Seaport Therapeutics, Inc. · NASDAQ:SPTX
Seaport Therapeutics — Investor Presentation (October 2026)
40 slides from Seaport Therapeutics's investor presentation, October 2026
Slide 1: Turning the Tide on Mental Health
Corporate Presentation October 2026 Turning the Tide on Mental Health CONFIDENTIAL
Slide 2: Disclaimer
Disclaimer This presentation includes forward-looking statements, including, but not limited to, express or implied statements about Seaport’s beliefs and expectations regarding: the potential of the Glyph platform to enhance oral bioavailability, bypass first-pass metabolism and reduce hepatotoxici
Slide 3: Charting a Proven Path in Neuropsychiatry
Charting a Proven Path in Neuropsychiatry Clinical GlyphTM Proven Validation Platform Team Clinically validated "GlyphTM" to overcome Apply team’s expertise to mechanisms previously limitations and create optimize clinical trials held back by issues novel drug candidates with and drive successful Gl
Slide 4: Our Proven Leadership Team
Our Proven Leadership Team A track record of success DAPHNE ZOHAR Co-founder, CEO, Board Member Former PureTech CEO & Founder; Co-founder Karuna (acquired by BMS for $14B) STEVEN PAUL, MD Co-founder, Board Chair Former Chair & CEO of Karuna; Former President of Lilly Research Labs. Developed ZYPREXA
Slide 5: Over 1 Billion People Are Living with Mental Illness
Over 1 Billion People Are Living with Mental Illness1 Depression and Anxiety are Highly Comorbid2,3 Disabling and Deadly ~332 ~359 million million ~20x increase in suicide risk in people with people with people with MDD5 MDD* anxiety disorders worldwide4 worldwide4 Suicide is a top 3 cause of death
Slide 6: Current Neuropsychiatry Medications
Current Neuropsychiatry Medications Widely prescribed but have limitations Peak Sales Limitations >$5B1 Modest Efficacy ~$5B1 Ineffective for ~1 in 3 patients 3 >$3.5B1 >$3.5B1 Slow Onset Generally take >$3B1 weeks to work >$3B1 Unfavorable ~$3B1 Side Effects >$2.5B1 Sexual dysfunction, weight gain,
Slide 7: A Neuroscience Renaissance
A Neuroscience Renaissance Driven by scientific progress and interest in Big Drugs for Big Diseases Additional Pharma Companies Acquirer Company Value Committed to CNS: $14.0B $14.6B $8.7B CONFIDENTIAL 7
Slide 8: Seaport Uniquely Positioned to Outperform in Neuropsychiatry Drug Development
Seaport Uniquely Positioned to Outperform in Neuropsychiatry Drug Development Neuropsychiatry Challenges Seaport’s Approach Fundamental >90% Identify drugs with clinical trial validated efficacy pathophysiology failure rate1 unknown Poor oral bioavailability Overcome hurdles Poor drug-like using Gly
Slide 9: Seaport's Proven Team & Approach
Seaport’s Proven Team & Approach Karuna case study: Successful outcome for patients and shareholders Identified drug with validated efficacy STEVEN PAUL, MD DAPHNE ZOHAR (xanomeline) Former Board Chair Co-founder of Karuna, & CEO, Karuna originator of KarXT Overcame hurdles with CobenfyTM FDA-approv
Slide 10: Glyph Platform: Transformative & Validated
GlyphTM Platform: Transformative & Validated Successfully applied to create over 24 different small molecules – novel CoM IP CoM = Composition of Matter 10
Slide 11: Our Proprietary Glyph Platform
Our Proprietary Glyph Platform Unlocks active drugs previously limited by high first-pass metabolism Conventional Glyph Platform Delivery Employs the lymphatic system’s natural lipid Oral drugs with high absorption and transport first-pass metabolism process to bypass the liver can have low bioavail
Slide 12: Design of Proprietary Prodrug Chemistry
