Fractyl Health to Present New Preclinical Data on Sustained Weight Maintenance and Blood Sugar from its Rejuva® RJVA-001 Single-Administration GLP-1 Pancreatic Gene Therapy Candidate at ObesityWeek® 2024
Fractyl Health (GUTS) presented new preclinical data for its Rejuva RJVA-001 single-administration GLP-1 pancreatic gene therapy candidate. The 13-week study in diet-induced obesity mice showed sustained weight maintenance and blood sugar control, with over 10% of islet cells expressing GLP-1 protein and no safety concerns. The company also announced RJVA-002, a GIP/GLP-1 dual agonist, as its first pancreatic gene therapy candidate for obesity. This AAV9 viral vector expresses human GIP and GLP-1 hormones from a human insulin promoter, targeting both receptors important for blood sugar and weight regulation.
Fractyl Health (GUTS) ha presentato nuovi dati preclinici per il suo candidato alla terapia genica pancreatica GLP-1, Rejuva RJVA-001, somministrato in un'unica dose. Lo studio di 13 settimane su topi con obesità indotta dalla dieta ha mostrato un mantenimento sostenuto del peso e un controllo della glicemia, con oltre il 10% delle cellule delle isole che esprimono la proteina GLP-1 e senza preoccupazioni per la sicurezza. L'azienda ha anche annunciato RJVA-002, un dual agonista GIP/GLP-1, come primo candidato alla terapia genica pancreatica per l'obesità. Questo vettore virale AAV9 esprime gli ormoni umani GIP e GLP-1 da un promotore dell'insulina umana, mirando a entrambi i recettori importanti per la regolazione della glicemia e del peso.
Fractyl Health (GUTS) presentó nuevos datos preclínicos para su candidato a terapia génica pancreática GLP-1, Rejuva RJVA-001, administrado en una sola dosis. El estudio de 13 semanas en ratones con obesidad inducida por la dieta mostró un mantenimiento del peso sostenible y control de la glucosa en sangre, con más del 10% de las células de los islotes expresando la proteína GLP-1 y sin preocupaciones de seguridad. La empresa también anunció RJVA-002, un dual agonista GIP/GLP-1, como su primer candidato a terapia génica pancreática para la obesidad. Este vector viral AAV9 expresa las hormonas humanas GIP y GLP-1 desde un promotor de insulina humana, enfocándose en ambos receptores importantes para la regulación de la glucosa y el peso.
Fractyl Health (GUTS)는 단일 투여 GLP-1 췌장 유전자 치료 후보인 Rejuva RJVA-001에 대한 새로운 전임상 데이터를 발표했습니다. 13주 동안의 연구에서는 식이 유도 비만 생쥐에서 지속적인 체중 유지와 혈당 조절이 나타났으며, 10% 이상의 섬세포가 GLP-1 단백질을 발현하고 안전성 문제는 없었습니다. 회사는 또한 비만을 위한 첫 번째 췌장 유전자 치료 후보인 GIP/GLP-1 이중 작용제 RJVA-002를 발표했습니다. 이 AAV9 바이러스 벡터는 인간 인슐린 프로모터에서 인간 GIP 및 GLP-1 호르몬을 발현하며, 혈당 및 체중 조절에 중요한 두 수용체를 타겟합니다.
Fractyl Health (GUTS) a présenté de nouvelles données précliniques sur son candidat à la thérapie génique pancréatique GLP-1, Rejuva RJVA-001, administré en une seule fois. L'étude de 13 semaines sur des souris obèses induites par le régime alimentaire a montré un maintien du poids et un contrôle de la glycémie durables, avec plus de 10 % des cellules des îlots exprimant la protéine GLP-1 et aucun problème de sécurité. L'entreprise a également annoncé RJVA-002, un agoniste double GIP/GLP-1, comme son premier candidat à la thérapie génique pancréatique pour l'obésité. Ce vecteur viral AAV9 exprime les hormones humaines GIP et GLP-1 à partir d'un promoteur d'insuline humaine, ciblant les deux récepteurs importants pour la régulation de la glycémie et du poids.
