prtc corporatepresentation · development and commercialization of new products, enhancements of...
TRANSCRIPT
July 2020
Important Information
2
The following presentation, including any printed or electroniccopy of these slides, the talks given by the presenters, theinformation communicated during any delivery of thepresentation and any question and answer session and anydocument or material distributed at or in connection with thepresentation (together, the "Presentation"), has been prepared byPureTech Health plc (the "Company"). The information in thePresentation is not intended to form the basis of any contract.By attending (whether in person or by telephone) or reading thePresentation, you agree to the conditions set out below.
THIS DOCUMENT AND THE PRESENTATION IS NOT APROSPECTUS. The Presentation does not constitute or form partof any offer or invitation to sell or issue, or any solicitation of anyoffer to purchase or subscribe for, any shares or other securitiesof the Company, nor shall there be any sale of these securities inany state or jurisdiction in which such offer, solicitation or salewould be unlawful prior to registration or qualification under thesecurities laws of any such state or jurisdiction. Any suchoffering of securities will only be made by means of a registrationstatement (including a prospectus) filed with the Securities andExchange Commission (the "SEC"), after such registrationstatement becomes effective. No such registration statementhas been filed as of the date of this presentation.
This document and the Presentation contain statements that areor may be forward-looking statements. These statements arebased on our management’s current beliefs, expectations andassumptions about future events, conditions and results, and oninformation currently available to us. This document and thePresentation also contain estimates and other statistical datamade by independent parties and by us relating to market sizeand growth and other data about our industry. This data involvesa number of assumptions and limitations, and you are cautionednot to give undue weight to such estimates. In addition,
projections, assumptions and estimates of our futureperformance and the future performance of the markets in whichwe operate are necessarily subject to a high degree ofuncertainty and risk.
All statements other than statements of historical facts includedin this document may be forward-looking statements, includingstatements that relate to the Company's future prospects,developments and strategies. Words such as “expect,”“anticipate,” “intend,” “plan,” “believe,” “seek,” “estimate,” “think,”“may,” “could,” “will,” “would,” “should,” “continue,” “potential,”“likely,” “opportunity” and similar expressions or variations ofsuch words are intended to identify forward-looking statements,but are not the exclusive means of identifying forward-lookingstatements. Additionally, statements concerning future matterssuch as our expectations of business and market conditions,development and commercialization of new products,enhancements of existing products or technologies, and otherstatements regarding matters that are not historical are forward-looking statements. Such statements are based on currentlyavailable operating, financial and competitive information and aresubject to various risks, uncertainties and assumptions thatcould cause actual results to differ materially from thoseanticipated or implied in our forward-looking statements due to anumber of factors including, but not limited to:
The Company’s business is subject to a number of risks anduncertainties. These risks are described in the Company’s mostrecent Annual Report and Accounts which can found on theCompany’s web site at http://puretechhealth.com/investors-reports-presentations.php.
Given these risks, uncertainties and other factors, many of whichare beyond the Company’s control, you should not place unduereliance on these forward-looking statements.
Each forward-looking statement speaks only as at the date ofthis document. Except as required by law, we assume noobligation to update these forward-looking statements publicly,or to revise any forward-looking statements to reflect events ordevelopments occurring after the date of this document, even ifnew information becomes available in the future.
The Presentation is confidential and should not be distributed,published or reproduced (in whole or in part) or disclosed by itsrecipients to any other person for any purpose, other than withthe consent of the Company.
By attending any delivery of, or electronically accessing, thePresentation, you agree to be bound by the above limitations andconditions and, in particular, you represent, warrant andundertake to the Company that: (i) you will not retain in anymanner the Presentation or forward the Presentation to any otherperson, or reproduce or publish this document, in whole or in part,for any purpose and (ii) you have read and agree to comply withthe contents of this notice.
This presentation is being made in reliance upon Section 105(c)of the Jumpstart Our Business Startup Act of 2012, as amended,and is intended solely for investors that are either qualifiedinstitutional buyers or institutions that are accredited investors(as such terms are defined under SEC rules).
References in the following presentation to our “ControlledFounded Entities” refer to Alivio Therapeutics, Inc., Follica,Incorporated, Entrega, Inc., Vedanta Biosciences, Inc., and SondeHealth, Inc. References to our “Non-Controlled Founded Entities”refer to Akili Interactive Labs, Inc., Karuna Therapeutics, Inc., VorBiopharma, Inc., Gelesis, Inc., and, for all periods prior toDecember 18, 2019, resTORbio, Inc.
PureTech: An advanced biotherapeutics company with a productive R&D engine
3
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 January 22, 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; 244.5 million in proceeds from the May 22, 2020 sale of 555.5 thousand Karuna common shares. 3 PureTech Level Cash Reserves represent cash balances and short-term investments held at PureTech Health LLC, PureTech Management, Inc., PureTech Health PLC, and 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 January 22, 2020 sale of 2.1 million Karuna common and the 44.5 million in proceeds from the May 22, 2020 sale of 555.5 thousand Karuna common shares.; 4Across PureTech and its Controlled and Non-Controlled Founded Entities; 5Funding figure includes private equity financings, public offering, and 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., and Eli Lilly. Number represents figure from January 1 – June 30, 2020. $758.8m (94.5%) came from third parties.
24 products and product candidates
and
13 are clinical stageof which
2 are FDA-cleared
Cash runway into 2024 via$321.5M Pro-forma Cash
Reserves at PRTC Parent Level1
$803.3M raised by Founded Entities since 20195
94% from third-parties
LSE Main Market (PRTC) FTSE 250
Relationships with multiple major pharma companies
or their investment arms4
Additional $45M Cash from Founded Equity Saleon May 25, 20202
Prior to receipt of proceeds from monetization of Founded Entities $120.6M Cash Reserves at PRTC
Parent Level as of December 31, 20193
Proven Team of Senior Executives
4
Oversaw R&D of products supporting 20 regulatory approvals and were in C-suite of companies acquired for more than $13 billion in the aggregate
Drove formation of team, scientific network & pipeline; Recognized as a top leader in biotech by EY, Scientific American, BioWorld & others; Board Member
Daphne Zohar Founder & Chief Executive Officer
Former COO Auspex (acq by Teva $3.5B), Nektar ($3B+ MC), GC SIRNA (acq by Merck $1.1B)
Bharatt Chowrira, PhD, JD President & Chief of Business and Strategy
Co-inventor of several PureTech external/internal programs; Formerly McKinsey, UCSD
Eric Elenko, PhD Co-founder & Chief Innovation Officer
Former CSO Millennium (acq. by Takeda $8.8B), Moderna, TA Head Oncology BMS
Joseph Bolen, PhD Chief Scientific Officer
Former Portfolio Manager at Life Sciences Partners, a leading European biotech investor group
Joep Muijrers, PhDChief of Portfolio Strategy
Former Partner Locke Lorde; Board Member
Stephen Muniz, Esq Co-founder & Chief Operating Officer
Former CEO & Board Member at Sanofi, Former President & Board Member at GSK
Christopher Viehbacher Board Chairman
MIT, Award winning materials science pioneer, Former member of the United States FDA’s SCIENCE Board
Robert Langer, ScDBoard and R&D Committee
Director of CATCH at MGH/MIT, Professor at HMS, Former Chief of Medicine at MGH, Board Director Alnylam, Former Pfizer Board
Dennis Ausiello, MDR&D Committee and Board Advisor
MIT, HHMI, Nobel Prize in Medicine, Scientific Advisory Board at Mitobridge & MPM Capital
Robert Horvitz, PhD R&D Committee Chair and Board Advisor
Former CEO Pearson, Former MacArthur Foundation Chair, Former Twitter Board
Dame Marjorie ScardinoBoard
Ben Shapiro, MDR&D Committee and Board Advisor
Former EVP of Research at Merck
Former President of Pfizer Global R&D
John LaMattina, PhDBoard and R&D Committee
Experienced Board of Directors and R&D Committee
5
Our board contributed to regulatory approvals of approximately 30 drugs, led multiple multi-billion dollar strategic transactions, and co-founded multiple companies
Harvard, Co-Founder of Millennium (acq. by Takeda $8.8B) & Abgenix (acq. by Amgen $2.2B)
Raju Kucherlapati, PhDBoard and R&D Committee
A unique collaborative research & development model for advancing new medicines
6The Brain-Immune-Gut (BIG) Axis: ~70% of immune cells and 500M neurons converge in the GI tract
Disease focused drug discovery based on proprietary insights and collaboration with the world’s leading experts on Brain, Immune, Gut
Successful model for bringing innovative medicines to patients
Collaborate with world’s leading domain experts on disease-specific discovery theme through the lens of
BIG Axis biology
Develop internally, partner, or advance through subsidiary
Value
Rigorous and disciplined approach to develop, de-
risk and validate the candidates in a cost-
effective way
VALIDATIONUnbiased Scientific
INNOVATION REALIZATIONBoundless
7
Our model enables the allocation of resources and cash to the most promising programs
34.4% Equity FDA Cleared,CE Mark 11.8% Equity Preclinical
PureTech’s Components of Value
78.6% Equity Preclinical
78.3% Equityplus Royalties Phase 3 Ready
45.9% Equity Phase 153.3% Equity Phase 2
22.0% Equityplus Royalties
FDA Cleared,CE Mark
(KRTX)18.1% Equityplus Royalties
Phase 3 Ready2
1This figure represents the stage of development for each Founded Entity’s most advanced product candidate. While PureTech maintains ownership of equity interests in its Founded Entities, the Company does not, in all cases, maintain control over these entities (by virtue of (i) majority voting control and (ii) the right to elect representation to the entities’ board of directors) or direct the management and development efforts for these entities. Consequently, not all such entities are consolidated in the financial statements. Relevant ownership interests for Founded Entities were calculated on a diluted basis (as opposed to a voting basis) as of December 31, 2019 (with the exception of Gelesis ownership which is as of April 1, 2020), including outstanding shares, options and warrants, but excluding unallocated shares authorized to be issued pursuant to equity incentive plans. Ownership of Vor (calculated as of June 30, 2020) and Sonde is based on the assumption that all future tranches of their most recent financing rounds are funded. Karuna ownership is calculated on an outstanding voting share basis as of May 26, 2020.; 2Following the completion of a successful End-of-Phase 2 meeting with the US FDA, Karuna remains on track to initiate the Phase 3 program by the end of 2020.; 3PureTech 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.; 4$44.5 million in proceeds from the May 22, 2020 sale of 555.5 thousand Karuna common shares.; 5PureTech Level Cash Reserves represent cash balances and short-term investments held at PureTech Health LLC, PureTech Management, Inc., PureTech Health PLC, and 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 January 22, 2020 sale of 2.1 million Karuna common and the 44.5 million in proceeds from the May 22, 2020 sale of 555.5 thousand Karuna common shares.
