On December 8, 2025 Genmab A/S (Nasdaq: GMAB) reported new and updated data from three arms of the ongoing Phase 1b/2 EPCORE CLL-1 trial (NCT04623541) evaluating the efficacy and safety of epcoritamab-bysp, a T-cell engaging bispecific antibody administered subcutaneously, as a monotherapy and in combination for the treatment of patients with Richter transformation (RT), a rare complication in which chronic lymphocytic leukemia (CLL) evolves into an aggressive lymphoma, most often diffuse large B-cell lymphoma (DLBCL). The results were presented today in two oral presentations (abstracts 1015 and 1017) at the 67th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), in Orlando, Florida.

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EPCORE CLL-1, Arm 2A (Epcoritamab Monotherapy)
In Arm 2A of the trial, patients with RT (n=42) received epcoritamab monotherapy in the first-line setting or in second- or later-line settings, with a median follow-up of 22.9 months. In the first-line setting (n=21), patients achieved an overall response rate (ORR) of 57%, with 52% experiencing a complete response (CR). The median overall survival (OS) was 27.5 months, progression-free survival (PFS) was 8.5 months, and the median duration of response (DOR) and duration of complete response (DOCR) were not reached. Among RT patients who received epcoritamab monotherapy in second- or third-line settings (n=21), ORR was 38% and the CR rate was 29%. The median DOR was 6.6 months, median PFS was 2.9 months, and median OS was 9.8 months. The results from Arm 2A have been simultaneously published in The Lancet Haematology.

"Patients with Richter transformation, an aggressive form of lymphoma, have limited treatment options and face a poor prognosis," said Arnon Kater, M.D., Ph.D., Department of Hematology, Amsterdam UMC. "The response and survival rates observed in this trial evaluating epcoritamab as a monotherapy treatment are encouraging, especially as a potential option for patients with Richter transformation."

In this arm, cytokine release syndrome (CRS) occurred in 86% of patients (79% with Grade 1/2), immune effector cell-associated neurotoxicity syndrome (ICANS) in 12% of patients (all Grade 1/2), and clinical tumor lysis syndrome (CTLS) in 5%. Most CRS events occurred after the first full dose and resolved within a median of three days in 97% of patients.

EPCORE CLL-1, Arm 2B (Epcoritamab Lenalidomide Combination)
In Arm 2B, previously-treated patients with RT (n=11) ineligible to receive chemoimmunotherapy who had two or less prior lines of therapy received epcoritamab in combination with lenalidomide. With a median follow-up of 16.7 months, the ORR was 82% and the CR rate was 73%. The median OS at nine months was not reached, and the median PFS was 5.7 months. The estimated median DOR and DOCR were not reached.

In this arm of the trial, CRS events were primarily low grade and resolved in 10 patients, with a median time to resolution of four days. One patient discontinued due to CRS. ICANS occurred in two patients (Grade 1/2) and resolved in a median of 2.5 days. There was one treatment-related Grade 5 event.

"With no standard of care for patients with Richter transformation, clinicians are in need of new, therapeutic options with the potential for patients to achieve and maintain remissions," said Philip A. Thompson, MB, MS, Peter MacCallum Cancer Center Melbourne, Australia. "These first results from the combination arms of the EPCORE CLL-1 study demonstrate the potential of epcoritamab combination regimens as potential therapeutic options for those living with Richter transformation."

EPCORE CLL-1, Arm 2C (Epcoritamab R-CHOP Combination)
In Arm 2C, previously untreated patients with RT (n=30) received epcoritamab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). With a median follow-up of 13.6 months, the ORR was 77% and the CR rate was 63%. The median OS was 16.4 months and the median PFS was 16.0 months. The estimated median DOR and median DOCR were not reached.

In this arm, CRS events were primarily low Grade (Grade 1, 7; Grade 2, 8; Grade 3, 2) and median time to resolution was 2.0 days. No patients discontinued due to CRS. ICANS occurred in four patients (Grade 1, 3; Grade 3, 1); three cases resolved in a median of one day, and one was ongoing at time of death. There were three treatment-related Grade 5 events.

"The results from these trials demonstrate the potential of epcoritamab as a monotherapy, and in combination, in patients with Richter transformation, a rare, often fatal, transformation of chronic lymphocytic leukemia into an aggressive lymphoma, mostly diffuse large B-cell lymphoma," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "We are deeply committed to exploring epcoritamab as a potential core therapy across a range of B-cell malignancies, both as an initial treatment and as a later line of therapy."

