SPTX

Trial met its primary endpoint, showing that evening dosing of GlyphAllo at 375 mg did not impair next-morning driving performance compared to placebo on Day 5, following multiple-day dosing Key secondary endpoint also met, showing a single evening dose of 250 mg GlyphAllo did not impair next-morning driving performance compared to placebo on Day 2 GlyphAllo was well-tolerated, with no serious adverse events reported Company plans to submit results to the U.S. Food and Drug Administration as part of the ongoing development program for GlyphAllo BOSTON, September 09, 2026--(BUSINESS WIRE)--Seaport Therapeutics, Inc., (Nasdaq: SPTX) ("Seaport" or the "Company"), a clinical-stage therapeutics company that is inventing and developing novel neuropsychiatric medicines, today announced positive topline results from the Phase 1 Driving Simulation Trial of GlyphAllo™ (SPT-300 or Glyph Allopregnanolone), a novel, Glyphed oral prodrug of allopregnanolone, in healthy volunteers. The trial evaluated the 375 mg dose of GlyphAllo, the highest dose currently being investigated in the Phase 2b BUOY-1 trial, as well as a 250 mg dose. The trial met its primary endpoint demonstrating that evening dosing of GlyphAllo at 375 mg did not impair next-morning driving performance compared to placebo on Day 5, following multiple-day dosing. The key secondary endpoint was also met, showing that a single 250 mg dose of GlyphAllo did not impair next-morning driving performance compared to placebo on Day 2. "We are very pleased by the results which showed no next-morning driving impairment at either dose evaluated. The trial used a validated driving simulator and trial design with an evening dosing regimen consistent with the Phase 2b BUOY-1 trial and GlyphAllo’s intended clinical use," said Daphne Zohar, Co-founder and Chief Executive Officer of Seaport Therapeutics. "We believe that GlyphAllo has the potential to deliver the benefits of allopregnanolone without next-morning effects on driving. These results further reinforce our view that GlyphAllo offers meaningful differentiation as we advance it as a potential first-in-class treatment for major depressive disorder." The trial also included a 7.5 mg dose of zopiclone as the positive control. Zopiclone did produce statistically significant impairment relative to both GlyphAllo and placebo on both Day 2 and Day 5, confirming the assay sensitivity of the trial and its ability to detect an effect on driving performance. GlyphAllo was well-tolerated at all doses, with most adverse events being mild and transient and no serious adverse events reported. Together with previously generated clinical and preclinical data and a favorable safety and tolerability profile observed to date, these findings provide additional support for the differentiation of the overall profile of GlyphAllo as the program advances in the ongoing potentially registration-enabling trial in major depressive disorder (MDD). Seaport plans to submit the results to the U.S. Food and Drug Administration as part of the ongoing development program for GlyphAllo. The Company also plans to present additional analyses at upcoming scientific meetings. Seaport is actively enrolling patients in BUOY-1, a two-arm, global, randomized, double-blind, placebo-controlled, potentially registration-enabling Phase 2b trial investigating the safety and efficacy of GlyphAllo in patients with MDD, with or without anxious distress. The Company expects to announce topline data from the BUOY-1 trial in the first half of 2027. About the Phase 1 Driving Simulation Trial The randomized, double-blind, placebo- and active-controlled, three-way, crossover Phase 1 trial was designed to investigate the effects of evening doses of GlyphAllo on next-morning simulated driving performance in 33 healthy volunteers. Participants received GlyphAllo at bedtime and underwent driving performance assessments the following morning, approximately nine hours following GlyphAllo administration, consistent with established driving simulation trial methodologies. Driving performance was assessed using the Cognitive Research Corporation Driving Simulator-MiniSim, a widely accepted and validated tool used in clinical development. The primary endpoint was Standard Deviation of Lateral Position (SDLP), a gold standard measure of lane weaving commonly used in clinical trials to evaluate driving impairment. SDLP was assessed on Day 2 following a single 250 mg dose and then on Day 5 following multiple-day dosing of GlyphAllo at 375 mg. The trial also included a 7.5 mg dose of zopiclone as a positive control. GlyphAllo, including the 375 mg dose, the highest dose being evaluated in the ongoing Phase 2b BUOY-1 trial, has previously demonstrated desirable pharmacokinetics and pharmacodynamics, and a favorable safety and tolerability profile in Phase 1 and Phase 2a clinical trials. About GlyphAllo (SPT-300 or Glyph Allopregnanolone) GlyphAllo (SPT-300 or Glyph Allopregnanolone) is a novel, Glyphed oral prodrug of allopregnanolone, an endogenous molecule that has been clinically validated in third-party trials for the treatment of postpartum depression, or PPD, a form of major depressive disorder (MDD), that shares symptomatology with MDD, as a rapidly acting antidepressant with anxiolytic and sleep-promoting effects. GlyphAllo is designed to overcome bioavailability limitations of allopregnanolone and deliver rapid and durable efficacy in MDD. Seaport has demonstrated in a Phase 1 clinical trial that GlyphAllo reaches therapeutically relevant exposures with oral dosing, and in a Phase 2a clinical trial, GlyphAllo demonstrated initial proof-of-concept with an objective biomarker of stress in healthy volunteers and a favorable tolerability profile. Seaport is actively enrolling patients in BUOY-1, a