72.9% Equity Preclinical
8
Founded Entities1
Cash at PureTech Parent Level
Wholly Owned Pipeline
Cash runway into 2024 via$321.5M Pro-forma Cash Reserves at PRTC
Parent Level3
Additional $45M Cash from Founded Equity Saleon May 25, 20204
Prior to receipt of proceeds from monetization of Founded Entities $120.6M Cash Reserves at PRTC
Parent Level as of December 31, 20195
Karuna (PRTC Ownership: 18.1% plus royalties*)Selectively activating muscarinic acetylcholine receptors in the brain
9*As of May 26, 2020, PureTech’s percentage ownership of Karuna was approximately 18.1 percent on an outstanding share basis. PureTech Health has a right to royalty payments as a percentage of net sales from Karuna. 1Return on Investment and value creation calculations were assessed based on PureTech’s percentage ownership of Karuna outstanding shares as of market close June 30, 2020. 2$200.9 million in proceeds from the January 22, 2020 sale of 2.1 million Karuna common shares and $44.5 million in proceeds from the May 25, 2020 sale of 555.5 thousand Karuna common shares.
Nasdaq IPO, Phase 2 data
KarXT for schizophrenia met the primary endpoint with a clinically meaningful 11.6 point improvement on the PANSS total score
Built top team of CNS experts led by former Lilly executive Steven Paul, MD
XanomelineCNS active agonistTrospium chloride Peripheral antagonist blocks side effects of agonist
Muscarinic agonist
Muscarinic antagonist
Current antipsychotics all rely on the same fundamental mechanism of action and are plagued with tolerability and compliance issues
Positive outcome of End-of-Phase 2 meeting with FDA; initiation of Phase 3 program by end of 2020
~2.7M living with schizophrenia in the US
Completed tolerability POC
Planned Phase 2 POC study
Invented and filed patents to cover the approach
Exclusively in-licensed xanomeline from Eli Lilly
$18.5M total PRTC spend
$774M value created1
$245M of which is cash generated from equity sales2
42XROI1
Potential to target additional indications, including dementia-related psychosis and pain
Advised by world’s leading schizophrenia & dementia-related psychosis experts:
ValidationInnovation Realization
Gelesis (PRTC Ownership: 22.0% plus royalties*)FDA-cleared for the broadest patient population of any weight management product
10
*As of 1 April 2020, PureTech’s percentage ownership of Gelesis was approximately 22.0 percent on a diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans and assumes all committed tranches are funded in the Series 3 Growth financing round. PureTech has a right to royalty payments as a percentage of net sales from Gelesis.; 1Important Safety Information: Plenity is contraindicated in patients who are pregnant or are allergic to cellulose, citric acid, sodium stearyl fumarate, gelatin, or titanium dioxide. Plenity may alter the absorption of medications. Read Sections 6 and 8.3 of the Instructions for Use carefully. Avoid use in patients with the following conditions: esophageal anatomic anomalies, including webs, diverticuli, and rings; suspected strictures (such as patients with Crohn’s disease); or complications from prior gastrointestinal (GI) surgery that could affect GI transit and motility. Use with caution in patients with active GI conditions such as gastro-esophageal reflux disease (GERD), ulcers or heartburn. The overall incidence of adverse events (AEs) in the Plenity group was no different than the placebo group. The most common side effects were diarrhea,distended abdomen, infrequent bowel movements, and flatulence. For the safe and proper use of Plenity, refer to U.S. Instructions for Use or the EU Instructions for Use.
Prescribed therapeutics for obesity are systemically and centrally acting with potential for serious safety concerns Phase 3 Pivotal Trial Met Primary Endpoint
with 59% of adults with overweight or obesity had a clinically meaningful response to Plenity, losing on average 10% of their weight (22 pounds) over 6 months
Partnership with Ro to support US commercialization of Plenity
Partnership with China Medical System Holdingsfor the commercialization of Plenity in China; includes $35 million up front, with future milestone payments of up to $388 million plus royalties
Developing oral therapeutics to target chronic diseases such as NAFLD/NASH, Mucositis/IBD, Chronic Constipation (CIC)
~150M individuals in the US with overweight and obesity within Plenity’s label
Broad US launch of Plenity anticipated in 2021
Gelesis’ proprietary approach is designed to act mechanically in the GI pathway to potentially alter the course of chronic diseases.
Planned and completed POC studies
Planned Phase 2 POC study
Identified and in-licensed the core IP from collaborator Alessandro Sannino, PhD
Co-invented additional IP around a novel class of biocompatible, superabsorbent hydrogels
Advised by world’s leading experts:
FDA-cleared Plenity®1 for the broadest patient population of any weight management product (BMI 25-40 kg/m2)
FDA Clearance & European CE Mark
ValidationInnovation Realization
Akili (PRTC Ownership: 34.4%*)First game-based digital therapeutic cleared by the FDA for ADHD
11*As of 31 December 2019, PureTech’s percentage ownership of Akili was approximately 34.4 percent on a diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.
FDA Clearance & European CE Mark
FDA cleared for pediatric patients age 8 to 12 years old with primarily inattentive or combined-type ADHD who have a demonstrated attention issue
EndeavorRxTM (AKL-T01), in a pivotal study for pediatric ADHD, showed a statistically significant improvement on the primary endpoint, a composite score from the Test of Variables of Attention (T.O.V.A.®)
Commercial and development partnership with Shionogi in Japan and Taiwan; includes $20 million in up front payments and the potential to receive milestone payments for an additional $105 million, in addition to substantial royalties on product sales
Potential to target cognitive impairments in other indications: ASD, MDD, MS, MCI andTBI
Helped to build top development and commercial team and raise funds The treatment of many neuropsychiatric
disorders is only partially served, or not served at all, by currently available medications or by in-person behavioral therapy
~6.4M pediatric ADHD patients in the US
Planned and completed initial pilot and POC studies
Engaged with leading experts who had been studying the effects of video games on cognition and the underlying neural processes accessible by sensory stimulation
Identified and in-licensed from University of California, San Francisco (UCSF) the intellectual property invented by Adam Gazzaley, MD, PhD
Oversaw the initial product development and design
ValidationInnovation Realization
100%
90.0%
60%
60%
63%
31%
18%
11%
0% 20% 40% 60% 80% 100%
Phase 1Success
Phase 1 &2 Success
Phase 2 &3 Success
Phase 1, 2& 3
Success
PureTech Industry Average
PureTech has a track record of creating significant multiples of value…
1 IRR over a 10 year period (since January 2010) according to historical PureTech investment and realized and unrealized gains; including the following Founded Entities (Gelesis, Karuna, Vedanta, Akili, resTORbio, Entrega, Follica, Sonde, Alivio, Vor, Tal, Sync, Commense and PureTech Corporate expenses as well as adjusted for management ownership of PureTech; 2PureTech clinical trial success defined as a positive readout and not all product candidates conducted a Phase 1 clinical trial; Akili and Gelesis are regulated as devices; 3 Includes clinical trials from 2009 onward; 4 Industry average data measures the probability of clinical trial success of therapeutics. BIO, Biomedtracker, Amplion (2015) Clinical Development Success Rates 2006 – 2015.
51% IRRFounded Entities
(2009 to present)1
PureTech has demonstrated high probabilities of clinical success; particularly notable in the stages where
industry failures are typically high
42, 3
12
24 products and product candidates
of which
2were taken from inception to FDA Regulatory Clearance
42XROI from Karuna (KRTX)
(2009 to present)
…and is set to replicate this success through the Wholly-Owned Pipeline
13
Wholly Owned Pipeline represents a key source of future growth, with value expected to be retained within PureTech, supported by
our strong cash position
Founded Entities1 Wholly Owned Pipeline
34.4% Equity FDA Cleared,CE Mark 11.8% Equity Preclinical
78.6% Equity Preclinical
78.3% Equityplus Royalties Phase 3 Ready
45.9% Equity Phase 153.3% Equity Phase 2
22.0% Equityplus Royalties
FDA Cleared,CE Mark
(KRTX)18.1% Equity
plus RoyaltiesPhase 3 Ready2
72.9% Equity Preclinical
Our Founded Entities are a validation of PureTech’s model, and a significant source of value and upside
20202009
Discovery Preclinical Phase 1 Phase 2OUR PROGRAMS
Initiation of POC study in 2020LYT-100Deupirfenidone Lymphatic flow disorders, incl. lymphedema
LYT-100Deupirfenidone
COVID-19 post-recovery respiratory complications
LYT-210Anti-Delta-1 MAb GI autoimmunity
LYT-210Anti-Delta-1 MAb Solid tumors
LYT-200Anti-Galectin-9 MAb Solid tumors IND and initiation of Phase 1 study in 2020
MENINGEAL LYMPHATICSPlatform
MILK EXOSOMEPlatform
LYMPHATIC TARGETINGChemistry Platform
Orphan & other neurological indications
Initiation of POC study in Q3 2020
LYT-100Deupirfenidone Other fibrotic & inflammatory disorders
1 This figure represents the stage of development for each Founded Entity’s most advanced product candidate. While PureTech maintains ownership of equity interests in its Founded Entities, the Company does not, in all cases, maintain control over these entities (by virtue of (i) majority voting control and (ii) the right to elect representation to the entities’ board of directors) or direct the management and development efforts for these entities. Consequently, not all such entities are consolidated in the financial statements. Relevant ownership interests for Founded Entities were calculated on a diluted basis (as opposed to a voting basis) as of December 31, 2019 (with the exception of Gelesis ownership which is as of April 1, 2020), including outstanding shares, options and warrants, but excluding unallocated shares authorized to be issued pursuant to equity incentive plans. Ownership of Vor (calculated as of June 30, 2020) and Sonde is based on the assumption that all future tranches of their most recent financing rounds are funded. Karuna ownership is calculated on an outstanding voting share basis as of May 26, 2020.; 2Following the completion of a successful End-of-Phase 2 meeting with the US FDA, Karuna remains on track to initiate the Phase 3 program by the end of 2020.
