency Announcement Information……………………………….………..………… p. 3

SECTION 2 – Contracting Officer Points of Contact……………………………….………..……………... p. 3

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: Vaccine Candidates ……………………………………….............. p. 5

3.3.2 – Research Area 002: Therapeutic Candidates ………………………….…………….. p. 8

3.3.3 – Research Area 003: In Vitro Diagnostics……………………………………………. p. 12

3.4 – Research Areas 001 and 002: Additional Technical Proposal Instructions ……….……….......... p. 15

3.5 – Research Areas 001 and 002: Reporting Requirements and Deliverables ……........….….……. p. 18

3.6 – Research Area 003: Additional Technical Proposal Instructions …………...………………….. p. 23

3.7 – Research Area 003: Reporting Requirements and Deliverables……………………………….. p. 27

SECTION 4 – Instructions, Conditions, and Notice to Offerors……………………………………………… p. 29

4.1 – General Instructions to Offerors …………………………………………………………………. p. 29

4.2 – General Information…………………………………………………………………………….. p. 32

4.3 – Instructions to Offerors…………………………………………………………………………. p. 34

4.3.1 – General Information…………………………...………………...………...……......... p. 34

4.3.2 – Technical Proposal Instructions …………………………………………….…….…. p. 39

4.3.3 – Business Proposal Instructions………………………………………………………….. p. 71

SECTION 5 – Special Contract Requirements………………………………………………………………... p. 87

SECTION 6 – Evaluation Factors for Award...……………………………………………………………….. p. 114

SECTION 7 – Definitions…………………….……………………………………………………………….. p. 122

SECTION 8 – Attachments…………………...……………………………………………………………….. p. 123

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 multiple distinct Research Areas. Offerors may submit a proposal in response to one, or more, of the 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 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 with all, some, one, or none of the proposals received in response to this BAA. If discussions are conducted, 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 the NIAID. The Contracting Officer (CO) point of contact for questions is identified below.

Please note, any correspondences regarding the BAA solicitation, including business and/or technical questions in addition to Notice of Intent letters, must be directed to the Contracting Officer in writing via the following Omnibus BAA email address: NIAID_DMIDOmnibusBAAQuestions@nih.gov .

Point of Contact:

Alexandra J. Buck, JD Contracting Officer Email: NIAID_DMIDOmnibusBAAQuestions@nih.gov

SECTION 3. - RESEARCH AREAS AND TECHNICAL OBJECTIVES

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

Research supported by the National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Department of Health and Human Services (DHHS), strives to understand, treat, and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives. NIAID also has a key role in the development of new medical countermeasures (MCMs) against potential agents of bioterrorism, drug-resistant pathogens, and emerging and re-emerging infectious diseases. Through a variety of research grants and contracts, NIAID’s Division of Microbiology and Infectious Diseases (DMID) supports basic and applied research to develop and evaluate therapeutics, vaccines, and diagnostics targeting multiple pathogens, including NIAID Emerging Infectious Diseases/Pathogens which encompass Category A, B, and C priority pathogens (https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens).

NIAID/DMID intends to use this BAA to help address goals articulated in a number of strategic plans to include pandemic preparedness. The National Biodefense Strategy and Implementation Plan released in October 2022 (https://www.whitehouse.gov/wp-content/uploads/2022/10/National-Biodefense-Strategy-and-Implementation-Plan-Final.pdf ) articulates the need to enhance preparedness through MCMs, including vaccines, therapeutics, and diagnostics. The World Health Organization (WHO) has prioritized diseases with epidemic potential and for which there are no or insufficient MCMs (https://www.who.int/blueprint/priority-diseases/en/), as well as pathogenic bacteria for which new antibiotics are currently urgently needed (https://www.who.int/publications/i/item/WHO-EMP-IAU-

2017.12 ). Similarly, the Centers for Disease Control and Prevention (CDC) has highlighted antibiotic resistant infections caused by urgent, serious, and concerning pathogens (https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf).

