Rhythm Acquires Global Rights to LG Chem’s Oral MC4R Agonist for Rare Obesities

Rare Daily Staff

Rhythm Pharmaceuticals has entered into a global licensing agreement with LG Chem for LB54640, an investigational oral small molecule melanocortin-4 receptor agonist now in phase 2 clinical trials.

“The development of an effective oral therapy for treating MC4R pathway diseases has been a major goal for the industry and the early data from LG Chem suggest they have identified a specific therapy for the MC4R without hyperpigmentation or cardiovascular side effects,” said David Meeker, chair, CEO and president of Rhythm Pharmaceuticals.

In a phase 1 trial in healthy overweight adults, LB54640 demonstrated dose-dependent weight reduction. LB54640 also demonstrated a favorable safety profile in the trial, with no changes in blood pressure or heart rate observed and no hyperpigmentation observed. In addition, LB54640 has received orphan drug designation from the U.S. Food and Drug Administration for leptin receptor (LEPR) deficiency and proopiomelanocortin (POMC).

Under the terms of the agreement, Rhythm will pay LG Chem $40 million in cash and $20 million in Rhythm equity at closing and an additional $40 million in cash 18 months after closing. Rhythm has also agreed to pay LG Chem up to $205 million upon achieving certain regulatory and sales milestones, as well as royalties.

Rhythm will assume sponsorship of two phase 2 studies designed to evaluate weight loss efficacy, safety, tolerability and pharmacokinetics of LB54640. The SIGNAL trial is a randomized, placebo-controlled, double-blind study designed to enroll and evaluate approximately 28 patients with acquired hypothalamic obesity. Participants will receive one of three doses of LB54640 by oral administration once daily for up to 52 weeks, and the primary endpoint of the study is the change from baseline in body mass index after 14 weeks of treatment. The open-label, single-arm, 52-week ROUTE trial is designed to enroll five patients with POMC, LEPR, or proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency obesity. Participants will receive LB54640 by oral administration once daily for up to 52 weeks, and the primary endpoint of the study is the change from baseline in body mass index after 14 weeks of treatment.

“Rhythm has pioneered the development and global commercialization of the first and best-in-class therapy for patients with hyperphagia and severe obesity associated with diseases like Bardet-Biedl syndrome (BBS), hypothalamic obesity and certain genetically-defined pathway diseases,” said Jeewoong Son, president of LG Chem Life Sciences. “We believe Rhythm is the ideal partner because of its extensive genetic obesity database, global network of clinical trial sites and investigators, and a track record of regulatory successes.”

Rhythm’s lead asset, Imcivree (setmelanotide) is an MC4R agonist designed to treat hyperphagia and severe obesity approved by the U.S. Food and Drug Administration for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission and the UK’s Medicines & Healthcare Products Regulatory Agency have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above.

Photo: David Meeker, chair, CEO and president of Rhythm Pharmaceuticals