HHS-NIH-NIAID-BAA2021-1.pdf

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2021 DMID Omnibus Broad Agency Announcement (BAA):

No. HHS-NIH-NIAID-BAA2021-1

Solicitation Issue Date: February 23, 2021

Participating NIAID Divisions: Division of Microbiology & Infectious Diseases (DMID)

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

5601 Fishers Lane, Room 3D39, MSC 9821, Bethesda, MD 20892-9821

Issuing Contracting Officer: Alexandra Buck Email: Alexandra.Buck@nih.gov Phone: (240)669-5174

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

RESEARCH

AREA

NIAID

DIVISION

TITLE PAGE NO. PROPOSALS DUE

DMID

Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases

6 05/24/2021

Development of Therapeutic Products for Biodefense, Anti- Microbial Resistant (AMR) Infections and Emerging

9 05/24/2021

Advanced Development of Sequencing- Based Diagnostics for Biothreats and Emerging Infectious Diseases

13 05/24/2021

* Proposals must be received before 3:00 PM Eastern Time on the date specified herein. Please see the Proposal Submission Instructions 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.

mailto:Alexandra.Buck@nih.gov

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2021 DMID Omnibus Broad Agency Announcement

No. HHS-NIH-NIAID-BAA2021-1

TABLE OF CONTENTS

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

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

SECTION 3 – Research Areas and Technical Objectives………………………………….………..……… p. 5

3.1 – Division of Microbiology and Infectious Diseases (DMID) Background………………..…… p. 5

3.2 – Research Areas

3.2.1 – Research Area 001: Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases………………………………………………………………. p. 6

3.2.2 – Research Area 002: Development of Therapeutic Products for Biodefense, Anti- Microbial Resistant (AMR) Infections and Emerging Infectious Diseases ……..…..…… p. 9

3.2.3 – Research Area 003: Advanced Development of Sequencing Based Diagnostics for Biothreats and Emerging Infectious Diseases ……..…………………………………………… p. 13

3.3 – Research Areas 001 and 002: Additional Technical Proposal Instructions ……….…….…... p. 16

3.4 – Research Areas 001 and 002: Reporting Requirements and Deliverables ………….….……. p. 21

3.5 – Research Area 003: Additional Technical Proposal Instructions ………….………………… p. 27

3.6 – Research Area 003: Reporting Requirements and Deliverables …………….………………. p. 33

SECTION 4 – Instructions, Conditions, and Notices to Offerors………………………………………...… p. 38

4.1 – General Instructions to Offerors……………………………………………… ………........... p. 38

4.2 – General Information………………………………………………………………………….. p. 41

4.3 – Instructions to Offerors ……………………………………………………………………... p. 44

4.3.1 – General Information…………………………...……………………...……............ p. 44

4.3.2 – Technical Proposal Instructions …………………………………………….…...... p. 50

4.3.3 – Business Proposal Instructions ………………………………….………………… p. 79

SECTION 5 – Special Contract Requirements …………………………………………………………. p. 95

SECTION 6 – Evaluation Factors for Award ………………………………………………………… p. 119

SECTION 7 – Attachments……………………………………………………………………………….. p. 128

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 FAR 35.016, as well as the National Institutes of Health (NIH) Policy 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 solicitation 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, shall be 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 this announcement.

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, budget or product. 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, importance to the agency programs, and the availability of funds.

SECTION 2. - CONTRACTING OFFICER POINTS 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 related to the specific DMID Research Areas is identified below:

Research Area 001: Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases

Research Area 002: Development of Therapeutic Products for Biodefense, Anti-Microbial Resistant (AMR) Infections and Emerging Infectious Diseases

Research Area 003: Advanced Development of Sequencing-Based Diagnostics for Biothreats and Emerging

Alexandra Buck Contracting Officer Email: Alexandra.Buck@nih.gov Phone: (240) 669-5174 mailto:Alexandra.Buck@nih.gov

SECTION 3. - RESEARCH AREAS AND TECHNICAL OBJECTIVES

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

Research supported by NIAID, 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 DMID supports basic and applied research to develop and evaluate therapeutics, vaccines, and diagnostics targeting multiple pathogens, including NIAID 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. The National Biodefense Strategy (https://www.whitehouse.gov/wp-content/uploads/2018/09/National-Biodefense-Strategy.pdf) articulates the need to enhance preparedness through medical countermeasures, including vaccines, therapeutics and diagnostics.

