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The Medical Technology Enterprise Consortium (MTEC) is excited to post this pre-announcement for a Request for Project Proposals (RPP) focused on the development of a bacteriophage prototype for the treatment of multidrug resistant (MDR) bacterial infections employing a tailored, precision approach. The overall end goal of the program is a commercial bacteriophage product that is approved by the U.S. Food and Drug Administration (FDA) and suitable for use by the U.S. Military.
Recent conflicts in Iraq and Afghanistan have seen a notable rise in the survival of combat casualties. These patients with anatomically complex wounds and extended, invasive treatment regimens are vulnerable to combat extremity wound infections. Furthermore, those infections are often clinically complicated or multidrug resistant and thus difficult to treat effectively. The bacterial species responsible for these types of infections often include the group called ‘ESKAPE’ pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp), which cause the majority of infections within the nosocomial environment and are noted for prevalence of antibiotic resistance.
Multidrug antibiotic resistance is an emerging medical challenge that is reaching crisis proportions. Existing antimicrobials are losing their efficacy, and the drug development pipeline for traditional small molecule antimicrobials (antibiotics) is limited in new alternative candidates. One alternative to traditional antibiotics for treatment of bacterial infections is bacteriophage therapy.
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 to delivering bacteriophage therapy. It should be possible to overcome both the genetic diversity of bacterial clinical pathogens and the selection for phage-resistant variants in the course of treatment using individualized phage therapeutics on a case by case basis. With a successful precision strategy, bacteriophage therapy may be an open-ended solution to the treatment of bacterial infections.
This precision medicine approach to bacteriophage therapeutics does face a challenging product development and production pathway. Given the complexity of phages themselves and the inherent novelty of precision therapeutic approaches, 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.
The goal of this program is to support the Research, Development, Test and Engineering (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. The successful offeror will include in their proposal a realistic regulatory strategy and development framework for reaching that objective.
This MTEC RPP focuses on the execution of clinical trial(s) for the treatment of complicated or MDR bacterial infections, treating appropriate ESKAPE infection indication(s) to most effectively advance a precision bacteriophage product toward FDA licensure.
The goal of this MTEC award is to evaluate human safety and efficacy of a bacteriophage prototype for treatment of MDR infections. Examples of bacterial infection diagnoses relevant for testing of bacteriophage therapy 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 complicated and MDR bacterial infections.
This program’s first Task seeks to test precision bacteriophage therapy using a suitable clinical indication that will maximize the probability of assessing efficacy. The Government may pursue optional follow-on tasks to continue product development through additional clinical trials for relevant FDA marketing approval/licensure. The intent of this prototyping effort is to secure a development partner to complete all requisite FDA-compliant manufacturing and packaging development, complete the Phase 1 / 2 clinical trials (2) (Task 1 and options, as denoted below), conduct Phase 2 clinical trials (option), conduct Phase 3 clinical trial(s) (option), and to complete all other developmental requirements to support a BLA application to FDA to ultimately support FDA licensure.
Offerors, as the regulatory sponsor for the eventual submission to FDA, will be expected to conduct all manner of development, test and evaluation activities (as necessary) to achieve an FDA-licensed precision bacteriophage product that is suitable for use by the U.S. Military. It is expected that the Offeror will work in close coordination with the DoD, and is encouraged to partner with medical treatment facility(ies) such as the Veteran’s Administration and/or Department of Defense (DoD) medical facilities for the conduct of the clinical trial. The Offeror shall identify any proposed U.S. Government (USG) or DoD partner medical treatment facilities, if a Government facility is proposed to be used in the performance of this proposed effect.
The full spectrum of work is expected to be conducted in several tasks over a minimum of a 6 year period of performance (PoP), as follows. Task 1 is the basis for the upcoming award but Tasks 2, 3, and 4 may be added as follow-on work dependent on the technical progress and/or outcome of Task 1, and therefore, may be of interest to potential Offerors. Potential Offerors are expected to propose a clinical trial in response to Task 1, only, and to include in their proposal a realistic regulatory strategy and development framework for ultimate BLA approval of a precision bacteriophage therapeutic that would encompass the follow-on Tasks 2-4 (or equivalent).
Task 1 (PoP up to 2 years): Conduct Phase 1 / 2 clinical trial(s) for MDR ESKAPE pathogen infections 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 compliant Phase 3 clinical trial(s) and submission of BLA for FDA licensure.
Potential Funding Availability:
The U.S. Department of Defense (DoD) currently has available approximately $2 Million (M) for the first Task of this effort. The Period of Performance (PoP) is 24 months for Task 1. Dependent on the results and deliverables from Task 1, additional time may be added to the period of performance for follow-on tasks.
It is expected that MTEC will make a single award to a qualified team to accomplish all tasks. The program shall be led by a centralized point of contact at the prime contracting organization. If a single proposal is unable to sufficiently address the entire scope of this RPP’s objectives, several Offerors may be asked to work together in a collaborative manner.
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, “nontraditional” government contractors, academic research institutions and not-for-profit organizations.
Full proposals will be required in response to this upcoming RPP. The RPP will be posted to the MTEC website and a notice will be posted on FedBizOpps (fbo.gov) to notify interested parties. MTEC membership is required for the submission of a full proposal in response to this upcoming MTEC RPP. To join MTEC, please visit http://mtec-sc.org/how-to-join/.
For inquiries regarding this pre-announcement, please direct your correspondence to the following contacts:
- Technical questions – Dr. Lauren Palestrini, MTEC Director of Research, email@example.com
- Administrative questions – Ms. Kathy Zolman, MTEC Program Manager, firstname.lastname@example.org
Filed Under: Funding Opportunities