PureTech Health (PRTC) H1 2025 Earnings Call August 28, 2025 09:00 AM ET Company ParticipantsAllison Talbot - SVP - CommunicationsRobert Lyne - Interim CEOSven Dethlefs - CEO - Celea TherapeuticsLuba Greenwood - CEOHeidi Jacobson - Equity Research AssociateEric Elenko - Co-Founder & PresidentConference Call ParticipantsMiles Dixon - Research Analyst - Healthcare & Life SciencesOperatorHello, everyone, and thank you for joining the Puretec Health twenty twenty five Half Year Earnings Webcast. My name is Samm ...

PureTech Health (PRTC) H1 2025 Earnings Call August 28, 2025 09:00 AM ET Speaker0Hello, everyone, and thank you for joining the Puretec Health twenty twenty five Half Year Earnings Webcast. My name is Sammy, and I'll be coordinating your call today. I would now like to hand over to your host, Alison Tolbert, Senior Vice President of Communications to begin. Please go ahead, Alison.Speaker1Thank you, everyone, for joining us for PureTech's twenty twenty five half year results webcast. Our half year report wa ...

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, 2024 | | | OR | | ☐ | TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | | | For the transition period from to ...

30 April 2025 Exhibit 99.1 PureTech Health plc PureTech Announces Annual Results for Year Ended December 31, 2024 Innovation engine drives meaningful clinical, regulatory, and financial milestones, including positive Phase 2b results for wholly-owned deupirfenidone (LYT-100) in IPF, compelling Phase 1b data for wholly-owned LYT-200 in AML and solid tumors, FDA approval of PureTech-invented Cobenfy™1 for schizophrenia, and rapid growth of Founded Entity 2, Seaport Therapeutics, which raised over $325 million ...

PureTech Health plc (NASDAQ:PRTC) Q4 2023 Earnings Conference Call April 25, 2024 9:00 AM ET Company Participants Allison Mead Talbot - Head, Communications Bharatt Chowrira - Chief Executive Officer Eric Elenko - Co-Founder and President Chip Sherwood - General Counsel Conference Call Participants Miles Dixon - Peel Hunt Lucy Codrington - Jefferies Operator Greetings, and welcome to the PureTech Health 2023 Year End Financial Results Conference Call. [Operator Instructions] As a reminder, this conference i ...