The safety and efficacy of epcoritamab have not been established for these investigational uses.

In all three study arms, safety was consistent with the known profiles of each agent. In Arm 2A, the most common treatment-emergent adverse events (TEAEs) were infection (74%), anemia (50%), thrombocytopenia (48%), neutropenia (45%), diarrhea (36%), and fatigue (31%). Four patients (10%) discontinued treatment due to a TEAE, and three (7%) experienced fatal events, none considered related to study treatment. In Arm 2B, common TEAEs were CRS (100%), neutropenia (82%), thrombocytopenia (73%), anemia and hypokalemia (45% each). Grade ≥3 TEAEs occurred in all patients, serious TEAEs in 10/11, and epcoritamab-related discontinuations and fatal TEAEs in one patient each. In Arm 2C, common TEAEs were CRS (56%), anemia (60%), neutropenia (73%), thrombocytopenia (46%), diarrhea (33%), and febrile neutropenia (30%). Grade ≥3 TEAEs occurred in 27 (90%) patients and serious TEAEs in 25 (83%). TEAEs led to epcoritamab discontinuations in six (20%) patients and there were three fatal TEAEs (one epcoritamab related). CTLS was not reported in Arms 2B or 2C.

About Richter Transformation (RT)
Richter transformation (RT) is a rare but aggressive evolution of chronic lymphocytic leukemia (CLL), most often into CD20+ diffuse large B-cell lymphoma (DLBCL).i Prognosis of RT is poor, with complete remission rates of approximately 20% and median survival often less than one year following chemoimmunotherapy.ii,iii

About the EPCORE CLL-1 Trial
EPCORE CLL-1 is a global, Phase 1b/2, open-label, multi-center trial to evaluate the safety and preliminary efficacy of epcoritamab as a monotherapy and in combination with standard of care agents in patients with difficult-to-treat relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), R/R small lymphocytic lymphoma (SLL) and Richter transformation (RT). The trial consists of two parts: a dose-escalation phase (Phase 1b) and an expansion phase (Phase 2). Patients with RT are only included in the expansion phase. In patients with RT, epcoritamab monotherapy (Arm 2A) and combination therapy with lenalidomide (Arm 2B) or R-CHOP (Arm 2C) will be evaluated to assess their efficacy, safety and tolerability profiles.

More information on this trial can be found at www.clinicaltrials.gov (NCT: 04623541).

About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.iv

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Where approved, epcoritamab is a readily accessible therapy. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials, among them a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with R2 compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744), and a trial evaluating epcoritamab in combination with lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

(Press release, Genmab, DEC 8, 2025, View Source [SID1234661259])

On December 8, 2025 BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, reported its position as the leader in chronic lymphocytic leukemia (CLL) innovation by showcasing the depth, quality, and momentum of its hematology portfolio at the 67th ASH (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida. The totality of BeOne’s ASH (Free ASH Whitepaper) data reinforce BRUKINSA (zanubrutinib) as the foundational Bruton’s tyrosine kinase inhibitor (BTKi) of choice.

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"At ASH (Free ASH Whitepaper) 2025, we will present new data from across our CLL franchise, highlighting both the strength of BRUKINSA and the potential of BGB-16673," said Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne. "Long-term data are the gold standard in CLL, and BRUKINSA continues to deliver the high levels of durable progression-free and overall survival that patients and physicians should demand from a BTK inhibitor. BGB-16673, the most advanced BTK degrader in the clinic with over 800 patients dosed to date, potentially represents the next wave of foundational innovation in oncology."

BRUKINSA continues to demonstrate unprecedented long-term efficacy with a favorable safety profile over more than six years of follow-up in treatment-naïve CLL/SLL.