The World Health Organization (WHO) has prioritized diseases with epidemic potential and for which there are no or insufficient countermeasures (https://www.who.int/blueprint/priority-diseases/en/), as well as bacteria for which new antibiotics are urgently needed (https://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed). Similarly, the Centers for Disease Control and Prevention (CDC) has highlighted threats for which antimicrobial resistance is concerning, serious or urgent https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.

The goal of DMID Omnibus BAA is to advance vaccines, therapeutics and diagnostics which could be deployed against biodefense and/or emerging pathogens to protect human health and well-being.

In particular, supporting these vaccines, therapeutics and diagnostics through early clinical development and manufacturing reduces risk and enables transition to other funding to support advanced clinical development and large-scale manufacturing. Through this solicitation, NIAID aims to advance research and development of promising new therapeutics, vaccines and diagnostics addressing infections caused by the pathogens specified in each of the three (3) Research Areas described below.

https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens https://www.whitehouse.gov/wp-content/uploads/2018/09/National-Biodefense-Strategy.pdf https://www.whitehouse.gov/wp-content/uploads/2018/09/National-Biodefense-Strategy.pdf https://www.who.int/blueprint/priority-diseases/en/ https://www.who.int/blueprint/priority-diseases/en/ https://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed https://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

3.2.1- Research Area 001 - Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases

3.2 - RESEARCH AREAS

3.2.1.1 - Budget and Award Information

NIAID estimates that three (3) or more awards may be issued across Research Areas 001 and 002.

The total cost and duration for each award may vary depending upon the scope of the project and the technical objectives of the award(s). NIAID estimates a total FY22 budget of up to $11 million for the non-severable base work (direct and indirect costs combined) across all contracts in Research Areas 001 and 002, depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds.

The total duration of a proposed contract should be consistent with the nature and complexity of the offeror’s proposed research. The total performance period comprised of the base and any options proposed by an Offeror shall not exceed five (5) years. Clinical trial activities are encouraged to start as soon as possible and be completed within the 5-year period.

Awards are anticipated to be made in or around May 2022; at the discretion of the government, awards may be streamlined to meet agency needs.

3.2.1.2 - Technical Objectives

Research Area 001 seeks to advance vaccine technologies and platforms that have sufficient proof of concept data and/or clinical data to support vaccine development through manufacturing, toxicology testing, and testing in phase 1 or 2 clinical trials. The goal of Research Area 001 is to advance vaccine technologies and platforms which could be deployed against agents important for biodefense and/or emerging pathogens to protect human health and well-being. The development of these platforms and technologies to rapidly progress into Phase 1 clinical trials will provide critical data to reduce the risk for future development of these technologies into approved therapies and vaccines.

Vaccines for Anti-Microbial Resistant (AMR) Organisms

One objective of Research Area 001 is to develop vaccines to address anti-microbial resistant (AMR) organisms including biodefense, Gram negative, Gram positive and fungal pathogens.

Pathogens of particular interest are described below:

Vaccines focused on biodefense pathogens, such as but not limited to, Burkholderia spp, Francisella tularensis and Yersinia pestis. NIAID will exclude, specifically for this BAA, vaccines for Bacillus anthracis.

Vaccines focused on antimicrobial resistant Gram-negative organisms, such as but not limited to, Pseudomonas aeruginosa and Escherichia coli.

Vaccines focused on multi drug resistant Gram-positive bacteria, such as but not limited to, Staphylococcus aureus.

Vaccines focused on fungal pathogens, such as but not limited to, Candida auris and other Candida species.

