Enhancing on-target efficacy
Enabling oral administration
Improving tolerability
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.
Unlocking the potential of validated efficacy
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.
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.
LYT-300
Allopregnanolone has proven efficacy but is only available as a 60-hour IV infusion. With LYT-300, we have achieved oral bioavailability approximately nine-fold greater than that of orally administered allopregnanolone, which significantly expands the potential of this validated mechanism.
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 potent and clinically-validated anti-fibrotic and anti-inflammatory activity of pirfenidone, and it has demonstrated favorable tolerability in multiple clinical studies.
Our publications
CASE STUDY
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 more than 21 million people globally. Up to 74% of patients discontinue medication within 18 months, 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 significant weight gain, sedation and movement disorders.
VALIDATED EFFICACY
At PureTech, we and our collaborators, including leading schizophrenia experts, were most excited about efficacy data generated in schizophrenia and Alzheimer’s disease by Eli Lilly with xanomeline, which had notable efficacy stemming from its activation of muscarinic receptors (M1 & M4) but had been held back by GI tolerability issues.
PURETECH APPROACH
To overcome this, we invented KarXT, an oral M1/M4-preferring muscarinic agonist, by combining xanomeline (a muscarinic agonist) with trospium (a peripherally acting muscarinic antagonist that doesn’t cross the blood brain barrier). This enabled the beneficial effects of M1/M4 activation in the brain without the peripheral side effects, and in doing so we unlocked development of the first new class of medicine for schizophrenia in over 50 years.
CASE STUDY
LYT-300
Allopregnanolone has proven efficacy but is only available as a 60-hour IV infusion. With LYT-300, we have achieved oral bioavailability approximately nine-fold greater than that of orally administered allopregnanolone, which significantly expands the potential of this validated mechanism.
Patient Need
For patients with a range of mental health conditions, such as depression, 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
Allopregnanolone has demonstrated meaningful and fast-acting efficacy for the treatment of PPD and has shown benefit in other neuropsychological conditions, but it must be delivered via an IV over 60 hours due to high first-pass liver metabolism.
PURETECH APPROACH
We created an oral prodrug of natural allopregnanolone 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-fold greater than that of previous efforts to develop oral allopregnanolone. This is exciting because 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.
CASE STUDY
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 potent and clinically-validated anti-fibrotic and anti-inflammatory activity 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 3 million people worldwide 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 nearly 75% of patients forego treatment with these otherwise efficacious medicines.
PURETECH APPROACH
LYT-100 (deuterated pirfenidone) is designed to retain the potent and clinically-validated anti-fibrotic and anti-inflammatory activity of pirfenidone, but with a highly differentiated PK profile that has translated into favorable tolerability in multiple clinical studies. We believe improved tolerability could unlock better outcomes for patients through increased medication adherence and potentially higher dosing and improved efficacy.