PureTech Health is stepping up its bid to challenge Sage Therapeutics for the depression market by moving a rival to Zulresso and zuranolone into the clinic. The study in healthy volunteers marks the start of PureTech’s effort to show its work to enable oral delivery translates into clinical benefits.
LYT-300 is an oral form of allopregnanolone, a neurosteroid and modulator of GABAA receptors that is at the heart of Sage’s work. As allopregnanolone has poor oral bioavailability, Sage initially worked on an intravenous drug, sold as Zulresso, and is now closing in on filings for an oral version that could spare patients from the 60-hour infusions used to give the approved product.
After failing a key clinical test in 2019, Sage brought the oral zuranolone back from the brink and now plans to seek FDA approval with its partner Biogen next year, but PureTech thinks it can come from behind to unseat the rival drug.
Sage overcame the poor oral bioavailability of allopregnanolone by developing a synthetic analogue of the neurosteroid. PureTech has taken a different, and in its view potentially better, approach to the development of LYT-300, making changes to avoid first-pass metabolism by trafficking via the lymphatic system. Joe Bolen, Ph.D., chief scientific officer of PureTech, talked up the potential for the approach taken by his team to yield better results.
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“Synthetic oral analogs of allopregnanolone have been developed, though the degree to which these compounds mimic the therapeutic effects of natural allopregnanolone remains to be seen,” Bolen said in a statement. “LYT-300 is designed to preserve the natural structure of allopregnanolone in an oral dosage form.”
PureTech has shown oral bioavailability in canine and nonhuman primate pharmacokinetic studies. The 90-subject phase 1 clinical trial will build on that preclinical work and give PureTech data on the blood plasma concentration of allopregnanolone after administration of LYT-300.