Our proposed work will result in translation of lead neurotherapeutic countermeasure (SB_NI_112) developed during NASA SBIR Phase I and II, for deployment in deep-space missions. During Phase I SBIR, we developed and tested countermeasures for: 1) reversal of immune dysregulation caused due to radiation, in vitro using human donor derived peripheral blood mononuclear cells (PBMCs); and 2) in vivo using an animal (mice) radiation model, showing reversal of neuroinflammation in brain. During work in Phase II SBIR we: 1) provided pharmacokinetic and pharmacodynamic (PK/PD) and biodistribution data; 2) determined dosing and dose frequency to obtain optimal therapeutic effect for reversing radiation-induced immune dysfunction and neuropathology/degeneration; 3) conduct small (mice) safety, toxicity, and maximum tolerable dose studies (IND-enabling studies), for translating the developed therapeutic; and 4) tested and validated the lead efficacy as neurotherapeutic countermeasure/therapeutics for SB_NI_111 and SB_NI_112 in relevant animal disease models (Multiple Sclerosis, Prion Disease, Parkinson’s Disease, Alzheimer’s Disease, Aging-induced Cognitive Decline and Dementia), and identified the top lead neurotherapeutic SB_NI_112. Our proposed work in Phase II E is geared for translating SB_NI_112 towards human clinical trials by: 1) identifying a beachhead indication (amongst Prion Disease and Amyotrophic Lateral Sclerosis or ALS) and developing a regulatory and clinical translation strategy; 2) filling Orphan Drug Designation (ODD) application with US Food and Drug Administration (FDA) for identified beachhead (Prion or ALS); 3) conduct key chemistry, manufacturing, and controls (CMC) studies, dose-response curve through one translatable route of administration (oral or sub-cutaneous injection) for identified beachhead, and clinical trial and GLP-tox study design, for filling for pre- Investigational New Drug (IND) and IND-filling with FDA.

Sachi is teaming with Sierra Space and Space Tango for deployment of rapid and low-cost drug-discovery in space (under InSPA SBIR Phase III), for therapeutic manufacturing and testing in space. Sachi and Space Tango will be flying two spaceflight missions to ISS within 24-36 months, to collect key commercial and scientific data for accelerated drug-discovery in space, using the Nanoligomer platform developed during the current SBIR Phase I and II. The lead molecule SB_NI_112 will also be tested in space, to assess safety and efficacy.

The space-based therapeutic screening can potentially accelerate drug-development for diseases such as neurodegeneration, cardiovascular, and cancer, by leveraging the accelerated disease progression due to microgravity and radiation. Commercialization objective also include translating the molecules developed here as therapy for Alzheimer’s, Parkinson’s, Multiple Sclerosis, to improve outcomes.