Vaccines for Pandemic Preparedness and Emerging Infectious Diseases

A second objective is to support development of vaccines for emerging viruses and pandemic preparedness. Pathogens of particular interest are described below:

Vaccines that target coronaviruses with pandemic potential. Specifically, NIAID seeks to support the development of pan-coronavirus (pan-CoV) vaccine candidates that provide broad and durable protective immunity to multiple CoV strains. Preference will be given to approaches that utilize novel immunogen design, as opposed to the development and ‘mixing’ of individual monovalent vaccines. NIAID will exclude, specifically for this BAA, vaccine candidates that only protect against SARS-CoV-2 alone.

Vaccines that target other emerging viruses to include Eastern equine encephalitis virus (EEEV), tick borne viruses, and non-Zaire Ebolaviruses/filoviruses (such as SUDV, MARV).

NIAID will exclude specifically for this BAA vaccines targeting the following pathogens:

Ebola Zaire, Lassa, Chikungunya, Zika and Nipah.

The candidate product(s) may also include adjuvant(s) that enhances the immune responses.

Preference will be given to novel adjuvants that have not previously been in clinical trials or have demonstrated enhanced immunogenicity appropriate for the associated antigen and disease.

Additionally, where feasible, vaccines providing protection with a single dose with adjuvant are also preferred over multi-dose administrations.

Novel delivery platforms that reduce logistical requirements, are readily scalable and/or provide other benefits such as generation of potent mucosal immunity may be developed as well. Cross-cutting technologies applicable to more than one vaccine component are also of interest.

3.2.1.3 - Technical Approach

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.

NIAID will prioritize technically acceptable proposals based on programmatic need, maturity of the candidate product, and risk/benefit assessment.

• Proposals shall provide:

1. Sufficient background to support development of the vaccine candidate including nonclinical proof of concept data, as well as, any clinical data that may be available.

2. A Target Product Profile and Product Development Plan for the candidate product, including regulatory, clinical, non-clinical, and manufacturing activities to be undertaken.

3. Nonclinical immunogenicity and efficacy studies in a relevant animal model(s) to demonstrate vaccine candidate refinement or optimization.

4. Description of current manufacturing process including product characterization and assay development.

5. Manufacturing and formulation process development.

6. Manufacturing, characterization and release of pilot lot current good manufacturing practice

(cGMP) material.

7. Real time and accelerated vaccine stability testing over the duration of the contract.

8. Conduct of non-clinical studies, including all Investigational New Drug (IND)-enabling toxicology studies, combination product approvals and multivalent immunogenicity and interference studies, as needed.

9. Development of all assays and reagents needed to support Phase 1, Phase 1/2 OR Phase 2 clinical trials.

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

11. Design, conduct, completion, and analysis of a Phase 1 or Phase 1/2 clinical trial of the candidate product in normal healthy volunteers shall be included. Upon completion of protocol development, DMID will determine if the offeror will hold the IND and conduct the clinical trial.

12. The provision of clinical and non-clinical samples from all studies to NIAID and, for clinical trials, obtaining future use consent from volunteers for their samples.

13. Proposed project shall include completion of clinical trial within the 5-year period of award.

Clinical trial activities are encouraged to start no later than year three and complete within the 5-year award period.

14. Proof of concept activities to leverage vaccine platform for pandemic preparedness.

• The scope of the product development activities to be undertaken will depend on the status of the individual candidate product, as well as regulatory requirements.

3.2.1.4 - Additional Requirements

I. This Research Area focuses on the development of promising lead vaccine candidates/products and testing these candidates in a clinical trial. Lead candidates shall have the following requirements provided in order of preference:

a. Lead vaccine candidates identified and optimized

b. Proof of concept data that includes immunogenicity using the adjuvant to be used in the clinical trial

c. Efficacy data in a relevant animal model

d. Development of upstream and downstream manufacturing processes

e. Lead vaccine candidate characterized by well controlled assays including potency assay(s)

II. Organizations responding to this Research Area, collectively with the proposed subcontractors and consultants where applicable, must have documented expertise in vaccine discovery and 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.

