Fractyl Health Gene Therapy Achieves Potent Weight Loss in Obesity Model

BURLINGTON, Mass. – October 7, 2025 – Fractyl Health, Inc. ($\text{Nasdaq}$: $\text{GUTS}$) announced compelling new preclinical data today for $\text{RJVA-002}$, a gene therapy candidate from its RejuvaR◯ $\text{Smart}$ GLP-1TM platform, positioning the technology as a potential single-intervention treatment for obesity. The data, presented at the $2025$ $\text{Cell}$ $\&$ $\text{Gene}$ $\text{Meeting}$ on the $\text{Mesa}$, expands the $\text{Rejuva}$ platform’s focus beyond Type $2$ $\text{Diabetes}$ ($\text{T2D}$) to include durable treatment for obesity.

Dual Hormone Gene Therapy Drives $30\%$ Weight Loss

$\text{RJVA-002}$ is an innovative gene therapy designed to treat the root causes of metabolic disease. It encodes for both the $\text{GIP}$ and $\text{GLP-1}$ hormones and is controlled by an engineered human insulin promoter. This design enables the production of these key metabolic hormones to be specific to pancreatic beta cells and responsive to nutrient levels.

In a diet-induced obesity ($\text{DIO}$) mouse model that expresses a humanized $\text{GIP}$ receptor, a single administration of $\text{RJVA-002}$ resulted in significant and rapid weight loss. Mice in the high-dose cohort lost a mean of $29\%$ of their body weight over just five weeks, with the weight loss trajectory continuing without plateau. No adverse effects were observed in the treated animals.

$\text{Harith}$ $\text{Rajagopalan}$, $\text{M.D}$., $\text{Ph.D}$., $\text{Co-Founder}$ and $\text{Chief}$ $\text{Executive}$ $\text{Officer}$ of $\text{Fractyl}$ $\text{Health}$, stated that the $\text{RJVA-002}$ data “further support [the] $\text{Smart}$ $\text{GLP-1}$ gene therapy platform approach and suggest that dual gut hormone expression has the potential to produce powerful metabolic effects.”

The $\text{Rejuva}$ platform aims to enable long-term remission of $\text{T2D}$ and obesity by durably reprogramming pancreatic islet cells to naturally produce metabolic hormones.

• $\text{RJVA-001}$, the first candidate, is on track to enter first-in-human clinical trials in $2026$ for patients with inadequately controlled $\text{T2D}$.
• $\text{RJVA-002}$ extends the platform to obesity by targeting dual incretin biology, with the goal of achieving durable, well-tolerated weight loss from a single intervention, offering a potential next-generation alternative to chronic drug therapy.

Further results from this ongoing study, including longer-term data and associated metabolic measurements, are expected to be presented at an upcoming scientific congress.