Spitfire Pharma, Inc., is developing a novel dual GLP-1/glucagon receptor agonist for the treatment of type 2 diabetes and obesity. The lead candidate, SP-1373, is a potent and highly efficacious and balanced agonist at both the GLP-1 and glucagon receptor that has demonstrated a robust glucose lowering and pronounced and sustained weight loss in animal models of type 2 diabetes and obesity. SP-1373 is a novel peptide with a proprietary EuPort ™ modification designed to achieve extended PK half-life and provide tunable physicochemical properties. The target product profile for SP-1373 is to achieve glycemic control comparable to the GLP-1 agonists but with more impressive weight loss with once-weekly subcutaneous administration.
The program, which includes a robust back-up effort, is in preclinical development and on track to file an IND for SP-1373 in 18 months.
The pharmacological rationale for the dual agonist approach is based on oxyntomodulin, a peptide hormone secreted by small intestine after meals. Oxyntomodulin is believed to exert its biological effects by activating both the GLP-1 receptor and the glucagon receptor. In humans, this hormone has been shown to have multiple beneficial effects on metabolism and obesity, improving glucose tolerance and causing substantial weight loss. A balanced agonist targeting both the GLP-1 and the glucagon receptor is potentially a more efficacious treatment for diabesity than GLP-1 receptor agonists alone due to decreased food intake and increased energy expenditure associated with the glucagon receptor.
Type 2 diabetes (T2D) and obesity are significant causes of morbity and mortality in the United States and globally Diabetes is the sixth leading cause of death in the United States and, together with obesity, is the largest public health challenge of this century. Sustained reduction of weight is important for obese individuals, particularly those who are insulin resistant or have T2D. Reduction of weight can improve insulin sensitivity and reduce fasting blood glucose concentrations,thus decreasing the need for drug therapy.
In the United States, more than 25 million people have been diagnosed with T2D and studies indicate that 80% to 90% of these individuals are also obese. Globally, the prevalence of T2D is estimated to be greater than 250 million and this is expected to reach 400 million by 2030.
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