Fractyl Health has revealed promising new preclinical findings for the first clinical candidate in its Rejuva pancreatic gene therapy platform. RJVA-001 is the company’s first GLP-1 gene therapy candidate to emerge from the platform, setting the stage for a potentially transformative approach to treating metabolic diseases, including obesity and T2D.
The Rejuva platform focuses on developing next-generation adeno-associated virus (AAV)-based, locally delivered gene therapies for the treatment of T2D and obesity. Rejuva leverages advanced delivery systems and proprietary screening methods to identify and develop metabolically active gene therapy candidates targeting the pancreas. The programme aims to transform the management of metabolic diseases by offering novel, disease-modifying therapies that address the underlying root causes of disease.
“As we advance our Rejuva program through preclinical development, we now observe that a single-dose administration of a human GLP-1 transgene (as in RJVA-001) can achieve durable lowering of blood sugar and body weight compared to vehicle or chronic semaglutide administration in the well-validated db/db mouse model of diabetes,” said Dr Timothy Kieffer, Fractyl Health Chief Scientific Officer. “With these data, we are one step closer to IND enablement for RJVA-001 as part of our broader preclinical development package.”
The results show that the human GLP-1 coding sequence of RJVA-001 demonstrates potency on both glucose lowering and weight loss in db/db mice, the standard rodent T2D efficacy model used for clinical development. The Company has reached alignment with European regulators on the use of this efficacy model to support the submission of a Clinical Trial Application (CTA) in Europe.
“While there are clear benefits of GLP-1 for weight loss, glucose control, and metabolic health in general, there remains a need for advances in care that can offer a major step forward in GLP-1 therapy,” said Dr Harith Rajagopalan, CEO of Fractyl Health. “Our goal with RJVA-001 is to change the trajectory of both obesity and T2D with a single administration therapy that offers the potential for the durable remission of metabolic disease.”
Fractyl Health anticipates progressing RJVA-001 through IND-enabling toxicity studies in 2024 and initiating First-in-Human clinical studies in the first half of 2025. The Rejuva platform is in preclinical development and has not yet been evaluated by regulatory agencies for investigational or commercial use.