Next-Gen Oral Therapeutics for Type 2 Diabetes

Next-Gen Oral Therapeutics for Type 2 Diabetes BioTherapeutics Inc (BTI) is a clinical-stage biotech company that synergistically combines the power of advanced computational modeling with translational and clinical experimentation to accelerate the development of novel precision medicine therapeutics for inflammatory and autoimmune diseases. The BTI team has extensive expertise in developing novel first-in-class therapeutics through IND filing and Phase 1-3 clinical testing and NDA approval. Type 2 diabetes (T2D) is a significant public health concern afflicting about 500 million people worldwide. Diabetes is the seventh leading cause of death in the U.S., and a significant cause of disability and low quality of life, with annual expenses exceeding $410 billion per year. Prediabetic or high-risk subjects (i.e. excess body weight, insulin resistance, high blood lipids and hypertension) are advised to follow dietary and lifestyle guidelines, which have a very low rate of adherence. The CDC estimates that 1 out of 3 US adults will become diabetic by 2050. This gloomy forecast calls for safer and more effective strategies to tackle the diabetic pandemic. This SBIR Phase I application aims to develop the next generation of oral, once-a-day precision medicine therapeutic candidates for the treatment of pre-diabetes and T2D that target a novel mechanism of action with no dose-limiting toxicities. The Specific Aims of this SBIR Phase I application are to: AIM 1. Determine the translational potential in human primary cells of diabetic patients. We will evaluate the therapeutic efficacy of our lead drug candidate on lipid metabolism, insulin sensitivity, glucose uptake and secretome profile in differentiated adipocytes and adipocyte-mediated changes in skeletal muscle function. AIM 2. Evaluate the comparative therapeutic efficacy of our lead product candidate versus approved T2D drugs in two mouse models of obesity and diabetes through analysis of weight change, glycemic control, including blood glucose, glucose and insulin tolerance tests (GTT and ITT), and glycated hemoglobin (HbAc1), plus systemic and local inflammation in plasma and visceral adipose tissue (VAT), respectively. Expected successful outcomes: i) ≥ 25% decrease area under the curve in GTT and ITT, and ≥30% decreased infiltration of inflammatory macrophages compared to the approved therapeutics, plus ii) ≥40% increase in IL6 and CCL2, and ≥35% increased glucose uptake in adipocytes from diabetic patients. SBIR Phase II will progress our lead product candidate to IND-enabling studies, evaluate combination therapies and initiate Phase 1b clinical testing in patients with T2D. Commercial Application: This proposal will validate the development of an oral, once-daily therapeutic candidate for the treatment of pre-diabetes and T2D with the potential to disrupt a rapidly expanding annual diabetes market estimated to reach $134 billion by 2030.