From Bench to Pill: Enantiomer Science and Oral Delivery

In an interview with PharmTech, Sandra Coufal, MD, CEO, Toragen, walks through the preclinical research that validated her team's preferred enantiomer compound for TGN-S11, Toragen’s small molecule inhibitor of the E5 oncogene protein, in patients with cancers associated with HPV.

Dr. Coufal describes two key rodent studies that shaped the direction of TGN-S11’s development program. The first was a neurotoxicity assessment, in which the non-preferred enantiomer triggered seizures in half of the test animals, while the preferred enantiomer showed no such effect. The second was a tumor model study using HPV-positive cancer cells, for which animals were treated for 69 days across three drug variants. The preferred enantiomer outperformed both the racemic compound and the non-preferred enantiomer in reducing tumor growth. As Dr. Coufal explains, "We were able to confirm the efficacy and also confirm the absence of neurotoxicity in the preferred enantiomer, and that's what gave us confidence to go forward."

From there, Dr. Coufal discusses the intellectual property strategy her team has pursued, focusing on patenting GRAS-designated salt forms of the preferred enantiomer. One salt form stood out for its pharmacokinetic profile, specifically a blunted peak drug concentration after ingestion. "That high Cmax in your bloodstream after taking a small molecule is what's really most associated with toxicity," Dr. Coufal notes.