12 June 2023, Shanghai – Abbisko Therapeutics Co., Ltd. (“Abbisko Therapeutics”hereafter) today announced that the first patient has been dosed in the phase II trial evaluating its CSF-1R inhibitor, Pimicotinib (ABSK021), in patients with cGVHD.

The primary underlying mechanism of cGVHD is immune inflammation, which leads to frequent pathological changes in chronic tissue repair and fibrosis. During this process, CSF-1-activated macrophages induce inflammatory response and tissue damage, accelerate abnormal tissue repair and fibrosis, and lead to cGVHD. Recent studies have shown that inhibition of CSF1-R can reduce the expansion and infiltration of donor-derived myeloid macrophages in recipient tissues, which may alleviate cGvHD.

About Pimicotinib

Pimicotinib is a novel, orally available, highly selective, and highly potent small molecule inhibitor of CSF-1R discovered and developed by Abbisko Therapeutics independently. 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. Prior to these, Pimicotinib demonstrated significant antitumor efficacy in a phase Ib trial in patients with TGCT, achieving ORR of 77.4% and favorable safety profile presented in the 2023 ASCO. Abbisko has advanced Pimicotinib into a global phase III MRCT trial for TGCT, and completed dosing of the first patient in April, 2023.

In addition to the ongoing TGCT and cGVHD clinical trials, Abbisko Therapeutics is actively exploring the potential of ABSK021 in treating many other types of solid tumors and non-oncology indications including amyotrophic lateral sclerosis (ALS). As of today, 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.

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.