In SEQUOIA (NCT03336333), a randomized, multicenter, global Phase 3 trial, BRUKINSA maintained progression-free survival (PFS) superiority versus bendamustine plus rituximab (BR) with an estimated 74% PFS at six years in treatment-naïve CLL or small lymphocytic lymphoma (SLL) compared with 32% PFS for BR. Highlights include:

Arms A, B and C: BRUKINSA vs BR, as well as BRUKINSA in patients with del(17p) (Poster Presentation: 2129)
COVID-19 adjusted PFS rates were 77% (95% CI, 70.1-81.8) for BRUKINSA and 33% (95% CI, 25.5-40.4) for BR.
The overall survival (OS) at 72 months was 84% for BRUKINSA and 80% with BR. After adjusting for COVID-19, the OS rates were 88% and 82%, respectively.
In patients with del(17p), the six-year PFS was 64% (65% after COVID-19 adjustment) and the 72-month OS was 83%.
The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.
"SEQUOIA’s longer follow-up strengthens the evidence for continuous zanubrutinib use," said Constantine Tam, M.B.B.S., M.D., Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University. "Patients continued to show durable disease control and consistent safety across study arms, meaningfully raising the bar for CLL patients, including those with harder-to-treat CLL."

Arm D: BRUKINSA plus venetoclax in patients with or without del(17p) and/or TP53 mutations (Poster Presentation: 5669)
In the overall patient population, in which 58% of patients had del(17p) and/or TP53 mutation, the median PFS was not reached; the 36-month PFS rate was 87%.
The 36-month PFS rate for patients with del(17p) and/or TP53 mutation was 87% and for patients without del(17p) and TP53 mutation was 89%.
A total of 42 patients completed the BRUKINSA plus venetoclax combination and continued BRUKINSA monotherapy.
At 12 months following the combination period, peripheral blood undetectable minimal residual disease (uMRD) was maintained in 100% (18/18) of patients without del(17p) and TP53.
At 18 months following the combination period, uMRD was maintained in 92% (22/24) of patients with del(17p) and/or TP53 mutation.
The safety profile of BRUKINSA plus venetoclax was generally tolerable and no unexpected safety signals were identified.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) now recommend zanubrutinib plus venetoclax as a preferred first-line regimen for CLL/SLL.
New patient-reported outcomes data in R/R CLL suggest BRUKINSA may offer a more manageable side effect profile. Up to six-years of follow-up data support BRUKINSA’s foundational role in CLL/SLL as the only BTK inhibitor with enduring PFS and long-term benefit over another BTK inhibitor.

ALPINE (NCT03734016) is a global, randomized, open-label, multicenter, Phase 3 study of BRUKINSA versus ibrutinib in patients with R/R CLL/SLL who received ≥1 prior systemic therapy. Highlights include:

Symptom-based progression-free survival as a clinically relevant and patient-centric endpoint (Oral Presentation: 711)
This study is among the first analyses of patients with CLL/SLL to demonstrate a statistically and clinically meaningful association between longitudinal symptom deterioration and disease progression using joint modeling.
Deterioration in patient-reported fatigue, insomnia, and nausea/vomiting emerged as strong symptomatic indicators of disease progression.
Compared with ibrutinib, patients on BRUKINSA showed reduced risk of symptom deterioration associated with earlier disease progression.
The analysis showed that patients on BRUKINSA had lower odds of symptom worsening for nausea/vomiting, fatigue, pain, and insomnia.
Up to six years of follow-up of patients from the BRUKINSA arm of ALPINE who continued in a long-term extension study (LTE-1; Poster Presentation: 2123)
With up to 73.5 months of follow-up, the median PFS for all patients was a striking 52.5 months; the 60-month PFS rate was 47.3% (50.4% adjusted for COVID-19). These results redefine what is expected for this patient population.
Among patients with del(17p), the median PFS was 49.9 months; the 60-month PFS rate was 38.2% (40.5% adjusted for COVID-19).
With longer follow-up, the prevalence of most adverse events of special interest remained stable year-over-year.
BGB-16673 (BTK degrader) clinical data demonstrates rapid, robust and deepening responses in patients with heavily pretreated R/R CLL/SLL, including those with prior BTKi treatment and mutations that confer resistance to BTK inhibitors. (Oral Presentation: 85)

Updated results from CaDAnCe-101 (NCT05006716), an ongoing open-label, Phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies, showed responses across R/R CLL/SLL patient types, including those who had previously been treated with BTK inhibitors, BCL2 inhibitors, noncovalent BTK inhibitors, and those with BTK inhibitor resistance mutations. Highlights include:

With a median follow-up of 19.8 months, 54.4% of patients remain on treatment. Across all doses, ORR was 85.3% and CR/CR with incomplete count recovery (CRi) rate was 2.9% with responses deepening over time.
In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%.
In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%.
The 12- and 18-month PFS rates were 73.5% and 65.9% respectively.
BGB-16673 was generally well tolerated in this heavily pretreated population with no treatment-related deaths and no new toxicities identified with a median treatment duration of 13.6 months.
For more information about our presence at the 2025 ASH (Free ASH Whitepaper) Annual Meeting and Exposition, please visit our meeting hub: congress.beonemedicines.com.

