Glyscend Therapeutics Releases New Phase 1 Biomarker Results and Initiates Phase 2 Clinical Trial under an IND for GLY-200 as a Potential First-in-Class Type 2 Diabetes Treatment

GLY-200 is a First-in-Class, Oral, Gut-Targeted Approach for Treatment of Type 2 Diabetes and Related Metabolic Conditions

Newly Released Phase 1 Biomarker Data is Consistent with Effects of Roux-en-Y Gastric Bypass Surgery and Duodenal Exclusion Devices

Initial Data from Phase 2 Trial Evaluating GLY-200 in Patients with Type 2 Diabetes Anticipated in Early 2023

BOSTON, Sept. 20, 2022 /PRNewswire/ -- Glyscend Therapeutics, a clinical-stage biotechnology company, today reported additional biomarker results from their Phase 1 study of GLY-200, a proprietary orally administered, gut-restricted therapeutic for the treatment of type 2 diabetes (T2D). Glyscend also received clearance from the U.S. Food and Drug Administration (FDA) on an Investigational New Drug (IND) application to evaluate GLY-200 for the treatment of T2D and has initiated a Phase 2 clinical trial in patients with T2D.

Metabolic surgery is a highly effective but invasive treatment for T2D and works in part by excluding the duodenum (the upper small intestine) from the digestive tract. GLY-200 is taken orally and is designed to mimic this duodenal exclusion by enhancing the natural mucus barrier in the duodenum. This pharmaceutical approach may non-invasively and safely reproduce many of metabolic surgery's beneficial effects including improvements in glycemic and bodyweight control. Results from a preclinical in vivo study showing retention of GLY-200 in the duodenum will be presented at the European Association for the Study of Diabetes (EASD) 2022 annual meeting this month.

As previously announced, in a completed single and multiple ascending dose (SAD/MAD) Phase 1 trial that enrolled 64 healthy adult volunteers, GLY-200 was well-tolerated with no safety signals observed. Today, Glyscend reported key results from the study's exploratory endpoints indicating that 5-days dosing with GLY-200 resulted in statistically significant effects on glucose, insulin, and bile acids, and was associated with changes in gut hormones such as GLP-1 and glicentin compared to placebo. These results were consistent with the effects observed following metabolic surgery and use of duodenal exclusion devices. Topline results of this study will be presented at The Obesity Society annual meeting, Obesity Week 2022, in November.

"These new biomarker results are very encouraging and strongly suggest that GLY-200 is modulating gut signaling in humans," said Professor Christopher Rayner MBBS, PhD, FRACP, Professor of Medicine at Adelaide Medical School, Consultant Gastroenterologist at the Royal Adelaide Hospital, and Principal Investigator of the Phase 1 study. "Duodenal exclusion, via metabolic surgery and devices, is a validated mechanism for the treatment of type 2 diabetes and obesity, but few patients have access to these treatments due to the invasiveness of the procedures. These data represent the first clinical evidence that duodenal exclusion may be possible with a non-invasive, orally administered, pharmaceutical treatment."

The initiation of the Phase 2 trial follows FDA clearance of the company's IND application for GLY-200 for T2D.

"We are thrilled to have expeditiously advanced GLY-200 into the Phase 2 trial in patients with T2D," said Ashish Nimgaonkar, M.D., President & CEO of Glyscend. "Type 2 diabetes remains a dangerous, growing, and expensive endemic worldwide, with a severe lack of pharmaceutical innovation over the last 15 years. U.S. FDA's recently revised guidance that eliminated cardiovascular outcomes trial requirements prior to approval of new T2D drugs will accelerate the clinical development timelines for GLY-200. The totality of the Phase 1 and preclinical data generated to date give us confidence in its therapeutic potential in T2D, and we are proud of what this milestone means, not just for the company, but for the many T2D patients who struggle daily with this condition."

The Phase 2 trial is a randomized, double-blind, placebo-controlled study of orally administered GLY-200, as an adjunct to diet and exercise, in patients diagnosed with T2D whose blood glucose levels have been inadequately controlled with metformin. Key objectives of the study are to evaluate the safety and tolerability of GLY-200 following 14 days of twice daily dosing. In addition, efficacy will be assessed by evaluating changes in fasting and postprandial glucose, insulin, and gut hormones. The Phase 2 trial is actively enrolling patients, and Glyscend expects to report initial clinical data in the first half of 2023.

"Diabetes is a progressive disease that requires the addition of multiple drug therapies over time to maintain glucose and weight control. Despite currently available therapies, half of patients in the U.S. suffer from uncontrolled diabetes, which can have debilitating consequences," said John Buse, M.D., Chief, Division of Endocrinology and Director of Diabetes at UNC School of Medicine. "The potential for an oral, non-absorbed therapy with a unique and complementary mechanism of action is a highly attractive offering to the T2D community. Patients need new options, and I am intrigued by the disease-modifying potential of this novel therapy."

About GLY-200

GLY-200 is a proprietary mucin-complexing polymer designed to enhance the natural mucus barrier in the duodenum (the upper small intestine). This enhanced barrier results in a pharmacologic 'duodenal exclusion' that may non-invasively and safely reproduce many of the beneficial effects of metabolic surgery including improvements in glycemic and bodyweight control. In a Phase 1 trial in healthy volunteers, oral administration of GLY-200 demonstrated a favorable safety profile and led to positive pharmacodynamic effects consistent with the acute effects of metabolic surgery and duodenal exclusion devices. GLY-200 is currently being evaluated in a Phase 2 clinical trial for type 2 diabetes.

About Type 2 Diabetes

Type 2 diabetes (T2D) affects approximately 500 million people worldwide and is characterized by complex metabolic dysfunctions resulting in high morbidity and mortality and significant treatment costs. The current standard of care begins with lifestyle alterations and escalates through oral drugs, injected medications, insulin, and, in a select few, metabolic surgery. Despite the many therapeutic options, nearly half of T2D patients continue to exhibit uncontrolled diabetes. Moreover, none of the currently available therapies are considered disease-modifying, with the exception of metabolic surgery, which involves surgical exclusion of the first part of the small intestine (the duodenum) and bypass of nutrient absorption in that region. Of all therapeutic interventions for T2D, metabolic surgery has shown the most immediate and profound effects on improving blood glucose and body weight, with longer-term reductions in microvascular complications related to T2D. However, while effective, a limited number of patients qualify for metabolic surgery due to its invasiveness and cost.

About Glyscend, Inc.

Glyscend Therapeutics is a clinical-stage biopharmaceutical company developing novel, orally administered, polymer therapies that work on targets inside the gastrointestinal tract to treat a variety of metabolic and chronic disorders. Polymer-based therapies are a unique class of therapeutics with more than three decades of clinical experience in a wide range of applications. Glyscend's polymer technology platform evolved out of research at Johns Hopkins University where scientists were evaluating the mechanisms that result in significantly improved glucose and metabolic regulation that precedes weight loss in certain types of metabolic surgery. The company's lead product candidate, GLY-200, is in clinical development initially for the treatment of type 2 diabetes. In addition, Glyscend is exploring program opportunities that address topical GI as well as systemic, inflammatory, and autoimmune conditions. The company is also investigating its technology to unlock novel GI tract targets using polymer-drug conjugates and to enhance the bioavailability of oral peptide therapies. For more information, please visit www.glyscend.com.