OPN-6602 / Opna Bio - LARVOL DELTA

Opna Bio Announces Fast Track Designation Granted to OPN-6602 for the Treatment of Multiple Myeloma (Businesswire) - "OPN-6602 is an oral, small molecule inhibitor of EP300 and CREB-binding protein (CBP) currently in a Phase 1 clinical trial evaluating safety, tolerability, pharmacokinetics and preliminary clinical activity in patients with relapsed and/or refractory MM."

Fast track • Trial status • Multiple Myeloma

OPN-6602, a potent dual EP300/CBP bromodomain inhibitor, targets multiple myeloma through concomitant suppression of IRF4 and c-MYC (AACR 2024) - "The effects of OPN-6602 with dexamethasone (dex) or lenalidomide (len) on the growth of OPM-2 and MM1.S cells were evaluated in a matrix combination study. The pharmacokinetic profile is favorable for oral QD dose administration due to a high Cmax (19 µg/mL at 24 mg/kg) and short half-life (T1/2 = 1.5 hr). A first-in-human study of OPN-6602 in patients with MM is planned for 2024."

First-in-human • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Solid Tumor • BRD4 • CREBBP • EP300 • IRF4 • MYC

Novel multifunctional degraders of EP300/CBP and IKZF1/3 with potent anti-myeloma activity (ASH 2025) - P1 | "OPN-6602 is a potent oral small molecule inhibitor of the BRDs of EP300and CBP that is currently in a Phase 1 clinical study to evaluate efficacy and safety in patients withrelapsed/refractory MM (NCT06433947).Preclinical MM studies that combine IMiDs with OPN-6602 demonstrate synergy with high xenografttumor response, including complete regressions and improved response durability (Matusow 2024). This set ofdata suggested that each molecule of OPN-5877 resulted in the degradation of many molecules of thetarget proteins.Further chemical optimization towards a development candidate is ongoing. This polypharmacologyapproach has potential to yield a novel therapeutic with multifunctional activity that targets severaloncogenic pathways concurrently in the same cancer cell, thus enabling effective single agent anti-canceractivity."

IO biomarker • Hematological Malignancies • Lymphoma • Multiple Myeloma • Targeted Protein Degradation • BCL2 • CRBN • CREBBP • EP300 • IKZF1 • IKZF3 • IRF4

OPN-6602, an Orally Bioavailable EP300/CBP Bromodomain Inhibitor, Targets Multiple Myeloma through Suppression of IRF4 and MYC (ASH 2024) - P1 | "The efficacy of OPN-6602 in combination with dexamethasone (dex) and/or with pomalidomide (pom) or mezigdomide (mezi) was evaluated in the OPM-2 xenograft model. Similar findings were observed in a dog GLP toxicology study. OPN-6602 is currently being evaluated in patients with MM in the Phase I clinical trial OPN6602-C01 (NCT06433947)."

Hematological Malignancies • Multiple Myeloma • Oncology • EP300 • IRF4 • MYC

A Phase 1b, Dose Escalation/Dose Expansion, Multicenter, Open-Label Study to Assess the Safety and Tolerability of OPN-6602 Monotherapy and in Combination with Dexamethasone in Subjects with Relapsed and/or Refractory Multiple Myeloma (ASH 2024) - P1 | "Dose limiting toxicities, treatment-emergent adverse events and changes in safety and lab parameters will be characterized in order to identify the RP2D. The primary objective and endpoint for dose expansion of OPN-6602 monotherapy or in combination with dexamethasone is to evaluate the preliminary antitumor activity using overall response rate based on the 2011 International Myeloma Working Group (IMWG) response criteria.Eligibility criteria include a confirmed diagnosis of MM per IMWG criteria, disease that is relapsed or refractory to 3 or more different prior lines of therapy that include immunomodulatory agents, proteasome inhibitors and an anti-CD38 antibody, measurable disease and adequate hematologic, renal and liver function.This multi-center study (NCT06433947) is currently open in the United States with additional sites planned to open in Switzerland, United Kingdom and the European Union."

Clinical • Combination therapy • Monotherapy • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • BRD3 • EP300 • IRF4

CBP/EP300 inhibitorOPN-6602inmarginal zone lymphomas: preclinical activity as a single agent and in combination with BTK inhibition (AACR-NCI-EORTC 2025) - P1 | "We then moved to three models of resistance to BTK inhibitors obtained after long exposure to the BTK inhibitor ibrutinib (VL51-IBR), the PI3K-delta inhibitor idelalisib (Karpas1718-IDE), and the BCL2 inhibitor venetoclax (SSK41-VEN). The CBP/EP300 inhibitor OPN-6602 has single-agent activity in MZL models, and it improves the anti-tumor activity of BTK pharmacological blockade. Our data support the clinical exploration of the compound also for MZL patients beyond the MM setting."