two-arm, global, randomized, double-blind, placebo-controlled, potentially registration-enabling Phase 2b trial investigating the safety and efficacy of GlyphAllo in patients with MDD with or without anxious distress. Topline data from the BUOY-1 trial are expected in the first half of 2027. About Seaport Therapeutics Seaport Therapeutics (Nasdaq: SPTX) is a clinical-stage therapeutics company focused on inventing and developing new medicines for patients with depression, anxiety, and other debilitating neuropsychiatric disorders. Through its differentiated approach, the Company identifies clinically validated mechanisms with established efficacy and safety which had historically been limited by high first-pass metabolism, low bioavailability, and/or side effects. Seaport applies its proprietary Glyph™ platform to overcome those limitations and invent innovative oral therapies. With an experienced team of industry leaders, Seaport has a proven track record in neuropsychiatry drug discovery and development and delivering successful business outcomes. Seaport aims to develop novel, leading treatment options that will make a significant impact for patients and their families. For more information, please visit www.seaporttx.com. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding our product candidates, including: the ongoing Phase 2b BUOY-1 trial of GlyphAllo, the enrollment status and anticipated timing of data readouts, including our anticipated readout of topline data for GlyphAllo in the first half of 2027, the interpretation and clinical regulatory implications of the topline results from the Phase 1 Driving Simulation Trial of GlyphAllo in healthy volunteers, and Seaport’s plans to submit the results to the U.S. Food and Drug Administration. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect Seaport’s business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company’s research and development activities, including with respect to the Phase 2b BUOY-1 trial; risks that interim results are not predictive of final results in a clinical trial. Seaport’s ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to Seaport’s preclinical and clinical development activities; the Company’s dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Seaport’s ability to attract, integrate and retain key personnel; risks related to the Company’s financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Seaport’s intellectual property protections; and risks related to the competitive landscape for Seaport’s product candidates; as well as other risks and uncertainties described in "Risk Factors," in Seaport’s Quarterly Report on Form 10-Q for the three months ended June 30, 2026 filed with the Securities and Exchange Commission ("SEC"), as well as in subsequent filings with the SEC. Seaport expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Seaport uses and intends to continue to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. View source version on businesswire.com: https://www.businesswire.com/news/home/20260909055068/en/ Contacts Seaport Therapeutics Media Contact: Shannon CostelloVice President, [email protected] Investor Contact: Adam Bero, Ph.D.Vice President, Head of Investor [email protected]

BOSTON, September 09, 2026--(BUSINESS WIRE)--PureTech Health plc (LSE: PRTC) ("PureTech" or the "Company"), a hub-and-spoke biotherapeutics company dedicated to giving life to science and transforming innovation into value, notes that its Founded Entity, Seaport Therapeutics, today announced positive topline results from the Phase 1 Driving Simulation Trial of GlyphAllo™ (SPT-300 or Glyph Allopregnanolone) in healthy volunteers. The trial met its primary endpoint, demonstrating that evening dosing of GlyphAllo at 375 mg did not impair next-morning driving performance compared to placebo on Day 5, following multiple-day dosing. Seaport plans to submit the results to the U.S. Food and Drug Administration as part of the ongoing development program for GlyphAllo. GlyphAllo is a novel, Glyphed oral prodrug of allopregnanolone in development for the potential treatment of major depressive disorder (MDD). Seaport is actively enrolling patients in BUOY-1, a two-arm, global, randomized, double-blind, placebo-controlled, potentially registration-enabling Phase 2b trial investigating the safety and efficacy of GlyphAllo in patients with MDD, with or without anxious distress. Seaport expects to announce topline data from the BUOY-1 trial in the first half of 2027. The full text of the announcement from Seaport is as follows: Seaport Therapeutics Reports Positive Topline Results from Phase 1 Driving Simulation Trial of GlyphAllo™ in Healthy Volunteers Trial met its primary endpoint, showing that evening dosing of GlyphAllo at 375 mg did not impair next-morning driving performance compared to placebo on Day 5, following multiple-day dosing Key secondary endpoint also met, showing a single evening dose of 250 mg GlyphAllo did not impair next-morning driving performance compared to placebo on Day 2 GlyphAllo was well-tolerated, with no serious adverse events reported Company plans to submit results to the U.S. Food and Drug Administration as part of the ongoing development program for GlyphAllo Seaport Therapeutics, Inc., (Nasdaq: SPTX) ("Seaport" or the "Company"), a clinical-stage therapeutics company that is inventing and developing novel neuropsychiatric medicines, today announced positive topline results from the Phase 1 Driving Simulation Trial of GlyphAllo™ (SPT-300 or Glyph Allopregnanolone), a novel, Glyphed oral prodrug of allopregnanolone, in healthy volunteers. The trial evaluated the 375 mg dose of GlyphAllo, the highest dose currently being investigated in the Phase 2b BUOY-1 trial, as well as a 250 mg dose. The trial met its