The coronavirus disease 2019 (COVID-19) pandemic has emphasized the need for a robust MCM development program, to include research resources and flexible platform technologies, aimed at preparedness against ribonucleic acid (RNA) viruses of pandemic potential. To this end, NIAID published a pandemic preparedness plan (https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf) that aims to develop countermeasures for prototype pathogens identified for each key RNA virus family that causes human disease and has high, pandemic potential. The viral families and prototype pathogens are outlined in a publication by NIAID leadership with input from the research community (https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac296/6649664. The NIAID pandemic preparedness plan contributes to 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 COVID-19 pandemic also highlighted the urgent need to develop safe and effective antivirals to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes COVID-19, and the necessity to identify and develop sustainable platforms for targeted drug discovery and generate a robust pipeline of antivirals against viruses of pandemic potential. To address this gap, the Antiviral Program for Pandemics (APP) (https://www.niaid.nih.gov/research/antivirals) was created to address the RNA virus families of pandemic potential. To protect people against Coccidioides infection, the NIAID Strategic Plan for Research to Develop a Valley Fever Vaccine reflects the NIAID research priorities for developing a Valley fever vaccine (https://www.niaid.nih.gov/sites/default/files/niaid-strategic-plan-for-research-to-develop-a-valley-fever-vaccine9.9.22.pdf).

Through this BAA, NIAID aims to advance the research and development of promising candidate vaccines, therapeutics and diagnostics for biodefense and emerging infectious diseases in each of three (3) Research Areas described in Section 3.3 below. NIAID BAA contracts advance products through early clinical trials, thereby reducing risk and becoming eligible for advanced clinical and manufacturing development funding.

3.2 – FUNDING AND AWARD INFORMATION

Contract funding for vaccine and therapeutic development will support candidate testing, manufacture, preclinical or nonclinical toxicology testing, and early clinical studies which may include Phase 1 and/or Phase 2 clinical trials; within funding and under special circumstances, platform trials that allow simultaneous comparison of multiple intervention 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 all 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 upon the scope of the project and the technical objectives. The total performance period comprising the combined Base Requirement and all Options 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 Areas 001, 002, and 003: For FY 25, the NIAID estimates up to $16 million for the award of 5 cost reimbursement type base contracts across all three Research Areas (001, 002 & 003). The estimated FY 25 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 Areas 001, 002, and 003, awards are anticipated to be made in or around May 2025. At the discretion of the Government, awards may be streamlined to meet agency needs.

3.3 – RESEARCH AREAS

3.3.1.1 – Technical Objectives

The goal of Research Area 001 is to protect human health and well-being by advancing specific vaccine candidates that utilize technology platforms that ideally elicit a rapid onset of immunity following a single dose, provide a durable response and are readily adaptable to multiple emerging pathogens. These vaccine technologies and platforms may include, but are not limited to, any of the following: novel adjuvant vaccine formulations, delivery platforms that are scalable or produce mucosal immunity, nucleic acid-based platforms, viral vectors, and nanoparticle/VLP approaches.

This research area is restricted to the following:

1. NIAID Emerging Infectious Diseases/Pathogens listed in Categories A-C

(https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens), with selected pathogens of special interest:

a. Improved vaccines for B. pertussis

3.3.1- Research Area 001 – Vaccine Candidates

b. Next generation vaccines for Vibrio cholerae.

c. Valley Fever (Coccidioidomycosis)

2. Urgent and serious antimicrobial resistance (AMR) threat pathogens as defined by the CDC (https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf). This research area will focus on vaccine candidates for the following AMR threats:

BACTERIA FUNGI

Urgent Threats Serious Threats

Acinetobacter baumannii* Campylobacter Candida auris

Clostridioides difficile Enterococci* Aspergillus fumigatus

Neisseria gonorrhoeae Pseudomonas aeruginosa* Candida spp

Enterobacterales* Nontyphoidal Salmonella

Salmonella serotype Typhi

Shigella

Staphylococcus aureus*

Streptococcus pneumoniae

Non-tubercular mycobacteria (NTM)

*ESKAPE Pathogens

Vaccine candidates capable of providing broad protection against multiple serotypes or species are of specific interest. Preference will be given to combination vaccines to protect against two or more enteric bacterial pathogens, i.e., Campylobacter, Shigella, Salmonella (iNTS, paratyphi A.); quadrivalent Shigella vaccines;

combination Salmonella vaccines, and improved vaccines for S. pneumoniae. Vaccines candidates for the prevention of life-threatening invasive fungal pathogens (e.g., Aspergillus, Candida) are also of special interest.

