Deupirfenidone

21 October 2024 PureTech Health plc PureTech Founded Entity Seaport Therapeutics Closes $225 Million Oversubscribed Series B Financing Round Financing led by General Atlantic with participation from other top tier investors Proceeds will support key clinical milestones in Seaport's pipeline of first and best-in-class neuropsychiatric medicines PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company, noted that its Founded Entity, Seaport Therapeutics, ("Seaport") a biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced the closing of an oversubscribed $225 million Series B financing round. The syndicate was led by General Atlantic, a leading global growth investor, with participation from funds and accounts advised by T. Rowe Price Associates, Inc., Foresite Capital, Invus, Goldman Sachs Alternatives, CPP Investments, and other new investors. Founding investors ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and co-founder PureTech also participated. Following the Series B financing, PureTech will hold equity ownership in Seaport of 36.7% on a diluted basis. The financing brings the total capital raised by Seaport to $325 million since the Company's launch in April 2024. Seaport will use the proceeds to advance its clinical-stage pipeline of first and best-in-class medicines through important clinical milestones as well as further advance the capabilities of the Glyph™ technology platform, which has demonstrated clinical proof-of-concept. The programs in Seaport's pipeline use the Glyph platform, which is designed to enable and enhance oral bioavailability, avoid first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects to advance clinically active drugs that were previously hindered by those limitations. Commenting on today's announcement, Bharatt Chowrira, PhD, JD, Chief Executive Officer of PureTech and a member of the Seaport Board of Directors, said: "We're very pleased with Seaport's $225 million Series B financing. Led by a syndicate of top-tier investors, this milestone highlights the significant progress we're making across our portfolio. The strong support from this stellar investor group not only reinforces the value generated by our unique R&D engine but also underscores our commitment to advancing transformative therapies for patients. As we look ahead to the upcoming data readout for our internal LYT-100 (deupirfenidone) program, we're excited to continue driving innovation across our portfolio with the goal of delivering impactful treatments that address significant medical needs." The full text of the announcement from Seaport is as follows: Seaport Therapeutics Closes $225 Million Oversubscribed Series B Financing Round Financing led by General Atlantic with participation from T. Rowe Price Associates, Foresite Capital, Invus, Goldman Sachs Alternatives, Canada Pension Plan Investment Board (CPP Investments) as well as other new investors Founding investors ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and PureTech Health also participated Proceeds will support key clinical milestones in Seaport's pipeline of first and best-in-class neuropsychiatric medicines BOSTON, October 21, 2024 - Seaport Therapeutics ("Seaport"), a clinical-stage biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced the closing of an oversubscribed $225 million Series B financing round. The syndicate was led by General Atlantic, a leading global growth investor, with participation from funds and accounts advised by T. Rowe Price Associates, Inc., Foresite Capital, Invus, Goldman Sachs Alternatives, CPP Investments, and other new investors. Founding investors ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and co-founder PureTech Health also participated. The financing brings the total capital raised by Seaport to $325 million since the company's launch in April 2024. Seaport will use the proceeds to advance its clinical-stage pipeline of first and best-in-class medicines through important clinical milestones as well as further advance the capabilities of the Glyph™ technology platform, which has demonstrated clinical proof-of-concept. "We are grateful to have the partnership of this incredible group of new and existing investors who share our commitment of delivering better medicines for those suffering from depression, anxiety and other neuropsychiatric disorders," said Daphne Zohar, Founder and CEO of Seaport Therapeutics. "Seaport is advancing novel therapeutics that have proven clinical efficacy but had previously been held back by an issue we can now address with our Glyph platform. This financing enables the important clinical work that brings us another step closer to delivering new medicines to make a difference in the lives of patients and their families." "We are excited to partner with Daphne Zohar, Steve Paul and the team at Seaport," said Brett Zbar, M.D., Managing Director and Global Head of Life Sciences at General Atlantic. "We are impressed with the team's outstanding CNS clinical track