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.2,3

About BGB-16673

BGB-16673 is a potential first-in-class Bruton’s tyrosine kinase (BTK) protein degrader and is the most advanced protein degrader in the clinic, with nearly 800 patients dosed to date in an extensive global clinical development program. This program includes three randomized Phase 3 trials in R/R CLL, including the head-to-head Phase 3 trial versus pirtobrutinib, which began enrolling in Q4 2025. Originating from BeOne’s chimeric degradation activation compound (CDAC) platform, BGB-16673 is designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease.

The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and adult patients with R/R mantle cell lymphoma (MCL). Additionally, the European Medicines Agency (EMA) granted BGB-16673 PRIority MEdicines (PRIME) designation for the treatment of patients with Waldenstrom’s macroglobulinemia (WM) previously treated with a BTK inhibitor.

About BRUKINSA (zanubrutinib)

BRUKINSA is an orally available, small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing. BRUKINSA is also the only BTK inhibitor to demonstrate superiority to another BTK inhibitor in a Phase 3 study.

The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 75 markets, and more than 247,000 patients have been treated globally.

Select Important Safety Information

Serious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity (including drug-induced liver injury).

In the pooled safety population (N=1729), the most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Please see full U.S. Prescribing Information including U.S. Patient Information.

The information provided in this press release is intended for a global audience. Product indications vary by region.

(Press release, BeOne Medicines, DEC 8, 2025, View Source [SID1234661276])

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 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported new data presented at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) 2025 Annual Meeting being held in Orlando, FL. Collectively, the oral and poster presentations reinforce the growing body of evidence supporting the potential of RYTELO (imetelstat), Geron’s first-in-class telomerase inhibitor, across lower-risk myelodysplastic syndromes/neoplasms (LR-MDS) and myelofibrosis (MF).

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"These new data confirm our understanding of how imetelstat works and highlight the potential long-term benefit in appropriate patients," said Joseph E. Eid, M.D., Executive Vice President, Research and Development and Chief Medical Officer of Geron. "The data suggesting the association between early treatment-emergent cytopenias and subsequent hemoglobin and transfusion independence response with imetelstat, together with the long-term outcomes from IMerge presented at ASH (Free ASH Whitepaper), continue to reinforce imetelstat as a differentiated treatment option for eligible patients with lower-risk MDS."

The oral presentation by Amer Zeidan, MBBS, MHS, Yale School of Medicine, and a principal investigator of the IMerge trial, featured pooled analyses of the IMerge population suggesting that early treatment-emergent neutropenia and thrombocytopenia may be associated with greater hemoglobin increases, which emerged as a main driver for achieving red blood cell transfusion independence (RBC-TI).

"What stands out in these analyses is the consistency between the clinical response we see in patients and the early treatment patterns observed in their blood counts when we use imetelstat in non-del5q lower-risk MDS patients with transfusion dependent anemia. This is reminiscent of similar trends we see with lenalidomide, which is a disease-modifying agent in del5q lower-risk MDS patients," said Amer Zeidan, Chief of the Division of Hematologic Malignancies and Professor of Medicine at Yale Cancer Center. "For patients with lower-risk MDS, transfusion dependence places a considerable physical and logistical burden on daily life, and treatment options beyond ESAs remain limited. The association we observed between early blood count changes and later improvements in hemoglobin provides valuable insight for clinicians and underscores the meaningful benefit imetelstat may offer to this population."

Additional poster presentations provided long-term outcomes data, including survival data in LR-MDS, exploratory biomarker analyses in MF, and ongoing combination and investigator-sponsored studies across the myeloid malignancy spectrum.

Highlights from the ASH (Free ASH Whitepaper) 2025 Presentations

Correlation between Treatment-Emergent Cytopenias and Clinical Response with Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes: Analysis from the IMerge Trial (Zeidan et al., Oral #490)

This oral presentation reported findings from post-hoc analyses examining the potential relationship between treatment-emergent cytopenias within the first two cycles of imetelstat treatment and key clinical outcomes in the pooled IMerge patient population. These analyses evaluated reductions in platelets and neutrophils alongside hemoglobin (Hb) rise, achievement of ≥8- or ≥24-week RBC-TI, and achievement of Hb rise ≥1.5 g/dL lasting ≥8 weeks.

