REQUEST FOR INFORMATION IMPROVED NERVE AGENT …

1 IMPROVED NERVE AGENT Treatment System (INATS) MMB4 RFI 18-08 Page 1 of 3 REQUEST FOR INFORMATION IMPROVED NERVE AGENT TREATMENT SYSTEM (INATS) MMB4 DEPARTMENT OF DEFENSE SOLUTION TO DEVELOP AN IMPROVED OXIME WITH INCREASED EFFICACY AGAINST NERVE AGENTS Objective: This is a REQUEST for INFORMATION (RFI) for planning purposes only. It is not to be construed as a commitment by the Government nor will the Government pay for the INFORMATION solicited. No solicitation document exists or is guaranteed to be issued as a result of this RFI.

2 The Joint Product Manager for Chemical Defense Pharmaceuticals (JPdM CDP) at the Joint Program Executive Office for Chemical and Biological Defense (JPEO CBD) Medical Countermeasures Systems (MCS) is seeking INFORMATION on the capabilities and willingness of private entities (non-profit and commercial) in the areas listed below. Background: Therapeutic pharmaceuticals against chemical, biological, radiological and nuclear (CBRN) warfare agents are required to support the Joint Forces across a range of military operations.

3 As such, the DoD has a need for developing and fielding systems that provide treatment for exposure to CBRN agents. The JPdM CDP is responsible for the development, procurement, fielding, and sustaining of medical treatment and prophylactic capabilities against chemical, radiological and nuclear threats. The current MCS-CDP portfolio includes NERVE AGENT therapeutics, pretreatments and prophylactics at varying stages of clinical development, including FDA-approved drugs. The DoD is developing the oxime MMB4 DMS for the self and buddy-aid reactivation of acetylcholinesterase (AChE) at neuromuscular junctions and other nicotinic and muscarinic sites.

4 MMB4 DMS will replace and provide IMPROVED product performance overly the currently the fielded oxime, pyridine-2- aldoxime methyl chloride (also known as pradiloxime chloride or 2-PAM). In nonclinical animal efficacy studies, MMB4 DMS has demonstrated substantial improvement in effectiveness and medical treatment outcomes as an AChE reactivator when compared to 2-PAM. If successful, MMB4 will replace 2-PAM in the ATNAA or an alternative auto-injector. Requirements: The objective of the INATS is to develop an IMPROVED NERVE AGENT treatment regimen consisting of a more effective oxime to replace the fielded oxime 2-pralidoxime chloride (2-PAM).

5 This development effort requires the study of an IMPROVED oxime prototype to include but not limited to: formulation, stability and compatibility studies; non-clinical and clinical studies; manufacturing process development; large-scale manufacturing; and the preparation and submission of a New Drug Application (NDA). The DoD lead prototype is MMB4 DMS (1,1 -methylenebis[4-[(hydroxyimino)methyl]-p yridinium] dimethanesulfonate). The objective of issuing this RFI is to gather INFORMATION that will assist in the determination of a suitable solution for the advanced development of the oxime.

6 The Government requests that potential performers provide an up to 5 page response containing the following INFORMATION on current industry capabilities from interested entities with potential to meet ANY of the following criteria, IN WHOLE OR IN PART: (1) Description of your company s experience with the program management of technically complex efforts, to include: IMPROVED NERVE AGENT Treatment System (INATS) MMB4 RFI 18-08 Page 2 of 3 Existing capabilities to manage pharmaceutical product development efforts through FDA approval, to include assuming product sponsorship.

7 A. Product(s) taken to FDA licensure/approval, including product type. Examples include small molecule therapeutics, large molecule therapeutics, vaccine, etc. b. Current products under development expected to achieve FDA licensure. Include explanation of product type and current stage of development. Examples include small molecule therapeutics, large molecule therapeutics, vaccine, etc. c. Experience with product development under 21 CFR 314 Subpart I or 601 Subpart H ( , the Animal Rule). Include any animal subject concerns.

8 (2) Description of your company s technical expertise in pharmaceutical product development, to include: Ability to manufacture current Good Manufacturing Practices (cGMP)-compliant clinical material to support Phase 1 and/or Phase 2 clinical studies. a. Experience with performing chemistry, manufacturing, and controls (CMC) studies and activities to include: standard characterization; assay development and validation; process development and validation; process scale-up assessments; preparation of technology transfer packages; formulation preparation and analysis; clinical trial formulation development; clinical dose delivery; container closure/extractables/leachables/compatab ility and sterilization.

9 B. Estimate of small and/or large-scale cGMP-compliant manufacturing capability, to include experience with successful scale-up activities to full scale. c. Experience implementing International Conference of Harmonization (ICH) stability test programs to establish product shelf life, storage conditions and stability; experience conducting stability and compatibility testing of the pharmaceutical with the delivery device. Ability to manage and conduct clinical study activities, Phase 1 dose escalation/pharmacokinetic studies and Phase 2 expanded safety/drug-drug interaction studies, in accordance with FDA regulations and Good Clinical Practices (GCP) guidelines.

10 A. Experience designing GCP-compliant clinical protocols, informed consent forms, and case report forms sufficient for submission to the Army Human Research Protection Office (HRPO). b. Experience managing day-to-day clinical study operations, to include study drug and study supplies inventory management, severe adverse event management, and safety monitoring board management. Experience with clinical study data management, archiving and final study report generation. c. Experience with the design and conduct of the bioanalytical and pharmacokinetic (BA/PK) aspects of human clinical trials as well as with the analysis and evaluation of BA/PK data from human clinical trials.