record, as well as Seaport's Glyph platform and innovative pipeline. The approach to clinical development and trial design demonstrates the deep neuropsychiatric expertise around the table, which we believe offers unique advantages that will contribute to Seaport's success. We look forward to supporting the company's next phase of development." The programs in Seaport's pipeline use the Glyph platform, which is designed to enable and enhance oral bioavailability, avoid first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects to advance clinically active drugs that were previously hindered by those limitations. The most advanced therapeutic candidate in the pipeline is SPT-300, an oral prodrug of allopregnanolone that is being advanced into a Phase 2b study for major depressive disorder with or without anxious distress that has the potential to be registration-enabling. Allopregnanolone is an endogenous neurosteroid with clinically validated rapid anti-depressant and anxiolytic activity, and SPT-300 retains this activity in an oral form. "The development of important new neuropsychiatric medicines is often halted due to poor drug-like properties or unacceptable tolerability, challenges that our Glyph platform can now uniquely address," said Steve Paul, M.D., Founder and Board Chair at Seaport Therapeutics. "For instance, xanomeline was an effective drug that faced tolerability challenges, but once resolved, led to the FDA approval of Cobenfy™ (formerly KarXT) for schizophrenia. With Glyph, we believe each of Seaport's programs could create similar life-changing value for patients." SPT-320, a novel prodrug of agomelatine being advanced into Phase 1 studies for the treatment of generalized anxiety disorder (GAD), has the potential to be the first new mechanism for GAD in decades. SPT-320 uses Glyph to bypass liver first-pass metabolism and thus has the potential to lower the dose and reduce liver exposure while retaining efficacious systemic exposure of agomelatine that has been validated in multiple clinical studies in GAD. The reduction in dose has the potential to eliminate the need for liver function monitoring that has previously held back agomelatine's development in GAD. SPT-348, a prodrug of a non-hallucinogenic neuroplastogen in development for the treatment of mood and other neuropsychiatric disorders, uses Glyph to create a potential first-in-class treatment. Beyond these programs, Seaport has multiple discovery and preclinical programs underway. About the Glyph™ Platform Glyph is Seaport's proprietary technology platform which uses the lymphatic system to enable and enhance the oral administration of drugs. With the Glyph platform, drugs are absorbed like dietary fats through the intestinal lymphatic system and transported into circulation. The Glyph platform has the potential to be widely applied to many therapeutic molecules that have high first-pass metabolism leading to low bioavailability and/or side effects, including liver enzyme elevations or hepatotoxicity. Seaport exclusively licensed this technology from Monash University based on the pioneering research of the Porter Research Group. Advanced initially at PureTech Health and now at Seaport, Glyph has been applied to create therapeutic candidates for the company's pipeline resulting in new intellectual property, including composition of matter. The group and its collaborators have published research in Nature Metabolism, Frontiers in Pharmacology and the Journal of Controlled Release supporting the Glyph platform's capabilities. See Glyph in action here. About Seaport Therapeutics Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph technology platform. All the therapeutic candidates in its pipeline of first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects. Seaport is led by an experienced team that invented and advanced important neuropsychiatric medicines and are guided by an extensive network of renowned scientists, clinicians and key opinion leaders. For more information, please visit www.seaporttx.com. Ownership Information PureTech contributed $14.4 million to the Series B financing and now holds equity ownership in Seaport of 36.7 percent on a diluted basis. Additionally, as the founder of Seaport, PureTech has a right to royalty payments on a percentage of net sales of any commercialized product as well as the right under the terms of the license agreement with Seaport to receive milestone payments upon the achievement of certain regulatory approvals and a percentage of sublicense income. About PureTech Health PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 29 therapeutics and therapeutic candidates, including three that have been approved by the U.S. Food and Drug Administration. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points. For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh. Cautionary Note Regarding Forward-Looking Statements This press release contains statements that are or may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those related to additional milestones or royalties potentially due to PureTech, Seaport's development plans for its pipeline of therapeutics for the treatment of depression, anxiety and other neuropsychiatric disorders, potential benefits to patients, the anticipated use of proceeds from the Series B financing and Seaport's and our future prospects, developments and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2023, filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise. Contact: PureTech Public Relations publicrelations@puretechhealth.com Investor Relations IR@puretechhealth.com UK/EU Media Ben Atwell, Rob Winder +44 (0) 20 3727 1000 puretech@fticonsulting.com US Media Justin Chen +1-609-578-7230 jchen@tenbridgecommunications.com END MSCDXBDGBUDDGSG

9 October 2024 PureTech Health plc PureTech Presents Research Highlighting Burden of Idiopathic Pulmonary Fibrosis (IPF) and Use of a Bayesian Statistical Analysis for LYT-100 (Deupirfenidone) at CHEST 2024 Annual Meeting IPF patient survey provides new insights into disease burden and patient experience one decade after the approval of the first antifibrotics for IPF Clinical abstract reviews the ability of Bayesian analysis to maximize statistical power and reduce the number of patients on placebo in Phase 2b ELEVATE IPF trial of LYT-100 Topline data from the Phase 2b ELEVATE IPF trial of LYT-100 expected by the end of 2024 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, presented two oral presentations and one poster supporting its clinical and patient engagement strategies related to LYT-100 (deupirfenidone) for the treatment of idiopathic pulmonary fibrosis (IPF) at the CHEST 2024 Annual Meeting in Boston, Massachusetts. "This month marks a decade since the first two antifibrotics for the treatment of IPF were approved, and since then, limited therapeutic advances have been made and people with IPF still face substantial challenges," said Camilla Graham, MD, MPH, Vice President of Medical Affairs at PureTech Health. "At PureTech, we are investing in changing this paradigm and this research highlights ongoing gaps with symptom management and supportive care in IPF. We hope this research will help improve communications between people with IPF and their healthcare teams. It also informs our work to develop a new IPF treatment option, which we believe will address key limitations of the current standard-of-care medicines." PureTech presented qualitative and quantitative research that highlights both the burden of IPF as well as gaps in disease management that exacerbate the quality of life for people with IPF. The 90-person survey found that the majority of participants experience a high burden of disease that interferes with their normal activities, including shortness of breath (86%), fatigue (78%) and cough (77%). In addition to the burden of the disease itself, comorbidities, side effects of antifibrotic treatment and the use of supplemental oxygen interfere with patients' quality of life, suggesting a need for improved interventions to manage symptoms. Beyond this, PureTech's research revealed commonalities and differences in the patient experience for those receiving care at interstitial lung disease (ILD) centers (n=45) versus community pulmonary practices (CPP) (n=45). When asked about their top resources for IPF information, nearly all people in both care settings listed their pulmonologist as their primary source, and the majority in each were very satisfied with their communications about their IPF diagnosis. Antifibrotic treatment rates at ILD centers and CPPs were similar, but differences existed in perceived communication around antifibrotic treatment options. 76% of people receiving care in ILD centers reported that their pulmonologist had discussed both FDA-approved antifibrotics with them, while this was only true of 56% of those receiving care at CPPs. Across a series of quality-of-life parameters, patients at CPPs indicated a higher impact and severity of their disease than patients at ILD centers, reflecting an important discrepancy that merits further investigation. PureTech also presented a clinical abstract reviewing its plan to evaluate the primary outcome of the Phase 2b ELEVATE IPF clinical trial using a prespecified Bayesian approach. ELEVATE IPF is PureTech's randomized, double-blind, placebo-controlled, dose-finding study designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 in patients with IPF compared to placebo. The trial will also assess the relative efficacy of two doses of LYT-100. Participants have been randomized in a ratio of 1:1:1:1 to receive either 550 mg of LYT-100, 825 mg of LYT-100, pirfenidone or placebo three times a day (TID) for up to 26 weeks and have the option to enroll in an open-label extension. The primary endpoint is the rate of decline in Forced Vital Capacity (FVC) for the combined LYT-100 arms versus placebo over the 26-week treatment period using a Bayesian linear mixed effects model including dynamic borrowing. This