Multiple well-tolerated doses with pharmacodynamic activity were identified and will be included in a planned Phase 2b study in major depressive disorder
BOSTON, December 11, 2024 – Seaport Therapeutics (“Seaport” or the “Company”), a clinical-stage biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced the presentation of additional data from its first-in-human, multi-part Phase 1 study of SPT-300 in healthy volunteers at the American College of Neuropsychopharmacology (ACNP) Annual Meeting, held December 8-11, 2024 in Phoenix, Arizona. SPT-300 is an oral prodrug of allopregnanolone that is designed to retain the pharmacological activity of allopregnanolone, an endogenous neurosteroid. Allopregnanolone has been clinically validated in third-party trials as a rapidly acting antidepressant with anxiolytic effects.
The Phase 1 study enrolled 99 participants (in three parts: double-blind single ascending dose, multiple ascending dose, and open-label food effect) and evaluated oral bioavailability, safety, tolerability, pharmacokinetics and GABAA target engagement. Pharmacodynamic assessments included quantitative electroencephalography (EEG) analyses of brain function and video-oculography (VOG) assessments of eye movement. SPT-300 was well-tolerated, with all adverse events (AE) being mild or moderate, transient and dose-dependent. The most common AE was somnolence, which was mild and transient in all cases. The study showed that SPT-300 had therapeutically relevant blood levels that were up to approximately nine times greater than published data on orally administered unmodified allopregnanolone, which has minimal bioavailability.
New data in the poster presented at the conference include further safety analyses and pharmacokinetic and pharmacodynamic data. In the Phase 1 study, increases in EEG beta frequency power and reduction in saccadic eye velocity were observed at approximately 4 hours post-dose. Somnolence peaked in this same timeframe and diminished by 6 to 8 hours post-dose, consistent with both pharmacodynamic markers and blood levels of allopregnanolone. Based on the Phase 1 study results, the profile of SPT-300 is suitable for chronic dosing and oral administration at night in the planned Phase 2b placebo-controlled study in major depressive disorder with or without anxious distress.
“Together with previous clinical efficacy data, the further analyses of the Phase 1 study demonstrate that these doses of SPT-300 are well-tolerated and have rapidly acting pharmacodynamic activity. This reinforces our confidence in SPT-300 as an oral modulator of GABAA receptors and as a potential rapidly acting antidepressant and anxiolytic agent,” said Tony Loebel, M.D., Chief Medical Officer and President of Clinical Development of Seaport Therapeutics. “There is a great need for innovative neuropsychiatric medicines, and an oral form of allopregnanolone has the potential to provide important advantages that we believe will allow for once-daily use on a chronic basis. We look forward to the next phase of our clinical development plan for SPT-300.”
About SPT-300
SPT-300 (Glyph allopregnanolone), an oral prodrug of allopregnanolone, an endogenous neurosteroid, is in clinical stage development for the treatment of major depressive disorder (MDD) with or without anxious distress. Allopregnanolone has demonstrated therapeutic benefit in a range of neuropsychiatric conditions, but is currently only approved as an intravenous infusion, which has limited the scope of its clinical use. Using the Glyph™ platform, SPT-300 is designed to retain the activity, potency and the breadth of the natural biological response of endogenous allopregnanolone in an oral form, which has the potential to capture clinically important antidepressant and anxiolytic effects. In a Phase 2a clinical study, SPT-300 demonstrated initial 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 study.
About Seaport Therapeutics
Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The Company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph technology platform. All the therapeutic candidates in its pipeline of potentially first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects. Seaport is led by an experienced team that invented and advanced important neuropsychiatric medicines and is guided by an extensive network of renowned scientists, clinicians and key opinion leaders. For more information, please visit www.seaporttx.com.
Former ImmunoGen CFO will join Seaport to steer capital financing strategy, accounting, FP&A and investor relations
BOSTON, November 5, 2024 – Seaport Therapeutics (“Seaport or the “Company”), a clinical-stage biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced the appointment of Lauren White as Chief Financial Officer. An accomplished biotech financial executive, Ms. White most recently served as the Chief Financial Officer at ImmunoGen (NASDAQ: IMGN) prior to its acquisition by AbbVie (NYSE: ABBV) for $10.1 billion in 2024.
“I am so pleased to welcome Lauren as our CFO as we progress our clinical-stage pipeline of therapeutics for the treatment of anxiety, depression and other neuropsychiatric disorders,” said Daphne Zohar, Founder and Chief Executive Officer at Seaport. “Her strong leadership background in biotech finance will be valuable as we chart an efficient path to delivering these important new medicines to patients.”
