- A once-weekly subcutaneous injection of CT-388 achieved a statistically significant placebo-adjusted weight loss of 22.5% (p < 0.001) at 48 weeks at the highest dose tested (24 mg), without reaching a weight loss plateau -

- 54% of participants on the 24 mg dose achieved resolution of obesity (BMI <30 kg/m2) vs. 13% in the placebo group -

- CT-388 demonstrated a safety and tolerability profile generally consistent with its drug class with no new or unexpected safety signals -

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today positive topline results from CT388-103, a Phase II clinical trial of CT-388, an investigational dual GLP-1/GIP receptor agonist being developed for the treatment of obesity. The study found that once-weekly subcutaneous injections of CT-388 (titrated up to 24 mg) resulted in significant and clinically meaningful placebo-adjusted weight loss of 22.5% (efficacy estimand) without reaching a weight loss plateau at 48 weeks. A clear dose-response relationship on the weight loss was observed. For the treatment-regimen estimand, the placebo-adjusted weight loss achieved with CT-388 was 18.3% (p-value < 0.001). At week 48 for the 24 mg dose, 95.7% of CT-388 treated participants achieved a weight loss of ≥5%, 87% achieved ≥10%, 47.8% achieved ≥20%, and 26.1% achieved ≥30%. 73% of participants who were pre-diabetic at baseline and treated with CT-388 at 24 mg achieved normal blood glucose levels at week 48 compared to 7.5% in the placebo group.

The treatment was well-tolerated, with the majority of gastrointestinal-related adverse events being mild-to-moderate, generally consistent with the incretin class of medicines. In addition, the treatment discontinuation rate due to adverse events was low (5.9% in CT-388 arms; 1.3% in placebo arm). The full results of the study will be presented at an upcoming medical congress.

“We are pleased to see such meaningful weight loss in people treated with CT-388,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development program as we advance to Phase III trials.”

With its growing cardiometabolic portfolio and strong diagnostic expertise of Roche, Genentech is advancing potentially transformative standards of care to improve the lives of people living with cardiometabolic diseases as well as reducing the significant burden on healthcare systems and society.

Obesity is recognized as the greatest single risk factor for chronic disease globally. By 2035, over four billion people (more than half of the global population) are projected to be living with excess weight or obesity, a trend affecting nearly every country. This rise is driven by a complex mix of genetics and biology as well as behavioral, environmental and socioeconomic factors, placing an increased strain on healthcare systems due to the associated burden of comorbidities and reduced quality of life.

Since integrating CT-388 into the pipeline, we have designated it within Genentech as a fast-track asset and significantly accelerated its clinical development with the goal to bring this potential therapy to patients as soon as possible. CT-388 is currently being investigated in an additional Phase II study (CT388-104) to evaluate the efficacy, safety and tolerability of CT-388 in participants who are living with obesity or are overweight and have type 2 diabetes. The Phase III clinical trial program of CT-388 in obesity (Enith1 and Enith2) is expected to start this quarter. In addition to offering robust efficacy as a standalone therapy, CT-388 also plays a key role in unlocking the promise of our obesity pipeline and is considered as a combination asset for petrelintide.

About the CT-388 (103) Phase II study [NCT06525935]

The multi-center, randomized, double-blind, placebo-controlled, parallel group dose-finding Phase II trial was designed to evaluate the efficacy and safety of CT-388 at low, middle, and high doses in 469 people with obesity. It includes adults with obesity (BMI≥30.0 kg/m2) or overweight (BMI ≥27.0 and <30.0 kg/m2) with at least one weight-related comorbidity without type 2 diabetes and evaluated five dosing cohorts with different up-titration schemes with 24 mg being the highest dose tested. The primary endpoint was percent change in body weight from baseline to week 48.

About CT-388

CT-388 is an investigational once-weekly subcutaneous injectable, dual GLP-1/GIP receptor agonist being developed for the treatment of obesity, type 2 diabetes, and other obesity-related comorbidities. It aims to reduce appetite and regulate blood sugar by selectively targeting and activating both receptors which integrate nutrient-derived signals to control energy homeostasis. CT-388 was designed to have potent activation of both GLP-1 and GIP receptors, but with minimal to no ß-arrestin recruitment on either receptor. This biased signaling significantly minimizes receptor internalization and consequent desensitization, which is expected to lead to prolonged pharmacological activity.

About Genentech

Founded 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit https://www.gene.com.

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