rogocekib (CTX-712) / Chordia Therap - LARVOL DELTA

Phase I Study of Rogocekib in Patients with Relapsed or Refractory Hematologic Malignancies. (PubMed, Blood Adv) - P=N/A, P1/2 | "This study was registered on the Japan Registry of Clinical Trials under jRCT2080224127. Currently, a Phase I/II Study of rogocekib in relapsed/refractory AML and higher risk MDS is ongoing in the United States (NCT05732103)."

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • CDK1

Chordia’s Lead Cancer Drug Rogocekib Wins Japan Orphan Drug Endorsement for AML (TipRanks) - "Chordia Therapeutic...is advancing a portfolio of targeted small-molecule therapies, led by rogocekib, a first-in-class CLK inhibitor in Phase 1/2 trials in the U.S."

Japanese regulatory • Orphan drug • Acute Myelogenous Leukemia

CLK INHIBITOR CTX-712 POTENTIATES THE ACTIVITY OF ABT-199 AND AZACYTIDINE IN MYELOID LEUKEMIA (EHA 2026) - "ABT-199 and azacytidine treatment alone had no significant effect on RNA splicing. Summary/Conclusion Taken together, our results suggested that the CLK inhibitor alone or in combination with ABT-199 and/or azacytidine could be a novel therapeutic approach for the treatment of MDS and AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ASXL1 • BAK1 • BAX • BCL2A1 • CD34 • CDK1 • CLK2 • CREBBP • IKZF1 • KRAS • SF3B1 • SRSF2 • SRSF4 • STAG2 • TET2 • U2AF1 • ZRSR2

SAFETY, TOLERABILITY, AND PRELIMINARY ACTIVITY OF ROGOCEKIB IN PATIENTS WITH RELAPSED/REFRACTORY MYELOID MALIGNANCIES: RESULTS FROM A PHASE 1/2 STUDY (CTX-712-CL-02) (EHA 2026) - P1/2 | "Summary/Conclusion Rogocekib demonstrated a manageable and tolerable safety profile and preliminary antileukemic activity in a heavily pretreated, high-risk population, with encouraging signals in AML (3 CRi, 16.7%). These findings support continued dose optimization and further clinical development in R/R AML and HR-MDS."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hypotension • Leukemia • Leukopenia • Myelodysplastic Syndrome • Neutropenia • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • ASXL1 • CDK1 • RUNX1 • SF3B1 • SRSF2 • TP53 • U2AF1 • ZRSR2

Phase I Study of Rogocekib in Patients with Advanced, Relapsed, or Refractory Malignant Solid Tumors. (PubMed, Clin Cancer Res) - "Although most toxicities were manageable, two treatment related deaths were observed, underscoring the need for vigilant safety monitoring. Overall, rogocekib demonstrated evidence of target engagement in most patients with solid tumors and preliminary antitumor activity, warranting further clinical investigation."

Journal • P1 data • Oncology • Ovarian Cancer • Solid Tumor • CDK1

A first-in-human phase I study of CTX-712 in patients with advanced, relapsed or refractory malignant tumors (CTX-712-CL-01 study): Efficacy and safety in a hematologic malignancies cohort (AACR 2024) - P=N/A | "CTX-712 demonstrated a manageable and tolerable safety profile and showed anti-tumor efficacy in patients with hematologic malignancies. Currently, a Phase I/II Study of CTX-712 in relapsed/refractory AML and higher risk MDS is ongoing using a new tablet formulation in the United States.Clinical trial information: jRCT2080224127"

Clinical • First-in-human • Metastases • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • CDK1 • SF3B1 • SRSF2 • U2AF1 • ZRSR2

A first-in-human phase I study of CTX-712 in patients with advanced, relapsed or refractory malignant tumors (CTX-712-CL-01 study): Efficacy and safety in solid tumor cohorts (AACR 2024) - P=N/A | "CTX-712 demonstrated an acceptable safety profile in patients with solid tumors. Additionally, CTX-712 demonstrated favorable clinical efficacy for patients with ovarian cancer and further investigation is warranted.Clinical trial information: jRCT2080224127"

Clinical • First-in-human • Metastases • P1 data • Oncology • Ovarian Cancer • Solid Tumor • CDK1

Biomarkers for CLK inhibitor CTX-712 treatment response in myeloid neoplasms: Paving the way toward clinical trials (AACR 2024) - "In conclusion, our results demonstrated a significant effect of CTX-712 on MDS/AML-derived models regardless of their splicing factor-mutation status. Additionally, we present novel biomarkers that could predict sensitivity to CTX-712."

