“NOT YOUR GRANDFATHER'S HDM2”

Oncolyze is developing what we hope to be a transformational approach to cancer treatment. It all starts with a molecule called HDM2 (human double minute-binding protein-2). This is a protein that regulates cell growth. In fact, it counterbalances another protein called p53, which is a ‘tumor suppressor’. Most cancers overexpress HDM2 inside the cell, thereby blocking the p53 tumor suppressive function.

However, researchers at SUNY Downstate Medical Center (from where Oncolyze has licensed the technology) discovered that cancer cells have a high concentration of HDM2 not only intracellularly, but also on the external surface of their cell membrane. Whether this is used to somehow communicate with other cells, we are not yet certain, but what we do know is that more than 80% of cancer types we have tested have a high amount of HDM2 present on their cell surface, whereas normal cells appear to hardly have any. The unique expression of extracellular HDM2 on cancer cells makes it an excellent, selective target for an anti-cancer therapeutic agent.

Our therapeutic approach does exactly this. We target the extracellular HDM2 for a therapeutic mechanism that works at the cell surface and does not rely on the intracellular HDM2 and its function on p53. We know this because our drug candidates work on p53-null cell lines (cancer cells that lack p53 protein).

Our collaborators around the world have shown efficacy of our peptides in various animal models of cancer. Most recently, our collaborators at City of Hope have shown effectiveness of OM-301 in a direct human transplant AML model, not only against ‘mature’ leukemia cells, but also the leukemia stem cells. Primary human AML CD34+ cells were transplanted into NSG-SGM3 mice that were subsequently treated with either OM-301 or vehicle for 2 weeks. The CD34+ cells were subsequently transplanted into a second group of mice and survival assessed.

OM-301 treatment resulted in significantly reduced self-renewal activity of human AML cells. At 4, 8, and 12 weeks, the % of CD45+ cells in the peripheral blood was significantly lower in the OM-301 treated mice. For example, by 12 weeks, the vehicle-treated mice had nearly 100% of CD45+ cells while those treated with OM-301 had approximately 60%. Furthermore, OM-301 almost doubled survival (p<0.0001). Only about 10% of secondary transplant mice survived at day 100, while all secondary transplant mice treated with OM-301 were alive at that point; no vehicle-treated mice survived past 110 days, while 50% of OM-301-treated mice survived past 150 days.

Although this was an initial proof of concept and not optimized for maximum therapeutic effect, it has presented us and our collaborators with undeniable promise for OM-301, especially in a difficult to treat cancer like AML.