zavabresib (OPN-2853) / Opna Bio - LARVOL DELTA

A Study of PLX2853 in Advanced Malignancies. (clinicaltrials.gov) - P1b/2a; N=166; Recruiting; Sponsor: Plexxikon; Trial completion date: Oct 2021 ➔ Jun 2022; Trial primary completion date: Feb 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Eye Cancer • Follicular Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Uveal Melanoma

BET inhibitor OPN-2853 in advanced solid tumors and lymphoma: results from the phase 1b PLX124-01 trial. (PubMed, Cancer Chemother Pharmacol) - "OPN-2853 was well tolerated at the RP2D in patients with advanced solid tumors and NHL, with modest clinical activity including two confirmed objective responses."

First-in-human • Journal • P1 data • Fatigue • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Thrombocytopenia

Progress of investigational bromodomain and extra-terminal domain inhibitors for myelofibrosis therapy. (PubMed, Expert Opin Investig Drugs) - "Trials assessing the efficacy of pelabresib, ABBV-744, INCB057643, BMS-986158, and OPN-2853 are detailed herein. Research into novel pan-and selective-BETis both as monotherapy and in combination with JAKis or other mechanism-based therapies are ongoing. Whether BETi therapy in MF will ultimately deliver substantial anti-clonal activity to modify disease biology and meaningfully impact clinical outcomes is yet to be determined."

Journal • Review • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • ABL1 • BCR

Opna Bio…announced that OPN-2853, a bromodomain and extra-terminal motif (BET) small molecule inhibitor, has been granted Orphan Drug Designation (ODD) for the treatment of myelofibrosis (MF) by the U.S. Food and Drug Administration (FDA). (Businesswire) - "Additionally, the generic name of zavabresib for OPN-2853 has been approved by the International Nonproprietary Names (INN) for Pharmaceutical Substances....In the ongoing Phase 1 PROMise study led by Professor Adam Mead at the University of Oxford through a collaboration with Cancer Research UK (CRUK), zavabresib is being evaluated as an add-on to ruxolitinib in patients with myelofibrosis who are no longer responding to ruxolitinib alone."

Commercial • Orphan drug • Myelofibrosis

Interim analysis of promise, a clinical study combining the BET inhibitor OPN-2853 with ruxolitinib in patients with advanced myelofibrosis experiencing an inadequate response to ruxolitinib (ASH 2025) - P1 | "Encouraging levels of spleen reduction and a manageable safety profile have been observedwith combination OPN-2853 & rux treatment. Clinical activity observed is supported by symptomassessment and molecular data, and no patients experienced leukemic progression."

Clinical • Metastases • Myelofibrosis • Thrombocytopenia

OPN-2853 Reduces Spleen Size in Patients with Advanced Myelofibrosis (Businesswire) - "As of October 2025, 29 patients had been enrolled across multiple sites in the United Kingdom. Fourteen patients were treated with 40 mg of OPN-2853 and 15 patients were treated with 80 mg of OPN-2853 added to ruxolitinib. In 16 of 26 evaluable patients, there was a 50% or greater reduction of their palpable spleen length on treatment when compared to baseline....The combination dose has been well tolerated, and the majority of patients have completed eight cycles of combination treatment."

P2 data • Myelofibrosis

Interim Analysis of Promise, a Clinical Study Combining the BET Inhibitor OPN-2853 with Ruxolitinib in Patients with Advanced Myelofibrosis Experiencing an Inadequate Response to Ruxolitinib (ASH 2024) - P1 | "Conclusion The ongoing PROMise study (EudraCT 2019-000916-27) combines a daily dose of OPN-2853 with standard of care ruxolitinib to test the hypothesis that a continuous daily dosing regimen of oral agents will improve disease burden. Encouraging levels of spleen reduction have been observed in the context of a well tolerated agent."

Clinical • Metastases • Anemia • Chronic Eosinophilic Leukemia • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia

Promise: Investigation into the Combination of a Potent Beti with Ruxolitinib in Patients with High or Intermediate-2 Risk Myelofibrosis Not Receiving an Adequate Response with Ruxolitinib Alone (ASH 2023) - "Additionally, pharmacokinetic samples are taken at specified timepoints pre and post dose to establish PK properties of OPN-2853 in combination with ruxolitinib. Current Status: To date PROMise has recruited 14 patients across all dose categories, and two TSC meetings have taken place."

