PureTech Announces Publication of New Preclinical Research from Collaborators that Supports Mesenteric Lymphatic Dysfunction as a Potential Cause of and Therapeutic Target for Obesity and Insulin Resistance

PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, today announced the publication of a research paper in Nature Metabolism, which showed for the first time that restoring normal function of the mesenteric lymphatics may reverse insulin resistance and modify obesity-associated metabolic disease. Results from the preclinical study provide further support for the therapeutic potential of PureTech’s Glyph technology platform, which is designed to enable the trafficking of small molecule drugs directly into the mesenteric lymphatic system following oral administration. The groundbreaking study was led by PureTech collaborators Natalie Trevaskis, Ph.D., Associate Professor at the Monash Institute of Pharmaceutical Sciences (MIPS) in Australia, Christopher Porter, Ph.D., MIPS Director, and Enyuan Cao, Ph.D., Post-Doctoral Research Fellow at MIPS, in collaboration with PureTech scientists.

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PureTech Health today announced the publication of a research paper in Nature Metabolism using its Glyph technology platform that showed - for the first time - that mesenteric lymphatic dysfunction may be a potential cause of and therapeutic target for obesity and insulin resistance. (Graphic: Business Wire)

The work demonstrates that obesity may be associated with profound and progressive dysfunction of the mesenteric lymphatic system. As shown in preclinical models, a high-fat diet stimulated the formation of new lymphatic vessels, which grew in a highly disorganized pattern. These tortuous, branching vessels tended to leak lymphatic fluid rich in lipid metabolites and pro-inflammatory mediators into the visceral adipose tissue in the abdomen, triggering the promotion of insulin resistance. Results from ex vivo experiments using clinical samples suggest that these observations may extend to humans as well.

“We have known for years that the accumulation of fat around the abdomen is correlated with higher rates of diabetes, but the biological reasons remained unclear. This is the first study to identify the profoundly damaging cycle in which the accumulation of abdominal fat leads to dysfunction of the mesenteric lymphatics, which in turn promotes more fat deposition and insulin resistance,” said Dr. Trevaskis. “Most exciting of all, we have preclinical evidence that intervening in this cycle by inhibiting the pathways associated with the lymphatic dysfunction may be a treatment for both obesity and associated metabolic disease. We believe that PureTech’s Glyph technology platform is key to this intervention, because it traffics the inhibitors directly where they are needed in the mesenteric lymphatics.”