3.2.1.5 - Contracts awarded under this Research Area will NOT support:

• Basic research and discovery of new series/candidates/products

• Development of devices or diagnostics in the absence of a companion product

• Development of therapeutics

• Vaccines candidates directed against Bacillus anthracis, Ebola Zaire, SARS-CoV-2 vaccines based on solely using the spike protein as the antigen, Lassa, Chikungunya, Zika, and Nipah.

• Research involving the use of Human Fetal Tissue.

3.2.2 - Research Area 002 - Development of Therapeutic Products for Biodefense, Antimicrobial Resistant (AMR) Infections and Emerging

3.2.2.1 - Budget and Award Information

NIAID estimates that three (3) or more awards may be issued across Research Areas 001 and 002.

The total cost and duration for each award may vary depending upon the scope of the project and the technical objectives of the award(s). NIAID estimates a total FY22 budget of up to $11 million for the non-severable base work (direct and indirect costs combined) across all contracts in Research Areas 001 and 002, depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds.

The total duration of a proposed contract should be consistent with the nature and complexity of the offeror’s proposed research. The total performance period comprised of the base and any options proposed by an Offeror shall not exceed five (5) years. Clinical trial activities are encouraged to start as soon as possible and be completed within the 5-year period.

3.2.2.2 - Technical Objectives

The objective of Research Area 002 is the development of promising new therapeutics to address infections caused by NIAID Category A, B, and C priority pathogens and select bacterial and fungal infections identified in the 2019 CDC Antibiotic Resistance Threats Report https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf. For the purposes of this solicitation, therapeutic activity is defined as the cure or mitigation of disease, preferably, once signs and symptoms of infection are evident. For the purposes of this solicitation, a therapeutic candidate refers to an advanced lead series, optimized leads, or product candidate, and is either a small molecule (synthetic or natural product) or a biological product (e.g. monoclonal antibodies, recombinant proteins).

Proposals are encouraged for the development of broad-spectrum therapeutics with extended therapeutic activity over more than one pathogen. Therapeutic candidates with a limited spectrum that target high-priority pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern are eligible. If needed, for narrow-spectrum candidates at later stages of development (IND enabling/Phase 1/Phase 2), efforts to incorporate investigation of novel diagnostics (useful for clinical development or clinical use) and/or collaborations with diagnostics developers are encouraged.

Proposals on non-traditional therapeutics and anti-toxins are encouraged, provided they have demonstrated therapeutic activity when used alone or in combination with an existing licensed product.

Research Area 002 will support lead optimization, pre-clinical (IND enabling) studies and clinical trials that include Phase 1 and Phase 2 studies or confirmatory trials no greater than 120 subjects.

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

Details below describe development phases in-scope of Research Area 002:

Lead Optimization

• Synthesize lead compounds from selected lead scaffolds: new analogs with improved potency, reduced off-target activities, and physiochemical/metabolic properties suggestive of reasonable in vivo pharmacokinetics.

• Conduct non-GLP in vivo toxicity in accordance with the product's intended use.

• Demonstrate in vivo activity and potential for efficacy consistent with the product's intended use (i.e. dose, schedule, duration, route of administration).

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

• Select lead candidate and initiate IND-enabling studies.

Pre-Clinical (IND Enabling) Studies

• Demonstrate acceptable ADME characteristics and/or immune responses in non-GLP animal studies as necessary for IND filing.

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

• Continue development of animal models for determining efficacy and defining PK/PD relationships for further pre-clinical and clinical studies.

• Develop a scalable and reproducible manufacturing process amenable to GMP.

Manufacture GMP-compliant pilot lots.

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

• Prepare and submit IND package to FDA.

Phase 1

Phase 1 clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article in healthy volunteers including Phase 2-enabling studies in special populations (i.e. renal-impairment, elderly).

Phase 2

Phase 2 clinical trials(s) to determine safety, pharmacokinetics and efficacy of the clinical test article in patients.

Proposals that initiate with a single therapeutic candidate for evaluation in clinical trials are expected to complete evaluation in a Phase 1 and/or Phase 2 clinical trial within the 5-year proposed period of performance. Phase 1 and 2 clinical trial completion is defined as completion of a Final Clinical Study Report following International Conference on Harmonization (ICH) Guidelines on Structure and Content of Clinical Study Reports E3.

