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

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

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

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 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) - "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 • 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) - "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 • 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

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

A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P1/2 | N=170 | Not yet recruiting | Sponsor: Chordia Therapeutics, Inc.

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A First-in-Human Phase I Study of CTX-712 in Patients with Advanced, Relapsed or Refractory Malignant Tumors - Hematologic Malignancies Dose Escalation Cohort (ASH 2022) - "Assessment of CTX-712 safety profile for hematologic malignancies is ongoing. CTX-712 showed preliminary anti-tumor efficacy for both AML and MDS."

Clinical • P1 data • Acute Myelogenous Leukemia • CNS Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Insomnia • Leukemia • Myelodysplastic Syndrome • Oncology • Pneumonia • Respiratory Diseases • Sleep Disorder • Solid Tumor • CDK1 • SF3B1 • SRSF2 • U2AF1 • ZRSR2

CTX-712, a Novel Splicing Modulator Targeting Myeloid Neoplasms (ASH 2022) - "Overall, 12 out of 13 PDX MDS/AML models showed anti-tumor effect of CTX-712 with a trend of better effects for larger splicing changes. In conclusion, our results demonstrated a potent effect of CTX-712 on both RNA splicing and tumor regression for MDS/AML-derived cells, providing mechanistic insight into CLK inhibition and its effect on RNA splicing and anti-leukemic effects and also a rationale for further investigation of CTX-712 in MDS/AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • SF3B1 • SRSF2 • U2AF1 • ZRSR2

A first-in-human phase I study of CTX-712 in patients with advanced, relapsed or refractory malignant tumors. (ASCO 2022) - "CTX-712 demonstrated an acceptable safety profile with early signs of clinical antitumor activity, establishing the initial proof of concept of the CLK inhibitor. Observed DLTs included dehydration, platelet count decreased, and hypokalemia. Investigation is ongoing to determine RD."

Clinical • P1 data • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • CDK1

Chordia Therapeutics Announces Interim Results of the Phase 1 Clinical Trial of CLK Inhibitor CTX-712 at the 2022 ASCO Annual Meeting (PRNewswire) - P1 | N=79 | "A Phase 1 clinical trial of CTX-712 in solid tumors and hematological malignancies demonstrated a clinically acceptable safety profile. As for antitumor efficacy, it was observed in multiple subjects, establishing an initial Proof of Concept (POC). Dose limiting toxicities (DLTs) observed included dehydration, decreased platelet count, and hypokalemia, and the maximum tolerated dose (MTD) for twice-weekly dosing was determined to be 140 mg. Additionally, two partial responses (PRs) and two complete responses (CRs) were observed in patients with ovarian cancer and acute myeloid leukemia, respectively. A dose-dependent increase in systemic exposure was observed in pharmacokinetics (PK) analysis, and a dose-dependent increase in exon skipping of RNAs set as pharmacodynamics (PD) markers confirmed mRNA splicing modification by CTX-712. Further studies are currently underway to determine the recommended Phase 2 dosing."

P1 data • Hematological Malignancies • Oncology • Solid Tumor

CTX-712, a novel splicing modulator targeting myeloid neoplasms (AACR 2022) - "Median survival time (days) was 34.5 (vehicle) and 93.5 (high dose) (N=2).Overall, 12 out of 13 PDX MDS/AML models showed anti-tumor effect of CTX-712 with a trend of better effects for larger splicing changes. These results provide mechanistic insights of CLK inhibition and a rationale for further investigation of CTX-712 in MDS/AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • SF3B1 • SRSF2 • U2AF1 • ZRSR2