Fractil Health Inc.
A single dose of Rejuva reduced fat mass and improved blood glucose levels in a well-validated diet-induced obesity (DIO) mouse model.
Rejuva also prevented weight and blood sugar rebound after semaglutide was stopped.
The data demonstrate for the first time that Rejuva treatment has the potential to mimic the natural release of GLP-1 from the pancreas.
BURLINGTON, Mass., June 23, 2024 (GLOBE NEWSWIRE) — Fractyl Health, Inc. (Nasdaq: GUTS) (the “Company”), a metabolic therapeutics company focused on pioneering new approaches in the treatment of obesity and type 2 diabetes (T2D), today presented new data from its preclinical Rejuva pancreatic gene therapy program in an oral presentation at the American Diabetes Association (ADA) 84th Scientific Sessions in Orlando, Fla. The presentation, titled “Single-Dose GLP-1-Based Pancreatic Gene Therapy Durably Preserves Body Composition and Glucose Following Semaglutide Withdrawal in an Obese Mouse Model,” was selected as one of eight President's Selected Abstracts to Note at the ADA this year.
Rejuva is the company's adeno-associated virus (AAV)-based GLP-1 pancreatic gene therapy program (PGTx) designed to durably produce GLP-1 in the pancreas for the treatment of obesity and type 2 diabetes. The study presented at ADA compared the effects of a single dose of Rejuva versus daily administration of semaglutide on body composition and glycemic parameters in a well-validated mouse model of diet-induced obesity (DIO). It also examined the effects of a single dose of Rejuva in DIO mice after semaglutide treatment was discontinued.
“These data demonstrate that Rejuva can provide durable improvements in body composition and fasting glucose levels comparable to or better than semaglutide by restoring GLP-1 production with a one-time treatment,” said Harith Rajagopalan, MD, PhD, co-founder and CEO of Fractyl. “These data also show that Rejuva may help maintain improvements after semaglutide is discontinued, highlighting the potential of our therapy to fill an important new need in the management of obesity and type 2 diabetes: a reliable 'off-ramp' from chronic GLP-1 medications, allowing patients to maintain their weight loss and glucose benefits even after stopping these medications.”
In a study published at ADA, obese (DIO) mice were randomly assigned 1:1:1 to one of the following and followed for four weeks:
Arm 1: A single dose of Rejuva GLP-1-based gene therapy candidate,
Arm 2: daily injections of semaglutide, or
Arm 3: placebo
After four weeks, treatment with semaglutide was discontinued for mice in arm 2 and they were further randomised 1:1 to receive either a single dose of the Rejuva gene therapy candidate or a placebo, with all animals followed for a further four weeks before moving on to the next evaluation arm at eight weeks.
The story continues
Arm 1: Continued follow-up of a single dose of Rejuva GLP-1-based gene therapy candidate
Arm 2a: Discontinue semaglutide at week 4
Arm 2b: Discontinue semaglutide and switch to single-dose Rejuva at week 4
Arm 3: Placebo follow-up
After 8 weeks, islets were isolated and the effect of glucose exposure on GLP-1-based gene transfer release from genetically modified islets was studied.
At week 4, the Rejuva group saw a fat mass loss of 21% of body weight and the semaglutide group saw a fat mass loss of 16% of body weight (both p<0.0001 compared to placebo, p<0.05 for Rejuva vs semaglutide), while both Rejuva and semaglutide maintained lean body mass with only a 5% loss in body weight (both p<0.0001 compared to placebo).
At week 8, semaglutide-withdrawal mice (Arm 2a) experienced a rebound in fat mass to 1% below baseline (ns), whereas semaglutide-withdrawn mice treated with Rejuva (Arm 2b) maintained 17% (p<0.01) and 22% (p<0.0001) fat loss at week 8.
Blood glucose and insulin levels in all intervention groups were consistent with changes in fat mass, with semaglutide and Rejuva-treated mice experiencing statistically significant improvements in fasting blood glucose and fasting insulin levels at four and eight weeks, but no improvement in blood glucose or insulin levels in semaglutide-discontinued mice who did not switch to Rejuva at week 8.
