On December 8, 2025 Opna Bio, a clinical-stage biopharmaceutical company focused on the discovery and development of novel oncology therapeutics, reported promising preclinical data from the company’s novel, multi-functional protein degrader program and positive updated data from an ongoing Phase 1 combination study with OPN-2853, a bromodomain and extra-terminal motif (BET) inhibitor, as an add-on to ruxolitinib in patients with advanced myelofibrosis.

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Data were shared in an oral and poster presentation this past weekend at the 67th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), taking place December 6-9, 2025, in Orlando, FL.

Multi-Functional Degraders Designed to Block Key Oncogenic Pathways Using Single Chemical Entity

Opna’s novel protein degraders are designed to block multiple oncogenic targets – EP300, CBP, IKZF1 and IKZF3 – concurrently in the same cancer cell, achieving potent single agent anti-tumor activity. EP300, CBP, IKZF1 and IKZF3 are known to promote the progression of multiple myeloma, a type of blood cancer derived from malignant plasma cells in the bone marrow. In a proof-of-concept OPM-2 multiple myeloma model, OPN-5667 potently reduced the levels of key oncoproteins in vitro and caused tumor regression in all treated animals in vivo. Opna’s medicinal chemistry campaign has produced compounds with improved potency and pharmacological properties, advancing the program towards clinical candidate selection.

The degrader program is built on foundational studies presented at ASH (Free ASH Whitepaper) in 2024 with OPN-6602, an oral EP300/CBP inhibitor, in combination with immunomodulatory drugs (IMiDs). The combination resulted in strong synergy in vivo including complete regressions and improved response durability. A Phase 1 study of OPN-6602 is currently enrolling patients with relapsed or refractory multiple myeloma at multiple sites in the U.S.

"These promising data support our goal of developing a single agent ‘super drug’ for hematological malignancies, such as multiple myeloma and lymphoma," said Gideon Bollag, PhD, chief scientific officer of Opna Bio. "We anticipate identifying a lead candidate in mid-2026 and submitting an IND in 2027."

OPN-2853 Reduces Spleen Size in Patients with Advanced Myelofibrosis

OPN-2853, a potent, orally active small molecule BET inhibitor, is being evaluated as an add-on to ruxolitinib in the PROMise study in patients with myelofibrosis who are no longer responding to ruxolitinib. Myelofibrosis is a type of blood cancer that causes bone marrow fibrosis, anemia and an enlarged spleen, amongst other symptoms.

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.

The 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.

"The emerging data from the PROMise study continue to be encouraging. We are now seeing consistent and clinically meaningful spleen size reductions, improvements in symptom burden, and durable benefit for patients who previously had limited options after an inadequate response to ruxolitinib alone," said Dr. Mead. "These findings strengthen our view that selective BET inhibition alongside JAK inhibition may offer a new therapeutic approach for patients with myelofibrosis."

(Press release, Opna Bio, DEC 8, 2025, View Source [SID1234661293])

On December 8, 2025 REVEAL GENOMICS, S.L., a Barcelona-based biotechnology company focused on advancing precision oncology through biomarker innovation, reported the presentation of seven studies at the upcoming San Antonio Breast Cancer Symposium (SABCS) 2025, held December 9–12 in San Antonio, Texas.

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These abstracts showcase the growing clinical utility and innovation of the company’s proprietary RNA platform and underscore REVEAL GENOMICS’ commitment to improving outcomes for individuals with breast cancer.

Across all studies, REVEAL GENOMICS and its collaborators analyzed more than 1,300 tumor samples from individuals with HER2-positive, ER-negative, and triple-negative breast cancer—one of the most extensive genomic contributions to SABCS 2025.

Seven independent studies validate the performance and clinical impact of REVEAL GENOMICS’ precision oncology platform

New HER2DX Genomic Scores: Predicting Overall Survival and Brain Progression in Advanced HER2+ Breast Cancer
REVEAL GENOMICS presents two new analyses in a cohort of 215 individuals with advanced HER2-positive breast cancer, including 93 cases from Spain and 122 from Poland. The studies show that the HER2DX ERBB2 score, together with two newly developed genomic scores, independently predicts overall survival and the risk of brain progression in individuals treated with first-line therapy and in subsequent treatment settings.

