ONCT-808 / Oncternal Therap, Ho’ola Therapeutics - LARVOL DELTA

Oncternal Therapeutics Announces the Sale of Select Development Programs and the Wind-Down of its Operations (GlobeNewswire) - "Oncternal Therapeutics, Inc. today announced the sale of its zilovertamab and ONCT-808 programs to Ho’ola Therapeutics, Inc. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1), and ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets ROR1 using the binding domain from zilovertamab...Ho’ola will pay Oncternal a $3.0 million upfront payment, with $2.25 million paid immediately and $750,000 upon resolution of certain outstanding contractual obligations with third parties. Oncternal will also be eligible to receive up to $65.0 million in development, regulatory approval and sales milestone payments for the acquired products (including any future products derived from the acquired intellectual property)...The asset sale was completed on June 27, 2025, pursuant to an asset purchase agreement as of the same date."

Commercial • Chronic Lymphocytic Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma

A Phase 1/2 Study of a ROR1-Targeting CAR T Cell Therapy (ONCT-808) in Adult Patients with Relapsed/Refractory (R/R) Aggressive B Cell Lymphomas (BCL) (ASH 2024) - "ONCT-808 utilizes a ROR1-binding moiety derived from zilovertamab, which, in a prior study of zilovertamab vedotin, demonstrated antitumor activity and no evidence of off-tumor toxicity in a population of heavily pretreated patients (pts) with aggressive lymphoma (Wang 2022, Spurgeon 2023)...ONCT-808 is administered as a single infusion following lymphodepletion with fludarabine and cyclophosphamide...Preliminary PK demonstrates successful expansion and persistence of ROR1-positive CAR T cells, including beyond 12 months post-infusion.CONCLUSIONS : ONCT-808 is a novel ROR1-targeting CAR T therapy with promising early activity and appears to be well-tolerated at 0.3 x 106 and 1 x 106 viable cells/kg dose in patients with R/R BCL. Dose escalation continues towards optimizing activity and safety (NCT 05588440)."

CAR T-Cell Therapy • Clinical • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ROR1

Oncternal Therapeutics Announces Termination of its Clinical Studies and Exploration of Strategic Alternatives (GlobeNewswire) - P1 | N=57 | NCT05588440 | Sponsor: Oncternal Therapeutics Inc. | "Oncternal Therapeutics...announced its decision to discontinue its clinical trials evaluating...ONCT-808, its ROR1-targeting autologous CAR T program for the treatment of patients with aggressive B-cell lymphoma, and to explore strategic alternatives...The results with ONCT-808 at an interim Phase 1 analysis showed anti-tumor activity at every dose tested, including a complete metabolic response lasting eight months and long-term persistence of the CAR-T cells, with expected treatment emergent adverse events for a CAR-T therapy, and one death due to complications of shock at the highest dose tested...Company will discontinue all product development activities....'In light of these data and the challenging financing environment, we intend to explore strategic options with the hope of advancing and realizing value from our pipeline including ONCT-534, ONCT-808, zilovertamab and ONCT-216.'"

Discontinued • P1 data • Pipeline update • Trial termination • Castration-Resistant Prostate Cancer • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Mediastinal B Cell Lymphoma • Metastatic Castration-Resistant Prostate Cancer • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

ONCT-808-101: A Clinical Study of ONCT-808 in Subjects with Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=9 | Terminated | Sponsor: Oncternal Therapeutics, Inc | N=57 ➔ 9 | Trial completion date: Dec 2037 ➔ Sep 2024 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Sep 2024; Based on the available clinical data and capital requirements for continued development, the Company has decided to terminate this study.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Oncology • CCND1

Oncternal Therapeutics Provides Business Update and Announces Second Quarter 2024 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: (i) ONCT-534, our dual-action androgen receptor inhibitor: Initial clinical data in the third quarter of 2024; Additional clinical data readouts in the fourth quarter of 2024; (ii) ONCT-808, our autologous ROR1-targeted CAR T cell therapy: Clinical data update in the fourth quarter of 2024."

