PureTech reports 'Glyph' milestone, disappointing long Covid results

PureTech Health said on Tuesday that it had met a milestone in proving its ‘Glyph’ therapeutic platform, while separately announcing disappointing results from a study into long Covid.

The FTSE 250 biotherapeutics developer said it had achieved ‘proof-of-principle’ for its Glyph platform in a healthy adult study of ‘LYT-300’, or oral allopregnanolone.

LYT-300 is its wholly-owned therapeutic candidate for the potential treatment of a range of neurological and neuropsychological conditions, with the board describing the achievement as a “key milestone” for the candidate, which is designed to overcome the “normally poor” oral bioavailability of allopregnanolone.

It was also the first mechanistic proof-of-principle in the clinic for PureTech's Glyph lymphatic targeting platform, which was designed to bypass first-pass metabolism to help maximise the therapeutic potential of validated targets and drugs where oral bioavailability was currently a barrier.

The Glyph platform was designed to have additional applications through its ability to “selectively traffic” therapeutics into the lymphatic system, potentially enabling more direct targeting of the immune system.

“Natural allopregnanolone has demonstrated efficacy for the treatment of postpartum depression and other neuropsychological conditions, but up to now has required IV delivery due to high first-pass liver metabolism,” said the company’s chief medical officer Julie Krop.

“LYT-300 is designed to unlock the validated pharmacology of natural allopregnanolone with a potential oral treatment option for PPD and a range of other neurological and neuropsychological conditions.

“Achieving significant systemic exposure of allopregnanolone with orally administered LYT-300 is also a key validation for our Glyph lymphatic targeting platform and represents proof-of-principle for being able to administer drugs orally that currently require IV administration due to first-pass liver metabolism.”

In its second announcement, PureTech announced results from a phase-2 study of ‘LYT-100-COV’, or deupirfenidone, in patients with post-acute ‘long’ Covid-19 with respiratory complications.

It said there was no treatment effect observed in the indication with LYT-100, though the “strong” safety and tolerability profile of LYT-100 was reaffirmed.

Based on the data, PureTech said it would not pursue further studies in the patient population, adding that it remained on track to initiate registration-enabling studies of LYT-100 in idiopathic pulmonary fibrosis later in the month.

LYT-100 is a selectively deuterated form of pirfenidone, which has been proven effective in idiopathic pulmonary fibrosis.

“Early in the Covid-19 pandemic, we identified a potential application for LYT-100 given the hypothesis that inflammation and fibrosis may play a role in prolonging respiratory symptoms experienced by many patients,” said founder and chief executive officer Daphne Zohar.

“We undertook this exploratory study, guided by a desire to address this emerging need, while further expanding the safety and tolerability data for our LYT-100 development program at large.

“Although we had hoped to offer a treatment to long Covid patients, these data further strengthen our confidence that LYT-100 has the potential to offer improved tolerability and therefore potentially improved treatment adherence and patient outcomes in IPF, a devastating condition that has been well-studied and where pirfenidone has proven efficacy.”

At 1051 BST, shares in PureTech Health were down 2.3% at 161.2p.

Reporting by Josh White at Sharecast.com.