LYT-300

SPT-300 demonstrated nine times greater allopregnanolone exposure in humans dosed orally than published data for oral allopregnanolone,1 validating Glyph™ platform’s ability to enhance oral bioavailability In a Phase 2a trial, SPT-3002 substantially reduced stress-induced levels of cortisol, supporting Seaport’s planned studies in mood and anxiety disorders, including anxious depression BOSTON--(BUSINESS WIRE)-- PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company, noted that its Founded Entity, Seaport Therapeutics, a biopharmaceutical company that is charting a proven path in neuropsychiatry, today announced two poster presentations detailing the results from multiple clinical trials of SPT-300 at the Society of Biological Psychiatry Annual Meeting in Austin, TX. SPT-300 has been shown to retain the activity and potency of natural allopregnanolone in an oral form and has the potential to capture the breadth of the naturally occurring neurosteroid, which is believed to have significant therapeutic potential in a range of mood and anxiety disorders, including anxious depression. The presentations detail data from the first-in-human, multi-part Phase 1 trial of SPT-300 and the Phase 2a trial of SPT-300 in the Trier Social Stress Test, a validated clinical model of anxiety in healthy volunteers, and include assessment of safety, tolerability, efficacy, oral bioavailability and GABAA receptor target engagement. The full text of the announcement from Seaport is as follows: Seaport Therapeutics Presents Data from Multiple SPT-300 Trials at Society of Biological Psychiatry (SOBP) Annual Meeting SPT-300 demonstrated nine times greater allopregnanolone exposure in humans dosed orally than published data for oral allopregnanolone, validating Glyph™ platform’s ability to enhance oral bioavailability In a Phase 2a trial, SPT-300 substantially reduced stress-induced levels of cortisol, supporting Seaport’s planned studies in mood and anxiety disorders, including anxious depression BOSTON, May 9, 2024 – Seaport Therapeutics, a clinical-stage biopharmaceutical company that is charting a proven path in neuropsychiatry, today announced two poster presentations detailing the results from multiple clinical trials of SPT-300 at the Society of Biological Psychiatry (SOBP) Annual Meeting in Austin, TX. SPT-300 has been shown to retain the activity and potency of natural allopregnanolone in an oral form and has the potential to capture the breadth of the naturally occurring neurosteroid, which is believed to have significant therapeutic potential in a range of mood and anxiety disorders, including anxious depression. The presentations detail data from the first-in-human, multi-part Phase 1 trial of SPT-300 and the Phase 2a trial of SPT-300 in the Trier Social Stress Test (TSST), a validated clinical model of anxiety in healthy volunteers, and include assessment of safety, tolerability, efficacy, oral bioavailability and GABAA receptor target engagement. “These data summarize some of the evidence supporting the core mechanisms of SPT-300 as we advance to later-stage clinical studies. Our proprietary GlyphTM platform allows SPT-300 to be absorbed like a dietary fat through the intestinal lymphatic system and transported into circulation. We believe this will address allopregnanolone’s naturally low bioavailability but retain its endogenous mechanism and range of potential therapeutic effects,” said Michael Chen, Ph.D., Co-founder and Chief Scientific Officer of Seaport Therapeutics. “These data validate that SPT-300 has the potential to make a difference for patients suffering from depression, anxiety and other neuropsychiatric conditions and also provides further validation for our Glyph platform as an elegant solution to multiple key obstacles in neuropsychiatric drug development.” Details of the poster presentations at SOBP Title: A First-in-Human Phase 1 Study of SPT-300, A First-in-Class Orally Bioavailable Prodrug of the Neurosteroid Allopregnanolone that is Absorbed via the Lymphatic System Presenter: Michael C. Chen, Ph.D. The topline results from the completed, multi-part Phase 1 trial of SPT-300 were reported in December 2022. Overall, the Phase 1 trial was well tolerated and evaluated oral bioavailability, safety, tolerability, pharmacokinetics and GABAA target engagement. This study included double-blind single ascending dose, multiple ascending dose and open-label food effect parts. Allopregnanolone is an endogenous neurosteroid of GABAA positive allosteric modulator with validated anti-depressant and anxiolytic activity, but orally administered allopregnanolone is poorly bioavailable. SPT-300 is absorbed through the intestinal lymphatic system, allowing it to avoid first-pass metabolism. Out of 99 participants enrolled in the first-in-human study, allopregnanolone exposure from SPT-300 was approximately nine times greater than published data for oral allopregnanolone. SPT-300 was generally well-tolerated and resulted in pharmacodynamic effects consistent with GABAA positive allosteric modulation. The pharmacodynamic and pharmacokinetic properties demonstrated warrant further clinical development. No treatment-related severe or serious adverse events (AE) were reported, and the most common AE was somnolence, which was mild in all cases. Title: SPT-300, an Oral Prodrug of Allopregnanolone, Potentially Reduces Salivary Cortisol Response to the Trier Social Stress Test in a Randomized, Placebo-Controlled Trial in Healthy Participants Presenter: Michael C. Chen, Ph.D. The topline results from Seaport’s SPT-300 Phase 2a proof-of-concept trial were reported in November 2023. The potential of SPT-300 to reduce physiological stress was tested in a randomized, placebo-controlled study using the TSST, a validated clinical model of anxiety in healthy volunteers exposed to unpredictable, novel, anticipatory and social stress. Among the enrolled healthy volunteers, SPT-300 substantially reduced salivary cortisol at all post-TSST timepoints compared to placebo and SPT-300 treated participants had significantly reduced cortisol versus placebo from baseline to peak (p=0.0001), meeting the study’s primary endpoint and demonstrating that