3. RNA viruses of pandemic potential. Preference will be given to vaccine platform technologies that are “plug-and-play” or “programmable”, capable of rapid swapping in of different antigens (e.g., new emerging variants, different viral antigens), rapid manufacturing and scale-up, and quick deployment in a pandemic consistent with Goal 1.1 of “American Pandemic Preparedness: Transforming Our Capabilities” (https://www.whitehouse.gov/wp-content/uploads/2021/09/American-Pandemic-Preparedness- Transforming-Our-Capabilities-Final-For-Web.pdf?page=29): “Vaccine design, testing, and authorization: Enable design, testing, and review of a safe and effective vaccine against any human virus within 100 days after the recognition of a potential emerging pandemic threat.” Preference will also be given to vaccine candidates capable of providing any of the following: durable protection, rapid onset to protection, greater breadth of protection (e.g., across different viral variants or species), elicitation of mucosal immunity in the case of respiratory viral pathogens. This research area will support vaccine candidates against any of the following viral families/orders:

a. Coronaviridae In the case of beta-coronaviruses, vaccine candidates must have one or more of the following attributes: capable of providing durable protection and/or immunity (superior to licensed vaccines for SARS-CoV-2) as well as breadth of immunity (i.e., high titer binding and neutralizing antibodies against recently circulating SARS-CoV-2 Variants of Concern, and SARS-CoV-1); incorporate novel immunogens or delivery platforms; elicit mucosal immunity.

b. Orthomyxoviridae (special emphasis on universal influenza; pandemic influenza—e.g., H5, H7).

c. Bunyavirales:

Arenaviridae Hantaviridae Nairoviridae

Phenuiviridae Peribunyaviridae

d. Paramyxoviridae

e. Picornaviridae

f. Flaviviridae

g. Togaviridae

3.3.1.2. – Technical Approach

Research Area 001 focuses on the advancement of a promising lead vaccine candidate from pre-clinical testing through evaluation in a Phase 1 and/or Phase 2 clinical trial. A lead vaccine candidate is defined by the following criteria:

1. Antigen, adjuvant (if applicable), and delivery route have been selected and are clinically relevant Preliminary data with clinically relevant vaccine candidate has demonstrated proof-of-concept immunogenicity in relevant animal model(s). Preliminary proof of concept immunogenicity data must be included for the same lead vaccine candidate (same pathogen) that is being proposed for the BAA proposal/submission.

2. Prefer, but do not require, evidence of proof-of-concept efficacy data in a relevant animal model.

3. Platform has been defined and is appropriate to support Phase 1 and/or 2 clinical trials.

4. Prefer, but do not require, a defined manufacturing process.

5. Prefer, but do not require, characterization of the lead candidate using well-characterized, quality-controlled assays including potency assay(s).

Proposals shall provide data on the lead vaccine candidate and experimental plans for the following:

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 data.

3. Characterization and optimization of the lead vaccine candidate.

4. Non-clinical immunogenicity and efficacy studies (to include 2. and 3. from the paragraph above) and Investigational New Drug (IND)-enabling toxicology studies.

5. Any clinical data available for the lead candidate and/or platform.

6. A Clinical Development Plan and Technical Development Plan for the candidate product, including nonclinical, manufacturing, regulatory, and clinical activities to be undertaken.

7. Description of current production processes including product characterization, assay development, formulation, and stability.

8. Process development and manufacture of non-GMP and GMP lots of product, if applicable.

9. Regulatory activities required to support proposed clinical trials.

10. Development of all assays and reagents needed to support clinical trials.

11. Clinical trial plan (proposals must include a clinical trial as part of the technical approach and statement of work).

Note: Upon completion of protocol development, DMID will determine if the offeror will hold the IND and conduct the clinical trial.

Note: Phase 2 trial designs shall be limited, e.g., 120 subjects.

