[Executive Summary & Company Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Company%20Highlights) PureTech Health demonstrated a strong financial position and significant pipeline advancement in 2022, with its wholly-owned candidates progressing and Founded Entities achieving key clinical and commercial milestones [Key Financial and Operational Highlights](index=1&type=section&id=Key%20Financial%20and%20Operational%20Highlights) PureTech Health reported a strong capital base with **$339.5 million** in PureTech level cash and **$350.1 million** consolidated cash as of December 31, 2022, extending its operational runway into Q1 2026. The company rapidly advanced its wholly-owned pipeline, with four clinical-stage therapeutic candidates, and saw significant clinical, commercial, and financial momentum across its Founded Entities, which raised **$1.28 billion** in 2022 Cash, Cash Equivalents and Short-Term Investments (as of Dec 31, 2022) | Category | Amount (Millions USD) | | :----------------------------------- | :-------------------- | | PureTech Level Cash | $339.5 | | Consolidated Cash | $350.1 | - Operational runway extends into Q1 2026[4](index=4&type=chunk)[17](index=17&type=chunk) - Founded Entities raised **$1.28 billion** in 2022, almost entirely from third parties[4](index=4&type=chunk)[17](index=17&type=chunk) - Wholly Owned Pipeline includes four clinical-stage therapeutic candidates: **LYT-100** (registration-enabling trial in IPF), **LYT-300** (Phase 2 ready in anxiety and postpartum depression), **LYT-200** (two Phase 1b trials in solid tumors and hematological malignancies), and LYT-503 (Phase 1 partnered program)[3](index=3&type=chunk)[14](index=14&type=chunk) - Founded Entities achieved significant milestones, including **Karuna's KarXT** two positive Phase 3 trials for **KarXT** in schizophrenia, clinical data from Vor and **Vedanta**, and commercial progress with **EndeavorRx®** and **Plenity®**[4](index=4&type=chunk) [CEO and Chair's Strategic Outlook](index=1&type=section&id=CEO%20and%20Chair's%20Strategic%20Outlook) The CEO highlighted 2022 as an exceptional year, shaping PureTech's next development phase and advancing its mission to create new classes of medicines. The company boasts a highly productive track record in biopharma, with **27 therapeutics** and candidates developed, two FDA/EU cleared, and a third (**KarXT**) expected for FDA filing soon. The unique model has generated significant non-dilutive funding, avoiding capital market raises for over five years. The Chair emphasized PureTech's disciplined approach, capital efficiency, and clinical success rate, which is **six times the industry average**, positioning the company for continued growth and impact - PureTech has developed **27 therapeutics** and therapeutic candidates across its Wholly Owned Pipeline and Founded Entities[8](index=8&type=chunk)[43](index=43&type=chunk) - Two therapeutics (**EndeavorRx®** and **Plenity®**) have received FDA and EU regulatory clearances, and a third (**Karuna's KarXT**) is expected to be filed soon for FDA approval[8](index=8&type=chunk)[43](index=43&type=chunk) - The company has generated approximately **$215.4 million** in non-dilutive funding in the last 8 months from stock sales and an upfront payment from **Royalty Pharma** for **KarXT** royalties[9](index=9&type=chunk) - PureTech's clinical success rate is **six times the industry average**[11](index=11&type=chunk)[43](index=43&type=chunk) - Multiple important catalysts are anticipated over the next 12 months, with new candidates expected to progress towards the clinic[10](index=10&type=chunk)[11](index=11&type=chunk) [Business Overview & Strategy](index=2&type=section&id=Business%20Overview%20%26%20Strategy) PureTech's strategy focuses on developing new classes of medicines by enhancing existing therapies, leveraging innovative technologies, and employing a disciplined R&D process to advance a diverse pipeline [Company Mission and Innovation Strategy](index=7&type=section&id=Company%20Mission%20and%20Innovation%20Strategy) PureTech's mission is to develop new classes of medicines for devastating diseases, driven by a strategy focused on unlocking the potential of therapies with proven efficacy but historical limitations. This approach involves leveraging a network of collaborators, applying innovative technologies (like **Glyph™ platform**), and employing a disciplined R&D process with 'killer experiments' to rapidly advance promising candidates and discontinue less successful programs - PureTech's strategy is underpinned by three pillars: a network of collaborators, innovative technologies and approaches (e.g., **Glyph™ platform**), and 'killer experiments' for disciplined R&D[44](index=44&type=chunk) - The company focuses on enhancing on-target efficacy, improving tolerability, or enabling oral administration for medicines previously held back by these issues[14](index=14&type=chunk)[45](index=45&type=chunk) - PureTech discontinued the Orasome technology platform and Meningeal lymphatics platform due to lack of promising candidates[44](index=44&type=chunk) [Wholly Owned Pipeline Advancement](index=2&type=section&id=Wholly%20Owned%20Pipeline%20Advancement) PureTech's wholly-owned pipeline rapidly advanced in 2022, completing five clinical trials and generating compelling data. Key candidates like **LYT-100**, **LYT-300**, **LYT-200**, and **LYT-310** are progressing, with several important milestones anticipated in the next 12 months. The **Glyph™ technology platform**, validated by **LYT-300**, shows potential for improving oral bioavailability and tolerability of other compounds [LYT-100 (deupirfenidone)](index=3&type=section&id=LYT-100%20(deupirfenidone)) **LYT-100** is an investigational