Merck, a renowned science and technology company, has reached a significant milestone in its efforts to combat cancer. The company announced a strategic licensing agreement with New York-based Inspirna, Inc. for the development of ompenaclid, a first-in-class oral inhibitor targeting the creatine transport channel SLC6A8, and its follow-on compounds. Ompenaclid, which is currently undergoing a Phase II study, shows promising potential as a second-line treatment for RAS-mutated (RASmut) advanced or metastatic colorectal cancer (mCRC).

Victoria Zazulina, MD, Head of the Development Unit, Oncology for the Healthcare business sector of Merck, highlighted the lack of major innovation in the treatment of RAS-mutated CRC, which accounts for approximately 45% of the second-line population. She emphasized that the agreement with Inspirna offers the opportunity to advance a potential new first-in-class therapy that may improve outcomes for patients.

The collaboration is centered on ompenaclid, a groundbreaking oral inhibitor of SLC6A8. Encouraging data from a Phase Ib/II study showed significant efficacy and safety, making it a promising candidate for second-line treatment of RASmut mCRC. As per the data presented at the 2023 ESMO Congress, the median progression-free survival was 10.2 months, and the median overall survival was 19.1 months across patients with RASmut mCRC.

Inspirna has initiated a Phase II double-blind randomized controlled trial comparing ompenaclid against a placebo plus FOLFIRI and bevacizumab in second-line RAS-mutant advanced or metastatic CRC. This trial is a critical step in evaluating the efficacy and safety of ompenaclid in a larger patient population.

The collaboration builds on Merck’s long-standing commitment to the colorectal cancer community. 2024 marks the 20th anniversary of ERBITUX, for which Merck has marketing rights outside the U.S. and Canada, as a backbone treatment in mCRC. Merck is also developing M9140, a CEACAM5-targeting antibody-drug conjugate currently in a Phase Ia/b study.

Dr. Usman “Oz” Azam, CEO of Inspirna, expressed excitement about partnering with Merck. He emphasized the potential of ompenaclid as a first-in-class therapy and the strength of Inspirna’s proprietary target discovery platform RNA-DRIVEr.

Under the terms of the license agreement, Merck will receive an exclusive license to ompenaclid outside of the United States, with an option for co-development and co-promotion in the US. Inspirna will receive an upfront payment of $45 million and is eligible for milestone payments and royalties on net sales outside of the US.

This partnership between Merck and Inspirna highlights the ongoing efforts to develop innovative treatments for cancer, particularly colorectal cancer, which remains a major global health challenge.

  Colorectal cancer, Dr. Usman Azam, Inspirna, Merck, Ompenaclid, Victoria Zazulina