Research & Development
PureTech Advances Wholly-Owned Candidate LYT-300 into Clinical Study for Potential Treatment of Neurological and Neuropsychological Conditions
7 December 2021 - - US-based biotherapeutics company PureTech Health plc (NASDAQ: PRTC) (LSE: PRTC) has initiated a clinical study of LYT-300 (oral allopregnanolone), PureTech's wholly-owned therapeutic candidate for the potential treatment of neurological and neuropsychological conditions, including depression, anxiety, sleep disorders, fragile X tremor-associated syndrome, essential tremor and epileptic disorders, among others, the company said.

LYT-300 is the third clinical-stage, wholly-owned candidate from PureTech's pipeline.

LYT-300 is an oral form of allopregnanolone. Allopregnanolone is a natural neurosteroid that is a positive allosteric modulator of γ-aminobutyric-acid type A (GABAA) receptors, which are known to play a key biological role in depression, epilepsy and other neurological and neuropsychological conditions.

Natural allopregnanolone has poor oral bioavailability, thus limiting its development as a therapeutic.

An injectable formulation of allopregnanolone is approved by the United States Food and Drug Administration as a 60-hour infusion for the treatment of post-partum depression, though the method of administration has limitations.

LYT-300 is designed to unlock the validated biology of allopregnanolone to potentially offer a new, oral treatment option for a range of conditions where there is significant patient need.

LYT-300 was developed from PureTech's proprietary Glyph technology platform, which generates novel prodrugs by reversibly linking small molecule drugs to dietary fat molecules.

This linkage is designed to enable the transport of small molecule drugs directly into systemic circulation via the lymphatic system following oral administration, thereby bypassing first-pass liver metabolism.

This platform also has the potential to deliver other drugs with poor bioavailability, including immune modulators that could directly target the mesenteric lymph nodes.

The Phase 1 study of LYT-300 involves multiple parts, including the evaluation of a single ascending dose, multiple ascending doses and the effect of food on oral absorption of the prodrug in healthy volunteers. Safety, tolerability and pharmacokinetics will be assessed.

Given the GABAA receptor modulating activity of allopregnanolone, the study will also explore the impact of LYT-300 on β-EEG, a marker of GABAA target engagement, thus potentially providing early insights into the mechanistic effects of LYT-300.

Results from the study are expected in the second half of 2022 and will be used to inform the design of possible future studies evaluating LYT-300 in indications that could include depression, anxiety, sleep disorders, fragile X tremor-associated syndrome, essential tremor and epileptic disorders, among others.

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 PureTech's Glyph technology platform, LYT-300 is an oral prodrug of natural allopregnanolone.

An IV formulation of allopregnanolone is approved by the US FDA and administered as a 60-hour infusion for the treatment of post-partum depression.

Allopregnanolone is a positive allosteric modulator of γ-aminobutyric-acid type A (GABAA) receptors and has been shown to regulate mood and other neurological conditions.

PureTech initiated a Phase 1 clinical study of LYT-300 in late 2021, which is designed to characterize the safety, tolerability and PK of orally administered LYT-300 in healthy volunteers.

Glyph is PureTech's synthetic lymphatic-targeting chemistry platform which is designed to employ the lymphatic system's natural lipid absorption and transport process to enable the oral administration of therapeutics. Glyph reversibly links a drug to a dietary fat molecule, creating a novel prodrug.

The linked fat molecule re-routes the drug's normal path to the systemic circulation, bypassing the liver and instead moving from the gut into the lymphatic vessels that normally process dietary fats.

PureTech believes this technology has the potential to enable direct modulation of the immune system via drug targets present in mesenteric lymph nodes and provide a broadly applicable means of enhancing the bioavailability of orally administered drugs that would otherwise be reduced by first-pass liver metabolism.

PureTech is leveraging validated biology to accelerate the development of a Glyph portfolio, prioritizing highly characterized drugs to enhance with the Glyph technology based on the potential value unlocked in improving their oral bioavailability or lymphatic targeting.

PureTech's lead Glyph therapeutic candidate, LYT-300 (oral allopregnanolone), is being evaluated in a Phase 1 study, with results expected in the second half of 2022.

PureTech has exclusively licensed the Glyph technology platform, which is based on the pioneering research of Christopher Porter, Ph.D., and his research group at the Monash Institute of Pharmaceutical Sciences at Monash University.

The Porter Research Group and collaborators have published research in Nature Metabolism and the Journal of Controlled Release supporting the Glyph platform's ability to directly target the lymphatic system with a variety of therapies.

PureTech is a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, including inflammatory, fibrotic and immunological conditions, intractable cancers, lymphatic and gastrointestinal diseases and neurological and neuropsychological disorders, among others.
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