Across analyses looking at single clinical factors, patients who experienced ≥75% reductions in neutrophils or ≥50% reductions in platelets during the first two cycles of imetelstat had greater maximum Hb increases compared with those who did not experience such reductions. Numerically higher rates of ≥8- or ≥24-week RBC-TI were also observed in these groups. When the analyses accounted for multiple clinical factors at the same time, the associations between early cytopenias and Hb improvements remained consistent: ≥75% neutrophil reduction was associated with greater Hb increase, whereas maximum ≥50% platelet reduction was associated with achieving Hb rise ≥1.5 g/dL lasting ≥8 weeks. Further, Hb rise emerged as a main driver of achieving transfusion independence. A strong association between platelet and neutrophil reductions was also observed.

These findings offer deeper context for interpreting patient responses and provide insight into how imetelstat’s biological effects may translate into meaningful clinical outcomes.

Long-Term Outcomes and Overall Survival from the Randomized, Double-Blind, Placebo-Controlled, Phase 3 IMerge Trial of Imetelstat for Lower-Risk Myelodysplastic Syndromes (Santini et al., Poster #2074)

This poster reported updated long-term outcomes data from the double-blind, placebo-controlled IMerge Phase 3 trial assessing overall survival (OS), progression-free survival (PFS), and time to progression to acute myeloid leukemia (AML) in patients with transfusion-dependent LR-MDS treated with imetelstat.

At a median follow-up of 45 months, the analysis showed a favorable trend toward improved secondary endpoints of OS, PFS, and time to AML progression for imetelstat-treated patients compared with placebo recipients in the overall population. OS favored imetelstat versus placebo in most predefined subgroups, regardless of transfusion burden, serum EPO (erythropoietin) level, and ring sideroblast positive or negative status. Additionally, OS outcomes were numerically improved in patients who achieved RBC-TI or hemoglobin improvement.

These results suggest that imetelstat may provide meaningful long-term benefit for patients with lower-risk MDS who are transfusion independent, although the trial was not powered to detect statistical significance for OS. The data support continued clinical exploration of telomerase inhibition as a potential disease-modifying approach for LR-MDS.

Correlation between IL-8 and TNF-Alpha Levels and Overall Survival in Patients with Myelofibrosis Relapsed or Refractory to a JAKi Treated with Imetelstat in the IMbark Trial​ (Mascarenhas et al., Poster #5585)

This poster reported results from a post hoc analysis of inflammatory cytokines in the Phase 2 IMbark trial of patients with JAK inhibitor relapsed/refractory myelofibrosis treated with imetelstat. The analysis evaluated how cytokine changes corresponded with clinical endpoints, including symptom improvement, spleen volume reduction, and survival trends.

The findings showed that patients treated with imetelstat experienced dose-dependent reductions in IL-8 and TNF-a (proinflammatory cytokines), with the 8.9 mg/kg dose showing more pronounced effects compared to the 4.4 mg/kg dose. Reductions in these cytokines corresponded with reductions in total symptom score or spleen volume, consistent with previously reported clinical activity. A longer survival trend was observed in patients receiving the higher dose, particularly among patients with elevated baseline IL-8 and TNF-a levels, although subgroup sizes were small.

These results suggest that cytokine modulation may contribute to the clinical activity of imetelstat and provide further support for its potential disease-modifying properties in myelofibrosis. These findings build on prior biomarker work demonstrating imetelstat’s impact on malignant progenitor cells in myelofibrosis.

IMproveMF: Phase 1b Trial of Imetelstat Plus Ruxolitinib in Patients with Intermediate-1/2 or High-Risk Myelofibrosis (Mascarenhas, et al., Poster #2052)

This poster reported enrollment progress and emerging observations from the Phase 1b IMproveMF trial evaluating imetelstat in combination with ruxolitinib for patients with intermediate-2 or high-risk myelofibrosis. The study is designed to determine safety, tolerability, and recommended dosing for future development.

As of the July 2025 cutoff, the trial had enrolled three patients in part 2 of the study, with the first patient treated in January 2025. The part 1 dose escalation phase of the study is complete, with 8.9 mg/kg imetelstat IV every 4 weeks identified as the recommended dose to be combined with ruxolitinib.

