The Medical Technology Enterprise Consortium (MTEC) is excited to post this summary announcement for a Request for Project Proposals (RPP) entitled, "Development of Personalized Bacteriophage Therapeutic for the treatment of Bacterial Infections." The goal of this research is to develop and optimize all aspects of practical precision bacteriophage therapy treatment(s) through clinical development to the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA). As understood, a "precision bacteriophage therapy treatment" refers to achieving reliable efficacy of a phage therapy by treating bacterial infections with phage therapeutics that are in some way customized to the individual cases being treated. As elaborated below, aspects of a bacterial infection that might require individual customization include the genetic diversity of circulating pathogens, and the potential for phage-resistant variant subcultures to arise in the course of treatment. Clinical questions to be addressed include determination of the ability of precision bacteriophage therapy to avoid or overcome emergence of bacterial resistance to therapeutic bacteriophages and assessment of systemic responses in human subjects following treatment with antimicrobial bacteriophage therapy. Practical questions to be addressed include assessment and improvement of the clinical feasibility of delivering a precision bacteriophage therapeutic, in terms of timely and high-quality design, production, and delivery of the characterized phage therapeutic; and development and demonstration of Current Good Manufacturing Practice (cGMP) production for clinical-grade bacteriophages suitable for use as a precision bacteriophage investigational / clinical therapeutic.

MTEC:
The MTEC mission is to assist the U.S. Army Medical Research and Materiel Command (USAMRMC) by providing cutting-edge technologies and supporting life cycle management to transition medical solutions to industry that protect, treat, and optimize Warfighters' health and performance across the full spectrum of military operations. MTEC is a biomedical technology consortium collaborating with multiple government agencies under a 10-year renewable Other Transaction Agreement (OTA), Agreement No. W81XWH-15-9-0001, with the U.S. Army Medical Research Acquisition Activity (USAMRAA). MTEC is currently recruiting a broad and diverse membership that includes representatives from large businesses, small businesses, "non-traditional" defense contractors, academic research institutions and not-for-profit organizations.

Technical Background:
Bacteriophages (phages) are viruses that specifically attack bacteria. Since their discovery a century ago, phages have been contemplated as potential therapeutic agents. However, the immature science of bacteriophage microbiology at the time, followed by the discovery and development of conventional antibiotics, diverted attention from bacteriophages. Now with the growing failure of antibiotics, bacteriophages are being reconsidered as therapeutic agents.

One key feature of bacteriophages is their host specificity. Any given bacteriophage typically will infect only a single species of bacteria, and indeed often has a restricted host range within that species, where naturally occurring genetic diversity of the host limits the bacteriophage to a subset of bacterial strains. Furthermore, it is common in a susceptible bacterial population for genetic variants to occur that gain resistance to the bacteriophage. These two points can significantly constrain the efficacy of a bacteriophage therapeutic: a single bacteriophage or defined combination of bacteriophages is unlikely to work against all clinically presented infections, and infections against which a bacteriophage therapeutic might initially be effective can ultimately overcome treatment through the emergence of a resistant subclone.

This program seeks to overcome both these failure points by using a precision medicine approach for delivering bacteriophage therapy. A submitted proposal should recognize and include means to overcome the genetic diversity of multi-drug resistant (MDR) bacterial clinical pathogens, and the possible emergence of phage-resistant bacterial variants during the course of precision bacteriophage treatment. At a minimum, a successful precision strategy will address both these concerns and thus help enable bacteriophage therapy to become a practical solution to the treatment of bacterial infections.

This precision medicine approach to bacteriophage therapeutics also faces a challenging product development and production pathway. Given the complexity of phages themselves and the inherent novelty of clinical, bacteriophage-based precision therapeutic approaches, US FDA requirements, including Pharmaceutical Quality/Chemistry, Manufacturing, and Controls (CMC), will entail demanding characterization and production procedures. The regulatory environment for licensure of a precision phage product is incompletely defined and as yet untested. The logistics of case-by-case design of a precision phage therapeutic and delivery to bedside in a clinically useful timeframe needs to be established. The prototyping effort sought here is intended to help resolve all these aspects of the clinical development of precision bacteriophage therapeutics for antimicrobial applications.

Program Description:
The goal of this program is to support the RDT&E activities required for the clinical development of a precision bacteriophage therapeutic. The ultimate objective is to support submission of a BLA for FDA approval, and thus any submitted proposal should have a defined and feasible pathway to licensure.
This MTEC RPP focuses on the execution of clinical trial(s) for the treatment of bacterial infections, for example, treating appropriate ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp), infection indication(s), to most effectively advance a precision bacteriophage product toward FDA licensure. Objectives of the program include:

• Clinical and scientific:
   o Clinical evaluation of the ability to safely and effectively treat bacterial infections via design and administration of a precision bacteriophage therapeutic.
   o Assessment of the safety and efficacy of a precision bacteriophage therapeutic approach across relevant model populations of affected patients.
   o Testing of the practical ability to adapt the phage therapeutic to dynamic changes in the patients' pathogens in the course of investigational clinical treatment. The successful therapeutic should prevent or overcome the emergence of bacteriophage resistance in the infection.
   o Assessment of the effect of bacteriophage therapy on changes in antibiotic susceptibility over the course of treatment, and on the outcomes of surgical intervention.
   o Assessment of the pharmacokinetics and pharmacodynamics of phage administration.

