Across our pipeline, there are examples of how we start with a patient need and identify an approach that has proof of human efficacy, but key limitations have hindered the class from reaching its full potential. Examples include off-target effects, low bioavailability or poor tolerability.
Across our pipeline, there are examples of how we start with a patient need and identify an approach that has proof of human efficacy, but key limitations have hindered the class from reaching its full potential. Examples include off-target effects, low bioavailability or poor tolerability.

Case Studies

Karuna's KarXT

KarXT, which was invented at PureTech, has demonstrated notable improvements across schizophrenia symptoms – without the debilitating side effects of existing drugs – and is now poised to be the first new class of medicine in over 50 years for patients living with schizophrenia.

PATIENT NEED

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.

VALIDATED EFFICACY

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.

PURETECH INNOVATION

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. 

LYT-100

Pirfenidone’s tolerability profile impacts patient adherence to an otherwise efficacious treatment, resulting in dose adjustments, discontinuations and ultimately poor patient outcomes. LYT-100 is designed to retain the beneficial pharmacology and clinically validated efficacy of pirfenidone, and it has demonstrated favorable tolerability in multiple clinical studies.

PATIENT NEED

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.

VALIDATED EFFICACY

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.

PURETECH INNOVATION

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.

LYT-300

Allopregnanolone has the potential to treat a range of neurological and neuropsychiatric indications, however it can only be administered via a long, cumbersome intravenous infusion. Oral chemical analogs have been developed but they may have different pharmacological effects than endogenous allopregnanolone. With LYT-300, we have achieved oral bioavailability approximately nine times greater than third party reported data with oral allopregnanolone, which significantly expands the potential of this validated mechanism.

PATIENT NEED

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.

VALIDATED EFFICACY

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.

PURETECH INNOVATION

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.

Improving tolerability

Enabling oral administration

Enhancing on-target efficacy

At PureTech, our R&D approach is centered on enhancing on-target efficacy, enabling oral administration or improving tolerability to unlock new classes of medicine that have been held back by one of these issues.