Janssen and Hanmi Pharmaceutical announced an agreement yesterday giving Janssen exclusive rights to develop and commercialize Hanmi’s phase 1 long-acting GLP-1/glucagon dual agonist HM12525A for metabolic diseases in all markets except China and Korea. The agreement also covers other potential oxyntomodulin-based therapies. Hanmi will receive an upfront payment of $105 million and is eligible for up to $810 million in potential clinical development, regulatory, and sales milestones. Hanmi would also be eligible for tiered double-digit royalty payments if HM12525A is successfully commercialized, according to its announcement. HM12525A is nearing the end of phase 1; Dr. Marcus Hompesch (Profil, Chula Vista, CA) presented results in healthy volunteers at ADA and indicated that Hanmi was conducting a multiple ascending dose trial in patients with type 2 diabetes. Janssen expects phase 2 trials to begin in 2016. In a conversation with us, Janssen’s Global Therapeutic Area Head, Cardiovascular & Metabolism Dr. James List indicated that the company is aiming for an “aggressive” clinical development timeline comparable to that for Invokana (canagliflozin), which took around six years between first-in-human trials and regulatory submission. Dr. List said that the data will determine which specific indications Janssen chooses to pursue but that there are many potential target populations within the type 2 diabetes-obesity spectrum.
This agreement is further reassuring evidence that Janssen’s interest in type 2 diabetes and metabolic diseases extends beyond the SGLT-2 inhibitor class. Dr. List indicated that Hanmi has been on Janssen’s radar for a long time and that the company is considered by many a “hidden gem” with a portfolio of highly innovative, potentially transformational therapies. He highlighted the fact that GLP-1/glucagon agonists address multiple key drivers of metabolic dysfunction: they promote weight loss by multiple mechanisms, increase beta cell function, and improve insulin sensitivity. The potential for once-weekly dosing with this candidate should be especially appealing for some patients. This announcement caps off a very exciting week for Hanmi, which licensed its long-acting GLP-1 agonist and insulin portfolio to Sanofi just a few days ago.
- We assume a type 2 diabetes indication is the most likely initial target for this candidate given the challenging environment for new obesity drugs. A narrower indication within obesity (à la Rhythm and Zafgen) could also be a possibility. In type 2 diabetes, this class should have fairly high potential for differentiation vs. existing drugs since it targets multiple metabolic defects and is expected to produce greater weight loss than GLP-1 single agonists. In an era of so many options, we assume any new type 2 diabetes drug will need to differentiate itself through either impressive glucose-lowering efficacy, favorable effects on non-glycemic parameters, or ideally a positive effect on cardiovascular outcomes.
- The competitive landscape for GLP-1/glucagon dual agonists is quite crowded. Other companies in the race include Lilly (phase 2), Transition Therapeutics (phase 2; partnered with Lilly), Sanofi (phase 1), AZ (phase 1), Xenetic Biosciences (phase 1), Zealand (preclinical), and OPKO Health (preclinical). Novo Nordisk has also indicated that it ultimately intends to co-formulate its phase 1 glucagon analog with liraglutide.
-- by Emily Regier and Kelly Close