Combination therapy • IO biomarker • Preclinical • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Oncology • CREBBP • EP300

TRIAL IN PROGRESS: PHASE 1B, DOSE ESCALATION/DOSE EXPANSION STUDY OF OPN-6602 MONOTHERAPY AND IN COMBINATION WITH DEXAMETHASONE IN SUBJECTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (EHA 2025) - P1 | "The primary objective and endpoint for dose expansion of OPN-6602 monotherapy or in combination with dex is to evaluate the preliminary antitumor activity using overall response rate based on the 2011 International Myeloma Working Group (IMWG) response criteria.Eligibility criteria include a confirmed diagnosis of MM per IMWG criteria, disease that is relapsed or refractory to 3 or more different prior lines of therapy that include immunomodulatory agents, proteasome inhibitors and an anti-CD38 antibody, measurable disease, and adequate hematologic, renal and liver function.This multi-center study (NCT06433947) is currently open in the United States with additional sites planned to open in the United Kingdom and the European Union. Further development of OPN-6602 in combination with other standard-of-care agents in multiple myeloma is also planned."

Clinical • Combination therapy • Monotherapy • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • EP300 • IRF4

Opna Bio Receives Orphan Drug Designation for OPN-6602, an Oral EP300/CBP Bromodomain Inhibitor, for Multiple Myeloma (Businesswire) - "Opna Bio...announced today that the FDA has granted orphan drug designation (ODD) to one of its lead programs, OPN-6602, for the treatment of multiple myeloma (MM)....The Phase 1 study in patients with relapsed or refractory multiple myeloma (NCT06433947) is taking place at multiple sites in the U.S. Opna Bio expects to complete the single agent, dose-escalation phase of the trial in 2026."

Orphan drug • Trial status • Multiple Myeloma

OPN-6602 Combinations Demonstrate Complete Tumor Regression in Preclinical Multiple Myeloma Models (Businesswire) - "In MM mouse xenograft models, OPN-6602 showed 71% tumor suppression as a single agent, and 100% tumor regression when combined with dexamethasone, pomalidomide or mezigdomide with a sustained duration of response. RNA sequencing of treated tumors showed that OPN-6602 downregulated key MM driver and signature genes, and has the potential to overcome resistance mechanisms to standard-of-care regimens."

Preclinical • Multiple Myeloma

Opna Bio Announces 2024 ASH Presentations Highlighting Interim Data from Phase 1 Combo Study of BET Inhibitor OPN-2853 with Ruxolitinib in Myelofibrosis, and Promising Preclinical Data with EP300/CBP Bromodomain Inhibitor OPN-6602 in Multiple Myeloma (Businesswire) - "The data presentations will include an interim analysis of the ongoing Phase 1 study of OPN-2853, a bromodomain and extra-terminal motif (BET) inhibitor being tested in combination with ruxolitinib, a Janus kinase 1/2 (JAK1/2) inhibitor, in patients with myelofibrosis who are no longer responding to ruxolitinib alone. A second presentation features preclinical data with OPN-6602, an oral, small molecule inhibitor of the E1A binding protein (EP300)..."

P1 data • Preclinical • Melanoma • Multiple Myeloma • Oncology • Solid Tumor

Opna Bio Doses First Patient in Phase 1 Study in Multiple Myeloma with OPN-6602, an EP300/CBP Bromodomain Inhibitor (Businesswire) - "Opna Bio announced that it has dosed the first patient with OPN-6602, a potent and selective EP300/CBP bromodomain inhibitor, in a Phase 1 clinical study in multiple myeloma. The trial is expected to enroll up to 130 total patients with relapsed or refractory multiple myeloma at sites in the U.S....The first patient was dosed at The START Center for Cancer Research in Grand Rapids, Michigan, with Dr. Andrew Sochacki, principal investigator, leading the study team."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

OPN6602-C01: Study to Assess Safety and Tolerability of OPN-6602 in Subjects With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Opna Bio LLC | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

OPN6602-C01: Study to Assess Safety and Tolerability of OPN-6602 in Subjects With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=130 | Not yet recruiting | Sponsor: Opna Bio LLC

Combination therapy • Monotherapy • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Opna Bio Presents Promising Preclinical Data in Multiple Myeloma with OPN-6602 and in Malignant Mesothelioma with OPN-9840 Showing Significant Tumor Growth Inhibition at the American Association of Cancer Research Annual Meeting (Businesswire) - "Opna Bio...presented promising preclinical data in...programs, OPN-6602, a dual EP300/CBP inhibitor in multiple myeloma....Data were shared at the American Association of Cancer Research (AACR) Annual Meeting....Significantly reduced tumor growth as single agent (71% tumor growth inhibition, or TGI) in the OPM-2 multiple myeloma cell xenograft model. Demonstrated increased anti-tumor activity (>100% TGI) and sustained duration of response in combination studies with dexamethasone, pomalidomide and mezigdomide....A first-in-human Phase 1 study of OPN-6602 is planned for mid-2024 in patients with multiple myeloma."

New P1 trial • Preclinical • Multiple Myeloma

OPN-6602, a dual EP300/CBP bromodomain inhibitor modulates androgen-driven transcription, including MYC, in mCRPC. (AACR-NCI-EORTC 2023) - No abstract available

Oncology • Prostate Cancer • EP300