Wholly OwnedHarnessing functions of the lymphatic system to develop PureTech’s internal programs
The mesenteric lymph nodes are the major
interface between the gut and immune system
Maintaining balance of fluidAddressing disorders involving lymphatic flow and lymphatic vessel restoration
Immune cell trafficking & programmingTargeting galectin-9 and immunomodulatory γδ1 T cells and related mechanisms with fully human mAbs
Absorbing dietary fatCommandeering the lymphatic system’s function of absorbing dietary fat to traffic therapeutics through the lymphatics
1
3
2
14
The BIG Axis: Lymphatic system connects all tissues to regional lymph nodes
Significant opportunity for an anti-fibrotic and anti-inflammatory approachDiscovery process
Wholly Owned LYT-100 development process
Stanley RocksonStanford Medicine
Babak MehraraMemorial Sloan Kettering
World’s leading lymphedema experts with proprietary insights & unpublished data:
A healthy lymphatic system drains interstitial fluid
Damaged lymphatics fail to drain
PureTech senior team member knowledge of LYT-100 clinical data & relationships (Auspex/Teva)
Fibrosis driven by TGF-β
Inflammation and pro-inflammatory cytokines, e.g.,
IL-6 and TNF-α
Anti-inflammatories do not address fibrosis-related
functional impairment
Anti-fibrotics limited by significant
tolerability issues
Need to target both mechanisms
Lymphatic Disorders
Lung Diseases
Other Inflammatory / Fibrotic Disorders
Inflammation Fibrosis
LYT-100 is a potent anti-inflammatory and anti-fibrotic molecule entering Phase 2 clinical development in 2020
15
Wholly Owned LYT-100 (deupirfenidone): Efficacy & tolerability advantages w/ pirfenidone’s de-risked clinical profile
19 large pills per day
Deuteration modifies metabolism
Short half-life and metabolic profile create limitations including: Differentiated PK profile provides potential advantages including:limited exposure enhanced exposure
frequent TID dosing & significant pill burden issues1 less frequent dosing & reduced pill burden
tolerability issues improved tolerability
dose-limited efficacy increased efficacy
No Composition of Matter Patent – currently under Orphan Drug Exclusivity
505(b)(2) pathway
Issued Composition of Matter Patent - exclusivity up to 2033
Potential for Orphan Drug Exclusivity for IPF and other orphan indications and proprietary implications (eg. Lymphedema)
Pirfenidone approved for IPF and has breakthrough designation for uILD
Clinical validation based on multiple investigator sponsored trials with pirfenidone
Pirfenidone validates efficacy of an anti-inflammatory and anti-fibrotic agent
LYT-100 showed favorable PK to pirfenidone
LYT-100 showed anti-fibrotic and anti-inflammatory activity
LYT-100 | DEUPIRFENIDONE – New Chemical EntityPIRFENIDONE
0
20000
40000
60000
80000
100000
120000
LYT-100 at same dose, 100mg/kg
Pirfenidone 100mg/kg
Control
Plas
ma
TNFα
con
cent
ratio
n 90
m
inut
es o
f ora
l pre
trea
tmen
t, pg
/mL
16
Wholly Owned LYT-100 has potential to address a range of inflammatory and fibrotic conditions
171Cormier et al., Cancer 2010;116(22):5138-49; 2Hayes et al.,Gynecol Oncol. 2017;146(3):623-629; 3Ridner et al., Lymphat Res Biol. 2016;14(4):198-205; 4 Noble et al., European Respiratory Journal 2016;47: 243-253.; 5 Cho et al., 20017, CJASN
Secondary lymphedema occurs in breast cancer and other cancer patients1, including gynecological and head and neck cancer patients2,3
Primary lymphedema includes rare, pediatric lymphatic diseases
Proprietary, preclinical POC
Clinical validation based on multiple
investigator sponsored trials with pirfenidone
Focal segmental glomerulosclerosis (FSGS);Radiation-induced fibrosis
Validation for LYT-100 or pirfenidoneIndications
~130k
~1M
in the United States withIPF or uILD
in the United States overall with lymphedema
Other Fibrotic & Inflammatory Disorders
Idiopathic pulmonary fibrosis (IPF);Unclassifiable interstitial lung disease (uILD);Serious respiratory complications following COVID-19
Clinical/approved
0
50
100
150
0 1 2 3 4 5 6
Chan
ge in
tail
volu
me,
m
m3
Time in weeks
Control LYT-100 Treatment
begins
Lymphedema
IPF4
FSGS5
LYT-100 development plan overview
2020: Initiated Phase 1b study
Multiple ascending dose study and food-effect study in healthy volunteers
• Safety & tolerability
• Pharmacokinetics (PK)
Phase 1b data in 2020
Acute toxicity
ADME
CMC and cGMP clinical supply
In silico PK modeling
Single dose crossover study in healthy volunteers
• Validated patient reported outcomes measuring:
‒ Physical functioning‒ Limb heaviness, pain, and tightness‒ Quality of life impact
• Bioimpedance spectroscopy
• Tonometry (fibrosis)
• Serum inflammatory biomarkers
• Relative limb volume
Exploratory Endpoints
Completed
Patient proof-of-concept and biomarker study in breast cancer-related, upper limb secondary lymphedema
18
2020: Expected POC initiation in lymphedema
Exploring additional fibrotic & inflammatory indications
Q3 2020: Expected POC initiation in post-COVID-19
LYT-100 for serious respiratory complications following resolution of COVID-19 infection
191Cell. 2016 Sep 8;166(6):1485-1499; Nat Med 23, 556–567 (2017).
• Targeting solid tumors with historically low rates of survivaland lack of therapies
• Reverse the immuno-suppressed tumor micro-environment to allow for potent immune-mediated cancer attack
• Galectin-9 and pathogenic γδ1 T cells in tumors correlate with aggressive disease features and lower efficacy of checkpoint inhibitors1
• Demonstrated single agent activity
‒ Demonstrated tumor reduction in preclinical models, including a pancreatic model where anti-PD-1s don’t work, as well as T cell activation in human tumor organoids
• Potential biomarker opportunities for patient selection
>50KMetastatic colorectal cancer
>28KMetastatic pancreatic cancer
>4KMetastatic cholangiocarcinoma
New US patients annually
LYT-200 & LYT-210: Fully human mAbs targeting galectin-9 & immunomodulatory γδ1 T cells in immunologically silent tumors
Wholly Owned
PureTech is executing and delivering results…
20
Since July 2018, PureTech and its Founded Entities have delivered:
11clinical stage trial
initiations
12clinical readouts
7 publications
2 FDA clearances& 2 European CE marksMultiple
strategic partnerships
>$880M raisedwith top-tier
co-investors in Founded Entities
EndeavorRx™
Relative Value of Karuna (KRTX) Stake to PureTech (PRTC) Market Cap
…but these value driving successes have significantly outpaced market capitalization
21
1 This figure represents the stage of development for each Founded Entity’s most advanced product candidate. While PureTech maintains ownership of equity interests in its Founded Entities, the Company does not, in all cases, maintain control over these entities (by virtue of (i) majority voting control and (ii) the right to elect representation to the entities’ board of directors) or direct the management and development efforts for these entities. Consequently, not all such entities are consolidated in the financial statements. Where PureTech maintains control, the entity is referred to as a Controlled Founded Entity in this report and is consolidated in the financial statements. Where PureTech does not maintain control, the entity is referred to as a Non-Controlled Founded Entity in this report and is not consolidated in the financial statements. As of 31 December 2019, Controlled Founded Entities include Alivio Therapeutics, Inc., Follica, Incorporated, Entrega, Inc., Vedanta Biosciences, Inc. and Sonde Health, Inc., and Non-Controlled Founded Entities include Akili Interactive Labs, Inc., Gelesis, Inc., Karuna Therapeutics, Inc., Vor Biopharma Inc. and, for all periods prior to December 18, 2019, resTORbio, Inc. Relevant ownership interests for Founded Entities were calculated on a diluted basis (as opposed to a voting basis) as of 31 December 2019 (with the exception of Gelesis ownership which is as of 1 April 2020), including outstanding shares, options and warrants, but excluding unallocated shares authorized to be issued pursuantto equity incentive plans. Ownership of Vor (calculated as of June 30, 2020) and Sonde is based on the assumption that all future tranches of their most recent financing rounds are funded. Karuna ownership is calculated on an outstanding voting share basis as of 26 May 2020.
Value Components of Other Assets
Founded Entities1
78.3% Equity+ Royalties
Phase 3 Ready
22.0% Equity+ Royalties
FDA Cleared,CE Mark
53.3% Equity Phase 2 78.6% Equity Preclinical 45.9% Equity Phase 1
72.9% Equity Preclinical
34.4% Equity FDA Cleared,CE Mark
11.8% Equity Preclinical
Wholly Owned Pipeline
Source: Management and Capital IQ market data as of June 13, 2020.Phase 1 Preclinical Preclinical
Royalties Only
LYT-100 LYT-200/210
Implied Value
of Other Assets
$--
$200
$400
$600
$800
$1,000
$1,200
Jul-19 Aug-19 Sep-19 Oct-19 Nov-19 Dec-19 Jan-20 Feb-20 Mar-20 Apr-20 May-20 Jun-20 Jul-20
PRTC Market Cap
PRTC Stake in KRTXKRTX
Phase 2 Clinical Trial Success
PRTC sells 2.1M shares
of KRTX
Market peak prior to global
COVID-19 sell-off($M)
Cash
18.1% Equity (KRTX)
End-of-Phase 2 meeting, Initiation of Phase 3 program, add’l. readouts
Numerous milestones expected, including at least 6 readouts and 10 initiations in 2020
22*Relevant ownership interests for Founded Entities were calculated on a diluted basis (as opposed to a voting basis) as of December 31, 2019 (with the exception of Gelesis ownership which is as of April 1, 2020), including outstanding shares, options and warrants, but excluding unallocated shares authorized to be issued pursuant to equity incentive plans. Ownership of Vor (calculated as of June 30, 2020) and Sonde is based on the assumption that all future tranches of their most recent financing rounds are funded. Karuna ownership is calculated on an outstanding voting share basis as of May 26, 2020.
ProductCandidate
Topline results from multiple clinical studies
Additional strategic partnerships
New clinical candidate selections
Progress of discovery/preclinicalprograms
PureTechOwnership* 2020 2021
LYT-200
Discovery programs
ALV-306
ENT-100
LYT-100
LYT-210
100%
100%
78.6%
72.9%
100%
Nomination of preclinical candidate(s)
Continued advancement of platform
Results from Phase 1b MAD & initiation of POC study in patients
Sonde 45.9% Readout from depression detection study
Preclinical and biomarker studies
IND filing; Initiation of Phase 1 study in solid tumors
100%
VOR33 11.8% Pre-IND meeting with the FDA
KarXT 18.1%
GS500
Plenity®
22.0% Initiation of Phase 3 study in chronic constipation
US limited commercial launch22.0%
AKL-T01 34.4% FDA cleared & European CE Mark granted in pediatric ADHD
FOL-004 78.3% End-of-Phase 2 meeting, Initiation of Phase 3 program in AGA
VE303 53.3% Results from Phase 2 study in high-risk CDI
VE202 53.3% PK/PD results from Phase 1 healthy subject studies for IBD
GS300 22.0% Initiation of Phase 2 study in NASH/NAFLD
LYT-100 100% Initiation of COVID-19 post-recovery respiratory complications study
Results from POC study in patients with breast cancer related lymph
IND filing; Initiation of clinical study in distal colitis & pouchitis
Broad US commercial launch
Results from COVID-19 post-recovery respiratory complications study
GS200 22.0% Results from Phase 2 study in patients with T2D and pre-diabetes
2022
ALV-107 78.6% IND filing
GS100 22.0% Initiation of Phase 2 weight management study in adolescents
VE416 53.3%
VE800 53.3%
Results from Phase 1/2 study in food allergies
Results from Phase 1 study in solid tumors
Initiation of Phase 2 study
indicates completed milestoneKey milestones are bolded
Product candidate related to the BrainProduct candidate related to the Immune systemProduct candidate related to the Gut
Indicates partially completed milestone
B
Results from Phase 1 study
Results from non-human primate POC study, Publishing key preclinical data
Initiations of second Phase 3 study; Open-label study on long-term safety
Initiation of Phase 1 study in acute myeloid leukemia
23
1PureTech 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$44.5 million in proceeds from the 22 May 2020 sale of 555.5 thousand Karuna common shares.; 3PureTech 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.