Ms. White brings over 22 years of corporate finance, accounting, strategic partnering and investor relations expertise to Seaport. As the CFO at ImmunoGen, Ms. White played a key role on the internal deal team, conducting thorough analysis and due diligence during the M&A process with multiple potential buyers, which ultimately led to the successful acquisition of the company by AbbVie. Additionally, Ms. White helped to maximize the successful commercial launch of ELAHERE®, a first-in-class antibody-drug conjugate (ADC) approved for platinum-resistant ovarian cancer. Before joining ImmunoGen, Ms. White served as Chief Financial Officer, Treasurer, and Principal Accounting Officer at C4 Therapeutics (NASDAQ: CCCC), where she was responsible for developing and leading the company’s financial, capital, and procurement strategies.
Prior to that, Ms. White held roles of increasing responsibility at Novartis (NYSE: NVS), most recently serving as Global Head of Financial Planning and Analysis for the Novartis Institutes for BioMedical Research (NIBR), where she drove financial strategy and business planning. Before Novartis, Ms. White held strategy and marketing roles with Boston Consulting Group and General Electric. Ms. White received a BS from the Carroll School of Management at Boston College and earned an MBA from Harvard Business School.
“I’m excited to join the outstanding team at Seaport at this important stage of development,” said Ms. White. “I look forward to working with our team and collaborators to leverage our recent financial progress and support Seaport’s mission to deliver meaningful medicines that positively impact the lives of patients and their families.”
About Seaport Therapeutics
Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The Company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph technology platform. All the therapeutic candidates in its pipeline of first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects. Seaport is led by an experienced team that invented and advanced important neuropsychiatric medicines and are guided by an extensive network of renowned scientists, clinicians and key opinion leaders. For more information, please visit www.seaporttx.com.
Financing led by General Atlantic with participation from T. Rowe Price Associates, Foresite Capital, Invus, Goldman Sachs Alternatives, Canada Pension Plan Investment Board (CPP Investments) as well as other new investors
Founding investors ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and PureTech Health also participated
Proceeds will support key clinical milestones in Seaport’s pipeline of first and best-in-class neuropsychiatric medicines
BOSTON, October 21, 2024 – Seaport Therapeutics (“Seaport” or the “Company”), a clinical-stage biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced the closing of an oversubscribed $225 million Series B financing round. The syndicate was led by General Atlantic, a leading global growth investor, with participation from funds and accounts advised by T. Rowe Price Associates, Inc., Foresite Capital, Invus, Goldman Sachs Alternatives, CPP Investments,and other new investors. Founding investors ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and co-founder PureTech Health also participated.
The financing brings the total capital raised by Seaport to $325 million since the Company’s launch in April 2024. Seaport will use the proceeds to advance its clinical-stage pipeline of first and best-in-class medicines through important clinical milestones as well as further advance the capabilities of the Glyph™ technology platform, which has demonstrated clinical proof-of-concept.
“We are grateful to have the partnership of this incredible group of new and existing investors who share our commitment of delivering better medicines for those suffering from depression, anxiety and other neuropsychiatric disorders,” said Daphne Zohar, Founder and CEO of Seaport Therapeutics. “Seaport is advancing novel therapeutics that have proven clinical efficacy but had previously been held back by an issue we can now address with our Glyph platform. This financing enables the important clinical work that brings us another step closer to delivering new medicines to make a difference in the lives of patients and their families.”
“We are excited to partner with Daphne Zohar, Steve Paul and the team at Seaport,” said Brett Zbar, M.D., Managing Director and Global Head of Life Sciences at General Atlantic. “We are impressed with the team’s outstanding CNS clinical track record, as well as Seaport’s Glyph platform and innovative pipeline. The approach to clinical development and trial design demonstrates the deep neuropsychiatric expertise around the table, which we believe offers unique advantages that will contribute to Seaport’s success. We look forward to supporting the Company’s next phase of development.”
The programs in Seaport’s pipeline use the Glyph platform, which is designed to enable and enhance oral bioavailability, avoid first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects to advance clinically active drugs that were previously hindered by those limitations. The most advanced therapeutic candidate in the pipeline is SPT-300, an oral prodrug of allopregnanolone that is being advanced into a Phase 2b study for major depressive disorder with or without anxious distress that has the potential to be registration-enabling. Allopregnanolone is an endogenous neurosteroid with clinically validated rapid anti-depressant and anxiolytic activity, and SPT-300 retains this activity in an oral form.
“The development of important new neuropsychiatric medicines is often halted due to poor drug-like properties or unacceptable tolerability, challenges that our Glyph platform can now uniquely address,” said Steve Paul, M.D., Founder and Board Chair at Seaport Therapeutics. “For instance, xanomeline was an effective drug that faced tolerability challenges, but once resolved, led to the FDA approval of Cobenfy™ (formerly KarXT) for schizophrenia. With Glyph, we believe each of Seaport’s programs could create similar life-changing value for patients.”
