Broad Agency Announcement (BAA): Immune-Based Antiviral Products for Suppression/Elimination of HIV-1, NIAID-DAIDS-NIH-AI-2015041

Notice Number: NOT-AI-15-046

Key Dates
Release Date:  June 22, 2015

Related Announcements
None    

Issued by
National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) supports research related to the basic understanding of microbiology and immunology leading to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases. The NIAID, The Division of Acquired Immune Deficiency Syndrome (DAIDS) has a requirement for advanced development and clinical evaluation of innovative therapeutic immune-based products that can elicit responses to destroy activated HIV reservoirs and persistent low level infection in subjects on suppressive antiretroviral drugs. 

The purpose of this BAA is to identify and develop new immune based products that have antiviral activity or elicit antiviral responses that effectively eliminate both autologous persistent infection and activated HIV reservoirs. The main objective supports development, manufacturing and investigational new drug (IND) enabling activities, and clinical study of the candidate innovate therapeutic and anti-HIV immunological product.

The Division of Acquired Immune Deficiency Syndrome (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) is committed to research necessary to end the HIV/AIDS epidemic and in finding new and more effective immune based therapies that complement antiretroviral drug combinations (cART). The Division of AIDS previously supported therapeutic teams under contracts awarded as a result of solicitations issued in 2004 and 2005 for the HIV Vaccine Design & Development Teams (HVDDT). Contract awards were issued to teams led by Profectus Biosciences, Inc. (HHSN272200800062C) and Argos Therapeutics, Inc. (HHSN266200600019C).  The therapeutic vaccine products developed by these teams were studied in multiple clinical trials.

The goal of research for the current program is to identify and develop new immune based products that elicit antiviral effector function(s) that contribute to suppression or elimination of both autologous persistent infection and activated HIV reservoirs. HIV vaccines designed to prevent infection are not the subject of this pre-solicitation notice. A need exists for innovative therapeutic immune-based products that suppress or eradicate HIV-1 in infected persons. These may be novel therapeutic vaccines, effector cells displaying chimeric antigen receptors (CARs), antiviral antibodies, and other molecules. Recent research has identified numerous anti-HIV neutralizing antibodies with properties that suggest they may be useful as therapeutic agents. These antibodies have useful and novel properties including potency, broad ranges of neutralization, and other antibody-mediated effector functions.

There is a heightened interest in the possibility of HIV eradication or sustained remission based on an apparent HIV cure due to therapeutic bone marrow transplant.  There is also a specific interest in therapeutic immune-based antiviral products being part of a cure armamentarium to be tested as part of HIV sustained suppression/eradication human clinical trials to determine safety and efficacy.  Those sustained suppression/eradication or cure trials may consist of the evaluation of multiple therapeutic components, including anti-checkpoint receptor antibodies, latency reversing agents, and anti-HIV receptor antibodies, in addition to defined anti-HIV immune based products. To encourage the development of innovative cure studies, NIAID will support development of therapeutic vaccines, antiviral antibodies, chimeric antigen receptor projects (CARs), and other antiviral biological products as an integral part of a clinical evaluation plan.  The purpose of this Broad Agency Announcement (BAA) solicitation is to provide support for multifunctional teams for the advanced development, manufacturing and IND enabling activities, and clinical study of their candidate innovative therapeutic immune-based product.

Long term suppressive cART or treatment with cART early in infection may reduce the amount of HIV-1 reservoir cells identified at later times. Further, use of pharmacological agents that inhibit histone deacetylases, in particular Vorinostat, indicate it is possible to use small molecules to activate HIV proviruses, i.e. latency reversal, in a portion of reservoirs cells that may be subsequently recognized by use of a novel immune-based antiviral product and destroyed.  A component for HIV-1 cure studies then is to have therapeutic vaccines, CARs, anti-viral antibodies and other products that can be critical components and provide the necessary immune effector functions in sustained suppression/eradication of HIV-1.  The overall goal of research supported by this BAA is to develop and evaluate the role of innovative therapeutic immune-based products to suppress/eradicate HIV in clinical studies and perform the relevant immunological analyses on study samples to identify or confirm the mechanism of action in vivo.   

For purposes of this BAA, a therapeutic vaccine product is defined to be material that will reasonably elicit and provide cytotoxic T lymphocyte (CTL) or other cell immunity responses that target autologous, conserved site, or broad reactivity sequences that would be useful in HIV-1 infected individuals.  Antiviral antibody products may be single or multiple monoclonal antibodies produced and formulated for ease of administration or encoded within an expression vector that is safe and useful for expression in infected subjects.  The choice of these or other antiviral products that are proposed should be supported by prior demonstrated activity both in vitro and in animal model experiments.
Product Development Plan: The contract issued as a result of this BAA will include a detailed Product Development Plan for all the milestone driven activities. These activities include cGMP production and related activities, pre-clinical safety and toxicity studies, activities related to quality assurance, compliance with regulatory requirements, product formulation and conduct of stability studies.  The Plan should have a schedule with proposed milestones. 

For purposes of this BAA, a milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. The Product Development Plan will be part of the overall and comprehensive strategic research plan for evaluation in sustained suppression/eradication studies. 