Design of Proprietary Prodrug Chemistry Designed to avoid first-pass metabolism by promoting lymphatic uptake API SI Linker Glyceride Self-Immolative (SI) Linker Glyceride Allows controlled release Tunes stability to gut esterases and Integrates prodrug into of parent drug compound recognition for t
Slide 13: Pipeline of Novel Potential Treatments for Neuropsychiatric Disorders
Pipeline of Novel Potential Treatments for Neuropsychiatric Disorders ANTICIPATED OUR PROGRAMS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONES GlyphAllo (SPT-300) Data from Phase 2b Major Depressive Disorder (MDD) Glyph Allopregnanolone BUOY-1 trial expected 1H 2027 Designed to overcome oral bioavail
Slide 14: GlyphAllo is Designed to Overcome Low Bioavailability of Allopregnanolone
GlyphAlloTM is Designed to Overcome Low Bioavailability of Allopregnanolone Allopregnanolone Benefits Key Limitation o Naturally occurring molecule Due to poor oral bioavailability, that reduces stress1 allopregnanolone has only been available via 60-hour infusion o Clinically validated in third- pa
Slide 15: GlyphAllo Reaches Therapeutically Relevant Exposures with a Favorable Tolerability Profile
GlyphAlloTM Reaches Therapeutically Relevant Exposures with a Favorable Tolerability Profile Clinical GlyphAlloTM Oral Systemic Key PK and Safety Data Exposure and Literature Data2,3 o Bioavailability >9X vs. oral allopregnanolone1 o Generally well-tolerated, adverse events generally mild & transien
Slide 16: Phase 2a Results: GlyphAllo Significantly Reduced Stress Response Compared to Placebo
Phase 2a Results: GlyphAlloTM Significantly Reduced Stress Response Compared to Placebo (p=0.0001)1 GlyphAlloTM Demonstrated GlyphAlloTM Potently Blunted Salivary Cortisol Response to the TSST* Initial Proof-of-Concept o Generally well tolerated: All treatment-related AEs were transient & mild or mo
Slide 17: Zuranolone Showed Strong Early Efficacy in MDD, But Treatment Duration Was Only Two Weeks
Zuranolone Showed Strong Early Efficacy in MDD, But Treatment Duration Was Only Two Weeks Zuranolone Had a Deepening Response in Zuranolone: Synthetic MDD Over Two-Week Treatment Period2 Analog of Allopregnanolone o Treatment duration in most MDD trials is 6-8 weeks o Zuranolone MDD trials had a hig
Slide 18: Number and Frequency of Clinical Assessments are Associated with Placebo Response in MDD Trials
Number and Frequency of Clinical Assessments are Associated with Placebo Response in MDD Trials Seaport Meta-Analysis of 0 0 Placebo group % Change from Baseline MDD Trials in Last 10 Years 0 0 o Increasing number and frequency of clinician- 0 administered assessments (CAAs) were significantly assoc
Slide 19: Driving Simulation Trial Met Primary Endpoint: GlyphAllo Did Not Impair Next-Morning Driving
Driving Simulation Trial Met Primary Endpoint: GlyphAllo Did Not Impair Next-Morning Driving Study Design: Trial Met Primary and Key Secondary Endpoints o Randomized, double-blind, placebo- Primary endpoint: Evening dosing of GlyphAllo and active-controlled, three-way (375 mg) did not impair next-mo
Slide 20: Design of Phase 2b BUOY-1 Trial of GlyphAllo in MDD With or Without Anxious Distress
Design of Phase 2b BUOY-1 Trial of GlyphAlloTM in MDD With or Without Anxious Distress BUOY-1: Global, randomized, double-blind, placebo-controlled Phase 2b trial to evaluate efficacy, safety, and tolerability of GlyphAlloTM in MDD Key Trial Objectives & Design Elements o ~360 participants randomize
Slide 21: Defining a Successful Outcome for GlyphAllo in the Phase 2b BUOY-1 Trial