P1/2 data • Diffuse Large B Cell Lymphoma • Mantle Cell Lymphoma • Metastatic Castration-Resistant Prostate Cancer

A MULTI-CENTER, OPEN-LABEL, PHASE 1/2 STUDY OF ONCT-808, A ROR1-TARGETING CAR-T CELL THERAPY, IN ADULTS WITH RELAPSED/REFRACTORY (R/R) AGGRESSIVE B CELL LYMPHOMAS (BCL) (EHA 2024) - "Zilovertamab vedotin demonstratedpromising antitumor activity in heavily pretreated aggressive lymphoma patients (pts), with no evidence oftoxicities due to off-tumor effects (Wang 2022, Spurgeon 2023)...ONCT-808 is given as a singleinfusion following lymphodepletion with fludarabine and cyclophosphamide... ROR1 CAR T is tolerated at 1 x 106 viable cells/kg with promising efficacy for R/R BCL. Dosing at lower levels isongoing to optimize safety profile and maintain efficacy."

CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ROR1

ONCT-808 autologous CAR T targeting ROR1 for patients with aggressive B cell lymphoma (FOB-USA 2024) - No abstract available

Clinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ROR1

Oncternal Therapeutics Provides Business Update and Announces Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: (i) ONCT-534, our dual-action androgen receptor inhibitor: Initial clinical data update in the second quarter of 2024; Additional clinical data readouts in the fourth quarter of 2024; (ii) ONCT-808, our autologous ROR1-targeted CAR T cell therapy: Clinical data update in mid-2024; Additional clinical data readouts in the fourth quarter of 2024."

P1/2 data • Diffuse Large B Cell Lymphoma • Metastatic Castration-Resistant Prostate Cancer • Richter's Syndrome

Oncternal Therapeutics Updates the Status of its Phase 1/2 Study of ONCT-808, a ROR1-Targeting Autologous CAR T, in Patients with Relapsed or Refractory Aggressive B-cell Lymphoma (GlobeNewswire) - P1/2 | N=57 | NCT05588440 | Sponsor: Oncternal Therapeutics, Inc | "Oncternal Therapeutics, Inc...today updated the status of its dose escalation/dose expansion Phase 1/2 Study ONCT-808-101, evaluating...ONCT-808 for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment...At the initial dose of 1x106 CAR T cells per kg, two of the three patients achieved complete metabolic response (CMR) and the third achieved a partial response (PR) by FDG PET-CT. Common adverse events in this dosing cohort included decreased blood counts, pneumonia and Grade 1-2 cytokine release syndrome (CRS) as of a 4 December 2023 data cutoff....Oncternal has been in communication and is aligned with the Food and Drug Administration (FDA) on our proposed protocol changes that include modified eligibility criteria and testing lower doses of ONCT-808 for future patients in the study."

Cytokine release syndrome • FDA event • P1/2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Trial-in-Progress: A Phase 1/2 Multi-Center Study of Onct-808, a ROR1-Specific CAR T, in Adult Patients with Relapsed/Refractory Aggressive B Cell Lymphoma (ASH 2023) - P1/2 | "Zilovertamab vedotin showed preliminary evidence of efficacy and no evidence of on-target off-tumor toxicity in patients with advanced B cell malignancies (Wang 2022)...Subjects will receive a conditioning regimen of intravenous (IV) cyclophosphamide and fludarabine, followed by ONCT-808 IV infusion...The trial is currently active and patients have been treated in the phase 1 dose escalation. Clinical Trial Identifier: NCT05588440"

Clinical • IO biomarker • P1/2 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ROR1

Oncternal Therapeutics Provides Business Update and Announces Third Quarter 2023 Financial Results (GlobeNewswire) - "ONCT-808, our autologous ROR1-targeted CAR T cell therapy: Initial clinical data available by the end of 2023; Additional clinical data readouts in 2024....ONCT-534, our dual-action androgen receptor inhibitor: Initial clinical data available in the first half of 2024."