SPT-320, a novel prodrug of agomelatine being advanced into Phase 1 studies for the treatment of generalized anxiety disorder (GAD), has the potential to be the first new mechanism for GAD in decades. SPT-320 uses Glyph to bypass liver first-pass metabolism and thus has the potential to lower the dose and reduce liver exposure while retaining efficacious systemic exposure of agomelatine that has been validated in multiple clinical studies in GAD. The reduction in dose has the potential to eliminate the need for liver function monitoring that has previously held back agomelatine’s development in GAD. SPT-348, a prodrug of a non-hallucinogenic neuroplastogen in development for the treatment of mood and other neuropsychiatric disorders, uses Glyph to create a potential first-in-class treatment. Beyond these programs, Seaport has multiple discovery and preclinical programs underway.
About the Glyph™ Platform
Glyph is Seaport’s proprietary technology platform which uses the lymphatic system to enable and enhance the oral administration of drugs. With the Glyph platform, drugs are absorbed like dietary fats through the intestinal lymphatic system and transported into circulation. The Glyph platform has the potential to be widely applied to many therapeutic molecules that have high first-pass metabolism leading to low bioavailability and/or side effects, including liver enzyme elevations or hepatotoxicity. Seaport exclusively licensed this technology from Monash University based on the pioneering research of the Porter Research Group. Advanced initially at PureTech Health and now at Seaport, Glyph has been applied to create therapeutic candidates for the Company’s pipeline resulting in new intellectual property, including composition of matter. The group and its collaborators have published research in Nature Metabolism, Frontiers in Pharmacology and the Journal of Controlled Release supporting the Glyph platform’s capabilities. See Glyph in action here.
About Seaport Therapeutics
Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The Company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph technology platform. All the therapeutic candidates in its pipeline of first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects. Seaport is led by an experienced team that invented and advanced important neuropsychiatric medicines and are guided by an extensive network of renowned scientists, clinicians and key opinion leaders. For more information, please visit www.seaporttx.com.
Prominent pharmaceutical leader from AstraZeneca, Abbott, GlaxoSmithKline and Eli Lilly, brings extensive regulatory affairs and clinical development expertise to Seaport Board
BOSTON, August 13, 2024 – Seaport Therapeutics, a clinical-stage biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced the appointment of David Wheadon, M.D., to its Board of Directors. Dr. Wheadon is a physician and psychiatrist with more than three decades of experience in regulatory affairs, clinical strategy, and global health policy at multinational companies across the pharmaceutical industry.
“It is our pleasure to welcome David Wheadon to our Board of Directors,” said Daphne Zohar, Founder and Chief Executive Officer at Seaport. “David brings extensive regulatory expertise, and a successful background in the development and approval of several important neuropsychiatric medicines which will benefit Seaport as we advance our clinical-stage pipeline of therapeutics for the treatment of depression, anxiety and other neuropsychiatric disorders.”
Dr. Wheadon is a distinguished pharmaceutical leader who most recently served as Senior Vice President, Global Regulatory Affairs, Patient Safety and Quality Assurance at AstraZeneca. While at AstraZeneca, he drove regulatory strategy for the development and approval of the company’s product portfolio and oversaw the global regulatory affairs, patient safety and quality assurance organization. Dr. Wheadon also served as a member of the company’s Global Medicines Development Leadership team and Late-Stage Product Committee, which was responsible for the progression of AstraZeneca’s late-stage portfolio through clinical development, regulatory approvals and market access.
“I’m excited to join the talented members of Seaport’s Board and executive team with deep experience and a proven track record of developing neuropsychiatric drugs,” said Dr. Wheadon. “Seaport has a promising pipeline of novel antidepressants and anxiolytics, and I look forward to being a part of the journey of delivering these important new treatments to the millions of patients suffering from devastating and debilitating mental health conditions, including depression and anxiety.”
Dr. Wheadon held previous leadership positions at the Pharmaceutical Research and Manufacturers of America (PhRMA), the Juvenile Diabetes Research Foundation as well as senior regulatory and clinical development leader roles at Abbott and GlaxoSmithKline. He also served on the Board of Directors at Karuna Therapeutics until its acquisition by Bristol Myers Squibb in March 2024. He began his career as a clinical research physician in neuroscience at Eli Lilly. Dr. Wheadon earned an A.B. from Harvard College and an M.D. from Johns Hopkins University School of Medicine. His residency was in psychiatry at the Tufts-New England Medical Center. He is a member of the American Academy of Pharmaceutical Physicians and the American Psychiatric Association.
“I had the privilege of working with David on the Karuna board, so I know how incredibly fortunate we are to gain his unparalleled level of expertise and industry perspective at Seaport,” said Steve Paul, M.D., Founder and Chair of the Board of Directors at Seaport. “He has an accomplished career and an astute understanding of the regulatory and clinical landscape, which will make him a valuable addition to Seaport as we continue to advance our novel neuropsychiatric medicines through clinical development.”
