바이오스펙테이터

by Sungmin Kim

Rhythm to Acquire Global Rights to Oral MC4R Agonist LB54640..LB54640 has shown targeted effect on MC4 receptor without hyperpigmentation

LG Chem has started its first global deal of the new year in the domestic pharmaceutical and bio industry.

Rhythm Pharmaceuticals announced on January 5 that it has entered into a global licensing agreement with LG Chem for LB54640, an investigational oral small molecule melanocortin-4 receptor (MC4R) agonist now in Phase 2 clinical trials.

Under the terms of the agreement, Rhythm has agreed to 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.

Also under the terms of the agreement, Rhythm has agreed to pay LG Chem up to $205 million upon achieving certain regulatory and sales milestones, as well as royalties.

Phase 1 clinical trial results appear to have facilitated this deal.

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 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.

“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, MD, Chair, Chief Executive Officer and President of Rhythm Pharmaceuticals. “We believe Rhythm’s deep developmental experience and global commercial presence uniquely positions us to move this molecule forward with the goal of offering a full portfolio of treatment options to patients struggling with hyperphagia and severe obesity and ensuring they get the treatment that is right for them.”

Dr. Jeewoong Son, President of LG Chem Life Sciences Company, said, “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. We believe Rhythm is the ideal partner because of its extensive genetic obesity database, global network of clinical trial sites and investigators, a track record of regulatory successes and - most importantly - because Rhythm values patients and addresses their urgent needs for care.”