Sironax says it has reached roughly 50 percent of targeted enrollment in FORGE-LM, a global Phase 2 trial reported on October 13, testing its oral drug SIR4156 alongside semaglutide in adults with obesity.

SIR4156 is described by the Waltham, Massachusetts company as a first-in-class, orally active allosteric NAMPT activator. NAMPT is nicotinamide phosphoribosyltransferase, an enzyme in the pathway that makes NAD+, and the human evidence for the compound does not exist yet: everything supporting the trial so far comes from preclinical work, including mouse data Sironax presented at the Aging Research and Drug Discovery conference in Boston.

The muscle problem

The pitch rests on a complaint that has followed GLP-1 drugs since they went mainstream, which is that some of the weight lost is lean mass. CEO Shefali Agarwal said significant unmet needs remain in obesity treatment, naming lean muscle preservation, fatigue, sustained metabolic health, inadequate weight loss and disproportional fat mass gain after people stop therapy.

Sironax describes NAD+ as critical for energy regulation, mitochondrial function and tissue homeostasis, and says its levels decline with age and metabolic dysfunction. In multiple preclinical models, the company says SIR4156 produced preferential fat loss, preserved lean mass, reduced muscle atrophy and improved physical performance.

What the trial is actually measuring

FORGE-LM is double-blinded, randomized, placebo-controlled and parallel-group. The primary objective is the effect of SIR4156 on body fat mass and body composition, with body weight, lean mass, safety, tolerability, pharmacokinetics and pharmacodynamics listed as secondary.

That ordering is worth noticing. Lean mass, the thing the whole rationale is built on, sits in the secondary column, so anyone waiting for a clean muscle-preservation number should know it is not the headline endpoint.

What the release leaves out

No enrollment target, no treatment length, no date for results, though the company says the trial remains on track. The press release also does not spell out the comparison arms.

Sironax itself notes that SIR4156 is an investigational candidate not approved by the FDA or any other regulator, that preclinical results may not predict clinical outcomes, and that safety and efficacy in humans have not been established.

Bottom line

Two well-funded storylines, GLP-1 muscle loss and age-related NAD+ decline, are being stitched together here, and the mouse data explain why the trial exists rather than what it will find. Human results are the next real test, and none have been reported.