Announcement • Jul 29
Caliway Biopharmaceuticals Co., Ltd. Submits Phase 2 IND To US FDA For CBL-514 Combination Therapy And Reports Clinical Data On Visceral Fat Reduction
Caliway Biopharmaceuticals Co., Ltd. issued the following news release: Phase 2 IND Submitted to FDA-Caliway has submitted an Investigational New Drug (IND) application to the U.S. FDA for CBL-0201WR, a multicenter Phase 2 clinical study to evaluate CBL-514 in combination with Zepbound (tirzepatide, Eli Lilly). The trial will evaluate the combination for the reduction of abdominal subcutaneous fat in adults with overweight or obesity and plans to enroll 120 subjects in the U.S., assessing changes in body weight, visceral fat, and lean body mass. The CBL-514 combination therapy demonstrates significant potential to address the global challenge of rebound weight gain following the discontinuation of GLP-1 receptor agonists. Preclinical data from the OI25 animal study revealed that post-treatment weight regain in the monotherapy group was 2.7 times higher than that observed in the CBL-514 combination group. CBL-514's clinical data on visceral fat reduction has been selected for an oral presentation at the European Association for the Study of Diabetes (EASD) 2026 Annual Meeting. This randomized, placebo-controlled, multicenter Phase 2 clinical study will evaluate the company's novel fat-reducing candidate, CBL-514 injection, in combination with Zepbound (tirzepatide, Eli Lilly). Indicated for the reduction of abdominal subcutaneous fat in adults with overweight or obesity, the trial is expected to enroll 120 subjects in the United States. The primary efficacy endpoint is the change in abdominal subcutaneous fat volume as measured by MRI, allowing investigators to assess the efficacy, safety, and tolerability of CBL-514 combined with tirzepatide. The study will also evaluate key secondary endpoints, including changes in total body weight, visceral adipose tissue, and lean body mass. This trial marks a significant milestone for CBL-514, expanding its clinical utility from localized fat reduction into the broader landscape of systemic weight management, directly targeting the most pressing limitation of current GLP-1 therapies: post-treatment weight regain. Current GLP-1 therapies primarily drive weight loss through appetite suppression. While effective at reducing overall body weight, they merely shrink adipocytes (fat cells) rather than reducing their absolute number. Furthermore, visceral fat tends to diminish much faster than subcutaneous fat, often leading to uneven fat reduction and leaving stubborn subcutaneous deposits, particularly around the abdomen, largely unaffected. This is because subcutaneous adipose tissue in these regions possesses biological defense mechanisms that naturally resist lipolysis (fat breakdown) signals. As patients lose weight, these resistant fat deposits become more visually prominent, frequently contributing to a weight-loss plateau. Compounding this issue, because GLP-1 drugs only shrink fat cells, the return of normal appetite upon treatment discontinuation causes these cells to rapidly re-expand. This results in a dual crisis of rebound weight gain and worsened body composition, a major unresolved challenge in chronic weight management. In contrast, CBL-514's revolutionary mechanism of action induces adipocyte apoptosis, fundamentally reducing the total number of fat cells. When utilized synergistically with GLP-1 therapeutics, it has the potential to eliminate stubborn fat deposits beyond standard weight loss, sustain body weight reduction, and maintain improved body composition long after treatment cessation, effectively mitigating rebound weight gain and metabolic deterioration. The therapeutic potential of this combination has been heavily validated in preclinical models. Preclinical data from the OI25 animal study indicates that following treatment discontinuation, the weight regain rate in the tirzepatide monotherapy group was 46.1%, whereas the CBL-514 combination group was limited to just 17.1%, meaning the rebound effect was 2.7 times greater without CBL-514. Furthermore, the combination group achieved an additional 106.7% reduction in liver fat and demonstrated significant improvements in insulin resistance (HOMA-IR). These robust findings provided a strong scientific rationale for the design of the CBL-0201WR Phase 2 clinical trial. Following recent data sharing at the American Diabetes Association (ADA) Annual Meeting, research detailing CBL-514's combination therapy and its impact on visceral fat reduction has been accepted for an oral presentation at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) this September. With the IND submission for the CBL-0201WR trial, Caliway noted that the clinical development of CBL-514 has officially expanded from localized aesthetics into the high-growth market of systemic weight management and metabolic health. CBL-514 is a patented, first-in-class small-molecule 505(b)(1) injection developed by Caliway. It is designed to selectively induce adipocyte apoptosis to precisely reduce subcutaneous fat at the injection site without causing necrosis or damage to surrounding tissues or cells. CBL-514 possesses therapeutic potential across multiple indications, including non-surgical subcutaneous fat reduction and moderate-to-severe cellulite. A separate formulation, CBL-514D, is being developed for the treatment of Dercum's Disease, a rare disease. To date, more than 544 subjects have participated in clinical trials related to CBL-514. Across the 10 completed clinical trials with finalized statistical reports, all primary and key secondary efficacy endpoints have been met, demonstrating excellent safety and tolerability.
