WALTHAM, Mass. — October 13, 2026
Sironax, a global clinical-stage biotechnology company, announced that its Phase 2 FORGE-LM clinical trial has achieved approximately 50% of its targeted patient enrollment. The randomized, double-blind, placebo-controlled study is evaluating SIR4156, an investigational, orally active NAMPT activator, in combination with semaglutide in adults with obesity. The trial aims to investigate whether SIR4156 can improve body composition during obesity treatment, with particular attention to reducing body fat while preserving lean body mass. The milestone marks continued progress in evaluating a potential approach to obesity treatment challenges that extend beyond total weight reduction, including muscle preservation and metabolic health. SIR4156 remains investigational, and its safety and efficacy in humans have not yet been established.
FORGE-LM Trial Focuses on Fat Loss and Lean Mass Preservation
The Phase 2 FORGE-LM study is designed as a global, randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluating SIR4156 in combination with semaglutide. Its primary objective is to assess the treatment’s effect on body fat mass and overall body composition. Secondary objectives include changes in body weight and lean mass, as well as assessments of safety, tolerability, pharmacokinetics and pharmacodynamic effects. Sironax reported that enrollment has reached approximately half of its target and that the trial remains on track. The company has not disclosed the exact number of participants enrolled, the total planned enrollment in the announcement, the treatment duration or an anticipated date for topline results. The study is intended to generate clinical evidence on whether adding SIR4156 to semaglutide can influence the composition of weight lost during treatment. While weight reduction remains a key objective in obesity management, changes in fat and lean tissue may also be important when assessing the broader effects of treatment. The ongoing trial will help determine whether the benefits observed in preclinical research can be demonstrated in adults with obesity.
SIR4156 Targets NAMPT and Cellular NAD+ Metabolism
SIR4156 is described by Sironax as a first-in-class, orally active allosteric activator of nicotinamide phosphoribosyltransferase (NAMPT). NAMPT plays an important role in maintaining levels of nicotinamide adenine dinucleotide (NAD+), a molecule involved in cellular energy production, mitochondrial function and tissue homeostasis. NAD+ levels can decline with aging and metabolic dysfunction, potentially affecting the ability of tissues to maintain normal energy balance. By activating NAMPT, SIR4156 is designed to restore NAD+ homeostasis and enhance cellular energy metabolism. According to Sironax, multiple preclinical models showed preferential fat loss, preservation of lean mass, reduced muscle atrophy and improved physical performance following treatment with SIR4156. The company also presented research on the candidate at the recent Aging Research and Drug Discovery conference in Boston. The presentation, titled “Pharmacological Activation of NAMPT by SIR4156 Restores Tissue NAD+ and Improves Metabolic and Skeletal Muscle Function to Promote Healthy Aging in Mice,” described findings from animal research. These results provide the scientific rationale for further investigation, but preclinical findings do not establish that the same effects will occur in humans.
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Clinical Program Addresses Remaining Obesity Treatment Challenges
Sironax believes SIR4156 could potentially address limitations associated with current obesity treatments, including inadequate weight loss in some patients, loss of lean muscle mass, fatigue and challenges maintaining metabolic health after treatment discontinuation. The company also highlighted concerns about disproportionate fat-mass gain following cessation of some therapies. Semaglutide is being used in combination with SIR4156 in the FORGE-LM trial to investigate whether NAMPT activation could complement an established approach to weight management. However, whether the combination provides additional benefits beyond semaglutide alone will require assessment through controlled clinical data. Sironax President and Chief Executive Officer Dr. Shefali Agarwal said preclinical findings support investigating SIR4156 across obesity, metabolic and neuromuscular diseases. The company’s broader pipeline includes SIR2501, a SARM1 inhibitor, and SIR9900, a RIPK1 inhibitor, alongside ongoing preclinical research. Sironax is a clinical-stage biotechnology company developing therapies for neurodegenerative, inflammatory, immunologic, metabolic and rare diseases. The next major milestone for SIR4156 will be the availability of clinical findings that clarify its effects on body composition, safety and tolerability in humans. Until those results are established, the candidate’s potential to preserve lean mass while reducing body fat remains a research hypothesis rather than a proven clinical benefit.
Source::Sironax, press release
