Frost Biologics' lead program, FROST-450, is a small molecule inhibitor of microtubule polymerization. FROST-450 is broadly effective against cell and animal models of cancer, but particularly against sex-specific cancers (prostate, breast, ovarian, endometrial), colon cancers, and gastric cancers. FROST-450 combines a low molecular weight with a very high potency; it has a molecular weight under 400Da, but affects cancer cell growth with IC50s in single digit nM range and inhibits microtubule polymerization with an IC50 of 240nM (compared to 684nM for vincristine in the same experiment). Importantly, evidence suggests that cell lines that develop resistance to other microtubule targeting agents, most notably taxanes, have not developed resistance to FROST-450. Oral bioavailability of this molecule approaches 100% and it exhibits a unique gastric absorption profile. Simple to synthesize, Frost Biologic fully owns the intellectual property around this molecule.
As of Q1 2016, FROST-450 is being manufactured at scale and undergoing GLP studies in readiness for Phase I clinical trials. The clinical trial will focus on solid tumor types that have proven unexpectedly difficult to treat with current microtubule targeting agents or that develop resistance to current microtubule targeting agents. The primary indication of interest is currently gastric cancer.
A cytotoxic DNA damaging agent with a novel targeting mechanism, Frost Biologic is developing prodrug analogs with reduced general toxicity and improved pharmacokinetic properties. These compounds show particular potency against mantle cell lymphoma in cell culture.
FROST-700 & -800
FROST-700 and -800 are analogs of FROST-450 and designed to maintain its unique pharmacokinetic properties, namely gastric absorption and high oral bioavailability. The biological activity of FROST-450 (microtubule polymerization) has been engineered out to create these new programs and new biological activities have been engineered into analogs of each program. Both programs are designed for efficacy in orthotopic models of gastric cancer.
Also based on the FROST-450 scaffold, FROST-900 compounds have been designed to retain gastric absorption and retention properties with novel biological activity. The microtubule targeting activity of FROST-900 analogs have been engineered out, while optimizing for antibacterial activity. The aim of this program is to use the gastric absorption and retention to target antibacterial activity to the gastric mucosa for treatment of Helicobacter Pylori.