On December 8, 2025 Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) ("Galmed" or the "Company"), a clinical-stage biopharmaceutical company for liver, cardiometabolic diseases and GI oncological therapeutics, reported the presentation of a late breaking abstract for its lead drug candidate, Aramchol at HEP-DART 2025 Meeting.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Previously, Galmed announced that Aramchol significantly enhances Bayer’s regorafenib effect in GI cancer models to kill GI tumor cells. SCD1 inhibition augments regorafenib (Stivarga) activity through ATM-AMPK-autophagy signaling. These findings provide the scientific and translational rationale for the initiation of a Phase 1/2 clinical trial of the combination of standard of care regorafenib with the SCD1 inhibitor Aramchol in HCC and other GI cancers. Once a recommended Phase 2 dose is found, Galmed plans to add a dose expansion cohort that will include Metformin and will evaluate the 3-drugs’ combination efficacy.

"The acceptance of our late-breaking abstract to the HEP-DART prestigious scientific meeting underscores the significance of our data. The research work presented has directly informed VCU Massey Comprehensive Cancer’s decision to initiate an investigator-initiated Phase 1/2 clinical trial of Aramchol and regorafenib in advanced GI cancers, including HCC, with planned enrollment starting in 2026. Positive findings would not only lay the groundwork for subsequent accelerated clinical development of Aramchol in key three GI cancers, but could potentially expand Galmed’s oncology pipeline and create value for investors and stakeholders" said Allen Baharaff, CEO of Galmed Pharmaceuticals.

About HEP-DART

HEP-DART started in 1995 as the "FIRST International Conference on Therapies for Viral Hepatitis." Since its inception in 1995, HEP-DART has provided a cutting-edge platform for tackling challenges in drug development for viral hepatitis and chronic liver disease. The aim of HEP-DART 2025 is to assemble clinicians, researchers, and physician together to advance our knowledge of the ongoing drug development processes in the treatment of viral hepatitis, fibrosis, Metabolic Dysfunction-Associated Steatohepatitis MASH), and hepatocellular carcinoma (HCC) and to provide the scientific community with an increased understanding of the current and future challenges in therapeutics for liver infection, disease and cancer.

(Press release, Galmed Pharmaceuticals, DEC 8, 2025, View Source [SID1234661258])

On December 8, 2025 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported the presentation of final data from its Phase 1/1b trial of soquelitinib in patients with T cell lymphoma in an oral session at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is taking place December 6-9, 2025 in Orlando, FL. The presentation highlights preclinical and clinical data supporting the development of soquelitinib in oncology and immune and inflammatory diseases, including data detailing its mechanism of action.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The T-cell lymphomas are devastating diseases, associated with dismal outcomes, and are thus an area of high unmet need," said Ryan Wilcox, M.D., Ph.D., Associate Professor of Internal Medicine, University of Michigan Medical School. "In the relapsed/refractory setting, complete and durable responses are rarely achieved with currently available agents. The Phase 1 data demonstrate impressive progression free and overall survival in relapsed/refractory patients treated with soquelitinib. Several patients experienced complete and durable responses, some of which were maintained on therapy more than two years. For most relapsed/refractory PTCL patients, an overall survival less than 6 months is anticipated. In the phase 1 study, median progression free survival was 6.2 months and median overall survival exceeded 2 years. These results provide the foundation for the ongoing registration Phase 3 trial in relapsed/refractory peripheral T cell lymphoma."

The trial enrolled 75 patients (27 in dose escalation portion and 48 in dose expansion portion) with various T cell lymphomas, including peripheral T cell lymphoma (PTCL), T follicular helper cell lymphoma (TFHC), natural killer cell T cell lymphoma (NKTCL), cutaneous T cell lymphoma (CTCL), anaplastic large cell lymphoma (ALCL) and adult T cell lymphoma/leukemia (ATLL). The median number of prior therapies was 3 (range 1-18), with only 31% achieving an objective response to their most recent prior therapy. In the dose escalation portion, patients received a twice-daily dose of soquelitinib of 100 mg, 200 mg, 400 mg or 600 mg, and the 200 mg twice-daily dose was selected for the dose expansion portion based on biomarker studies indicating that doses of 200mg or higher achieved complete occupancy of the ITK target with the drug.

Key highlights from the data supporting the ongoing registration Phase 3 trial in relapsed/refractory PTCL include:

No dose limiting toxicities or significant adverse events were observed in any patients in all dose cohorts up to 600 mg twice-daily, including no myelosuppression or immunosuppression
Objective and durable tumor responses were seen in the 200 mg twice-daily cohort (N=36) with 6 patients experiencing complete responses
In the 200 mg twice-daily cohort, it was determined that patients with between ≥1 and ≤3 prior therapies and an adequate peripheral blood lymphocyte count (N=24) were most likely to be responders to therapy. In this patient population:
Objective responses were seen in 9 of 24 patients including 6 complete responses and 3 partial responses
Median progression free survival (PFS) was 6.2 months, including an 18-month PFS of 30%
Median overall survival (OS) was 28.1 months, including a 24-month OS of 67%

Key highlights from the data supporting soquelitinib’s mechanism of action (Th1 skewing and blocking Th2 and Th17 differentiation) and use in immune and inflammatory diseases include:

In vitro studies demonstrated that at appropriate doses, soquelitinib produces Th1 skewing, which is an immunologic property resulting from the blockade of Th2 differentiation and a shift to Th1
Biomarker studies evaluating blood samples and tumor biopsies showed an increase in Th1 in blood and tumor samples and a reduction in serum IL-5, consistent with inhibiting Th2 and Th17 cells
For 6 patients, paired tumor biopsies were compared at baseline and day 8 and showed an increase in intratumor Th1 cells with treatment analyzed using RNA sequencing

"The data presented at ASH (Free ASH Whitepaper) provides foundational information for the future development of soquelitinib and our ITK platform across oncology, immune disease and inflammation," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "In oncology, the data show that soquelitinib could be a new treatment option for T cell lymphomas, including in patients with advanced, aggressive disease. The data not only support our ongoing registration Phase 3 trial in PTCL, but also show immunobiological effects that demonstrate soquelitinib’s mechanism of action of affecting T cell differentiation via ITK inhibition. The mechanism operates upstream in T cell signaling pathways, which may indicate that resistance pathways are unlikely to evolve."

Dr. Miller added, "Outside of oncology, we are focused on the development of soquelitinib in atopic dermatitis and evaluating its potential in a broad range of immune and inflammatory diseases. We plan to present additional data from extension cohort 4 of our Phase 1 atopic dermatitis trial in January and initiate a Phase 2 trial in this indication in early Q1 2026."

Corvus is currently enrolling patients in a registration Phase 3 clinical trial of soquelitinib in patients with relapsed/refractory PTCL at multiple clinical sites. This randomized controlled trial is anticipated to enroll a total of 150 patients with relapsed/refractory PTCL and is evaluating soquelitinib versus physicians’ choice of either belinostat or pralatrexate. The primary endpoint of the trial is progression free survival. There are no FDA fully approved agents for the treatment of relapsed/refractory PTCL, and the FDA has granted soquelitinib Orphan Drug Designation for the treatment of T cell lymphoma and Fast Track designation for treatment of adult patients with relapsed or refractory PTCL after at least 2 lines of systemic therapy. The Company anticipates reporting interim data from the Phase 3 trial in late 2026 and completing the trial in 2027.

The ASH (Free ASH Whitepaper) oral presentation slides are available on the Publications and Presentations page of the Corvus website.

(Press release, Corvus Pharmaceuticals, DEC 8, 2025, View Source [SID1234661275])

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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])