Proposals that initiate with a single therapeutic candidate for support of IND-enabling studies are expected to complete evaluation in a Phase 1 clinical trial within the 5-year proposed period of performance. Phase 1 clinical trial completion is defined as completion of a Final Clinical Study Report following ICH Guidelines on Structure and Content of Clinical Study Reports E3.

Proposals that initiate with more than one lead compound (or lead series) for support of lead optimization are expected to provide clear plans and criteria for selecting a single clinical candidate therapeutic by the end of the second year of funding to enable completion of IND-enabling activities and submission of the IND within a 5-year period of performance.

3.2.2.3 - Technical Approach

Proposals are encouraged for the development of broad-spectrum therapeutics with extended therapeutic activity over more than one pathogen; priorities are listed below but broad-spectrum activity does not require activity against this list. Limited spectrum therapeutic candidates that target high-priority pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern are eligible if they target one of the specific pathogens listed below:

1. Antimicrobial Therapeutics

a. Active against the effects of one or more of the urgent or serious, and concerning drug-resistant bacterial threats or urgent fungal threats (Candida auris) listed in the 2019 CDC Antibiotic Resistance Threats Report (https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf); OR

b. Display activity against the effects of one of the following bacterial pathogens: Bacillus anthracis, Francisella tularensis, Yersinia pestis, Burkholderia pseudomallei, and especially Burkholderia mallei.

2. Antiviral Therapeutics

a. Active against viruses that are classified as NIAID Category A, B, or C viral threat agents, OR

b. Display activity against infection caused by one of the following viral families:

i. Flaviviruses (esp. Zika, Dengue, and Yellow Fever virus)

ii. Filoviruses (esp. Ebola, Sudan, and Marburg virus)

iii. Orthopox virus representative of Variola major

iv. Pathogenic Coronaviruses (e.g. MERS, SARS-CoV and SARS-CoV-2) https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

• Small molecules, preference will be given for oral delivery

• Monoclonal antibodies, shall be at IND-enabling or Phase 1 stage.

v. Alphaviruses (especially EEEV)

vi. Influenza (e.g., H1N1, H3N2)

vii. Other hemorrhagic fever viruses (e.g. Lassa fever)

3. Anti-toxin Therapeutics

Anti-toxin lead series/lead/product candidate must meet at least one of the following criteria:

a. Displayed activity against Ricin intoxication;

b. Displayed activity against the effects of Staphylococcus enterotoxin B;

c. Biological product: displayed broad-spectrum activity against the effects of all the known serotypes of Clostridium botulinum neurotoxin (serotype A, B, C, D, E, F, G);

d. Small molecule product: displayed activity against the effects of at least two of the known serotypes of Clostridium botulinum neurotoxin;

e. Function as small molecule agents against the effects Bacillus anthracis Protective Antigen, Lethal Factor and/or Edema Factor.

For this Research Area, an anti-toxin therapeutic lead series/lead/product candidate is a single product meeting the following criteria/definitions:

a. An agent intended for use in the cure, mitigation or treatment of intoxication;

b. An agent that has demonstrated activity against a specific toxin in an appropriate in vivo model of disease.

3.2.2.4 - Additional Requirements

I. Regardless of the proposed entry point, therapeutic lead series/lead/product candidate must show demonstrated, phase-appropriate evidence of all the following characteristics:

• Chemical structure and if appropriate, relevant Structure Activity Relationships to support lead optimization strategy

• Synthesis/manufacturing feasibility;

• Appropriate in vitro AND in vivo efficacy; and

• Appropriate in vitro AND in vivo pharmacokinetic and toxicology.

These characteristics must be reflected in the draft Target Product Profile (TPP).

