China CDE has accepted the IND application for JS125/WJ47156 submitted by Junshi Bioscience. JS125/WJ47156, a novel HDAC1/2/3 inhibitor, is co-developed by Junshi and Wigen Biomedicine.
In 2020, they announced the first collaboration agreement including 4 cancer drug candidates (XPO1 inhibitor, Aurora-A inhibitor, EGFR-exon20 inhibitor, and 4th generation EGFR inhibitor). In the 2022 interim financial results, Junshi disclosed that they had expanded their collaboration with Wigen to include four additional cancer drug candidates (IDH1 inhibitor, SHP2 inhibitor, FGFR2 inhibitor, and ATR inhibitor). JS125/WJ47156 may be part of the third collaboration (not disclosed so far) patch between Junshi and Wigen Biomedicine.
JS125/WJ47156
JS125/WJ47156, a novel HDAC inhibitor, is co-developed by Junshi and Wigen Biomedicine as a cancer treatment. According to the press release, JS125/WJ47156 selectively inhibits HDAC1, HDAC2, and HDAC3, leading to cell cycle arrest, cell differentiation, anti-angiogenesis, and autophagy.
In 2022, Wigen filed a patent (WO2024120448) covering HDAC inhibitors and their use in cancer treatment. Several deuterated chidamides were synthesized and tested in vivo and in vitro. Compound 5, a deuterated chidamide, demonstrated HDAC1/2/3 IC50 values of 67 nM, 153 nM, and 657 nM, compared with Chidamide's values of 80 nM, 128 nM, and 583 nM.
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Domestic Innovative HDACi in China
Chidamide (Tucidinostat)
Chidamide, developed by Chipscreen, is the first China-discovered drug to be approved. It has been launched as a treatment for PTCL, breast cancer, and DLBCL.
In 2007, Chipscreen granted its ex-China rights of Chidamide to Huya Bioscience. In 2021, Huya received approval for Chidamide in ATLL in Japan.
Chidamide is currently being evaluated in clinical trials in combination with anti-PD-1 therapies for solid tumors.
Purinostat
Purinostat, currently under investigation in DLBCL, MM, PTCL/CTCL, and solid tumors, is developed by Zenitar Biomedical. Purinostat has highly selective inhibition activity against class I and IIb HDAC subtypes with IC50 values as 0.81, 1.4, 1.7, and 3.8 nmol/L for class I HDAC1, 2, 3, and 8, and 11.5, 1.1 nmol/L for class IIb HDAC6 and 10, respectively.
| Purinostat |
Currently, purinostat is in the phase 2 clinical study in patients with rrDLBCL. In 2024, Zenitar presented the results of the phase 2a study in rrDLBCL: The ORR (20/28) was 71.4% (95%CI:51.3-86.8) with 5 CR and 15 PR. Fifteen pts at 8.4 mg/m2 achieved an ORR of 66.7%(95%CI:38.4-88.2) with 1 CR and 9 PR. Thirteen pts at 11.2 mg/m2 achieved ORR of 76.9%(95%CI:46.2-95.0) with 4 CR and 6 PR. As of the data cut off in Feb. 2024, 7 pts remained on treatment and the longest treatment has lasted 17 cycles. Median PFS was 4.3m (95%CI:2.8-8.5), OS were immature. In subgroup analyses, 7 DE DLBCL pts obtained 42.9%(3/7) ORR and 11 pts with TP53 abnormal by FISH or NGS test achieved 45.5%(5/11) ORR. Fifteen pts with non-DE or without TP53 abnormal achieved ORR of 86.7%(13/15). The most frequently reported Grade≥3 TRAE were thrombocytopenia, neutropenia, lymphocytopenia.
Heptyphemide
Heptyphemide is a novel HDAC inhibitor developed by Hisun Pharmaceutical. Hisun initiated a phase 1 trial of heptyphemide in China in 2017, but there have been no further updates reported.
Bisthianostat
Bisthianostat is an HDAC inhibitor discovered by Shanghai Institute of Materia Medica Chinese Academy of Sciences and Theorion Pharmaceutical. The first IND application was cleared by China CDE in 2016. After the completion of the phase 1 trial, Shanghai Institute of Materia Medica terminated the phase 1b trial of bisthianostat in combination with Ixazomib and dexamethasone in patients with rrMM.
HG146
HG146, currently under evaluation in MM, lymphomas, and solid tumors, is a selectively Class I/IIb HDAC inhibitor discovered by HitGen. In the press release of IND approval, HitGen stated HG146 showed a better efficacy and safety profile than existing HDAC inhibitors such as Novartis’ panobinostat.
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