Rhythm Acquires Global Rights to Oral MC4R Agonist LB54640

On January 4, 2024, Rhythm Pharmaceuticals, a commercial-stage biopharmaceutical company specializing in rare neuroendocrine disorders, announced a global licensing agreement with LG Chem, a significant South Korean company whose core business includes life sciences. The agreement pertains to LB54640, an oral small molecule melanocortin-4 receptor (MC4R) agonist currently undergoing Phase 2 clinical trials.

David Meeker, MD, Chair, CEO, and President of Rhythm Pharmaceuticals, expressed enthusiasm about building on LG Chem's foundational work. He highlighted that LG Chem's early data indicate LB54640 as a promising therapy for MC4R pathway diseases without causing hyperpigmentation or cardiovascular side effects. Rhythm's extensive development experience and global commercial reach are expected to advance this therapy for patients with hyperphagia and severe obesity, aiming to provide a comprehensive treatment portfolio.

In a Phase 1 trial involving overweight adults, LB54640 showed a dose-dependent reduction in weight, maintaining a favorable safety profile with no observed changes in blood pressure, heart rate, or hyperpigmentation. Additionally, the U.S. Food and Drug Administration has granted LB54640 orphan drug designation for treating leptin receptor (LEPR) deficiency and proopiomelanocortin (POMC) deficiency.

Dr. Jeewoong Son, President of LG Chem Life Sciences Company, acknowledged Rhythm's groundbreaking work in developing and commercializing first-class therapies for hyperphagia and severe obesity related to disorders like Bardet-Biedl syndrome (BBS) and hypothalamic obesity. He emphasized Rhythm's extensive genetic obesity database, clinical trial network, regulatory successes, and patient-centric approach, making them an ideal partner.

Under the agreement, Rhythm will sponsor two Phase 2 studies to evaluate LB54640's efficacy, safety, tolerability, and pharmacokinetics for weight loss. The SIGNAL trial is a randomized, placebo-controlled, double-blind study involving roughly 28 patients with acquired hypothalamic obesity. Participants will receive one of three LB54640 doses orally once a day for up to 52 weeks, with the primary endpoint being the change in body mass index after 14 weeks. The open-label, single-arm, 52-week ROUTE trial will involve five patients with POMC, LEPR, or proprotein convertase subtilisin-kexin type 1 (PCSK1) deficiency obesity. These participants will also receive LB54640 orally once daily for up to 52 weeks, with a similar primary endpoint focused on changes in body mass index.

Per the agreement terms, Rhythm will pay LG Chem $40 million in cash and $20 million in Rhythm equity upon closing, plus an additional $40 million in cash 18 months later. Rhythm will also make up to $205 million in payments based on achieving specific regulatory and sales milestones, along with royalty payments.

LG Chem is a global chemical company with diverse business interests including petrochemicals, advanced materials, and life sciences. Within life sciences, LG Chem focuses on oncology, immunology, and metabolic diseases, striving to transform lives through scientific and innovative advancements.

Rhythm Pharmaceuticals, with headquarters in Boston, MA, is dedicated to improving the lives of those suffering from rare neuroendocrine diseases. Its lead product, IMCIVREE (setmelanotide), an MC4R agonist, is approved by the FDA for chronic weight management in individuals with certain types of genetic obesity. Rhythm continues to pursue broad clinical development for setmelanotide and other treatments for rare disorders.