17 Jan 2023, Shanghai – Abbisko Therapeutics Co., Ltd. (“Abbisko Therapeutics” hereafter) today announced that its CSF-1R inhibitor, pimicotinib (ABSK021), has been approved by the National Medical Products Administration (“NMPA”) of the People’s Republic of China for a phase II clinical study in patients with chronic graft-versus-host disease (“cGVHD”). Pre-clinical data indicated that pimicotinib is a highly potent and selective small molecule inhibitor of CSF-1R that may play  important roles for treating many human diseases including complications associated with transplantations.

About Pimicotinib (ABSK021) 

Pimicotinib is a novel, orally available, highly selective, and highly potent small molecule inhibitor of CSF-1R, independently discovered and developed by Abbisko Therapeutics. A number of studies have shown that blocking the CSF-1R signaling pathway could effectively modulate and change macrophage functions, and potentially treat many macrophage-dependent human diseases. Pimicotinib is currently being investigated as a treatment for tenosynovial giant cell tumor (TGCT) and cGVHD, and under evaluation as treatment for a number of other indications. 

In July 2022, pimicotinib was granted Breakthrough Therapy Designation from the Center for Drug Evaluation, NMPA for the treatment of TGCT that is not amenable to surgery. Subsequently in October 2022, Abbisko Therapeutics obtained CDE approval to conduct a Phase III clinical trial in TGCT for pimicotinib. Prior to these, pimicotinib demonstrated significant antitumor efficacy in a phase Ib trial in patients with TGCT, achieving a preliminary ORR of 68.0% and favorable safety profile.

Abbisko Therapeutics also completed a Phase Ia dose escalation study for ABSK021 in the U.S. and is conducting an ongoing Phase Ib multi-cohort expansion trial in both the U.S. and China. In addition to TGCT and cGVHD, Abbisko Therapeutics is actively exploring the potential of ABSK021 in treating many other types of solid tumors and has collaborated with Sperogenix (Shanghai) MedTech Co., Ltd. in exploring its potential for treating amyotrophic lateral sclerosis (ALS) among other central nervous system disorders. As of current, no highly selective CSF-1R inhibitor has been approved in China.

About cGVHD

Chronic graft-versus-host disease (cGVHD) is the clinicopathological syndrome (including classical cGVHD and overlap syndrome) caused by donor lymphocytes attacking the recipient organs during the process of rebuilding recipient immunity after allogeneic hematopoietic stem cell transplantation, which is one of the major complications after transplantation. According to Chinese consensus on the diagnosis and management of cGVHD (2021), the incidence ranges from 30 to 70%^{[1] [2]}.

The clinical manifestations of cGVHD are diverse with great individual differences, and the course of cGVHD is long-lasting. Multiple vital organs can become involved, thereby seriously affecting the quality of life and long-term survival of patients. Glucocorticoids are still the standard first-line treatment for cGVHD but more than half of treated patients will develop resistance and require second-line therapy. There are currently no approved therapeutic agents for patients with cGVHD who have failed to respond to glucocorticoid therapy in China.

The main pathophysiological process of cGVHD is immune inflammation, and the common characteristic pathological changes are chronic tissue repair and fibrosis. In this process, macrophage activation dependent on colony stimulating factor (CSF-1) promotes inflammatory response and tissue damage, and accelerates abnormal tissue repair and fibrosis, leading to the manifestations of cGVHD.

References

1. Xu L, Chen H, Chen J, et al. The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in Chinarecommendations from the Chinese Society of Hematology［J］. J Hematol Oncol, 2018, 11（1）: 33. DOI: 10.1186/s13045- 018- 0564-x

2. Wang Y, Chen H, Chen J, et al. The consensus on the monitoring, treatment, and prevention of leukemia relapse after allogeneic hematopoietic stem cell transplantation in China. Cancer Lett. ［J］. Cancer Lett, 2018, 438: 63- 75. DOI: 10.1016/j.canlet.2018.08.030.