PureTech Health announces topline results from LYT-300 study

PureTech Health announced topline results from the completed, multi-part Phase 1 trial of LYT-300. PureTech announced topline results for LYT-300, a therapeutic candidate in development for neurological and neuropsychological conditions. The results show that oral administration of LYT-300 achieved blood levels of allopregnanolone at or above those associated with therapeutic benefit and results in exposure-dependent target engagement of GABAA receptors. Additional data from the Phase 1 trial will be presented in a scientific forum, and a Phase 1b/2a trial is expected to begin in the first half of 2023. Topline results announced show that oral administration of LYT-300 achieved blood levels of allopregnanolone at or above those associated with therapeutic benefit1 and resulted in exposure-dependent target engagement with gamma-aminobutyric-acid type A, or GABAA, receptors. Earlier this year, PureTech announced that LYT-300 also demonstrated oral bioavailability of allopregnanolone approximately ninefold greater than third-party reported data with orally administered allopregnanolone.1 Additional data from the Phase 1 trial will be presented in a scientific forum, and a Phase 1b/2a trial is expected to begin in the first half of 2023. Allopregnanolone is a natural neurosteroid with well-validated biological effects. It has demonstrated a rapid onset of action for the treatment of depression, as well as the potential to treat other neurological conditions, but its poor oral bioavailability has limited its therapeutic potential. The FDA has approved a 60-hour intravenous infusion formulation of allopregnanolone for the treatment of postpartum depression, or PPD, though this method of administration has inherent limitations. To overcome this, synthetic oral analogs of allopregnanolone have been developed, though these may not capture the full therapeutic potential of natural allopregnanolone. To potentially harness the broad applicability of this natural neurosteroid through oral administration, PureTech has applied its GlyphTM platform, which is designed to enable the oral administration of certain therapeutics with low oral bioavailability due to first pass metabolism. The Glyph platform has yielded two candidates to date. Overall, 72 healthy volunteers were dosed in the multi-part, Phase 1 clinical trial, which was designed to evaluate oral bioavailability, safety and tolerability of LYT-300 across a range of doses, and to inform dose selection moving forward. As part of the trial, single and multiple ascending doses were evaluated along with cohorts to evaluate the effect of food on oral absorption. The impact of LYT-300 on b-EEG and other markers of GABAA target engagement were also assessed. LYT-300 was generally well-tolerated with no treatment-related severe or serious adverse events observed. Doses have been selected to carry forward into the planned Phase 1b/2a clinical trial. A second candidate from the Glyph platform, LYT-310, an oral cannabidiol, or CBD, is designed to greatly expand the therapeutic application and potential of CBD. LYT-310 has demonstrated a three to fourfold increase in oral exposure versus unmodified CBD in multiple preclinical models, including large animal and non-human primate. This has the potential to translate into improved safety and reduced side effects. Lymphatic transport has also been confirmed in preclinical models, with up to 30% of LYT-310 entering the lymphatics, compared to 5% for unmodified CBD – which further supports the novel Glyph mechanism of enhancing oral bioavailability. LYT-310 is expected to enter the clinic in Q4 of 2023.