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])

On December 8, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that at the 2025 ESMO (Free ESMO Whitepaper) Asia Congress, updated results from the pivotal Phase III HARMONi-6 study (AK112-306) were shared in an oral presentation by Professor Shun Lu from Shanghai Chest Hospital. The study evaluates ivonescimab (a first-in-class PD-1/VEGF bispecific antibody) combined with chemotherapy versus tislelizumab combined with chemotherapy in first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC).

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Beyond the previously reported efficacy data presented at the ESMO (Free ESMO Whitepaper) 2025 Presidential Symposium and simultaneously published in The Lancet, this presentation further disclosed patient-reported quality of life outcomes based on the EORTC QLQ-C30 questionnaire.

Both prolonging survival and improving quality of life are core indicators for evaluating cancer treatments. The results published at 2025 ESMO (Free ESMO Whitepaper) Asia demonstrate that, compared to the tislelizumab-based regimen, treatment with ivonescimab plus chemotherapy not only significantly prolongs progression-free survival (PFS) but also offers better tolerability, enables higher treatment adherence, and provides patients to maintain better overall health status and quality of life over a longer period. These findings highlight the comprehensive clinical value of the ivonescimab regimen in delivering both survival and quality-of-life benefits for patients.

Quality of life (QoL) assessments from the HARMONi-6 study show that, compared with PD-1 inhibitor plus chemotherapy, ivonescimab plus chemotherapy not only significantly prolongs progression-free survival (PFS) but also helps patients maintain better overall health status. Time to deterioration in "Global Health Status/Quality of Life" was meaningfully delayed in the ivonescimab arm (HR = 0.94), indicating a trend toward reduced risk of QoL worsening versus the control group.
The ivonescimab-based regimen met the primary PFS endpoint versus the tislelizumab-based regimen, delivering a decisive, strongly positive outcome with both statistical significance and clear clinical benefit. PFS was substantially prolonged with ivonescimab plus chemotherapy compared with tislelizumab plus chemotherapy.
The hazard ratio for PFS between the ivonescimab and tislelizumab arms was 0.60 (P < 0.0001), corresponding to an absolute PFS improvement (ΔPFS) of 4.24 months (11.14 months vs. 6.90 months). This benefit was consistent across all PD-L1 expression subgroups.
The HARMONi-6 study enrolled 532 patients with well-balanced baseline characteristics. Among these patients, 92.3% had stage IV disease at enrollment. The squamous histology profile of the patients reflected real-world patterns, with approximately 63% of patients exhibiting the central squamous subtype (66.9% in the ivonescimab arm vs. 59.4% in the control arm). PD-L1 expression levels were also aligned with clinical expectations.

The results from the HARMONi-6 study further validate the breakthrough clinical value of the ivonescimab-plus-chemotherapy regimen compared to PD-1-plus chemotherapy regimen. The ivonescimab-plus chemotherapy regimen addresses a critical clinical gap when anti-angiogenic agents such as bevacizumab demonstrated severe safety considerations in the treatment of sq-NSCLC. Since ivonescimab’s initial approval in 2024, it has been evaluated in multiple clinical studies and used in real-world settings involving over 40,000 patients, where its transformative clinical benefits have been consistently demonstrated.

Across the immuno-oncology landscape, ivonescimab has shown clinical superiority to both PD-1 based treatments, which are currently the optimal standard of care for many cancers, and to also VEGF-targeted therapies in anti-angiogenesis based treatments.

In July 2025, based on the HARMONi-6 study results, the supplemental New Drug Application (sNDA) for ivonescimab in combination with chemotherapy as first-line treatment for sq-NSCLC was accepted for review by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA). Akeso’s partner, Summit Therapeutics, is currently carrying out a global multicenter Phase III HARMONi-3 study, evaluating ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy as first-line therapy for advanced NSCLC (both squamous and non-squamous subtypes).

(Press release, Akeso Biopharma, DEC 8, 2025, View Source [SID1234661288])

On December 8, 2025 HanchorBio Inc. (TPEx: 7827), a global clinical-stage biotechnology company advancing next-generation immunotherapies for oncology and autoimmune diseases, reported new first-in-human data from its ongoing Phase 1 monotherapy study of HCB101, a 3.5th-generation SIRPα-Fc fusion protein, in relapsed/refractory non-Hodgkin lymphoma (R/R NHL) at the 67th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), held December 6-9, 2025, in Orlando, Florida.

