Development of stapled oxyntomodulin-Fc fusion proteins for the treatment of diabetes and obesity

The rising obesity rate across all age groups underlines the dramatic increase in the incidence of diabetes in the United Statesaccording to CDCmillion people orof the population in the U Shave diabetes with an estimated total cost of $billion to the healthcare systemThe medical community has recognized that diabetes treatments should ideally lead to both blood glucose control and weight lossThe mission of Transira Therapeutics is to develop innovative best in class therapies for diabetes obesity using our proprietary peptide and protein cross linking chemistriesThe goal of this project is to develop the chemically cross linkedstapledoxyntomodulin Fc fusion protein as a once weekly therapy for treatment of diabetes and obesityIn our preliminary studieswe designed a series of stapled oxyntomodulinOXManalogs that show a balanced subnanomolar dual GLPR GCGR agonist activity along with the extended in vivo half lifeIn this phase I applicationwe have two specific aimsPreparation and biological evaluation of the stapled OXMIgG Fc fusion protein for higher potency and extended plasma half lifeandPre clinical evaluation of the weight lossglucose controland acute metabolic effects of the stapled OXM Fc fusion protein in DIO miceWe expect to identify one stapled OXM Fc fusion protein with andgthours of plasma half life following subcutaneouss cadministration in micecomparable to dulaglutidealong with a balanced subnanomolar in vitro potency toward GLPR and GCGRAimand that the stapled OXM Fc fusion protein achieves andgtdecrease in fasting glucose levels and andgtbody weight reductiongreater than dulaglutideafter s cadministration compared to placebo overweeks with improved glucose metabolismandgtreduction in AUC for OGTT at daymetabolic profile and body mass compositionAimThe successful conclusion of the proposed phase I studies should lay a solid foundation for IND enabling PK and toxicology studies in the phase II period To combat the rising incidence of diabetes to the epidemic proportion in the U Sdiabetes treatments should ideally lead to both blood glucose control and weight lossThis project aims to develop innovative best in class therapies for diabetes and obesity through the design and pre clinical evaluation of our proprietary chemically cross linked oxyntomodulin Fc fusion proteins in DIO mice