Shanghai-based biotech firm Abbisko Therapeutics Co., Ltd (HKG: 2256) has announced the first patient dosing in a Phase II clinical study for its Category 1 drug ABSK021 (pimicotinib), which is aimed at treating chronic graft versus host disease (cGVHD).
Understanding cGVHD and the Role of CSF-1R Inhibition
The pathological and physiological process of cGVHD is characterized by immune inflammatory responses, with chronic tissue repair and fibrosis being common pathological changes. In this context, macrophages activated by Colony-stimulating factor (CSF-1) exacerbate inflammation and tissue damage, leading to the expression of cGVHD. Recent studies indicate that inhibiting the CSF-1 receptor (CSF1-R) can reduce the expansion and infiltration of donor-derived myeloid macrophages in recipient tissues, potentially alleviating cGVHD.
Pimicotinib’s Mechanism of Action and Previous Study Results
ABSK021 is an orally administered, highly potent, and selective small-molecule inhibitor of CSF-1R. Research has demonstrated that blocking the CSF1/CSF-1R signaling pathway can modulate macrophage function, impacting various macrophage-related diseases. In a Phase Ib study, the drug achieved a 77.4% objective response rate (ORR) in inoperable tenosynovial giant cell tumor (TGCT), showcasing a good safety and PK/PD profile. These positive results were presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting. Pimicotinib is currently undergoing Phase III clinical studies in TGCT in China and the US and is also being explored for other solid tumors and non-tumor indications such as amyotrophic lateral sclerosis (ALS). To date, there is no similar drug approved in China.-Fineline Info & Tech
