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Immune-Based Antiviral Products for Suppression/Elimination of HIV-1

Solicitation Number: NIAID-DAIDS-NIHAI2014011
Agency: Department of Health and Human Services
Office: National Institutes of Health
Location: National Institute of Allergy and Infectious Diseases
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NIAID-DAIDS-NIHAI2014011
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Solicitation
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Added: Sep 22, 2014 1:27 pm

Introduction
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 anti-HIV therapeutic immune-based products that have antiviral properties or can elicit responses to destroy activated HIV reservoirs and persistent low level infection in subjects on suppressive antiretroviral drugs. 


Description
The Division of AIDS, NIAID 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 either have intrinsic antiviral properties or elicit antiviral responses that effectively eliminate both autologous persistent infection and activated HIV reservoirs. HIV prevention vaccines are
designed to address outcomes of exposure in uninfected persons, i.e. acquisition of virus or attenuation of viral load when infection occurs.  Thus far, such vaccines have not demonstrated therapeutic efficacy when used in infected subjects. Thus the need exists for innovative therapeutic biological products that work in infected persons. Recent research has also 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. Additional research indicates certain antibodies may be engineered to improve binding specificity, potency, or antibody effector function.


 


There is a heightened interest in the possibility of HIV eradication or sustained remission based on one apparent HIV cure due to therapeutic bone marrow transplant, and one apparent cure due to immediate and aggressive antiretroviral therapy in a newborn.  There is also a specific interest in therapeutic anti-HIV vaccine, anti-HIV antibody products, or other immune-based anti-HIV 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, anti-latency agents, and anti-HIV receptor antibodies, in addition to the defined anti-HIV immune based products developed through this BAA. To encourage the development of innovative cure studies, NIAID will support development of therapeutic vaccines, antiviral antibodies 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 a contractor’s team to complete the advanced development, manufacturing and IND enabling activities, and clinical study of their candidate innovative, therapeutic immune-based antiviral product. 


This BAA targets development and production of innovative anti-HIV therapeutic products for use in sustained suppression/eradication trials.  Work in the field indicates immune responses may contribute to control in HIV-1 infected individuals who maintain undetectable levels of HIV-1 replication without combination antiretroviral therapy (cART).  The search for anti-HIV-1 broadly reactive neutralizing antibodies has progressed significantly and to a stage where some of these molecules may be considered as therapeutic components in HIV-1 functional cure studies, based on suppression of viral replication in non-human primate (NHP) or humanized mouse model studies, presumably through the action of the antibody.  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 in a portion of reservoirs cells for subsequent immune recognition and destruction.  A useful component for HIV-1 cure studies then is to have therapeutic vaccines and any other antiviral products that can be critical components and provide the necessary immune effector functions for achieving sustained suppression/eradication of HIV-1. The overall goal of research supported by this BAA is to develop and evaluate the role of such products to suppress 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.  Antiviral antibody products may include products that were engineered to improve performance regarding target specificity, potency, or effector function.  Other immune-based products may be engineered T cells expressing chimeric antigen receptors (CARs) or other artificial T cell receptors. The choice of any type of product should be supported by prior demonstrated activity in vitro or in animal model experiments.


 The NIAID plans to use a phased approach for performance of work under the contract.  Phase 1 activities will include support for three essential developmental phase components of the overall contract work. 


Product Development Plan: The contract issued as a result of this BAA will include the 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 scheduling and 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 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 persists during cART.  The data from this plan is essential to establish the correlation between effector outcome and specific immunologic response measurements.        


Clinical Evaluation Plan:  Design and implement a clinical study protocol(s) 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).


Activities during Phase 1 may include the general areas of manufacture, IND enabling studies, formulation and release of product for the planned clinical studies.  During this period, assay selection and refinement will be completed to support immune correlate analyses and effects of the therapy on viral replication and reservoirs, and any other mechanism of action analysis the offeror determines is essential to the evaluation.  Since our understanding of HIV reservoirs and related assay development will continue to evolve, it is expected that the Mechanism of Analysis Plan would include appropriate additional sample collection and banking for use in mechanism of action related laboratory studies not currently anticipated.


During Phase 2, 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.  The decision to fund the options will depend upon scientific priority, program balance, and availability of funds.  It is anticipated that multiple clinical studies may constitute separate contract options.  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).  This approach will allow NIAID flexibility to advance therapeutic candidate products into milestone driven cGMP manufacturing for testing in clinical studies. 


All activities must be performed in strict adherence to FDA regulations and guidance, including requirements for manufacturing of the vaccine 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).


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 therapeutic vaccine or therapeutic antibody 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; Product Development and Manufacturing under Current Good Manufacturing Practices; 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, and Small Disadvantaged Business (SDB) participation.  The selection of proposals for award will be based upon the evaluation factors, importance to the agency programs (programmatic balance), and fund availability.


It is anticipated that 1 to 2 cost reimbursement, completion type contracts will be awarded for a 7-year period of performance beginning on or about September 1, 2015.   


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 $3.5M per year for a performance period of up to 4 years.


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 23, 2014, 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.

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Solicitation 1

Type:
Solicitation
Posted Date:
September 22, 2014
Description: Solicitation No, RFP-NIAID-DAIDS-NIHAI2014011

Amendment 1

Type:
Mod/Amendment
Posted Date:
September 22, 2014
Description: Amendment 1 to Solicitation NIAID-DAIDS-NIHAI2014011

Amendment 2

Type:
Mod/Amendment
Posted Date:
October 22, 2014
Description: Amendment 2
Description: Attachment 2
Description: Attachment 3

Amendment 3

Type:
Mod/Amendment
Posted Date:
December 4, 2014
Amendment_3.pdf (21.44 Kb)
Description: Amendment 3

Amendment 4

Type:
Mod/Amendment
Posted Date:
December 9, 2014
Amendment_4.pdf (109.30 Kb)
Description: Amendment 4
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