primary endpoint demonstrating that evening dosing of GlyphAllo at 375 mg did not impair next-morning driving performance compared to placebo on Day 5, following multiple-day dosing. The key secondary endpoint was also met, showing that a single 250 mg dose of GlyphAllo did not impair next-morning driving performance compared to placebo on Day 2. "We are very pleased by the results which showed no next-morning driving impairment at either dose evaluated. The trial used a validated driving simulator and trial design with an evening dosing regimen consistent with the Phase 2b BUOY-1 trial and GlyphAllo’s intended clinical use," said Daphne Zohar, Co-founder and Chief Executive Officer of Seaport Therapeutics. "We believe that GlyphAllo has the potential to deliver the benefits of allopregnanolone without next-morning effects on driving. These results further reinforce our view that GlyphAllo offers meaningful differentiation as we advance it as a potential first-in-class treatment for major depressive disorder." The trial also included a 7.5 mg dose of zopiclone as the positive control. Zopiclone did produce statistically significant impairment relative to both GlyphAllo and placebo on both Day 2 and Day 5, confirming the assay sensitivity of the trial and its ability to detect an effect on driving performance. GlyphAllo was well-tolerated at all doses, with most adverse events being mild and transient and no serious adverse events reported. Together with previously generated clinical and preclinical data and a favorable safety and tolerability profile observed to date, these findings provide additional support for the differentiation of the overall profile of GlyphAllo as the program advances in the ongoing potentially registration-enabling trial in major depressive disorder (MDD). Seaport plans to submit the results to the U.S. Food and Drug Administration as part of the ongoing development program for GlyphAllo. The Company also plans to present additional analyses at upcoming scientific meetings. Seaport is actively enrolling patients in BUOY-1, a two-arm, global, randomized, double-blind, placebo-controlled, potentially registration-enabling Phase 2b trial investigating the safety and efficacy of GlyphAllo in patients with MDD, with or without anxious distress. The Company expects to announce topline data from the BUOY-1 trial in the first half of 2027. About the Phase 1 Driving Simulation Trial The randomized, double-blind, placebo- and active-controlled, three-way, crossover Phase 1 trial was designed to investigate the effects of evening doses of GlyphAllo on next-morning simulated driving performance in 33 healthy volunteers. Participants received GlyphAllo at bedtime and underwent driving performance assessments the following morning, approximately nine hours following GlyphAllo administration, consistent with established driving simulation trial methodologies. Driving performance was assessed using the Cognitive Research Corporation Driving Simulator-MiniSim, a widely accepted and validated tool used in clinical development. The primary endpoint was Standard Deviation of Lateral Position (SDLP), a gold standard measure of lane weaving commonly used in clinical trials to evaluate driving impairment. SDLP was assessed on Day 2 following a single 250 mg dose and then on Day 5 following multiple-day dosing of GlyphAllo at 375 mg. The trial also included a 7.5 mg dose of zopiclone as a positive control. GlyphAllo, including the 375 mg dose, the highest dose being evaluated in the ongoing Phase 2b BUOY-1 trial, has previously demonstrated desirable pharmacokinetics and pharmacodynamics, and a favorable safety and tolerability profile in Phase 1 and Phase 2a clinical trials. About GlyphAllo (SPT-300 or Glyph Allopregnanolone) GlyphAllo (SPT-300 or Glyph Allopregnanolone) is a novel, Glyphed oral prodrug of allopregnanolone, an endogenous molecule that has been clinically validated in third-party trials for the treatment of postpartum depression, or PPD, a form of major depressive disorder (MDD), that shares symptomatology with MDD, as a rapidly acting antidepressant with anxiolytic and sleep-promoting effects. GlyphAllo is designed to overcome bioavailability limitations of allopregnanolone and deliver rapid and durable efficacy in MDD. Seaport has demonstrated in a Phase 1 clinical trial that GlyphAllo reaches therapeutically relevant exposures with oral dosing, and in a Phase 2a clinical trial, GlyphAllo demonstrated initial proof-of-concept with an objective biomarker of stress in healthy volunteers and a favorable tolerability profile. Seaport is actively enrolling patients in BUOY-1, a two-arm, global, randomized, double-blind, placebo-controlled, potentially registration-enabling Phase 2b trial investigating the safety and efficacy of GlyphAllo in patients with MDD with or without anxious distress. Topline data from the BUOY-1 trial are expected in the first half of 2027. About Seaport Therapeutics Seaport Therapeutics (Nasdaq: SPTX) is a clinical-stage therapeutics company focused on inventing and developing new medicines for patients with depression, anxiety, and other debilitating neuropsychiatric disorders. Through its differentiated approach, the Company identifies clinically validated mechanisms with established efficacy and safety which had historically been limited by high first-pass metabolism, low bioavailability, and/or side effects. Seaport applies its proprietary Glyph™ platform to overcome those limitations and invent innovative oral therapies. With an experienced team of industry leaders, Seaport has a proven track record in neuropsychiatry drug discovery and development and delivering successful business outcomes. Seaport aims to develop novel, leading treatment options that will make a significant impact for patients and their families. For more information, please visit www.seaporttx.com. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding our product candidates, including: the ongoing Phase 2b BUOY-1 trial of GlyphAllo, the enrollment status and anticipated timing of data readouts, including our anticipated readout of topline data for GlyphAllo in the first half of 2027, the interpretation and clinical regulatory implications of the topline results from the Phase 1 Driving Simulation Trial of GlyphAllo in healthy volunteers, and Seaport’s plans to submit the results to the U.S. Food and Drug Administration. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect Seaport’s business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company’s research and development activities, including with respect to the Phase 2b BUOY-1 trial; risks that interim results are not predictive of final results in a clinical trial. Seaport’s ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to Seaport’s preclinical and clinical development activities; the Company’s dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Seaport’s ability to attract, integrate and retain key personnel; risks related to the Company’s financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Seaport’s intellectual property protections; and risks related to the competitive landscape for Seaport’s product candidates; as well as other risks and uncertainties described in "Risk Factors," in Seaport’s Quarterly Report on Form 10-Q for the three months ended June 30, 2026 filed with the Securities and Exchange Commission ("SEC"), as well as in subsequent filings with the SEC. Seaport expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Seaport uses and intends to continue to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. About PureTech Health PureTech Health is a hub-and-spoke biotherapeutics company dedicated to giving life to science and transforming innovation into value. We do this through a proven, capital-efficient R&D model focused on opportunities with validated pharmacology and untapped potential to address significant patient needs. This strategy has produced dozens of therapeutic candidates, including three that have received U.S. FDA approval. By identifying, shaping, and de-risking these high-conviction assets, and scaling them through dedicated structures backed by external capital, we accelerate their path to patients while creating sustainable value for shareholders. For more information, visit www.puretechhealth.com or connect with us on LinkedIn and 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 those related to Seaport's development plans for its pipeline of neuropsychiatric therapeutics based on the Glyph™ Platform, the potential of GlyphAllo™ (SPT-300™ or Glyph Allopregnanolone) and the Glyph platform, the broader applicability of the platform, the addressable market for Seaport's product candidates, if approved, potential benefits to patients, 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, 2025, 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. View source version on businesswire.com: https://www.businesswire.com/news/home/20260909957620/en/ Contacts PureTech Public [email protected] Investor [email protected]

Enrollment in Phase 2b BUOY-1 trial of GlyphAllo™ in major depressive disorder (MDD) is on track with topline data expected in 1H 2027 Phase 1 driving simulation trial of GlyphAllo on track to report topline data in 2H 2026 Following positive data from completed Phase 1 proof-of-concept trial of GlyphAgo™, Company plans to initiate Phase 2a trial in patients with generalized anxiety disorder (GAD) and sleep disturbance in 2H 2026, and Phase 2b trial in patients with GAD in 1H 2027 Glyph2BLSD™, a novel non-hallucinogenic neuroplastogen, is on track to complete first-in-human-enabling studies by the end of 2027 Upsized IPO in May generated $260.0 million in gross proceeds; $427.3 million in cash, cash equivalents, and investments as of June 30, 2026, expected to fund operations into 2029 BOSTON, August 03, 2026--(BUSINESS WIRE)--Seaport Therapeutics, Inc., (Nasdaq: SPTX) ("Seaport" or the "Company"), a clinical-stage therapeutics company that is inventing and developing novel neuropsychiatric medicines, today announced financial results for the second quarter of 2026 and highlighted recent corporate and clinical progress. "The second quarter of 2026 was marked by two major milestones for Seaport – positive results from our Phase 1 proof-of-concept trial of GlyphAgo and the successful completion of our IPO," said Daphne Zohar, Co-Founder and Chief Executive Officer at Seaport Therapeutics. "We believe the GlyphAgo Phase 1 data package significantly derisks future clinical development of this program, and we expect to initiate Phase 2 development of GlyphAgo in generalized anxiety disorder in the second half of this year. "In parallel, we are executing on two clinical trials of our lead product candidate, GlyphAllo, including the Phase 2b BUOY-1 trial in patients with major depressive disorder, and the Phase 1 driving simulation trial in healthy volunteers. Both trials are on track, and we look forward to data from the driving simulation trial in the coming months, ahead of topline data from BUOY-1 in the first half of next year. "With the data that continue to emerge from psychedelics in neuropsychiatry, including LSD, we are excited about the potential of Glyph2BLSD, which is designed to harness the pharmacology of a psychedelic without causing a ‘trip,’ and may therefore avoid limitations of psychedelics, including the need for supervised administration. "With a strong balance sheet and cash runway through multiple important clinical data readouts for our two lead programs, we are well-positioned to