therapy for idiopathic pulmonary fibrosis, demonstrating improved gastrointestinal tolerability compared to pirfenidone, with a registration-enabling trial underway - **LYT-100** is in development for idiopathic pulmonary fibrosis (IPF), a condition where current treatments have significant tolerability issues[17](index=17&type=chunk)[51](index=51&type=chunk) - It has shown a **50% reduction** in gastrointestinal tolerability issues in a head-to-head study versus pirfenidone[17](index=17&type=chunk)[51](index=51&type=chunk) - A global, randomized, double-blind, placebo-controlled trial in IPF patients is ongoing, expected to be the first of two registration-enabling trials, with topline results anticipated in 2024[17](index=17&type=chunk)[51](index=51&type=chunk) [LYT-300 (oral allopregnanolone)](index=3&type=section&id=LYT-300%20(oral%20allopregnanolone)) **LYT-300**, utilizing **Glyph™ technology**, is being developed for anxiety and postpartum depression, showing significantly enhanced oral bioavailability and preparing for Phase 2 trials - **LYT-300** is being developed for anxiety disorders and postpartum depression (PPD), aiming for faster, better-tolerated, and orally administered treatments[17](index=17&type=chunk)[50](index=50&type=chunk) - A Phase 2a proof-of-concept trial for anxiety is expected to begin in H1 2023 with results by end of 2023; an open-label Phase 2a trial for PPD is expected in H2 2023[17](index=17&type=chunk) - Achieved **ninefold greater** oral bioavailability in humans compared to published data for orally administered allopregnanolone, leveraging the **Glyph™ technology**[50](index=50&type=chunk) [LYT-200 (anti-galectin-9 mAb)](index=3&type=section&id=LYT-200%20(anti-galectin-9%20mAb)) **LYT-200** is an anti-galectin-9 monoclonal antibody in Phase 1b trials for metastatic solid tumors and hematological malignancies, with initial results expected in 2023 and 2024 - **LYT-200** is in development for metastatic solid tumors and hematological malignancies like acute myeloid leukemia (AML)[17](index=17&type=chunk) - A Phase 1b trial in AML was initiated in 2022, with initial results from a subset of patients expected by end of 2023[17](index=17&type=chunk)[48](index=48&type=chunk) - A Phase 1b trial of **LYT-200** in combination with an anti-PD-1 antibody (tislelizumab) for urothelial or head and neck cancer was initiated post-period, with topline results expected in 2024[17](index=17&type=chunk) [LYT-310 (oral cannabidiol [CBD])](index=3&type=section&id=LYT-310%20(oral%20cannabidiol%20%5BCBD%5D)) **LYT-310** aims to improve the safety and oral administration of cannabidiol for epilepsies and neurological disorders, with clinical entry anticipated in Q4 2023 - **LYT-310** aims to expand CBD's therapeutic application across epilepsies and neurological disorders through patient-friendly oral administration[17](index=17&type=chunk) - Designed to improve safety, reduce GI and liver exposure, and allow for scalable, consistent, cost-effective production[17](index=17&type=chunk) - Expected to enter the clinic in Q4 2023[17](index=17&type=chunk) - PureTech completed five clinical studies in 2022, including compelling safety and tolerability data for **LYT-100** and proof-of-principle, oral bioavailability, and tolerability for **LYT-300**[48](index=48&type=chunk) - The **Glyph™ technology platform** received its first clinical validation with **LYT-300**, demonstrating potential for compounds with challenging oral bioavailability, safety, and tolerability profiles[49](index=49&type=chunk) - Multiple important catalysts are anticipated over the next 12 months to guide pipeline prioritization, including potential commercial launches, partnerships, sales, or spinouts[52](index=52&type=chunk) [Founded Entities Progress and Contributions](index=9&type=section&id=Founded%20Entities%20Progress%20and%20Contributions) PureTech's Founded Entities continued to achieve significant milestones, generating non-dilutive funding and advancing their respective programs. **Karuna Therapeutics** is preparing for FDA submission of **KarXT** for schizophrenia after strong Phase 3 data, and its value increased **over 60%** in 2022. **Gelesis** and **Akili** made commercial progress with their FDA-cleared products, **Plenity** and **EndeavorRx**, respectively, with **Gelesis's** sales increasing **129% YoY**. Vor Bio delivered initial positive data for trem-cell in AML - PureTech generated approximately **$115.4 million** from the sale of **Karuna** stock in August 2022[17](index=17&type=chunk)[54](index=54&type=chunk) - **Royalty Pharma** acquired an interest in PureTech's royalty in **Karuna's KarXT** for up to **$500 million** (**$100 million** upfront cash, up to **$400 million** contingent on milestones)[54](index=54&type=chunk) - **Karuna** delivered strong Phase 3 clinical data for **KarXT** in schizophrenia, with its value increasing **over 60%** in 2022[55](index=55&type=chunk) Gelesis Plenity Sales Performance | Metric | Amount (Millions USD) | | :----- | :-------------------- | | Total Sales since launch | $39.5 | | Sales in 2022 | $25.5 | | YoY Increase (2022) | 129% | - **Gelesis** applied with the FDA to make **Plenity** available without a prescription, potentially by Q3 2023[56](index=56&type=chunk) - **Akili** formed a partnership with Roblox to expand growth opportunities for **EndeavorRx**[56](index=56&type=chunk) - Vor Bio delivered initial data for trem-cell in AML, supporting its potential[57](index=57&type=chunk) [Components of Value](index=11&type=section&id=Components%20of%20Value) PureTech's value is derived from four key components: its Wholly Owned Programs, its Founded Entities (through equity appreciation, royalties, and sublicense revenues), its