Seaport Therapeutics (SPTX) TD Cowen 6th Annual Novel Mechanisms in Neuropsychiatry Summit summary

Key achievements and strategic outlook

• Advanced lead program GlyphAllo into phase II-B for major depressive disorder, with top-line data expected in H1 2027.

• GlyphAgo, based on agomelatine, showed clinical proof of concept and is entering two phase II trials in generalized anxiety disorder, with data expected in 2028.

• Glyph2BLSD is in preclinical development, aiming to harness psychedelic pharmacology without hallucinogenic effects.

• $427 million cash runway projected to fund operations into 2029, covering key clinical milestones.

• Leadership team leverages experience from Karuna, focusing on proven mechanisms and addressing prior drug limitations.

Platform innovation and differentiation

• Glyph platform enables oral delivery of drugs with poor bioavailability by bypassing first-pass liver metabolism via lymphatic transport.

• Each "Glyph-ed" molecule is a new chemical entity with novel IP, improving PK profiles and reducing side effects.

• GlyphAllo demonstrated a 9-fold increase in bioavailability over allopregnanolone and retained pharmacology with improved tolerability.

• GlyphAgo achieved a 6.8-fold increase in bioavailability and a 10-fold reduction in PK variability compared to agomelatine.

• Platform has broad applicability, with ongoing discussions for partnerships and recent ARPA-H grant for gut lymphatic targeting.

Clinical development highlights

• GlyphAllo phase II-A showed statistically significant reduction in stress-induced salivary cortisol, similar to alprazolam but with a different mechanism.

• Driving simulation study confirmed no next-morning impairment, differentiating GlyphAllo from zuranolone.

• Phase II-B trial in MDD includes patients with and without anxious distress, addressing a large unmet need and leveraging allopregnanolone’s anxiolytic effects.

• Trial design incorporates lessons from Karuna to minimize placebo response and optimize success probability.

• Primary endpoint is HAM-D, chosen for its sensitivity to anxiety and insomnia subscales relevant to the drug’s profile.