advance our pipeline through key inflection points and develop novel treatments for the hundreds of million people living with depression and anxiety." Recent Business Updates and Anticipated Milestones GlyphAllo (SPT-300 or Glyph Allopregnanolone) Program for Patients with Major Depressive Disorder (MDD) Enrollment on Track in Phase 2b BUOY-1 Trial in MDD. Seaport is actively enrolling patients in BUOY-1, a two-arm, global, randomized, double-blind, placebo-controlled, potentially registration-enabling Phase 2b trial investigating the safety and efficacy of GlyphAllo in patients with MDD with or without anxious distress. Topline data from the BUOY-1 trial are expected in the first half of 2027. Phase 1 Driving Simulation Trial in Healthy Volunteers is On Track - Topline data Expected in 2H 2026. This randomized, double-blind, placebo-controlled Phase 1 trial is designed to evaluate the potential impact of multiple dose levels of GlyphAllo on simulated driving performance in healthy volunteers. In this trial, GlyphAllo is dosed in the evening, and simulated driving performance is assessed the following morning, approximately nine hours following GlyphAllo administration, as is typical in driving simulation trials. Topline data from the driving simulation trial are expected in the second half of 2026, in advance of the expected topline readout of the BUOY-1 trial. Presented Overview of the GlyphAllo Development Program at the Main Session of the 2026 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting. In May 2026, Seaport presented oral and poster presentations highlighting the key clinical data generated in the Phase 1 and Phase 2a clinical trials of GlyphAllo and the design of the ongoing Phase 2b BUOY-1 trial of GlyphAllo in patients with MDD with or without anxious distress. GlyphAgo (SPT-320 or Glyph Agomelatine) Program for Patients with Generalized Anxiety Disorder (GAD) Positive Proof-of-Concept Topline Results from Completed Phase 1 Trial in Healthy Volunteers Company Plans to Initiate a Phase 2a Proof-of-Pharmacology Trial in the Second Half of 2026. This randomized, double-blind trial of two dose levels of GlyphAgo is designed to demonstrate proof-of-pharmacology by characterizing the potential benefits of GlyphAgo on sleep, including objective measures of sleep architecture, in patients with GAD and sleep disturbance. Topline data from this trial are expected in early 2028. Company Plans to Initiate a Phase 2b Trial in the First Half of 2027. This randomized, double-blind, placebo-controlled, potentially registration-enabling trial is designed to evaluate the efficacy and safety of GlyphAgo in patients with GAD. Topline data from this trial are expected by year-end 2028. Preclinical and Discovery Programs Glyph2BLSD (SPT-348 or Glyph 2-bromo-LSD) Program on Track. Seaport is developing Glyph2BLSD for neuropsychiatric and headache disorders with significant unmet need. Glyph2BLSD is a non-hallucinogenic neuroplastogen designed to harness the pharmacology of a psychedelic without the hallucination, or "trip." Completion of first-in-human-enabling studies is expected by year-end 2027. Corporate Upsized IPO Raising $260.0M Completed. In May 2026, Seaport closed its initial public offering (IPO), in which the Company raised gross proceeds of $260.0 million, before deducting underwriting discounts, commissions, and other offering expenses. The net proceeds from the offering together with the Company’s current cash, cash equivalents and investments are expected to support Seaport’s current operating plans into 2029, which includes multiple anticipated topline data readouts, including the Phase 2b BUOY-1 trial of GlyphAllo in patients with MDD, the Phase 2a trial of GlyphAgo in patients with GAD and sleep disturbance, and the Phase 2b trial of GlyphAgo in patients with GAD. Sharon Mates, Ph.D. Appointed to Board of Directors in April 2026. Dr. Mates served as Co-Founder, Chairman, and Chief Executive Officer of Intra-Cellular Therapies, Inc., which she co-founded in 2002, until its acquisition by Johnson & Johnson (J&J) for $14.6 billion in 2025. Second Quarter 2026 Financial Results Cash Position: Cash, cash equivalents, and investments totaled $427.3 million as of June 30, 2026. Seaport expects its cash, cash equivalents, and investments to support its current operating plans into 2029. R&D Expenses: Research and development (R&D) expenses were $24.6 million for the quarter ended June 30, 2026, as compared with $13.4 million for the quarter ended June 30, 2025. The increase in R&D expenses of $11.2 million was primarily due to increases in clinical development expenses of GlyphAllo and GlyphAgo as they advanced into later stage development. G&A Expenses: General and administrative (G&A) expenses were $41.2 million for the quarter ended June 30, 2026, as compared with $5.1 million for the quarter ended June 30, 2025. The increase in G&A expenses of $36.1 million was primarily due to one-time, non-cash stock-based compensation costs related to the successful completion of the Company’s IPO, as described in its previous SEC filings, and additional equity grants issued under the Company’s 2024 and 2026 Equity Plans. Net Loss: Net loss was $62.6 million for the second quarter of 2026, as compared to a net loss of $15.1 million for the second quarter of 2025. The increase in net loss was primarily due to one-time, non-cash stock-based compensation costs related to the successful completion of the Company’s IPO, as described in its previous SEC filings, and additional equity grants issued under the Company’s 2024 and 2026 Equity Plans. About Seaport Therapeutics Seaport Therapeutics (Nasdaq: SPTX) is a clinical-stage therapeutics company focused on inventing and developing new medicines for patients with depression, anxiety, and other debilitating neuropsychiatric disorders. Through its differentiated approach, the Company identifies clinically validated mechanisms with established efficacy and safety which had historically been limited by high first-pass metabolism, low bioavailability, and/or side effects. Seaport applies its proprietary Glyph™ platform to overcome those limitations and invent innovative oral therapies. With an experienced team of industry leaders, Seaport has a proven track record in neuropsychiatry drug discovery and development and delivering successful business outcomes. Seaport aims to develop novel, leading treatment options that will make a significant impact for patients and their families. For more information, please visit www.seaporttx.com. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding our product candidates, including the ongoing Phase 2b trial of GlyphAllo, enrollment status and anticipated timing of topline data in the first half of 2027, the Phase 1 driving simulation trial for GlyphAllo in healthy volunteers and timing of results in the second half of 2026, the completed Phase 1 trial of GlyphAgo, results related thereto, and the anticipated Phase 2a proof-of-pharmacology trial (initiating in the second half of 2026) and the Phase 2b trial (initiating in the first half of 2027) and related data in 2028, preclinical and clinical development activities and timelines, including preclinical and first-in-human-enabling activities for Glyph2BLSD (SPT-348), and our expectations regarding uses of capital, expenses and financial results, including the expected cash runway and financial performance. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect Seaport’s business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company’s research and development activities; risks that interim results are not predictive of final results in a clinical trial, Seaport’s ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to preclinical and clinical development activities; the Company’s dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Seaport’s ability to attract, integrate and retain key personnel; risks related to the Company’s financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Seaport’s intellectual property protections; and risks related to the competitive landscape for Seaport’s product candidates; as well as other risks described in "Risk Factors," in Seaport’s Quarterly Report on Form 10-Q for the three months ended March 31, 2026 filed with the Securities and Exchange Commission (SEC), as well as subsequent filings with the SEC. Seaport expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Seaport uses and intends to continue to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. View source version on businesswire.com: https://www.businesswire.com/news/home/20260803578717/en/ Contacts Seaport Therapeutics Media Contact: Shannon CostelloVice President, [email protected] Investor Contact:Adam Bero, Ph.D.Vice President, Head of Investor [email protected]

New data from Phase 1 trial of GlyphAgoTM build upon previously reported topline data and further demonstrate GlyphAgoTM can achieve therapeutic exposures of agomelatine at doses projected to avoid liver enzyme elevations and reduce or eliminate the need for liver function testing Enrollment in Phase 2b BUOY-1 trial of GlyphAlloTM is on track with topline data expected in 1H 2027; Seaport dosed first participant in Phase 1 driving simulation trial of GlyphAlloTM, with data expected in 2H 2026 Dr. Sharon Mates, Co-Founder, Chair, and CEO of Intra-Cellular Therapies until its acquisition by Johnson & Johnson for $14.6 billion, was appointed to Board of Directors Upsized IPO generated $260.0 million in gross proceeds; in addition to $212.6 million on hand as of March 31, 2026, total cash, cash equivalents, and investments expected to fund operations into 2029 BOSTON, June 08, 2026--(BUSINESS WIRE)--Seaport Therapeutics, Inc., (Nasdaq: SPTX) ("Seaport" or the "Company"), a clinical-stage therapeutics company that is inventing and developing novel neuropsychiatric medicines, today announced financial results for the first quarter of 2026 and highlighted recent corporate and clinical progress. "The first quarter of 2026 was filled with meaningful progress for Seaport, and we significantly advanced the clinical development of our lead GlyphAlloTM and GlyphAgoTM programs," said Daphne Zohar, Co-Founder and Chief Executive Officer at Seaport Therapeutics. "We previously reported data from the single-ascending dose and crossover portions of the Phase 1 proof-of-concept trial of GlyphAgoTM, which we believe substantially derisk future clinical development of the program. Today, we announced new multiple-ascending dose data from this trial, which further reinforce the ability of GlyphAgoTM to achieve therapeutic exposures of agomelatine at doses projected to avoid liver enzyme elevations. We continue to progress our potentially registration-enabling Phase 2b BUOY-1 trial of GlyphAlloTM and anticipate topline data from that trial in the first half of next year. With a pipeline of novel programs based on clinically validated mechanisms, an experienced team with a track record of success in neuropsychiatry, and a strong balance sheet bolstered by our recent IPO, we look forward to executing on our mission to transform the treatment of neuropsychiatric disorders and improve patients’ lives." Recent Business Updates and Anticipated Milestones GlyphAlloTM (SPT-300 or Glyph Allopregnanolone) Program for Patients with Major Depressive Disorder (MDD) Enrollment on Track in Phase 2b BUOY-1 Trial in MDD. Seaport is actively enrolling patients in BUOY-1, a two-arm, global, randomized, double-blind, placebo-controlled, potentially registration-enabling Phase 2b trial