Synergy Therapeutics is advancing SYN-126 which restores p53 functions by repressing the two most important p53 inhibitors, MDM2 and MDM4, and inhibiting two antiapoptotic proteins Bcl-xL and MCL-1. The human albumin component of SYN-126 enables heavy tumor loading based on tumor hunger for amino acids. SYN-126 has a unique profile, acting on four essential targets, providing efficacy against both p53 wildtype and mutant cancers. No p53-targeting drug is approved in the US or EU.

SYN-126 is tumoricidal and provides significant synergy to the anti-cancer efficacy of chemotherapeutics and kinase inhibitors. Synergy projects partnering SYN-126 after Phase I/II studies based on proven synergy with kinase inhibitors, chemotherapeutics and (we project) checkpoint inhibitors. We expect that SYN-126 will increase efficacy, reduce toxicity and slow resistance development. Please click on Our Science for more details.

The Problem at Hand

No p53-targeting drugs have been approved as a result of escape resistance driven by MDM4 (MDM2 homolog), unacceptable toxicity profile, or lack of intracellular penetration. The broad spectrum of p53 mutations presents a severe challenge. Significant unmet needs persist for patients with triple-negative breast cancer, ovarian, pancreatic and colorectal cancer and

leukemia/lymphoma. Many small molecule MDM2 inhibitors are in development by competitors, but this class has failed to demonstrate efficacy after nine years of clinical studies.

Origins and Platforms

Synergy Therapeutics is a spin-out from the Philadelphia College of Pharmacy and has licensed exclusive rights to four US and one EP patent. Synergy’s license from Saint Joseph’s University includes use of human serum albumin (HSA) platform technology as a feasible and powerful ADC alternative to target tumor cells with DNA, RNA, peptides or small molecules. This approach could strengthen tumor loading and extend circulation time for the new category of peptide-drug conjugates (PDCs), such as Novartis’ LUTATHERA, which have a number of advantages over antibody-drug conjugates.