OUR SCIENCE
The Creation of SYN-126
Synergy has created an albumin fusion protein, SYN-126, possessing a p53-derived
peptide (shown below on the left in yellow and red) with conserved residues (in red) binding to MDM2, MDM4, Bcl-xL, and MCL1. Below on the right, we show this peptide fused to human serum albumin, which is taken up by tumor cells as a nutrient source and enables heavy tumor loading.
SYN-126 is tumoricidal and is active against both p53 Wild-Type (WT) and Mutant (MT) cancers. The figure on the right shows mechanisms of action of SYN-126 via p53 transcription-dependent and independent pathways.
Our Progress
Our fusion protein has shown tremendous synergy in combination with chemotherapy compounds (paclitaxel, 5FU, irintotecan, cisplatin, doxorubicin, methotrexate and cytarabine), as well as potent synergy in combination with a large panel of kinase inhibitors. For each kinase inhibitor, the Synergy compound in combination showed at least double the activity using half the concentration of the other compound and in some cases, showed greater synergy in combination. Combining tumoricidal SYN-126 with tumoristatic kinase inhibitors holds significant promise to slow drug resistance. This has potential to improve treatment options for leukemia and lymphoma patients to lower systemic toxicity, commonly observed during treatment and highlighted by FDA (Oncology Drugs Advisory Committee on 4/21/2022). Combination with kinase inhibitors also provides multiple opportunities to reduce unmet medical needs in treatment of solid tumors.
In xenograft tumor model studies, SYN-126 remains present in tumor cells for at least 72 hours after dosing. Due to the long-lasting properties of SYN-126, a weekly injection may be required. Synergy also plans to investigate lipid nanoparticle formulations to enable the p53-derived peptide to be delivered in a daily capsule or other patient-friendly
formulation.
FDA has approved over 100 peptide drugs, including diabetes and weight loss products commercialized by Novo Nordisk and Eli Lilly, as well as five peptides for oncology. In 2005 FDA approved the ABRAXANE formulation of nanoparticle albumin–bound paclitaxel. Both components of SYN-126 have demonstrated safety and efficacy across large patient populations. SYN-126 preferentially accumulates inside tumors which minimizes risk of systemic toxicity. Please contact us if you have additional science questions.