P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Development of a high yield, fully automated ONCT-808 autologous ROR1 CAR T cell clinical manufacturing process (SITC 2023) - "ONCT-808 cells are genetically modified via ex vivo transduction with lentivirus vector to express a CAR construct containing a ROR1-directed single chain variable fragment (scFv) derived from Oncternal’s clinical stage anti-ROR1 mAb zilovertamab. Combination of the automated closed process with optimization of release testing methodologies resulted in a vein-vein time for patient administration of 15–17 days. Conclusions A closed, high yield, robust and high-performance CAR T manufacturing process was developed and verified."

CAR T-Cell Therapy • Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CD4 • CD8 • ROR1

ONCT-808 ROR1 CAR T cells induce significant cancer cell death in mantle cell lymphoma cell line-derived CDX models and in vitro killing assays (SITC 2023) - "Oncternal’s ONCT-808 autologous CAR T cells are genetically modified via ex vivo transduction with a self-inactivating lentivirus vector to express a ROR1-directed CAR containing single chain variable fragment derived from Oncternal’s clinical stage anti-ROR1 zilovertamab. In cancer therapy efficacy studies using CDX models, treatment with ONCT-808 cells resulted in complete tumor remission in ROR1 Jeko-1 cell-derived CDX mice, and controlled tumor growth in Raji cell-derived CDX mice, reflecting the specificity of the ONCT-808 cells to the ROR1 target. Conclusions ONCT-808 demonstrated high efficacy in inducing ROR1 specific cancer cell death in both in vivo and in vitro studies, suggesting its potential in treating human cancer patients."

CAR T-Cell Therapy • IO biomarker • Preclinical • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Solid Tumor • IFNG • ROR1 • TNFA

Oncternal Therapeutics Provides Business Update and Announces Second Quarter 2023 Financial Results (Oncternal Therapeutics Press Release) - "Oncternal Therapeutics, Inc...today provided a business update and reported second quarter 2023 financial results...Expected Upcoming Milestones: ONCT-808...Initial clinical data available by the end of 2023; Additional clinical readouts in 2024...ONCT-534...Initial clinical data available in the first half of 2024."

P1/2 data • Genito-urinary Cancer • Hematological Malignancies • Oncology • Prostate Cancer • Solid Tumor

A Clinical Study of ONCT-808 in Subjects With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=57 | Recruiting | Sponsor: Oncternal Therapeutics, Inc | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2023 ➔ May 2023

Enrollment open • Trial initiation date • Hematological Malignancies • Oncology • CCND1 • ROR1

Oncternal Therapeutics Announces First Patient Dosed in Phase 1/2 Study of ROR1 targeting autologous CAR T, ONCT-808, in patients with relapsed or refractory aggressive B-cell lymphoma (GlobeNewswire) - "Oncternal Therapeutics...announced that the first patient has been dosed in the Phase 1/2 dose escalation/dose expansion study of ONCT-808, the company’s ROR1 targeting autologous CAR T cell therapy....The company expects to present initial clinical data in late 2023, with additional clinical data readouts in 2024."

P1/2 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Oncternal Therapeutics Provides Business Update and Announces First Quarter 2023 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: ONCT-808, our autologous ROR1-targeted CAR T cell therapy. Initial clinical data available by the end of 2023. Additional clinical readouts in 2024; ONCT-534, our dual-action androgen receptor inhibitor. U.S. IND application submission in mid-2023. Phase 1/2 clinical study initiation in the second half of 2023. Initial clinical data available in the first half of 2024."

IND • New P1/2 trial • P1/2 data • Oncology

Oncternal Therapeutics Announces Strategic Reprioritization, Stops Two Zilovertamab Studies (Yahoo Finance) - "Oncternal Therapeutics Inc...will suspend Phase 3 and the Phase 1/2 studies of zilovertamab in combination with ibrutinib, citing the rapidly changing commercial landscape for Bruton's tyrosine kinase inhibitors (BTK inhibitors)....ONCT-808: ROR1 targeting autologous CAR T cell therapy is being tested in a recently initiated Phase 1/2 clinical trial for relapsed or refractory aggressive B-cell lymphoma."

