What is organ editing?

Organ editing is the process of targeting and modifying the duodenum and the pancreas directly as a means of addressing the organ-level root causes of T2D.

We believe that blood sugar is a symptom of T2D, not the disease itself. The underlying problem that leads to T2D is caused by the dysfunction of key metabolic organs, leading to insulin resistance and insulin insufficiency.

Recent advances in our understanding of the dysfunction of key metabolic organs in the intestine and in the pancreas have enabled the development of new approaches aimed at reversing T2D. We have developed what we believe to be broadly accessible therapies that target the gut and the pancreas directly. This approach, known as organ editing, can transform T2D treatment from chronic blood glucose management to disease-modifying therapies that focus on the organ-level root causes of disease.

Our approach involves identifying diseased metabolic organs at the root of the T2D disease process and designing disease-modifying treatments that aim to reverse the core pathology in these organs that is driving the disease process. We believe that addressing the diseased organs in a manner that is designed to restore their metabolic health and function offers the potential for disease eradication in a manner that current approaches, focused on lifestyle intervention or pharmacological management, have not been able to achieve. We call this approach “organ editing.”

Revita, our lead product candidate, targets duodenal dysfunction, which we believe to be a driver of insulin resistance in T2D, via a minimally invasive endoscopic procedure. In this outpatient procedure, the Revita catheter is introduced through the mouth and into the duodenum. The catheter is designed to isolate the mucosa from the deeper layers of the duodenum, to separate these layers, and then hydrothermally ablate the excess surface layers of the duodenal lining. In the days following the ablation procedure, the duodenal mucosa regenerates, which we believe leaves the duodenal lining revitalized and better able to function in a manner that has the potential to improve metabolic health.

We believe the function of the duodenum is negatively impacted by diets high in fat and sugars.

Revita is designed to remodel the duodenal lining via hydrothermal ablation.

The Revita DMR system comprises (i) the Revita console that houses our proprietary technology and software and (ii) a single-use Revita catheter and single-use lineset. The image seen here depicts a prototype rendering of the modular Revita console with the current touchscreen user interface.

Led by our ongoing Revitalize-1 pivotal study, we have initiated a broad clinical program, Revitalize T2D, which is designed to evaluate Revita in multiple concurrent clinical studies across a range of patient populations from prediabetes to T2D patients on long-acting insulin.

We are now enrolling patients in the Revitalize-1 clinical study. Revitalize-1 is evaluating the effectiveness and safety of Revita for people with inadequately controlled type 2 diabetes despite being on standalone metformin or multiple antidiabetic agents and long-acting insulin.

Fractyl Health is currently developing Rejuva, a novel pancreatic gene therapy platform to enable long-term remission of T2D.

The Rejuva platform is our pipeline program that is designed to restore insulin production capacity in the pancreas in people with advanced type 2 diabetes. Our approach involves an endoscopic, locally administered adeno-associated virus (AAV) to the pancreas to enable local gene therapy. Our platform is designed to enable the local production of key metabolic hormones that are known to be necessary for proper insulin production in the beta cells of the pancreas.