PureTech Health has kicked off a clinical study of LYT-300 (oral allopregnanolone), its 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. 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 (FDA) 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.
Joe Bolen, Ph.D., Chief Scientific Officer of PureTech source: https://puretechhealth.com/
“Allopregnanolone is a powerful, natural regulator of mood disorders and other neurological conditions, but its therapeutic development has been limited by its poor oral bioavailability. 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,” said Joe Bolen, Ph.D., Chief Scientific Officer of PureTech. “LYT-300 is designed to preserve the natural structure of allopregnanolone in an oral dosage form, which we believe could potentially offer much-needed treatment options in large indications, such as depression, anxiety and sleep, as well as for more rare conditions, including certain epileptic disorders. Advancing LYT-300 into human clinical development offers the opportunity to potentially address many important psychiatric conditions without good treatment options, especially amid the growing mental health crisis in the United States wherein one in four adults report experiencing symptoms of depression or anxiety.”
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 (PK) will be assessed. Given the GABAA receptor modulating activity of allopregnanolone, the study will also explore the impact of LYT-300 on b -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.