12. A provision of human samples from all studies to be delivered to NIAID and, for subjects in clinical trials, obtaining future use consent form from volunteers for evaluation of their samples.

Offerors may propose a vaccine against a single pathogen or multiple 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.

Adjuvant formulations and/or delivery platforms that reduce dosing requirements, lessen logistical requirements, bypass supply chain limitations, are readily scalable, and/or provide other benefits such as generation of potent mucosal immunity, are of specific interest. Cross-cutting technologies applicable to more than one vaccine component are also encouraged.

Organizations responding to this Research Area, 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 and/or biological threats identified in the Technical Objectives. An offeror may propose a foreign subcontractor, not otherwise prohibited by law, to perform animal studies. 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. Additionally, a written animal welfare assurance approval from the NIH Office of Laboratory Animal Welfare (OLAW) is required prior to the initiation of an animal study conducted domestically or globally. See Sections 4.3.2.4, 4.3.2.5, 5.30, 5.31, and 6.6 of the BAA.

Proposals are expected to complete clinical evaluation within the 5-year period. Any revision to the completion date beyond the 5-year period will be considered by the Government during contract performance. Within funding and under special circumstances, platform trials that allow simultaneous comparison of multiple intervention groups against a single control group or a trial that includes sequential stages are permitted.

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:

1. Basic research, selection of antigen or platform, and discovery of new candidates/products.

2. Development of devices, diagnostics, or adjuvants in the absence of a companion vaccine antigen.

3. Development of therapeutics.

4. Vaccine candidates against viral, bacterial, or fungal pathogens not specifically listed in 3.3.1.1, above.

5. The BAA does not support early-stage vector development.

6. Research involving the use of Human Fetal Tissue.

7. Trained immunity: vaccine candidates or immunoprophylactics that do not elicit an antigen-specific adaptive immune response.

8. Bacillus anthracis (anthrax)

9. Modified Vaccinia Ankara (MVA)-based technologies for Orthopoxviruses (e.g., smallpox, Mpox), and

Orthopoxvirus vaccine candidates that are not suitable for all ages and the immunocompromised.

10. Clostridium botulinum toxin (botulism),

11. Zaire ebolavirus

12. Adenovirus, Modified Vaccinia Ankara (MVA), and recombinant vesicular stomatitis virus (rVSV) vectored vaccine platforms for filoviruses.

13. Filovirus vaccine candidates that fail to demonstrate efficacy after a single dose in a relevant animal model using wild type challenge virus.

3.3.2 - Research Area 002 – Therapeutic Candidates

3.3.2.1 - Technical Objectives

The objective of Research Area 002 is the development of new therapeutic products for diseases caused by specific viral, bacterial and fungal pathogens and their drug resistant variants in the following list:

Viral Hemorrhagic Fever viruses (e.g.. https://www.cdc.gov/vhf/index.html) Coronaviruses, targeting a novel mechanism of action (MOA) different from SARS-CoV-2 approved drugs or with demonstrated pan-coronavirus activity Pseudomonas aeruginosa Candida auris, Aspergillus fumigatus or Mucorales

Important notice to Offerors: Research Area 002 only supports development of therapeutic products.

“Therapeutic” activity refers to elimination or substantial reduction of infective pathogens by administration of a pharmaceutical agent after challenge. “Pan-coronavirus” activity requires demonstrated SARS-CoV-1, SARS- CoV-2 and MERS-CoV activity.

A candidate therapeutic may be a lead series, a preclinical candidate, or a clinical candidate. The product must be based on a small molecule (e.g., natural products, nucleosides, oligonucleotides or peptides) or bacteriophages. The following are not included: proteins, monoclonal antibodies, other biologic entities (except bacteriophages), and conjugates of such entities.

3.3.2.2 - Technical Approach

Proposals are required to address at least one of the pathogens in the following list. 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 Target Product Profile (TPP).