Advanced Myelodysplastic Neoplasms or AML Failing HMA-based Therapy – Preliminary Results of the IMpress Study​ (Ades, et al, Poster #5115)

This poster reported interim results from an investigator-sponsored Phase 2 study evaluating imetelstat in patients with advanced myelodysplastic neoplasms or acute myeloid leukemia who were refractory to, relapsed after, or intolerant to hypomethylating agent, or HMA, therapy.

The results showed that imetelstat administered at 7.1 mg/kg IV every 2 weeks in this patient population did not appear to be associated with additional toxicity, and that treatment-emergent adverse events were manageable in this heavily pre-treated population. While limited single-agent clinical activity was observed – consistent with the aggressive disease biology and prior treatment history – several patients were able to complete protocol-specified visits, and one remained on treatment at the time of the analysis.

These findings suggest that single agent imetelstat has a predictable and manageable safety profile at this exposure in these advanced diseases and provides important insights for potential combination strategies in high-risk populations, where unmet needs remain substantial.

The ASH (Free ASH Whitepaper) presentations are available on Geron’s website in the Investor section under publications.

Dr. Zeidan has served as a consultant for Geron and has received honoraria. The views expressed in this press release and in the presentation are his own and do not necessarily reflect those of his employer.

About RYTELO (imetelstat)
RYTELO is an oligonucleotide telomerase inhibitor approved in the U.S. for the treatment of adult patients with LR-MDS with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.
In addition, RYTELO is approved in the European Union as a monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration and the European Commission.

US IMPORTANT SAFETY INFORMATION ABOUT RYTELO

WARNINGS AND PRECAUTIONS

Thrombocytopenia

RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO.
Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Neutropenia

RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO.
Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Infusion-Related Reactions

RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion.
Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.

Embryo-Fetal Toxicity

Based on animal findings, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%).
Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

(Press release, Geron, DEC 8, 2025, View Source [SID1234661260])

On December 8, 2025 Autolus Therapeutics plc (Nasdaq: AUTL), an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation programmed T cell therapies, reported presentation of preliminary data from the CATULUS Phase 1 trial of obe-cel in pediatric relapsed or refractory (r/r) B-ALL patients, as well as further insights from the registrational FELIX study in adult r/r B-ALL, at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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Dr. Matthias Will, Chief Development Officer of Autolus, said: "Pediatric patients with r/r B-ALL have a poor prognosis, particularly those who relapse early. We were pleased to share the first data from the Phase 1 CATULUS trial showing obe-cel can produce high remission rates in this pediatric patient population, including in patients with high-risk relapse and patients with primary CNS relapse. Consistent with our experience in the adult population, data show low rates of severe CRS and ICANS. We are now advancing into the Phase 2 portion of the study in line with our commitment to address the significant unmet need for new treatment options for pediatric patients with r/r ALL."

Dr. Will continued, "Insights from post-hoc analyses from our FELIX pivotal trial in r/r adult B-ALL explored various factors that may help to predict long-term patient outcomes. Specifically, investigators showed that detection of obe-cel in the blood three months post-treatment may be a predictor for long-term outcomes. They also identified characteristics of the product’s cell phenotype as additional factors for treatment outcomes."

He concluded, "In addition to Autolus’ presentations, we were highly encouraged by data from the real-world experience of the ROCCA consortium evaluating CAR T therapy for r/r adult ALL patients. These real world data mirror obe-cel’s safety profile observed in the pivotal FELIX trial with low single digits rates of CRS and ICANS as one of the differentiating characteristics of the therapy."

Abstract 740 – Poster presentation
Title: Treatment of pediatric patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) with obecabtagene autoleucel (obe-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy: preliminary findings from the Phase Ib/II CATULUS trial
Session Name: Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster II
Session Date and Time: December 7, 2025; 6:00 – 8:00pm ET
Session Room: Orange County Convention Center; West Halls B3-B4
Publication Number: 3337
Presenting Author: Sara Ghorashian, Consultant Haematologist at Great Ormand Street Hospital for Children (GOSH) and Honorary Associate Professor at UCL

Summary: CATULUS is a single-arm, open-label, multi-center study enrolling high-risk patients under age 18 with r/r B-ALL that is primary refractory, in high-risk first relapse, or in second or later relapse. The safety profile of obe-cel in pediatric patients was consistent with that previously reported in adults, with low rates of high-grade CRS and ICANS (both 8.7%). The ORR was high at 95.5% (n=21), with 90.9% (n=20) achieving complete response (CR). Twenty patients were in ongoing remission at data cut-off with a median follow-up of 8.8 months. These preliminary findings support further exploration of obe-cel in pediatric R/R B-ALL and planning for the Phase II expansion is underway.