LSE Main Market / FTSE-indexed: PRTCMarket capitalization ~$939M (£758) as of June 30, 2020; 1.24 USD:GBP
Jefferies International Peel Hunt LLP Liberum
Peter Welford Amy Walker Alistair Campbell
Analyst Coverage
Headquartered in Seaport, Boston
$321.5M Pro-forma Cash Reserves at PRTC Parent Level1$45M Cash from KRTX Equity Sale on May 25, 20202
$120.6M Cash Reserves at PRTC Parent Level as of December 31, 20193
285,512,461 outstanding shares as of July 1, 2020
Board & Management
Disclosed Shareholders
Other Shareholders
Disclosed Shareholders as of March 31, 2020 include: Invesco Asset Management Limited, Baillie Gifford & Co., Jupiter Asset Management Ltd., Canaccord Genuity Wealth Management, and M&G Investment Management, LTD.
~11%
~29%
~60%
PureTech is executing and delivering results
24
Partnerships
FDA Clearance &European CE Mark (Gelesis100)
Regulatory
Financings
R&D and data presentations
Akili’s partnership with ShionogiUp to $20M in upfront payments with the potential to receive milestone payments for Japan and Taiwan commercialization of up to an additional $105M in addition to royalties on product sales
Alivio’s partnership with Imbrium TherapeuticsUp to $14.75M in upfront and near-term license exercise payment & eligible to potentially receive $260M+ in research and development milestones in addition to royalties on product sales
Gelesis’ partnership with Ro to support US commercialization of Plenity® Phase 2 results for Karuna’s KarXT Phase 1 results for Vedanta’s VE303 & VE202 Topline results for Follica in AGA Pivotal data for Gelesis100 published in Obesity Pivotal data for AKL-T01 ADHD study published in Lancet
Digital Health Results for Akili’s AKL-T01 in children with ADHD alone or
as an adjunct to stimulants Akili’s AKL-T03 data on MDD presented at ACNP Vedanta’s IO candidate selected and being advanced
with BMS Vedanta’s Nature publication for its IO candidate, VE800 PureTech programs published in Nature and Nature
Neuroscience POC study for Vor published in PNAS Presentations on PureTech’s LYT-200 and LYT-210 at
AACR & SITC
Karuna’s $124M Series A+B financings; $103M IPOKey investors include ARCH Venture Partners, Fidelity, Eventide, Pivotal bioVenture Partners, Partner Fund
Akili’s $68M Series C financingKey investors include Temasek, Amgen Ventures, JAZZ, M Ventures
Vor’s $153M Series A+B financingsKey investors include RA Capital Management, Fidelity Management & Research Company, Pagliuca Family Office, Alexandria Venture Investments,5AM Ventures, Johnson & Johnson Innovation—JJDC, Inc. (JJDC), Osage University Partners, Novartis Institutes for BioMedicalResearch
Vedanta’s $71M Series C financingKey investors include Bill & Melinda Gates Foundation, Bristol-Myers Squibb, Rock Springs Capital
Sonde’s $16M Series A financingKey investors include M Ventures, MP Healthcare Venture Management, Neoteny 4
Gelesis’ $85M in new capital to support commercialization of Plenity®
Consists of $63.4M financing round led by Vitruvian Partners and $21.2M in new, non-dilutive grant funding and loans
EndeavorRx™ (AKL-T01)
Wholly OwnedPureTech’s track record of success, set to be repeated through our Wholly-Owned Pipeline
25
Initiation of POC study in 2020LYT-100Deupirfenidone Lymphatic flow disorders, incl. lymphedema
LYT-100Deupirfenidone
COVID-19 post-recovery respiratory complications
LYT-210Anti-Delta-1 MAb GI autoimmunity
LYT-210Anti-Delta-1 MAb Solid tumors
Discovery Preclinical Phase 1 Phase 2 Phase 3
LYT-200Anti-Galectin-9 MAb Solid tumors IND and initiation of Phase 1 study in 2020
OUR PROGRAMS
MENINGEAL LYMPHATICSPlatform
MILK EXOSOMEPlatform
LYMPHATIC TARGETINGChemistry Platform
Orphan & other neurological indications
Initiation of POC study in Q3 2020
LYT-100Deupirfenidone Other fibrotic & inflammatory disorders
in progress
completed
Lymphedema: A chronic progressive disease with no FDA approved therapies
261 Patient image: “A comprehensive overview on the surgical management of secondary lymphedema of the upper and lower extremities related to prior oncologic therapies; Figure 1” by Garza et al., 2017 is licensed under CC BY 4.0. 2. DiSipio et al., 2013, Lancet Oncology
~500K breast cancer survivors with secondary lymphedema
~20% of all new breast cancer patients who undergo surgery2
~1M individuals in the US have lymphedema
including
Current treatment options include compression, physical therapy, and surgery (liposuction, lymphovenous transplant)
A progressive disease with disability, disfigurement, and risks of serious comorbidities1
Injury to the lymphatics blocks fluid flow and creates inflammation and fibrosis
27Patient images: Kataru et al., 2019, Translational Res.
Fluid accumulates, causing inflammation and fibrosis
LYMPHEDEMATOUS ARM
Damaged lymphatics create blocked flow
Surgery and radiation damage
lymphatics
HEALTHY ARM
Normal lymphatics drain fluid from tissue
Fluid pumped from arm through lymphatic vesselsHealthy arm
fluorescent tracer image
Lymphedema fluorescent
tracer image
Lymphedema: A feedback loop between inflammation and fibrosis
1Rockson et al., 2019, Nat Rev Dis Primer.; 2Gousopolos et al., 2016, JCI Insight – CD-45 stain.; 3Avraham et al., 2010; Am J Pathology – TGF-β stain
Fibrosis in arm tissue impairs flow and blocks regeneration3
Immune cell infiltration in arm promotes fibrosis2
CD45 stain
Control
Lymphedema
TGF-β stain
A healthy lymphatic system drains interstitial fluid
Damaged lymphatics fail to drain
Healthy lymphatics maintain fluid homeostasis1
28
Preclinical model mimics human pathophysiology and tissue changes
291Ly et al., 2017, Int. J. Mol. Sci.; 2Zampell et al., 2012, PLoS One.; 3Rutkowski et al., 2006, Microvasc Res.
Fibrosis and collagen deposition3
Immune cell infiltration in affected tissue2
Mouse tail lymphatics Lymphatic damage blocks flow1
Lymphedema Control
CD45
+ce
lls (%
)
p<0.01
0
10
20
30
40
Lymphedematous Tail Tissue Stained for Collagen (blue)
A healthy lymphatic system drains interstitial fluid
Damaged lymphatics fail to drain
Control
Healthy tail lymphatics drain fluid
Fibrotic tissue and tail volume
increase
Lymphedematous tail
0
20
40
60
80
100
120
0 1 2 3 4 5 6
Cha
nge
in ta
il vo
lum
e, m
m3
Time in weeks
Control
LYT-100
Treatment begins
LYT-100 once-daily treatment reduced swelling in preclinical models
1Tail volume ± SEM
Mouse lymphedema model: ablation of tail lymphatics results in chronic tail swelling, inflammation, and fibrosis
– Drug started at 2 weekspost-surgery
– N=7: LYT-100N=7: control carboxymethycellulose (CMC)
Systemic treatment(Q.D. oral gavage; 400 mg/kg/d)
WTWT
Tailsurgery
2 wks
LYT-100control
4 wks
Control LYT-100
2 weeks
6 weeks
2 weeks
6 weeks
LYT-100 reduced tail volume in lymphedema model1
30
In vitro reduction of TGF-β induced soluble collagen production (mouse fibroblasts)
Preclinical plasma concentrations of TNFα with LYT-100 versus control
LYT-100 is designed to address underlying mechanisms of lymphedema
31
36% reduction
LYT-100 reduced TGF-β
induced fibrosis
LYT-100 development plan overview
2020: Initiated Phase 1b study
Multiple ascending dose study and food-effect study in healthy volunteers
• Safety & tolerability
• Pharmacokinetics (PK)
Phase 1b data in 2020
Acute toxicity
ADME
CMC and cGMP clinical supply
In silico PK modeling
Single dose crossover study in healthy volunteers
• Validated patient reported outcomes measuring:
‒ Physical functioning‒ Limb heaviness, pain, and tightness‒ Quality of life impact
• Bioimpedance spectroscopy
• Tonometry (fibrosis)
• Serum inflammatory biomarkers
• Relative limb volume
Exploratory Endpoints
Completed
Patient proof-of-concept and biomarker study in breast cancer-related, upper limb secondary lymphedema
32
2020: Expected POC initiation in lymphedema
Exploring additional fibrotic & inflammatory indications
Q3 2020: Expected POC initiation in post-COVID-19
LYT-100 for serious respiratory complications following resolution of COVID-19 infection
Respiratory complications of COVID-19
1Xie, L. Chest Journal. June 2005.; 2Das, K. Indian Journal of Radiology and Imaging. Vol. 27 2017.