available cash, cash equivalents, and short-term investments, and its commitment to returning capital to shareholders through initiatives like share buyback programs - Value components include Wholly Owned Programs, Founded Entities (equity, royalties, sublicense revenues), available cash, and return of capital to shareholders[63](index=63&type=chunk)[65](index=65&type=chunk)[66](index=66&type=chunk) - PureTech implemented a share buyback program of up to **$50 million** in 2022 as part of its capital allocation strategy[68](index=68&type=chunk) - The company prioritizes funding its Wholly Owned Pipeline and strategic investment in Founded Entities, while also planning to return proceeds to shareholders via buybacks or special dividends[68](index=68&type=chunk) [Risk Management](index=12&type=section&id=Risk%20Management) PureTech operates in a high-risk biotherapeutics environment, facing principal business and financial risks that are mitigated through rigorous due diligence, diversified assets, and careful monitoring of external disruptions [Principal Business Risks](index=12&type=section&id=Principal%20Business%20Risks) PureTech operates in a high-risk biotherapeutics environment, facing principal business risks such as science and technology failure, clinical trial failure, regulatory approval challenges, therapeutic safety concerns, and issues with therapeutic profitability due to competition or reimbursement. The company mitigates these risks through extensive due diligence, a capital-efficient approach, diversified assets, expert consultation, and robust clinical program design - Key business risks include science and technology failure, clinical trial failure, regulatory approval, therapeutic safety, therapeutic profitability, intellectual property protection, enterprise profitability, and hiring/retaining qualified employees[73](index=73&type=chunk)[77](index=77&type=chunk)[80](index=80&type=chunk)[81](index=81&type=chunk)[82](index=82&type=chunk)[93](index=93&type=chunk)[94](index=94&type=chunk)[95](index=95&type=chunk) - Mitigation strategies include extensive due diligence, a capital-efficient approach, diversified assets, board/management oversight, expert network utilization, and rigorous R&D committee reviews[75](index=75&type=chunk)[76](index=76&type=chunk)[88](index=88&type=chunk) - The company maintains insurance for product liability claims during clinical trials to mitigate therapeutic safety risks[89](index=89&type=chunk) [Financial Risks](index=15&type=section&id=Financial%20Risks) PureTech identifies business, economic, financial, or geopolitical disruptions as increasing risks, which could harm development efforts and increase costs. The company monitors its suppliers, clinical trial sites, regulators, and financial service providers, and develops contingency plans. While the investment portfolio is conservative, the company acknowledges potential adverse changes in market conditions and equity price risks from its holdings in public Founded Entities - Business, economic, financial, or geopolitical disruptions (e.g., global health concerns, invasion of Ukraine, banking system stability) are considered increasing risks[102](index=102&type=chunk)[103](index=103&type=chunk) - The company monitors its suppliers, clinical trial sites, regulators, and financial service providers, and develops contingency plans[104](index=104&type=chunk) [Financial Review](index=15&type=section&id=Financial%20Review) PureTech Health's 2022 financial performance showed a reduced net loss, driven by decreased revenue, increased R&D expenses, and significant shifts in other income and net finance income, while total assets and liabilities decreased [Reporting Framework and Basis of Presentation](index=15&type=section&id=Reporting%20Framework%20and%20Basis%20of%20Presentation) PureTech Health's Consolidated Financial Statements are prepared in accordance with UK-adopted International Financial Reporting Standards (IFRS) and comply with IFRSs issued by the IASB. The financial statements consolidate subsidiaries and include interests in associates and investments held at fair value, with the accounting treatment depending on the level of control or significant influence over each entity - Financial statements are prepared in accordance with UK-adopted IFRS and comply with IFRSs issued by the IASB[106](index=106&type=chunk) - Founded Entities are classified as subsidiaries (control), associates (significant influence), or investments held at fair value (neither control nor significant influence)[107](index=107&type=chunk) [Segment Information](index=18&type=section&id=Segment%20Information) PureTech's operating segments are based on financial information provided to its Directors for resource allocation and performance assessment. The company aggregates multiple operating segments into four reportable segments: Internal, Controlled Founded Entities, Non-Controlled Founded Entities, and Parent Company and Other. Changes in control, such as the deconsolidation of **Sonde Health, Inc.** in May 2022, lead to restatement of segment disclosures - Operating segments are based on financial information provided to Directors for resource allocation and performance assessment[126](index=126&type=chunk) - Reportable segments include Internal, Controlled Founded Entities, Non-Controlled Founded Entities, and Parent Company and Other[131](index=131&type=chunk)[132](index=132&type=chunk)[133](index=133&type=chunk)[135](index=135&type=chunk) - **Sonde Health, Inc.