Jiangsu Yayao Biotech submitted the Investigational New Drug (IND) application for YY2201, an ATR Inhibitor, in China on June 28, 2024. This marks the first time a novel Category 1 drug from the company has reached the IND stage. According to the company's public information, the IND application for YY2201 is also underway in the USA.
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| Yayao Biotech Logo |
Yayo Biotech was founded by scientists who returned to China and local experts in the Pharmaceutical Valley of the Jiangbei New District in Nanjing. They prioritize the development of generic drugs, followed by novel drugs. Currently, their first p53-MDM2 inhibitor is in the process of being patented, although they already filed the first patent covering MDM2 inhibitors in 2021.
In 2022, Yayao Biotech filed a patent (CN117247386) covering novel pyrazolopyrimidine compounds as ATR inhibitors with inventors XIAO Fei (肖飞), WENG Yali (翁亚丽), and WU Meng (吴萌) in China. The positive control drug is ceralasertib developed by AstraZeneca, which is currently under investigation in NSCLC and other solid tumors. Two compounds, M1a and M3, showed ATR IC50 values of 25nM and 7nM, respectively (ceralasertib 15 nM).
| Compounds in patent |
ATR Inhibitors in China
Seven China-made products are currently in clinical trials, either as monotherapy or in combination with PARP inhibitors, chemotherapies, or immunotherapies.
| ATRi Landscape in China |
SC0245
SC0245 is a novel ATR inhibitor developed by WuXi AppTec, Shijiazhuang Sagacity, Wuxi Biocity. In 2024, Biocity presented the preliminary results of the phase 1 trial of SC0245 at the ASCO Annual Meeting. "As of the data cut-off-date of January 10, 2024, 27 pts (median age, 56; male, 48.1%) were enrolled and treated with SC0245 doses of 1, 1, 4, 4, 4, 2, 4, 3 and 4 pts in 40, 80, 120, 160, 200, 240 and 300mg QD, and 160 and 200mg BID cohort, respectively. No DLTs have been observed to date......Eleven of 21 pts who were evaluable for tumor assessment had stable disease as their best response, with seven pts having reductions in target lesions......"
HRS2398
HRS2398 is Hengrui's ATR inhibitor which is currently in the phase 1b/2 clinical stage in combination with anti-PD-L1 antibody. No results of the clinical trials have been reported.
IMP9064
IMP9064 is IMPACT's ATR inhibitor, another DDR pathway inhibitor besides the PARP target. In 2023, IMPACT reported the results of its FIH clinical study at the ESMO Annual Meeting. "As of Feb 14th,2023, 16 patients were enrolled: Cohort 1 (n=1, 7.5 mg); Cohort 2 (n=1,15 mg); Cohort 3 (n=4, 30 mg); Cohort 4 (n=3, 45 mg); Cohort 5 (n=4, 80 mg); Cohort 6 (n=3, 120 mg). No dose-limiting toxicities were observed in the dose range of 7.5 to 80 mg......9 of 13 evaluable patients had stable disease as their best response. A patient with advanced renal tumor from cohort 4 experienced stable disease and remains on trial with more than 7 cycles to date. In Cohort 3, a non-small cell lung cancer patient displayed a 158% ctDNA increase on C2D1, followed by a 58.2% decrease on C4D1 and an 84% decrease on C6D1 relative to C2D1......"
LF0397
LF0397 is a small molecule ATR inhibitor discovered by Lingfang Biomedical. No reports of either preclinical or clinical trials have been reported.
ATG-018 (Terminated in July 2024)
ATG-018 is an orally available, potent, selective small molecule ATR inhibitor discovered by Antegene. "For cell proliferation inhibition, the IC50 of ATG-018 ranged from 0.22μM to 10μM in 137 out of 143 cell lines, including both solid tumor and hematological malignancies, while ATG-018 did not affect the viability of normal PBMCs. For ATR activity inhibition, the IC50 of ATG-018 required for ATR downstream (CHK1) phosphorylation inhibition was 1.4nM in HT-29 cells and the IC50 required for inhibiting ATR kinase reaction was 16nM."
Updated in July 2024, the clinical study was terminated early due to lack of efficacy with an enrollment of 25 patients.
DN020198
DN020198 is De Novo's ATR inhibitor which is currently in the phase 1 study. For now, no results have been reported.
By the way, De Novo licensed a PARP inhibitor SC10914 to its parent company Qingfeng Pharmaceutical.
TCC1727
TCC1727 is a selective ATR kinase inhibitor developed by Tide Pharmaceutical, a subsidiary of CTTQ.
TQB3015
TQB3015 is an ATR inhibitor discovered by CTTQ. However, the phase 1 trial was soon suspended after the initiation without any explanation.
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