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, 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 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. 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 www.seaporttx.com

Footnotes

1 U.S. Food and Drug Administration. (2018). FDA drug approval package: Zulresso (Application No. 211,371)

2SPT-300, formerly known as LYT-300

Denice Torres, J.D., former Board Member of Karuna Therapeutics and accomplished healthcare executive at Johnson & Johnson, Janssen Neuroscience and Eli Lilly, appointed to Seaport Board of Directors

Eric Green, MBA, former development and commercialization leader at Alnylam Pharmaceuticals, joins as Chief Operating Officer

Michael Chen, Ph.D., Co-Founder of Seaport and former Head of Innovation at PureTech Health named Chief Scientific Officer

BOSTON, May 7, 2024 – Seaport Therapeutics, a clinical-stage biopharmaceutical company that is charting a proven path in neuropsychiatry, today announced the appointment of Denice Torres, J.D., to its Board of Directors. In addition, Michael Chen, Ph.D., Co-founder, was named Chief Scientific Officer, and Eric Green, MBA, was appointed Chief Operating Officer. The appointments follow the recent launch of Seaport with a $100 million Series A financing round to advance the development of novel neuropsychiatric medicines.

“We are incredibly honored to welcome Denice to our Board of Directors. She is an exceptional healthcare leader with a track record of successfully guiding organizations through significant growth and transformation,” said Steve Paul, M.D., Founder and Chair of the Board of Directors at Seaport. “Denice was a key contributor on the Karuna Board and I am delighted to have the opportunity to work with her again as we deliver on our mission to bring first and best-in-class medicines to those who are suffering from depression, anxiety and other neuropsychiatric disorders.”

Ms. Torres brings notable public and private board experience to Seaport, including a position on the Board of Directors at Karuna Therapeutics until its acquisition by Bristol Myers Squibb in March 2024. She has over 30 years of P&L, strategy, and leadership experience in pharmaceuticals, consumer healthcare and medical devices. Ms. Torres held several leadership positions at Johnson & Johnson, including President of J&J Consumer Healthcare, President of Janssen Neuroscience, and Chief Strategy Officer for the medical device division. Before joining Johnson & Johnson, she held senior leadership roles at Eli Lilly, including Executive Director of Global Neuroscience and Head of Women’s Healthcare. Ms. Torres has received numerous awards, including Healthcare Businesswomen’s Association Woman of the Year, Johnson & Johnson Working Mother of the Year, and the Johnson & Johnson Special Recognition Leadership Award for her work in diversity and inclusion.

“It’s an honor to join Seaport’s Board of Directors and a team of world-class innovators with an incredible track record of advancing the field of neuropsychiatry,” said Ms. Torres. “The company’s Glyph™ platform, fueled by breakthrough science, has the exciting potential to enhance the lives of millions of people living with neuropsychiatric disorders.”

Mr. Green steps into the role of Chief Operating Officer bringing nearly 25 years of biopharmaceutical development, commercialization and operational experience. Most recently, Mr. Green was Senior Vice President, Head of Development Programs at Alnylam Pharmaceuticals where he led a team responsible for global development and pre-commercialization activities for a portfolio of development stage programs. His initial role at Alnylam was as Senior Vice President, Global General Manager for the TTR Franchise, leading the first ever global approval of a RNAi therapeutic, ONPATTRO® (patisiran) and late-stage development of vutrisiran (now AMVUTTRA®). Mr. Green’s diverse experience spans across R&D process engineering, pharmaceutical manufacturing and operations, and global development and commercialization strategy with former roles at Synageva BioPharma, Infinity Pharmaceuticals, Genzyme Corporation and Pfizer. He received an MBA from MIT Sloan School of Management and a M.S. in chemical engineering from MIT School of Engineering. He earned a B.S. in chemical engineering from University of Michigan. At Seaport, he will be responsible for implementing strategies to support the growth and development of the company’s pipeline across the organization.

Dr. Chen is Co-founder and has now been appointed Chief Scientific Officer of Seaport. In his most recent role, Dr. Chen was the Head of Innovation at PureTech Health, where he oversaw the rapid advancement of the neuropsychiatric medicines that led to the launch of Seaport. These novel medicines are now being advanced within Seaport’s clinical-stage pipeline powered by the Glyph platform, which leverages the lymphatic system to create new medicines building on clinically validated mechanisms. Dr. Chen was previously Co-founder and Head of Research and Strategy at Sonde Health, a company developing vocal biomarkers for depression and other neuropsychiatric disorders. He was a postdoctoral fellow at Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology. Dr. Chen completed his Ph.D. at Stanford University, focusing on the neurobiological mechanisms of risk for depression and sleep disorders. He received a B.A. from Yale University.

“Denice exudes incredible passion and exuberance for making a difference for patients, and we are delighted to enrich our board with her energy and experience in neuroscience, manufacturing, commercialization and organizational growth and culture. I feel privileged to be able to work closely with her as we build out our team and advance our pipeline programs,” said Daphne Zohar, Founder and Chief Executive Officer at Seaport. “I’m also excited to welcome two key members to our executive team. I had the pleasure of working with Michael as he played a critical role in the development of our Glyph platform and pipeline and I look forward to working closely with him in this expanded role. Eric is an accomplished leader and he will help propel Seaport forward as we rapidly execute on our growth strategy and progress our pipeline of important new medicines for patients in need.”