** was transferred to the Non-Controlled Founded Entities segment due to deconsolidation on May 25, 2022[127](index=127&type=chunk)[129](index=129&type=chunk) [Internal Segment](index=19&type=section&id=Internal%20Segment) The Internal segment focuses on advancing PureTech's wholly-owned therapeutic programs, funded internally or through non-dilutive sources, with operational oversight by the PureTech Health team - The Internal segment advances Wholly Owned Programs, funded by PureTech Health or non-dilutive sources, with operational management by the PureTech Health team[131](index=131&type=chunk) - As of December 31, 2022, this segment included PureTech LYT, Inc., PureTech LYT-100, Inc., and Alivio Therapeutics, Inc[131](index=131&type=chunk) [Controlled Founded Entities Segment](index=19&type=section&id=Controlled%20Founded%20Entities%20Segment) This segment comprises consolidated operational subsidiaries with independent management, active R&D programs, and plans to secure third-party dilutive capital - Controlled Founded Entities are consolidated operational subsidiaries with active R&D programs, independent management teams, and plans to raise third-party dilutive capital[132](index=132&type=chunk) - As of December 31, 2022, this segment included Entrega, Inc., Follica, Inc., and **Vedanta Biosciences, Inc**[132](index=132&type=chunk) [Non-Controlled Founded Entities Segment](index=20&type=section&id=Non-Controlled%20Founded%20Entities%20Segment) This segment includes entities over which PureTech no longer exercises control, with their operational results consolidated only up to the date of deconsolidation - Non-Controlled Founded Entities are those over which PureTech no longer has control, with operational results included up to the deconsolidation date[133](index=133&type=chunk)[134](index=134&type=chunk) - As of December 31, 2022, this segment included **Sonde Health, Inc**[133](index=133&type=chunk) [Parent Company and Other Segment](index=20&type=section&id=Parent%20Company%20and%20Other%20Segment) This segment encompasses corporate support functions, R&D support, intercompany eliminations, and accounting for holdings in deconsolidated entities and other non-operating activities - This segment includes activities not directly attributable to operating segments, corporate support, R&D support, intercompany eliminations, and accounting for holdings in deconsolidated entities[135](index=135&type=chunk) - It captures gains/losses on deconsolidation, investments held at fair value, realized losses on sales, share of net income/loss of associates, and impairment of investments[135](index=135&type=chunk) [Recent Developments (Post-December 31, 2022)](index=17&type=section&id=Recent%20Developments%20(Post-December%2031%2C%202022)) Subsequent to December 31, 2022, PureTech Health reported several key developments. **Vedanta Biosciences** issued convertible debt, leading to PureTech losing control over **Vedanta**. PureTech entered an agreement with **Royalty Pharma** for **Karuna's KarXT** royalty, receiving **$100 million** upfront. Additionally, PureTech invested **$5.0 million** in **Gelesis** via a convertible note and warrants, and later submitted a non-binding proposal to acquire all outstanding equity of **Gelesis**, following its delisting from the NYSE - On March 1, 2023, **Vedanta** issued convertible debt for approximately **$88.5 million**, resulting in PureTech losing control over **Vedanta**[119](index=119&type=chunk) - On March 22, 2023, PureTech agreed with **Royalty Pharma** for an interest in **Karuna's KarXT** royalty, with **$100.0 million** upfront cash and up to **$400.0 million** contingent on milestones[120](index=120&type=chunk) - On February 21, 2023, PureTech invested **$5.0 million** in **Gelesis** via a convertible senior secured note and warrants[121](index=121&type=chunk) - **Gelesis** was delisted from the NYSE in April 2023, and PureTech submitted a non-binding proposal to acquire all its outstanding equity[122](index=122&type=chunk)[123](index=123&type=chunk) [Results of Operations (Income Statement Analysis)](index=21&type=section&id=Results%20of%20Operations%20(Income%20Statement%20Analysis)) PureTech Health reported a net loss attributable to owners of **$50.4 million** for 2022, an improvement from a **$60.6 million** loss in 2021, but a significant decline from a **$6.0 million** net income in 2020. Total revenue decreased by **10.2%** in 2022 to **$15.6 million**, primarily due to a drop in Internal Segment contract revenue. Operating expenses increased, driven by a **38.0%** rise in R&D to **$152.4 million**. Other income shifted from a gain of **$160.0 million** in 2021 to a loss of **$26.0 million** in 2022, mainly due to fair value adjustments of investments. Net finance income significantly increased to **$138.9 million** in 2022, largely from changes in fair value of subsidiary preferred share liabilities Net Income/(Loss) Attributable to Owners of the Company (in thousands USD) | Year | Amount | | :--- | :----- | | 2022 | $(50,354) | | 2021 | $(60,558) | | 2020 | $5,985 | Total Revenue (in thousands USD) | Year | Amount | Change (YoY) | | :--- | :----- | :----------- | | 2022 | $15,618 | $(1,770) (10.2%) | | 2021 | $17,388 | $5,621 (47.8%) | | 2020 | $11,768 | | Research and Development Expenses (in thousands USD) | Year | Amount | Change (YoY) | | :--- | :----- | :----------- | | 2022 | $(152,433) | $(41,962) (38.0%) | | 2021 | $(110,471) | $(28,612) (35.0%) | | 2020 | $(81,859) | | Other Income/(Loss) (in thousands USD) | Year | Amount | Change (YoY) | | :--- | :----- | :----------- | | 2022 | $(25,981) | $(185,965) | | 2021 | $159,983 | $(18,749) | | 2020 | $178,732 | | Net Finance Income/(Costs) (in thousands USD) | Year | Amount | Change (YoY) | | :--- | :----- | :----------- | | 2022 | $138,924 | $133,875 | | 2021 | $5,050 | $11,164 | | 2020 | $(6,115) | | [Total Revenue](index=25&type=section&id=Total%20Revenue) Total revenue for PureTech Health