Clinical • Acute Myelogenous Leukemia • Chronic Eosinophilic Leukemia • Fibrosis • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Opna Bio Announces 2025 ASH Presentations Highlighting…Updated Interim Data from Phase 1 Combination Study of OPN-2853 with Ruxolitinib in Advanced Myelofibrosis (Businesswire) - "The poster presentation will highlight updated interim data from the ongoing Phase 1 study of OPN-2853 in patients with myelofibrosis who are no longer responding to ruxolitinib. This investigator-initiated study is led by Professor Adam Mead at the University of Oxford through a collaboration with Cancer Research UK (CRUK) and is run through the Cancer Research UK Clinical Trials Unit at the University of Birmingham."

P1 data • Myelofibrosis

PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P1/2 | N=19 | Terminated | Sponsor: Opna Bio LLC | Phase classification: P1b/2a ➔ P1/2

Phase classification • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

OPN-2853 Shows Spleen Reduction in Patients with Advanced Myelofibrosis (Businesswire) - P1 | N=16 | PROMise (2019-000916-27) | "In 12 evaluable patients, the median spleen size was reduced from baseline with spleens no longer palpable in 50% of evaluable patients. The combination dose has been well tolerated, and the majority of patients have completed eight cycles of combination treatment....We are very encouraged by these data to date, which demonstrate that daily dosing of OPN-2853 in combination with ruxolitinib was well tolerated, and showed spleen reduction in patients with myelofibrosis who have very limited options once they have progressed...We are enthusiastic about the OPN-2853 and ruxolitinib combination and expect to have a recommended Phase 2 dose in early 2025."

P1 data • Myelofibrosis • Oncology

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

PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=37 | Terminated | Sponsor: Opna Bio LLC | Phase classification: P2a ➔ P1/2

Combination therapy • Metastases • Monotherapy • Phase classification • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ARID1A

PROMISE: INVESTIGATION INTO THE COMBINATION OF PLX2853 WITH RUXOLITINIB IN PATIENTS WITH INTERMEDIATE-2 OR HIGH RISK MYELOFIBROSIS NOT RECEIVING AN ADEQUATE RESPONSE WITH RUXOLITINIB ALONE (EHA 2024) - "The MANIFEST study looked at pelabresib (a BETi) in combination with ruxolitinib and foundthis combination was well tolerated with evidence of symptom improvement in patients, further supporting thisarea of research (7). PROMise has to date recruited 17 patients across the study, with four TSC meetings having taken place. Theinvestigators are looking to extend recruitment beyond the current end date of April-2024."

Clinical • Bone Marrow Transplantation • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Myelofibrosis • Oncology • Transplantation

Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer. (PubMed, JCO Precis Oncol) - "This study confirmed the safety profile of PLX2853 and demonstrated the feasibility of combination with carboplatin. Although these results did not meet the prespecified response criteria, evidence of clinical activity highlights the rationale for further exploration of BET inhibitors in patients with ARID1A-mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway."

Journal • P1/2 data • P2a data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ARID1A

Testing the Safety and Effectiveness of Combining Two Drugs, PLX2853 and Trametinib in the Treatment of Advanced Uveal Melanoma (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Alliance for Clinical Trials in Oncology | N=54 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Metastases • Trial withdrawal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Phase 1b/2a clinical trial of the oral BET inhibitor PLX2853 as monotherapy for ARID1A mutated gynecologic cancers and in combination with carboplatin for platinum resistant ovarian cance (AACR 2023) - P2a | "This study in a larger cohort of gynecologic cancer patients confirmed the safety profile of the agent and demonstrated the feasibility of combination with carboplatin. While these results did not meet the pre-specified response criteria, evidence of clinical activity nevertheless highlights the rationale for further exploration of BRD4 inhibitors in patients with ARID1A-mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway, frequently activated in these cancers."

Clinical • Combination therapy • Monotherapy • P1/2 data • Gynecologic Cancers • Hematological Malignancies • Lymphoma • Oncology • Ovarian Cancer • Solid Tumor • ARID1A • BRD2 • BRD3 • BRD4 • BRDT