Viral Hemorrhagic Fever viruses (https://www.cdc.gov/vhf/index.html) Coronaviruses, targeting a novel mechanism of action (MOA) different from SARS-CoV-2 approved drugs or with demonstrated pan-coronavirus activity Pseudomonas aeruginosa Candida auris, Aspergillus fumigatus or Mucorales

Research Area 002 will support lead optimization, pre-clinical (IND enabling) studies and clinical trials that include Phase 1 and/or Phase 2 studies or confirmatory trials of a limited size, e.g., 120 subjects. For some pathogens, product efficacy determination under the Animal Rule is supported. Within funding and under special circumstances, platform trials that allow simultaneous comparison of multiple intervention groups against a single control group or a trial that includes sequential stages are permitted.

Development Activities in-scope for Research Area 002:

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-Good Laboratory Practices (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.

Proposals that include Lead Optimization must not include a clinical trial.

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.

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 limited in size, e.g., 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. Any revision to the completion date beyond the 5-year period will be considered by the Government during contract performance. A clinical trial may be proposed only if a preclinical candidate will be identified at the time of contract award.

Proposals that include Lead Optimization are expected to provide clear plans and criteria for selecting a single clinical candidate therapeutic by the end of the base period of funding to enable completion of IND-enabling activities and submission of the IND within a 5-year period of performance. A clinical trial may be proposed only if a preclinical candidate will be identified at the time of contract award.

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 shall include the following additional criteria and supporting data:

For non-bacteriophage products:

Complete chemical structure of the most advanced lead, preclinical candidate or, in the case of biologicals, a precise description of the candidate composition. The proposal is confidential and 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, to be executed in the base period, if Lead Optimization is proposed. Lead Optimization may only be proposed in the base period of performance.

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 the pathogen identified in the TPP.

In vitro assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET).

Therapeutic efficacy in an animal model of disease must be relevant to the indication identified in the TPP. Efficacy testing must include dosing after challenge.

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

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

For bacteriophage products:

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

Full discussion on the characterization of the phage or phage cocktail including: specificity, complete phage sequence(s), confirmation of absence of deleterious genes, and sequences of engineered genes

Potential for toxicology requirements if the phage or cocktail contain engineered genes.

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 directed against emerging infectious diseases.

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):

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

2. Development of a product from a proposal lacking one or more “Additional Requirements” in Section

3.3.2.3.

3. Development of a biological product, protein, monoclonal antibody and conjugates of such entities except where the product is a bacteriophage product.

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

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

6. 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.

7. 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) , except where the product is a bacteriophage product.

8. Development of a product that is derived from, substantially similar to, or identical to an entity that has ever entered a Phase 3 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, and alternate salt forms, crystal forms, formulations, dosing regimens, or clinical indications, except where the product is a bacteriophage product.

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

10. Development of a product derived from serum.

11. 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.

12. 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).

13. Research involving Human Fetal Tissue.

3.3.3.1 Technical Objective

NIAID is interested in supporting the development of promising diagnostics technologies in three areas for detection of signatures from biothreat pathogens and toxins, as well as pathogens causing emerging, reemerging, antimicrobial resistant infectious diseases, and for pandemic preparedness.

1. Untargeted (Agnostic) and Targeted Nucleic Acid Sequencing on Portable or Laboratory-Automated

Systems

The first objective of Research Area 003 is to improve the overall performance of nucleic acid sequencing solutions on portable or laboratory-automated commercial sequencing platforms for the targeted or agnostic detection and identification of viral pathogens for biodefense, emerging infectious diseases, and pandemic preparedness.

Development activities that are IN SCOPE for this objective:

Automated nucleic acid extraction and preparation method development Metagenomic sequencing assay development for agnostic (untargeted) detection from a broad panel of viral pathogen families Software development that accelerates data reduction and analysis processing to decrease overall time to result Initial clinical testing to establish validation of performance

Areas of focus to improve performance could include, but are not limited to:

Reduced turnaround time: Pathogen ID in < 2hours beginning with specimen processing Increased throughput on laboratory-automated sequencing systems: > 10 patient samples processed per sequencing run Sensitivity: False negative rate of < 5% for infectious pathogen identification Specificity: False positive rate of < 5% for infectious pathogen identification Improved ease of use: Automated nucleic acid extraction and sample preparation, simplified transfer to portable sequencing system, data analyses operated, and interpreted with minimal training

Development activities should be consistent and compliant with presumed eventual submission to FDA for pre-Emergency Use Authorization (EUA) and/or 510(k) clearance.