These findings are particularly relevant in a landscape where multiple therapeutic options now exist, each with different levels of efficacy and tolerability. CNS progression remains a major unmet need, and until now no biomarker has been available to identify those at highest risk.

The newly developed HER2DX CNS Progression Score demonstrated a strong ability to stratify risk. In the Polish validation cohort, the 3-year cumulative incidence of CNS progression was 39.2% in the high-risk group, 13% in the intermediate-risk group, and 4.3% in the low-risk group.

Taken together, these results highlight the potential of HER2DX genomic scores—including the new CNS Progression Score—to guide treatment selection, personalize CNS surveillance, and ultimately improve outcomes for individuals with advanced HER2-positive breast cancer.

Operational Feasibility of HER2DX in the DEFINITIVE Trial
The DEFINITIVE trial (NCT06446882) is an ongoing, international, multicenter, randomized prospective clinical trial across Europe and Israel. Funded by the European Union, it has been designed to evaluate the impact of HER2DX-guided treatment in stage II-III HER2-positive breast cancer. The poster presented at SABCS 2025 shows real-time operational insights from the first 122 patients screened. HER2DX testing was successfully completed in 115 cases (success rate 94.3%). The median turnaround time from sample reception to result was 7 working days, confirming the feasibility of rapid, centralized genomic testing. These results support the integration of genomic classifiers into real-time treatment decision-making in prospective clinical trials.

HER2DX Genomic Test: SABCS 2025 & Newly Published Data
REVEAL GENOMICS also presents new data showing that HER2DX scores reflect pathological features from both the tumor and its immune microenvironment. However, no clinical-pathological variable could fully capture the information contained in the HER2DX scores. Most importantly, the HER2DX pCR score emerged as the only variable independently associated with pathologic complete response (pCR), even after adjusting for tumor-infiltrating lymphocytes (TILs). Notably, TILs were no longer predictive once the HER2DX pCR score was included in the analysis. These findings were recently published in Clinical Cancer Research.

HER2DX pCR Score vs. TILs in the COMPASSHER2 pCR Trial
A proffered paper (GS1-04) evaluated TILs in the COMPASSHER2 pCR trial from ECOG-ACRIN, comparing their performance with the HER2DX pCR score in 569 patients. HER2DX was assessed as a secondary aim within a pre-specified, prospectively planned analysis embedded in COMPASSHER2 pCR (EA1181; NCT04266249), a large multicenter phase II trial evaluating neoadjuvant THP in more than 2,000 patients with stage II–III HER2-positive breast cancer. The results are fully consistent with the previous work developed: although TILs are associated with pCR, their predictive value disappears once the HER2DX pCR score is included in the model. This further reinforces the superior predictive ability of the HER2DX pCR score compared with TILs alone for identifying patients most likely to achieve a pCR.

Prospective Evaluation of ERBB2 mRNA Score in ER-Negative Breast Cancer
A prospective pilot study evaluated whether the ERBB2 mRNA score—integrated into the HER2DX and TNBCDX assays—could streamline HER2 assessment in ER-negative breast cancer. Both assays were run blinded to HER2 status using their standard RNA-based platform. Based on the ERBB2 mRNA level, samples were automatically routed to the appropriate assay: ERBB2-low tumors generated a TNBCDX output, whereas ERBB2-medium/high tumors generated a HER2DX output. In parallel, all tumors underwent routine HER2 testing by IHC/ISH.

The ERBB2 mRNA score demonstrated perfect concordance with standard HER2 classification, correctly identifying every HER2-positive and HER2-negative case. These findings support RNA-based HER2 assessment as an accurate, rapid, and operationally simple approach that can help accelerate neoadjuvant decision-making in ER-negative disease.

Independent Validation of TNBCDX in Early Triple-Negative Breast Cancer
A new independent validation study in 164 patients from two Spanish academic centers confirms that the TNBCDX 15-gene assay—used to generate both the pCR score and the risk score—accurately predicts pCR and recurrence risk in early-stage TNBC, irrespective of anthracycline or pembrolizumab use. These results build on the Annals of Oncology publication, where TNBCDX was originally developed and validated in 527 patients across three prospective neoadjuvant studies. In that analysis, the TNBCDX pCR score was significantly associated with pCR, and the TNBCDX risk score consistently predicted long-term outcomes including distant disease-free survival, and overall survival.

