Development of Oral Immunotherapy for the Prevention of Bacterial Diarrheal Disease

Purpose

This solicitation, issued by MTEC, represents a Request for Project Proposals (RPP) for MTEC support of the U.S. Department of Defense (DoD) U.S. Army Medical Research and Development Command (USAMRDC) Military Infectious Diseases Research Program (MIDRP). Proposals selected for award as a result of this RPP will be awarded under the authority of 10 U.S.C. § 2371b. Strategic oversight for the award(s) supported by this RPP will be provided by the MIDRP.

This RPP is focused on the development of a self-administered oral immunotherapy (not a vaccine) to prevent endemic diarrheal disease by targeting multiple bacterial pathogens. The self-administered oral immunotherapy should mitigate symptoms, shorten the duration of illness, and/or reduce the risk of contracting bacterial diarrheal illnesses. The proposed immunotherapy product would target enterotoxigenic Escherichia coli (ETEC), and at least one other common bacterial diarrheal pathogen such as Campylobacter or Shigella. The oral immunotherapy must be stable without requiring a cold-chain and therefore could be utilized by the Warfighter in austere environments.

Scope of Work

An ideal solution would meet all of the following requirements (not listed in order of importance) by the end of the proposed Period of Performance (PoP). Therefore, Offerors shall address within the proposal submission how and when each of these will be accomplished during the PoP.

Note: Although Enhanced White Papers that propose to meet all of the product requirements outlined below are preferred, the Government may consider responses demonstrating only a portion of the final product attributes if the team’s approach can address how the remaining requirements can be met over time. Therefore, it is expected that an Offeror’s Enhanced White Paper will describe in detail what they plan to accomplish and how they plan to satisfy all of the product requirements either during the proposed PoP or beyond that period (Offerors should specify the projected timeline), as applicable.

• An immunotherapy product in an oral formulation for delivery to the gut.
• An oral immunotherapy product that prevents diarrhea attributable to ETEC and one or more other pathogens with evidence that multiple pathogens are feasibly targeted.
• The oral immunotherapy product would be self-administered, before or during deployment, offering protection throughout a routine deployment period (6 weeks-6 months). The requiring activity (or end user) seeks to minimize in-theater dosing. If it must be administered in the field, three doses per day is the maximum frequency sought. Demonstration of less than three doses per day is highly favorable. Requirements for administration and re-supply storage must be consistent with prolonged care in austere environments, where evacuation and logistics capabilities will be minimal.
• The oral immunotherapy product: (1) would have ease of use (administration, easy-open packaging, components, suspension needs), (2) be usable and efficacious in austere environment conditions (packaging should maintain integrity in wide temperature ranges between 0-45ºC, and in conditions of high and low humidity), (3) be small and lightweight without the need for additional logistic considerations, e.g., cold/warm storage, impact protection, and additional supplies/products to enable use (e.g. water-based suspensions).

At the end of the PoP, the Offeror(s) is expected to have successfully achieved all the following milestones:

• Completed studies which refine and optimize the prototype immunotherapy to prevent endemic diarrheal disease: (i) Completed proof-of-concept efficacy studies, dose-dependent efficacy studies (studies to minimize dosing while maintaining efficacy); and (ii) Completed Good Laboratory Practice (GLP) compliant studies demonstrating sufficient safety and efficacy profile in relevant animal model(s), human dose equivalent, and route of administration as intended for human use; and (iii) Completed Investigational New Drug (IND)-enabling studies, including in vivo toxicity studies (if needed), human tissue cross reactivity studies, and stability studies.
• A completed Phase 1 and/or Phase 2 clinical trial demonstrating adequate safety and preliminary efficacy profile against all target pathogens in optimized dose and schedule.
• All completed clinical studies shall be reported in a Final Clinical Study Report following ICH E3 Structure and Content or its current iteration.
• Evidence that production is capable of scale-up and available quantities of the product are adequate to support the remainder of clinical development.
• Demonstrated stability of product(s) for at least one year at 0-45ºC and under conditions of low and high humidity. Offerors should put accelerated conditions in their stability protocol to demonstrate limits of the technology.
• A defined regulatory pathway: An adequately defined, detailed regulatory pathway toward a Medical Device, Biologics License, or New Drug Application, including (but not limited to) Phase 2 and/or Phase 3 study plans validated by formal communication with the U.S. Food and Drug Administration (FDA).

Points of Contact

For inquiries, please direct your correspondence to Biomedical Research Associate Chuck Hutti, Ph.D. at Chuck.Hutti@ati.org.