Biomarker • Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • SRSF2

Chordia Therapeutics Inc…announced that it has confirmed that the first patient has been dosed in the Initial Expansion Cohort of the ongoing Phase 1/2 clinical trial of rogocekib in the United States (hereinafter, the “Study”). (Chordia Therapeutics Press Release) - "Following the recommendation of the Study’s Safety Review Committee, the Company decided to initiate the Initial Expansion Cohort and promptly notified all participating clinical sites of this decision."

Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

More than CLK bait? Rogocekib for MDS and AML. (PubMed, Blood Adv) - No abstract available

Journal • Acute Myelogenous Leukemia

Synergistic apoptotic effect by the combination of clk inhibitor CTX-712 and BCL-2 inhibitor ABT-199 with or without azacytidine in AML and MDS (ASH 2025) - "96% of apoptosis was observed for the combination of all thethree drugs. Taken together, our results suggested that the CLK inhibitor is a noval therapeutic approach for thetreatment of MDS and AML; the combination of CTX-712 with ABT-199 and /or azacytidine could havesignificant antileukemia activity."

IO biomarker • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ASXL1 • CD34 • CDK1 • CREBBP • GLI2 • IKZF1 • KRAS • SF3B1 • SRSF2 • SRSF4 • STAG2 • TET2 • U2AF1

Srsf2P95H and Nf1 deficiency synergistically activate JAK-STAT signaling and exacerbate age-related clonal hematopoiesis in mice (ASH 2025) - "We hypothesized that under RAS hyperactivation,Srsf2P95H amplifies JAK-STAT signaling via mis-splicing of its key components.To validate this, we treated BMT mice with DMSO, ruxolitinib (RUX) or CTX-712 (CTX). Our findings elucidate the synergistic effects of Srsf2P95H and Nf1 loss in CH progression,uncovering an unanticipated JAK-STAT-dependent mechanism mediated by Srsf2P95H. Furthermore, wehighlight a conserved, age-related pathophysiological trajectory of CH between humans and mice,providing a preclinical model to dissect molecular interactions in age-related CH and to supporttherapeutic development in hematologic malignancies."

Preclinical • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • T Acute Lymphoblastic Leukemia • ASXL1 • CCND1 • CCND2 • CDK1 • IDH1 • IDH2 • IL6R • JAK2 • NF1 • RUNX1 • SRSF2 • STAT5 • TET2

Phase 1/2 Multicenter, Open-Label Study of CTX-712 in Patients with Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes (ASH 2023) - P1/2 | "Use of azole antifungals that are not strong CYP3A4 inhibitors (e.g., isavuconazole) is permitted. The phase 2 part of the study will commence after the RP2D has been identified and confirmed and aims at evaluating therapeutic activity in R/R AML (Cohort 2a) or R/R HR-MDS (Cohort 2b), in addition to confirmation of the safety profile. Clinical trial registry number: NCT05732103"

Clinical • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • CDK1

CDC2-like Kinases (CLKs) Inhibition As a Novel Targeted Therapeutic Strategy in Myelodysplastic Syndromes (MDS) (ASH 2024) - "CTX-712 is a potent pan-CLK inhibitor, it is highly selective against CLK1-4 through inhibits phosphorylation of SRSFs...Apoptosis induction effect was observed in all three patients. We further did the same test in 2 healthy donor controls, the IC-50s were 89.5±13.6 nM and 37.25±6.7 nM separately.Our study suggests that CLKs may have roles in MDS pathogenesis, the inhibition of CLKs have therapeutic potential, more specific CLKs inhibitor development is needed."

Acute Myelogenous Leukemia • Aplastic Anemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • CD34 • CDK1 • CLK1 • CREBBP • GLI2 • IKZF1 • KRAS • SF3B1 • SRSF2 • SRSF4 • STAG2 • TET2 • U2AF1

Discovery of Rogocekib (CTX-712): A Potent and Selective CLK Inhibitor for Cancer Treatment. (PubMed, ACS Med Chem Lett) - "Treatment with CTX-712 reduced the phosphorylation of serine- and arginine-rich proteins in a dose-dependent manner, leading to potent in vitro cell growth suppression and in vivo antitumor activity in lung cancer NCI-H1048 xenograft model. These findings highlight the promise of CTX-712 as a novel CLK inhibitor and its potential as a therapeutic for cancers, particularly those characterized by RNA splicing alterations."

Journal • Lung Cancer • Oncology • Solid Tumor • CDK1

Publication of Research on the Discovery of CLK Inhibitor Rogocekib (Chordia Therapeutics Press Release) - "Based on this new scaffold, we proceeded with structure optimization and discovered rogocekib, which exhibits strong CLK kinase inhibitory activity. Rogocekib showed IC₅₀ values of 0.69, 0.46, 3.4, and 8.1 nM against CLK1, CLK2, CLK3, and CLK4, respectively. Kinome profiling against 468 kinases confirmed that rogocekib exhibits high selectivity for CLK kinases with minimal effects on other kinases."

