Amyotrophic Lateral Sclerosis Research Program Therapeutic Development Award

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The Therapeutic Development Award supports a wide range of development activities ranging from validation of therapeutic leads to U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) submission. The proposed studies are expected to be empirical in nature and product-driven. Applications supported by this award must begin with lead compounds in hand. Examples of activities that will be supported by this award include: • Secondary validation of lead compounds obtained from screening or by other means to demonstrate target selectivity and mechanism of action, • Optimization of potency and pharmacological properties, development of structure-activity maps via synthesis, and testing of derivatives and sister compounds, • Studies on formulation and stability, • Development of GMP production methods, • Collection of data for FDA IND applications, to include compound characterization, absorption, distribution, metabolism, and excretion (ADME) studies, and dose/response and toxicology studies. In parallel with lead compound validation and development, applicants are strongly encouraged to assess in vivo efficacy or target engagement (measurement of target binding or proximal downstream effects) in a relevant preclinical ALS model(s). Applications must include preliminary data and other supporting information relevant to the phase(s) of the preclinical development, such as the following: • Background data supporting the putative mechanism of action as a viable therapeutic approach An identified bioactive compound or limited group of identified lead molecules with: ○ Proof of identity and purity ○ Selectivity for the intended target over closely related targets (when the target is known) • Availability of primary and secondary in vitro bioactivity assays for optimization or structure-activity relationship studies • Availability of appropriate preclinical animal models of ALS to assess in vivo efficacy or desirable mechanism-specific drug activity at the intended target (target engagement) Investigators interested in basic research focused on ALS drug discovery are encouraged to apply for the FY16 ALSRP Therapeutic Idea Award (Funding Opportunity Number: W81XWH-16-ALSRP-TIA), which does not require preliminary data (http://cdmrp.army.mil/funding/alsrp.shtml). Collaborations: The preclinical drug development process may require resources beyond those available at single institutions. Collaborations with other research institutions and partnerships with biotechnology/pharmaceutical industry partnerships are encouraged. Biotechnology or pharmaceutical companies intending to apply for the Therapeutic Development Award are encouraged to leverage their own resources to complement the funding provided by this award. Participating organizations should ensure the success of the collaboration by resolving potential intellectual and material property issues and by removing organizational barriers that might interfere with achieving high levels of cooperation. Applicants with limited ALS experience are strongly encouraged to collaborate with those having substantial expertise in ALS research and/or ALS model systems. Letters confirming/supporting the collaboration are required.

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