P1/2 data • Trial suspension • Hematological Malignancies • Lymphoma • Oncology

Oncternal Therapeutics Provides Business Update and Announces Fourth Quarter and Full Year 2022 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: (i) Zilovertamab, our ROR1 antibody: Opening of additional countries for global clinical registrational Phase 3 Study ZILO-301; Continuing evaluation of potential to treat patients with CLL & MCL and TP53 mutations and/or 17p deletions; (ii) ONCT-808, our autologous ROR1-targeted CAR T cell therapy: Initial clinical data available by the end of 2023; (iii) ONCT-534, our dual-action androgen receptor inhibitor: U.S. IND application submission planned in mid-2023."

IND • P1/2 data • Trial status • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Oncternal Therapeutics Provides Business Update and Announces Third Quarter 2022 Financial Results (GlobeNewswire) - "ONCT-808, lead candidate in our autologous ROR1-targeted CAR T cell therapy program Initiation of Phase 1/2 Study in patients with aggressive B-cell lymphoma in the first quarter of 2023. Initial clinical data update in 2023....ONCT-534, lead candidate in our DAARI program: U.S. FDA pre-IND feedback in December 2022."

Enrollment status • FDA event • P1/2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Clinical Study of ONCT-808 in Subjects With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=57 | Not yet recruiting | Sponsor: Oncternal Therapeutics, Inc

New P1/2 trial • Hematological Malignancies • Oncology • CCND1 • CD19 • ROR1

Oncternal Therapeutics Receives IND Clearance for ONCT-808, its autologous CAR T Product Candidate Targeting ROR1 for the Treatment of Aggressive B Cell Lymphoma (GlobeNewswire) - "Oncternal Therapeutics, Inc...announced the receipt of a ‘Study May Proceed’ letter from the U.S. Food and Drug Administration (FDA), 30 days after submitting its Investigational New Drug (IND) application for a Phase 1/2 dose escalation study of ONCT-808, an autologous chimeric antigen receptor (CAR) T therapy targeting ROR1, in patients with aggressive B cell non-Hodgkin’s lymphoma (B NHL), including those who have failed previous CD19 CAR T treatment....'We expect to initiate the study in the coming months and to present interim results at a scientific conference in 2023'."

IND • P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Oncternal Therapeutics Provides Business Update and Announces Second Quarter 2022 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: (i) ONCT-808, lead candidate in our autologous ROR1-targeted CAR-T cell therapy program: Investigational New Drug (IND) application submission in August 2022; (ii) ONCT-534, lead candidate in our DAARI program: FDA pre-IND interactions in the fourth quarter of 2022."

FDA event • IND • Oncology • ROR1

Oncternal Therapeutics Presents New Preclinical Data from its anti-ROR1 Cell Therapy Collaboration with the Karolinska Institutet at the EHA2022 Congress (GlobeNewswire) - "Oncternal Therapeutics...announced that preclinical data from its ROR1-targeting cell therapy programs will be highlighted in a poster presentation at the European Hematology Association (EHA) 2022 Hybrid Congress....The ROR1 CAR mediated target recognition and cell activation when expressed in either T cells or NK cells. Also, ROR1 CAR-T cells demonstrated dose-dependent anti-tumor activity in a mantle cell lymphoma mouse model....'we are looking forward to dosing the first patient with our autologous ROR1 CAR-T cell therapy, ONCT-808, in the coming months'. ONCT-808...program is advancing towards an Investigational New Drug (IND) application submission expected in mid-2022."

IND • Preclinical • Trial status • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Oncternal Therapeutics Deprioritizes Development of ONCT-216 to Focus Resources on Phase 3 Trial for Zilovertamab in the Treatment of Mantle Cell Lymphoma (GlobeNewswire) - "The Company’s lead autologous ROR1-targeted CAR-T cell therapy program candidate, ONCT-808, is advancing according to plan towards an Investigational New Drug (IND) application submission expected in mid-2022....Oncternal is...developing ONCT-808, a chimeric antigen receptor T cell (CAR-T) therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors."

IND • Hematological Malignancies • Oncology • Solid Tumor