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 invented and advanced important neuropsychiatric medicines and are guided by an extensive network of renowned scientists, clinicians and key opinion leaders. For more information, please visit www.seaporttx.com.
Antony Loebel, M.D., CNS drug development expert and former CEO and CMO at Sunovion Pharmaceuticals, appointed as Seaport’s Chief Medical Officer and President of Clinical Development
Lana Gladstein, J.D., experienced attorney across all legal matters, including corporate governance, M&A transactions, alliance management and intellectual property, joins Seaport as General Counsel
BOSTON, June 18, 2024 – Seaport Therapeutics, a clinical-stage biopharmaceutical company that is advancing novel neuropsychiatric medicines with a proven strategy and team, today announced it has expanded its executive team with the appointment of Antony Loebel, M.D., as Chief Medical Officer and President of Clinical Development, and Lana Gladstein, J.D., as General Counsel. Seaport’s senior leadership team also includes Steven M. Paul, M.D., Founder and Chair of the Board of Directors; Daphne Zohar, Founder, Chief Executive Officer and Board Member; Eric Green, MBA, Chief Operating Officer; and Michael Chen, Ph.D., Co-founder and Chief Scientific Officer.
“I’m delighted to welcome two more outstanding members to our senior executive team. As we design and run studies to advance our clinical-stage pipeline of novel therapeutics focused on important mental health conditions, Tony’s deep understanding of neuropsychiatric drug development builds on our team’s distinct advantages,” said Daphne Zohar, Founder and Chief Executive Officer of Seaport. “We are rapidly growing our company and Lana’s experience across all facets of legal, including corporate governance, transactions, and IP, will be an important resource to Seaport. I’m thrilled to have both Tony and Lana onboard.”
Dr. Loebel was most recently the President and Chief Executive Officer of Sunovion Pharmaceuticals, a global pharmaceutical company focused on CNS drug development and commercialization, from 2019 to 2023. He served as the company’s Chief Medical Officer from 2011 to 2019. Dr. Loebel was instrumental in the growth of Sunovion from a small to mid-size company with over $2.5 billion in net revenue. He played a key role in the development and commercialization of LATUDA® for the treatment of patients with bipolar depression and schizophrenia, with the product achieving commercial success in the U.S. and globally under his leadership. Other products developed and approved under Dr. Loebel’s leadership included APTIOM® for partial-onset seizures and KYNMOBI® for the treatment of “OFF” episodes in patients with Parkinson’s disease. Prior to Sunovion, Dr. Loebel’s industry experience included drug development and medical affairs roles at Dainippon Sumitomo Pharma America and Pfizer, Inc. A board-certified psychiatrist, Dr. Loebel is a Fellow of the American College of Neuropsychopharmacology and a Life Fellow of the American Psychiatric Association. He has received multiple recognitions and awards including the International Society of CNS Drug Development’s 20th Anniversary Award for a consistent track record of innovation and leadership in CNS drug development in 2022. He was also named to PharmaVOICE’s list of “100 Most Inspiring People” in 2013 and 2019. He received his M.D. from the University of Washington School of Medicine.
“I’m excited to join Daphne, Steve and the rest of the incredible team at Seaport to help further advance its robust pipeline of important neuropsychiatric medicines,” said Dr. Loebel. “We have a unique opportunity to make a meaningful difference for the millions of people struggling with serious mental health conditions, including depression and anxiety.”
Lana Gladstein joins Seaport as General Counsel with over two decades of legal expertise, including corporate governance, navigating M&A transactions, licensing and partnerships, and intellectual property matters. Most recently, she was the Group General Counsel at APRINOIA Therapeutics, a clinical-stage company developing therapeutics and diagnostics for neurodegenerative diseases. Her prior roles include Chief Legal Officer at Recipharm (Americas), Chief Legal Officer and General Counsel at Arranta Bio (acquired by Recipharm), and Executive Vice President, General Counsel and Officer at Brammer Bio (acquired by Thermo Fisher for $1.7 billion). Prior to Brammer Bio, Ms. Gladstein was a partner at Pepper Hamilton (now Troutman Pepper) and Nutter, and held previous positions at Goodwin and Nixon Peabody, where she advised life science companies on corporate and intellectual property matters. She holds a J.D. from Northeastern University School of Law and a B.A. in biology from Brandeis University.
“I am humbled and thrilled to be joining the team at Seaport,” said Ms. Gladstein. “This is a team with an incredible track record of achievement and an unwavering commitment to advancing innovative therapeutics for patients. I look forward to leveraging my experience to build upon Seaport’s strong legal foundation and support its continued growth.”
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 invented and advanced important neuropsychiatric medicines and are guided by an extensive network of renowned scientists, clinicians and key opinion leaders. For more information, please visit www.seaporttx.com.
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