Together, the original 527-patient dataset and this new independent 164-patient cohort provide converging evidence that TNBCDX is a robust and reproducible tool for refining risk stratification and supporting more individualized systemic therapy decisions in early-stage TNBC.

Company Leadership Highlights the Impact and Vision Behind These Breakthroughs
The leadership of REVEAL GENOMICS highlights the importance of the SABCS 2025 findings, emphasizing their impact on advancing precision oncology and supporting clinicians and patients.

Prof. Aleix Prat, MD, PhD, Co-founder and CSO, remarks: "These results reflect years of collaborative research and our commitment to translating genomic science into real-world benefits for patients. We are proud to see our tools making a tangible difference in breast cancer care. The breadth of data presented at SABCS 2025 demonstrates the versatility and clinical impact of our genomic platforms. We are excited to continue advancing precision oncology through robust science and innovation."

Dr Patricia Villagrasa, Co-founder and CEO, adds: "Our mission is to empower clinicians and patients with the best possible information for treatment decisions. The progress showcased at SABCS 2025 is a clear reflection of our team’s dedication and the trust placed in us by the oncology community."

(Press release, REVEAL GENOMICS, DEC 8, 2025, View Source [SID1234661292])

On December 8, 2025 Aleta Biotherapeutics, a clinical stage immuno-oncology company developing CAR T-cell engager biologics that enable CAR T-cell cancer therapies to work more effectively, and Cancer Research UK’s Centre for Drug Development, reported promising results from the phase I/II clinical trial of ALETA-001 in patients who have received anti-CD19 CAR T-cell therapy for the treatment of B-cell malignancies.

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The multi-centre, open-label clinical trial (NCT06045910) is ongoing across the United Kingdom. The study examines patients with B-cell malignancies who have received standard-of-care anti-CD19 CAR T-cell therapy. It encompasses dose escalation from 0.4 mg/kg to 6.0 mg/kg of ALETA-001 following CD19-targeting CAR T-cell therapy. Two phase 1 cohorts have been enrolled having distinct dosing regimens, designed to determine safety and tolerability along with a recommended dose, timing and schedule of administration for a subsequent phase II expansion.

The late dosing cohort has enrolled patients who were at least four weeks post-CAR T-cell therapy and had not achieved a complete metabolic remission (CMR) on PET/CT scan or had achieved an initial CMR but subsequently relapsed with biopsy-proven disease within nine months. ALETA-001 demonstrated a highly tolerable safety profile at all doses, with no ALETA-001-related serious adverse events greater than Grade 1 observed. Robust CAR T-cell expansion was observed in four of six patients who received the lowest doses, demonstrating the ALETA-001 mechanism of action. In addition, a proportion of patients in the late dosing cohort showed encouraging clinical responses and achieved durable CMRs after ALETA-001 administration.

In the early dosing cohort, ALETA-001 is being administered to patients between 10 to 18 days post-CAR T-cell therapy. Patients in the early dosing cohort have shown no signs of toxicity and are being evaluated for signals of biomarker response and for durable efficacy.

Sridhar Chaganti, MD, PhD, Chief Investigator, University Hospitals Birmingham NHS Foundation Trust, Birmingham UK, said: "The majority of B-cell lymphoma patients relapse early after CD19-targeted CAR T-cell therapy. For these patients, time is critical and outcomes with further treatments are poor. ALETA-001 is a promising, off-the-shelf therapeutic that increases and maintains CD19 antigen density, thereby optimizing CD19-targeted CAR T-cell activity and offering the potential for a cure."

Marco Ruella, MD, Associate Professor of Medicine at the University of Pennsylvania, Scientific Director of the Lymphoma Program, and advisor to Aleta Biotherapeutics, said, "Having agents that can enhance or even rescue CAR T-cell anti-tumor activity is highly desirable. These promising preliminary clinical results initially suggest that ALETA-001 can revitalize CAR T-cells that have struggled to clear the tumor."

"The data presented by Dr. Chaganti and colleagues provide proof of mechanism for ALETA-001" said Paul Rennert, President and Chief Scientific Officer, Aleta Biotherapeutics. "This is an exciting milestone. ALETA-001 is now being provided to patients shortly after they receive a CD19 CAR T-cell therapy, giving these patients the opportunity for a robust and durable response."

