ARPA-H award supports the development of an oral prodrug, based on the Glyph™ platform initially developed at the Monash Institute of Pharmaceutical Sciences (MIPS), to address dysfunctional gut lymphatics linked to metabolic disease and pancreatic cancer.
Monash University has announced the award of support from the Advanced Research Projects Agency for Health (ARPA-H) to advance an oral prodrug of celecoxib – using the GlyphTM platform and designed to deliver therapy directly to the gut lymphatics – aiming to improve lymphatic function and advance the treatment of metabolic disease and pancreatic cancer by directly addressing local inflammation and lymphatic dysfunction.
The project is being led by the Monash Institute of Pharmaceutical Sciences (MIPS) in partnership with long term collaborator, Seaport Therapeutics, and is being backed by up to AUD$21.5M via the ARPA-H GLIDE (Groundbreaking Lymphatic Interventions and Drug Exploration) program.
The grant will support the development of GlyphCeleTM or Cele-ProTM, an oral prodrug of the COX-2 inhibitor celecoxib, that uses the Glyph lymphatic-targeting platform, initially developed at MIPS and now exclusively licensed to Seaport. GlyphCele is specifically engineered to target and normalize dysfunction in the gut lymphatic system, which plays a central role in metabolic disease and pancreatic cancer.
In metabolic disease, lymphatic vessels that normally move dietary fats and immune signals out of the gut can lose their structure and begin leaking fluid into nearby abdominal fat, fueling inflammation, weight gain, and insulin resistance. Using the GlyphTM platform, GlyphCele is designed to address this defect at its source by delivering therapy directly into the gut lymphatics. If successful, it would be the first oral therapeutic restoring normal vessel function, reducing lymphatic leakage, and breaking the cycle that drives metabolic dysfunction. Preclinical studies published by the MIPS researchers in Nature Metabolism provided initial proof of concept that lymphatic targeted COX2 inhibition can correct this lymphatic damage, improve metabolic markers and reverse insulin resistance.
In pancreatic cancer, tumour associated lymphatics can allow inflammatory and tumor-promoting signals to spread into surrounding tissues, supporting disease progression. By delivering GlyphCele directly into the lymphatic network that connects the gut and pancreas, the Glyph platform is intended to strengthen local anti-tumor activity and suppress metastasis. Across both conditions, GlyphCele is designed to treat the underlying disease biology rather than managing downstream symptoms.
Professor Chris Porter, Director of the Monash Institute of Pharmaceutical Sciences (MIPS) said, “This program builds upon decades of scientific progress in lymphatic physiology and transport of therapeutics, but brings something truly new: a practical, patient-friendly strategy to directly correct gut lymphatic dysfunction rather than work around it.”
“This collaboration brings together a team at MIPS led by myself, Dr Enyuan Cao and Professor Natalie Trevaskis and our collaborators at Seaport that have worked together closely since the earliest days of the Glyph platform. I am delighted that the support form ARPA-H will allow us to strengthen and deepen our understanding of the Glyph platform and importantly will allow us to pursue a therapeutic approach that could meaningfully change how lymphatic-driven diseases are treated,” Professor Porter said.
Daniel Bonner, Ph.D., Co-Founder and Senior Vice President, Platform, at Seaport Therapeutics said, “The work behind GlyphCele represents an opportunity to address fundamental aspects of disease biology that current treatments overlook, and we are delighted to work with ARPA-H and the Monash team to advance a program that could ultimately transform outcomes for patients across multiple complex diseases.”
“While our internal focus at Seaport remains on developing neuropsychiatric medicines, the Glyph platform has broad applicability across diseases, and we’re pleased to advance its potential beyond CNS through non-dilutive funding,” Mr Bonner said.
The success of this program could establish a disease-modifying approach in both metabolic disease and pancreatic cancer. It may also help lay the foundation for future lymphatic-targeted therapies and support the broader applicability of the Glyph platform across high-impact diseases.
There are currently no approved lymphatic-targeted oral medicines and no non-surgical method to normalize gastrointestinal lymphatic dysfunction. This underscores the potential of this program to advance a completely new mechanism of action for diseases driven by lymphatic dysfunction.
This effort is part of ARPA-H’s Groundbreaking Lymphatic Interventions and Drug Exploration (GLIDE) program. GLIDE aims to develop physical, pharmacologic, gene, and cell-based therapeutic interventions to treat primary and rare lymphatic disease and chronic conditions complicated by lymphatic dysfunction. GLIDE is led by ARPA-H Program Manager, Kimberley Steele, M.D., Ph.D.
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