1 As of October 18, 2024, PureTech’s percentage ownership of Seaport Therapeutics was approximately 36.7% on a partially diluted basis. This calculation includes outstanding shares, options, and warrants, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans. PureTech ownership reflects current ownership and does not take into account any potential future dilution, if applicable, as a result of conversion of that debt amount.
Charting a proven path in neuropsychiatry
Seaport is advancing a clinical-stage pipeline of neuropsychiatric medicines that includes its most advanced therapeutic candidate, SPT-300 (formerly known as LYT-300), an oral prodrug of allopregnanolone, which is being advanced for the treatment of major depressive disorder with or without anxious distress, SPT-320 (formerly known as LYT-320), a novel prodrug of agomelatine, which is being advanced for the treatment of Generalized Anxiety Disorder (GAD), and SPT-348, a prodrug of a non-hallucinogenic neuroplastogen, which is in development for the treatment of mood and other neuropsychiatric disorders.
With intersecting interests in enabling promising neuropsychiatric drugs to reach their full potential and the emerging science around the lymphatic system, we identified a breakthrough technology being developed at Monash University that had the potential to selectively transport therapeutic molecules through the lymphatic system.
With the Glyph platform, drugs are absorbed like dietary fats through the intestinal lymphatic system and transported into circulation. 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. We prioritized areas of high unmet patient need where the broad application of treatment options with validated efficacy was untapped due to these issues. The Glyph platform has been refined at PureTech and Seaport to efficiently generate multiple therapeutic candidates within Seaport’s pipeline.
In October 2024, Seaport announced the close of its $225 million oversubscribed Series B. 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.
In April 2024, Seaport launched with a $100 million oversubscribed Series A financing to progress the development of novel neuropsychiatric candidates enabled by the Glyph platform. Seaport is led by PureTech Founder and former CEO and Seaport Founder Daphne Zohar, with Steven M. Paul, M.D., former CEO and Chair of Karuna, as Founder and Chair of the Seaport Board of Directors.
In December 2023, SPT-320 (Glyph-agomelatine) was nominated as a new therapeutic candidate powered by the Glyph platform. A novel prodrug of agomelatine, SPT-320 is in development for the treatment of GAD. Agomelatine is effective in treating GAD and major depressive disorder (MDD) and offers superior tolerability to standard of care. However, agomelatine has low (~1%) bioavailability due to high first-pass metabolism, resulting in increased liver enzymes in some patients and necessitating frequent liver function monitoring that has held back the drug. SPT-320 uses the Glyph platform to bypass first-pass metabolism by the liver and thus has the potential to reduce liver exposure, hepatotoxicity, and the need for liver function monitoring.
In November 2023, successful topline results from the randomized, proof-of-concept Phase 2a trial of SPT-300 (Glyph-allopregnanolone) were reported. The trial was designed to evaluate the salivary cortisol response in the Trier Social Stress Test, a validated clinical model of anxiety in healthy volunteers. Oral administration of SPT-300 achieved the trial’s primary endpoint of a statistically significant reduction versus placebo in the increase from baseline to peak levels of the stress hormone salivary cortisol (p=0.0001) with a treatment effect size versus placebo of 0.72, measured by Cohen’s d.
In August 2023, it was announced that the U.S. Department of Defense awarded up to $11.4 million to advance SPT-300 for the treatment of Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).
SPT-300, an oral prodrug of allopregnanolone, 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.
SPT-320, a novel prodrug of agomelatine, is being advanced into Phase 1 studies for the treatment of generalized anxiety disorder (GAD).
SPT-348, a prodrug of a non-hallucinogenic neuroplastogen, is in development for the treatment of mood and other neuropsychiatric disorders.
Multiple discovery and preclinical programs underway.
As of December 31, 2023, the extensive Glyph intellectual property portfolio includes 20 families of patent filings directed to platform technologies which provide expansive coverage for a broad range of novel linker chemistries, as well as product technologies directed to compositions of matter for a wide variety of prodrugs and methods of use for the treatment of various indications, including several CNS-related indications. This intellectual property estate comprises eight (8) families of patent filings that provide exclusive rights to IP that is co-owned or exclusively licensed with Monash University and twelve (12) families of company-owned patent applications covering various aspects of the Glyph prodrug technologies, including compositions of matter, formulations, synthetic processes, and methods of therapeutic uses. Any patents to issue from these patent families are expected to expire in 2035 through 2044, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. PureTech retains the right to develop non-CNS therapies utilizing the Glyph platform, subject to certain contractual constraints.
Seaport Therapeutics is advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. All the therapeutic candidates in the pipeline of first and best-in-class medicines are based on the Glyph platorm, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce hepatotoxicity and other side effects.