CTX-439 / Chordia Therap - LARVOL DELTA

A novel CDK12 inhibitor induces homologous recombination deficiency to enhance PARP inhibitor efficacy in uterine serous carcinoma. (PubMed, Mol Cancer Ther) - "This study investigated cyclin-dependent kinase 12 (CDK12), a transcriptional regulator of HR genes, and evaluated the efficacy of a novel CDK12 inhibitor, CTX-439, combined with a PARP inhibitor, olaparib, in patient-derived xenograft (PDX) models of USC. Furthermore, CDK12 inhibition enhanced tumor sensitivity to the PARP inhibitor, olaparib in USC PDX models. This study indicates that CDK12 is a potential therapeutic target for enhancing the antitumor effects of PARP inhibitors in patients with USC."

Journal • Endometrial Cancer • Endometrial Serous Adenocarcinoma • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • Uterine Cancer • BRCA1 • BRCA2 • HRD • TP53

Novel CDK12/13 inhibitor CTX-439 downregulates MCL1 via transcriptional mRNA read-through and synergistically acts with BCL-XL inhibitors for cancer therapy (AACR 2025) - "Moreover, dual inhibition of CTX-439 and AZD4320, which targets BCL-XL, synergistically induced rapid apoptosis in vitro and significantly suppressed tumor growth in vivo. Interestingly, our study revealed a novel CDK12/13 inhibition mechanism targeting short mRNAs, such as MCL1, that can be used to establish new therapeutic combination strategies with BCL-XL inhibitors. Additionally, our study provides a new avenue to improve cancer therapy outcomes."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1 • BRCA1 • BRCA2 • CDK12 • MCL1

Chordia presents new data at the American Association for Cancer Research Annual Meeting 2025 (Chordia Therapeutics Press Release) - "Chordia Therapeutics Inc...announces that Chordia presents new data of CDK12 inhibitor CTX-439 and GCN2 inhibitor at the American Association for Cancer Research (AACR) Annual Meeting, April 25-30, 2025, in Chicago, Illinois....CTX-439 suppresses the production of MCL1, a protein critical for cancer cell survival, and exhibits marked antitumor activity when combined with a BCL2/BCL-xL inhibitor....CRD-799, in combination with existing proteasome inhibitors, demonstrated clear anti-tumor efficacy. In this combination therapy, CRD-799 controls the stress response pathway in cancer cells and induces cell death, which is the mechanism underlying its antitumor effects."

Preclinical • Multiple Myeloma

Presentation of data from our pipeline at the American Association for Cancer Research Annual Meeting 2025 (Chordia Therapeutics Press Release) - "Chordia Therapeutics Inc...announces that Chordia will present new data at the American Association for Cancer Research (AACR) Annual Meeting, April 25-30, 2025, in Chicago, Illinois. Two presentations will be given on Chordia's pipeline of CDK12 inhibitor CTX-439, and a GCN2 inhibitor."

Preclinical • Multiple Myeloma

Translational research of CDK12/13 inhibitor, CTX-439, informing clinical trial strategy (AACR 2024) - "Collectively, the results from these translational research studies provide a foundation for developing a clinical trial by clearly defining PD monitoring, patient stratification biomarkers, and combination strategies. These findings highlight the therapeutic potential of CTX-439 as a single-agent and in combination with inhibitors, such as PARP, for the treatment of cancers characterized by transcriptional addiction."

Clinical • Oncology • BRCA1 • BRCA2 • CDK12