CTX-177 / Chordia Therap - LARVOL DELTA

ONO-7018-03: A Study of ONO-7018 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: Ono Pharmaceutical Co., Ltd. | N=24 ➔ 2 | Trial completion date: Dec 2029 ➔ Apr 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2027 ➔ Apr 2026; Sponsor decided to discontinue development of the compound

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MALT1

ONO-7018-01: A Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of ONO-7018 in Patients With R/R NHL or CLL (clinicaltrials.gov) - P1 | N=9 | Terminated | Sponsor: Ono Pharmaceutical Co., Ltd. | N=108 ➔ 9 | Trial completion date: Dec 2027 ➔ Aug 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2027 ➔ Aug 2025; The study was terminated due to a strategic decision to discontinue development.

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Trial termination • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MALT1

Chordia Therapeutics Inc…announces that it has executed a termination agreement with Ono Pharmaceutical Co., Ltd. (“Ono”) regarding the license agreement for CTX‑177 (ONO‑7018), a MALT1 inhibitor originating from Chordia’s pipeline (Chordia Therapeutics Press Release) - "Pursuant to the terms of the license agreement, Ono will transfer to Chordia the clinical and non‑clinical data obtained to date. Discussions regarding the procedures and specific conditions of the data transfer have now been finalized. The transfer will be made without any financial consideration, and Chordia will not incur any financial burden related to the data transfer. In addition, Chordia and Ono have agreed that Chordia will become the sole applicant for the jointly filed patent applications concerning combination therapies involving CTX‑177 and other anticancer agents. Chordia will bear the associated filing and examination costs going forward. The clinical trials conducted by Ono will be terminated under Ono’s responsibility."

Licensing / partnership • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

ONO-7018, a First-in-Class MALT1 Inhibitor, Provides Novel Therapeutic Strategies for B Cell Malignancies: Overcoming BTK Inhibitor Acquired Resistance and Enhancing the Antitumor Effect of BTK Inhibitors (ASH 2023) - P1 | "For example, BTK C481S mutation is well known as a resistant mutation to covalent BTK inhibitors and several mutations of BTK (such as T474I and L528W mutation) have recently been reported in relapsed or refractory CLL patients with acquired resistance to pirtobrutinib, a non-covalent BTK inhibitor...ONO-7018 and tirabrutinib were orally administered to the mice twice a day... ONO-7018 would provide novel therapeutic strategies to overcome the BTK inhibitor acquired resistance and enhance the antitumor effect of BTK inhibitors in clinic. Phase 1 study of ONO-7018 (NCT05515406) is currently ongoing."

Preclinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IRF4 • MALT1 • PLCG2

Notice of Discontinuation of Development of CTX-177 (ONO-7018) (Chordia Therapeutics Press Release) - "Ono will discontinue development of CTX-177 (ONO-7018) for strategic reasons and return the rights to develop, manufacture and commercialize CTX-177 (ONO-7018) to Chordia....Going forward, Chordia will have all rights of CTX-177 (ONO-7018) worldwide. Ono and Chordia will discuss the termination of the license agreement, including the management of ongoing studies, the transfer of data obtained to date, and the control of intellectual property, and Chordia will consider business options for the future. No funds will be exchanged as a result of this matter."

Licensing / partnership • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

ONO-7018-01: A Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of ONO-7018 in Patients With R/R NHL or CLL (clinicaltrials.gov) - P1 | N=108 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MALT1

ONO-7018-03: A Study of ONO-7018 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of ONO-7018 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of ONO-7018 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ONO-7018-01: A Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of ONO-7018 in Patients With R/R NHL or CLL (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | N=54 ➔ 108

Enrollment change • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MALT1

A phase I, first-in-human study of ONO-7018 in patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia. (ASCO 2024) - P1 | "Secondary endpoints include pharmacokinetics, objective response rate, duration of response, progression-free survival, and overall survival. The study began February 13, 2023, and is currently recruiting; part 1 is ongoing."

Clinical • P1 data • Chronic Lymphocytic Leukemia • CNS Tumor • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CARD11 • MALT1

A Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of ONO-7018 in Patients With R/R NHL or CLL (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Ono Pharmaceutical Co. Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MALT1

Preclinical Translational Research Suggests a Clinical Trial Strategy for a Novel MALT1 Inhibitor ONO-7018/CTX-177 Against Malignant Lymphomas (ASH 2022) - "Conclusion The results from these translational research studies support the preparation of a clinical trial by clearly defining patient stratification biomarkers, combination strategies, and PD monitoring. These data underscore the potential therapeutic impact of ONO-7018 as a single-agent or combination partner with other inhibitors like BTK inhibitor and elucidate the sensitivity and response of ONO-7018 for the treatment of malignant lymphomas."

IO biomarker • Preclinical • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CARD11 • CD79A • MALT1

A Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of ONO-7018 in Patients With R/R NHL or CLL (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

New P1 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MALT1

ONO Enters into Exclusive License Agreement with Chordia Therapeuticson CTX-177, a MALT1 Inhibitor, and its Related Compounds (Ono Pharmaceuticals Press Release) - "Ono Pharmaceutical...announced that it entered into a license agreement with Chordia Therapeutics...on CTX-177, Chordia’s MALT1 inhibitor and its related compounds. Under the terms of the agreement, ONO will have exclusive global rights to develop, manufacture and commercialize CTX-177 and its related compounds. ONO will pay to Chordia JPY0.8 billion as an upfront payment and JPY2.5 billion at the time of starting Phase 1 clinical study, as one of development milestones."

Licensing / partnership • Hematological Malignancies • Oncology

[VIRTUAL] Preclinical Evaluation of a Novel MALT1 Inhibitor CTX-177 for Relapse/Refractory Lymphomas (ASH 2020) - "In summary, the novel, selective, small-molecule MALT1 inhibitor CTX-177 demonstrated preclinical efficacy along with target engagement in several lymphoma models with activated antigen receptor signaling and NF-κB pathway. Our results underscore the preclinical therapeutic potential of CTX-177 as a single-agent or in combination with other inhibitors like BTK inhibitor for the treatment of malignant lymphomas."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CARD11 • IRF4