PureTech Health plc – Half-Year Report

Strong progression of PureTech’s Wholly Owned Pipeline, with three clinical-stage therapeutic candidates being evaluated across four clinical trials to address large patient needs in pulmonary, oncology and CNS indications, and a growing pipeline of four additional preclinical CNS programs

Advancements across Founded Entities, including Karuna’s third positive registrational trial for KarXT and planned filing for FDA approval, Akili’s commercial release of EndeavorOTC^TM for adults with ADHD, Gelesis’ application to make Plenity® available without a prescription, additional positive results from Vor’s Phase 1/2a leukemia trial and Vedanta’s $106.5 million financing

PureTech plans to pursue a more robust capital return strategy enabled by cash generated via the Founded Entities segment, while potentially advancing certain Wholly Owned Programs through one or more new Founded Entities, asset sales and/or partnerships

Well-capitalized with Consolidated Cash and cash equivalents of $350.5 million¹ as of June 30, 2023, and operational runway into Q1 2026; PureTech’s Founded Entities collectively raised over $575 million during the six months ended June 30, 2023, and $3.8 billion since July 2018

Company to host a webcast and conference call today at 9:00am EDT / 2:00pm BST

BOSTON–(BUSINESS WIRE)–PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) (“PureTech” or the “Company”) today announces its half-yearly results for the six months ended June 30, 2023. The following information will be filed on Form 6-K with the United States Securities and Exchange Commission (the “SEC”) and is also available at https://investors.puretechhealth.com/financials-filings/reports.

Commenting on PureTech’s half-yearly results, Daphne Zohar, Founder and Chief Executive Officer of PureTech, said:

“The first half of 2023 has been a strong period across both our Founded Entities and Wholly Owned Pipeline. We have achieved important clinical and financial milestones, while executing on our mission of giving life to new classes of medicine to change the lives of patients with devastating diseases. Our R&D engine has produced 27 new therapeutics and therapeutic candidates, with two taken from inception at PureTech to U.S. Food and Drug Administration (FDA) and European regulatory clearances and a third that is expected to be filed soon for FDA approval. We are proud that our track record of clinical success is six times greater than the industry average.²

“The maturation of our Wholly Owned Programs now gives us several pathways to realize their value as we determine the ideal path for each program’s advancement – this may be through internal development, the creation of new Founded Entities, asset sales, and/or partnering and royalty transactions – and we will be guided by the optimal route to generate value for our shareholders. We are proud that for nearly six years, including during a time that was extremely challenging to the biotech sector at large, we not only created important new medicines, but we also generated almost $800 million in cash without approaching the capital markets or diluting our shareholders. This has allowed us to focus on what we do best: recognize value in potential new medicines before anyone else sees it and unlock that value through focused experiments, relentlessly prioritizing and advancing programs with the highest probability of success.

“Our unique model and disciplined execution have provided a safe harbor through the stormy market challenges, and while we can navigate in any environment, we are also very well-positioned to benefit if the tides potentially turn in favor of the biotech sector.

“I am tremendously proud of the achievements across our Founded Entities and Wholly Owned Pipeline, and I am grateful to our skilled and dedicated team who continue to shepherd this important work forward. I look forward to another exciting period ahead and to sharing more about our progress in the coming months.”

Webcast and conference call details

Members of the PureTech management team will host a conference call at 9:00am EDT / 2:00pm BST today, August 29, 2023, to discuss these results. A live webcast and presentation slides will be available on the investors section of PureTech’s website under the Events and Presentations tab. To join by phone, please dial:

United Kingdom (Local): +44 20 4587 0498

United Kingdom (Toll-Free): +44 800 358 1035

USA (Local): +1 646 787 9445

USA (Toll-Free): +1 855 979 6654

Access Code: 957610

For those unable to listen to the call live, a replay will be available on the PureTech website.

Key Wholly Owned & Founded Entity Programs

Wholly Owned Candidates		Ownership		Indication
LYT-100 (deupirfenidone)		100%		Conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis
LYT-200 (anti-galectin-9 mAb)		100%		Metastatic/locally advanced solid tumors, including urothelial and head and neck cancers, and hematological malignancies, such as acute myeloid leukemia
LYT-300 (oral allopregnanolone)		100%		A range of neurological and neuropsychological conditions, including anxiety, mood disorders and Fragile X-associated Tremor/Ataxia Syndrome
LYT-310 (oral cannabidiol)		100%		Epilepsies and other neurological conditions
Founded Entities		Ownership3		Overview
Karuna		2.8% Equity plus milestone payments, 20% sublicense revenue, royalties, and up to $500M from agreement with Royalty Pharma4		Advancing transformative medicines for people living with psychiatric and neurological conditions
Akili		14.6% Equity		Pioneering the development of cognitive treatments through game-changing technologies
Gelesis		22.8% Equity plus Royalties5		Advancing a novel category of treatments for weight management and gut related chronic diseases
Vedanta		41.0% Equity6		Pioneering a new category of oral therapies based on defined bacterial consortia
Vor Bio		4.0% Equity		Engineering hematopoietic stem cells to enable targeted therapies for patients with blood cancers
Sonde		35.2% Equity		A voice-based artificial intelligence platform to detect changes in health
Entrega		73.8% Equity		Engineering hydrogels to enable the oral administration of peptide therapeutics (e.g., GLP-1 agonists)