Fractyl Health (GUTS) hat neue präklinische Daten für seinen GLP-1-Pankreasgen-Therapiekandidaten Rejuva RJVA-001 bei einmaliger Verabreichung präsentiert. Die 13-wöchige Studie an mit Diät induzierten Fettleibigkeitsmäusen zeigte eine nachhaltige Gewichtserhaltung und Blutzuckerkontrolle, wobei über 10% der Inselzellen das GLP-1-Protein exprimieren und keine Sicherheitsbedenken auftraten. Das Unternehmen kündigte außerdem RJVA-002, einen GIP/GLP-1-Dualagonisten, als seinen ersten Pankreasgen-Therapiekandidaten für Fettleibigkeit an. Dieser AAV9-Virusvektor exprimiert menschliche GIP- und GLP-1-Hormone aus einem menschlichen Insulinpromoter und zielt auf beide für die Blutzucker- und Gewichtregulation wichtigen Rezeptoren ab.
- 13-week study demonstrated sustained weight maintenance and blood sugar control
- Over 10% of islet cells expressed GLP-1 protein after single treatment
- No safety signals observed in preclinical studies
- Independent validation by top academic researcher
- None.
Insights
The new preclinical data for RJVA-001 represents significant progress in developing a potentially groundbreaking treatment for obesity and Type 2 diabetes. The 13-week durability data showing sustained weight loss and blood sugar control in mice, even while continuing a high-fat diet, is particularly noteworthy. The 10% islet cell expression demonstrates meaningful pancreatic engagement.
The nomination of RJVA-002, a dual GIP/GLP-1 agonist candidate, is strategically significant as it follows the proven success of drugs like Mounjaro (tirzepatide). The key advantage here is the potential for a single-administration gene therapy approach versus current weekly injections, which could dramatically improve treatment adherence and long-term outcomes.
However, investors should note that mouse model success doesn't guarantee human efficacy and the path to FDA approval for gene therapies is typically complex and lengthy.
13-week follow-up represents the longest data to-date demonstrating durable efficacy of RJVA-001 on weight and blood sugar in the diet-induced obesity (DIO) mouse model
Company plans to use durable efficacy results as part of its FIH data package for RJVA-001
Fractyl also announces the nomination of RJVA-002, a GIP/GLP-1 dual agonist, as its first pancreatic gene therapy candidate for obesity
BURLINGTON, Mass., Nov. 04, 2024 (GLOBE NEWSWIRE) -- Fractyl Health, Inc. (Nasdaq: GUTS) (the “Company”), a metabolic therapeutics company focused on pioneering new approaches that treat root causes of obesity and Type 2 Diabetes (T2D), will present new preclinical data on sustained weight maintenance from its Rejuva RJV-001 single-administration GLP-1 pancreatic gene therapy candidate in an oral presentation on Tuesday, November 5, 2024, during The Obesity Society’s Annual Meeting at ObesityWeek 2024 in San Antonio, Texas. The presentation is titled “Islet-Targeted GLP-1 Receptor Agonist Gene Therapy Reduces Fat and Improves Metabolism in Obese Mice.”
Rejuva is the Company’s adeno-associated virus (AAV)-based pancreatic gene therapy program (PGTx), designed to enable durable pancreatic production of therapeutic peptides. RJVA-001 is the Company’s gene therapy candidate encoding a Smart GLP-1TM for the treatment of T2D. The presentation at ObesityWeek includes new results from preclinical studies in the well-validated DIO mouse model, providing independent confirmation of the efficacy of the RJVA-001 candidate in the laboratory of Dr. Randy J. Seeley at the University of Michigan Medical School.
“The new results in this model demonstrate the durability of our human GLP-1 expressing RJVA-001 candidate 13 weeks after treatment, which is the longest follow-up for Rejuva so far, and a considerable portion of the mouse lifespan,” said Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of Fractyl. “This latest independent evaluation by a top academic researcher in obesity, Dr. Randy J. Seeley, validates and builds on results we previously reported in the DIO model at 8 weeks. Rejuva has the potential to be a pattern-breaking therapy that can finally deliver on the promise of the GLP-1 mechanism in the treatment of obesity and T2D – as shown by these results.”
The ObesityWeek presentation will include new results demonstrating:
- Sustained maintenance of weight loss and blood sugar levels at week 13 in DIO mice receiving RJVA-001 and continuing a high fat diet.
- Over
10% of islet cells expressing immunoreactivity for GLP-1 protein following a single treatment of mice with PGTx. - No safety signals observed.