Financial Performance and Position - As of December 31, 2023, the company had never generated revenue from its therapeutic candidates within its Internal Programs[16] - The company has not generated operational profits and may never achieve profitability[16] - The company considers its working capital to be sufficient for its present requirements[205] - There are no known trends or uncertainties that are likely to materially affect the company's net revenue, income, profitability, liquidity, or capital resources from January 1, 2023, to the present[207] - The preferred shares issued by subsidiaries are classified as liabilities and are redeemable only upon liquidation events, which are unpredictable[203] - The company has no off-balance sheet arrangements that are likely to have a material effect on its financial condition or results of operations[204] - The financial statements consolidate the company's subsidiaries and include interests in associates and investments held at fair value[197] - The company is required to make royalty payments in connection with the sale of products developed under various license and collaboration agreements, contingent upon successful sales[202] - The company has incorporated various financial reviews and key performance indicators in its annual report for 2023[198] - The company's financial statements are prepared in accordance with IFRS, reflecting its financial position as of December 31, 2023[196] Funding and Development Challenges - The company may require substantial additional funding to achieve its business goals, which could delay or limit therapeutic development efforts[16] - The therapeutic candidates within the company's Internal Programs and most of its Founded Entities' candidates are in preclinical or clinical development, which is a lengthy and expensive process[16] - The marketing approval and certification process for therapeutic candidates is expensive, time-consuming, and uncertain, potentially hindering commercialization efforts[16] - The company relies on third parties for conducting clinical trials and research, which may not perform satisfactorily and could affect timelines[16] - The COVID-19 pandemic and future global health crises may materially and adversely affect the company's business operations[17] Competition and Market Landscape - The company faces significant competition in the biotechnology and pharmaceutical industries, with the potential for competitors to achieve regulatory approval before it does[33] - The Glyph technology platform currently has no direct competitors but may face future competition from new therapies[41] Regulatory and Approval Processes - The regulatory approval process in the U.S. requires substantial time and financial resources, including the submission of an IND before clinical trials can begin[42] - The FDA aims to review applications for original biologics or new-molecular-entity drugs within ten months, or six months for priority reviews[54] - The clinical investigation of a drug is divided into three phases, with Phase 3 trials providing statistically significant evidence of clinical efficacy[56] - The FDA may condition approval of an NDA or BLA on the sponsor's agreement to conduct additional clinical studies post-approval[49] - The FDA requires inspections of manufacturing facilities before approving an NDA or BLA to ensure compliance with cGMP requirements[57] - An approval letter from the FDA allows for commercial marketing of the product, while a Complete Response letter outlines deficiencies in the application[58] - The FDA may impose a Risk Evaluation and Mitigation Strategy (REMS) to manage serious risks associated with a product post-approval[59] - Combination products are regulated based on their primary mode of action, with the FDA assigning a lead center for review[60] - The FDA offers expedited programs like fast track and breakthrough therapy designations to accelerate the review process for qualifying product candidates[61] - Priority review designation aims for FDA action on marketing applications within six months for new-molecular-entity NDAs and original BLAs[64] - Accelerated approval may be granted if a product candidate shows effects on a surrogate endpoint likely to predict clinical benefit[65] - Orphan drug designation can provide exclusivity for seven years if the product is the first approved for a rare disease[70] - Post-approval, products are subject to ongoing FDA regulation, including record-keeping and reporting of adverse experiences[72] - The FDA may withdraw approval if compliance with regulatory requirements is not maintained after the product reaches the market[74] - The Hatch-Waxman Act allows for five years of non-patent data exclusivity for new drugs containing new chemical entities not previously approved by the FDA[79] - An ANDA or 505(b)(2) NDA cannot be approved until all listed patents have expired, unless a Paragraph IV certification is provided[77] - The BPCIA establishes a 12-year exclusivity period for reference products, during which biosimilars cannot be approved[81] - Pediatric exclusivity can add six months to existing exclusivity periods and patent terms if a pediatric study is completed[82] - The FDA's 510(k) clearance process typically takes three to twelve months for medical devices to demonstrate substantial equivalence to predicate devices[90] - Class III devices require a more rigorous PMA approval process if deemed not substantially equivalent to a predicate device[91] - The DEA regulates controlled substances, requiring annual registration for facilities handling these substances[84] - The FDA may impose civil penalties or refuse to renew registrations for non-compliance with controlled substance regulations[86] - The Hatch-Waxman Act provides three years of non-patent exclusivity for new formulations if new clinical studies were essential for approval[79] - The FDA's 510(k) clearance is necessary for any significant modifications to a device that could affect its safety or effectiveness[92] - The PMA process requires manufacturers to demonstrate device safety and effectiveness, supported by extensive data from pre-clinical studies and human clinical trials[94] - The FDA has 180 days to complete its review of a PMA application, although actual review times can extend to several years[94] - Manufacturers may be required to conduct post-approval surveillance to ensure ongoing safety and effectiveness of the device[95] - Changes to an approved device that affect safety or effectiveness require submission of a PMA supplement, which may not need as extensive clinical data[96] - The de novo classification process allows manufacturers to request down-classification of devices automatically classified as Class III, streamlining the approval process for low-to-moderate risk devices[97] - The FDA must classify a de novo request within 120 days, but this process can take longer in practice[98] - Clinical