Department of Defense Amyotrophic Lateral Sclerosis, Therapeutic Development Award to Advance Preclinical Therapeutic Leads Towards FDA IND Studies

The FY23 ALSRP Therapeutic Development Award supports research ranging from preclinical validation of therapeutic leads through U.S. Food and Drug Administration (FDA) Investigational New Drug (IND)-enabling studies. The proposed studies are expected to be empirical in nature and product driven. Applicants with limited ALS experience are strongly encouraged to include collaborators with substantial experience in the relevant ALS model systems, endpoints, and pathophysiology. Examples of activities that will be supported by this award include:

• Confirmation of candidate therapeutics obtained from screening or by other means, including optimization of potency and pharmacological properties and testing of derivatives and sister compounds.

• Validation of pilot efficacy studies (such as from an ALSRP Therapeutic Idea Award), including the use of additional ALS model systems and/or replicating preliminary data with more time points or additional doses.

• IND-enabling studies to include: compound characterization; absorption, distribution, metabolism, and excretion (ADME) studies; studies on formulation and stability leading to Good Manufacturing Practice production methods; dose/response and toxicology studies in relevant model systems.

Applications supported by this award must begin with lead compounds in hand and must include preliminary data relevant to the phase of development, such as:

• Proof of identity and purity
• Selectivity for the intended target over closely related targets
• Availability of primary and secondary in vitro bioactivity assays for optimization or structure–activity relationship studies
• Availability of clear efficacy data in at least one relevant preclinical Amyotrophic Lateral Sclerosis (ALS) model, with adequate power and methods.

Applicants seeking support for basic research focused on ALS drug discovery are encouraged to apply for the FY23 ALSRP Therapeutic Idea Award (Funding Opportunity Number HT9425-23-ALSRP-TIA), which does not require preliminary data (https://cdmrp.health.mil/funding/alsrp).

The FY23 ALSRP Therapeutic Development Award supports research ranging from preclinical validation of therapeutic leads through U.S. Food and Drug Administration (FDA) Investigational New Drug (IND)-enabling studies. The proposed studies are expected to be empirical in nature and product driven. Applicants with limited ALS experience are strongly encouraged to include collaborators with substantial experience in the relevant ALS model systems, endpoints, and pathophysiology. Examples of activities that will be supported by this award include:

• Confirmation of candidate therapeutics obtained from screening or by other means, including optimization of potency and pharmacological properties and testing of derivatives and sister compounds.

• Validation of pilot efficacy studies (such as from an ALSRP Therapeutic Idea Award), including the use of additional ALS model systems and/or replicating preliminary data with more time points or additional doses.

• IND-enabling studies to include: compound characterization; absorption, distribution, metabolism, and excretion (ADME) studies; studies on formulation and stability leading to Good Manufacturing Practice production methods; dose/response and toxicology studies in relevant model systems.

Applications supported by this award must begin with lead compounds in hand and must include preliminary data relevant to the phase of development, such as:

• Proof of identity and purity
• Selectivity for the intended target over closely related targets
• Availability of primary and secondary in vitro bioactivity assays for optimization or structure–activity relationship studies
• Availability of clear efficacy data in at least one relevant preclinical Amyotrophic Lateral Sclerosis (ALS) model, with adequate power and methods.

Applicants seeking support for basic research focused on ALS drug discovery are encouraged to apply for the FY23 ALSRP Therapeutic Idea Award (Funding Opportunity Number HT9425-23-ALSRP-TIA), which does not require preliminary data (https://cdmrp.health.mil/funding/alsrp).