Operational Highlights

Accelerated development of our Wholly Owned Programs⁷ driven by significant clinical and strategic progress

• Progressed Phase 2b dose-ranging trial of LYT-100 (deupirfenidone) in patients with idiopathic pulmonary fibrosis (IPF).
• Announced plans to advance LYT-300 (oral allopregnanolone) for the potential treatment of anxiety and depression, and initiated a Phase 2a proof-of-concept trial using a validated clinical model of anxiety in healthy volunteers.
• Awarded up to $11.4 million from the U.S. Department of Defense to advance LYT-300 for Fragile X-associated Tremor/ Ataxia Syndrome (FXTAS).
• Initiated a Phase 1b trial of LYT-200 (anti-galectin-9 mAb) in combination with tislelizumab in urothelial and head and neck cancers and progressed the ongoing Phase 1b trial evaluating LYT-200 as a single agent for the treatment of acute myeloid leukemia (AML).
• Created and advanced multiple preclinical programs for central nervous system (CNS) indications produced from our Glyph^TM technology platform.

Commercial and clinical momentum across Founded Entities⁸ demonstrates success of our R&D model

• PureTech and Royalty Pharma entered into a KarXT Royalty Agreement for consideration of up to $500 million with $100 million in cash up front and up to $400 million in additional payments contingent on the achievement of certain regulatory and commercial milestones.
• Karuna Therapeutics (Nasdaq: KRTX) (Karuna) announced that the company remains on track to file KarXT for FDA approval in schizophrenia in the third quarter of 2023, with a launch in the second half of 2024, if approved.
• Akili, Inc. (Nasdaq: AKLI) (Akili) shared positive topline results from the STARS-ADHD-Adult clinical trial evaluating the efficacy and safety of EndeavorRx®⁹ in adults with attention-deficit/hyperactivity disorder (ADHD). Akili subsequently released EndeavorOTC,¹⁰ a video game treatment to improve attention in adults 18 years and older with ADHD, available without a prescription. Akili also submitted data from the STARS-ADHD-Adolescents trial to the FDA to expand its current EndeavorRx label to include adolescents aged 13-17.
• Gelesis Holdings, Inc. (Gelesis) has helped over 200,000 people with their weight loss journeys and generated more than $40 million in revenue since launch. Gelesis and PureTech have entered into an Agreement and Plan of Merger, subject to agreed upon terms and conditions.
• Vor Biopharma Inc. (Nasdaq: VOR) (Vor Bio) announced successful primary engraftment of trem-cel (VOR33) in five AML patients. Vor also announced the FDA has cleared its Investigational New Drug application for a Phase 1/2 clinical trial of VCAR33^ALLO.
• Vedanta Biosciences (Vedanta) received Fast Track designation for VE303, its Phase 3 ready therapeutic candidate designed for the prevention of recurrent Clostridioides difficile infection (rCDI). Vedanta also raised $106.5 million to advance its pipeline.

Financial Highlights:

• Consolidated Cash and cash equivalents as of June 30, 2023, were 350.5 million¹ (December 31, 2022: Consolidated Cash, cash equivalents and Short-term investments of $350.1 million¹) and PureTech Level Cash and cash equivalents as of June 30, 2023, were $348.5 million^11,12 (December 31, 2022: PureTech Level Cash, cash equivalents and Short-term investments of $339.5 million¹¹)
• Operating expenses for the six months ended June 30, 2023, were $79.3 million (June 30, 2022: $108.2 million).