II. Organizations 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 and/or biological threats.

3.2.2.5 -Contracts awarded under this Research Area will NOT support:

• Basic research and discovery of new series

• Hit-to-Lead optimization and studies

• Development of candidates/products or lead series that have not demonstrated therapeutic activity in a relevant animal model of disease OR have not demonstrated stage appropriate pharmacokinetics

• Development of candidates/products or lead series from a known class that don’t demonstrate a unique advantage over other members of the class

• Development of licensed products as new formulations or prodrugs

• Development of licensed products for additional clinical indications

• Development of licensed products in combination with other licensed products

• Development of topical sanitation products

• Development of serum-derived products

• Development of devices

• Development of probiotics and other microbiome related products

• Research involving the use of Human Fetal Tissue.

3.2.3 - Research Area 003 - Advanced Development of Sequencing-Based Diagnostics for Biothreats and Emerging

3.2.3.1 – Budget and Award Information

NIAID estimates that one (1) or more awards may be issued across Research Area 003. The total cost and duration for each award may vary depending upon the scope of the project and the technical objectives of the award(s). NIAID estimates a total FY22 budget of up to $4 million for the non-severable base work (direct and indirect costs combined) across all contracts in Research Areas 003, depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds.

The total duration of a proposed contract should be consistent with the nature and complexity of the offeror’s proposed research. The total performance period comprised of the base and any options proposed by an Offeror should not exceed five (5) years. Clinical trial activities are encouraged to start as soon as possible and be completed within the 5-year period.

3.2.3.2 – Technical Objectives

NIAID is interested in supporting the development of promising sequencing-based diagnostics for biothreat pathogens as well as pathogens causing emerging and re-emerging infectious diseases.

Specifically, the objective of Research Area 003 is to advance the research and development of nucleic acid and protein sequencing solutions on established commercial platforms for the targeted and agnostic detection of bio-threat and naturally emerging infectious pathogens. It is not required to complete the development and FDA clearance of the diagnostic during the project period;

however, the targeted metrics for the final diagnostic product should include:

• Turnaround time – pathogen ID within 1-2 hours of specimen collection;

• Throughput – minimum of 10 patient samples processed per sequencing run;

• Sensitivity – analytical sensitivity of > 97% for infectious pathogen detection;

• Specificity – limited off- target detection of < 3%;

• Ease of use – automated nucleic acid or protein extraction and sample preparation; simplified transfer to sequencing system; data analyses operated and interpreted with minimal training;

• Regulatory – FDA pre-EUA and/or 510(k) clearance; and

• System utility – other commercially sustainable assays cleared or in development or in planning on same or equivalent system.

Details below describe development activities that are IN SCOPE of Research Area 003:

• Nucleic acid or protein extraction method development;

• Automated nucleic acid or protein preparation method development;

• Sequencing assay development to detect one or more required pathogens;

• Metagenomic sequencing assay development for agnostic detection of untargeted pathogens;

• Internal and external controls development;

• Integration of chemistry processing on automated platforms;

• Software development, including database improvement for faster and/or more comprehensive analysis patient sample data;

• Reagent scale-up for process validation and pilot manufacturing; and

• Establishment of clinical studies to validate performance.

3.2.3.3 – Technical Approach

Proposed program must be in early through late-stage development for a sequencing-based diagnostic test that supports biodefense and naturally emerging and re-emerging infectious pathogen preparedness. Diagnostic must detect one of the following agents:

o Bacillus anthracis, including genotypic resistance markers o Yersinia pestis, including genotypic resistance markers o Francisella tularemia, including genotypic resistance markers o Burkholderia sp., including genotypic resistance markers o Botulinum toxin , including identifying and distinguishing relevant serotypes o ESKAPE pathogens (Enterococcus faecium, Staph. aureus, Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, Enterobacter species), including genotypic resistance markers o Lassa virus o Nipah virus o Rift Valley Fever virus o Enterovirus D68 virus o Candida auris o Coccidioides sp.

o Novel coronaviruses

At the end of the performance period, it is expected that the diagnostic or diagnostic prototype shall:

• Detect proposed pathogen analyte reproducibly and with clinical accuracy directly from a relevant clinical matrix (blood, urine, respiratory swab, cerebrospinal fluid, stool, or bronchoalveolar lavage) without a culture step;

• Be designed either for low-throughput use in near-patient settings such as physician’s office, community pharmacy, and hospital emergency room, or for high-throughput or rapidly scalable use in hospital laboratories or central reference testing labs;

• Require a maximum of 5 minutes of manual preparation prior to loading the clinical sample for automated extraction, sample prep, and sequencing; and

• Generate actionable diagnostic results within 1-2 hours without additional manual intervention.