trials for medical devices must comply with FDA regulations, including obtaining IDE approval for significant risk devices[99] - Post-market regulations require compliance with QSR, including maintaining device master files and undergoing FDA inspections[102] - The FDA issued a final rule to amend the QSR, expected to take effect on February 2, 2026, aligning with ISO 13485:2016 standards[103] - The approval process for foreign markets varies significantly and may involve additional testing beyond FDA requirements[106] - The company must obtain separate regulatory approvals to market its product candidates in the EU, with a maximum evaluation timeframe of 210 days for a Marketing Authorization Application (MAA) under the centralized procedure[115] - Innovative medicinal products receive eight years of data exclusivity and an additional two years of market exclusivity upon MA, potentially extending to 11 years if new therapeutic indications are authorized[119] - Orphan medicinal products are entitled to ten years of market exclusivity for the approved indication, which can be extended by two years if a Pediatric Investigation Plan is complied with[122] - The company is required to establish and maintain a pharmacovigilance system and appoint a qualified person for pharmacovigilance (QPPV) to oversee safety profiles and emerging safety concerns[129] - All new MAAs must include a risk management plan (RMP) detailing the risk management system and measures to minimize associated risks[130] - The advertising and promotion of medicinal products must comply with EU directives, prohibiting off-label promotion and direct-to-consumer advertising of prescription medicines[131] - Payments made to physicians in certain EU member states must be publicly disclosed, and agreements often require prior notification and approval[133] - Non-compliance with EU and member state laws may result in administrative, civil, or criminal penalties, including delays or refusals to authorize clinical trials or grant MA[134] - The EU regulates drug-device combination products separately, requiring compliance with both medicinal product and medical device regulations[136] - The EMA evaluates the quality, safety, and efficacy of MAAs submitted through the centralized procedure, including the safety and performance of the medical device[137] - The EU Medical Devices Regulation became effective on May 26, 2021, establishing a uniform regulatory framework across the EU for medical devices[144] - Manufacturers must comply with new requirements under the EU Medical Devices Regulation, including registration in the Eudamed system and assigning unique identifiers to devices[146] - The IVDR fully applies since May 26, 2022, introducing a modernized framework for in vitro diagnostic medical devices[152] - Companion diagnostics now require a conformity assessment by a notified body, with a scientific opinion from the EMA if the medicinal product is authorized through the centralized procedure[155] - The UK Government's Windsor Agreement will take effect on January 1, 2025, transferring regulatory authority for Northern Ireland to the MHRA[156] - The UK regulatory framework for clinical trials is derived from existing EU legislation, with ongoing consultations to streamline approvals and enhance transparency[158] - Manufacturers must report serious incidents and Field Safety Corrective Actions to EU authorities under the reinforced vigilance system[147] - Compliance with ISO 13485:2016 is viewed as a practical way to satisfy essential requirements for medical devices[141] - The EU Medical Devices Directive has been replaced by the EU Medical Devices Regulation, which is directly applicable in member states[144] - Regulatory authorities in the EU have broad powers to enforce compliance, including inspections and penalties for non-compliance[149] - The MHRA has introduced a 150-day assessment and a rolling review procedure to prioritize access to new medicines for patients[159] - All existing EU marketing authorizations (MAs) for centrally authorized products were automatically converted to UK MAs effective January 1, 2021[159] - Medical devices must be registered with the MHRA, and manufacturers outside the UK must appoint a UK responsible person since January 1, 2022[161] - The UK Government has confirmed that core elements of the new medical device regulatory regime are likely to apply from July 2025[162] - CE marked medical devices can be placed on the GB market until the sooner of certificate expiry or June 30, 2028[169] - The UKCA mark will be required for products without existing CE certification from July 2025 to be sold in Great Britain[162] - The Northern Ireland Protocol requires devices marketed in Northern Ireland to follow EU rules, necessitating a CE mark or a 'UKNI' mark[163] Pricing and Reimbursement - Coverage and reimbursement for medical products depend significantly on third-party payors, with no uniform policy existing in the U.S.[175] - The company may need to conduct expensive pharmacoeconomic studies to demonstrate medical necessity and cost-effectiveness for product approval, which could impact sales and financial condition[176] - In the EU, drug pricing must be approved before marketing, with member states controlling reimbursement levels and requiring clinical trials for cost-effectiveness comparisons[177] - The Inflation Reduction Act of 2022 requires manufacturers to negotiate drug prices with Medicare starting in 2026 and imposes penalties for price increases that exceed inflation[183] - The Right to Try Act allows certain patients to access investigational drugs without FDA permission, but manufacturers must submit annual usage summaries to the FDA[185] - Health Technology Assessment (HTA) in the EU significantly influences pricing and reimbursement decisions, with negative assessments potentially undermining reimbursement prospects[188] - The company faces challenges in ensuring adequate payment for products due to government-controlled pricing in many countries, which may delay commercialization[187] - Legislative changes in the U.S. have included reductions in Medicare payments, which will remain in effect through 2032 unless further action is taken[182] - Increased scrutiny over drug pricing has led to state and federal legislation aimed at enhancing transparency and controlling pharmaceutical pricing[184] Human Resources and Management - The company’s future success depends on its ability to retain key personnel and attract qualified talent[17] - The board of directors consists of 6 members, with 2 females and 4 males, reflecting a diverse leadership structure[212] Operational Structure - The company operates as a foreign private issuer, exempting it from certain U.S. regulatory requirements applicable to domestic public companies[190] - The company has not disclosed any significant new strategies or market expansions in the current report[207]

