While Kallyope’s drugs are mechanistically unique, the biotech is competing in a crowded space, with other therapies that appear to elicit superior weight-loss.
Kallyope quietly updated the clinicaltrials.gov page for a mid-stage obesity study Wednesday, revealing middling weight-loss benefits.
The Phase II study enrolled 155 adults with obesity who had tried and were unable to lose weight at least once in the past. Kallyope tested two of its investigational nutrient receptor agonists: KL-757, which was administered as a monotherapy or in combination with another Kallyope molecule, K-833.
Results posted on the federal database on Wednesday showed that participants on K-757 alone saw a 1.57% reduction in body weight after 13 weeks of treatment—an effect that fell short of statistical significance. Combining K-757 with K-833, however, elicited a significant 2.94% drop in weight at 13 weeks. Those on placebo lost only 0.15% body weight over the same time span.
In absolute terms, patients who were on the K-757 monotherapy dropped around 1.6 kg over 13 weeks of observation, while counterparts on the combination regimen shed 3.11 kg.
Kallyope is seeking to set itself apart in the crowded and competitive obesity market by introducing a novel mechanism of action: activating nutrient receptors to simulate satiety. Both K-757 and K-833 are taken in pill form, and are “the only known oral nutrient receptor agonists being studied for the treatment of obesity,” according to the company. Per a Kallyope news release in September 2023, K-757 and K-833 work by enhancing the body’s natural metabolic signaling to trigger the secretion of hormones that help suppress appetite.
In particular, K-757 and K-833 stimulate the production not just of GLP-1, but also of PYY and CCK, gut hormones released in response to meals and which are known to activate receptors in the brain to tone down appetite. Through this mechanism of action, Kallyope’s obesity drugs elicit an effect like that of bariatric surgery.
Based on Wednesday’s data, however, a unique mechanism of action might not be enough for Kallyope. Eli Lilly’s orforglipron, currently the most highly anticipated obesity pill in the clinic, has shown better efficacy—though direct comparisons are inconclusive in the absence of well-designed head-to-head studies.
Still, in a Phase II readout released June 2023, Lilly’s candidate cut 8.6% to 12.6% of body weight at 26 weeks. Higher doses of orforglipron led to even better weight-loss, and patients taking the drug were able to keep the weight off for 36 weeks.
Meanwhile, fellow biotech Metsera is advancing a long-acting GLP-1 injection that, in a Phase IIa readout last month, triggered an average weight-loss of 11.3% versus placebo after 12 weekly doses. In some cases, patients saw weight reduction reaching as high as 20%. A few days later, Metsera filed for an initial public offering, targeting a $289 million raise.
