Zhangjiang Biotech Secures $85M Milestone Payment from Merck for Global Rights to Pimicotinib

On March 28, Merck announced that it would pay Abbisko $85 million (approximately 616 million yuan) as an option exercise fee to further acquire the global commercialization rights for the bone tumor treatment drug Pimitinib.

Pimicotinib (ABSK021), a CSF-1R small molecule inhibitor independently developed by Abbisko, has the initial indication for the treatment of unresectable tenosynovial giant cell tumor. It has previously received Breakthrough Therapy Designation and Priority Medicine Designation in China, the United States, and Europe, and is currently conducting global multicenter Phase III clinical trials simultaneously in China, the United States, Canada, and Europe.

This $85 million commercial rights expansion is a continuation of the 2023 collaboration.

In December 2023, Abbisko and Merck Group entered into an exclusive licensing agreement for Pimitinib. Merck Group paid a one-time, non-refundable upfront fee of $70 million (nearly 500 million yuan) and a potential total payment of $605.5 million (approximately 4.32 billion yuan) to obtain the exclusive commercialization rights for Pimitinib in mainland China, Hong Kong, Macau, and Taiwan, as well as the exclusive option for global commercial rights to Pimitinib.

In terms of clinical development and commercialization strategy, Abbisko and Merck Group started with Tenosynovial Giant Cell Tumor (TGCT) to accelerate the approval and market launch of Pimitespib, with the key factor being the global shortage of TGCT treatment drugs.

Tenosynovial Giant Cell Tumor (TGCT) is a rare, locally aggressive mesenchymal tumor that occurs in joints, bursae, and tendon sheaths, including nodular and diffuse types. This rare benign tumor predominantly affects young and middle-aged individuals of working age, presenting with joint swelling, pain, stiffness, and restricted movement, significantly impacting daily activities and limiting patients' work and social life.

TGCT grows along the tendon sheath and invades joints; therefore, timely surgical treatment is currently recommended in clinical practice. However, diffuse TGCT generally presents a series of clinical challenges, such as a high postoperative recurrence rate and complications caused by repeated surgeries. In terms of medication, there is a global shortage – China has no drugs for TGCT treatment; in the United States, two drugs are available on the market. The first-generation drug, due to its potential liver toxicity, requires patients to go through a Risk Evaluation and Mitigation Strategy (REMS) program, a restricted procedure, to obtain it. Vimseltinib, approved for marketing this February, is used to treat adult patients with non-metastatic tenosynovial giant cell tumor (TGCT) whose surgical resection may lead to functional deterioration or severe morbidity, covering a limited patient population.

It is not difficult to see that the significant barriers in daily life, the young and middle-aged patient population, and the clear clinical needs have paved the way for Pimitinib’s expedited market entry into a highly focused market with well-defined application scenarios. Merck Group first set its sights on the excellent data Pimitinib demonstrated on this “promising path.”

A month before the signing of the $4.3 billion agreement, Abbisko announced further updates to the one-year long-term follow-up data of TGCT patients in the Phase Ib clinical trial of Pimicotinib at the CTOS Annual Meeting. In the 50 mg QD cohort, the best ORR reached 87.5% (28/32, including 3 CRs), showing excellent efficacy data.

In 2024, the global pivotal Phase III study of Pimitinib for TGCT succeeded, achieving a statistically significant improvement in the objective response rate (ORR) at Week 25, reaching 54.0%, compared to 3.2% for placebo. Additionally, statistically and clinically significant improvements were observed across all key secondary endpoints, including ORR based on tumor volume score, as well as active joint range of motion, stiffness, pain levels, and physical function assessed by scales.

From a clinical perspective, the trial data of Pimitinib has well addressed clinical concerns:

First, there is an urgent clinical need for long-term, systemic therapies that can control tumor growth. In trials, pemigatinib demonstrated sustained efficacy over the long term. The median treatment duration reached 20.67 months, with 54.8% of patients having a treatment duration ≥18 months and 38.1% of patients having a treatment duration ≥24 months. During the extended treatment period, continuous tumor shrinkage, relief in pain and stiffness, and gradual improvement in joint mobility were observed.