decreased in 2022, primarily due to a significant reduction in contract revenue from the Internal Segment, partially offset by increases in grant revenue - Total revenue decreased by **$1.8 million** (**10.2%**) in 2022, primarily due to an **$8.1 million** decrease in Internal Segment contract revenue, partially offset by a **$4.5 million** increase in Controlled Founded Entities grant revenue and a **$1.6 million** increase in Internal Segment grant revenue[159](index=159&type=chunk) [Operating Expenses (R&D, G&A)](index=25&type=section&id=Operating%20Expenses%20(R%26D%2C%20G%26A)) Operating expenses increased in 2022, driven by a substantial rise in R&D costs within the Internal segment for clinical testing, alongside an increase in general and administrative expenses - R&D expenses increased by **$42.0 million** (**38.0%**) in 2022, mainly due to a **$50.6 million** increase in the Internal segment for clinical testing, partially offset by decreases in Controlled and Non-Controlled Founded Entities[161](index=161&type=chunk) - G&A expenses increased by **$3.8 million** (**6.6%**) in 2022, driven by a **$7.1 million** increase in the Parent Company and other segment (headcount, compensation, taxes), offset by decreases in Founded Entities[162](index=162&type=chunk) [Other Income/(Loss)](index=26&type=section&id=Other%20Income%2F(Loss)) Other income shifted from a significant gain in 2021 to a loss in 2022, primarily due to fair value adjustments of investments, partially offset by gains from deconsolidation and a back-stop agreement - Other income shifted from a **$160.0 million** gain in 2021 to a **$26.0 million** loss in 2022, a **$186.0 million** change[163](index=163&type=chunk) - This was primarily due to a **$32.1 million** loss on investments held at fair value in 2022 (vs. **$179.3 million** gain in 2021), partially offset by a **$27.3 million** gain from **Sonde** deconsolidation and a **$7.6 million** gain from the **Gelesis** back-stop agreement[163](index=163&type=chunk) [Net Finance Income/(Costs)](index=27&type=section&id=Net%20Finance%20Income%2F(Costs)) Net finance income saw a substantial increase in 2022, predominantly driven by favorable changes in the fair value of subsidiary preferred shares, warrant, and convertible note liabilities - Net finance income increased by **$133.9 million** to **$138.9 million** in 2022, primarily due to a **$127.5 million** increase from changes in fair value of subsidiaries' preferred shares, warrant, and convertible note liabilities (mainly **Vedanta**)[164](index=164&type=chunk) [Share of Net Income/(Loss) of Associates & Impairment](index=27&type=section&id=Share%20of%20Net%20Income%2F(Loss)%20of%20Associates%20%26%20Impairment) The share in net loss of associates decreased in 2022, mainly due to reduced equity interest and lower IFRS losses from **Gelesis**, alongside a gain on dilution and an impairment charge - Share in net loss of associates decreased to **$27.7 million** in 2022 from **$73.7 million** in 2021, mainly due to a decrease in equity interest and lower IFRS losses from **Gelesis**[165](index=165&type=chunk) - PureTech recorded a **$28.2 million** gain on dilution of its equity ownership in **Gelesis** and an **$8.4 million** impairment in its **Gelesis** investment in 2022[165](index=165&type=chunk) [Taxation](index=27&type=section&id=Taxation) PureTech Health reported an income tax benefit in 2022, a shift from an expense in the prior year, primarily attributable to increased non-taxable gains and changes in state apportionment - Income tax expense was a benefit of **$55.7 million** in 2022, compared to an expense of **$3.8 million** in 2021, primarily due to an increase in non-taxable gains and a change in state apportionment[166](index=166&type=chunk) [Financial Position (Balance Sheet Analysis)](index=34&type=section&id=Financial%20Position%20(Balance%20Sheet%20Analysis)) PureTech Health's total assets decreased by **$243.4 million** to **$702.6 million** as of December 31, 2022, primarily driven by a **$145.3 million** decrease in investments held at fair value and a **$115.6 million** decrease in consolidated cash, cash equivalents, and short-term investments. Total liabilities also decreased significantly by **$206.8 million** to **$155.1 million**, mainly due to declines in deferred tax liabilities and preferred share liabilities Summary Financial Position (in thousands USD) | Category | 2022 | 2021 | Change | | :------------------------------------ | :----- | :----- | :------- | | Total assets | $702,647 | $946,006 | $(243,359) | | Total liabilities | $155,057 | $361,859 | $(206,802) | | Net assets (Total equity) | $547,589 | $584,147 | $(36,557) | - Investments held at fair value decreased by **$145.3 million** to **$251.9 million**, primarily consisting of common shares in **Karuna**, Vor, **Akili**, and preferred shares in **Sonde**[203](index=203&type=chunk) - Consolidated cash, cash equivalents, and short-term investments decreased by **$115.6 million** to **$350.1 million**, reflecting operating losses partially offset by proceeds from **Karuna** and Vor share sales[204](index=204&type=chunk) - Non-current liabilities decreased by **$77.6 million**, driven by declines in long-term lease liability (**$4.9 million**) and deferred tax liabilities (**$70.1 million**)[205](index=205&type=chunk) - Preferred share liability in subsidiaries decreased by **$146.7 million** to **$27.3 million**, mainly due to a **$130.8 million** decrease in fair value and a **$15.9 million** decrease from **Sonde** deconsolidation[208](index=208&type=chunk) [Cash Flow and Liquidity](index=31&type=section&id=Cash%20Flow%20and%20Liquidity) PureTech Health's net cash used in operating activities increased to **$178.8 million** in 2022, reflecting higher operating losses and increased R&D. Net cash from investing activities shifted from a **$197.4 million** inflow in 2021 to a **$107.2 million** outflow in 2022, primarily due to decreased proceeds from investment sales and significant purchases of short-term investments. Financing activities also shifted from a **$22.7 million** inflow to a **$29.8 million** outflow, mainly due to no subsidiary preferred share issuance and treasury share purchases in 2022. The company believes its existing financial assets will fund operations into Q1 2026 but anticipates substantial future funding needs Summary Cash Flows (in thousands USD) | Activity | 2022 | 2021 | 2020 | | :---------------------------------- | :--------- | :--------- | :--------- | | Net cash used in operating activities | $(178,792) | $(158,274) | $(131,827) | | Net cash provided by (used in) investing activities | $(107,223) | $197,375 | $364,478 | | Net cash provided by (used in) financing activities | $(29,827) | $22,727 | $38,869 | | Net increase (decrease) in cash and cash equivalents | $(315,842) | $61,827 | $271,520 | - As of December 31, 2022, PureTech had **$339.5 million** in PureTech Level cash, cash equivalents, and short-term investments[189](index=189&type=chunk) - Existing financial assets are believed to be sufficient to fund operations and capital expenditure requirements into Q1 2026[198](index=198&type=chunk) [Operating Activities](index=32&type=section&id=Operating%20Activities) Net cash used in operating activities increased in 2022, reflecting higher operating losses primarily driven by increased research and development expenditures in the Internal Segment - Net cash used in operating activities increased by **$20.5 million** to **$178.8 million** in 2022, primarily due to higher operating losses from increased R&D in the Internal Segment[191](index=191&type=chunk) [Investing Activities](index=32&type=section&id=Investing%20Activities) Net cash from investing activities shifted from a significant inflow to an outflow in 2022, mainly due to decreased proceeds from investment sales and substantial net purchases of short-term investments - Net cash from investing activities decreased by **$304.6 million**, shifting from a **$197.4 million** inflow in 2021 to a **$107.2 million** outflow in 2022[193](index=193&type=chunk) - This change was mainly attributed to a **$99.4 million** decrease in proceeds from investment sales and **$198.7 million** in net purchases of short-term investments[193](index=193&type=chunk) [Financing Activities](index=32&type=section&id=Financing%20Activities) Net cash from financing activities shifted from an inflow to an outflow in 2022, primarily due to the absence of subsidiary preferred share issuances and the initiation of treasury share purchases - Net cash from financing activities decreased by **$52.6 million**, shifting from a **$22.7 million** inflow in 2021 to a **$29.8 million** outflow in 2022[195](index=195&type=chunk) - This was primarily due to no issuance of subsidiary preferred shares in 2022 (vs. **$37.6 million** in 2021) and **$26.5 million** in treasury share purchases in 2022[196](index=196&type=chunk) [Funding Requirements](index=33&type=section&id=Funding%20Requirements) PureTech anticipates substantial future expenditures and operating losses, with funding dependent on planned financings, monetization of public Founded Entity shares, and potential business development activities - PureTech expects to incur substantial additional expenditures and net operating losses for the foreseeable future[198](index=198&type=chunk) - Future funding will depend on planned financings, monetization of public Founded Entity shares, and potential business development activities[198](index=198&type=chunk) - The company currently has no credit facility or other committed sources of capital beyond existing financial assets[200](index=200&type=chunk) [Critical Accounting Policies and Estimates](index=29&type=section&id=Critical%20Accounting%20Policies%20and%20Estimates) PureTech's financial reporting relies on critical accounting policies and estimates, particularly for financial instruments, consolidation, and investments in associates, which involve complex judgments about control and fair value [Critical Accounting Policies and Estimates](index=29&type=section&id=Critical%20Accounting%20Policies%20and%20Estimates) PureTech's financial statements, prepared under IFRS, require significant judgments and estimates, particularly concerning financial instruments, consolidation, and investments in associates. Key areas include classifying financial instruments as liability or equity, valuing financial instruments at fair value through profit and loss (FVTPL), and determining control or significant influence over investees. These assessments involve complex evaluations of contractual obligations, voting power, board representation, and the nature of financial instruments held - Financial statements are prepared in accordance with UK-adopted IFRS, requiring judgments and estimates for asset and liability carrying amounts[176](index=176&type=chunk) - Critical policies involve financial instruments (liability/equity classification, embedded derivatives), consolidation (power, variable returns, ability to affect returns), and investment in associates (significant influence, classification of instruments)[179](index=179&type=chunk)[181](index=181&type=chunk)[182](index=182&type=chunk)[185](index=185&type=chunk) - Valuation of financial instruments at FVTPL requires significant estimates, including future expected returns, earnings potential, discount rates, volatility, and term to exit[180](index=180&type=chunk) [Additional