Kalohexis Announces Publication in Frontiers in Endocrinology Defining Design Criteria for Next-Generation Melanocortin Drugs for General Obesity

Novel dual melanocortin-3 and -4 receptor (MC3R/MC4R) agonists with improved potency, selectivity, central exposure and cardiac safety profiles may unlock broad use in general obesity

NORTHBROOK, Ill., March 25, 2026 /PRNewswire/ -- Kalohexis, a clinical-stage biotechnology company harnessing the melanocortin system to shape the next era of metabolic disease care starting with obesity and cancer cachexia, today announced the publication of a peer-reviewed article in Frontiers in Endocrinology. Titled, "The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives," the review examines the factors that have historically limited the success of melanocortin (MC) drug development for obesity and identifies a new set of design criteria for next-generation MC therapeutics based on these insights.

Following a systemic review of MC drugs, the authors conclude that prior MC drug development failures stemmed from insufficient receptor potency, narrow therapeutic windows, cardiac activation and selective targeting of the melanocortin-4 receptor (MC4R), limiting treatments to rare genetic obesity indications. The Company's previous research, including a preprint posted on bioRxiv, demonstrates the importance of dual activation of both melanocortin-3 receptor (MC3R) and MC4R for optimal and durable weight loss, reinforcing the MC system as a highly validated target for the treatment of general obesity. The Frontiers in Endocrinology review outlines key characteristics necessary for next-generation MC treatments including high potency and preferred selectivity and PK profiles.

"Our analysis in Frontiers in Endocrinology shows that prior melanocortin system obesity drug development targeted MC4R selectively, missing the complementary role of MC3R in energy regulation. New science indicates that co-activating both MC3R and MC4R, rather than MC4R alone, is the key to unlocking meaningful, durable weight loss, while avoiding the safety and efficacy challenges of previous approaches. This insight enabled us to define improved characteristics for next-generation melanocortin drugs, suggesting MC agonists could emerge as a major therapeutic class for general obesity," said Dr. Daniel Marks, Chief Scientific and Medical Officer of Kalohexis and co-author of the article.

"Dual agonism of both receptors produces greater efficacy, a wider therapeutic window and a body composition profile that compares favorably to GLP-1 therapies. Our analysis highlights the promise of emerging melanocortin therapeutics both as monotherapies and as GLP-1 adjuvants for general obesity," Dr. Marks continued. 

Kalohexis was recently spun out from Endevica Bio, a world leader in the discovery of first-in-class synthetic peptidomimetics, with its melanocortin assets. Endevica Bio's research into dual MC3R/MC4R agonism was established over a decade of discovery and pre-clinical development. 710GO, the company's novel, oral, equipotent dual MC3R and MC4R agonist, was found to be safe and well-tolerated and has shown promising pre-clinical efficacy. In initial studies of diet-induced obese non-human primates (NHP), 710GO demonstrated an average weight reduction of 11.7% compared to control over 13 weeks, with no cardiac safety signals at six times its efficacious dose and without the side effects commonly associated with standard-of-care GLP-1 receptor agonist obesity treatments: significant lean body mass loss¹, rapid weight rebound following treatment cessation² and gastrointestinal distress³. Furthermore, combination treatment of obese NHPs with 710GO and the GLP-1 receptor agonist semaglutide over 19 days demonstrated an average weight reduction of 6.5% compared to a reduction of 3.0% with semaglutide monotherapy over the same time period. 

About Kalohexis
Kalohexis is a clinical-stage biotechnology company shaping the next era of metabolic disease care by harnessing the melanocortin (MC) system, the body's natural regulator of metabolic homeostasis, to help people live healthier lives. Kalohexis' first- and best-in-class therapeutic peptides are designed to safely and effectively drug central melanocortin-3 and -4 receptors (MC3R/MC4R) to treat many metabolic disorders. Kalohexis' lead pipeline programs are 710GO, an oral dual MC3R/MC4R agonist to induce healthier, more durable weight loss in general obesity, and mifomelatide, a dual MC3R/MC4R antagonist to prevent and treat cachexia in patients with advanced cancers. For more information, visit www.kalohexis.com or follow us on LinkedIn and X. 

¹ Neeland IJ, et al.  Diabetes Obes Metab. 2024:26 Suppl 4:16-27.
² NHP Weight rebound: Jensen MH, et al. Mol Metab., 2024;88:102006
³ Sodhi M, et al. JAMA. 2023;330:1795-1797

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SOURCE Kalohexis