Memorandum

Lilly and KeyBioscience AG partner to develop amylin/calcitonin receptor dual agonists for diabetes – June 20, 2017

Executive Highlights

  • Lilly announced recently a new strategic partnership with KeyBioscience AG to develop Dual Amylin Calcitonin Receptor Agonists (DACRAs) for the treatment of type 2 diabetes and other metabolic diseases. Lilly will receive global rights to develop and commercialize this family of products, while KeyBioscience AG will receive $55 million in upfront payment and is eligible for subsequent milestone payments and royalties.
  • Gut hormone expert Dr. Daniel Drucker pointed to the robust weight loss and improved metabolic health seen with amylin analogs, which we find quite exciting. We look forward to more details on these investigational candidates – including with regards to the calcitonin aspect – and ideally we’d love to see Lilly develop these therapies for diabetes, obesity, and NASH.

Lilly announced recently a new strategic partnership with KeyBioscience AG to develop Dual Amylin Calcitonin Receptor Agonists (DACRAs) for the treatment of type 2 diabetes, among other metabolic diseases. Lilly will receive global rights to develop and commercialize several products in the KeyBioscience AG pipeline, the most advanced being phase 2 KBP-042. Along with KBP-089 and KBP-056 (two other candidates included in the partnership that range from preclinical to phase 1 development), KBP-042 is a dual agonist of amylin as well as the calcitonin receptor. As the great Dr. Daniel Drucker (Mount Sinai Hospital, Toronto, Canada) emphasized shortly after the news was released, amylin has been associated with robust weight loss and improved metabolic health, making it a logical next step and scientific advance for therapeutic areas like type 2 diabetes, obesity, and NASH. Indeed, Zealand and BI recently announced amylin as the biological target for their cardiometabolic partnership, and the two companies are jointly advancing amylin analog ZP4982 into phase 1 studies. Notably, ZP4982 will be investigated as an obesity therapy, and Novo Nordisk also has a long-acting amylin analog in phase 1 for obesity. AZ’s Symlin (pramlintide) is an amylin analog marketed for type 1 diabetes, but has never quite taken off commercially, due at least in part to dosing challenges (injections at every meal) and adverse side-effects such as GI symptoms and hypoglycemia (though these could very well be attributed to lack of patient/provider knowledge on how to properly titrate the dose). Still, we imagine Lilly will have to address these shortcomings through clinical development of KBP-042 and other agents in the DACRA family. We’ll have our eyes and ears peeled for data on this front. Calcitonin levels are often elevated in patients with diabetes, so making the calcitonin receptor more active to uptake this hormone and reduce its concentration in the bloodstream could yield additional therapeutic benefits – we’re not aware of any other diabetes candidates focused on calcitonin as a therapeutic target and we’re eager to learn more about this novel mechanism.

Also stipulated in the agreement, KeyBioscience AG will receive an initial payment of $55 million, and remains eligible for additional milestone payments and royalties as these amylin/calcitonin drug candidates progress through clinical development, regulatory review, and (hopefully) commercialization down the line.

We see this partnership as very positive for the diabetes community, and we applaud Lilly for investing in this potential next-generation therapy class. As clinical trials proceed, there will be lots to sort through – what works so well about dual agonism of amylin and calcitonin receptors, and how can new therapies in this class circumvent or overcome the hurdles faced by pramlintide? Given Lilly’s expertise in pharmaceutical development and long history of success in diabetes specifically, we view the company as very well-suited to carry forward these investigational agents.

  • Dr. Drucker emphasized that amylin could have an important therapeutic role to play not only in diabetes, but in obesity and other inflammatory conditions like NASH as well. Lilly’s announcement of its acquisitions from KeyBioscience AG remains vague on the scope of therapeutic areas that may be explored, and we’d certainly love to see studies in obesity and NASH in addition to type 2 diabetes. NASH is an area of particularly high unmet need, as no therapies are yet FDA approved – see our competitive landscape for more. Of-late, many pharma companies have added NASH candidates to their pipeline or have doubled-down on their investments in NASH. Lilly already has a DGAT-2 inhibitor and a once-weekly GLP-1/glucagon dual agonist in phase 1 for NASH (alongside other indications – dyslipidemia and type 2 diabetes, respectively). There is also a clear need for better obesity medicines, given that only Novo Nordisk’s Saxenda (liraglutide 3.0 mg) is faring well on the market right now, and given that only 2% of 600 million people with obesity worldwide are currently receiving adequate medical treatment for the chronic condition. We’ll be supremely interested to see how DACRAs factor into this, and we’ll be thrilled to see Lilly invest further in its obesity pipeline. See our competitive landscape of obesity pharmacotherapies in development for more.

-- by Payal Marathe, Helen Gao, and Kelly Close