Serious post-acute respiratory complications are an emerging issue for those who survive
Recent publications suggest a high proportion of mild, moderate and severe COVID-19 patients show signs of lung fibrosis at three weeks post symptom onset
In SARS, patients can develop persistent pulmonary fibrosis1
and up to 1/3 of SARS and MERS patients have pulmonary fibrosis after recovery2
Many interstitial lung diseases (ILDs) are characterized by inflammation and fibrosis, which can result in impaired lung function and progressive pulmonary fibrosis
Clinical trials in the post-acute setting are important as millions of people have been infected by COVID-19
33
Rationale
LYT-100 for serious respiratory complications following resolution of COVID-19
341 Spagnolo, P. The Lancet May 2020
Trial Design
Global, randomized, placebo-controlled trial will evaluate LYT-100 in non-critical COVID-19
patients with respiratory complications
N = approximately 150
Topline results expected mid-2021
LYT-100 showed anti-fibrotic and anti-inflammatory activity
0
20000
40000
60000
80000
100000
120000
Plas
ma
TNFα
con
cent
ratio
n 90
m
inut
es o
f ora
l pre
trea
tmen
t,
pg/m
L
LYT-100 at same dose, 100mg/kg
Pirfenidone 100mg/kg
Control
LPS Model (Rats), n=6-8 per group, 100mg/mL
Pirfenidone mechanisms in acute and chronic interstitial lung diseases
• Reduces pro-inflammatory cytokines: IL-6, TNF-α
• Suppresses TGF-β and downstream signaling
Primary outcome
• Pulmonary function testing
Secondary endpoints
• Safety and tolerability
• Pharmacokinetics
• Acute inflammatory biomarkers
• Hospitalization events
• Imaging and patient reported outcomes
Multimodal mechanism of action
LYT-100 for focal segmental glomerulosclerosis (FSGS)
351Sim et al., 2016, Am J Kidney Dis.; 2Cho et al., 2007, CJASN. Image: (L) Chiang & Inagi, 2010, Nat Rev Nephrol; (R) Stokes et al., 2006, Kidney International
• Rare, progressive fibrotic kidney disease that can lead to kidney failure and dialysis1
‒ 4,500 to 8,000 individuals develop FSGS every year
• Clinical proof of concept with pirfenidone in FSGS demonstrated in NIH study (N=21)2:‒ 25% median improvement in
the rate of decline of glomerular filtration rate
‒ Projected renal survival prolonged by ~55%
• No specific treatments designed to reduce fibrosis and inflammation
• Current treatment with immunosuppression is symptomatic and often ineffective in preventing relapse and progression to end-stage renal disease
• LYT-100 has favorable PK over pirfenidone which enables lower dosing and potentially improved safety
Segmental lesion in FSGS
361Cell. 2016 Sep 8;166(6):1485-1499; Nat Med 23, 556–567 (2017).
• Targeting solid tumors with historically low rates of survivaland lack of therapies
• Reverse the immuno-suppressed tumor micro-environment to allow for potent immune-mediated cancer attack
• Galectin-9 and pathogenic γδ1 T cells in tumors correlate with aggressive disease features and lower efficacy of checkpoint inhibitors1
• Demonstrated single agent activity
‒ Demonstrated tumor reduction in preclinical models, including a pancreatic model where anti-PD-1s don’t work, as well as T cell activation in human tumor organoids
• Potential biomarker opportunities for patient selection
>50KMetastatic colorectal cancer
>28KMetastatic pancreatic cancer
>4KMetastatic cholangiocarcinoma
New US patients annually
LYT-200 & LYT-210: Fully human mAbs targeting galectin-9 & immunomodulatory γδ1 T cells in immunologically silent tumors
Wholly Owned
Foundational biology:
Proof-of concept in preclinical models:
LYT-200: Aimed at galectin-9, a fundamental modulator of the immune system
37Image adapted from J Mol Biol; 428 (16): 3266-3281; 2016Treg = T regulatory cell; MDSC = myeloid derived suppressor cell; M1/M2 = tumor associated macrophage (TAM)1 (immunoactive) and 2 (immunosuppressed) cell; Th1 = T helper1 cell*CPI=checkpoint inhibitor
Affects multiple pathways of immunosuppression, potentially enabling a single-agent therapeutic
Promotes expansion of
MDSCs
Induces Treg cell differentiation
and stability
Induces apoptosis of Th1 and
CD8+ T cells
Treg
CD8
Th1
MDSCs
CD8
Tumor
Galectin-9
Switching M1 to M2 macrophage
M1 M2
A model where anti-PD1s do not work
T cell activation with LYT-200 in patient-derived organoid model
Single agent activity in KPC (pancreatic cancer) model
T cell activation with LYT-200 in patient-derived organoid model1
Multiple lines of preclinical data supporting therapeutic potential of LYT-200
381For patient-derived organoids, n = 20 tumor samples; Success defined as: >20% upregulation of at least two out of three T cell activation markers; success achieved in 60% of tumors with majority showing >2 fold activation
n = 10 / armP < 0.01
800
600
400
200
Tum
or w
eigh
t (m
g)LYT-200 drug properties make it an
excellent clinical clone:
• High affinity and specificity for galectin-9
• Desired function: Blocking galectin-9 mediated immunosuppression
• Robust activity in preclinical studies:‒ Single agent causes tumor reduction in
pancreatic and melanoma mouse models
‒ Observed ~50% tumor reduction with LYT-200 vs. ~22% tumor reduction with anti-PD1 in melanoma model
‒ Increase in intra-tumoral CD8 T cells in combination with anti-PD1
‒ Activation of intra-tumoral immunity in patient-derived tumor models
A model where anti-PD1s do not work
Dose escalation and dose expansion study Clinical Investigators
Planned LYT-200 Phase 1 study design for metastatic solid tumors
39
Dose finding (all comers), safety, tolerability, RP2D, PK/PD
Further expansion aimed at enabling accelerated approval single agent and/or combo
Safety and efficacy– exploratory endpoints –
Pancreatic Colorectalcholangiocarcinoma
Other amenable GI/non-GI indications
Filip Janku Osama Rahma
Aparna Parikh
Richard Carvajal
Zev Wainberg
Neil Segal
Manji Gulam
Brian Wolpin
2nd Clinical Advisory Board held at ASCO 2019
LYT-210: Monoclonal antibody aimed at immunosuppressive γδ1 T cells
40Image adapted from CellPress: REVIEW: γδ T Cells: Unexpected Regulators of Cancer Development and Progression. DC = dendritic cell; TAM = tumour associated macrophage; MDSC = myeloid derived suppressor cell; IL17 = interleukin 17
Immunosuppressive γδ1 T cells
Solid tumors harbor immunosuppressive γδ1 T cells that correlate with tumoraggressiveness / lower rate survival
LYT-210 is a fully human monoclonal IgG1 antibody (cross reacts with monkey)
Works through multiple pathways to cause immunosuppression in the tumor micro-environment
Pro-tumor γδ1 T cells
Restrict cytotoxic γδ T cells activity
Chemoattract MDSCs, TAMs neutrophils
Immunosuppressive cytokine production (exp. IL17)
Restrict and suppress cytotoxic αβ T cell activity
TUMOR PROGRESSION
Inhibit maturation and antigen presentation of DCs
Multiple lines of preclinical data supporting therapeutic potential of LYT-210
411For patient-derived organoids: Analyzed n = 22 tumor samples; success defined as: >20% upregulation of at least two out of three T cell activation markers; Success achieved in 63% of tumors with majority showing >2-fold activationCell. 2016 Sep 8;166(6):1485-1499 ; * Tool antibody that blocks mouse immunosuppressive γδ T cells
Single agent activity in KPC (pancreatic cancer) model
(Published in Cell)T cell activation with an anti-δ1 mAb in
patient-derived organoid model1
n = 10 / armP =0.009
%IF
Nγ+
(CD8
+ T c
ells
)
15
0
5
10
%TF
N⍺+
(CD8
+ T c
ells
)
15
0
5
10
LYT-210 candidate clone has excellent drug properties:
• High affinity and specificity/ selectivity for pathogenic γδ1 T cells
• Species cross reactivity to enable IND tox
• Desired function: Inducing ADCC/ ADCP and activating suppressed effector T cells in patient-derived tumor models
• Proof of principle in animal models:‒ Targeting immunosuppressive γδT
cells significantly prolongs survival in a KPC model
‒ Targeting immunosuppressive γδT cells synergizes with checkpoint inhibitors in melanoma and lung cancer models
• A Phase 2 study of KarXT for schizophrenia met the primary endpointwith a statistically significant (P<0.0001) and clinically meaningful 11.6 point improvement on the PANSS total score from baseline vs. placebo
• KarXT was well-tolerated in the Phase 2 trial, with similar discontinuation rates between KarXT and placebo
• Xanomeline, exclusively licensed from Eli Lilly, previously demonstrated dose-dependent decreases in multiple psychotic symptoms and related behaviors in schizophrenia and Alzheimer’s disease patients, as compared to patients on placebo
• Potential to target additional indications, including dementia-relatedpsychosis and pain
Karuna: Selectively activating muscarinic acetylcholine receptors in the brain
42*As of May 26, 2020, PureTech’s percentage ownership of Karuna was approximately 18.1 percent on an outstanding share basis. PureTech Health has a right to royalty payments as a percentage of net sales from Karuna.
KarXT
Positive outcome of End-of-Phase 2 meeting with FDA; initiation of Phase 3 program by end of 2020
Key Highlights
• KarXT is a selective muscarinic receptor agonist for the treatment of psychosis and cognitive impairment across CNS disorders
XanomelineCNS active agonist
Trospium chloride Peripheral antagonist blocks side effects of agonist
Muscarinic agonist
Muscarinic antagonist
~2.7Mliving with schizophrenia in the US
Current antipsychotics in use all rely on the same fundamental mechanism of action
At least half of patients fail to adequately respond to current antipsychotics, with others discontinuing medication due to severe side effects, including sedation, extrapyramidal side effects and significant weight gain
PRTC Ownership: 18.1%*
KarXT Phase 2 primary endpoint: PANSS Total Score at week 5, and topline results
Source: Karuna Phase 2 results from company presentation
• Clinically meaningful and statistically significant improvement in total PANSS vs. placebo, with 11.6 point improvement at Week 5 with p<0.0001
• Statistical separation at every assessed time point
• Statistically significant reduction in the secondary endpoints of PANSS-positive and PANSS-negative subscales at all assessed timepoints
• The overall discontinuation rate and the discontinuation rate due to treatment emergent adverse events on KarXT was similar to placebo
• 91% of patients escalated to the high dose of KarXT as part of the flexible dose design
• No evidence of somnolence, extrapyramidal side effects, or weight gain
43
Karuna pipeline and upcoming milestones
Product candidate Indication Discovery/Preclinical Phase 1 Phase 2 Phase 3 Upcoming
Milestone
KarXT
Schizophrenia – psychosisPhase 3 study
initiation by end of 2020
Schizophrenia – cognitive symptoms Phase 1b study initiation H1 2020
Schizophrenia – negative symptoms Phase 1b study initiation H1 2020
Dementia-related psychosis Phase 1b topline data end of 2020
Pain Phase 1b topline data mid-2020
Other Muscarinic-targeted drug candidateIND-enabling
studies2020
Phase Completed
Phase In-progress 44
Gelesis: FDA-cleared for the broadest patient population of any weight management aid
45
*As of 1 April 2020, PureTech’s percentage ownership of Gelesis was approximately 22.0 percent on a diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans and assumes all committed tranches are funded in the Series 3 Growth financing round. PureTech has a right to royalty payments as a percentage of net sales from Gelesis.; 1Important Safety Information: Plenity is contraindicated in patients who are pregnant or are allergic to cellulose, citric acid, sodium stearyl fumarate, gelatin, or titanium dioxide. Plenity may alter the absorption of medications. Read Sections 6 and 8.3 of the Instructions for Use carefully. Avoid use in patients with the following conditions: esophageal anatomic anomalies, including webs, diverticuli, and rings; suspected strictures (such as patients with Crohn’s disease); or complications from prior gastrointestinal (GI) surgery that could affect GI transit and motility. Use with caution in patients with active GI conditions such as gastro-esophageal reflux disease (GERD), ulcers or heartburn. The overall incidence of adverse events (AEs) in the Plenity group was no different than the placebo group. The most common side effects were diarrhea, distended abdomen, infrequent bowel movements, and flatulence. For the safe and proper use of Plenity, refer to U.S. Instructions for Use or the EU Instructions for Use.
