Schizophrenia is a chronic psychiatric condition affecting approximately 2.7M people in the U.S. Current antipsychotics have significant side effects and poor adherence, with many failing to find an effective and/or tolerable therapy. Patients are in need of medicines that work differently than the current standards of care, which can cause weight gain, sedation and movement disorders.

At PureTech, we engaged with a group of leading schizophrenia experts who were most excited about efficacy data generated by Eli Lilly with xanomeline, which was not advanced due to tolerability issues.

To overcome this, we invented KarXT by combining xanomeline (a muscarinic receptor agonist) with trospium (a peripherally acting antagonist that doesn’t cross the blood brain barrier), and in doing so we unlocked development of the first new class of medicine for schizophrenia in over 50 years. 

Idiopathic pulmonary fibrosis (IPF) is a terminal condition that affects about 120,000 patients in the US and about 110,000 in the EU5 and has a median survival of 2 to 5 years from diagnosis.

Pirfenidone is one of only two drugs approved to treat IPF, and a recent study showed that pirfenidone improves survival by approximately three years compared to supportive care alone. Despite this, tolerability issues with both standard of care drugs result in patients discontinuing or dose reducing so they are unable to benefit from efficacy, and 3 out of every 4 patients are not on these otherwise efficacious medicines.

LYT-100 (deuterated pirfenidone) is designed to retain the beneficial pharmacology and clinically validated efficacy of pirfenidone, but with a highly differentiated PK profile that has translated into substantially improved tolerability in multiple clinical trials. We believe improved tolerability could unlock better outcomes for patients through increased medication adherence and potentially improved efficacy at a higher dose.

For patients with a range of mental health conditions, such as anxiety and mood disorders, there is a growing need for new treatments. Standard of care treatments like selective serotonin reuptake inhibitors (SSRIs) can have mixed efficacy, delayed onset of action and poor tolerability.

Lower levels of allopregnanolone have been documented in patients with mood disorders, such as depression, and there is evidence that allopregnanolone has therapeutic potential in both anxiety and depression, however it can only be administered via a long, cumbersome intravenous infusion.

We created an oral prodrug of endogenous allopregnanolone that retains the activity and potency of allopregnanolone and may have better target engagement, in a more convenient oral form. We’ve done so by linking it to our Glyph™ technology, which allows it to bypass liver degradation. With this approach, we have demonstrated oral bioavailability that is approximately nine times greater than that of previous efforts to develop oral allopregnanolone. This means LYT-300 may significantly expand the potential of this validated mechanism across multiple patient populations where current treatments are burdensome to administer or take weeks to have an effect.