PureTech's LYT-300 (Oral Allopregnanolone) Demonstrates Oral Bioavailability, Tolerability and GABAA Receptor Target Engagement in Healthy Volunteers
Orally administered LYT-300 achieved blood levels of allopregnanolone at or above those associated with therapeutic effect.1 Allopregnanolone is a natural neurosteroid with proven efficacy that is currently only available as a 60-hour intravenous infusion.
Preliminary pharmacodynamic data indicate that oral administration of LYT-300 results in allopregnanolone target engagement with GABAA receptors, which have been shown to regulate mood and other neurological conditions.
LYT-300 was generally well-tolerated across the trial with no treatment-related severe or serious adverse events observed.
Topline results announced today 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 γ-aminobutyric-acid type A (GABAA) receptors. Earlier this year,
"Today's results make us very excited about the potential of LYT-300 to unlock the full therapeutic benefit of allopregnanolone, which to date has been limited to a small subset of patients," said
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.
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 (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.
LYT-300 is a clinical therapeutic candidate that is in development as a potential treatment for a range of neurological and neuropsychological conditions. Developed using
About the Glyph™ Platform
For more information, visit www.puretechhealth.com or connect with us on Twitter @puretechh.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those statements that relate to our expectations around timelines and key milestones associated with clinical trials for LYT-300, the therapeutic potential of LYT-300, the potential for improved tolerability associated with LYT-310 as compared to unmodified CBD, that such potential improved tolerability and oral dosing could expand the therapeutic application of CBD across a wider range of age groups and indications, our expectations regarding the Glyph™ technology platform including the potential for new treatment applications, the applicability of preclinical results to human subjects, our product candidates and approach towards addressing major diseases, and our future prospects, developments, and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended
1) Brexanolone NDA 211371 Multi-disciplinary Review and Evaluation, FDA CDER, 2018.
2) Ghit, A., Assal, D., Al-Shami,
3) Bullock, A., Kaul, I., Li, S., Silber, C., Doherty, J., & Kanes, S. J. (2021). Zuranolone as an oral adjunct to treatment of Parkinsonian tremor: A phase 2, open-label study. Journal of the neurological sciences, 421, 117277. https://doi.org/10.1016/j.jns.2020.117277
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