Caliway Advances CBL-514 With FDA-Cleared Tirzepatide Trial and Phase 3 Enrollment

Caliway Biopharmaceuticals has cleared two important U.S. development milestones for CBL-514, with the FDA clearing the IND for a Phase 2 trial combining CBL-514 with tirzepatide and a U.S. central IRB approving the amended protocol for the pivotal Phase 3 SUPREME-01 study. The company will also present new visceral fat reduction findings at the 62nd EASD Annual Meeting on September 30, 2026.

CBL-514 Expands into Combination Weight Management

The FDA-cleared CBL-0201WR study is a randomized, single-blind, placebo-controlled Phase 2 trial that will evaluate CBL-514 combined with tirzepatide in 120 overweight or obese adults in the U.S.

Investigators will use magnetic resonance imaging (MRI) to measure changes in abdominal subcutaneous fat volume, with safety and tolerability as additional study assessments. Exploratory measures will include body weight, visceral fat and lean body mass.

The study tests a complementary approach to obesity treatment. Tirzepatide, a GIP and GLP-1 receptor agonist, produces systemic weight loss through effects on appetite, energy intake and metabolism. CBL-514 takes a localized approach by selectively inducing apoptosis of adipocytes at the injection site, with the goal of reducing subcutaneous fat in targeted areas.

That distinction provides the rationale for studying the combination in people who lose weight with tirzepatide but retain localized abdominal fat. It also gives the program a potential role in post-weight-management strategies, although whether the combination can improve long-term weight maintenance or body composition remains a clinical question for the Phase 2 study.

SUPREME-01 Enters Phase 3 Enrollment

The pivotal Phase 3 SUPREME-01 trial (NCT07733947), also known as CBL-0301, has received U.S. IRB approval following a protocol amendment and has begun enrolling participants. The global study evaluates CBL-514 for reduction of abdominal subcutaneous fat.

The trial uses a multicomponent responder endpoint that combines MRI-measured abdominal fat-volume reduction with improvement in abdominal fat level assessed by the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS). Caliway’s published Phase 3 plan specifies at least a 13% reduction in abdominal fat volume by MRI and at least a 2-grade improvement from baseline on the PR-AFRS four weeks after the final treatment.

This endpoint is more specific than a generic AFRS improvement because PR-AFRS captures the participant’s assessment of abdominal fat, while the MRI component provides an objective measure of fat-volume change. The study’s design and endpoints were previously evaluated in Phase 2b studies CBL-0204 and CBL-0205.

Visceral Fat Data Head to EASD

The clinical program will add another dimension in September, when CBL-514 visceral fat findings are presented orally at the 62nd EASD Annual Meeting in Italy on September 30.

1. Timothy Garvey, MD, a scientific advisor to Caliway, will present MRI-based findings on changes in visceral adipose tissue at the L2-L3 level alongside subcutaneous fat reduction. The data could help clarify whether localized CBL-514 treatment affects fat compartments beyond the subcutaneous tissue directly targeted by injection.

Development Program Broadens

More than 544 participants have received CBL-514 across clinical studies, according to the company. Caliway reports that all primary and key secondary efficacy endpoints were met across 10 completed trials with finalized statistical reports, with favorable safety and tolerability findings. These remain company-reported results rather than independently adjudicated evidence.

CBL-514 is a small-molecule injectable being developed under the 505(b)(1) pathway for non-surgical subcutaneous fat reduction and moderate-to-severe cellulite. A separate formulation, CBL-514D, is being investigated for Dercum’s disease.

The immediate priorities are enrollment and execution of SUPREME-01, initiation of the CBL-0201WR Phase 2 combination study, and presentation of the visceral fat findings at EASD. Together, these programs will test whether selective adipocyte apoptosis can complement systemic pharmacologic weight loss and expand CBL-514 from localized fat reduction into broader obesity and body-composition applications.

Reference

Caliway’s CBL-514 Combination Therapy Cleared by U.S. FDA for Phase 2 Trial; Pivotal Phase 3 Trial SUPREME-01 Initiates Enrollment-Caliway Biopharmaceuticals Co., Ltd