investigating the safety and efficacy of GlyphAlloTM in patients with MDD with or without anxious distress. Topline data from the BUOY-1 trial are expected in the first half of 2027. Given the strength in enrollment and to maximize the likelihood that the BUOY-1 trial could be used to support registration, the Company plans to enroll the full prespecified target sample size of approximately 360 patients and no longer intends to perform a sample size re-estimation (SSRE). Dosed First Participant in Phase 1 Driving Simulation Trial. This randomized, double-blind, placebo-controlled Phase 1 trial is designed to evaluate the potential impact of multiple dose levels of GlyphAlloTM on simulated driving performance in healthy volunteers. GlyphAlloTM will be dosed in the evening, and simulated driving performance will be assessed the following morning, approximately nine hours following GlyphAlloTM administration, as is typical in driving simulation trials. Topline data from the driving simulation trial are expected in the second half of 2026, in advance of the expected topline readout of the BUOY-1 trial. Phase 1 and Phase 2a and Preclinical Data Published in Science Translational Medicine. This publication details the design, optimization, preclinical evaluation, and Phase 1 and 2a clinical development of GlyphAlloTM in healthy volunteers. In Phase 1 and 2a trials, GlyphAlloTM was generally well-tolerated following single- and multiple-ascending oral doses ranging from 70–1000 mg, provided dose-dependent, therapeutically relevant plasma exposures of allopregnanolone, demonstrated pharmacodynamic effects in the brain, and potently blunted the acute physiological stress response on a validated clinical model of anxiety. GlyphAgoTM (SPT-320 or Glyph Agomelatine) Program for Patients with Generalized Anxiety Disorder (GAD) New Data Reported from Multiple-Ascending Dose (MAD) Portion of Phase 1 Proof-of-Concept Trial in Healthy Volunteers New data demonstrate that seven-day dosing of GlyphAgoTM achieved therapeutic exposures of agomelatine at doses projected to avoid liver enzyme elevations and reduce or eliminate the need for liver function testing. GlyphAgoTM AUC0-24 and Cmax increased dose-dependently over the range of doses studied, and agomelatine exposures following GlyphAgoTM administration were consistent with data from the single-ascending dose (SAD) and crossover portions of the trial. There was no unmodified agomelatine arm in the MAD portion. Repeat dosing of GlyphAgoTM confirms favorable safety, tolerability, and pharmacokinetics across the Phase 1 program, with no serious or liver-related adverse events observed. In April 2026, Seaport reported results from the head-to-head crossover portion of the trial, in which GlyphAgoTM demonstrated a statistically significant 6.8-fold increase in bioavailability compared to unmodified agomelatine in healthy volunteers, exceeding the program’s two-fold target to mitigate liver exposure. GlyphAgoTM also showed significantly lower (10-fold) PK variability compared to unmodified agomelatine. The crossover portion included participants who were taking estrogen-containing oral contraceptives that are known to increase agomelatine exposure due to liver drug-drug interaction. In contrast, GlyphAgoTM exposure was unaffected by oral contraceptives, further supporting the ability of GlyphAgoTM to bypass first-pass liver metabolism. GlyphAgoTM demonstrated a 9.6 to 14.5-fold increase in dose-normalized exposure compared to agomelatine in a separate SAD portion of the trial in which no participants were on oral contraceptives. GlyphAgoTM was well-tolerated across all evaluated doses, and no serious or severe adverse events or liver-related adverse effects were reported. Results support dose selection and planned advancement into two parallel Phase 2 trials in patients with GAD. Company Expects to Initiate a Phase 2a Proof-of-Pharmacology Trial in the Second Half of 2026. This randomized, double-blind trial of two dose levels of GlyphAgo is designed to demonstrate proof-of-pharmacology by characterizing the potential benefits of GlyphAgoTM on sleep, including objective measures of sleep architecture, in patients with GAD and sleep disturbance. Topline data from this trial are expected in early 2028. Company Expects to Initiate a Phase 2b Trial in the First Half of 2027. This randomized, double-blind, placebo-controlled, potentially registration-enabling trial is designed to evaluate the efficacy and safety of GlyphAgoTM in patients with GAD. Topline data from this trial are expected by year-end 2028. Preclinical and Discovery Programs Glyph2BLSDTM (SPT-348 or Glyph 2-bromo-LSD) Program on Track. Seaport is developing Glyph2BLSDTM for depressive disorders, including treatment-resistant depression, post-traumatic stress disorder, and headache disorders with significant unmet need. Glyph2BLSD is a non-hallucinogenic neuroplastogen designed to harness the pharmacology of a psychedelic without the hallucination, or "trip." Completion of first-in-human-enabling studies is expected by year-end 2027. Seaport and Monash Institute of Pharmaceutical Sciences Awarded Up to $15 Million from ARPA-H. Advanced Research Projects Agency for Health (ARPA-H) award supports the development of GlyphCeleTM or Cele-ProTM, an oral prodrug designed using Seaport’s proprietary GlyphTM platform to address dysfunctional gut lymphatics and local inflammation linked to metabolic disease and pancreatic cancer. Corporate Upsized IPO Raising $260.0M Completed. Seaport closed its upsized initial public offering (IPO) in May 2026, and the Company raised gross proceeds of $260.0 million, before deducting underwriting discounts, commissions, and other offering expenses. The net proceeds from the offering together with the Company’s current