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

3.2.3.4 – Additional Requirements

I. Developers must present proof-of-concept data that the proposed sequencing 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) and has the capability for agnostic detection of any relevant infectious pathogen.

II. 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.

3.2.3.5 – Contracts awarded under this Research Area will NOT support:

• Development of a diagnostic that does not include one (1) of the above-listed agents.

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

• Development of diagnostics that rely solely on the detection of host-response antibodies.

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

• Development of platforms that will require more than 5 minutes of manual steps to process the sample prior to loading it into the diagnostic.

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

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

3.3 - 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 or 002.

Separate and distinct proposals must be submitted for each Research Area to which you are proposing.

3.3.1 - PRODUCT DEVELOPMENT PLAN

Technical Proposals shall include a Product Development Plan that describes the critical path for the proposed candidate/product to eventual licensure and identifies the decision points/gates for progress of the candidate/product. Offerors should point out areas of significant uncertainty and propose likely alternatives.

The Product Development Plan should detail the specific tasks and stages to be performed with contract funding that can be reasonably completed within the period of performance. The Product Development Plan should include a summary of the following:

a. A description of the intended use/indication of the proposed candidate product and the public health gap the product is intended to fill.

b. A Target Product Profile for the candidate product, including the performance specifications and features the candidate product should have including potential stability, dosing and safety.

c. A description of the candidate product as it is currently configured. Include a description of how the candidate meets the technical objectives.

d. Data to support the characterization and selection of the candidate/product for further development. A summary of the data that demonstrates activity in an appropriate animal model.

e. A synopsis of any discussions and meetings with the U.S. Food and Drug Administration (FDA) for the proposed product. Provide in an appendix any relevant FDA documents such as meeting agendas, presentations, and meeting minutes.

f. A brief description of critical activities and/or issues that are part of the product development strategy through submission of a biologics license application (BLA) or new drug application

(NDA).

g. A description of regulatory activity plans to support the proposed work.

h. A description of good laboratory practice (GLP) safety and clinical plans to support the proposed work.

3.3.2 - WORK PLAN

Technical proposals shall include a work plan detailing the specific tasks that the Offeror proposes to perform with contract funding that can reasonably be completed within the period of performance. The technical proposal shall include a SOW that includes base and options, milestones, and deliverables. An associated Gantt chart shall be included in the technical proposal while the associated task linked budget shall be included in the business proposal.

In addition, the SOW shall provide for updates of the technical approaches in the Work Plan, as applicable, upon a change in any task, that must be approved by the Contracting Officer’s Representative (COR) and the CO prior to the initiation of any activities related to its execution.

The Work Plan shall include:

a. Base, options and milestones for key project/task objectives.

b. Deliverables with appropriate specifications or references to assess successful completion of the activities and milestones.

c. A Gantt chart of proposed activities that can be correlated with a task-linked budget at a level that facilitates Government oversight of those activities. The task-linked budget should provide a breakdown of direct costs linked to each activity, task and subtask contained on a detailed chart.

d. A detailed discussion of the proposed technical approach for each activity to be performed to achieve the key project objectives, with sufficient detail to fully explain and justify the scientific/technical rationale for the proposed approach and/or methodologies.

e. The following, as applicable for the project being proposed:

• Approach for manufacturing and Chemistry, Manufacturing, and Controls (CMC) development of candidate product to optimize production, formulation and delivery.

• Description of non-clinical studies for safety, toxicology, pharmacology, immunogenicity and efficacy, as applicable, including all IND-enabling studies.

• Approach for development of assays and reagents needed to support product development activities.

