Caliway has submitted an FDA IND for a Phase 2 trial evaluating CBL-514 with tirzepatide (Zepbound) in adults with overweight or obesity. The study will assess abdominal fat reduction, body composition, and weight regain prevention.
Written By: Kirti Kumbhar,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Caliway Biopharmaceuticals has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration for CBL-0201WR, a randomized, placebo-controlled, multicenter Phase 2 clinical trial evaluating CBL-514 in combination with Zepbound® (tirzepatide). The study marks the company’s expansion from localized fat reduction into systemic weight management and will enroll approximately 120 adults with overweight or obesity across the United States.
The trial will assess whether adding CBL-514 to tirzepatide can further reduce abdominal subcutaneous fat while improving body composition. Investigators will also evaluate changes in total body weight, visceral adipose tissue, lean body mass, along with the treatment’s safety and tolerability.
Targeting a Key Limitation of GLP-1 Therapy
GLP-1 receptor agonists have transformed obesity treatment by suppressing appetite and producing substantial weight loss. However, these therapies primarily shrink fat cells rather than reducing the number of adipocytes. After treatment discontinuation, fat cells can rapidly refill, contributing to weight regain and deterioration in body composition.
Subcutaneous fat, particularly around the abdomen, also tends to resist lipolysis more than visceral fat. This biological resistance may contribute to weight-loss plateaus despite continued therapy.
CBL-514 uses a different mechanism by inducing selective adipocyte apoptosis, permanently reducing the number of fat cells at the treatment site without causing tissue necrosis or damaging surrounding cells. The company believes combining this approach with GLP-1 therapy could improve long-term fat reduction while lowering the risk of rebound weight gain.
Phase 2 Trial Will Measure Fat Reduction by MRI
The Phase 2 CBL-0201WR study will use MRI-based assessment of abdominal subcutaneous fat volume as its primary efficacy endpoint. Secondary endpoints include changes in body weight, visceral fat, and lean body mass.
The randomized, placebo-controlled design will evaluate the efficacy, safety, and tolerability of CBL-514 administered alongside tirzepatide in adults with overweight or obesity.
Preclinical Findings Supported Clinical Development
The IND submission follows encouraging preclinical findings from the OI25 animal study evaluating the combination therapy.
According to the company, animals treated with tirzepatide alone regained 46.1% of lost weight after treatment cessation, compared with 17.1% in the CBL-514 combination group. The monotherapy group therefore experienced 2.7-fold greater weight regain.
The combination therapy also produced an additional 106.7% reduction in liver fat and significantly improved insulin resistance measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), providing scientific support for advancing into Phase 2 clinical testing.
Scientific Recognition Continues
The clinical development program has also gained attention within the obesity research community. Following presentation of CBL-514 data at the American Diabetes Association Scientific Sessions, new findings on visceral fat reduction have been selected for an oral presentation at the 2026 European Association for the Study of Diabetes (EASD) Annual Meeting.
The presentation will be delivered by obesity expert W. Timothy Garvey, MD, who serves as a scientific advisor to Caliway.
Vivian Ling, Chief Executive Officer of Caliway, said the company believes combining CBL-514 with GLP-1 therapies could overcome resistance to subcutaneous fat reduction, improve body contour, help patients progress beyond weight-loss plateaus, and reduce post-treatment weight regain.
Next Steps for CBL-514
CBL-514 is a patented first-in-class small-molecule injectable being developed through the FDA’s 505(b)(1) pathway. Beyond obesity, the investigational therapy is under development for non-surgical subcutaneous fat reduction and moderate-to-severe cellulite, while a separate formulation, CBL-514D, is being evaluated for Dercum’s disease.
More than 544 participants have received CBL-514 across clinical studies. Caliway reported that all primary and key secondary efficacy endpoints were achieved in 10 completed clinical trials with finalized statistical reports, alongside a favorable safety and tolerability profile.
If the FDA allows the IND to proceed, the Phase 2 CBL-0201WR study will provide the first clinical evaluation of CBL-514 combined with tirzepatide for improving fat distribution, body composition, and long-term weight management in adults with overweight or obesity.
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About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.