Mechanism of Action Analysis Plan: A Mechanism of Action Analysis Plan is needed to confirm activity of the product(s) in vivo. The plan should include the refinement of research assay(s) or other assay(s) that will be used to evaluate the action of the product in vivo, particularly in regard to action on activated HIV-1 reservoirs and low level replication that persist during cART. The data from this plan are essential to establish the correlation between effector outcome and specific immunologic response measurements.        

Clinical Evaluation Plan:  Design of a clinical study protocol(s) to be implemented either independently, or in collaboration with one of the NIAID funded clinical trials networks. (http://www.niaid.nih.gov/about/organization/daids/Networks/Pages/daidsnetworks.aspx).

All activities must be performed in strict adherence to FDA regulations and guidance, including requirements for manufacturing of the product candidate under cGMP (21 CFR 11, 210, 211, 600-680, and 820) and the conduct of animal studies and assays under GLP (21 CFR 58).

NIAID plans to support contract activities beyond the base period for performance of the Clinical Evaluation Plan (i.e., clinical studies/trials) through contract options.  These options will be exercised at the Government’s discretion and will be based on Go/No Go decisions.  This approach will allow NIAID flexibility to advance therapeutic immune-based antiviral product candidates into milestone driven cGMP manufacturing for testing in clinical studies.  It is anticipated that multiple clinical studies may constitute separate contract options.     

The contract will not support the following:

  • Basic or observational research in HIV-1 pathogenesis
  • Proof-of-concept, non-human primate (NHP) efficacy studies. Any preclinical GLP NHP or small animal toxicology or immunogenicity study will be allowed for necessary safety evaluation or GLP assay development.
  • Extensions of projects already funded by NIAID.
  • Evaluation of cytokines or other immune response modifiers in the absence of a novel immune-based therapeutic product.     
  • Prevention vaccine or prevention product development. So-called dual use vaccine products will be considered if:
  • There is demonstrated efficacy in a prevention trial
  • The vaccine product can elicit an immune effector function that will act on HIV reservoirs or low level persistent HIV replication
  • The product can reasonably be expected to be useful in sustained remission/eradication studies by targeting conserved or autologous viral epitopes

Proposals submitted in response to this solicitation will be evaluated against specific technical evaluation criteria including: Scientific and Technical Merit of the Comprehensive Research Plan; Plans for Product Development and Manufacturing under cGMP; Quality Control, Quality, Regulatory Compliance, and Data Management; Facilities, Equipment, and Other Resources; Scientific and Technical Personnel; and Project Management.  In addition to the technical evaluation criteria, selection factors to be used in making an award decision will include cost. 

The selection of proposals for award is based upon the evaluation factors, importance to the agency programs (programmatic balance), and fund availability.

It is anticipated that 1 or 2 cost reimbursement, completion type contracts will be awarded for up to a 7-year period of performance beginning on or about September 1, 2016.   

The NIAID plans to use a phased approach for performance of work.  The contract will be awarded for up to a 3 year base period for Phase 1 at approximately $2.6M per year.  For Phase 2, NIAID estimates costs at approximately $3.2M per year for a performance period of up to 4 years.  However, it is anticipated that the total cost for the award(s) may vary depending upon the scope of the project and the technical objectives of the award(s).  The length of time for which funding is requested should be consistent with the nature and complexity of the proposed research.  In no event shall the period of performance proposed by an offeror exceed 7 years.

The NIAID is aware that no single organization or institution may have the expertise and facilities required to perform all parts of their proposed Statement of Work.  Therefore, it may be necessary for the Contractor to subcontract a portion of the work.  In addition, the Contractor is not limited to a domestic institution or organization, and subcontracting to foreign organizations/institutions is permitted.  The Contractor shall be responsible for ALL work performed under this contract including that performed by any subcontractor(s).

All responsible sources may submit a proposal which shall be considered by the Agency.   This BAA will be available electronically on/about July 1, 2015, and may be accessed through FedBizOpps http://www.fedbizopps.gov/.  This notice does not commit the Government to award a contract.  No collect calls will be accepted.  No facsimile transmissions will be accepted. See Government-Wide Numbered Note 26.

For this solicitation, the NIAID requires proposals to be submitted via two methods: (1)
Disc (CD or DVD) and (2) Online via the NIAID electronic Contract Proposal Submission (eCPS) website. The content of the disc and online proposals must be identical. Submission of proposals by facsimile or e-mail is not acceptable.

For directions on using eCPS, go to the website https://ecps.niaid.nih.gov and then click on "How to Submit."

Inquiries

Please direct all inquiries to:

Ashley Virts
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health, DHHS
5601 Fishers Lane Dr., Room 3D10
Bethesda, MD 20892-9821
For Express Mail, change zip code to 20817-9821
Telephone: 240-669-5155
Email: virtsa@niaid.nih.gov

Eileen Webster-Cissel
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health, DHHS
5601 Fishers Lane Dr., Room 3D10
Bethesda, MD 20892-9821
For Express Mail, change zip code to 20817-9821
Telephone: 240-669-5156
Email: webstere@niaid.nih.gov