Identification of Relevant Genomic Signatures and Potential Targets in Gynecologic Malignancies by Whole Genome and Transcriptomic Profiling (USCAP 2023) - "Results Table: Tumor Type Site N High-TMB cases Biomarkers Treatment Select Molecular signature/ phenotype UEC Uterus 27 15 PTEN, MSI-H, KRAS, PIK3CA, ATM, ARID1A, FGFR2, NF1, PTCH1, CDK12 AZD8186, Trametinib, Alpelisib, Olaparib, PLX2853, Evdafitinib, Sonidegib, Cemiplimab HRD (n=1) MMR (n=11) CDK12/ CCNE1 amp (n=3) USC Uterus 7 0 ERBB2, PIK3CA, KRAS, CHEK2, SMARCB1 Pembrolizumab, Alpelisib, Trametinib, Olaparib, Tazematostat HRD (n=1) CDK12/ CCNE1 amp (n=7) LGSO Ovary 2 0 CDKN2A Abemaciclip MMR (n=2) HGSOF Ovary and Tube 13 1 BRCA1, BRCA2, ARID1A, ERBB2, TSC2, ERCC2, CDKN2A, NF1, Olaparib, Niraparib, PLX2853, Pembrolizumab, Everolimus, Cisplatin, Abemaciclip, Trametinib HRD (n=7) CDK12/ CCNE1 amp (n=2) ECOV Ovary 7 0 PIK3CA, KRAS, CDKN2A, PTEN, ARID1A, BRCA2 Alpelisib, Trametinib, Abemaciclip, AZD8186, PLX2853, Olaparib MMR (n=1) MMMT Uterus and Adnexa 9 2 PIK3CA, PTEN, ERBB2, KRAS, ARID1A, RET, Alpelisib, AZD8186, Pembrolizumab, Trametinib, PLX2853, Pralsetinib HRD..."

Tumor mutational burden • Cervical Cancer • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Gynecologic Cancers • Microsatellite Instability • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Sarcoma • Squamous Cell Carcinoma • Uterine Cancer • AKT1 • ARID1A • BRCA1 • BRCA2 • CCNE1 • CDK12 • CDKN2A • CHEK2 • ERCC2 • FANCL • FGFR2 • HER-2 • HRD • KRAS • MSI • NF1 • PIK3CA • PTCH1 • PTEN • RAD51B • SMARCB1 • TMB • TSC1 • TSC2

Testing the Safety and Effectiveness of Combining Two Drugs, PLX2853 and Trametinib in the Treatment of Advanced Uveal Melanoma (clinicaltrials.gov) - P1/2 | N=54 | Not yet recruiting | Sponsor: Alliance for Clinical Trials in Oncology

Metastases • New P1/2 trial • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Opna Bio Launches with $38 Million Series A Financing to Advance Novel Oncology Discovery Program and Diversified Pipeline of Clinical and Preclinical Programs (Businesswire) - "Opna Bio...announced today that it has raised $38 million in a Series A financing, led by Longitude Capital and Northpond Ventures, with additional participation from Menlo Ventures. The proceeds will be used to develop novel fragile-X mental retardation protein (FMRP) inhibitors in oncology as well as a diverse portfolio of clinical and preclinical oncology programs acquired from Plexxikon Inc....As part of Opna’s formation, the company acquired a portfolio of small molecule oncology therapeutics from Plexxikon Inc. The clinical-stage assets include: OPN-2853 (formerly PLX2853), a potential best-in-class bromo and extra terminal (BET) domain inhibitor currently in a Phase 1/2 clinical trial in combination with ruxolitinib (Jakafi^®) for myelofibrosis, a rare myeloid cancer; OPN-7486 (formerly PLX7486), a colony-stimulating factor 1 (CSF1) receptor inhibitor expected to begin a Phase 2 study in 2023."

Financing • New P2 trial • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Final Results of a Phase 1b Study of BET Inhibitor PLX2853 in Patients with Relapsed or Refractory Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome (ASH 2021) - P1b, P1b/2a | "Daily dosing of PLX2853 was well tolerated as a monotherapy and showed early signs of clinical activity in some patients with relapsed or refractory AML or high risk MDS, with potential for combination with other agents. The RP2D is 80 mg QD continuous dosing. This clinical trial is registered at clinicaltrials.gov: NCT03787498."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Anemia • Cardiovascular • CNS Disorders • Constipation • Diabetes • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Infectious Disease • Insomnia • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pulmonary Disease • Renal Disease • Sarcoma • Septic Shock • Sleep Disorder • Solid Tumor • BCL2

PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P1b/2a | N=19 | Terminated | Sponsor: Opna-IO LLC | N=110 ➔ 19 | Active, not recruiting ➔ Terminated; study terminated due to business realignment

Combination therapy • Enrollment change • Trial termination • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of PLX2853 in Advanced Malignancies. (clinicaltrials.gov) - P1b | N=49 | Completed | Sponsor: Opna-IO LLC | Phase classification: P1b/2a ➔ P1b

Phase classification • Diffuse Large B Cell Lymphoma • Eye Cancer • Follicular Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Uveal Melanoma

PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer (clinicaltrials.gov) - P2a | N=37 | Terminated | Sponsor: Opna-IO LLC | N=67 ➔ 37 | Active, not recruiting ➔ Terminated; study terminated due to business realignment

Combination therapy • Enrollment change • Monotherapy • Trial termination • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ARID1A

PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer (clinicaltrials.gov) - P2a | N=67 | Active, not recruiting | Sponsor: Opna-IO LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Monotherapy • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ARID1A