approach augments the placebo arm sample size with external placebo data from historical IPF trials. A Bayesian approach has the advantage of enhancing overall statistical power and improving decision-making while limiting the number of patients required to be treated with placebo in a fatal disease. This approach has been used previously in Phase 2 trials of novel IPF therapeutics. "Bayesian dynamic borrowing allows us to leverage historical trial data for the placebo arm to maximize the number of patients exposed to active treatment arms and minimize the number exposed to placebo," said Carol Ann Satler, MD, PhD, Senior Director, Clinical Development at PureTech. "IPF is a rare, fatal disease, underscoring the importance of efficient clinical trial design. Bayesian analyses have previously been leveraged in IPF studies for this reason, especially given the substantial historical placebo dataset in IPF, and we look forward to sharing results from our Phase 2b trial by the end of this year." Topline results from the Phase 2b ELEVATE IPF trial are expected by the end of 2024. A streamlined development program for LYT-100 is planned using the same endpoints that have supported past IPF product approvals. Pending positive clinical outcomes and regulatory feedback, the program will advance into a Phase 3 clinical trial. PureTech believes the results of the Phase 2b trial, together with a successful Phase 3 trial, could serve as the basis for registration in the U.S. and other geographies. About Idiopathic Pulmonary Fibrosis (IPF) IPF is a rare, progressive and fatal lung disease with a median survival of 2-5 years.[1] Pirfenidone is one of only two drugs approved to treat IPF, and for those patients able to tolerate treatment, it has been shown to improve survival by approximately 2.5 years compared to supportive care alone.1 However, tolerability issues with both of the standard-of-care drugs result in patients discontinuing treatment or reducing their dose. This contributes to nearly three out of every four people with IPF choosing to forego treatment with these otherwise efficacious medicines.[2] About LYT-100 (Deupirfenidone) LYT-100 (deupirfenidone) is being advanced for the treatment of conditions involving inflammation and fibrosis, including IPF. It is a deuterated form of pirfenidone that is designed to retain the beneficial pharmacology and clinically-validated efficacy of pirfenidone with a highly differentiated PK profile. LYT-100 has also demonstrated favorable tolerability across multiple clinical studies in more than 400 individuals. Pirfenidone is one of the two standard-of-care treatments approved for IPF, along with nintedanib, both of which are efficacious but associated with significant tolerability issues. These tolerability issues result in treatment discontinuations and/or dose reductions below the FDA-approved dose, thereby limiting the effectiveness of these otherwise efficacious medicines. With LYT-100, PureTech aims to deliver better outcomes for patients by enabling individuals to maintain comparable or higher pirfenidone-equivalent doses for longer. PureTech believes LYT-100 has the potential both to supplant the current standard-of-care treatments and to serve a larger market of patients who are unable to tolerate current therapies. Topline data for the global Phase 2 ELEVATE IPF trial are expected by the end of 2024. About PureTech Health PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 29 therapeutics and therapeutic candidates, including three that have been approved by the U.S. Food and Drug Administration. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points. For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh. Cautionary Note Regarding Forward-Looking Statements This press release contains statements that are or may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those related to the LYT-100 development program and development plans, its potential benefits to patients, the timing for results from the Phase 2b clinical trial of LYT-100, the advancement of the program into a Phase 3 trial, and our future prospects, developments and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2023, filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise. Contact: PureTech Public Relations publicrelations@puretechhealth.com UK/EU Media Ben Atwell, Rob Winder +44 (0) 20 3727 1000 puretech@fticonsulting.com US Media Justin Chen +1-609-578-7230 jchen@tenbridgecommunications.com [1] Fisher, M., Nathan, S. D., Hill, C., Marshall, J., Dejonckheere, F., Thuresson, P., & Maher, T. M. (2017). Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis. Journal of Managed Care & Specialty Pharmacy, 23(3-b Suppl), S17-S24. https://doi.org/10.18553/jmcp.2017.23.3-b.s17 [2] Dempsey TM, Payne S, Sangaralingham L, Yao X, Shah ND, Limper AH. Adoption of the Antifibrotic Medications Pirfenidone and Nintedanib for Patients with Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2021 Jul;18(7):1121-1128 END NRAUPGRWUUPCPWR