Key Highlights• Plenity is FDA-cleared for the broadest
patient population of any weight management product (BMI 25-40 kg/m2)
• Granted European CE mark to market Plenity as a class III medical device
• Differentiated risk/benefit profile• Consumer-driven approach enabled by
unique risk benefit profile, unlike any previously launched obesity drug
• Partnership with Ro to support US commercialization of Plenity
• Proprietary mechanically-acting hydrogel platform, made from naturally-derived building blocks
Plenity®1, GS100, Gelesis200, GS300, GS400, GS500
Broad US launch of Plenity anticipated in 2021
PRTC Ownership: 22.0%*
Other prescribed therapeutics for obesity are systemically and centrally acting with potential for serious safety concerns, greatly limiting their use
~150MIndividuals in the US with overweight and obesity within Plenity’s label
Consumer expectations for weight loss provide an opportunity for Plenity® in target population of BMI <35
461 Shannon K, et.al,. Obesity disease coverage. Datamonitor Healthcare report 2017:56-59; 2 Based on KOL and clinical experience.; Note: Placement of treatment logos reflects the BMI where most usage occurs – not the FDA indication or label
Current Rx options have safety and tolerability challenges
So, they are reserved for highest risk high BMI patients (60% of use in
24% of the population)1
The weight loss they offer is not generally satisfying for higher
BMI patients2
Patient/Physician Willingness to Accept Safety RiskLow Higher
BMI 25-27 BMI 27-30 BMI 30-35 BMI 35-40 BMI >40
>75% of adults affected with
Overweight/Obesity
19M
33M
50M47M
23M
(Gelesis100)
US PopulationPlenity’s Target
Hope to lose 15 – 30 LBS
Plenity meets consumer expectations
Hope to lose >40 LBS Current therapies don’t meet
consumer expectations
Key findings from Plenity® pivotal study
47TEAE = Treatment Emergent Adverse Event; For the safe and proper use of Plenity, refer to the Instructions for Use in the US and EU.
RESPONDERSADULTS ACHIEVING 5% OR GREATER WEIGHT LOSS
SUPER RESPONDERSADULTS ACHIEVING 10% OR GREATER WEIGHT LOSS
• 59% of adults with overweight or obesity had a clinically meaningful response to Plenity®, losing on average 10% of their weight (22 pounds) or ~3.5 inches from their waist
• Plenity doubled the odds of achieving 5% or greater weight loss compared with placebo
• 26% of adults with overweight or obesity were super-responders to Plenity, losing on average 14% of their weight (30 pounds)
6 out of 10
26%Co-primary endpoint – The study also demonstrated statistically superior weight loss compared with the placebo group (−6% vs −4%, respectively; P=0.0007) and did not meet the predefined super-superiority margin of 3%
Safety – Plenity had no overall increased risks versus placebo, no serious adverse events and a lower dropout rate versus placebo
Most common side effects are fullness, bloating, flatulence, and/or abdominal pain
Plenity (n) Placebo (n)
% of subjects with severe TEAE 3.6% (8) 4.7% (10)
# of subjects with serious TEAE 0 1*
Plenity go-to-market approach
48Important Safety Information: Plenity is contraindicated in patients who are pregnant or are allergic to cellulose, citric acid, sodium stearyl fumarate, gelatin, or titanium dioxide. Plenity may alter the absorption of medications. Read Sections 6 and 8.3 of the Instructions for Use carefully. Avoid use in patients with the following conditions: esophageal anatomic anomalies, including webs, diverticuli, and rings; suspected strictures (such as patients with Crohn’s disease); or complications from prior gastrointestinal (GI) surgery that could affect GI transit and motility. Use with caution in patients with active GI conditions such as gastro-esophageal reflux disease (GERD), ulcers or heartburn. The overall incidence of adverse events (AEs) in the Plenity group was no different than the placebo group. The most common side effects were diarrhea, distended abdomen, infrequent bowel movements, and flatulence. For the safe and proper use of Plenity, refer to U.S. Instructions for Use or the EU Instructions for Use.
Lower barrier to access by both driving telehealth and traditional physician visits while leveraging mail order to create an Amazon-like experience
A support program that encourages diet, exercise, mindful eating, plus packaging that fits into lifestyle
Directly tap consumer demand via targeted digital engagement and influencer focus1 Patients drive
demand of
2 Strong base of physicians ready to
prescribe via telehealth
3 Member-centric customer experience
Gelesis pipeline and upcoming milestones:
*Products are investigational and have not been cleared by the FDA for use in the United States.; **Contingent on FDA review of the research plan.
Product candidate Indication Discovery/Preclinical Phase 1 Phase 2 Phase 3 FDA
ClearanceUpcoming Milestone
Plenity®
(GELESIS100) Weight management in overweight and obese patients
Broad US launch 2021
GS100* Weight management in adolescent overweight and obese patients
Phase 2 study initiation2021**
GELESIS200* Weight management and glycemic control in patients with T2D and pre-diabetes
Phase 2 study topline data 2021
GS300* NAFLD / NASHPhase 2 study
initiation2020**
GS400* Mucositis / IBD
GS500* Chronic Constipation (CIC) Phase 3 study initiation 2020**
Cleared by FDAEuropean CE mark granted
Phase Completed
Phase In-progress
Mechanical properties regenerating gut barrier and other mechanisms have led to compelling preclinical and clinical data in additional indications (e.g., NASH/NAFLD, CIC, and IBD)
49
Follica: Growing new hair based on innovative findings in regenerative biology
50*PureTech Health has a right to royalty payments as a percentage of net sales from Follica. As of 31 December 2019, PureTech’s percentage ownership of Follica was approximately 78.3 percent on a diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.
• Proprietary in-office treatment combines targeted scalp micro-disruption device with a topical on-market drug to create and grow new hairs
Follica Platform
PRTC Ownership: 78.3%*
~90MTotal addressable
population of androgenetic alopecia (AGA) sufferers Key Highlights
• Follica is developing an in-office treatment to grow new hair in patients with AGA, a large, cash-pay, unaddressed multi-billion market
• Selected treatment regimen demonstrated 44% improvement of visible hair count over baseline
• Attractive physician practice economics consistent with in-office aesthetic procedures
• Strong IP and proprietary device create high barriers to entry and protect against off label use
• Significant future growth opportunities: female pattern hair loss, skin rejuvenation, and proprietary amplification compounds
Follica is developing a treatment for a condition unresolved today, unlocking a multi-billion market of unmet need
Planned initiation of Phase 3 program in 2020
Currently-approved treatments work with only the hair you already have, either transplanting existing hair, or reviving shrunken hair folliclesFollica is the first company to grow new hair
Broad range of individuals with hair loss (e.g., age, severity, income levels) have significant interest in a more effective option
Even in the absence of effective treatment options, the AGA market today is $1B+ in the US and $3.5B globally
Sample patient outcome from FOL-004 data
Note: Results depicted in the images are above the average demonstrated in the optimization trial.
• Follica is developing an approximately five-minute in-officeexperimental procedure associated with limited downtime
• Follica’s approach is comprised of a proprietary device designed to stimulate hair follicle growth, followed by treatment with a pharmaceutical compound to thicken and maintain newly created hair follicles
• Follica’s selected treatment regimen demonstrated a statistically significant 44% improvement of visible (non-vellus) hair count after three months of treatment compared to baseline (p < 0.001, n=19)
• A prespecified analysis comparing the 44% change in non-vellus hair count to a 12% historical benchmark with approved pharmaceutical products was statistically significant (p = 0.005)
• Blinded head-to-head bench testing of the proprietary Follicadevice has shown advantages in scalp treatment versus commercially available skin disruption devices
• Initiation of Phase 3 registration program is anticipated in 2020
51
Day 85Screening
Akili: First game-based digital therapeutic cleared by the FDA for ADHD
52*As of 31 December 2019, PureTech’s percentage ownership of Akili was approximately 34.4 percent on a diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant toequity incentive plans.