“GLP-1 drugs have proven efficacious in obesity, but their durability remains a significant challenge because patients typically regain weight upon discontinuing treatment,” said Dr. Randy J. Seeley, Professor of Surgery, Internal Medicine, and Nutritional Sciences at the University of Michigan Medical School, whose laboratory conducted the latest Rejuva study. “These efficacy data in obese mice suggest that RJVA-001, a human GLP-1 gene therapy targeting islets in the pancreas, has the potential to advance the treatment of obesity by offering a durable, single-dose off-ramp from GLP-1 receptor agonist drugs to help maintain weight loss.”
The Company announces the nomination of RJVA-002 as its first Smart GIP/GLP-1 pancreatic gene therapy lead candidate designed for the treatment of obesity. RJVA-002 is a locally administered AAV9 viral vector that expresses human GIP and GLP-1 hormones from a human insulin promoter.
RJVA-002 is designed to activate both GIP and GLP-1 receptors, which together play crucial roles in regulating blood sugar and body weight.
About Fractyl Health
Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including obesity and T2D. Despite advances in treatment over the last 50 years, obesity and T2D continue to be rapidly growing drivers of morbidity and mortality in the 21st
century. Fractyl Health’s goal is to transform metabolic disease treatment from chronic symptomatic management to durable disease-modifying therapies that target the organ-level root causes of disease. Fractyl Health is based in Burlington, MA. For more information, visit www.fractyl.com or https://twitter.com/FractylHealth.
About Rejuva
Fractyl Health’s Rejuva® platform focuses on developing next-generation adeno-associated virus (AAV)-based, locally delivered gene therapies for the treatment of obesity and T2D. The Rejuva platform is in preclinical development and has not yet been evaluated by regulatory agencies for investigational or commercial use. Rejuva leverages advanced delivery systems and proprietary screening methods to identify and develop metabolically active gene therapy candidates targeting the pancreas. The program aims to transform the management of metabolic diseases by offering novel, disease-modifying therapies that address the underlying root 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 matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the promise and potential impact of our preclinical or clinical trial data, the design, initiation, and results of clinical enrollment and any clinical studies or readouts, our participation and presentation at conferences, the potential benefits, launch or commercialization of any of our product candidates or products, the potential treatment population for any of our product candidates or products, our strategic and product development objectives and goals, including with respect to enabling long-term control over obesity and Type 2 diabetes without the burden of chronic therapies, and the timing of any of the foregoing. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause the Company’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the Company’s limited operating history; the incurrence of significant net losses and the fact that the Company expects to continue to incur significant net losses for the foreseeable future; the Company’s need for substantial additional financing; the restrictive and financial covenants in the Company’s credit agreement; the lengthy and unpredictable regulatory approval process for the Company’s product candidates; uncertainty regarding its clinical studies; the fact that the Company’s product candidates may cause serious adverse events or undesirable side effects or have other properties that may cause it to suspend or discontinue clinical studies, delay or prevent regulatory development, prevent their regulatory approval, limit the commercial profile, or result in significant negative consequences; additional time may be required to develop and obtain regulatory approval or certification for the Company’s Rejuva gene therapy candidates; the Company’s reliance on third parties to conduct certain aspects of the Company’s preclinical studies and clinical studies; the Company’s reliance on third parties for the manufacture of the materials for its Rejuva gene therapy platform for preclinical studies and its ongoing clinical studies; the regulatory approval process of the FDA, comparable foreign regulatory authorities and lengthy, time-consuming and inherently unpredictable, and even if we complete the necessary clinical studies, we cannot predict when, or if, we will obtain regulatory approval or certification for any of our product candidates, and any such regulatory approval or certification may be for a more narrow indication than we seek; and the potential launch or commercialization of any of Company’s product candidates or products and our strategic and product development objectives and goals, and the other factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on August 14, 2024 and in our other filings with the SEC. These forward-looking statements are based on management’s current estimates and expectations. While the Company may elect to update such forward-looking statements at some point in the future, the Company disclaims any obligation to do so, even if subsequent events cause its views to change.
Contacts
Corporate 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 Contact
Stephen Jasper, Gilmartin Group
stephen@gilmartinir.com, 619.949.3681
FAQ
What were the key findings of Fractyl Health's (GUTS) RJVA-001 preclinical study?
What is Fractyl Health's (GUTS) new obesity treatment candidate RJVA-002?
How long did Fractyl Health's (GUTS) RJVA-001 maintain its effects in the preclinical study?