SPT-300 regulates hypothalamic-pituitary-adrenal axis reactivity to acute stress. The most common treatment-emergent adverse event was somnolence (29% SPT-300 vs. 13% placebo), which was transient and mild or moderate. SPT-300 was generally well-tolerated and demonstrated GABA modulatory pharmacological activity that merits further investigation in stress-related mood and anxiety disorders, including anxious depression. About SPT-300 SPT-300 (Glyph-allopregnanolone), an oral prodrug of allopregnanolone, an endogenous neurosteroid, is in clinical stage development for the treatment of mood and anxiety disorders, including anxious depression. Allopregnanolone has demonstrated therapeutic benefit in a range of neuropsychiatric conditions, but it is only approved as an intravenous infusion, which has limited the scope of its clinical use. Using the Glyph platform, SPT-300 retains the activity and potency of endogenous allopregnanolone in an oral form and has the potential to capture the breadth of the natural biological response. In a Phase 2a clinical trial, SPT-300 demonstrated proof-of-concept in a validated clinical model of anxiety in healthy volunteers. SPT-300 also demonstrated oral bioavailability, tolerability and γ-aminobutyric-acid type A (GABAA) receptor target engagement in healthy volunteers in a Phase 1 clinical trial. About the GlyphTM 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. Seaport believes the Glyph technology 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 hepatotoxicity. The Glyph platform has been refined at Seaport to efficiently generate multiple therapeutic candidates within the company’s pipeline. Seaport has exclusively licensed this technology from Monash University based on the pioneering research of the Porter research group, along with the co-inventors from PureTech Health and Seaport. 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. 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 GlyphTM 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 hepatotoxicity and other side effects. Seaport is led by an experienced team that was involved in inventing and advancing KarXT and other neuropsychiatric medicines and are guided by an extensive network of renowned scientists, clinicians and key opinion leaders across neurological specialties. For more information, please visit . 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 two that have received both U.S. FDA clearance and European marketing authorization and a third (KarXT) that has been filed for FDA approval. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points. For more information, visit 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 therapeutic potential of SPT-300, our expectations regarding the Glyph platform including the potential for new treatment applications, Seaport’s development plans 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. 1 U.S. Food and Drug Administration. (2018). FDA drug approval package: Zulresso (Application No. 211,371) 2SPT-300, formerly known as LYT-300

Pictured: Photo illustration of hundred dollar bill and graph/Nicole Bean for BioSpace Two biotech companies, Nvelop Therapeutics and Seaport Therapeutics, emerged from stealth Tuesday with $100 million in financing as they look to target the neuropsychiatric and gene editing spaces, respectively. Seaport is the next venture by some of the key people behind Karuna Therapeutics, the schizophrenia drug developer that Bristol Myers Squibb recently acquired for $14 billion. Daphne Zohar, the founding CEO of PureTech Health and co-founder of Karuna, has helped to set up Seaport and will serve as its CEO. Steven Paul, the Eli Lilly veteran who led Karuna to the BMS buyout, is founder and chair of the board of directors at Seaport. The pair have closed a $100 million Series A financing round that was co-led by ARCH Venture Partners and Sofinnova Investments. Boston-based Seaport will use the money to advance a clinical-stage pipeline of novel neuropsychiatric medicines based on its Glyph technology platform. Glyph is PureTech’s answer to the question of how to traffic small molecule therapeutics directly into the lymphatic system via oral administration. PureTech created Seaport in 2023 to advance certain central nervous system programs. Seaport’s pipeline is led by SPT-3001, an oral prodrug of the endogenous neurosteroid allopregnanolone, that is in development in anxious depression. Allopregnanolone has shown promise in neuropsychiatric conditions but is currently given intravenously, leading PureTech to identify it as a good fit for Glyph and take the candidate, then known as LYT-300, through a Phase IIa trial in acute anxiety. Seaport is also the new home for LYT-320, a prodrug of agomelatine that PureTech disclosed late in 2023. The candidate, now known as SPT-3202, is designed to bypass first-pass metabolism by the liver, enabling the treatment of generalized anxiety disorder at lower doses and eliminating the need to monitor liver function. Massachusetts-based Nvelop was founded in 2022 and has raised $100 million from investors including Newpath Partners, Atlas Venture, F-Prime Capital and 5AM Ventures to fund the development of programmable, non-viral vehicles for the in vivo delivery of therapeutic cargo. Nvelop’s platforms are based on two approaches developed at the Broad Institute of MIT and Harvard and Massachusetts General Hospital by its co-founders David Liu and Keith Joung. Using the platforms, Nvelop hopes to enable delivery of genetic medicines, which have largely been limited to the eyes and liver to date, to cells and tissues that have been historically difficult to reach. The biotech named the diversity of the cargo that the vehicles can carry and safety as other potential advantages over the array of other delivery platforms that companies are developing to unlock the full power of genetic therapies. Jeff Walsh and ​Melissa Bonner, the former chief financial officer and head of research of bluebird respectively, have come on board to oversee the development of the platforms. Walsh has taken up the CEO post and Bonner is serving as chief scientific officer. Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.