Tobira, Dong-A to develop combination evogliptin, cenicriviroc for NASH

Tobira Therapeutics and Dong-A ST have entered into two licensing agreements, the first of which gives Tobira exclusive development and marketing rights to evogliptin as a single agent and in combination with cenicriviroc in the U.S., Canada, Europe and Australia for all indications, and the second of which gives the same exclusive rights to Dong-A in the Republic of Korea, according to a press release.

The companies also plan to begin development of evogliptin and cenicriviroc combination therapy for non-alcoholic steatohepatitis, and plan to collaborate on a global phase 3 program for cenicriviroc single agent therapy for NASH.

Evogliptin (Suganon) is an oral selective dipeptidyl peptidase-4 inhibitor that was approved in October 2015 and launched in March 2016 for blood glucose control in patients with type 2 diabetes mellitus in the Republic of Korea. It is not currently approved by the FDA. Some data suggest that the incretin/GLP-1 pathways that evogliptin targets may play a role in the progression of non-alcoholic fatty liver disease and NASH, according to the press release.

Cenicriviroc is an oral immunomodulatory that blocks two chemokine receptors (CCR2 and CCR5), which play a role in the inflammatory and fibrogenic pathways in NASH. It has been granted Fast Track status in patients with NASH and liver fibrosis, and is currently being evaluated in the phase 2b CENTAUR study.

“Tobira believes this novel approach will establish [cenicriviroc] as both a single-agent and as a cornerstone treatment in multi-therapy regimens for NASH, for which there is currently no approved drug,” according to the press release.

With the end goal of greater improvements in liver-related outcomes, the combination of evogliptin and cenicriviroc intends to address the metabolic pathogenesis of NASH and, at the same time, the inflammation and fibrosis that cause liver damage, according to the press release.

Tobira intends to perform preclinical toxicology and pharmacokinetics studies with evogliptin before beginning a phase 1 study of the combination therapy late this year.

“This relationship with Dong-A is an important step toward our goal of developing much needed combination therapies for the millions of patients suffering from NASH and to become the preferred partner for companies seeking to develop NASH therapies,” Laurent Fischer, MD, CEO of Tobira, said in the press release. “While incretin therapies are already standard of care for diabetes, they also have the potential to impact the metabolic issues that play a role in NASH disease progression. Evogliptin is a potent DPP-4 inhibitor administered as a small 5 mg once-daily tablet and has demonstrated compelling preclinical and clinical activity for the treatment of type 2 diabetes. It complements the anti-inflammatory and anti-fibrotic effects of cenicriviroc and has the potential to be combined in a fixed dose combination tablet.”

Per the agreement, Dong-A received an upfront $1.5 million cash payment and can receive as much as $25 million in additional payments upon phase 3 completion and approval milestones for the first indication, as much as $10 million more for additional indications, and as much as $35 million more for commercial milestones, according to the press release. Tobira received an upfront $500,000 cash payment and can receive as much as $2.5 million in additional payments upon achievement of similar milestones in Korea. Each company will also receive tiered royalty payments based on net sales, and they are individually responsible for their own development costs.

Disclosure: Fischer is employed by Tobira.