ForePass Shows Surgery-Like Benefits While Advancing a Less Invasive Approach to Obesity Treatment
Keyron has announced the publication of new preclinical research in Gut, one of the world’s highest-ranked gastroenterology journals, highlighting the potential of its ForePass endoscopic metabolic bypass platform to reproduce metabolic effects historically associated with highly invasive bariatric surgery. According to the company, the findings demonstrated that ForePass achieved insulin sensitivity levels comparable to those observed following biliopancreatic diversion (BPD) surgery while significantly outperforming the GLP-1 therapy semaglutide in weight management outcomes in a randomized preclinical study.
The publication represents a major milestone for Keyron as the company advances its minimally invasive metabolic disease platform toward first-in-human clinical studies. ForePass is being developed as an incision-free, fully reversible endoscopic intervention designed to deliver surgery-level metabolic benefits without the risks, recovery demands, or permanence associated with conventional bariatric surgery.
The study focused on evaluating ForePass against both semaglutide and control groups in preclinical models of obesity and metabolic dysfunction. Researchers observed substantial improvements in insulin sensitivity, glucose control, and body weight regulation among ForePass-treated subjects.
According to the study, insulin sensitivity levels achieved with ForePass closely mirrored those historically reported following biliopancreatic diversion, a bariatric surgical procedure widely considered one of the most metabolically effective interventions ever developed for obesity and type 2 diabetes. BPD has been associated with diabetes remission rates approaching 80% and total body weight loss of approximately 40% to 50% in human patients.
Despite its efficacy, however, BPD remains rarely performed due to its highly invasive nature and the significant surgical risks involved. Industry estimates cited by Keyron suggest that only around 1% of eligible patients ultimately undergo bariatric surgery, leaving millions of patients without access to interventions capable of producing durable metabolic reversal.
At the same time, the company highlighted limitations associated with currently available pharmacological approaches, including GLP-1 receptor agonists such as semaglutide, marketed as Ozempic and Wegovy. Although these therapies have transformed obesity treatment in recent years, many patients with severe obesity and advanced metabolic disease still fail to achieve the level of weight reduction required for meaningful disease reversal.
According to data referenced by the company, approximately 92% of semaglutide-treated patients fail to achieve 15% weight loss, a threshold that may still be insufficient for patients with advanced metabolic dysfunction. Researchers and clinicians increasingly recognize that patients with severe obesity often require substantially greater weight reduction to reverse diabetes, improve insulin resistance, and reduce long-term cardiovascular risk.
Within the randomized preclinical study, ForePass demonstrated marked improvements in glucose metabolism and insulin sensitivity. During oral glucose tolerance testing, animals treated with ForePass showed near-complete suppression of post-meal glucose excursions while requiring substantially lower insulin levels to maintain glycemic control. These findings were interpreted as evidence of significant restoration of insulin sensitivity.
The company stated that insulin sensitivity levels observed in ForePass-treated animals were more than double those achieved in semaglutide-treated subjects, underscoring the potential of the platform to address underlying metabolic dysfunction rather than simply reducing appetite or slowing gastric emptying.
ForePass also delivered significantly stronger outcomes in body weight management compared with semaglutide. Animals treated with ForePass experienced only 4.3% weight gain over the study period, compared with 36% weight gain in semaglutide-treated animals and 47% weight gain in untreated controls. According to Keyron, these findings indicate that ForePass limited weight gain more than eight-fold relative to semaglutide and more than ten-fold relative to untreated animals.
The study was led by Ivo Boskoski, a leading gastrointestinal endoscopist and Professor of Digestive Endoscopy at Università Cattolica del Sacro Cuore. Boskoski stated that the findings demonstrate the possibility of reproducing metabolic effects previously achievable only through invasive bariatric surgery by using a minimally invasive and reversible endoscopic approach.
According to Boskoski, the magnitude of the observed improvements in insulin sensitivity and glycemic regulation was particularly noteworthy. He emphasized that the study supports the growing scientific understanding that metabolic interventions targeting the upper intestine may fundamentally alter glucose regulation and insulin resistance pathways.
Giorgio Castagneto Gissey, Founder and Chief Executive Officer of Keyron, said the ForePass platform was designed around the concept that the proximal intestine plays a critical role in metabolic disease biology, particularly in insulin resistance and glucose homeostasis.
Gissey explained that the new findings support the possibility that metabolic benefits historically achievable only through major surgery may soon become available through a scalable and fully reversible endoscopic procedure. He noted that such an approach could reduce dependence on lifelong drug therapy while expanding access to effective metabolic interventions for a much larger patient population.
The study also received support from Geltrude Mingrone, Professor of Diabetes at King’s College London and a recognized expert in metabolic surgery and diabetes research.
Mingrone stated that biliopancreatic diversion has long demonstrated the importance of excluding the proximal intestine in achieving profound metabolic improvements. However, she noted that the invasiveness and complexity of BPD have significantly limited its adoption in routine clinical practice.
According to Mingrone, ForePass represents an exciting development because it seeks to replicate these established metabolic mechanisms through a minimally invasive and reversible endoscopic solution. She added that the insulin sensitivity improvements observed in the large-animal model support continued advancement toward human clinical evaluation.
The newly published study builds on earlier peer-reviewed research involving ForePass that appeared in both Diabetes, Obesity and Metabolism and Gut. Previous studies demonstrated favorable effects on metabolic markers, insulin sensitivity, microbiome composition, and body weight control in preclinical obesity models.
Keyron believes the cumulative evidence generated to date supports ForePass as a potentially transformative approach for patients with severe obesity and metabolic disease who are either unwilling or unable to undergo major bariatric surgery.
Unlike traditional bariatric procedures, ForePass is designed to be deployed using a short outpatient endoscopic procedure that does not require surgical incisions. The system is also intended to be fully reversible, which could offer important advantages for patients and physicians concerned about the permanence and risks associated with surgical interventions.
The company believes these characteristics could dramatically broaden access to metabolic intervention by offering surgery-level efficacy through a less invasive and potentially safer procedure. Such an approach may be particularly important as global obesity and metabolic disease rates continue to rise and healthcare systems face increasing pressure to manage associated complications including type 2 diabetes, cardiovascular disease, and fatty liver disease.
The global obesity epidemic continues to represent one of the largest unmet medical challenges worldwide. While pharmaceutical therapies have expanded treatment options significantly in recent years, many experts believe additional solutions are needed for patients with severe or advanced disease who require deeper metabolic intervention.
Keyron’s ForePass platform seeks to address this treatment gap by combining principles traditionally associated with metabolic surgery with the accessibility and reversibility of advanced endoscopic technologies. By targeting the biological pathways underlying insulin resistance and glucose dysregulation, the company aims to provide a therapy capable of delivering durable metabolic improvement without the burden of major surgery.
Based on the encouraging preclinical findings now published in Gut, Keyron is advancing ForePass toward first-in-human clinical studies focused on severe obesity and metabolic disease. The upcoming trials are expected to further evaluate the safety, feasibility, and metabolic efficacy of the platform in human patients as the company works toward broader clinical development and potential commercialization.
About Keyron
Keyron is an endoscopic metabolic platform designed to reproduce key biological effects of metabolic surgery without incisions or permanent anatomical modification. Its lead product, ForePass®, is a minimally invasive, fully reversible treatment for patients with severe obesity and metabolic disease too advanced for drugs and unwilling or unable to undergo surgery.