Defining a Successful Outcome for GlyphAllo in the Phase 2b BUOY-1 Trial Demonstrate a Statistically Significant and Clinically Meaningful Difference for GlyphAllo vs. Placebo on the Primary Endpoint Marketed Antidepressants Have Effect Sizes Ranging From 0.16 to 0.421,2 Exploratory Opportunities fo
Slide 22: GlyphAllo Clinical Development Plan Overview
GlyphAlloTM Clinical Development Plan Overview Completed and ongoing trials Phase 1 and 2a Trials in Healthy Volunteers (Completed) ✓ Phase 1: Demonstrated therapeutically relevant allopregnanolone exposures, dose- dependent PD*, and a favorable tolerability profile that supports chronic dosing ✓ Ph
Slide 23: Pipeline of Novel Potential Treatments for Neuropsychiatric Disorders
Pipeline of Novel Potential Treatments for Neuropsychiatric Disorders ANTICIPATED OUR PROGRAMS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONES GlyphAllo (SPT-300) Data from Phase 2b Major Depressive Disorder (MDD) Glyph Allopregnanolone BUOY-1 trial expected 1H 2027 Designed to overcome oral bioavail
Slide 24: GlyphAgo is Designed to Overcome Liver Monitoring Requirements of Agomelatine
GlyphAgoTM is Designed to Overcome Liver Monitoring Requirements of Agomelatine Agomelatine Benefits Key Limitation o Novel mechanism: Melatonin Due to high first-pass metabolism, receptor (MT1/MT2) agonist agomelatine can cause liver and 5-HT2C antagonist enzyme elevations and requires o Statistica
Slide 25: Agomelatine is an Effective Treatment for Generalized Anxiety Disorder (GAD)
Agomelatine is an Effective Treatment for Generalized Anxiety Disorder (GAD) Agomelatine Significantly Reduces Agomelatine Profile in GAD Anxiety in Patients with GAD4 o Statistical separation from placebo in all four third-party HAM-A Total Score Placebo trials in GAD1-4 N=140 o Better efficacy and
Slide 26: Agomelatine Improves Sleep in GAD and MDD
Agomelatine Improves Sleep in GAD and MDD Agomelatine Improves Sleep Sleep Disturbances: a Core Compared to SSRIs1 Feature of Mood Disorders o Agomelatine improves sleep latency, sleep architecture, and daytime sleepiness compared to SSRIs1,2 o SSRIs can exacerbate insomnia and sleep problems in MDD
Slide 27: Despite Known Efficacy, Agomelatine Has Been Held Back by Need for Liver Function Testing
Despite Known Efficacy, Agomelatine Has Been Held Back by Need for Liver Function Testing Agomelatine Can Cause Dose- Agomelatine Treatment Dependent Liver Enzyme Elevations1 Requires Frequent Liver Function Tests2 o Before starting treatment o After 3, 6, 12, and 24 weeks o When increasing dose o T
Slide 28: DILIsym Simulations Demonstrate that GlyphAgo is Not Projected to Cause Liver Enzyme Elevations
DILIsym Simulations Demonstrate that GlyphAgoTM is Not Projected to Cause Liver Enzyme Elevations DILIsym: Model Used to Predict and Explain DILI* o Liver enzyme elevations observed in previous clinical trials of agomelatine are recapitulated with DILIsym o GlyphAgo doses designed to generate compar
Slide 29: Phase 1 Topline: GlyphAgo Provided Therapeutic Exposures at Doses Projected to Avoid Liver Issues
Phase 1 Topline: GlyphAgoTM Provided Therapeutic Exposures at Doses Projected to Avoid Liver Issues GlyphAgoTM Exceeded Target of Two-Fold Data from Head-to-Head Increase in Bioavailability Compared to Crossover Portion of Trial Unmodified Agomelatine Crossover o GlyphAgo achieved 6.8-fold increase
Slide 30: Phase 1 Topline: GlyphAgo Provided Therapeutic Exposures at Doses Projected to Avoid Liver Issues
Phase 1 Topline: GlyphAgoTM Provided Therapeutic Exposures at Doses Projected to Avoid Liver Issues GlyphAgoTM Exceeded Target of Two-Fold Data from SAD and MAD Increase in Bioavailability Compared to Portions of Trial Unmodified Agomelatine Single-Ascending Dose o SAD: GlyphAgo demonstrated 9.6-14.