Cancer Research UK’s Centre for Drug Development is sponsoring and conducting the phase I/II clinical trial of ALETA-001, the lead agent in Aleta Biotherapeutics’ portfolio. Additional clinical trial sites are planned across the United Kingdom in 2026 to increase patient access.

About the CAR T-Cell Therapy Engager Protein, ALETA-001

ALETA-001 was designed specifically for the treatment of B-cell malignancies in patients who have received a CD19-directed CAR T-cell therapy and are at risk of treatment failure. ALETA-001 binds CD19 to the lymphoma antigen CD20 and thereby enables dual-antigen targeting by CD19 CAR T-cells. This mechanism of action improves the effectiveness of CD19-directed CAR T-cell therapies by increasing CD19 antigen density and restoring lost CD19 expression on the cancer cell. This allows CD19+/CD20+ cancer cells to be easily recognized and killed by CD19-directed CAR T-cells that were previously administered and are already circulating within a patient.

Aleta previously secured landmark clinical support and funding from Cancer Research UK for the ALETA-001 phase I/II clinical trials, and ALETA-001 has received a UK Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the UK Medicines and Healthcare products Regulatory Agency. ILAP designation is granted to medicines that address life-threatening or seriously debilitating conditions, and where there exists a significant patient or public health need.

(Press release, Aleta Biotherapeutics, DEC 8, 2025, View Source [SID1234661291])

On December 8, 2025 AbCellera (Nasdaq: ABCL) reported that the Company will present at the 44th Annual J.P. Morgan Healthcare Conference on January 14, 2026.

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A live audio webcast of the presentation may be accessed through a link that will be posted on AbCellera’s Investor Relations website. A replay will be available through the same link following the presentation.

(Press release, AbCellera, DEC 8, 2025, View Source [SID1234661290])

On December 8, 2025 Incyte (Nasdaq:INCY) reported updated clinical data from two Phase 1 studies evaluating the safety, tolerability and efficacy of INCA033989, a first-in-class mutant calreticulin (mutCALR)-targeted monoclonal antibody, as a treatment for patients with mutCALR-expressing myeloproliferative neoplasms (MPNs). These data, which are featured in oral presentations at the 2025 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando (Session 634, Publication #1024; Session 631, Publication #71), focus on the dose escalation portion of the studies in patients with essential thrombocythemia (ET) harboring a CALR mutation who are resistant or intolerant to at least one cytoreductive therapy.

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"The compelling efficacy and safety data presented today at the 2025 ASH (Free ASH Whitepaper) Annual Meeting provide additional evidence of the potential for INCA033989 to provide disease modification for high-risk ET patients harboring a CALR mutation," said Pablo J. Cagnoni, M.D., President, Head of Research and Development, Incyte. "We are proud to be advancing a portfolio of novel targeted therapies, including INCA033989, that could offer a mutation-specific treatment for patients with mutCALR-expressing MPNs."

Results presented today evaluate the safety and efficacy of INCA033989 in patients with ET, as measured by hematologic response and reduction in mutCALR variant allele frequency (VAF), and build upon previously announced data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress.

The new results (data cut-off September 25, 2025) demonstrate rapid and durable normalization of platelet counts across all dose levels in patients with ET treated with INCA033989 (n=55), with optimal responses at higher doses. Of note, most (90%) ET patients treated with starting doses of 400 to 2,500 mg (n=30) INCA033989 achieved a hematologic response. Of those, 83.3% achieved a complete hematologic response (CHR), defined as platelet count ≤400 × 109/L and leukocytes <10 × 109/L, and nearly half (46.4%) achieved a durable (≥12 weeks) CHR. Among patients treated at lower doses (24 to 250 mg, n=25), 88% achieved a hematologic response, with 68% achieving a CHR and of those 44% achieving a durable CHR.

Additionally, molecular responses were frequent, rapid, durable and correlated with hematologic responses seen with INCA033989 monotherapy. A reduction in mutCALR VAF from baseline occurred in 96.2% of ET patients with ≥1 post-baseline VAF measurement, with approximately half (52%) achieving a ≥25% best reduction in VAF and nearly one third (31%) achieving a ≥50% best reduction in VAF. Reduction in mutCALR VAF was observed within three to six months and has maintained over time in most patients, with deeper and more consistent mutCALR VAF reductions observed at higher doses of INCA033989.