• Logistical:
   o Assessment and improvement of the feasibility of delivering a precision bacteriophage therapeutic, in terms of timely and high-quality design, production, and delivery of the characterized phage therapeutic.
   o Development and demonstration of cGMP production for clinical-grade bacteriophages suitable for use as a precision bacteriophage investigational/ clinical therapeutic.

Work Plan:
The goal of this MTEC award is to evaluate human safety and efficacy of a bacteriophage prototype for treatment of bacterial infections. This program seeks to test precision bacteriophage therapy using a suitable clinical indication that will maximize the probability of assessing efficacy. Examples of bacterial infection diagnoses relevant for testing of bacteriophage therapy can include asymptomatic bacteriuria, symptomatic refractory MDR genitourinary (GU) infections, and potentially other clinically relevant infections suitable to support development and evaluation of precision phage interventions for bacterial infections. The Government may pursue optional follow-on tasks to continue product development through additional clinical trials for relevant supplemental FDA marketing approval/licensure.

    Task 1 (PoP up to 2 years): Conduct Phase 1 / 2 clinical trial(s) for ESKAPE pathogen or other relevant, strategically selected indications as a part of a full-spectrum FDA-compliant clinical development to support a BLA submission to FDA. Task 1 is expected to be completed within two (2) years. Proposals may request support for Task 1 that includes, but is not limited to, subject matter expertise, appropriate consultation for regulatory strategy, and ensuring reproducibility of the manufacturing process at scale for the ultimate fielding of the innovative biologic bacteriophage product to DoD stakeholders and to commercial market. Anticipated Task 1 activities include (but are not limited to):
    • Manufacture (cGMP) of bacteriophage therapeutic product suitable for clinical investigation in Phase 1 / 2 clinical trials;
    • Conception and execution of appropriate regulatory strategy (e.g., submission of Investigational New Drug [IND] application and other FDA-compliant responsibilities); conduct of Phase 1 / 2 clinical trial as the regulatory sponsor (accordingly, the development partner bears the legal responsibilities of sponsor under 21 CFR 312 Subpart D);
    • Establishment and management of clinical trial sites;
    • Enrollment and clinical monitoring at all enrollment sites;
    • Provisions of all aspects of data configuration, data management, analysis, and reporting in compliance with all applicable regulatory guidance and Code of Federal Regulations (CFRs).

Potential Follow-on Task 2: Prepare for and conduct additional FDA compliant Phase 1 / 2 clinical trial(s).

Potential Follow-on Task 3: Prepare for and conduct FDA compliant Phase 2 clinical trial(s).

Potential Follow-on Task 4: Prepare for and conduct FDA complaint Phase 3 clinical trial(s) and submission of BLA for FDA licensure.

Financial Framework:
The U.S. Government (USG) potentially has available $3-6 Million (M) Defense Health Program (DHP) Research, Development, Test and Engineering (RDT&E) and other RDT&E dollars. The work is expected to be conducted in several tasks. The Period of Performance (POP) is 24 months for Task 1. The USG may apply additional dollars for follow-on tasks with the evaluation and acceptance of work and cost plan with appropriate contract modification.

MTEC anticipates that a single award will be made.

Administrative Information:
Full proposals are due no later than February 25, 2019 at 12:00pm EST. The RPP is posted to the MTEC website (mtec-sc.org) and FedBizOpps (fbo.gov) to notify interested parties. MTEC membership is required for the submission of a full proposal in response to this MTEC RPP. Offerors submitting Full Proposals as the prime contractor must be MTEC members of good standing by February 20, 2019. To join MTEC, please visit http://mtec-sc.org/how-to-join/

A Proposers Conference via webinar will be held for interested parties to have their questions answered by the USG after the RPP is posted. MTEC Members will be notified when the Proposers Conference is scheduled.

For inquiries regarding this announcement, please direct your correspondence to the following contacts:

• Technical questions
Dr. Lauren Palestrini, MTEC Director of Research, [email protected]
• Contracting questions
Ms. Rebecca Harmon, MTEC Contracts Administrator, [email protected]
• Administrative questions
Ms. Kathy Zolman, MTEC Program Manager, [email protected]
• Membership questions
Ms. Stacey Lindbergh, MTEC Executive Director, [email protected]

For more information about the RPP, please visit the MTEC webiste (a link is included in the attachment incorporated into this posting)

Bid Protests Not Available