EndeavorRxTM (AKL-T01), AKL-T02, AKL-T03, AKL-T04
~6.4MPediatric ADHD patients in the US
FDA cleared for pediatric patients age 8 to 12 years old with primarily inattentive or combined-type ADHD who have a demonstrated attention issue
Key Highlights• First game-based digital therapeutic cleared by the FDA for ADHD or any type of
condition. Providing a non-drug approach to target cognitive challenges
• Granted CE Mark to market EndeavorRx in European Economic Area member countries
• Novel mode of activating neural systems in the brain
• EndeavorRx (AKL-T01) met primary endpoint in double-blind, placebo-controlled pivotal study for pediatric ADHD (with active comparator game), and recently showed statistically significant improvement in ADHD Impairment Rating Scale (IRS), when used alone and as adjunct to stimulants
• AKL-T03 achieved primary endpoint, improving cognitive impairments in major depressive disorder trial
• Commercial and development partnership with Shionogi in Japan and Taiwan
• Potential to target cognitive impairments in other indications: ASD, MDD, MS, MCI, and TBI
• Personalized digital therapeutics engineered to directly improve cognitive and attention impairments
• Delivered through immersive action video game experience
PRTC Ownership: 34.4%*
The treatment of many neuropsychiatric disorders is only partially served, or not served at all, by currently available medications or by in-person behavioral therapy
Achieved primary endpoint in pivotal study for pediatric ADHD
531Kollins, et. al., The Lancet Digital Health. 2020 Apr. 2: e168–78. SE: Standard Error
• Achieved primary endpoint in randomized, controlled pivotal study for AKL-T01 in pediatric ADHD in Q4 2017
• AKL-T01 showed statistically significant change in the Attention Performance Index on T.O.V.A.®, an FDA-cleared objective measure of sustained attention and inhibitory control, compared to active control (p=0.006)
• Improvements in behavioral symptoms and functional impairments, though not separated from control
• No serious adverse events or discontinuations
Tests of Variables of Attention (T.O.V.A.), FDA-cleared ADHD treatment monitor
The Lancet Digital Health, 20201
Akili pipeline
1 Davis et al., PLoSONE. 2018, 13(1):e0189749. Kollins et al., JAACAP. 2018 Oct. V57(10) S172. NCT02828644. No data published yet. NCT03649074. On-going. NCT03844269. On-going.; 2 Yerys et al. Journal of Autism and Developmental Disorders. 2018 Dec. 3 Anguera et. al. Depression and Anxiety. Jan. 2017
Phase Completed
Phase In-progress
Product candidate Indication Discovery/Preclinical
Phase 1 (Feasibility)
Phase 2 (POC)
Phase 3(Pivotal)
FDA Clearance
Behavioral
EndeavorRxTM
(AKL-T01) Pediatric ADHD1
AKL-T02 Pediatric autism2
Mood & affective
AKL-T03 Major depressive disorder3
AKL-T04 Major depressive disorder
Immune AKL-T03 Multiple sclerosis
OtherAKL-T01 Parkinson’s / MCI
AKL-T01 Traumatic brain injury
Product candidate Indication In Development Clinical Trials Released
Health care solutions apps AKL-X01 ADHD caregiver app
Cleared by FDAEuropean CE Mark Granted
54
• Four clinical-stage programs in development• VE303, in development for high risk C. difficile,
demonstrated rapid, durable, dose-dependent colonization and accelerated gut microbiota restoration after antibiotics in a Phase 1a/1b study
• VE202, in development for IBD, demonstrated durable and dose-dependent colonization after antibiotics in two Phase 1 studies
• VE800 being evaluated with OPDIVO® (nivolumab) in advanced or metastatic cancers
• Strong IP portfolio
• Defined consortia to shift microbiota, stimulate immune responses, and provide colonization resistance against infectious pathogens
Vedanta: Developing a new class of drugs to modulate the human microbiome
55*As of 31 December 2019, PureTech’s percentage ownership of Vedanta Biosciences was approximately 53.3 percent on a diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.
Clinical data readout for VE303 expected in 2020
Key Highlights
VE303, VE202, VE416, VE800CDI is typically treated using antibiotics which damage the microbiome, leaving patients vulnerable to re-infection
IBD interventions are limited by toxicities and systemic immune suppression
Treatment centers around allergen avoidance and desensitization therapies in development, which may not prove cost-effective
Checkpoint inhibitors are only effective in 20 – 30% of patients
100 – 120Khigh-risk CDI cases per year
in the US
~3MIBD patients in the US
~2.5MLiving with peanut allergy in the US
>66K/yearMetastatic and/or
advanced MSS CRC, gastric, and melanoma
patients in the US
PRTC Ownership: 53.3%*
Vedanta pipeline and upcoming milestones
Phase Completed
Phase In-progress
Product candidate Indication Discovery/Preclinical Phase 1 Phase 2 Phase 3 Upcoming
Milestone
VE303 High-risk C. difficile (CDI) Phase 2 data readout 2020
VE416 Food allergy Phase 1/2 data readout 2021
VE202 Inflammatory bowel disease Phase 2 initiation 2021
VE800 Cancer immuno-therapy indication Phase 1 datareadout 2021
56
Vor: Selectively protecting healthy cells from targeted cancer therapies
57*As of June 30, 2020, PureTech’s percentage ownership of Vor was approximately 11.8 percent on a diluted basis. Ownership is based on the assumption that all future tranches of their most recent financing rounds are funded.
Key Highlights• Ex vivo and mouse proof-of-concept studies led
by Siddhartha Mukherjee, MD, PhD, published in PNAS
• Designed to optimize targeted therapies including ADCs, T cell engager / bispecific antibodies, and CAR-T cells
• Approach may lead to lower on-target toxicity, enable earlier therapy, and enable chronic dosing of targeted therapies
• Platform broadly applicable to other targets across and beyond heme malignancies
• Engineered hematopoietic stem cells (eHSCs) deleting redundant epitopes, protecting healthy cells from targeted therapies
eHSC Platform~60KAcute myeloid leukemia patients in the US
The prognosis for relapsed and refractory blood-borne malignancies is very poor
Only 30% of AML patients relapsing following stem cell transplants survive beyond one year
Targeted therapies have shown excellent outcomes, but frequently target both cancer and normal cells, causing substantial toxicities and limiting their potential
PRTC Ownership: 11.8%*
Initiation of Phase 1 study in acute myeloid leukemia in 2021
Alivio: Locally-acting therapeutic for devastating GI disease
58*As of December 31, 2019, PureTech’s percentage ownership of Alivio was approximately 78.6 percent on a diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.
IND filing expected for ALV-306 in 2021
Key Highlights• Alivio’s platform has been validated in multiple
preclinical models and indications• Technology could be applied to diseases, such
as IBD, pouchitis, inflammatory arthritis, organ transplantations, and IC/BPS
• Proprietary platform that can use small molecules and biologics, with potential for partnership targeting non-GI indications
• Ongoing partnership with Imbrium to advance ALV-107
• Novel technology designed to selectively bind to inflamed tissues and allow for targeted treatment of inflammatory disorders
ALV-306, ALV-304, ALV-107
Current drugs for GI autoimmune conditions focus on symptomatic relief and act systemically, causing toxicity
Pouchitis is a debilitating inflammation of the ileal pouch
Distal colitis represents a subtype of ulcerative colitis for which refractory disease is difficult to manage
~225KIndividuals in the US have
distal colitis
70 – 135KIndividuals in the US have
pouchitis
PRTC Ownership: 78.6%*
Sonde: Voice-based technology with the potential to transform how we monitor health
59*As of December 31, 2019, PureTech’s percentage ownership of Sonde was approximately 45.9 percent on a diluted basis. This calculation assumes all future closings of the Series A financing and includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.
Sonde
Key Highlights• Launched Sonde One, a voice-enabled health detection and
monitoring app, to potentially help employers reopen offices in COVID-19 environment
• Technology has demonstrated the potential to screen and monitor for disease in individuals from brief samples of speech
• Ongoing collaborations with multiple US and ex-US hospitals, clinics, and academic medical centers
• Collected 300,000 voice samples from over 50,000 subjects as part of ongoing validation of platform
• Expanded development of its proprietary technology in neurodegenerative disease, respiratory and cardiovascular disease, and other health and wellness conditions
• Developing proprietary technology to enable effective disease screening and management solutions based on an analysis of seconds of voice capture through consumer devices
PRTC Ownership: 45.9%*
~17MIndividuals in the US are affected by depression
The lag between onset of disease and accurate diagnosis and beginning of treatment can be measured in years for many high-burden health conditions
Topline results from a depression detection study expected in 2020
Product Candidate Details (1 of 3)
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* PureTech is not responsible for development of all of these product candidates and FDA-cleared product. Our Non-Controlled Founded Entities and certain of our Controlled Founded Entities, Follica and Vedanta, have independent development teams and PureTech does not control the day-to-day development of their respective product candidates. However, with respect to these Controlled Founded Entities, we exert control through majority stock ownership, board representation, and voting decisions. ** As of 31 December 2019, Controlled Founded Entities include Alivio Therapeutics, Inc., Follica, Incorporated, Entrega, Inc., Vedanta Biosciences, Inc. and Sonde Health, Inc., and Non-Controlled Founded Entities include Akili Interactive Labs, Inc., Gelesis, Inc., Karuna Therapeutics, Inc., Vor Biopharma Inc. and, for all periods prior to December 18, 2019, resTORbio, Inc. Relevant ownership interests for Founded Entities were calculated on a diluted basis (as opposed to a voting basis) as of December 31, 2019 (with the exception of Gelesis ownership which is as of April 1, 2020), including outstanding shares, options and warrants, but excluding unallocated shares authorized to be issued pursuant to equity incentive plans. Ownership of Vor (calculated as of June 30, 2020) and Sonde is based on the assumption that all future tranches of their most recent financing rounds are funded. Karuna ownership is calculated on an outstanding voting share basis as of May 26, 2020. R PureTech Health has a right to royalty payments as a percentage of net sales.
Product Candidate*
PureTech Ownership**
Indication(US Patient Population)
Potential Key Differentiation Results & Milestones Expected milestones
LYT-100 100% (Internal) Lymphatic flow disorders, incl. Lymphedema (~1M),COVID-19 post-recovery respiratory complicationsOther fibrotic and inflammatory disorders
Product candidate for the potential treatment of a range of conditions involving fibrosis, inflammation and impaired lymphatic flow. Pre-clinical anti-fibrotic and anti-inflammatory activity
• Acquired LYT-100 in July 2019 from Auspex Pharmaceuticals • Initiated LYT-100 multiple ascending dose study in March 2020• Presented preclinical data supporting LYT-200 and LYT-210 at AACR
2019• Presented additional preclinical data on LYT-200 and LYT-210 at SITC in
November 2019• Announced issuance of patent covering compositions of matter directed
to fully human anti-galectin-9 antibodies to support LYT-200 in 2019
• Initiation of LYT-100 human proof-of-concept study in people with breast cancer-related, upper limb secondary lymphedema in 2020, as well as additional studies in people with other fibrotic and inflammatory conditions
• Initiation of proof-of-concept study for serious respiratory complications following resolution of COVID-19 in Q3 2020
• Plans to file an IND application and initiate a Phase 1 study in solid tumors for LYT-200 in 2020
• Plans to continue to advance preclinical and biomarker studies for LYT-210 in 2020
LYT-200 Solid tumors, including colorectal (>50K/year), pancreatic (>28K/year), cholangiocarcinoma (>4K/year)
Capacity to concurrently modulate multiple immunosuppressive pathways and deliver significant single agent activity
LYT-210 Solid tumorsGI Autoimmunity
Focused on a therapeutic strategy which is distinct from other interventions using or targeting cytotoxic γδ T cells
ALV-306 78.6%(Alivio)
Pouchitis (70 – 135K), distal colitis (~225K),
Novel technology that selectively binds to inflamed tissues and allows for targeted treatment of chronic and acute inflammatory disorders
• Preclinical study of technology published in Nature Communications in April 2018, with two previous publications in Sci Transl Med
• Technology evaluated in 10 animal models; multiple therapies (small molecules and biologics) successfully incorporated
• $3.3M Department of Defense award• Announced partnership with Imbrium to advance ALV-107; Alivio will
receive up to $14.75M in upfront and near-term license exercise payments and is eligible to receive royalties on product sales and $260M+ in R&D milestones
• Expects to file IND for ALV-306 and initiate clinical trial in pouchitis and distal colitis in 2021
• Expects to file an IND for ALV-107 for IC/BPS in 2021 and an IND for ALV-304 in IBD in 2022
ALV-304 IBD (~3M)
ALV-107 IC/BPS (4 – 12M)
FOL-004 78.3%(Follica) R
AGA (~90M) Pioneering technology focused on the creation of new hair follicles via skin disruption and subsequent treatment to enhance effect
• Continued development to address androgenetic alopecia based on three clinical studies which showed hair follicle neogenesis following skin disruption
• Identified and tested next-generation, proprietary compounds• Announced topline results from a safety and efficacy optimization study of
lead candidate in December 2019• Positive feedback from End of Phase 2 meeting with the FDA for FOL-
004 to treat male AGA
• Initiation of Phase 3 registration study in male androgenetic alopecia is expected in 2020
FOL-005 Skin rejuvenation
Product Candidate Details (2 of 3)
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* PureTech is not responsible for development of all of these product candidates and FDA-cleared product. Our Non-Controlled Founded Entities and certain of our Controlled Founded Entities, Follica and Vedanta, have independent development teams and PureTech does not control the day-to-day development of their respective product candidates. However, with respect to these Controlled Founded Entities, we exert control through majority stock ownership, board representation, and voting decisions. ** As of 31 December 2019, Controlled Founded Entities include Alivio Therapeutics, Inc., Follica, Incorporated, Entrega, Inc., Vedanta Biosciences, Inc. and Sonde Health, Inc., and Non-Controlled Founded Entities include Akili Interactive Labs, Inc., Gelesis, Inc., Karuna Therapeutics, Inc., Vor Biopharma Inc. and, for all periods prior to December 18, 2019, resTORbio, Inc. Relevant ownership interests for Founded Entities were calculated on a diluted basis (as opposed to a voting basis) as of December 31, 2019 (with the exception of Gelesis ownership which is as of April 1, 2020), including outstanding shares, options and warrants, but excluding unallocated shares authorized to be issued pursuant to equity incentive plans. Ownership of Vor (calculated as of June 30, 2020) and Sonde is based on the assumption that all future tranches of their most recent financing rounds are funded. Karuna ownership is calculated on an outstanding voting share basis as of May 26, 2020. R PureTech Health has a right to royalty payments as a percentage of net sales.