2. Multiplex Protein or Nucleic Acid Detection in Near-Patient Testing Systems

The second objective of Research Area 003 is to develop methods that improve pathogen analyte detection in one of two ways:

First, protein technology improvements such as protein sequencing or mass spectrometry, especially in ways that bring protein-identification testing nearer to the patient; or near-patient rapid antigen testing improvements for rapid and highly sensitive toxin or other protein detection; or solutions for

3.3.3 - Research Area 003 – In Vitro Diagnostics rapid development of synthetic binding moieties for capture of novel proteins. The emphasis here is on methods improvement in time and analytical sensitivity.

Second, multiplex nucleic acid detection that is near-patient, rapid, low-complexity, low-cost, and sensitive for detection of sexually transmitted infections. Design and development can be for testing from care provider-collected or self-collected specimens. The emphasis here is on expanded breadth of infectious pathogens detected, especially, but not limited to, those identifiable from genital ulcer diagnostic (GUD) testing.

Development areas that are IN SCOPE for this objective include but are not limited to:

Mass spectrometry methods development for faster and more sensitive protein identification, especially near-patient protein identification Sample preparation and cycling methods for delivering high accuracy protein sequencing in a model system Improved detection chemistries, including enzymatic signal amplification, as well as detection methods, such as amperometric, voltametric, or potentiometric, for faster, more-sensitive signal output

Technology platforms that design, create, and produce synthetic binders (such as nanobodies or aptamers) for specific capture of novel analytes Methods development to extract nucleic acid targets from lesion swabs and follow-up amplification methods for multiplex identification

Areas of focus to improve performance include but are not limited to:

Multi-cycle protein sequence identification from model toxin proteins in plasma or serum matrix Antigen detection times < 2 min Antigen detection sensitivities < 10 pg/mL of clinical specimen Development of specific synthetic binders in < 1 week Antimicrobial resistance genotype detection—as necessary--for STI identification tests

3. Bacterial Identification and Phenotypic Antimicrobial Resistance Characterization

The third objective of Research Area 003 is to improve direct-from-blood or other biofluid detection and identification of microbial infection coupled with phenotypic antibiotic susceptibility testing (AST) characterization.

Development areas that are IN SCOPE for this objective include but are not limited to:

Sample preparation methods, such as: improving ratio of pathogen-to-human nucleic acid ahead of molecular testing; improving barcoding chemistries; strategies for pooling clinical specimens for multi-sample sequencing

Target amplification methods to improve analytical sensitivity Targeted and agnostic whole-genome sequencing methods to improve accuracy of bacterial identification Phenotypic AST prediction or characterization

Areas of focus to improve performance in this objective could include but are not limited to:

Smaller volume of whole blood to detect bloodstream infection direct from patient specimen Greater clinical sensitivity to detect pathogen analyte direct from whole blood Shorter detection time to identify pathogen of infection without blood culture, < 3 hours

Shorter reaction time for phenotypic detection of antibiotic resistance, < 2 hours

3.3.3.2- Technical Approach: Priority Pathogen and Resistance Targets

The proposed program must have sufficient feasibility research completed and be working in early (planning and design) through late-stage (design verification) development for a diagnostic test system that supports biodefense and naturally emerging and re-emerging infectious pathogen preparedness. Diagnostic test system must detect one of the following agents or markers:

ESKAPE+ pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp, Escherichia coli), including genotypic resistance markers

Mycobacterium tuberculosis Neisseria gonorrhea and antibiotic resistance markers Treponema pallidum Identification and genotypic resistance markers for Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia spp, Botulinum toxin, including identifying and distinguishing relevant serotypes

Lassa virus Nipah virus Rift Valley Fever virus Enterovirus D68 virus Novel coronaviruses Hepatitis C virus Filoviruses (Sudan ebolavirus, SEBOV; Marburg virus, MARV, Zaire ebolavirus, ZEBOV) Monkeypox virus (MPXV) Herpes simplex virus (HSV) Candida spp. and genotypic resistant markers Aspergillus fumigatus and genotypic resistant markers Coccidioides spp.