Key Upcoming Milestones (next 12 to 24 months)

Several significant milestones are anticipated over the next 12 to 24 months from both PureTech and our Founded Entities:

Wholly Owned Pipeline

• We expect topline results from the Phase 2b dose-ranging trial of LYT-100 in patients with IPF in 2024. We plan to pursue a streamlined development program for LYT-100 in IPF and are using the same endpoints that have supported past approvals. Pending positive clinical and regulatory feedback, we intend to advance the program into a Phase 3 trial. We believe the results of the Phase 2b trial, together with a Phase 3 trial, could serve as the basis for registration in the U.S. and other geographies.
• We expect results from the Phase 2a proof-of-concept trial of LYT-300 using a validated clinical model of anxiety in healthy volunteers by the end of 2023.
• We expect to initiate a Phase 1 trial of LYT-310 (oral cannabidiol) in Q4 2023.
• We expect initial results from a subset of patients from the Phase 1b trial of LYT-200 as a single agent for the treatment of AML by the end of 2023.
• Planning is underway for a Phase 2 trial of LYT-300 in FXTAS in collaboration with the University of California, Davis.

Founded Entities

• Karuna plans to file KarXT for FDA approval in schizophrenia in the third quarter of 2023, with a launch in the second half of 2024, if approved. Karuna also expects to initiate its second Phase 3 trial in psychosis in Alzheimer’s disease, ADEPT-2, in the second half of 2023.
• Akili expects to submit data to the FDA to pursue marketing authorization for EndeavorOTC to be made available without a prescription as a treatment for adults with ADHD in the second half of 2023. Akili also expects data in the second half of 2023 from Shionogi’s pivotal trial of SDT-001 in children aged 6-17 years old with ADHD in Japan.
• Gelesis filed an initial 510(k) application with the FDA to change the classification of Plenity¹³ from prescription-only to be available without a prescription. Gelesis anticipates the FDA’s decision on its 510(k) submission by the first quarter of 2024. PureTech has also entered into an Agreement and Plan of Merger to purchase all of the outstanding stock of Gelesis and take the company private. The closing of this transaction is contingent on, among other things, Gelesis receiving shareholder approval for the transaction and the satisfaction of various closing conditions.
• Vor Bio expects additional trem-cel engraftment and Mylotarg^TM hematologic protection data updates by year-end 2023.
• Vedanta plans to initiate a Phase 3 clinical trial of VE303 in patients at high risk for rCDI in Q4 2023 and expects topline data from the Phase 1/2 clinical trial of VE416, Vedanta’s therapeutic candidate for food allergy, in 2023, subject to investigator timelines.

About PureTech Health

PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech’s R&D engine has resulted in the development of 27 therapeutics and therapeutic candidates, including two (Plenity® and EndeavorRx®) that have received both U.S. FDA clearance and European marketing authorization and a third (KarXT) that is expected to be filed soon for FDA approval. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points.

For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh.

Cautionary Note Regarding Forward-Looking Statements

This press release contains statements that are or may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those related to our and our Founded Entities’ plans, future prospects, objectives, developments, strategies and expectations, the progress and timing of clinical trials and data readouts, the timing of potential Investigational New Drug (IND) and NDA submissions, the timing of regulatory approvals or clearances from the FDA, the sufficiency of cash and cash equivalents and expected cash runway, and the anticipated closing of the Gelesis transaction. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, the following: our history of incurring significant operating losses since our inception; our need for additional funding to achieve our business goals, which may not be available and which may force us to delay, limit or terminate certain of our therapeutic development efforts; our limited information about and limited control or influence over our Non-Controlled Founded Entities; the lengthy and expensive process of preclinical and clinical drug development, which has an uncertain outcome and potential for substantial delays; potential difficulties with enrolling patients in clinical trials, which could delay our clinical development activities; side effects, adverse events or other safety risks which could be associated with our therapeutic candidates and delay or halt their clinical development; our ability to obtain regulatory approval for and commercialize our therapeutic candidates; our ability to realize the benefits of our collaborations, licenses and other arrangements; our ability to maintain and protect our intellectual property rights; our reliance on third parties, including clinical research organizations, clinical investigators and manufacturers; our vulnerability to natural disasters, global economic factors, geo-political actions and unexpected events; and those risks, uncertainties and other important factors described under the caption “Risk Factors” in our Annual Report on Form 20-F for the year ended December 31, 2022 filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.

Interim Management Report

Introduction

PureTech was founded with a mission to change the lives of patients with devastating diseases. Our R&D engine has been tremendously successful in pursuit of this goal, having generated 27 therapeutics and therapeutic candidates to date, including two (Plenity® and EndeavorRx®) that have received U.S. Food and Drug Administration (FDA) clearance and European Marketing Authorization and a third, KarXT, that is expected to be filed soon for FDA approval. We attribute our track record of productivity and clinical success to our distinctive approach to drug development, which is underpinned by three key pillars. First, we identify an area with unmet patient need. We then identify therapeutic approaches that often have validated human efficacy but have not reached their full potential due to key limitations, such as the route of administration or side effects. Our second pillar involves applying our proprietary insights and technologies to overcome these limitations, thereby unlocking a new medicine’s benefit for patients. Our third pillar is centered on efficient de-risking, which we achieve in two ways – by building on well-defined clinical and regulatory paths and conducting “killer” experiments early on. We believe in disciplined R&D, and we quickly shut down programs that don’t reach our pre-specified thresholds for advancement. This allows us to pivot resources towards the programs with the greatest likelihood of advancement and has resulted in our success rate, which is about six times higher than the industry average.²