Abstract 4060 – Poster presentation
Title: Chimeric antigen receptor (CAR) T-cell persistence at Month 3 predicts clinical outcomes in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with obecabtagene autoleucel (obe-cel)
Session Name: Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster III
Session Date and Time: December 8, 2025; 6:00 – 8:00pm ET
Session Room: Orange County Convention Center; West Halls B3-B4
Publication Number: 5118
Presenting Author: Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL)

Summary: Of 99 patients who achieved remission (CR/CRi) in the FELIX study, 79 (79.8%) had ongoing remission at month three following obe-cel infusion and comprised the subgroup of interest for the analyses. At month three post infusion, 60/79 patients (75.9%) had ongoing CAR T-cell persistence, while 19/79 patients (24.1%) had loss of persistence. In patients who remained in remission beyond month three, including those with deep MRD-negative remission and no post obe-cel SCT, ongoing CAR T-cell persistence at month three, measured by droplet digital PCR (ddPCR), was associated with longer event-free survival (EFS) and overall survival (OS) compared with loss of persistence. These results suggest that persistence status at month three may be a marker for predicting long-term outcomes following obe-cel treatment in patients with r/r B-ALL.

Abstract 4031 – Poster presentation
Title: Evaluation of commercially available chimeric antigen receptor (CAR) detection reagents for monitoring of CAR T-cell (CAR T) expansion and persistence in patients (pts) treated with obecabtagene autoleucel (obe-cel)
Session Name: Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Session Date and Time: December 6, 2025; 5:30 – 7:30pm ET
Session Room: Orange County Convention Center; West Halls B3-B4
Publication Number: 2367
Presenting Author: Rehan Hussain, Translational Medicine Senior Scientist

Summary: Measuring obe-cel expansion and persistence using flow cytometry (FC) is feasible with commercially available antibodies that directly target regions of the CAR construct, such as the G4S linker. These reagents show high correlation with anti-idiotype antibodies and provide a reliable method for tracking CAR expression in patients. Use of the G4S binder enabled tracking of CAR T expansion kinetics and phenotypic profiles in patients with different disease burdens. Reagents based on the CD19 protein, commonly used in other CAR T therapies, are unsuitable for obe-cel due to the unique features of the CAT19 binder, which limits effective detection.

Abstract 4429 – Oral presentation
Title: Impact of chimeric antigen receptor (CAR) product cell phenotypes on clinical outcomes following treatment with obecabtagene autoleucel (obe-cel)
Session Name: Acute Lymphoblastic Leukemias: Biomarkers, Molecular Markers, and Measurable Residual Disease in Diagnosis and Prognosis: Prognostic Genetic and Therapeutic Response Factors in Adult and Pediatric B-ALL
Session Date and Time: December 6, 2025; 10:00 – 10:15am ET
Session Room: Orange County Convention Center; W224CDGH
Publication Number: 33
Presenting Author: Benjamin Simpson, Ph.D., Bioinformatics & Data Management Principal Scientist, Autolus Therapeutics

Summary: Clinical data show the potential for obe-cel to produce long-term outcomes. This analysis details certain product features potentially affecting clinical outcomes, including how drug product phenotypes correlate with treatment outcomes following infusion with obe-cel. A higher percentage of central memory cells (Tcm) in the drug product samples was an independent predictor of positive clinical outcomes, including overall survival (OS), following obe-cel infusion. While the T-cell phenotype composition in the leukapheresis product (LP) was weakly correlated with that in the drug product, CD25+ HLADR+ CD4+ cells in the LP independently predicted less favorable clinical outcomes. However, other factors (e.g. tumor characteristics) are also likely to affect outcomes; therefore, further investigations are needed to better understand and predict favorable clinical outcomes, and to potentially guide studies of additional cell manipulations during CAR T-cell manufacturing.

(Press release, Autolus, DEC 8, 2025, View Source [SID1234661277])