MitoRx Therapeutics has announced promising preclinical data highlighting the potential of its lead compound, Myo4, in addressing obesity and related metabolic disorders. Presented at the 85th Scientific Sessions of the American Diabetes Association in Chicago, the findings suggest that Myo4 restores insulin sensitivity and promotes fat loss while preserving muscle and bone mass in a murine diet-induced obesity model.
Unlike traditional GLP-1 receptor agonists, which often lead to muscle loss and gastrointestinal side effects, Myo4 operates by targeting mitochondrial sulfide-signaling pathways with the aim of correcting underlying metabolic impairments. By harnessing a natural mechanism that can restore insulin sensitivity and drive fat loss activated by a single small molecule as a monotherapy, patients can expect a weight-loss journey without the concerning side-effect profile of GLP-1 drugs – and without any loss of lean mass. Myo4 is not an activin or myostatin inhibitor, nor an amylin mimic/agonist, nor GLP-1RA or uncoupler, but “an entirely new category of weight loss drug”, according to CEO Jon Rees. Additional studies in more relevant diabetes models, however, are needed to fully understand the potential in type 2 diabetes.
It would be remiss to extrapolate too far, but Rees sees multiple beneficial changes in the insulin system in animal models of obesity. Hinting that the body does not need to produce as much insulin with treatment, yet more studies to evaluate the impact in islet cells preservation are also required.
“We are considering obesity-related indications initially, including a gentler form of maintenance therapy (monotherapy) following weight-loss with a much cleaner side-effect profile than GLP-1 drugs. We already have data in animal models suggesting utility in Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 1 diabetes,” Rees said.
So what’s so exciting? There are two main factors, according to Rees: “One involves combining in one molecule the benefits of several other weight loss medications. These offer the potential to bring much simpler solutions with easier patient compliance for long-term obesity treatment and any associated cardio-metabolic disorders. The other is that the happenstance that GLP-1 drugs became obesity medicines (having been developed for type 2 diabetes), which means that they have downsides that don't necessarily fit with a significant number of patients. “Patients can't always be expected to exercise or grossly modify their behaviors alongside a drug treatment for weight-loss. They don't like feeling unwell (as a result of GLP-1 induced gastrointestinal muscle effects) and won't continue treatment. Weight bounceback is not, therefore, properly addressed. We shouldn't blame the patient if the drug doesn't fit what they can achieve or tolerate. Instead, we should set out to make a better drug.”
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