Information](index=4&type=section&id=Additional%20Information) This section provides essential supplementary details, including the upcoming Annual General Meeting, an overview of PureTech Health's mission, cautionary notes on forward-looking statements, contact information, and its foreign private issuer status [Annual General Meeting (AGM)](index=4&type=section&id=Annual%20General%20Meeting%20(AGM)) PureTech Health's 2023 Annual General Meeting (AGM) is scheduled for June 13, 2023, at 11:00am EDT / 4:00pm BST at its Boston headquarters. Shareholders are strongly encouraged to submit proxy votes in advance and appoint the Chair as their proxy, with a deadline of 4:00 pm (BST) on June 9, 2023. The company encourages remote participation due to the location and will keep shareholders updated on any changes - The 2023 AGM will be held on June 13, 2023, at 11:00am EDT / 4:00pm BST in Boston, Massachusetts[20](index=20&type=chunk) - Shareholders are encouraged to submit proxy votes by 4:00 pm (BST) on June 9, 2023, and to participate remotely[21](index=21&type=chunk)[22](index=22&type=chunk)[23](index=23&type=chunk) [About PureTech Health](index=4&type=section&id=About%20PureTech%20Health) PureTech Health is a clinical-stage biotherapeutics company focused on developing new classes of medicines for devastating diseases. It has built a broad pipeline through its R&D team and network, resulting in **27 therapeutics** and candidates. Two products (**Plenity®** and **EndeavorRx®**) have received FDA and EU clearances, and **KarXT** is expected to be filed soon for FDA approval. The company's model involves identifying, discovering, and advancing programs through key validation points, both internally and via its Founded Entities - PureTech is a clinical-stage biotherapeutics company focused on developing new classes of medicine for devastating diseases[25](index=25&type=chunk) - The company has developed **27 therapeutics** and therapeutic candidates, with two (**Plenity®** and **EndeavorRx®**) having received FDA and EU regulatory clearances, and a third (**KarXT**) expected for FDA approval filing soon[25](index=25&type=chunk) - All underlying programs and platforms were initially identified or discovered and advanced by the PureTech team through key validation points[25](index=25&type=chunk) [Cautionary Note Regarding Forward-Looking Statements](index=5&type=section&id=Cautionary%20Note%20Regarding%20Forward-Looking%20Statements) This press release contains forward-looking statements regarding PureTech's future prospects, development plans, clinical trials, regulatory submissions, and operational runway. These statements are based on current expectations and are subject to known and unknown risks, uncertainties, and important factors that could cause actual results to differ materially. Key risks include operating losses, need for additional funding, limited control over Non-Controlled Founded Entities, lengthy and expensive drug development, clinical trial delays, safety risks, regulatory approval challenges, intellectual property, reliance on third parties, and macroeconomic conditions. The company disclaims any obligation to update these statements, except as required by law - The press release contains forward-looking statements about future prospects, development plans, clinical trials, regulatory submissions, and operational runway[28](index=28&type=chunk) - These statements are subject to known and unknown risks, uncertainties, and important factors that could cause actual results to differ materially[28](index=28&type=chunk) - Key risks include significant operating losses, need for additional funding, limited control over Non-Controlled Founded Entities, lengthy and expensive drug development, clinical trial delays, safety risks, regulatory approval challenges, intellectual property, reliance on third parties, and vulnerability to global events[28](index=28&type=chunk) [Contact Information](index=5&type=section&id=Contact%20Information) Contact information for PureTech Health's Public Relations and Investor Relations teams is provided for both EU media and U.S. media inquiries Contact Information | Department | Contact (EU Media) | Contact (U.S. Media) | | :--------- | :----------------- | :------------------- | | Public Relations | Ben Atwell, Rob Winder (+44 (0) 20 3727 1000, ben.atwell@FTIconsulting.com) | Nichole Sarkis (+1 774 278 8273, nichole@tenbridgecommunications.com) | | Investor Relations | IR@puretechhealth.com | IR@puretechhealth.com | [Foreign Private Issuer Status](index=36&type=section&id=Foreign%20Private%20Issuer%20Status) As a foreign private issuer under the U.S. Securities Exchange Act of 1934, PureTech Health is exempt from certain provisions applicable to U.S. domestic public companies. These exemptions include rules regarding proxy solicitations, insider stock ownership and trading reports, quarterly reports on Form 10-Q, current reports on Form 8-K, and Regulation FD - PureTech Health qualifies as a foreign private issuer under the Exchange Act[218](index=218&type=chunk) - Exemptions include rules on proxy solicitations, insider trading reports, quarterly reports (Form 10-Q), current reports (Form 8-K), and Regulation FD[220](index=220&type=chunk)

Our Distinctive Approach Drives Success PureTech's Proven Expertise 8 1 References in this presentation to "Wholly Owned Programs" refer to the Company's six therapeutic candidates (LYT-100, LYT-200, LYT-300, LYT-310, LYT-510, and LYT-503/IMB-150), lymphatic and inflammation platforms and potential future therapeutic candidates and platforms that the Company may develop or obtain. References to "Wholly Owned Pipeline" refer to LYT-100, LYT-200, LYT-300, LYT-310, LYT-510, and LYT-503/IMB-150. On July 23, 202 ...