• Development and submission of an IND and performance of clinical trials to demonstrate product safety and/or early immunogenicity.

f. A project management plan identifying project manager, processes, and activities for contractor and subcontractor(s).

g. Plans for quality control over the implementation, coordination and conduct of the activities set forth in the Work Plan, including plans to conduct regulatory audits.

h. A Risk Management and Mitigation Plan.

i. A plan describing which data and resources, reagents, assays and animal models developed with contract funding will be shared with the scientific community.

j. Offerors proposing subcontracts and/or consultants to perform portions of the proposed work should clearly identify the specific tasks for which they plan to utilize subcontractors and/or consultants.

The entire proposal will be subject to negotiations including Product Development Plan, work activities, SOW, timeline and budget.

3.3.3 - CLINICAL TRIAL PROTOCOL DEVELOPMENT AND IMPLEMENTATION

Human subjects research may be carried out under this contract with the approval of DMID.

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. 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 protection

• Provisions for data monitoring and safety reports

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

• Summary of statistical approach

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.

3.3.4 - 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 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.

https://grants.nih.gov/policy/clinical-trials.htm https://grants.nih.gov/policy/clinical-trials.htm https://www.niaid.nih.gov/research/niaid-clinical-research-standards https://www.niaid.nih.gov/research/niaid-clinical-research-standards https://www.niaid.nih.gov/research/dmid-clinical-research-policies

3.3.5- UNIFORM COST ASSUMPTIONS

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

a. 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.

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

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

d. Programmatic Presentations and Meetings: Assume attendance at the following meetings:

1) 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 after award date. Attendees should include all Key Personnel and Key Subcontractor Personnel.

2) Annual Contract Review Meetings

For each year of performance, the Contractor shall attend an Annual Contract Review meeting. The meetings will be held on an alternating-year basis at the Contractor’s facility or a location at 5601 Fishers Lane, Rockville, MD. Each meeting will be one-day in length. Attendees should include all Key Personnel and Key Subcontractor Personnel.

3) Monthly Meetings/Teleconferences

The Contractor’ 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 those 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 Technical Progress Reports.

3.3.6 - 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.

3.3.6.1 - Contractual Commitments

Upon award of a contract, the contractor shall be required to make legal commitments through acceptance of Government contract clauses contract. The outline that follows is illustrative of the types of provisions required by the FAR that shall be included in the contract. This is not a complete list of provisions to be included in contracts, nor does it contain specific wording of these clauses.

Copies of complete terms and conditions applicable to your contract will be provided during negotiations.

1) Inspection: Work performed under the contract is subject to Government inspection and evaluation at all times.

2) American-made Equipment and Products: When purchasing equipment or products under a contract award, the contractor shall purchase American-made items whenever possible.

3) Termination for Default: The Government may terminate the contract for default if the contractor fails to perform the work described in the contract and such failure is not the result of excusable delays.

4) Contract Work Hours: The contractor may not require an employee to work more than eight hours a day or forty hours a week unless the employee is compensated accordingly (i.e., overtime pay).

5) Covenant Against Contingent Fees: No person or agency has been employed to solicit or secure the contract upon an understanding for compensation except bona fide employees or commercial agencies maintained by the contractor for the purpose of securing business.

6) Disputes: Any dispute concerning the contract that cannot be resolved by agreement shall be decided by the CO with right of appeal.

7) Equal Opportunity: The contractor will not discriminate against any employee or applicant for employment because of race, color, religion, sex, or national origin.

8) Gratuities: The Government may terminate the contract if any gratuities have been offered to any representative of the Government to secure the contract.

9) Termination for Convenience: The Government may terminate the contract at any time for convenience if it deems termination to be in its best interest, in which case the contractor will be compensated for work performed and for reasonable termination costs.

10) Patent Infringement: The contractor shall report each notice or claim of patent infringement based on the performance of the contract.

3.4 - RESEARCH AREAS 001 AND 002 – REPORTING REQUIREMENTS AND

DELIVERABLES

3.4.1 - Reporting Requirements

In addition to reporting requirements and deliverables identified elsewhere in this solicitation, it is expected that awards resulting from Research Areas 001 and 002 will include the following reports and deliverables:

a. Monthly Progress Reports

This report shall include a description of the technical…