ARPA-H Awards Up to $15 Million to Seaport Therapeutics and Monash Institute to Advance First Oral Therapy Targeting Gut Lymphatic Dysfunction
Seaport Therapeutics, a clinical-stage biopharmaceutical company focused on developing innovative medicines, has announced that it has been awarded up to $15 million from the Advanced Research Projects Agency for Health (ARPA-H). The funding will support the continued development of GlyphCele™ (also referred to as Cele-Pro™), an investigational oral therapeutic engineered using Seaport’s proprietary Glyph™ platform. The program is being advanced in collaboration with the Monash Institute of Pharmaceutical Sciences (MIPS) at Monash University.
The award represents a significant milestone for Seaport and its academic partner, enabling further development of what could become the first oral therapy specifically designed to restore normal gut lymphatic function. The gut lymphatic system plays a critical role in maintaining metabolic balance and immune regulation. Dysfunction in this system has been increasingly linked to serious conditions such as metabolic disease and pancreatic cancer.
Targeting the Root Cause of Lymphatic Dysfunction
The GlyphCele program focuses on addressing structural and functional abnormalities in the gut lymphatic vessels. Under healthy conditions, lymphatic vessels in the gastrointestinal tract transport dietary fats, immune cells, and inflammatory signals away from the gut and into systemic circulation. This transport system is essential for maintaining metabolic homeostasis and immune balance.
However, in metabolic disease, these lymphatic vessels can become damaged. Structural integrity is compromised, leading to leakage of lymphatic fluid into surrounding abdominal adipose tissue. This leakage triggers chronic inflammation, promotes weight gain, and contributes to insulin resistance. Over time, this inflammatory cycle drives metabolic dysfunction and increases the risk of type 2 diabetes and other related disorders.
GlyphCele has been specifically engineered to intervene at the source of this dysfunction. By delivering therapeutic activity directly into the gut lymphatic system, the drug candidate aims to restore vessel integrity, reduce leakage, and interrupt the inflammatory cascade that fuels disease progression. If successful, GlyphCele could represent a first-in-class, disease-modifying oral therapy for metabolic disorders linked to lymphatic damage.
Preclinical studies published in Nature Metabolism have provided proof-of-concept evidence supporting this approach. These studies demonstrated that lymphatic-targeted inhibition of COX-2 corrected lymphatic vessel damage, improved metabolic parameters, and reversed insulin resistance in animal models. These findings form the scientific foundation for advancing GlyphCele into further development.
Expanding Potential into Pancreatic Cancer
In addition to metabolic disease, GlyphCele is being developed with potential applications in pancreatic cancer. Tumor-associated lymphatic vessels can act as conduits for inflammatory signals and tumor-promoting factors, enabling the spread of cancer-related signaling into adjacent tissues. This process may contribute to tumor progression and metastasis.
By delivering therapy directly into the lymphatic network connecting the gut and pancreas, GlyphCele aims to enhance local immune responses against tumors while suppressing pro-inflammatory signals that promote cancer growth. This lymphatic-directed strategy offers a novel way to target disease biology rather than simply addressing downstream symptoms.
Across both metabolic disease and pancreatic cancer, GlyphCele is designed as a disease-modifying therapy. Rather than managing isolated clinical manifestations, the therapy seeks to correct fundamental biological abnormalities in lymphatic function.
The Glyph Platform: Enabling Lymphatic Delivery
Central to this innovation is Seaport’s proprietary Glyph™ platform. The Glyph technology enables the modification of a wide range of therapeutic molecules, including immunomodulators, to enhance their transport through the lymphatic system. Traditional oral drugs are primarily absorbed into the bloodstream via the portal circulation, which can result in systemic exposure and potential side effects.
In contrast, the Glyph platform is engineered to preferentially direct therapeutics into the lymphatic system. This targeted delivery approach provides more direct access to immune tissues while potentially reducing systemic drug levels. The result may be improved safety profiles and enhanced therapeutic precision.
GlyphCele itself is an investigational Glyphed oral prodrug of celecoxib, a well-known COX-2 inhibitor. By modifying celecoxib using the Glyph platform, Seaport aims to optimize lymphatic transport while minimizing systemic exposure. This approach is intended to harness the anti-inflammatory benefits of COX-2 inhibition in a localized, lymphatic-focused manner.
