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Metabolic benefits of oral polymer-based duodenal exclusion therapy

Glyscend Therapeutics has presented preclinical study results at EASD 2021 evaluating the metabolic effects of once-daily oral therapy in an obese T2D Zucker Diabetic Fatty (ZDF) rat model over eight weeks. The results showed a statistically significant (p<0.0001) reduction in peak post-prandial glucose after chronic treatment, with simultaneously decreased early peak insulin levels.

Glyscend's synthetic polymers (Credit: Glyscend Therapeutics)

A separate eight-week study in a lean T2D Goto-Kakizaki (GK) rat model with once daily oral therapy resulted in a similar profound reduction in post-prandial glucose (PPG) along with improvement in insulin resistance. There was significant weight loss without difference in food intake and no safety signals were observed. The company said the results show strong evidence that oral, polymer-based duodenal exclusion therapy is a viable method of improving glucose homeostasis and provided the impetus for a first-in-human trial, initiated recently in South Australia in collaboration with Professors Chris Rayner and Michael Horowitz.

Glyscend’s patient-friendly, orally administered polymer therapy is intended to work locally in the GI tract by temporarily augmenting the natural mucus barrier lining in specific portions of the intestine. The novel synthetic polymers are inert, non-absorbed, and naturally eliminated through the GI tract within 24 hours. This barrier would alter food uptake in those portions of intestine to induce dramatic changes in hormonal signalling via the gut-liver-brain axis. Glyscend aims to replicate the beneficial effects of bariatric surgery via the “duodenal exclusion” mechanism, without the need for surgery. The duodenal exclusion mechanism has been well validated via other invasive endoscopic approaches.

Glyscend is developing a new class of oral gut-restricted therapies targeting mechanisms underlying bariatric surgery and validated by endoscopic approaches, which have shown to be beneficial in treating Type 2 diabetes (T2D). The therapy is intended to temporarily augment the natural mucus barrier lining in specific portions of the GI tract and affect hormonal signalling via the gut-liver-brain axis. The synthetic, inert, nonabsorbable polymer is then naturally eliminated via the GI tract within 24 hours.

“Our technology was inspired by the remarkable efficacy of gastric bypass surgery in correcting the metabolic alterations associated with Type 2 diabetes,” said Dr Ashish Nimgaonkar, President and CEO of Glyscend. “However, gastric bypass will likely never fully scale due to surgical risks, degree of invasiveness, access, and cost considerations. Therefore, our goal is to develop an oral medication that works locally in the GI tract and provides the benefits of surgery while greatly reducing the cost, risks, and potential complications.”

“While the data confirm a key role for chronic duodenal exclusion in restoring glucose homeostasis, ongoing research and development continue to provide further understanding of the impact that polymer science can play in shaping future therapies in the metabolic disease space,” added Dr Thomas Jozefiak, Co-Founder and Chief Scientific Officer of Glyscend.


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