At PureTech, we are developing new categories of therapeutics by leveraging the science of the Brain-Immune-Gut (BIG) axis

 

 

Our Publications

Our team, network and expertise in the BIG Axis enable us to identify and advance the latest scientific discoveries at the interface of the BIG systems.

We begin by collaborating with a cross-disciplinary group of experienced clinicians and the world’s leading experts in brain, immune and gut biology in a discovery process that breaks down specific diseases and comprehensively identifies, reviews and empirically tests unpublished scientific discoveries in a modality agnostic and unbiased way. We identify potential programs from their laboratories of origin, our internal discovery platforms or through other companies. Our key relationships have consistently provided us access to important discoveries before they were known to others in the industry.

CASE STUDIES

DISCOVERY REINVENTED

New mechanism for treating psychosis and cognitive impairments (KarXT)

Open Case Study

The Challenge

 

Psychosis, negative symptoms, and cognitive impairments in schizophrenia, Alzheimer’s disease and other mental illnesses remain poorly treated

There are approximately 2.7M living with schizophrenia and 5.7M living with Alzheimer's in the US

Existing Approaches

Antipsychotics are the mainstay therapy targeting dopamine pathways, however with no new treatment mechanism in 60 years, the prognosis for patients remain poor

Cuurent antipsychotics only address psychosis (positive symptoms) and are associated with serious side effects such as sedation, extrapyramidal side effects such as motor rigidity, tremors and slurred speech, and weight gain 

The Big Idea

A class of medicines (M1/M4 agonists) that showed enormous potential in clinical studies was never developed due to tolerability issues.

We asked “What if you you could selectively target M1/M4 receptors in the central nervous system without affecting the peripheral tissues where most side effects occur?”

The Result

Karuna is developing a potentially first-in-class oral modulator of muscarinic receptors

KarXT combines xanomeline, a novel muscarinic receptor agonist, with trospium chloride, a muscarinic receptor antagonist that acts peripherally and does not measurably cross the blood-brain barrier

Currently in Phase 2b study for schizophrenia with topline data expected YE 2019

Selective mTORC1 Inhibitors (resTORbio)

Open Case Study

The Challenge

Many of the afflictions of a rapidly aging population – from declines in cognition, to immunosenescence and cancer – remain poorly addressed. One such indication is respiratory tract infection, or RTI, a leading cause of mortality in elderly people

Existing Approaches

Limited therapeutic options exist today to prevent and treat viral respiratory tract infections.

Some vaccines protect against specific viruses; however there is no available treatment for most RTIs, a leading cause of mortality in high risk, elderly populations.

The Big Idea

Can we develop an anti-viral that works by boosting the immune system?

The Result

A new approach in targeting the mTOR pathway by selectively targeting TORC1, linked to increased lifespan and other beneficial effects. We are focusing initially on the reduction of RTIs in elderly individuals at increased risk of RTI related morbidity and mortality. Our selective mTORC1 inhibition program has potential in other aging related indications including cognition, cardiovascular and cancer.

Rationally defined, immune modulating non-pathogenic human microbes (VE202)

Open Case Study

The Challenge

The human microbiome is increasingly implicated in various immune-mediated disease states

Vedanta has discovered specific bacteria that induce T regs (which form the basis for Vedanta's IBD and food allergy candidates) and CD8+ cells (which form the basis for Vedanta's IO candidate)

Existing Approaches

Many existing IBD interventions are limited by toxicities and systemic immune suppression

Food Allergy treatment today primarily centers around allergen avoidance, and new immunotherapies focused on desensitization may note prove cost-effective relative to this approach

Checkpoint Inhibitors are only effective in 20-30% of patients

C. difficile is typically treated using antibiotics (damage the microbiome and leave patients vulnerable to re-infection) or FMT (uncharacterized safety issues)

The Big Idea

What if we could treat immune and infectious disease by mimicking the ways in which the gut microbiota maintains a healthy immune system in humans?

The Result

Vedanta is developing a potentially new category of therapies based on a rationally-defined consortia of human microbiome-derived bacteria

Defined consortia have potential to shift microbiota, stimulate immune responses, and provide colonization resistance against infectious pathogens

Clinical results for VE303, VE800, and VE416 are anticipated in 2020

Foundational patents issued in key territories 

Targeting immunologically silent tumors with first-in-class mAbs (LYT-200)

Open Case Study

The Challenge

Low survival rate for many solid tumors, including pancreatic, colorectal cancer, and cholangiocarcinoma

Large unmet need for patients with tumor types that don’t respond to checkpoint inhibitors 

Existing Approaches

Immuno-suppressed tumor micro-environment makes tumors “cold”

Lack of therapies that reverse the immunosuppressed tumor micro-environment to allow for potent immune-mediated cancer attack 

The Big Idea

Can we target the immunosuppressive agentsthat solid, malignant tumors establish to ward off the body’s natural defenses?

The Result

Advancing fully human mAbs targeting galectin-9 and immunosuppressive γδ1 T cells in immunologically silent tumors

Collaborating with Industry Leaders Across Our Affiliate and Internal R&D Pipelines

 

 

Amgen Novartis Lilly Merck Boehringer Ingelheim Bristol-Myers Squibb Janssen Roche