One + one may be better than two

Partners to combine agonists in hopes of treating NASH

Register for free to listen to this article
Listen with Speechify
INGELHEIM, Germany & SEOUL, South Korea—The long-standing partnership between Boehringer Ingelheim and Yuhan Corp. has deepened with a recent license agreement to develop a first-in-class dual agonist as a potential treatment for cardiometabolic diseases. By combining activity of the gut-derived hormone glucagon-like peptide-1 (GLP-1) with that of fibroblast growth factor 21 (FGF21), a protein widely expressed in the liver, the two companies believe they may have a novel approach to treating some cardiometabolic diseases. The resulting molecule, a dual agonist, may successfully tackle nonalcoholic steatohepatitis (NASH) at multiple levels.
The two entities have been in ongoing dialogue for years, and took their first formal steps to partner in 2015 through a fruitful marketing relationship of diabetes-related products in South Korea. That success initiated deeper conversations between the two, leading to an active exploration of complimentary assets.
According to Dr. Michael Mark, head of Global Department Cardio Metabolic Diseases Research at Boehringer Ingelheim, they had conducted enough successful experiments together, and had comprehensively profiled the compound. Boehringer Ingelheim has developed a broad portfolio of pharmaceutical treatments for NASH and saw that the new molecule being tested by Yuhan would be another weapon in the arsenal. “We determined that now is the right time to partner formally on this asset. We have an open, trustful relationship, and now we have this science-driven partnership,” he remarked.
What makes this dual agonist promising is the potential ability to treat several factors in the presentation of NASH at the same time. NASH is characterized by three drivers: steatosis (also known as fatty liver), inflammation and fibrosis. Fat accumulates in the liver, which in turn causes inflammation in the system, which can result in liver fibrosis and cirrhosis. By combining their two compounds in a new molecule, the companies can attack several causes at once.
GLP-1 agonists are a class of antidiabetic drugs known to improve insulin sensitivity, while also having a direct effect on the lipid metabolism of hepatocytes, reducing hepatic steatosis. Simultaneously, FGF21 correlates with severe steatohepatitis and, in particular, fibrosis. And together, they can accomplish even more.
“We know that the combination of the two molecules creates a positive cooperation that increases the effect and makes their respective actions more powerful,” said Mark, suggesting that in this case, the whole is more effective than the sum of its two parts.
“We look forward to working jointly with Boehringer Ingelheim, with its strong track record of bringing new treatments to patients with cardiometabolic disease. Boehringer Ingelheim’s clinical expertise will now be applied to the development of this drug which has the potential to make a real difference for patients with NASH,” added Jung Hee Lee, president and CEO at Yuhan. “This molecule, which is a fusion protein utilizing the long-acting (HyFc) technology of Genexine, has been developed in-house by Yuhan Corporation. Not only is our collaboration with Boehringer Ingelheim on this molecule Yuhan’s first external partnership with biologics, it is also the very first out-licensing of biologics targeting NASH from Korea.”
At this point, the resulting molecule is being tested both preclinically and clinically; it is in the late stage of the discovery period, heading into the early stages of the development stage. The next major step will be to commence Phase 1 clinical trials, although no formal timeline has been announced. The two companies have carefully considered the potential side effects based on what the literature says about each component, and have determined that any concerns that could arise have been clearly ruled out.
“This combination agonist has strong potential. Based on the GLP-1 action, it could also be helpful in treating obesity or type 2 diabetes—those are just some of the potential indications,” asserts Mark. “This is the basis of solid collaboration between the two companies. Yuhan gives us a new technology with the detailed architecture of this molecule to open up new spaces for drug discovery and development.”
Under the terms of the agreement, Boehringer Ingelheim will develop the new molecule as a potential commercial medication, while Yuhan will receive upfront and near-term payments of $40 million. Yuhan is eligible to receive up to $830 million in potential milestone payments, plus tiered royalties on future net sales.

Subscribe to Newsletter
Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

DDN Magazine May 2024

Latest Issue  

• Volume 20 • Issue 3 • May 2024

May 2024

May 2024 Issue