cash, cash equivalents and investments are expected to support Seaport’s current operating plans into 2029, which includes multiple anticipated topline data readouts, including the Phase 2b BUOY-1 trial of GlyphAlloTM in patients with MDD, the Phase 2a trial of GlyphAgoTM in patients with GAD and sleep disturbance, and the Phase 2b trial of GlyphAgoTM in patients with GAD. Sharon Mates, Ph.D. Appointed to Board of Directors. Dr. Mates served as Co-Founder, Chairman, and Chief Executive Officer of Intra-Cellular Therapies, Inc., which she co-founded in 2002, until its acquisition by Johnson & Johnson (J&J) for $14.6 billion in 2025. Under Dr. Mates’ leadership, Intra-Cellular Therapies developed medicines for mental health disorders including bipolar disorder, depression, and schizophrenia, and received U.S. Food and Drug Administration (FDA) approval for its novel antipsychotic CAPLYTA®, which generated greater than $1.5 billion in sales prior to the company’s acquisition by J&J, and continued its commercial growth thereafter driven by expanded market reach and additional FDA approvals. In connection with Seaport’s IPO, Robert Nelson, Eric Elenko, Ph.D., and Robert Lyne transitioned off of the Company’s Board of Directors. First Quarter 2026 Financial Results Cash Position: Cash, cash equivalents, and investments totaled $212.6 million as of March 31, 2026. Subsequent to March 31, 2026, Seaport completed its IPO, in which the Company raised gross proceeds of an additional $260.0 million, before deducting underwriting discounts, commissions, and other offering expenses. Seaport expects its current cash, cash equivalents, and investments to support its current operating plans into 2029. R&D Expenses: Research and development (R&D) expenses were $21.4 million for the quarter ended March 31, 2026 as compared with $10.5 million for the quarter ended March 31, 2025. The increase in R&D expenses of $10.9 million was primarily due to increases in clinical development expenses of GlyphAlloTM and GlyphAgoTM as they advanced into later stage development, and related personnel costs to support the Company’s R&D operations. G&A Expenses: General and administrative (G&A) expenses were $6.1 million for the quarter ended March 31, 2026 as compared with $5.7 million for the quarter ended March 31, 2025. The increase in G&A expenses of $0.5 million was primarily due to increased personnel costs and was partially offset by reduced professional fees, as compared to the same period in the prior year. Net Loss: Net loss was $25.4 million for the first quarter of 2026, as compared to a net loss of $13.1 million for the first quarter of 2025. About Seaport Therapeutics Seaport Therapeutics (Nasdaq: SPTX) is a clinical-stage therapeutics company focused on inventing and developing new medicines for patients with depression, anxiety, and other debilitating neuropsychiatric disorders. Through its differentiated approach, the Company identifies clinically validated mechanisms with established efficacy and safety which had historically been limited by high first-pass metabolism, low bioavailability, and/or side effects. Seaport applies its proprietary GlyphTM platform to overcome those limitations and invent innovative oral therapies. With an experienced team of industry leaders, Seaport has a proven track record in neuropsychiatry drug discovery and development and delivering successful business outcomes. Seaport aims to develop novel, leading treatment options that will make a significant impact for patients and their families. For more information, please visit www.seaporttx.com. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding our product candidates, including the ongoing Phase 2b trial of GlyphAllo, enrollment status and anticipated timing of topline data in the first half of 2027, the Phase 1 driving simulation trial for GlyphAllo in healthy volunteers and timing of results in the second half of 2026, the ongoing Phase 1 trial of GlyphAgo, results related thereto, and anticipated Phase 2a proof-of-pharmacology and Phase 2b trials and related data in 2028, preclinical and clinical development activities and timelines, including preclinical and first-in-human-enabling activities for Glyph2BLSD (SPT-348), and our expectations regarding uses of capital, expenses and financial results, including the expected cash runway and financial performance. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect Seaport Therapeutics’ business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company’s research and development activities; risks that interim results are not predictive of final results in a clinical trial, Seaport Therapeutics’ ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to preclinical and clinical development activities; the Company’s dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Seaport Therapeutics’ ability to attract, integrate and retain key personnel; risks related to the Company’s financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Seaport Therapeutics’ intellectual property protections; and risks related to the competitive landscape for Seaport Therapeutics’ product candidates; as well as other risks described in "Risk Factors," in Seaport Therapeutics’ Registration Statement on Form S-1 filed with the Securities and Exchange Commission (SEC), as well as subsequent filings with the SEC. Seaport Therapeutics expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Seaport uses and intends to continue to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. View source version on businesswire.com: https://www.businesswire.com/news/home/20260608629588/en/ Contacts Seaport TherapeuticsMedia Contact:Shannon CostelloVice President, [email protected] Investor Contact:Adam Bero, Ph.D.Head of Investor [email protected]