Monash scientists and collaborators Seaport Therapeutics publish further data exemplifying the benefits of the Glyph™ drug targeting platform
13 February 2025
- Published data shows new site of Glyph prodrug attachment demonstrated highest reported level of lymphatic transport to date of the studied immunomodulatory drug;
- New linkers display up to two-fold higher release in lymph nodes compared to top-performing previously reported linkers;
- Research builds on prior evidence supporting the versatility of Glyph platform.
A new study led by the Monash Institute of Pharmaceutical Sciences (MIPS) has evaluated ways of modifying mycophenolic acid (MPA), an immunomodulatory drug, in order to enhance targeting to the lymphatic system and delivery to lymph nodes - a major site of immune response.
The paper, published in Molecular Pharmaceutics probed the impact of structural change to the GlyphTM drug delivery platform, a lymph-targeted prodrug technology initially discovered by Professor Chris Porter and his team at MIPS, now licenced to the Boston-based Seaport Therapeutics .
Subsequently, the MIPS team has worked closely with Seaport to help successfully progress the platform and advance development candidates including SPT-300, an oral form of the drug allopregnanolone, through clinical proof of concept.
The current study is the first to show the impact of changing the drug attachment points of a lymph-targeted prodrug on lymphatic drug transport and targeted drug exposure. This work took advantage of the chemical structure of MPA which allowed comparison of two distinct prodrug attachment points on the same drug molecule and showed that conjugation via a newly examined phenol attachment point gave the highest lymphatic transport of MPA reported to date (55 percent) and two-fold higher release in lymph nodes than the previously reported acid attachment point.
This research demonstrates the impact of linker characteristics on the extent of lymphatic transport and drug delivery and release in the lymph nodes. Overall, these results underscore the benefits of a tailored lymphatic drug design approach.
Professor Porter said this research highlights the importance of integrating a careful and individualized balance of intestinal stability, transport efficiency and release in the mesenteric lymph nodes to maximise therapeutic exposures as part of a tailored lymphatic drug design approach.
“This study expands our understanding of lymphatic drug delivery and offers new insights for designing drugs with improved exposure to reach their intended targets more effectively,” Professor Porter said.
“This study highlights the importance of integrating a careful and individualized balance of intestinal stability, transport efficiency and release in the mesenteric lymph nodes to maximize therapeutic exposures as part of a tailored prodrug design approach.”
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.
“Our Glyph platform allows for a bespoke design approach, and this research reinforces the significance of the innovation behind our prodrug chemistry technology,” said Daniel Bonner, Ph.D., Co-founder, Senior Vice President, Platform, at Seaport Therapeutics. “Most importantly, Glyph has been clinically validated with demonstrated proof-of-concept data in humans and is being applied across Seaport’s pipeline of novel neuropsychiatric medicines, with enormous potential across a broad range of applications beyond CNS and neuropsychiatry.”
About the GlyphTM Platform
GlyphTM 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, Journal of Controlled Release and Molecular Pharmaceutics supporting the Glyph platform’s capabilities. See Glyph in action here.