Seaport Therapeutics, a clinical-stage biotechnology company focused on developing neuropsychiatric medicines, has secured funding of up to USD 15 million from the Advanced Research Projects Agency for Health (ARPA-H) to advance its investigational therapy GlyphCele (Cele-Pro). The project is being conducted in collaboration with the Monash Institute of Pharmaceutical Sciences (MIPS).

GlyphCele has been developed using Seaport’s proprietary Glyph technology platform and is designed to target and restore dysfunction in the gut lymphatic system, a key pathway involved in metabolic disorders and pancreatic cancer progression. The platform enhances lymphatic transport of therapeutic molecules, allowing drugs to directly access immune pathways and disease sites.

In metabolic disease, damage to lymphatic vessels in the gut can cause leakage of fluid into abdominal fat tissue, contributing to inflammation, weight gain and insulin resistance. GlyphCele aims to address this problem by delivering treatment directly to the gut lymphatics, potentially restoring vessel function and reducing lymphatic leakage. Preclinical studies published in Nature Metabolism demonstrated that targeting the lymphatic system with COX-2 inhibition could repair lymphatic damage, improve metabolic markers and reverse insulin resistance.

The therapy also has potential applications in pancreatic cancer. Tumour-associated lymphatic vessels can spread inflammatory and tumour-promoting signals into surrounding tissues. By delivering the drug into the lymphatic network linking the gut and pancreas, GlyphCele is designed to enhance local anti-tumour activity and limit cancer spread.

Daniel Bonner, Ph.D., Co-Founder and Senior Vice President of platform at Seaport Therapeutics, said the research could address fundamental biological mechanisms underlying complex diseases. He added that while the company’s primary focus remains on neuropsychiatric medicines, the Glyph platform may have broader applications across multiple therapeutic areas.

The ARPA-H award will support the development of GlyphCele, an investigational oral prodrug of the COX-2 inhibitor celecoxib. The therapy is engineered to selectively target the lymphatic system, potentially reducing systemic exposure while improving safety and therapeutic efficacy. If successful, the programme could establish a new disease-modifying approach for both metabolic disorders and pancreatic cancer.

Professor Christopher Porter, Director of the Monash Institute of Pharmaceutical Sciences, noted that the project builds on decades of research into lymphatic drug transport and aims to provide a practical strategy to directly correct gut lymphatic dysfunction.

The initiative forms part of ARPA-H’s Groundbreaking Lymphatic Interventions and Drug Exploration (GLIDE) programme, which supports the development of novel therapeutic approaches to treat diseases linked to lymphatic dysfunction.

Seaport’s Glyph platform enables oral drugs to be absorbed through the intestinal lymphatic system in a manner similar to dietary fats, allowing more efficient delivery of therapies that otherwise suffer from low bioavailability or high liver metabolism. The technology has already generated several therapeutic candidates in the company’s pipeline.