Chordia Therapeutics, Inc. Chordia Presents Preclinical Results of CLK Inhibitor CTX-712 and MALT1 Inhibitor CTX-177 at the 2022 American Society of Hematology (ASH) Annual Meeting

Chordia Therapeutics, Inc.
Chordia to Present Preclinical Results of CLK Inhibitor CTX-712 and MALT1 Inhibitor CTX-177 at the 2022 American Society of Hematology (ASH) Annual Meeting

Chordia Therapeutics Co., Ltd. (hereinafter “our company”, CEO: Hiroshi Miyake, location: Fujisawa City, Kanagawa Prefecture), a research and development bio-venture company specializing in cancer, will be held from December 10 to 13, 2022. At the 64th ASH Annual Meeting of the American Society of Hematology (ASH), the first selective pan-CDC2-like kinase (CLK) inhibitor, CTX-712 Announcement of interim and non-clinical results of phase clinical trials, as well as pre-clinical results of CTX-177 (ONO-7018), a mucosa-associated lympho-tissue lymphoma translocation protein 1 (MALT1) inhibitor I will let you know what I did.
In the cohort of hematological cancers in the phase I clinical trial of CTX-712, 8 patients with acute myeloid leukemia and myelodysplastic syndrome had 4 CRs (complete remission) and 1 CRi (complete remission without neutrophil recovery) was confirmed, and POC (Proof of Concept) in clinical trials was confirmed. A dose-dependent increase in systemic exposure was observed in PK (pharmacokinetics) analysis, and a dose-dependent increase in exon skipping of two RNAs set as PD (pharmacodynamics) markers. Therefore, it was confirmed that CTX-712 caused mRNA splicing changes. Further studies are currently underway to determine the recommended dose for Phase 2 clinical trials. Toshiyuki Yokoyama, M.D., associate professor of hematology at Tohoku University Hospital and lead author of the presentation, said: “I am very honored to be the first in the world to be involved in a phase I clinical trial of an anti-cancer drug with a completely new mechanism of action. We are pleased that more than half of the patients in the targeted clinical trial were in remission.In the future, CTX-712 will be used to treat advanced, relapsed, or refractory acute myeloid leukemia and myelodysplastic syndrome. We hope that it will become an effective therapeutic drug for patients.”
ーASH Abstract No.: 2763
Title: A First-in-Human Phase I Study of CTX-712 in Patients with Advanced, Relapsed or Refractory Malignant Tumors – Hematologic Malignancies Dose Escalation Cohort
In addition, regarding the non-clinical studies on CTX-712 and CTX-177 (ONO-7018), the announcements made by our company and our joint research institutions are as follows.
ーASH Presentation No.: 202
Title: CTX-712, a Novel Splicing Modulator Targeting Myeloid Neoplasms ーASH Abstract No.: 4000
Title: Preclinical Translational Research Suggests a Clinical Trial Strategy for a Novel MALT1 Inhibitor ONO-7018/CTX-177 Against Malignant Lymphomas
[About CTX-712]
CTX-712 is a first-in-class, selective, oral, small-molecule inhibitor of CLK, a key regulator of the RNA splicing reaction that plays an important role in cell proliferation. CTX-712 exhibits
anti-proliferative effects against various human tumor cell lines in vitro and anti-tumor activity against multiple xenograft mouse models in vivo.
[Details of the Phase 1 clinical trial for CTX-712]
The Phase 1 clinical trial in Japan is investigating the tolerability, safety, pharmacokinetics, etc. of CTX-712 in patients with
advanced/recurrent or refractory malignant tumors in solid tumors and hematological cancers. For exam details, please refer to
[About splicing]
RNA immediately after being transcribed is called precursor mRNA. Precursor mRNA has base sequences (introns) that do not encode proteins, and the introns are removed, and through a process called “splicing” that joins the necessary parts (exons) together, it becomes mature mRNA and is translated into proteins.
[About CDC2-like kinase (CLK)]
Kinase is a general term for enzymes that catalyze reactions that transfer phosphate groups contained in biological substances such as ATP to target substances (called substrates). It is believed that there are more than 500 types of protein kinases in humans, one of which, CLK, is composed of four family members, CLK1, CLK2, CLK3, and CLK4, and has a serine/arginine-rich (SR ) phosphorylates proteins. [About exon skipping]
When CTX-712 inhibits the kinase activity of CLK and dephosphorylates the SR protein, a splicing change called exon skipping occurs in which exons fail to be incorporated into the mature mRNA.
[About CTX-177 (ONO-7018)]
CTX-177 (ONO-7018) is a selective inhibitor of mucosa-associated lymphoid tissue lymphoma translocating protein 1 (MALT1), which is known to be involved in intracellular signaling pathways in
lymphocytic blood cells. Activation of MALT1 has been reported to play an important role in lymphocytic malignancies. CTX-177 (ONO-7018) is expected to exert antitumor effects against these malignant tumors by inhibiting MALT1 activity. CTX-177 (ONO-7018) is undergoing Phase 1 clinical trials in the United States by Ono Pharmaceutical Co., Ltd. For more information, visit (NCT05515406). [Important Notice]
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[About Chordia Therapeutics Co., Ltd.]
Chordia Therapeutics Co., Ltd. was established in Shonan Health Innovation Park in Fujisawa City, Kanagawa Prefecture as a bio-venture company specializing in cancer research and development. We aim to create innovative new drugs.
In addition to the lead program CTX-712, we have been conducting research and development of multiple pipelines such as the CDK12 inhibitor CTX-439, which is expected to be effective against cancers with specific abnormalities, and the GCN2 inhibitor. Professionals who have been involved in drug discovery are working every day to develop new drugs that will play a role in the future of cancer treatment, making use of their experience and specialized skills in each field of research and development. On September 8, 2022, we received the “Minister of Education, Culture, Sports, Science and Technology Award” at the “University Startup Awards 2022 ~Award for Academic Startups~” sponsored by the Organization for Small & Medium Enterprises and Regional Innovation, Japan.
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