Slide 31: GlyphAgo Clinical Development Plan Overview
GlyphAgoTM Clinical Development Plan Overview Completed and near-term trials Phase 1 Proof-of-Concept Trial in Healthy Volunteers (Completed) ✓ GlyphAgoTM provided therapeutic exposures of agomelatine at doses projected to avoid liver issues, and was generally well-tolerated, with no serious or seve
Slide 32: Pipeline of Novel Potential Treatments for Neuropsychiatric Disorders
Pipeline of Novel Potential Treatments for Neuropsychiatric Disorders ANTICIPATED OUR PROGRAMS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONES GlyphAllo (SPT-300) Data from Phase 2b Major Depressive Disorder (MDD) Glyph Allopregnanolone BUOY-1 trial expected 1H 2027 Designed to overcome oral bioavail
Slide 33: Neuroplastogens are Poised to Transform Psychiatric Treatment
Neuroplastogens are Poised to Transform Psychiatric Treatment 33
Slide 34: Glyph2BLSD is Designed to Harness Efficacy of Psychedelics While Eliminating Hallucinations
Glyph2BLSDTM is Designed to Harness Efficacy of Psychedelics While Eliminating Hallucinations Neuroplastogen Benefits Key Limitations o Offer potential to enhance Functional unblinding of clinical neuroplasticity in brain trials, need for supervised circuits implicated in administration, concerns ov
Slide 35: Anticipated Key Milestones Across our Portfolio
Anticipated Key Milestones Across our Portfolio Program 2025-2026 2027-2028 GlyphAllo (SPT-300) ✓ Q3 2025: Initiated Phase 2b BUOY-1 trial • 1H 2027: Phase 2b BUOY-1 trial topline data Glyph Allopregnanolone ✓ 2H 2026: Phase 1 driving trial topline data • 2028: Initiate Phase 3 program in MDD GlyphA
Slide 36: Seaport Board of Directors and Scientific and Clinical Advisory Board
Seaport Board of Directors STEVEN PAUL, MD DAPHNE ZOHAR SANDI PETERSON DENICE TORRES, JD DAVID WHEADON, MD Co-founder, Board Chair of Seaport; Co-founder, CEO of Seaport; Lead Independent Director at Microsoft, Previously Karuna, J&J, Previously AstraZeneca, Abbott, Former Chair & CEO of Karuna Foun
Slide 37: Unlocking Better Days
Corporate Presentation October 2026 Unlocking Better DaysTM CONFIDENTIAL
Slide 38: Appendix
Appendix SEAPORT ee eee nee souaiis is iauiscsuiaeiis suai tuusenineica . THERAPEUTICS
Slide 39: GlyphAllo Showed Dose-Dependent Allopregnanolone Levels and PD Effects in Phase 1
GlyphAlloTM Showed Dose-Dependent Allopregnanolone Levels and PD Effects in Phase 1 PK PD Beta EEG Power Stanford Sleepiness Score (SSS) Saccadic Eye Velocity (SEV) Pooled Placebo (N=15) GlyphAllo 250 mg (N=9) Allopregnanolone Plasma Levels and PD Signals GlyphAllo 375 mg (N=9) Peaked 3-5 Hours Post
Slide 40: Design of Phase 2a Trial of GlyphAllo
Design of Phase 2a Trial of GlyphAlloTM Randomized, placebo-controlled trial using the Trier Social Stress Test (TSST) Pre-TSST 1. Anticipation: prepare a speech saliva sample Post-TSST salivary cortisol Dosing (Baseline) 2. Public speaking to a panel reflects stress during TSST 3. Live math test to
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