Financial Position - As of December 31, 2023, the company had cash and cash equivalents of $191.1 million and short-term investments of $136.1 million, totaling $326.0 million in PureTech Level cash[174]. - The company believes existing financial assets will be sufficient to fund operations and capital expenditures into at least 2027[183]. - The company has no committed sources of capital beyond existing financial assets, indicating potential future funding needs[186]. - Cash and cash equivalents of $191.1 million and short-term investments of $136.1 million were reported, with a total of $326.0 million in PureTech Level cash[194]. Cash Flow - Net cash used in operating activities decreased to $105.9 million in 2023 from $178.8 million in 2022, a reduction of $72.9 million attributed to lower operating losses[177]. - Net cash provided by investing activities increased to $69.0 million in 2023, compared to a net cash outflow of $107.2 million in 2022, resulting in a $176.2 million improvement[179]. - Net cash provided by financing activities was $78.1 million in 2023, an increase of $108.0 million from a net cash outflow of $29.8 million in 2022, primarily due to a $100.0 million upfront payment from Royalty Pharma[181]. - The company reported a net increase in cash and cash equivalents of $41.2 million for the year ended December 31, 2023, compared to a decrease of $315.8 million in 2022[176]. - The company’s cash flow fluctuations are influenced by various factors, including operating losses and investment activities[174]. Investments - Investments held at fair value increased by $65.9 million to $317.8 million as of December 31, 2023, primarily due to a $73.5 million increase in the value of Karuna shares[189]. - The fair value of investments in common shares of Karuna, Vor, and Akili was $280.7 million, $6.0 million, and $6.1 million, respectively, as of December 31, 2023[199]. - A 10.0 percent adverse change in the market price of Karuna, Vor, and Akili common shares would result in a loss of $29.3 million[200]. Liabilities - Non-current liabilities increased by $126.2 million to $184.4 million, driven by a $100.0 million non-refundable initial payment from Royalty Pharma[191]. - Trade and other payables decreased by $10.7 million to $44.1 million, reflecting the deconsolidation of Vedanta[192]. - Preferred share liability decreased by $27.2 million, primarily due to a $24.6 million decrease from the deconsolidation of Vedanta[193]. Future Outlook - The company expects to incur substantial additional expenditures to support ongoing and future activities, anticipating continued net operating losses for the foreseeable future[184]. - The company does not expect significant effects on operating results or cash flows from changes in market interest rates due to the conservative nature of its investment portfolio[194]. - The company maintains a low exposure to credit risk due to a limited number of counterparties and high credit quality of these counterparties[203].

