SBIR TOPIC 395: IDENTIFICATION OF BI-SPECIFIC ANTIBODIES TO INHIBIT GDF-15 AND ACTIVIN A FOR ANOREXIA-CACHEXIA

Anorexia cachexia is a debilitatinglife threatening diseaseassociated with pronounced loss of appetiteskeletal muscle and fat massAnorexia cachexia constitutes a major unmet medical needasof patients with advanced cancers exhibit cachexia andof mortalities are derived from cachexia rather than tumor burdenPatients are less tolerant to radiotherapychemotherapypharmacotherapy and surgeryThere are no approved treatments representing a high unmet medical needThe etiology of cancer anorexia cachexia is attributed to abnormal metabolisminduced by tumor derived cytokinesPatients with elevated plasma levels of tumor derived GDFand Activin A are associated with weight loss and poor survivalGDFand Activin A are causal factors mediating anorexia and muscle wastingrespectivelyOverexpressing GDFand Activin A results in anorexia and muscle atrophyBlocking endogenous GDFand Activin A in tumor induced weight loss modelsreverses cachexia and dramatically prolongs survivalThe goal is to identify bispecific antibodies against GDFand Activin AA successful outcome will be to prioritizediverse leadsThe clinical candidate will suppress plasma levels of GDFto ltng mL and Activin A to ltng mL in cancer patientsSuppressing GDFand Activin A will increase appetitedecrease catabolismreverse muscle atrophyincrease bone strength and suppress metastatic lesionsCollectivelythis unique profile will enable patients to receive optimal anti cancer therapy to increase survival and quality of life