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 www.seaporttx.com

Seaport Therapeutics Announces Management Appointments

Daphne Zohar, Founding CEO of PureTech Health and Co-Founder of Karuna Therapeutics, is Founder, Chief Executive Officer and Member of the Board of Directors of Seaport

Steven M. Paul, M.D., former CEO and Chair of Karuna Therapeutics, President of Lilly Research Laboratories, is Founder and Chair of the Board of Directors of Seaport

BOSTON, April 9, 2024 – Seaport Therapeutics, a clinical-stage biopharmaceutical company that is charting a proven path in neuropsychiatry, today announced the closing of a $100 million oversubscribed Series A financing round. The round was co-led by ARCH Venture Partners and Sofinnova Investments along with Third Rock Ventures and Seaport founder PureTech Health. Seaport also announced the appointment of Daphne Zohar as Founder, Chief Executive Officer and a member of the Board of Directors, and Steven M. Paul, M.D., as Founder and Chair of the Board of Directors.

Seaport is advancing a clinical-stage pipeline of novel neuropsychiatric medicines powered by its proprietary GlyphTM Technology Platform, which leverages the lymphatic system to create new medicines building on clinically validated mechanisms. The financing will support the rapid advancement of Seaport’s clinical-stage pipeline of first and best-in-class medicines as well as further development of the Glyph platform, which has demonstrated clinical proof-of-concept.

The company is built on a proven development strategy and is led by the team that created and advanced the groundbreaking drug candidate KarXT (xanomeline-trospium), which is now poised to be the first new class of medicine in over 50 years for patients living with schizophrenia. Daphne Zohar, the Chief Executive Officer of Seaport, is the founder and former CEO of PureTech Health where she also co-founded Karuna Therapeutics. Under Ms. Zohar’s leadership, PureTech’s R&D engine led to 28 new medicines, including two that received U.S. FDA clearance and a third (KarXT) that has been filed for FDA approval.

Dr. Paul, Founder and Chair of the Seaport Board of Directors, is the former CEO and Chair of the Board of Directors of Karuna Therapeutics, which was recently acquired by Bristol Myers Squibb. Dr. Paul is also the former President of Research and Development at Eli Lilly, where he oversaw the development of CNS drugs such as Zyprexa® and Cymbalta® as well as xanomeline, where its anti-psychotic and pre-cognitive properties were initially demonstrated.

“Major depression and anxiety disorders are among the most common, disabling and potentially fatal of all medical conditions. Current standard-of-care treatments provide inadequate relief for far too many patients. Seaport’s pipeline of investigational antidepressants and anxiolytics are well positioned to more effectively treat these disorders and to help millions of people and their families,” said Steven M. Paul M.D. “Given the historically low success rates within neuropsychiatric drug development, precisely solving the previous limitations of clinically validated mechanisms improves the probability of success and enables us to significantly accelerate development.”

“We are dedicated to bringing first and best-in-class medicines to those that are suffering from depression, anxiety and other neuropsychiatric disorders,” said Daphne Zohar, Founder and CEO of Seaport Therapeutics. “I’m excited to deliver on this mission along with a stellar team of senior leaders and investors.”

All of the programs in Seaport’s pipeline are based on the Glyph platform, which is designed to enable and enhance oral bioavailability, avoid first-pass metabolism and reduce hepatotoxicity and other side effects to advance active drugs that were previously held back by those limitations. Seaport’s most advanced therapeutic candidate is SPT-3001, which is an oral prodrug of allopregnanolone, an endogenous neurosteroid, in development for the treatment of 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.

Seaport’s pipeline also includes SPT-3202, a novel prodrug of agomelatine being advanced for the treatment of Generalized Anxiety Disorder, which uses the Glyph platform to bypass first-pass metabolism by the liver and thus has the potential to lower its effective dose, reduce liver exposure and eliminate the need for liver function monitoring that has held back agomelatine. SPT-348, a prodrug of a non-hallucinogenic neuroplastogen in development for the treatment of mood and other neuropsychiatric disorders, leverages Glyph to create a potential first-in-class treatment with improved pharmacokinetics and tolerability compared to conventional psychedelics. Beyond these programs, Seaport has multiple discovery and preclinical programs underway.

The additional members joining the Seaport Board of Directors are Robert Nelsen (Managing Partner and Co-founder of ARCH Venture Partners), James Healy, M.D., Ph.D. (Managing Partner of Sofinnova Investments), Eric Elenko, Ph.D. (Co-founder and President of PureTech and Co-inventor of KarXT), and Bharatt Chowrira Ph.D., (newly appointed Chief Executive Officer of PureTech). Courtney Wallace (Venture Partner at Third Rock Ventures) is joining as Board Observer.

“I’m thrilled to be partnering again with this outstanding team, led by Daphne and Steve, to change the lives of people with neuropsychiatric disorders,” said Robert Nelsen, Co-founder and Managing Director of ARCH Venture Partners. “We were the lead investors in Karuna’s Series A and Series B financing rounds, and I’m excited to partner with these strong leaders again to deliver on Seaport’s proven strategy and robust pipeline and bring important new medicines to patients.”

“Seaport has the potential to meaningfully change the lives of patients with neuropsychiatric disorders,” said James Healy, M.D., Ph.D., Managing Partner at Sofinnova Investments. “We’ve had the pleasure of knowing Steve and Daphne for a number of years, as one of the investors in Karuna, and we believe this team has the unique expertise to help solve the challenges of treating serious mental health conditions. I am eager to support Seaport as an investor and board member as the team continues to advance its clinical-stage pipeline of novel therapeutics.”

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. 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. We have a proven strategy of advancing clinically validated mechanisms previously held back by limitations we overcome with our proprietary GlyphTM technology platform. All the therapeutic candidates in our 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. We are 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 www.seaporttx.com

Footnotes
1 SPT-300, formerly known as LYT-300
2 SPT-320, formerly known as LYT-320

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