Date posted – 26 February 2021
Researchers from the Monash Institute of Pharmaceutical Sciences (MIPS) and PureTech Health (LSE: PRTC, Nasdaq: PRTC) have developed a novel technology platform that directly targets gut lymphatics and has great potential to enhance the utility of orally administered immunomodulators.
Published in the Journal of Controlled Release, the study shows preclinical proof-of-concept for the GlyphTM platform technology (a lymphatic-targeting technology platform), which is designed to traffic small molecule therapeutics into the lymphatic system and directly into gut-draining mesenteric lymph nodes (MLNs) after oral administration.
As a key nexus of immune cell trafficking, MLNs play major roles in the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, cancer, and metabolic diseases.
In this study the researchers demonstrated the ability of a therapeutic modality built from the Glyph platform to target administration of mycophenolic acid (MPA), an immunosuppressant, into lymph and directly into the MLNs.
The Glyph technology platform is designed to employ the body’s natural lipid absorption and transport process to orally administer drugs via the lymphatic system. The technology has the potential to (1) enable direct modulation of the immune system via drug targets present in mesenteric lymph nodes and (2) provide a broadly applicable means of enhancing the bioavailability of orally-administered drugs that would otherwise become inactive by first-pass liver metabolism. It was created based on intellectual property initially developed by Professor Chris Porter and his team at MIPS that was exclusively licenced to PureTech Health – a Boston based clinical-stage biotherapeutics company. The current study was led by Professor Porter, Dr Natalie Trevaskis and Dr Sifei Han and the key studies were conducted by Dr Ruby Kochappan.
Professor Porter said: “The Glyph platform has tremendous therapeutic potential for orally administered medicines because it allows us to bypass first-pass metabolism in the liver and directly target the lymphatic system, which is a critical site for immune cell programming and trafficking. With this study, we have shown that the platform enhances immunomodulation by MPA in the mesenteric lymph nodes. We are equally excited about the possibility to enhance bioavailability and in this regard, PureTech’s lead Glyph product candidate, LYT-300 (oral allopregnanolone) is expected to enter clinical trial by the end of 2021”.
“What’s interesting here is the idea that one might be able to target and administer immunomodulatory drugs to the mesenteric lymph nodes and therefore selectively suppress immune responses that emanate from those lymph nodes,” said, Joseph Bolen, Ph.D., Chief Scientific Officer at PureTech. “The Glyph platform is a highly innovative technology and we are moving quickly to build off this foundational research and establish additional therapeutic applications, including bypassing first pass metabolism and enabling oral bioavailability of parenteral drugs.”
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About the GlyphTM Platform
Glyph is PureTech’s synthetic lymphatic-targeting chemistry platform, which is designed to employ the body’s natural lipid absorption and transport process to orally administer drugs via the lymphatic system. PureTech believes this technology has the potential to (1) enable direct modulation of the immune system via drug targets present in mesenteric lymph nodes and (2) provide a broadly applicable means of enhancing the bioavailability of orally-administered drugs that would otherwise become inactive by first-pass liver metabolism. PureTech has demonstrated proof-of-concept by achieving therapeutically relevant plasma levels following oral administration of a neurosteroid, allopregnanolone, in small animal and non-human primate model systems. This and other work have resulted in the generation of PureTech’s lead Glyph product candidate, LYT-300 (oral allopregnanolone), which is expected to enter a clinical trial by the end of 2021. Additionally, PureTech announced an alliance with Boehringer Ingelheim in 2019, which is initially focused on evaluating the feasibility of applying the Glyph technology platform to one of its immuno-oncology product candidates. PureTech retains rights to all other applications of this technology outside of the specific BI candidates being studied. The Glyph technology platform is based on the pioneering research of Christopher Porter, Ph.D., Director of the Monash Institute of Pharmaceutical Sciences and his team at Monash University in Melbourne, which PureTech has exclusively licensed.