Exhibit 99.1 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 ...

Industry Overview - The biotechnology and pharmaceutical industries are characterized by intense competition and rapid technological advancements, with a strong emphasis on intellectual property and proprietary products[31]. - The company faces competition from various sources, including major pharmaceutical companies and biotechnology firms, for its product candidates[32]. Product Development and Pipeline - The company has a pipeline that builds on validated biology of known therapeutics, applying unique inventive steps to improve clinical pharmacology, which provides a competitive advantage[31]. - The company is aware of one current drug product candidate targeting galectin-9, expected to enter clinical development in the second half of 2023[34]. - In the field of idiopathic pulmonary fibrosis (IPF), there are two approved drugs with unfavorable tolerability profiles, indicating a sustained unmet need for novel therapies[33]. - In the field of GABAA positive allosteric modulators, there are three approved drugs, with additional candidates in various stages of development[35]. Regulatory Environment - Regulatory processes for drug approval require substantial time and financial resources, including compliance with FDA regulations and conducting extensive clinical trials[39][40]. - The company’s clinical trials must adhere to Good Clinical Practice (GCP) and require approval from independent review boards before initiation[42][43]. - The FDA may condition approval of a new drug application on the sponsor's agreement to conduct additional studies post-approval, known as Phase 4 clinical studies[45]. - The FDA aims to review original biologics or new-molecular-entity drugs within ten months after filing, or six months for priority review applications[51]. - The FDA may refuse to file any NDA or BLA deemed incomplete, requiring resubmission with additional information[51]. Drug Designations and Exclusivity - A product candidate can receive breakthrough therapy designation if preliminary evidence indicates substantial improvement over existing therapies[59]. - Fast track designation allows for more frequent interactions with the review team and may qualify for priority review[57]. - Orphan drug designation is granted for drugs intended to treat rare diseases affecting fewer than 200,000 individuals in the U.S.[65]. - Products with orphan drug designation receive seven years of exclusivity upon first FDA approval for the designated condition[66]. Post-Market Regulations - The FDA may require post-market studies to monitor a product's safety and effectiveness after commercialization[55]. - The FDA requires ongoing compliance with regulations for approved drugs, including record-keeping and reporting of adverse experiences[69]. - Non-compliance with FDA regulations may lead to severe consequences, including product withdrawal and civil penalties[70]. - The FDA enforces strict marketing and promotional regulations, prohibiting off-label promotion of biologics[71]. Medical Device Regulations - Medical devices are classified into three classes based on risk, with Class III devices requiring premarket approval[83]. - Most Class II devices require a 510(k) premarket notification for commercial distribution[84]. - The FDA's 510(k) clearance process typically takes between 3 to 12 months, but may extend longer depending on the need for additional information[85]. - If a device is deemed "not substantially equivalent," it is classified as Class III, requiring more rigorous PMA approval[86]. - The PMA process requires extensive data, including pre-clinical and human clinical trial results, and can take up to several years for FDA review[88]. International Regulations - Approval by one regulatory authority does not guarantee approval by others, as requirements vary significantly across countries[101]. - The Clinical Trials Regulation (CTR) introduces a centralized process for clinical trial applications, allowing a single submission for multi-center trials, streamlining the approval process across EU member states[106]. - Innovative medicinal products in the EU receive eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization (MA), totaling a potential ten years[113]. - The EMA requires a risk management plan (RMP) to be included in all new MAAs, detailing the risk management system and measures to minimize associated risks[123]. Financial Overview - The company considers its working capital sufficient for its present requirements[201]. - The company has no off-balance sheet arrangements that are likely to have a material effect on its financial condition or results of operations[200]. - The company does not have a present obligation to make milestone payments related to its license agreements as of December 31, 2022[198]. - The company’s financial statements comply fully with IFRSs as issued by the IASB[191]. Shareholder Information - The company has a total of 278,461,805 ordinary shares outstanding as of March 31, 2023, with Invesco Asset Management Limited holding 23.3% of the shares[213][215]. - The company has significant shareholders, including Lansdowne Partners Limited with 8.8% and Baillie Gifford & Co with 8.1% of shares[215]. - Invesco Asset Management Limited holds 64,945,474 shares beneficially[1]. - Lansdowne Partners Limited holds 24,528,171 shares beneficially[2]. - Baillie Gifford & Co. holds 22,521,433 shares beneficially[3]. - M&G Investment Management, LTD holds 11,761,956 shares beneficially[4]. - Vanguard Group, Inc. holds 11,256,029 shares beneficially[5]. - Patient Capital Management, Inc. holds 9,806,500 shares beneficially[6]. - Recordati S.p.A. holds 9,554,140 shares beneficially[7]. - The Zohar Family Trusts and Zohar LLC collectively hold 12,564,189 shares[8]. - Langer Family 2020 Trust and Dr. Langer collectively hold 2,955,324 shares[9].

[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)