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Topic: 3,4-DAP Investigational New Drug Filing Background Botulinum neurotoxins (BoNT) are a serologically diverse family of proteins produced by organisms of the genus Clostridium (Simpson, 2004). In... Topic: 3,4-DAP Investigational New Drug Filing Background Botulinum neurotoxins (BoNT) are a serologically diverse family of proteins produced by organisms of the genus Clostridium (Simpson, 2004). Intoxication with BoNTs, either through ingestion of contaminated food, injection drug use, or through inhalational exposure leads to botulism, a condition often requiring intensive care with mechanical ventilation. The only FDA-approved medical countermeasure currently available is an antitoxin, which prevents circulating toxin from causing any more harm, but does not heal the damage the toxin has already done (Centers for Disease Control and Prevention , National Center for Emerging and Zoonotic Infectious Diseases, Division of Foodborne, Waterborne, and Environmental Diseases , 2018). A capability to mitigate the effects of botulinum neurotoxin intoxication to reduce/eliminate reliance on mechanical ventilation is required. The drug 3,4-diaminopyridine (DAP), which is currently approved for treatment of Lambert-Eaton myasthenic syndrome (LEMS), has shown promise as a treatment for botulism (McNutt et al, 2018)). Current efforts are further evaluating 3,4-DAP for efficacy against botulinum serotypes in animals models. Filing an IND for 3,4-DAP against BoNT will lay the groundwork for a clinical study and, given the drugs recent approval for symptomatic treatment of LEMS, a potentially accelerated pathway for approval of a new drug for the symptomatic treatment of botulinum intoxication. Capability Sought Information is being sought on approaches to filing an investigational new drug (IND) application with the US Food and Drug Administration for 3,4-DAP against botulinum toxin. Specifically, respondents shall describe: Approach to filing the IND, including any activities to collect data and/or cross-reference existing IND/NDA filings for 3,4-DAP, and proposed rights to the USG. Any restrictions on cross-referenced label, specific formulations and route of administration. Timeline to file the IND. Rough order of magnitude cost to file the IND. Response Instructions Respondents shall address the information described above (and any additional information the respondent shall deem appropriate) via a Capability Statement (five-page limit) in Microsoft Word format. In addition, respondents shall include their name, address, CAGE code, and DUNS, and submit company size standard under the 541714 Research and Development in Biotechnology code. The information shall be submitted via e-mail to dtra.belvoir.rd.list.cbm-therapeutics@mail.mil. Hard copy submissions will not be accepted. Submissions shall be submitted by no later than 2:00 pm local Ft. Belvoir time on July 28, 2020. Disclaimer This Sources Sought notice is solely for the purpose of gathering information and does not constitute a solicitation or the issuance thereof. All information received in response to this notice that is marked proprietary will be handled accordingly. Responses to this notice are not offers and cannot be accepted by the Government to form a binding contract. Any information submitted will not be returned, and no payment will be made by the Government for such information. No formal RFPs or other solicitations regarding this announcement are available at this time. Information provided herein is subject to change and in no way binds the Government to solicit for proposals or award contracts. It is the respondent’s responsibility to monitor Contract Opportunities at https://beta.sam.gov for the release of any subsequent information. DTRA is accepting questions regarding this notice but will not be providing responses. References: Centers for Disease Control and Prevention , National Center for Emerging and Zoonotic Infectious Diseases, Division of Foodborne, Waterborne, and Environmental Diseases . (2018, October 4). Botulism Diagnosis and Treatment. Retrieved from https://www.cdc.gov/botulism/testing-treatment.html McNutt et al, P. (2018). 3,4-diaminopyridine reverses paralysis in botulinum neurotoxin-intoxicated diphragms through two functionally distinct mechanisms. Toxicology and Applied Pharmacology, 77-86. Simpson, L. L. (2004). Identification of the Major Steps in Botulinum Toxin Action. Annual Review of Pharmacology and Toxicology, 167-93.