Clinical • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Notice regarding the Publication of the Revised Clinical Trial Protocol Summary for rogocekib (Chordia Therapeutics Press Release) - "As a result of these revisions, the total number of patients to be enrolled in the study has increased from the originally planned 170 to 225. Two new clinical trial sites have been added, bringing the total to six....Although the interim data presentation at a international conference has been rescheduled from the second half of 2025 to mid-2026, patient enrollment is progressing steadily....Chordia plans to initiate the expansion cohort in early 2026 and is actively expanding trial sites to accelerate enrollment."

Clinical protocol • P1/2 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

CTX-712-CL-02: A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P1/2 | N=225 | Recruiting | Sponsor: Chordia Therapeutics, Inc. | N=170 ➔ 225 | Trial completion date: Apr 2028 ➔ Feb 2029 | Trial primary completion date: Apr 2026 ➔ Jun 2028

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

THERAPEUTIC STRATEGIES TARGETING SRSF2 AND KIT MUTATIONS IN SYSTEMIC MASTOCYTOSIS (EHA 2025) - "The efficacy of KIT TKIs midostaurin and avapritinib, and the synergistic effects of spliceosome inhibitors MS023, RKI-1447, and CTX-712 were also evaluated. Our findings suggest that combining KIT TKIs with spliceosome inhibitors represents a promising therapeutic approach for SM. The study highlights the role of SRSF2 and KIT mutations in driving MC malignancy and emphasizes the potential of targeting the spliceosome machinery to overcome drug resistance, potentially improving treatment outcomes for advanced SM."

Oncology • KIT • SRSF2 • STAT5

Biomarkers for CLK inhibitor CTX-712 treatment response in myeloid neoplasms: Paving the way toward clinical trials (JSMO 2025) - No abstract available

Biomarker • Clinical • Hematological Malignancies • Oncology

Rogocekib for the treatment of Refractory or Relapsed Acute Myeloid Leukemia (AML) has been granted Orphan Drug Designation (ODD) in the US by the Food and Drug Administration (FDA) (Chordia Therapeutics Press Release) - "Chordia Therapeutics K.K...announced that Chordia received Orphan Drug Designation (ODD) in the US by the Food and Drug for rogocekib, which is developing for Refractory or Relapsed Acute Myeloid Leukemia (AML)."

Orphan drug

Announcement of International Nonproprietary Name (INN) for CTX-712 (Chordia Therapeutics Press Release) - "Chordia Therapeutics K.K...announced that the World Health Organization (WHO) has released the following International Nonproprietary Name (INN) for our CLK inhibitor CTX-712 as a recommended INN (rINN)."

Commercial • Oncology

Chordia to Present Results of Phase 1 Clinical Trial of CLK Inhibitor CTX-712 at the 2024 The 86th Annual Meeting of the Japanese Society of Hematology (Chordia Therapeutics Press Release) - P1/2 | N=170 | NCT05732103 | Sponsor: Chordia Therapeutics, Inc. | "Chordia Therapeutics Inc...announce that it presented the results of an analysis of 14 patients with hematologic malignancies from a Japanese Phase 1 clinical trial of its CLK inhibitor, CTX-712, at the 86th Annual Meeting of the Japanese Society of Hematology being held at the Kyoto International Conference Center from October 11 to 13, 2024....Among 14 patients, four patients achieved complete remission (CR), one patient achieved complete remission with incomplete hematologic recovery (CRi), and one patient achieved morphologic leukemia-free state (MLFS). The overall response rate was 42.9% (6/14). The median duration of treatment for responders ranged from 14 to 924 days, with a median duration of 164 days."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P1/2 | N=170 | Recruiting | Sponsor: Chordia Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2028 ➔ Apr 2028 | Trial primary completion date: Dec 2026 ➔ Apr 2026

Enrollment open • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

CTX-712, A NOVEL SPLICING INHIBITOR TARGETING MYELOID NEOPLASMS (MDS 2023) - "Importantly, the effect of CTX-712 positively correlated with the degree of altered splicing in cassette exon events induced by the drug in AML cell lines, primary AML cells and PDX models, suggesting that the anti-leukemic effects of CTX-712 are mediated by inhibition of RNA splicing. Conclusions CTX-712 is a potent and specific inhibitor of CLK kinases showing a broad activity to a wide variety of MDS and AML, highlighting a rationale for further investigation of CTX-712 in MDS/AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • SRSF2