Mucorales

The capability to detect and distinguish a required agent from among multiple other agents common to a geographic region or population is strongly encouraged.

3.3.3.3– Additional Requirements

Developers should present sufficient and convincing proof-of-concept data that the proposed diagnostic method can detect the targeted pathogen analyte (see pathogen list above) preferably from a relevant clinical matrix (e.g., blood, urine, respiratory swab, cerebrospinal fluid, stool, or bronchoalveolar lavage).

Organizations responding to this Research Area, 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 research, such as antibodies or other capture reagents, virulent pathogens, clinical samples, and biocontainment facilities. They should also have documented or planned expertise in product development in order to have the capability to advance the development and validation of a candidate diagnostic through FDA clearance and commercial launch.

3.3.3.4– 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:

1. Development of a diagnostic that does not include at least one (1) of the above-listed agents in Section 3.3.3.2

2. Development of diagnostic tests to identify pathogens from positive blood culture or isolate (bacterial plate)

3. Development of diagnostics that rely solely on the detection of host-response antibodies, other proteins, or RNAs

4. Basic research and discovery of new host-based diagnostic targets

5. Development of diagnostics that will require additional manual steps after the clinical sample has been loaded to start the test

6. Development of diagnostics that will only be validated using non-pathogenic or surrogate organisms

3.4 – RESEARCH AREAS 001 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 and 002.

Separate and distinct proposals must be submitted for each Research Area 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 will 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 subject research 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 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 Summary of statistical approach 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 good clinical practice (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 - UNIFORM COST ASSUMPTIONS

Offerors should use the following assumptions for the purposes of estimating costs and preparing the technical proposal:

1. Audits: Assume QA audits of critical phases for the duration of the contract period of performance. For example, anticipate a GLP audit of toxicology site, GMP audit of manufacturing site, and GCP audit of clinical site.

2. Purchase of Equipment: Cost will NOT be allowed for the purchase of any equipment, hardware, or software under this contract.

3. Alterations and Renovations: Cost will NOT be allowed for any facility construction, alterations, or renovations under this contract.

4. Programmatic Presentations and Meetings:

a. Post Award Contract Initiation Meeting

The Contractor shall be responsible for arranging a one-day meeting at 5601 Fishers Lane, Rockville, MD, within 60 days from effective date of award and shall be attended by the Contractor’s key personnel. Assume all cost for the travel of key personnel. Non-key personnel may participate virtually.

b. Annual Contract Review Meetings

For each year of performance, the Contractor shall arrange a one-day Annual Contract Review Meeting and shall be attended by the Contractor’s key personnel, non-key personnel may attend virtually. The meeting may be held at either the Contractor’s facility or at 5601 Fishers Lane, Rockville, MD, at the discretion of the COR. The first annual meeting will be held 12-18 months after effective date of award and thereafter, every 12 months from anniversary date.

Assume all cost for the travel of key personnel.

c. Monthly Meetings/Teleconferences

The Contractor Principal Investigator (PI) and Project Manager shall plan, conduct, and participate in meetings with the COR at a minimum of monthly intervals via teleconference to discuss progress, problems, proposed solutions, and any matter that is relevant to the scientific and financial administration of the project and future activities. The schedule for these meetings will be established by the COR after contract award. The Contractor shall prepare and submit the meeting agenda and distribute the agenda and background materials to all meeting participants at least 2 business days in advance of the meeting. The Contractor shall prepare and provide a summary of all meeting and teleconferences to the COR within the timeframe stated in the delivery schedule and include each summary in the Monthly Progress Reports.

3.4.4 - POST-AWARD REQUIREMENTS

The following post award requirements will apply to all awards made under Research Areas 001 and 002 of this BAA.

Offerors are instructed to address responsibility for complying with these requirements in the proposed SOW for the Technical Proposal. Offerors are NOT required to submit documentation to address these post-award requirements in their technical proposals. Instructions for submitting documentation associated with post-award requirements will be provided during negotiations.

3.4.4.1 - Contractual Commitments

Upon award of a contract, the contractor shall be required to make legal commitments through acceptance of Government contract clauses.