Product Candidate*
PureTech Ownership**
Indication(US Patient Population)
Potential Key Differentiation Results & Milestones Expected milestones
VE303 53.3% (Vedanta)
High-risk CDI (100 – 120K per year) Developing a new category for immune-mediated diseases based on a rationally-defined consortia of human microbiome-derived bacteria
• Announced successful Phase 1a/1b for VE303 showing VE303 was well tolerated and demonstrated proof of mechanism in healthy volunteers in Q4 2018
• Announced initiation of Phase 2 trial for VE303 in Q4 2018• Raised $71.1M in total Series C financing round• Announced PK/PD results from VE202 Phase 1 healthy subject trials in
Q2 2020• Announced initiation of Ph1/2 trial for VE416 in July 2019• Announced an IO collaboration with BMS to evaluate OPDIVO®
(nivolumab) and VE800 in advanced or metastatic cancers in Q4 2018• Announced initiation of first in patient trial for VE800 in Q4 2019
• Topline results for VE303 Phase 2 expected in 2020
• Topline data from the Phase 1/2 clinical trial of VE416 are expected in 2021
• Topline results from first-in-patient clinical trial of VE800 anticipated in 2021
• Initiate a VE202 Phase 2 study in IBD in 2021
VE202 IBD (~3M)
VE416 Peanut allergy (~2.5M)
VE800 Solid tumors including MSS CRC (>46K/year), gastric (>11K/year), and melanoma (>9K/year)
Sonde 45.9%(Sonde)
Depression detection (~17M) Developing a voice-based technology platform to measure health when a person speaks that is designed to sense and analyze subtle changes in the voice to create a range of persistent brain, muscle, and respiratory health measurements that provide a more complete picture of health in seconds
• Launched Sonde One to potentially help employers reopen offices in COVID-19 environment in July 2020
• Demonstrated accuracy for measuring depression from brief samples of speech
• Expanded development of proprietary technology in neurodegenerative disease, respiratory and cardiovascular disease, and other health and wellness conditions
• Collected 300,000 voice samples from over 50,000 subjects as part of ongoing validation of platform
• Completed $16M financing in Q2 2019
• Topline results from a depression detection study expected in 2020
• Expects to launch its API platform, which will allow the world to license and build products with Sonde’s voice biomarker based health detection technology, in 2020
EndeavorRXTM
(AKL-T01)34.4%(Akili)
Pediatric ADHD (~6.4M) Pioneering the development of treatments designed to have direct therapeutic activity, delivered through a high-quality action video game experience
• EndeavorRxTM (AKL-T01) granted FDA clearance as a prescription treatment for children with attention-deficit/hyperactivity disorder (ADHD)
• CE Mark approval to market EndeavorRx in European Economic Area member countries
• Announced study achieved its primary endpoint evaluating the effects of lead product candidate AKL-T01 in children with ADHD when used with and without stimulant medication in January 2020
• Announced achievement of primary endpoint in randomized, controlled pivotal study in pediatric ADHD in Q4 2017
• Announced achievement of primary endpoint in randomized, controlled study of AKL-T03 in major depressive disorder in December 2019
• Completed $68M financing round in Q2 2018• FDA filing for AKL-T01 in pediatric ADHD in Q2 2018• Announced partnership with Shionogi in March 2019
• EndeavorRx will be released as the centerpiece of the Endeavor Care Program, which includes the EndeavorRxtreatment and Akili CareTM
• The EndeavorRx treatment will be available with a prescription to families soon
AKL-T02 Pediatric autism (~1.5M)
AKL-T03 MDD (~17M), MS (~900K)
AKL-T04 MDD (~17M)
Product Candidate Details (3 of 3)
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* PureTech is not responsible for development of all of these product candidates and FDA-cleared product. Our Non-Controlled Founded Entities and certain of our Controlled Founded Entities, Follica and Vedanta, have independent development teams and PureTech does not control the day-to-day development of their respective product candidates. However, with respect to these Controlled Founded Entities, we exert control through majority stock ownership, board representation, and voting decisions. ** As of 31 December 2019, Controlled Founded Entities include Alivio Therapeutics, Inc., Follica, Incorporated, Entrega, Inc., Vedanta Biosciences, Inc. and Sonde Health, Inc., and Non-Controlled Founded Entities include Akili Interactive Labs, Inc., Gelesis, Inc., Karuna Therapeutics, Inc., Vor Biopharma Inc. and, for all periods prior to December 18, 2019, resTORbio, Inc. Relevant ownership interests for Founded Entities were calculated on a diluted basis (as opposed to a voting basis) as of December 31, 2019 (with the exception of Gelesis ownership which is as of April 1, 2020), including outstanding shares, options and warrants, but excluding unallocated shares authorized to be issued pursuant to equity incentive plans. Ownership of Vor (calculated as of June 30, 2020) and Sonde is based on the assumption that all future tranches of their most recent financing rounds are funded. Karuna ownership is calculated on an outstanding voting share basis as of May 26, 2020.; R PureTech Health has a right to royalty payments as a percentage of net sales.; †Products are investigational and have not been cleared by the FDA for use in the United States.; 1Following the completion of a successful End-of-Phase 2 meeting with the U.S. FDA, Karuna remains on track to initiate the Phase 3 program by the end of 2020.
Product Candidate*
PureTech Ownership**
Indication(US Patient Population)
Potential Key Differentiation Results & Milestones Expected milestones
Plenity®
(GS100)22.0%(Gelesis) R
Overweight and obesity (~150M) Only prescription weight management product to be FDA-cleared for use by overweight adults with a BMI as low as 25 kg/m2, with and without comorbidities such as hypertension, type 2 diabetes, or dyslipidemia
• Plenity® received FDA clearance as an aid for weight management in adults with a Body Mass Index (BMI) of 25-40 kg/m2, when used in conjunction with diet and exercise
• CE mark approval to market Plenity throughout the European Economic Area
• Announced partnership with Ro to support US commercialization of Plenity
• Announced partnership with China Medical System Holdings Ltd. for the commercialization of Plenity in China
• Presented data from first-in-human, randomized, double-blind, placebo-controlled study of Gelesis200 in Q2 2016
• Initiated proof-of-concept study of Gelesis200, optimized for patients with prediabetes and type 2 diabetes, in Q1 2017
• Initiated a Plenity early experience program in the United States in the second half of 2019
• Plans to bring Plenity to the US first, where it is now available to a limited extent while the company ramps up its commercial operations and inventory for a broad launch in 2021
• Expect to initiate a Phase 2 study for NASH/NAFLD in 2020
• Results are anticipated from the Gelesis200 LIGHT-UP study for weight loss and glycemic control in people with prediabetes or type 2 diabetes in 2021
• Plans to initiate a Phase 2 study of GS100 for weight management in adolescents with overweight and obesity in 2021
• Initiation of Phase 3 study of GS500 for chronic idiopathic constipation in 2020
GS100† Adolescent overweight and obesity Developing oral therapeutics based on a novel, superabsorbent hydrogel technology platform to treat excess weight and other chronic diseases related to the gastrointestinal (GI) pathway
Gelesis200† Weight management in T2D (~80M) and prediabetes (~34M)
GS500† CIC (~35M)
GS300† NASH/NAFLD (80 – 100M)
GS400† IBD (~3M)
KarXT 18.1%(Karuna) R
Schizophrenia (~2.7M), Dementia related psychosis (~1.2M), pain
Designed to preferentially simulate M1/M4 muscarinic receptors in the brain without stimulating muscarinic receptors in peripheral tissues to significantly improve tolerability
• Announced its Phase 2 study of KarXT for schizophrenia met the primary endpoint with a statistically significant (P<0.0001) and clinically meaningful 11.6 point improvement on the PANSS total score from baseline vs. placebo in Q4 2019
• Completed $42M and $82M financings in Q3 2018 and H1 2019• IPO on Nasdaq in June 2019 (Nasdaq: KRTX), raising $103M• Completed a follow-on offering of 2,600,000 shares of common stock,
with gross proceeds of approximately $250M
• Phase 3 initiation by end of 20201
• Topline Phase 1b pain data in healthy volunteers mid-2020
• Topline Phase 1b data in healthy elderly volunteers by YE 2020
VOR33 11.8%(Vor)
AML (~60K) Novel approach for targeting cancer selectivity be addressing the detrimental effects of on-target toxicity to healthy tissue by developing engineered hematopoietic stem cells (eHSCs) for the treatment of hematological cancers
• In May 2019, preclinical research was published in the scientific journal Proceedings of the National Academy of Sciences supporting novel approach to treating cancer via eHSCs
• In January 2020, held a pre-IND meeting with the FDA• Obtained ex vivo proof-of-concept data for technology• Granted foundational intellectual property which covers therapeutic
approach
• Initiation of Phase 1 study in acute myeloid leukemia in 2021