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The ASH (Free ASH Whitepaper) Annual Meeting is the world’s premier platform for clinical and translational advances in hematology. This year, over 8,200 abstracts were accepted globally, reaffirming ASH (Free ASH Whitepaper)’s position as one of the most competitive and influential medical congresses in hematology and oncology, with historical rejection rates of approximately 28%.

The accepted abstract (#3299) features a focused sub-analysis from HanchorBio’s ongoing multinational, open-label Phase 1 study (NCT05892718) evaluating HCB101 monotherapy across solid and hematologic malignancies, highlighting results from the R/R NHL cohort.

Key Results (data cutoff: October 14, 2025):

Thirteen patients with R/R NHL received HCB101 (5.12 – 24.0 mg/kg QW). No dose-limiting toxicities (DLTs) were observed, and the maximum tolerated dose (MTD) was not reached.
All treatment-related adverse events were Grade 1-2, confirming a cytopenia-sparing safety profile.
CD47 receptor occupancy (RO) reached ≥ 75-85% at 1.2 mg/kg and ≥ 90% at 8 mg/kg, demonstrating a broad pharmacologic window.
A confirmed partial response (PR) was observed in a patient with marginal zone B-cell lymphoma at 8.00 mg/kg, with -43.3% tumor reduction at Week 8 deepening to -89.5% by Week 16 at the same dose.
The results were presented by Alvin Luk, PhD, MBA, CCRA, President & Chief Medical Officer and Chief Executive Officer (U.S.) of HanchorBio during the ASH (Free ASH Whitepaper) 2025 poster session. Dr. Luk recently joined HanchorBio to lead the company’s global development of late-stage products and U.S. operations, advancing its next-generation immuno-oncology pipeline.

"Despite ASH (Free ASH Whitepaper)’s highly competitive selection process, the inclusion of HCB101 monotherapy data reflects the strong translational foundation and clinical potential of our SIRPα-CD47 backbone," said Scott Liu, Ph.D., Founder, Chairman, and Chief Executive Officer of HanchorBio. "We’re encouraged by the favorable safety and early signs of clinical activity seen in the heavily pretreated patient population. These findings validate the translational strength of our FBDB platform, and we look forward to engaging with the global hematology community as we expand HCB101 into hematologic malignancies and macrophage/T-cell combination strategies."

"Presenting these data at ASH (Free ASH Whitepaper) marks an important step for HanchorBio and our team," added Dr. Alvin Luk. "Moving from molecular design to early clinical validation highlights the potential of selective SIRPα-CD47 blockade to achieve both safety and effective immune activation in patients with limited treatment options."

About HCB101: A Differentiated CD47-SIRPα Blockade
HCB101 is a 3.5th-generation, affinity-optimized SIRPα-Fc fusion protein with an intact IgG4 Fc backbone, developed using HanchorBio’s proprietary FBDB platform. It is engineered for selective CD47 targeting with low red blood cell (RBC) binding, thereby avoiding the anemia and thrombocytopenia commonly associated with earlier anti-CD47 monoclonal antibodies, while preserving strong antibody-dependent cellular phagocytosis (ADCP) and innate-to-adaptive immune bridging. Key differentiators of HCB101:

Enhanced safety: Cytopenia-sparing profile, with no DLTs observed up to 30 mg/kg and receptor occupancy >90% at ≥1.28 mg/kg, supporting a broad therapeutic window.
Robust immune activation: Engineered to enhance ADCP and bridge innate-to-adaptive immunity, with evidence of durable immune-mediated tumor control in monotherapy.
Broad tumor applicability: Demonstrated activity across >80 PDX and CDX preclinical models, with early clinical signals in gastric cancer, TNBC, HNSCC, non-Hodgkin lymphoma, and ovarian cancer.
Clinical translation: Shows durable disease control as monotherapy and a 100% confirmed partial response rate (6/6) in 2L gastric cancer when combined with ramucirumab and paclitaxel, with additional confirmed responses in 1L TNBC and 2L HNSCC, substantially exceeding historical benchmarks.

(Press release, Hanchor Bio, DEC 8, 2025, View Source [SID1234661287])