At PureTech, we are creating new categories of medicine by leveraging the science of the Brain-Immune-Gut (BIG) axis
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PureTech's Components of Value
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1. PureTech Level Pro-forma Cash Reserves is an alternative performance measure (APM) which includes the PureTech Level Cash Reserves of $120.6 million and the $200.9 million in proceeds from the 22 January 2020 sale of 2.1 million Karuna common shares. PureTech Pro-forma Cash Reserves is therefore considered to be more representative of the Corporate’s cash available for the year 2020 and beyond to advance product candidates within the full breadth of its operations.
2. PureTech Level Cash Reserves represent cash balances and short-term investments held at PureTech Health LLC, PureTech Management, Inc., PureTech Health PLC, PureTech Securities Corporation of $112.0 million for the year ended 2019 and the internal pipeline of $8.6 million for the year ended 2019, all of which are wholly-owned entities of PureTech, excluding cash balances and short-term investments of Controlled Founded Entities. The balance excludes the $200.9 million in proceeds from the 22 January 2020 sale of 2.1 million Karuna common shares.
3. Funding figure includes private equity financings, public offerings or grant awards. Funding figure excludes upfront payments and future milestone considerations received in conjunction with partnerships and collaborations such as those with Roche, Boehringer Ingelheim, Imbrium Therapeutics L.P., Shionogi & Co., Ltd. or Eli Lilly.
New mechanism for treating psychosis and cognitive impairments (KarXT)
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
Selective mTORC1 Inhibitors (resTORbio)
The Challenge
Existing Approaches
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)
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)
The Challenge
Low five year survival rate for many aggressive solid tumors, including metastatic pancreatic and colorectal cancer, and metastatic cholangiocarcinoma
Many aggressive solid tumors do not benefit from approved immuno-oncology agents
Low response rate to immunotherapy
Existing Approaches
"Cold" tumors lack cancer-killing immune cells
Finding targets that suppress multiple immunosuppressive pathways simultaneously has proven challenging, and combination therapies are limited by toxicity
The Big Idea
Can we target the immunosuppressive cells that solid, malignant tumors establish to ward off the body’s natural defenses?
The Result
Developing first-in-class fully human mAbs targeting immunologically silent tumors with galectin-9 and immunosuppressive γδ T cells that mediate immunosuppression through multiple mechanisms and has the potential for single efficacy as well as combinations.
