Abbisko Therapeutics Co. Ltd. has out-licensed China rights to its colony-stimulating factor 1 receptor (CSF-1R) inhibitor, pimicotinib, to Merck KGaA in a deal worth up to $605.5 million. Pimicotinib is in phase III trials in patients with tenosynovial giant cell tumors (TGCT) in China, the U.S., Canada and Europe.

Under terms of the deal, Merck, of Darmstadt, Germany, will be granted an exclusive license to commercialize products comprising pimicotinib (ABSK-021) for all indications in mainland China, Hong Kong, Macau and Taiwan. Abbisko will receive $70 million up front and is eligible for development and commercialization milestone payments that are worth up to $605.5 million inclusive of the up-front payment.

Abbisko is also eligible for double-digit sales-based royalties. Merck has the option to commercialize the drug globally for an additional payment, Hua Jiang, Abbisko’s business development director told BioWorld.

“Abbisko is working on the phase III study, and we will keep going on that because we don't want to slow that down, and Merck will have the right to commercialize in greater China and will be the marketing authorization holder,” he said, noting that it was not yet clear whether Abbisko or Merck would submit marketing applications.

Abbisko, of Shanghai, decided to out-license the molecule because the company lacks a commercialization engine and is strongly focused on being IND-driven. “We have a lot of projects in the pipeline we are focusing on,” he said noting that 10 programs are in clinical trials and six in preclinical development.

The purpose of the license agreement is to expand coverage of pimicotinib through Merck’s commercial organizational structure and to extend the availability of medicines to patients in China. In 2022, Merck generated sales of €22.2 billion (US$24.04 billion) in 66 countries.

For Merck, the deal provides an opportunity to address a significant unmet medical need and to expand its commercial footprint in oncology in China, the second largest pharmaceutical market in the world, said Andrew Paterson, chief marketing officer for the health care business sector of Merck.

“We have the opportunity through our partnership with Abbisko to deliver a first-in-class treatment for a critically underserved patient

population in China and potentially beyond,” he added. “The collaboration with Merck is an important milestone in advancing the global commercialization process of pimicotinib and provides a

new model for the commercialization path of the company's pipeline in the future,” said Abbisko Chairman Xu Yao-chang.

First CSF-1R inhibitor developed in China to enter global trials Internally discovered and developed by Abbisko, pimicotinib is an orally bioavailable, selective, small molecule and is the first CSF-1R

inhibitor developed in China to enter global phase III trials. Registrational trials led by Chinese pharmaceutical companies and launched simultaneously worldwide are rare, Abbisko Chief Medical Officer Jing Ji told BioWorld in an earlier interview.

The molecule has been granted breakthrough therapy designation (BTD) and priority medicine (PRIME) designation by China’s National Medical Products Administration (NMPA), the U.S. FDA and the EMA for treatment of patients with TGCT that are not amenable to surgery. Also known as pigmented villonodular synovitis, TGCT is a locally aggressive neoplasm that affects synovial joints, mucous sacs and tendon membranes, resulting in swelling, pain, stiffness and decreased activity of the affected joints.

Currently, there are no highly selective CSF-1R inhibitors approved in China, and for those TGCT patients not able to have surgery, there is no approved drug available in China. The only drug approved to treat TGCT, Turalio (pexidartinib, Daiichi Sankyo Co. Ltd.) won FDA clearance in 2019 for adults with symptomatic TGCT associated with severe morbidity or functional limitations and not responsive to improvement with surgery. Prescribing information for Turalio includes a boxed warning about the risk of serious and potentially fatal liver injury, and the FDA requires a risk evaluation and mitigation strategy (REMS) program.

In comparison, pimicotinib has no apparent liver toxicity, Ji said, noting that there were no grade 3 adverse events seen in the phase I trial. In addition to TGCT, Abbisko is actively exploring the potential of pimicotinib in treating other indications, including solid tumors, and has obtained approval from the NMPA to conduct a phase II trial in chronic graft-vs.-host disease (GVHD) and advanced pancreatic cancer. Next in line is FGFR4 inhibitor irpagratinib (ABSK-011) for liver cancer, which is a big problem in Asia Pacific, and there is no proven drug in this class yet, Jiang said. “We are in the first tier in the competition and have shown some exciting data at the recent ESMO Europe meeting,” he said.

Abbisko has built an extensive pipeline of 15 innovative small-molecule programs focused on precision oncology and immuno-oncology. “Pimicotinib is just the beginning,” Jiang said, noting that the company is in other deal discussions, and he expects numerous deals in 2024.

Abbisko’s stock on the Hong Kong Stock Exchange (HKSE:2256) dropped 6.87% on news of the deal from HK$4.22 (US53 cents) to HK$3.93 per share on Dec. 5, 2023.

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