CicadaBio to Present CC-18, a Novel GLP-1/ActRII Fusion Protein for Muscle-Sparing Weight Loss, at ADA 2026
CicadaBio has announced new preclinical findings for CC-18, its investigational dual-pathway fusion protein targeting both the GLP-1 receptor and the activin type II receptor (ActRII) pathway. The data were presented in an oral session at the American Diabetes Association (ADA) Scientific Sessions 2026, highlighting a potential next-generation approach to obesity treatment that goes beyond weight reduction alone to focus on body composition, metabolic health, and durability of response.
CC-18 is designed as a bifunctional biologic that integrates two complementary mechanisms into a single therapeutic molecule. The GLP-1 receptor agonism component is intended to drive appetite suppression, improved glycemic control, and reductions in body weight, consistent with currently approved GLP-1-based obesity and diabetes therapies. In parallel, the ActRII pathway blockade is intended to address a key limitation observed with existing treatments: the loss of lean muscle mass during weight reduction. By modulating this pathway, CC-18 aims to preserve or potentially enhance lean mass while preferentially reducing fat mass, thereby improving overall body composition.
The rationale behind this dual mechanism reflects a growing shift in obesity medicine. While GLP-1 therapies have demonstrated transformative efficacy in achieving significant weight loss, increasing attention is being paid to the composition of that weight loss. Clinical and real-world data have shown that a portion of weight reduction associated with GLP-1 receptor agonists may come from lean body mass, including skeletal muscle. This has raised concerns among clinicians and researchers, as preservation of muscle mass is closely linked to metabolic health, functional capacity, and long-term weight maintenance.
Against this backdrop, CicadaBio’s CC-18 program is being positioned as a potential next-generation therapy designed not only to reduce body weight but also to optimize the quality of weight loss. The company believes that improving body composition—specifically by preserving or increasing lean mass while reducing fat mass—may lead to more durable and clinically meaningful outcomes for patients with obesity.
The preclinical data presented at ADA 2026 were derived from both diet-induced obesity (DIO) mouse models and non-human primate (NHP) studies, providing a broad translational assessment of CC-18’s pharmacological profile.
In diet-induced obesity mouse models, CC-18 demonstrated superior weight reduction compared with semaglutide, one of the most widely used GLP-1 receptor agonists in clinical practice. Importantly, the weight loss observed with CicadaBio CC-18 was driven primarily by reductions in fat mass rather than lean mass. This resulted in a more favorable body composition profile, with animals not only losing more weight overall but also maintaining or increasing lean mass during treatment.
One of the most notable findings from the mouse studies was the impact on weight regain following treatment discontinuation. Animals treated with CicadaBio CC-18 exhibited approximately 58% less weight regain compared with those treated with semaglutide after therapy was stopped. This suggests that CC-18 may have the potential to support more durable metabolic changes beyond active treatment, addressing a known challenge in obesity management where weight regain is common after discontinuation of pharmacotherapy.
The preservation and enhancement of lean mass observed in the preclinical models are particularly significant in the context of long-term metabolic health. Lean body mass, particularly skeletal muscle, plays a critical role in glucose metabolism, energy expenditure, and physical function. Loss of muscle during weight reduction can contribute to decreased metabolic rate and may increase the likelihood of weight regain over time. By contrast, therapies that preserve lean mass while reducing fat mass may support more sustainable weight management outcomes.
In non-human primate studies, CC-18 demonstrated sustained reductions in body weight along with favorable changes in body composition, reinforcing findings observed in rodent models. The data also indicated prolonged pharmacodynamic activity and durable target engagement, suggesting that the molecule may support extended dosing intervals. Based on these findings, the company has proposed the potential for monthly dosing, which could represent a meaningful improvement in treatment convenience compared with more frequent administration schedules required by some existing therapies.
The CicadaBio extended duration of pharmacological activity observed in the primate studies may also have implications for patient adherence and long-term treatment persistence. In chronic conditions such as obesity, where long-term therapy is often required, reduced dosing frequency is frequently associated with improved adherence and patient satisfaction.
“These data support our vision that the future of obesity treatment extends beyond simply losing weight,” said Dr. Jia Ni, Chief Executive Officer of CicadaBio. “As the field evolves beyond first-generation GLP-1 therapies, increasing attention is being directed toward approaches that improve body composition, preserve lean mass and support durable outcomes. We believe the next generation of therapies will be defined by high-quality weight loss and the data presented at the ADA meeting reinforce the potential of CicadaBio CC-18 to address several important limitations associated with current obesity treatment.”
Dr. Ni’s comments reflect a broader evolution in the obesity treatment landscape, where clinical success is increasingly defined not only by the magnitude of weight loss but also by its quality and durability. As GLP-1-based therapies continue to reshape standards of care, researchers and developers are exploring combination mechanisms that may enhance efficacy while mitigating unwanted effects such as muscle loss or weight rebound.
CC-18’s dual-pathway design represents one such strategy. By combining metabolic regulation through GLP-1 receptor activation with modulation of muscle and tissue signaling pathways via ActRII inhibition, the therapy is intended to address both sides of the body composition equation—fat reduction and lean mass preservation.
CicadaBio is advancing CC-18 through ongoing clinical development efforts, including participation in Lilly’s Catalyze360 initiative, which is designed to support early-stage clinical programs and accelerate proof-of-concept studies. Through this collaboration, the company is working to further evaluate the safety, pharmacokinetics, and translational potential of CC-18 as it progresses toward human clinical trials.
As obesity continues to represent a major global health challenge, with increasing prevalence and associated comorbidities such as type 2 diabetes, cardiovascular disease, and metabolic syndrome, the demand for more effective and comprehensive treatment approaches remains high. Current therapies have demonstrated substantial progress, but limitations in lean mass preservation, weight regain, and long-term durability continue to drive innovation in the field.
Within this context, CicadaBio CC-18 is being positioned as part of a broader shift toward next-generation metabolic therapies that prioritize not only weight reduction but also improvements in physiological function and long-term metabolic health. The preclinical findings presented at ADA 2026 suggest that dual-pathway biologics targeting both appetite regulation and muscle preservation pathways may represent a promising direction for future obesity treatment strategies.
About CicadaBio
CicadaBio is a biotechnology company developing innovative therapies for obesity, metabolic disease, and related chronic conditions. The company is focused on advancing differentiated therapeutic approaches that improve both metabolic outcomes and the quality of weight loss through novel biological mechanisms.