We are a well-capitalized organization with a unique business model that helps fuel our Wholly Owned Programs as well as maximize shareholder returns. Our Founded Entities, which are akin to partnered programs, provide a significant source of non-dilutive capital. To date, we have generated nearly $800 million from Founded Entity equity and royalty monetization events, and we have not had to raise funds at the PureTech level from the capital markets in almost six years. We’re exceedingly proud of this model and the advancements our Founded Entities have made across a range of conditions, providing value to patients and shareholders alike.

KarXT is an excellent example of how our Founded Entities are able to generate value for our shareholders, and it is a hallmark of our capital efficient approach. We allocated $18.5 million to the program, and our return on investment has been almost 50x.¹⁴ This figure does not account for the $100 million upfront we received in connection with our March 2023 announcement that Royalty Pharma acquired an interest in our 3% royalty on KarXT that provides Royalty Pharma the full amount of royalties due to us up to $2 billion in annual net sales of KarXT. Beyond that, we are entitled to up to $400 million in additional payments associated with regulatory and commercial milestones. Importantly, once KarXT achieves $2 billion in annual sales, we will retain 67% of the royalty payments, and Royalty Pharma will continue to receive 33%. We also continue to retain 2.8% equity ownership in Karuna as well as milestone payments, and we are eligible to receive 20% of sublicense income.

The same successful strategy and proven team that generated our Founded Entities have also produced our Wholly Owned Programs. We intend to evaluate the strong progress of our Wholly Owned Programs and determine the ideal path for each program’s advancement – this may be through internal development, the creation of new Founded Entities, asset sales, and/or partnering and royalty transactions – and we will be guided by the optimal route to generate value for our shareholders. Having the flexibility to advance programs to an inflection point before determining the most expedient and cost-effective path forward is a hallmark of our model, and it allows us to continue to nominate new candidates for advancement without compromising ongoing development efforts.

As we realize that value and as we share program development costs with partners, we expect to be in a position to evaluate returning additional capital to our shareholders, beyond the current $50 million stock buyback program. We have many options available to us, and we are committed to maximizing shareholder returns while we also make a difference for patients. We will be engaging with our shareholders in the coming weeks for feedback, and the Board will also consider factors including market conditions and PureTech’s ongoing cash requirements as we explore the exciting paths forward.

Notable Developments

Wholly Owned Programs

In the first half of 2023 we have continued to strengthen and grow our Wholly Owned Programs, which are based on a strategy of leveraging validated efficacy to rapidly advance therapeutics with proven profiles. This approach is designed to preserve the pharmacology of efficacious drugs while maximizing their unrealized potential to meet significant patient needs.

Our most advanced clinical-stage therapeutic candidate, LYT-100 (deupirfenidone), is currently in development for idiopathic pulmonary fibrosis (IPF), which is a rare, progressive and fatal lung disease with a median survival of 2-5 years.¹⁵ Pirfenidone is one of only two drugs approved to treat IPF, and it has been shown to improve survival by approximately three years compared to supportive care alone.¹⁵ However, tolerability issues with both of the standard of care drugs result in patients discontinuing treatment or reducing their dose. As a result, nearly three out of every four people with IPF forego treatment with these otherwise efficacious medicines.¹⁶ LYT-100 is a deuterated form of pirfenidone and is designed to retain the beneficial pharmacology and clinically-validated efficacy of pirfenidone with a highly differentiated pharmacokinetic profile that has translated into favorable tolerability in multiple clinical studies and has the potential to keep patients on treatment longer to enable more optimal disease management. LYT-100 has also demonstrated that it can be safely dosed with a higher total drug exposure than the currently approved dose of pirfenidone, which could translate into improved efficacy over pirfenidone. With this profile, we believe LYT-100 has the potential both to supplant the current standard of care treatments and to serve a larger market of patients who are unable to tolerate current therapies.

The first of two potentially registration-enabling studies for LYT-100 is underway, with topline results from the Phase 2b trial expected in 2024. This is a global trial designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 against placebo.

Contacts

PureTech

Public Relations

[email protected]
Investor Relations

[email protected]

EU media

Ben Atwell, Rob Winder

+44 (0) 20 3727 1000

[email protected]

U.S. media

Nichole Sarkis

+1 774 278 8273

[email protected]

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