Secondly, targeting the primary affected population of TGCT, which consists mainly of young and middle-aged adults, Pimitinib enhances accessibility and long-term patient adherence through its dosing mechanism while addressing the potential hepatotoxicity issues of previous treatments. Pimitinib, administered as a once-daily oral treatment for TGCT, demonstrated good tolerability in the pivotal Phase III study, with a very low rate of treatment discontinuation due to treatment-related adverse events. Additionally, no cholestatic hepatotoxicity was observed.

In terms of mechanism, based on the high selectivity and effective inhibition of CSF-1R, this oral, highly selective, and highly active CSF-1R small molecule inhibitor will explore potential efficacy in anti-tumor, inflammation-related diseases, and bone-related diseases.

CSF-1R is a cell surface protein that is believed to control the survival and function of monocytes and macrophages. The CSF-1R (Colony Stimulating Factor 1 Receptor) / CSF-1 pathway is involved in regulating the survival, proliferation, differentiation, and recruitment of Tumor-Associated Macrophages (TAMs).

In terms of anti-tumor effects, high levels of CSF-1 have been found in solid tumors such as breast cancer, prostate cancer, pancreatic cancer, renal cancer, and ovarian cancer. The overexpression of CSF-1 and its receptor CSF-1R in tumors is associated with poor prognosis. In inflammation-related diseases and bone-related diseases, targeting CSF-1R to inhibit signaling has been shown to reduce the number of disease-mediated macrophages and their monocyte precursors in preclinical models. This has been proven to play a critical role in the fibrotic disease processes of underlying conditions such as chronic GVHD and idiopathic pulmonary fibrosis (IPF).

Therefore, CSF-1R is regarded as a promising new target for immune regulation following PD-1, PD-L1, and CTLA-4, with several multinational corporations (MNCs) already involved, including Roche, Bristol-Myers Squibb, Novartis, and AstraZeneca.

Currently, more than 15 selective CSF-1R (or M-CSF) inhibitors have entered clinical research stages, with indications primarily focused on tenosynovial giant cell tumor, chronic graft-versus-host disease, and idiopathic pulmonary fibrosis. Antibody drugs include Axatilimab, Emactuzumab, and Cabiralizumab, while small molecule drugs include Pimicotinib, Vimseltinib, and Edicotinib. In China, among large molecules, only BC006, a CSF-1R antibody developed by BioShip, has entered the clinical stage for the treatment of solid tumors such as tenosynovial giant cell tumor.

Notably, a Biotech has successfully developed this target.On August 14, 2024, Axatilimab (Niktimvo), the world's first CSF-1R antibody developed by Incyte and Syndax, was approved by the FDA for marketing to treat chronic graft-versus-host disease. This is also the first approved CSF-1R antibody targeting the inflammatory and fibrotic drivers of chronic GVHD. Trials showed that the ORR for the low, medium, and high dose groups were 74%, 67%, and 50%, respectively.

On February 14, 2025, Ono Pharmaceutical Co., Ltd. announced that the FDA had approved Romvimza (Vimseltinib) for the treatment of adult patients with non-metastatic tenosynovial giant cell tumor (TGCT) whose surgical resection may lead to functional deterioration or severe morbidity.

Public information shows that, in terms of the TGCT indication, Pimitinib has received Breakthrough Therapy Designation and Priority Medicine (PRIME) designation in China, the U.S., and Europe. It is also conducting a global multi-center Phase III clinical trial simultaneously in China, the United States, Canada, and Europe. While accelerating the market entry through key indications, Abbisko and Merck Group are jointly exploring other potential indications for Pimitinib, including chronic graft-versus-host disease (NMPA has approved Phase II clinical trials), amyotrophic lateral sclerosis, advanced pancreatic cancer (NMPA has approved Phase II clinical trials), as well as extensive combination therapy regimens for solid tumors.

The highly promising novel targets, excellent efficacy data, and vast potential market for indications might all be reasons why Merck made a substantial investment.