We are a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including type 2 diabetes and obesity. (Incorporated in Delaware)

Despite advances in treatment over the last 50 years, type 2 diabetes, or T2D, and obesity continue to be principal and rapidly growing drivers of morbidity and mortality. According to the Centers for Disease Control and the International Diabetes Federation, approximately 100 million people in the United States have prediabetes and/or obesity, and an additional 25 million people have T2D on medical therapy. In 2022, there was an estimated $65 billion in annual pharmaceutical spending on drugs aimed at controlling glucose and body weight, all attributable to medicines requiring chronic administration, none of which modifies underlying disease progression. Highly potent drugs in the GLP-1RA class are now available to lower blood sugar, lower weight, and prevent cardiovascular mortality, but up to two-thirds of patients discontinue weekly GLP-1RA therapy within the first year, which typically leads to an immediate loss of metabolic benefit and weight rebound.

Emerging consensus on the role of the gut in driving human metabolic disease led our founders to design novel, differentiated disease-modifying therapies aiming to advance patient care from management into prevention and remission of underlying disease. The Revita DMR System, or Revita, our lead product candidate, is an outpatient procedural therapy designed to durably modify duodenal dysfunction, a major pathologic consequence of a high fat and high sugar diet, which can initiate T2D and obesity in humans. The duodenum regulates the human metabolic response to food intake, and modern diets drive dysfunctional hyperplasia of the duodenal mucosa. This results in alterations to physiologic signaling that affect glucose control and satiety. The Revita system is designed to enable durable and repeatable metabolic improvement via hydrothermal ablation of the dysfunctional duodenal mucosa to address duodenal pathology and consequent metabolic disease progression directly.

We have initiated a broad clinical program designed to evaluate Revita in multiple clinical studies across a range of patient populations from prediabetes and obesity to advanced T2D patients on long-acting insulin. We have obtained Breakthrough Device designation from the U.S. Food and Drug Administration, or the FDA, for Revita to perform hydrothermal ablation of the duodenal mucosa, or the Revita DMR Procedure, to improve glycemic control and eliminate insulin needs in T2D patients who are inadequately controlled on long-acting insulin.

We are currently enrolling our pivotal Revitalize-1 study in patients with inadequately controlled T2D despite being on up to three anti-diabetic agents, or ADAs, and daily insulin. We anticipate completing enrollment in the second quarter of 2024 and expect to report topline data in the fourth quarter of 2024. We are also planning to evaluate Revita in a clinical study, which we refer to as the Remain-1 study, for weight maintenance in patients with obesity who have lost weight on GLP-1RA therapy and wish to discontinue their GLP-1RA without weight regain.

We expect to submit an IDE and comparable documents to the FDA and comparable foreign regulatory authorities or notified bodies in the first half of 2024 for a potentially pivotal Remain-1 study. Revita is already approved for patients with inadequately controlled T2D in Europe. After securing reimbursement for Revita Germany in the first half of 2023, we initiated our pilot commercial launch along with a Real World Registry study. We believe Revita has the potential to serve as a backbone therapy to prevent progression of T2D and for the prevention of weight gain, working in concert with behavioral therapies and standard of care pharmacology.

We are also developing Rejuva, a novel, locally administered, adeno-associated virus, or AAV, delivered pancreatic gene therapy, or PGTx, platform. Rejuva is designed to enable long-term remission of T2D and obesity by durably altering metabolic hormone function in the pancreatic islet cells of patients. In a preclinical head-to-head study, a glucagon-like peptide 1, or GLP-1, PGTx candidate demonstrated improvement in glycemic control, delayed T2D progression and reduction in weight compared to semaglutide (the active agent in Ozempic and Wegovy), an FDA-approved GLP-1RA. We believe these results highlight the potential benefits of metabolic treatment at the locus of disease in the pancreas. Our approach to pancreatic gene therapy is enabled by our expertise in developing proprietary delivery systems that target the gut locally and precisely. We plan to nominate our first GLP-1 PGTx candidate for T2D in the first quarter of 2024 and expect to submit an Investigational New Drug application, or IND, or IND-equivalent for our nominated candidate in the second half of 2024.

We believe Revita and Rejuva, if approved, have the potential to revolutionize treatment across the spectrum of T2D and obesity, align the clinical and economic interests of key stakeholders around the long-term regression of metabolic disease, and, at their fullest potential, significantly reduce the burden of metabolic disease globally.

*Note: Net loss and revenue figures are for the 12 months that ended Sept. 30, 2023.

(Note: Fractyl Health, Inc. priced its IPO at $15.00 – the mid-point of its $14.00-to-$16.00 range – on 7.33 million shares – the number of shares in the prospectus – to raise $109.95 million on Feb. 1, 2024. Background:  Fractyl Health, Inc. filed its S-1/A dated Jan. 29, 2024, and disclosed terms for its IPO: 7.33 million shares (7,333,333 shares) at a price range of $14.00 to $16.00 to raise $109.95 million. Background: Fractyl Health,  Inc. filed its S-1 on Dec. 14, 2023, without disclosing terms for its IPO.)