“In addition to the compelling durability of the improvements in weight loss, body composition and glycemic control seen in this model, we are pleased to see that genetically modified islets isolated from mice treated with Rejuva release GLP-1 in response to nutrients,” said Timothy Kieffer, PhD, chief scientific officer at Fractyl. “We believe this is a clear indication that Rejuva can mimic the physiological release of GLP-1 that occurs naturally in the human body.”
About Fractil Health
Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including obesity and type 2 diabetes. Despite treatment advances over the past 50 years, obesity and type 2 diabetes remain the fastest growing causes of morbidity and mortality in the 21st century. Fractyl Health's goal is to transform the treatment of metabolic diseases from chronic, symptomatic care to durable, disease-modifying therapies that target the root causes of disease at the organ level. Fractyl Health is based in Burlington, Massachusetts. For more information, please visit www.fractyl.com or https://twitter.com/FractylHealth.
About Rejuva
Fractyl Health's Rejuva® platform is focused on developing next-generation adeno-associated virus (AAV)-based locally administered gene therapies for the treatment of obesity and type 2 diabetes. The Rejuva platform is in preclinical development and has not yet been evaluated by regulatory authorities for research or commercial use. Rejuva leverages advanced delivery systems and proprietary screening methods to identify and develop metabolically active gene therapy candidates targeted to the pancreas. The program aims to transform the management of metabolic disease by providing novel disease-modifying therapies that address the underlying causes of disease.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to historical facts are deemed to be forward-looking statements, including, but not limited to, statements regarding the prospects and potential impact of preclinical or clinical trial data, the design, initiation, timing and results of clinical registration and clinical trials or readouts, the content, information used, timing or results of IND-enabling studies or IND applications, the potential launch or commercialization of our product candidates or products, the sufficiency of our cash, cash equivalents and investments to fund business activities in a particular period, and our strategy and product development objectives and goals, including enabling long-term management of obesity and type 2 diabetes without the burden of chronic treatment. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.These include, but are not limited to, our limited operating history, the occurrence of significant net losses and the fact that we expect to continue to incur significant net losses for the foreseeable future, our need for substantial additional financing, our ability to continue as a going concern, restrictive and financial covenants in our credit agreement, the lengthy and unpredictable regulatory approval process for our product candidates, uncertainties regarding our clinical trials, the fact that our product candidates may cause significant adverse events or undesirable side effects or have other characteristics that could cause clinical trials to be suspended or terminated, delay or prevent regulatory developments, prevent regulatory approvals, limit our commercial profile or have other characteristics that could have a material adverse effect. that additional time may be required to develop and obtain regulatory approval or certification for our Rejuva gene therapy candidates, our reliance on third parties to conduct certain aspects of our preclinical and clinical studies, our reliance on third parties for the manufacture of materials for our Rejuva gene therapy platform for our preclinical studies and ongoing clinical studies, the regulatory approval process with the FDA or comparable foreign regulatory authorities is lengthy and inherently unpredictable and we cannot predict when or whether we will be able to obtain regulatory approval or certification for our product candidates, even if we complete the necessary clinical studies, and any such regulatory approval or certification may be for a narrower indication than we seek, the potential launch or commercialization of our product candidates or products, our strategy and product development objectives and goals, and other factors discussed under the heading “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on May 13, 2024, and in our other filings with the SEC. These forward-looking statements are based on management's current estimates and expectations. Although the Company may elect to update such forward-looking statements at some point in the future, it assumes no obligation to do so, even if subsequent events cause the Company's views to change.
contact address
Company Contact
Lisa Davidson, Chief Financial Officer
ir@fractyl.com, 781.902.8800
Media Contact
Jessica Cotrone, Corporate Communications
jcotrone@fractyl.com, 978.760.5622
Investor Contacts
Stephen Jasper Gilmartin Group
stephen@gilmartinir.com, 619.949.3681
