TOPIC CALL 6.pdf

CB BAA HDTRA122S0002 CALL 6

THE PROPOSAL SUBMISSION DEADLINE FOR THE

FOLLOWING TOPICS IS APRIL 10, 2025 AT 2:00PM EASTERN

DAYLIGHT TIME (EDT).

THE DEADLINE TO SUBMIT QUESTIONS RELATED TO THE

FOLLOWING TOPICS IS FEBRUARY 27, 2025.

CBM-01: Tissue protective and regenerative, broad-spectrum medical countermeasures

Background:

Uniformed military personnel perform operations in environments that are at high risk for exposure to chemical and biological threats that could threaten effective military operations within an area of concern. In the past, the number of known chemical and biological threats was defined and limited, thereby allowing targeted drug development. Presently, however, the broadening horizon of chemical and biological threats coupled with the unpredictability of new and emerging threats increases the risk that one-bug, one-drug medical countermeasures (MCMs) will not provide an adequate defensive posture. As a result, the chemical and biological defense program (CBDP) is pivoting away from agent-specific solutions and toward drugs that exhibit broad-spectrum preventive and therapeutic actions. The definition of broad-spectrum herein is a drug that is capable of either preventing or treating the pulmonary, cardiac, and/or neurological pathogenic effects of multiple threat agent species. Drugs that target tissue regeneration processes and accelerate restoration of tissue homeostasis are of higher interest than drugs that target common pathogenic pathways, although the latter are not excluded. Drug formulation strategies that enable rapid oral availability are also preferred.

Objective:

The primary objective of this topic is to solicit proposals that aim to develop orally available small-molecule drugs that target tissue regeneration processes in the lung, heart and/or brain. However, proteins and monoclonal antibodies that target tissue regeneration processes are not outside the scope but are lower in priority to orally available small-molecule drugs. Proposals with a rigorous drug discovery strategy to produce scalable drugs with the desired effect are within the scope of the objectives.

Impact:

Successful projects in this topic area will provide uniformed military personnel with the freedom to perform operations in environments that are at high risk for exposure to chemical and biological threats, including those at risk for exposure to new and emerging threats.

CBM-02: Prophylactic Medical Countermeasures (MCMs) against Chemical Agents of Concern

Background:

The deliberate release of a chemical agent on the battlefield poses a threat to the operational effectiveness of the Joint Force. The management of casualties with exposures to chemical warfare agents (CWAs) is well documented since the first battlefield use of chemical weapons in World War I (WWI). Medical management has evolved from supportive care only to the development of specific therapeutic countermeasures. This approach has been successful in providing targeted solutions in both the prevention and the treatment of insult or injury from many CWAs, however the need to treat casualties of chemical agent exposure decreases force readiness and lethality. Ideally, forces will not be affected by exposure to any chemical agent. By providing a prophylactic medical countermeasure that is widely targeted against multiple chemical agents or will attenuate the effects of chemical agent toxidromes with no side-effects, the warfighter can be protected.

Objective:

Proposals are sought for novel and innovative prophylactic MCMs to protect against chemical agents that cause either the Cholinergic or Convulsant Toxidromes such as those caused by organophosphate nerve agents (OPNAs) (https://chemm.hhs.gov/toxicsyndromes.htm). Proposals for solutions with the following characteristics are highly desired:

1. Minimally provide 10 days of protection prior to agent exposure.

2. Utilize routes of administration conducive to protecting the total force.

3. Utilize advanced technologies to enable rapid development and deployment of medical countermeasures against emerging agents, to include:

a. Technologies that optimize and accelerate the development and manufacturing of medical countermeasures.

b. Technologies that accelerate the safety and efficacy testing of medical countermeasures and adhere to and inform regulatory guidelines.

c. Technologies that enable point-of-need manufacturing that is far-forward, expeditionary, on-shored, or friend-shored.

Proposals should address safety and efficacy studies, i.e., the solution must be demonstrated as safe and effective. Proof of efficacy should use quantitative metrics such as decrease in seizure activity, decrease in secretions, increase in time to symptom onset, increase in survival time, increase in ID50, ED50 or LD50 of the toxicant, etc.

We expect a variety of tools to be considered for use in addressing the requirement, including in silico, in vitro, ex vivo, or in vivo systems, possibly including established models as well as development of novel approaches if needed. Standardized data formats supportive of sophisticated modeling and machine learning are desirable, as are organ-on-a-chip or other approaches that appropriately reduce time and animal use requirements. The use of surrogates for CWAs vs. CWAs themselves over the course of the evaluation strategy should be carefully weighed to optimize cost and convenience of the assessment vs. the relevance of the results to the intended use. Ultimately, the proposal must clearly demonstrate how the solution will be tested against CWAs.

Offerors are encouraged to develop Research & Development collaborations with other organizations in government, academia, and the private sector to broaden and strengthen their knowledge, experience, and capabilities. Additionally, offerors are encouraged to take advantage of specialized resources in DoD and other Government agencies such as facilities/capabilities with chemical surety certification, https://chemm.hhs.gov/toxicsyndromes.htm and for non-Good Laboratory Practices (GLP) preclinical studies, ADME (Absorption, Distribution, Metabolism, and Excretion) testing and manufacturing. If applicable, it is encouraged that engagement with the Food and Drug Administration (FDA) be pursued throughout the contract with the intent that the product will ultimately achieve licensure.

The following attributes should be considered to develop the most attractive proposal:

1. Medical Countermeasure (MCM) candidates which demonstrate compatibility with military operations, for example in terms of ease of administration, storage stability (2-5 years at freezer, refrigerate, or room temperature), and minimal number of administrations to provide desired protection

2. Potential side effects of MCM

3. MCM with broad spectrum application across a wide spectrum of chemical agents

4. Demonstration of previous clinical testing/use or safety of the delivery technology

5. Minimal cost per dose

6. MCM allowing for repeat administration with limited immunogenicity

7. Fully developed comprehensive Target Product Profile (TPP) and regulatory strategy, appropriate to program maturity

8. Preliminary data supportive of proof-of-concept

Types of proposals that do not meet the intent of this topic include those that propose development of:

• Countermeasures against opioids, countermeasures that are not amenable toward use for the total force,

• Countermeasures against toxic industrial chemicals or toxic industrial materials, or

• Countermeasures which do not meet the requirement to provide lasting protection prior to chemical exposure.

Areas of research that will not receive consideration under this topic include:

• Research using Schedule 1 drugs or related compounds

• Research using natural products that produce the same effects as Schedule 1 drugs

• Research with products from endangered plant or animal species

Impact:

The results of proposed research efforts will ultimately provide the Warfighter and the Chemical and Biological Defense Program with improved protection against the adverse effects of the Cholinergic and/or Convulsant Toxidromes and the agents that cause them. Additionally, it will provide a more agile and robust discovery and development pipeline for chemical medical countermeasures. Furthermore, this research will provide risk reduction to the current candidates in the pipeline for both the early and advanced developers.

References:

1. Food and Drug Administration (FDA), (2015). Product Development under the Animal Rule FDA Guidance: https://www.fda.gov/downloads/drugs/guidances/ucm399217.pdf

2. U.S. Health and Human Services (U.S. HHS), U.S. HHS Chemical Hazards Emergency Medical Management (CHEMM) https://chemm.hhs.gov/toxicsyndromes.htm