The development of a lymphatic-targeted oral therapy is particularly significant because there are currently no approved oral medicines designed specifically to normalize gastrointestinal lymphatic dysfunction. Moreover, no non-surgical treatments currently exist to restore structural integrity to compromised gut lymphatic vessels. This highlights the transformative potential of GlyphCele as a new therapeutic category.
Collaboration Between Seaport and Monash
The partnership between Seaport Therapeutics and the Monash Institute of Pharmaceutical Sciences reflects a long-standing scientific collaboration. Researchers at MIPS have contributed decades of foundational research in lymphatic physiology and drug transport mechanisms.
Professor Christopher Porter, Ph.D., Director of MIPS, emphasized that the program builds on years of scientific progress in understanding lymphatic transport but introduces a practical, patient-friendly solution. Instead of working around lymphatic dysfunction, the goal is to directly correct it through an orally administered therapeutic.
The collaboration strengthens continuity and scientific depth, combining Seaport’s drug development expertise with Monash’s academic leadership in pharmaceutical sciences. Together, the teams aim to translate fundamental lymphatic research into meaningful clinical outcomes.
ARPA-H and the GLIDE Program
The funding for this initiative comes from ARPA-H’s Groundbreaking Lymphatic Interventions and Drug Exploration (GLIDE) program. The GLIDE initiative is designed to accelerate the development of innovative therapies targeting primary lymphatic diseases, rare lymphatic disorders, and chronic conditions complicated by lymphatic dysfunction.
GLIDE supports a range of intervention strategies, including physical, pharmacologic, gene-based, and cell-based therapies. By funding high-impact, high-risk projects, ARPA-H seeks to catalyze breakthroughs that may not otherwise receive traditional funding support.
This particular award underscores the growing recognition of lymphatic biology as a critical yet underexplored driver of human disease. Lymphatic dysfunction has historically been overlooked compared to blood vascular systems, but emerging evidence suggests it plays a pivotal role in inflammation, metabolism, immunity, and cancer progression.
Strategic Importance for Seaport
For Seaport Therapeutics, the award provides non-dilutive funding to expand the reach of its Glyph platform beyond its primary focus area of neuropsychiatric medicines. While the company continues to prioritize central nervous system drug development, the success of GlyphCele could validate broader applications for lymphatic-targeted therapies.
Daniel Bonner, Ph.D., Co-Founder and Senior Vice President of Platform at Seaport, highlighted the transformative potential of the program. He noted that GlyphCele represents an opportunity to address fundamental aspects of disease biology that current treatments often overlook.
The company believes that the Glyph platform may have broad applicability across multiple disease areas. By demonstrating clinical proof-of-concept in metabolic disease and pancreatic cancer, Seaport could open the door to additional therapeutic programs targeting lymphatic dysfunction in other high-impact conditions.
A New Therapeutic Frontier
The development of GlyphCele represents more than a single drug program—it signals the emergence of a new therapeutic paradigm centered on lymphatic biology. By targeting the gut lymphatic system directly, researchers aim to interrupt disease processes at their biological roots.
If successful, GlyphCele could:
- Restore structural integrity to damaged lymphatic vessels
- Reduce inflammatory leakage into abdominal fat
- Improve metabolic markers and insulin sensitivity
- Strengthen local anti-tumor immune responses
- Suppress metastatic signaling pathways
Such outcomes could significantly alter treatment strategies for both metabolic disorders and pancreatic cancer.
With up to $15 million in ARPA-H funding supporting further research and development, Seaport Therapeutics and the Monash Institute of Pharmaceutical Sciences are advancing a program that may reshape how lymphatic-driven diseases are treated. As research progresses, GlyphCele could establish the first oral, lymphatic-targeted therapy designed to normalize gut lymphatic dysfunction—marking a potential breakthrough in modern medicine.
About Seaport Therapeutics
Seaport Therapeutics is a clinical-stage therapeutics company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The Company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph technology platform. All the therapeutic candidates in its pipeline of first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects. Seaport is led by an experienced team that invented and advanced important neuropsychiatric medicines and is guided by an extensive network of renowned scientists, clinicians, and key opinion leaders