Exploratory analyses in a subset of ET patients showed that INCA033989 reduced circulating mutCALR-positive hematopoietic stem and progenitor cells (HSPC) and mutCALR-positive platelet producing cells called megakaryocytes (MK) in the bone marrow, and improved MK hyperplasia. Together, these findings demonstrate the disease-modifying activity of INCA033989 in patients with mutCALR-expressing ET.

The safety analysis (n=55) showed that INCA033989 was well tolerated across all dose cohorts (24 to 2,500 mg), with no dose-limiting toxicities observed. Only one (1) patient discontinued treatment due to treatment emergent adverse events (TEAEs). One (1) dose reduction and one (1) infusion interruption due to TEAEs were reported, and a maximum tolerated dose was not reached. Fifty-three (53) patients across the dose cohorts reported a TEAE, thirty-six (36) of which were treatment related. The most common TEAEs were fatigue (30.9%), headache (27.3%), upper respiratory tract infection (27.3%) and anemia (20%). Grade >3 anemia and/or neutropenia TEAEs (>1 patient) occurred in five (5) patients (3.6% and 7.3%, respectively). No Grade ≥3 thrombocytopenia TEAEs were observed.

"Approximately 25 to 35 percent of ET patients have mutCALR-expressing ET, yet current treatments are broadly myelosuppressive, not mutant targeted and have limited efficacy in reducing mutCALR allele frequency," said John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mt. Sinai and Director, Center of Excellence for Blood Cancers and Myeloid Disorders, The Tisch Cancer Institute. "These emerging data suggest that INCA033989 could offer a novel treatment approach by selectively targeting mutCALR in a way that enables rapid and durable hematologic responses, while maintaining safety and tolerability for ET patients who are resistant or intolerant to prior cytoreductive therapy. I’m encouraged by these findings and the potential for INCA033989 to redefine treatment paradigms for patients with ET."

INCA033989 was recently granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with ET harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy. Incyte plans to develop INCA033989 for patients with Type 1 and non-Type 1 CALR mutations and, following discussions with regulatory agencies, plans to initiate a registrational program evaluating patients with ET with a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy in the first half of next year.

More information regarding the 2025 ASH (Free ASH Whitepaper) Annual Meeting can be found on the ASH (Free ASH Whitepaper) website: View Source

About Essential Thrombocythemia
Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by persistently elevated platelet counts due to abnormal blood cell production in the bone marrow. People living with ET are at increased risk for blood clots and bleeding and a proportion of patients may progress over time to myelofibrosis or acute leukemia.

About Mutations in Calreticulin (mutCALR)
Calreticulin (CALR) is a protein involved in the regulation of cellular calcium levels and normal protein folding. Somatic, or non-inherited, DNA mutations in the CALR gene (mutCALR) can result in abnormal protein function and lead to the development of myeloproliferative neoplasms (MPNs),1 a closely related group of clonal blood cancers in which the bone marrow functions abnormally, overproducing blood cells.2,3 Among two types of MPNs, essential thrombocythemia (ET) and myelofibrosis (MF), mutCALR drives 25-35% of all cases.2,3

Incyte is at the forefront of developing novel therapies for patients with mutCALR ET or MF that target only malignant cells, sparing normal cells, including INCA033989, a first-in-class, mutCALR-specific therapy.

About the INCA033989 Trial Program
The clinical trial program for INCA033989 includes two multicenter, open-label Phase 1 studies, INCA33989-101 (NCT05936359) and INCA33989-102 (NCT06034002). The studies are evaluating the safety, tolerability and efficacy of INCA033989 in ~455 adult (≥18 years old) patients with mutCALR-expressing myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET) and myelofibrosis (MF).

The primary endpoint of the studies is measured by the number of participants with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs) and the number of participants with TEAEs leading to dose modification or discontinuation. Secondary endpoints include response rates, mean change of ET total symptom score, percentage of MF patients achieving spleen volume reduction, MF patient anemia response, mean change in disease-related allele burden and various pharmacokinetics measures.

For more information on the studies, please visit: View Source and View Source

(Press release, Incyte, DEC 8, 2025, View Source [SID1234661289])