PURETECH GIVING LIFE TO SCIENCE® August 2022 BRAIN IMMUNE GUT Important Information The following presentation, including any printed or electronic copy of these slides, the talks given by the presenters, the information communicated during any delivery of the presentation and any question and answer session and any document or material distributed at or in connection with the presentation (together, the "Presentation"), has been prepared by PureTech Health plc (the "Company"). The information in the Presen ...

Financial Performance - Total revenue for the six months ended June 30, 2022, was $7.0 million, compared to $5.8 million for the same period in 2021, marking an increase of approximately 19.5%[126]. - The company incurred a loss of $23.5 million for the period ended June 30, 2022, compared to a loss of $77.6 million for the same period in 2021, indicating a reduction in losses[126]. - Net loss for the six months ended June 30, 2022, was $28,344,000, compared to a net loss of $75,395,000 for the same period in 2021, representing a 62.4% improvement[133]. - Total comprehensive income for the period ended June 30, 2022, was a loss of $28,880,000, compared to a loss of $77,553,000 in 2021, reflecting a 62.9% reduction in comprehensive losses[133]. - The Group reported a net loss of $23.472 million for the six months ended June 30, 2022, compared to a net loss of $28.880 million in the same period of 2021, showing an improvement of 18.9%[159]. Cash Flow and Liquidity - As of June 30, 2022, the company had consolidated cash and cash equivalents of $365.9 million, down from $465.7 million as of June 30, 2021, representing a decrease of approximately 21.4%[116][128]. - Net cash used in operating activities for the six months ended June 30, 2022, was $87.2 million, an increase of $21.9 million compared to $65.4 million for the same period in 2021, reflecting higher operating losses primarily due to increased research and development activities[119]. - Cash flows from operating activities resulted in a net cash used of $87,249,000 for the first half of 2022, compared to $65,366,000 in the same period of 2021, indicating a 33.4% increase in cash outflow[133]. - Cash and cash equivalents at the end of the period were $365,910,000, down from $439,766,000 at the end of June 2021, marking a decrease of 16.7%[134]. - The company expects its existing financial assets will be sufficient to fund operations and capital expenditures into the first quarter of 2026, despite ongoing net operating losses typical for pre-revenue biotechnology companies[122]. Operating Expenses - Operating loss for the six months ended June 30, 2022, was $101.2 million, compared to a loss of $68.1 million for the same period in 2021, indicating a significant increase in operating expenses[126]. - Research and development expenses totaled $84.579 million for the six months ended June 30, 2022, compared to $20.877 million in 2021, indicating a significant increase of 304.5%[159]. - Total operating expenses reached $73.92 million, up from $31.58 million, indicating a year-over-year increase of 134%[160]. Investments and Fair Value - The company experienced a gain on investments held at fair value of $59,019,000 in 2022, contrasting with a loss of $74,415,000 in 2021, indicating a significant turnaround[133]. - The fair value of investments held at fair value decreased to $367.95 million as of June 30, 2022, down from $493.89 million at the beginning of the year, reflecting a decline of 25.5%[161]. - The Group recorded a loss of $29.9 million on investments held at fair value during the six months ended June 30, 2022, which was reflected in the Condensed Consolidated Statements of Comprehensive Income/(Loss)[233]. - The balance of investments held at fair value as of June 30, 2022, was $142.394 million, down from $239.533 million at the beginning of the year, after accounting for a loss of $(30.217) million[234]. Shareholder Equity and Stock Activity - The total equity of the parent company as of June 30, 2022, was $576,024,000, compared to $561,372,000 at the end of June 2021, reflecting a 2.6% increase[132]. - The company commenced a $50 million share repurchase program, with the first tranche amounting to $25 million[217]. - As of June 30, 2022, the company had 288,611,120 common shares outstanding, including 2,010,269 shares repurchased and held in treasury[219]. - The company reported a cash outflow of $4,267,000 from the purchase of treasury stock in 2022, with no such outflow reported in 2021[133]. Tax and Financing - The Group recorded a consolidated tax provision of $(32.5) million benefit for the six months ended June 30, 2022, representing an effective tax rate of 58.1%[277]. - The company incurred finance costs of $56,320,000 in the first half of 2022, compared to a net income of $16,252,000 in the same period of 2021, indicating a significant shift in financial performance[133]. - Total finance income for the six months ended June 30, 2022, was $630,000, compared to $119,000 in 2021, representing a significant increase of 429%[209]. - The total finance costs decreased from $2,755,000 in 2021 to $1,961,000 in 2022, a reduction of approximately 29%[209]. Management and Compensation - Key management personnel compensation for the six months ended June 30, 2022, totaled $(337) thousand, reflecting a net income in share-based compensation due to a decrease in RSU value[266]. - The Group incurred share-based payment expenses of $3.6 million for the six months ended June 30, 2022, down from $5.6 million in the same period of 2021[189]. - The Group's share-based payment expense for stock options was $4.5 million for the six months ended June 30, 2022[203].

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 20-F | (Mark One) | | | --- | --- | | ☐ | REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 | | | OR | | ☒ | ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | | | For the fiscal year ended December 31, 2021 | | | OR | | ☐ | TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | | | For the transition period from to ...

As filed with the Securities and Exchange Commission on April 15, 2021. UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 20-F | (Mark One) | | | --- | --- | | ☐ | REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 | | | OR | | ☒ | ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | | | For the fiscal year ended December 31, 2020 | | | OR | | ☐ | TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE ...