On December 7, 2025 Genmab A/S (Nasdaq: GMAB) reported primary data from the pivotal Phase 3 EPCORE FL-1 study evaluating fixed duration EPKINLY (epcoritamab-bysp) in combination with rituximab and lenalidomide (EPKINLY + R2) in adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). The study showed that treatment with EPKINLY + R2 reduced the risk of disease progression or death by 79% (HR 0.21, 95% CI: 0.14-0.31, p<0.0001) compared to standard of care R2. Additionally, the overall response rate (ORR) in patients treated with EPKINLY + R2 was 95% (95% CI: 91.5, 97.4) compared to 79% in patients treated with R2 (95% CI: 73.6, 84.1; P<.0001). The EPCORE FL-1 study results were presented during an oral presentation (abstract 466) at the 67th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando, Florida, featured in the "Emerging Therapies and Immunotherapies in Blood Cancers" ASH (Free ASH Whitepaper) press briefing, and have been simultaneously published in The Lancet.

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"Patients with relapsed or refractory follicular lymphoma have historically had limited treatment options," said Lorenzo Falchi, M.D., Lymphoma Specialist, Department of Medicine, Memorial Sloan Kettering Cancer Center. "The EPCORE FL-1 results demonstrate that epcoritamab plus R2 is the first bispecific antibody-based, chemotherapy-free combination to show superior clinical benefit over standard of care in a Phase 3 trial, underscoring its potential to redefine the second-line treatment landscape for follicular lymphoma."

The EPCORE FL-1 study included patients with R/R FL following at least one prior line of treatment across a broad range of patient characteristics and disease risk factors. Among patients who were treated with EPKINLY + R2 at the second planned interim analysis (median follow-up, 14.8 months), 83% achieved a complete response (CR) (n=201/243, 95% CI: 77.4, 87.3) compared to a 50% CR rate among patients treated with R2 (n=122/245, 95% CI: 43.4, 56.2). The 12-month duration of response (DOR) was 89% (95% CI: 83.6, 93.0) versus 49% (95% CI: 38.8, 57.5) for patients treated with EPKINLY + R2 and R2, respectively.

The safety profile of EPKINLY + R2 in the EPCORE FL-1 study was consistent with the known safety profiles of the individual regimens (epcoritamab and R2). Grade 3 or 4 treatment-emergent adverse events (TEAE) were reported in 90.1% of patients treated with EPKINLY + R2 compared to 67.6% of patients treated with R2, the difference being primarily driven by higher rates of Grade 3 or 4 neutropenia (68.7% vs. 42.0%) and infections (33.3% vs. 15.1%). Fatal TEAEs occurred in 1.6% of patients treated with EPKINLY + R2 compared to 3.8% patients treated with R2. TEAEs leading to discontinuation occurred in 18.9% and 12.2% of patients treated with EPKINLY + R2 and R2, respectively. With the three step-up dosing regimen, CRS events were low grade and occurred in 26.3% of patients (21.2% Grade 1, 5.3% Grade 2).

"The pivotal results from the EPCORE FL-1 trial demonstrate the potential of epcoritamab, in combination with established therapies, to enable earlier intervention across sites of care and deliver improved outcomes for patients with relapsed or refractory follicular lymphoma," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "We remain committed to developing epcoritamab, as a monotherapy and in combination, as a potential core therapy for B-cell malignancies and as a therapeutic innovation that can shift the treatment paradigm."

In November 2025, the U.S. Food and Drug Administration (FDA) approved the combination of EPKINLY + R2 for the treatment of patients with relapsed or refractory FL after one or more lines of systemic therapy. EPKINLY is also approved in the U.S. to treat adults with relapsed/refractory FL after two or more prior treatments.

About the EPCORE FL-1 Trial
EPCORE FL-1 (NCT05409066) is a Phase 3 open-label interventional trial to evaluate the safety and efficacy of epcoritamab plus rituximab and lenalidomide (R2) versus R2 alone in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Patients were randomized to receive EPKINLY in combination with rituximab and lenalidomide (n=243) or rituximab and lenalidomide alone (n=245). Patients received EPKINLY in 28-day cycles for a total of 12 cycles or until disease progression or unacceptable toxicity, whichever occurred first. Efficacy was established based on the dual primary endpoints of progression free survival (PFS) and overall response rate (ORR) determined by Lugano 2014 criteria as assessed by Independent Review Committee (IRC). Additional efficacy outcome measures include complete response (CR) and duration of response (DOR).

About Follicular Lymphoma (FL)
Follicular lymphoma (FL) is typically an indolent, or slow-growing, form of non-Hodgkin lymphoma (NHL), that arises from B-lymphocytes. The second most common form of NHL, FL accounts for 20-30% of all NHL cases and is diagnosed in approximately 15,000 people in the U.S. every year.i,ii FL is considered incurable with current standard of care therapies.iii Patients often relapse, and with each relapse the remission and time to next treatment shorten.iv Over time, transformation to diffuse large B-cell lymphoma (DLBCL), an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.v

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.vi

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 7, 2025, View Source [SID1234661201])

On December 7, 2025 Eli Lilly and Company (NYSE: LLY) reported results from the Phase 3 BRUIN CLL-314 clinical trial evaluating Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, versus Imbruvica (ibrutinib), a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve or were BTK inhibitor-naïve. Pirtobrutinib met its primary endpoint of non-inferiority on overall response rate (ORR) compared to ibrutinib (87.0% [95% CI, 82.90-90.44] versus 78.5% [95% CI, 73.73-82.85]; p<0.0001) in the intent-to-treat (ITT) population. Pirtobrutinib also had numerically higher ORR rates and, while immature, progression-free survival (PFS) was also trending in favor of pirtobrutinib compared to ibrutinib across all populations, including a 76% reduction in the risk of disease progression or death (HR=0.239 [95% CI, 0.098-0.586]) in treatment-naïve patients, the subgroup with the longest follow-up.

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These data will be highlighted at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Orlando, Florida and simultaneously published in the Journal of Clinical Oncology.

"These data from BRUIN CLL-314 are both novel and clinically significant, demonstrating an improved overall response rate and a favorable trend in progression-free survival outcomes with pirtobrutinib compared to ibrutinib across all populations, including treatment-naïve patients where covalent BTK inhibitors are a cornerstone of treatment," said Jennifer A. Woyach, M.D., professor, hematologist-oncologist, and Director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. "BRUIN CLL-314 is the first randomized study to compare covalent and non-covalent BTK inhibitors and to directly compare any BTK inhibitors in the treatment-naïve setting, offering findings that are important for advancing the field and patient care. These efficacy results, along with pirtobrutinib’s safety profile, offer strong evidence on the role of pirtobrutinib earlier in the treatment course for patients with CLL or SLL."

The BRUIN CLL-314 study enrolled 662 patients who were randomized to receive pirtobrutinib (n=331) or ibrutinib (n=331), with the ITT population consisting of 225 treatment-naïve and 437 relapsed/refractory patients. The efficacy results utilize a June 10, 2025, data cutoff date.

The study achieved its primary endpoint demonstrating that pirtobrutinib was statistically non-inferior to ibrutinib in independent review committee (IRC)-assessed ORR for the ITT population, and results numerically favored pirtobrutinib (87.0% [95% CI, 82.90-90.44] versus 78.5% [95% CI, 73.73-82.85]; nominal p = 0.0035). Additionally, ORR consistently favored pirtobrutinib versus ibrutinib across all populations evaluated, including relapsed/refractory and treatment-naïve, as well as across pre-specified subgroups such as patients with and without 17p deletions, IGHV status and complex karyotype.

PFS, a key secondary endpoint, was not yet mature at this analysis but was trending in favor of pirtobrutinib compared to ibrutinib in the ITT (HR=0.569 [95% CI, 0.388-0.834]), relapsed/refractory (HR=0.729 [95% CI, 0.471-1.128]), and treatment-naïve (HR=0.239 [95% CI, 0.098-0.586]) populations, with a median follow-up of 22.0 months, 18.4 months, and 22.5 months, respectively. Among all subgroups, the largest PFS effect size was observed in the treatment-naïve subgroup, which had the longest follow-up at this data cut, with a 76% reduction in the risk of disease progression or death. A formal PFS analysis testing for superiority is planned at a future analysis. There was no detriment in overall survival (OS) (HR=0.961 [95% CI, 0.55-1.69]) for the ITT population.

The overall safety profile for patients treated with pirtobrutinib in BRUIN CLL-314 was similar to previously reported trials, and the most common treatment-emergent adverse events were similar between arms. Most adverse events (AE) of interest were lower with pirtobrutinib compared to ibrutinib, including atrial fibrillation/flutter (2.4% versus 13.5%) and hypertension (10.6% versus 15.1%). Fewer AE-related dose reductions (7.9% versus 18.2%) and discontinuations (9.4% versus 10.8%) were seen with pirtobrutinib versus ibrutinib.

"We are excited to share these compelling new findings for pirtobrutinib with the scientific community at ASH (Free ASH Whitepaper) and in the Journal of Clinical Oncology," said Jacob Van Naarden, executive vice president and president, Lilly Oncology. "These data build on additional results from the BRUIN development program and the recent FDA approval for pirtobrutinib in the post-covalent BTK inhibitor setting to reinforce the medicine’s potential to deliver meaningful benefit for people living with CLL or SLL across various disease settings."

As part of the Late-Breaking Abstract Session on Dec. 9, Lilly will also share results from the Phase 3 BRUIN CLL-313 study of pirtobrutinib versus chemoimmunotherapy in patients with treatment-naïve CLL/SLL without del(17p). These data were also selected to be highlighted as part of the ASH (Free ASH Whitepaper) Annual Meeting press program session on Dec. 8.

Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.

About BRUIN CLL-314
BRUIN CLL-314 is a Phase 3, randomized, open-label study of Jaypirca (pirtobrutinib) versus Imbruvica (ibrutinib) in patients with CLL/SLL who were either treatment-naïve, or who were previously treated and were BTK inhibitor-naïve. The trial planned to enroll 650 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or ibrutinib (420 mg orally, once daily). The primary endpoint is ORR as assessed by blinded IRC. Secondary endpoints include investigator and IRC-assessed PFS, duration of response (DoR) and event-free survival (EFS), and time to next treatment (TTNT), OS, safety and tolerability, and patient-reported outcomes (PRO).

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of slow-growing non-Hodgkin lymphoma that develop from white blood cells known as lymphocytes.4 CLL is one of the most common types of leukemia in adults.4 In the U.S., CLL accounts for about one-quarter of the new cases of leukemia and there will be approximately 23,690 new cases of CLL diagnosed this year.4,5 SLL is identical to CLL from a pathologic and immunophenotypic standpoint, with the main difference between them being the location of the cancer cells.4 In CLL, the cancer cells are present in the blood, and in SLL, the cancer cells are found in the lymph nodes.4

INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is indicated for the treatment of

Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.
Adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical trial benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. Across clinical trials, Grade ≥3 infections occurred (25%), most commonly pneumonia (20%); fatal infections (5%), sepsis (6%), and febrile neutropenia (3.8%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor for signs and symptoms, evaluate, and treat. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider withholding Jaypirca 3-7 days pre- and post-surgery based on surgery type and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%), developed. Grade 4 decreased neutrophils (15%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients taking Jaypirca. Across clinical trials, atrial fibrillation or flutter were reported in 3.4% of Jaypirca treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.6%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.4%). Cardiac risk factors such as hypertension or previous arrhythmias may increase risk. Monitor and manage signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea). Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Across clinical trials, second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients, most frequently non-melanoma skin cancer (4.4%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. If DILI is confirmed, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥30%) ARs in the pooled safety population of patients with hematologic malignancies (n=704) were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), calcium decreased (30%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients, with pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%) occurring in ≥2% of patients. Fatal ARs within 28 days of last dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%) and Select Laboratory Abnormalities (≥10%) (all Grades %; Grade 3-4 %): hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), fatigue (29; 1.6), musculoskeletal pain (27; 3.9), calcium decreased (19; 1.6), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), AST increased (17; 1.6), pneumonia (16; 14), bruising (16; -), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), ALT increased (11; 1.6), potassium increased (11; 0.8), alkaline phosphatase increased (11; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma from Single-Arm and Randomized Controlled Clinical Trials

Serious ARs occurred in 47-56% of patients across clinical trials. Serious ARs in ≥5% of patients in the single-arm trial were pneumonia (18%), COVID-19 (9%), sepsis (7%), febrile neutropenia (7%). Serious ARs in ≥3% of patients in the randomized controlled trial were pneumonia (21%), COVID-19 (5%), sepsis (3.4%). Fatal ARs within 28-30 days of last Jaypirca dose occurred in 8-11% of patients, most commonly due to infections (7-10%), including sepsis (5%), COVID-19 (2.7-5%), and pneumonia (3.4%).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 3.6-10%, treatment interruption in 42-51%, and permanent discontinuation of Jaypirca in 9-17% of patients. Permanent discontinuation in >1% of patients included second primary malignancy, pneumonia, COVID-19, neutropenia, sepsis, anemia, and cardiac arrythmias.

Most common ARs and Select Laboratory Abnormalities (≥20%) (all Grades %, Grade 3-4 %)–in a randomized controlled trial: neutrophil count decreased (54; 26), hemoglobin decreased (45; 10), platelet count decreased (37; 17), pneumonia (28; 16), ALT increased (25; 1.8), creatinine increased (25; -), calcium decreased (23; 0.9), sodium decreased (22; 0.9), bilirubin increased (21; 0.9), upper respiratory tract infections (21; 0.9); in a single-arm trial: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), platelet count decreased (30; 15), sodium decreased (30; -), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), dyspnea (22; 2.7), hemorrhage (22; 2.7), lipase increased (21; 7), alkaline phosphatase increased (21; -), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid using strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dose according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid using Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dose according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Use with Jaypirca increased their plasma concentrations, which may increase risk of ARs related to these substrates for drugs sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Specific Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca. Presence of pirtobrutinib in human milk is unknown. Advise women to use effective contraception and to not breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dose in these patients according to approved labeling.

PT HCP ISI MCL_CLL Q42025

Please see Prescribing Information and Patient Information for Jaypirca.

On December 6, 2025 Evaxion A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported new data demonstrating that its AML vaccine candidate, EVX-04, triggers strong specific T-cell responses and effectively prevents tumor growth in preclinical models.

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The data was presented today in an oral session at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida. Evaxion will discuss the new findings with scientists, doctors and potential business partners throughout the meeting.

"AML is characterized by high mortality rates and massive unmet medical need as current treatment options are limited and often insufficient. The new data confirms our belief that EVX-04 could significantly improve treatment options for AML patients. It is another example of the unique capabilities of AI-Immunology in finding novel targets enabling the design of therapies with transformative potential," says Birgitte Rønø, CSO of Evaxion.

Broad tumor coverage
Developed with our AI-Immunology platform, EVX-04 targets non-conventional ERV tumor antigens from the dark genome. These antigens are selectively expressed in specific tumors but absent in normal tissue, making them highly attractive cancer vaccine targets.

Using sequencing data from AML patients, the AI-Immunology platform first identified ERV tumor antigens and then mined these to determine smaller fragments with the potential for immune recognition. From the five million ERV antigens fragments discovered, AI-Immunology combined and selected 16 optimal sets of ERV fragments based on their cross-patient relevance and immunogenic potential. The new data confirms that all 16 ERV fragments included in EVX-04 elicit a specific immune response and that EVX-04 prevents tumor growth in preclinical tumor models.

The data-driven target selection ensures that EVX-04 provides broad tumor coverage regardless of immune and tumor ERV antigen differences across patients. Thus, EVX-04 is developed as an off-the-shelf vaccine preproduced and ready for immediate administration after diagnosis. The same concept is broadly applicable across cancers where immunotherapies remain inadequate and conserved immunogenic antigens can be identified.

About AML
AML is an aggressive hematologic malignancy characterized by the clonal expansion of undifferentiated myeloid precursor cells (AML blasts) in the bone marrow. The malignant proliferation leads to suppression of normal hematopoiesis, resulting in cytopenia, increased susceptibility to infections, bleeding, and fatigue (Döhner et al. 2022).

AML is the most frequent leukemia. It occurs across all age groups, however, it is predominantly a disease observed in older adults with a median age at diagnosis of 68 years.

Approximately 50% of AML patients are considered fit for intensive chemotherapy and stem cell transplantation. This combination is associated with a long-term overall survival rate of only 40% in younger patients and less than 10% in fit older patients.

For the approximately 50% not fit for intensive treatment, typically the elderly, the standard of care is low-intensity chemotherapy. Remissions are, however, short lived with a 3‐year overall survival rate at only 25% reported (Kantarjian et al. 2025).

About ERVs
ERVs are remnants of ancient viruses lying dormant in our genome. ERVs are often overexpressed in cancer but not in healthy tissue, making them visible to the immune system and hence promising targets for cancer vaccines. AI-Immunology is crucial in allowing the identification of therapeutically relevant ERV tumor antigens from genomic patient tumor data.

(Press release, Evaxion, DEC 6, 2025, View Source [SID1234661254])

On December 6, 2025 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported new positive data from its pivotal Phase 2 iMMagine-1 study of anitocabtagene autoleucel (anito-cel), in patients with relapsed or refractory multiple myeloma (RRMM). These data are being presented during an oral presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Saturday, December 6, 2025 at 2:45 p.m. ET. Anito-cel is partnered with Kite, a Gilead Company.

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October 7, 2025, is the data cutoff date for this presentation and the BLA submission. These data are for all 117 patients with a median follow-up of 15.9 months. All patients received a single infusion of anito-cel (target dose of 115×106 CAR+ viable T cells). Within the study population, 102 of 117 patients (87%) were triple refractory, 48 of 117 patients (41%) were penta refractory, 21 of 117 patients (18%) had extramedullary disease, and 47 of 117 patients (40%) had high risk cytogenetics. Patients received a median of three prior lines of therapy, with 65 of 117 patients (56%) having received three prior lines.

Overall response rate (ORR) was 96% (112/117) with a complete response/stringent complete response (CR/sCR) rate of 74% (86/117) and a very good partial response or higher (≥VGPR) rate of 88% (103/117), per Independent Review Committee (IRC) assessment. Of those evaluable for minimal residual disease (MRD) testing at the time of this data cut, 95% (91/96) achieved overall MRD negativity. Of the MRD evaluable group with sufficient follow up, 83% (54/65) sustained MRD negativity for >6 months, at a minimum of 10-5 sensitivity. Six-month progression-free survival (PFS) and overall survival (OS) rates were 93.1% and 95.7%, respectively; 12-month PFS and OS rates were 82.1% and 94.0%, respectively; 18-month PFS and OS rates were 67.4% and 88.0% respectively, and 24-month PFS and OS rates were 61.7% and 83.0% respectively. Median PFS and median OS have not been reached.

To date, no delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, no Guillain-Barré syndrome, and no immune effector cell-associated enterocolitis have been observed with anito-cel with all patients dosed more than 12 months ago.

Conclusions

Preliminary results from the Phase 2 iMMagine-1 study continue to demonstrate deep and durable responses with a predictable and manageable safety profile in a fourth-line or higher (4L+) RRMM population, including triple- and penta-refractory disease. Notably, no delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, no Guillain-Barré syndrome, and no immune effector cell-associated enterocolitis have been observed with anito-cel to date.

"These data are compelling and are an important advancement for patients living with multiple myeloma," said Dr. Krina Patel, Associate Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and iMMagine-1 and iMMagine-3 clinical investigator. "I am encouraged by the depth of responses in the iMMagine-1 study. For clinicians, we rely on therapies that deliver continued meaningful efficacy, a predictable safety profile, and reliable manufacturing. Anito-cel demonstrates that it could become a significant new treatment option in our efforts to improve outcomes for patients with multiple myeloma."

Rami Elghandour, Arcellx’s Chairman and Chief Executive Officer, said, "The data from iMMagine-1 continue to reinforce our belief that anito-cel is poised to become a category leader in treating multiple myeloma patients. Our plans for a 2026 commercial launch are well underway. We are building a world-class commercial and medical affairs organization to ensure broad patient access and physician support. We remain committed to a launch of unparalleled scale and impact to meet the needs of the myeloma community and to demonstrate the true potential of cell therapy. We could not have reached this transformational moment without the collaboration of the physicians and patients who participated in the iMMagine-1 study, our team members who go above and beyond the status quo every day, and our partners at Kite. We believe we can set a new standard for what’s possible with a CAR T treatment option for multiple myeloma. We have come so far together, and the best is yet to come as we sit on the precipice of helping so many more patients in need."

ASH Presentation Details
Title: Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma: Updated results from iMMagine-1

Speaker: Krina K. Patel, MD, MSc, MD Anderson Cancer Center
Session Name: 655. Multiple Myeloma: Cellular Therapies: Clinical Trial Advances in CAR T-Cell Therapy for Multiple Myeloma
Session Date: Saturday, December 6, 2025
Session Time: 2:00 p.m. – 3:30 p.m. ET
Presentation Time: 2:45 p.m. ET
Location: OCCC – West Hall E1
Publication Number: 256
Submission ID: abs25-4541

Webcast Event:

Arcellx will host a live webcast event with a panel of clinician experts to discuss the iMMagine-1 clinical results on Saturday, December 6, 2025 at 8:00 p.m. ET. The event will be accessible from Arcellx’s website at www.arcellx.com in the Investors section. A replay of the webcast will be archived and available for 30 days following the event.

About Multiple Myeloma

Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. MM is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.

About Anitocabtagene Autoleucel (anito-cel)

Anitocabtagene autoleucel (anito-cel, previously CART-ddBCMA) is the first BCMA-directed CAR T-cell therapy to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact binder known as the D-Domain. The small, stable D-Domain binder enables high CAR expression without tonic signaling and is designed to quickly release from the BCMA target. This combination may allow for the effective elimination of multiple myeloma cells without severe immunotoxicity. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

(Press release, Arcellx, DEC 6, 2025, View Source [SID1234661229])

On December 6, 2025 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported data from multiple studies demonstrating the clinical benefits of CASGEVY (exagamglogene autotemcel) in people ages 5 years and older living with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). The results, including the first presentation of clinical data from pivotal studies in children ages 5-11 years, and longer-term data from the pivotal studies of people with severe SCD and TDT ages 12 years and older, will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. CASGEVY is currently approved for eligible people ages 12 years and older with SCD or TDT in the United States, Great Britain, the European Union, the Kingdom of Saudi Arabia, the Kingdom of Bahrain, Kuwait, Qatar, Canada, Switzerland and the United Arab Emirates.

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"These results — the first clinical data ever presented on any genetic therapy for children ages 5-11 years with SCD — again demonstrate the transformative potential of CASGEVY," said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. "With dosing completed in the 5-11 age group and the Commissioner’s National Priority Voucher for CASGEVY in this population in hand, we are excited to begin global regulatory filings in the first half of next year and bring this potentially transformative therapy to eligible children as soon as possible."

"As an investigator in the clinical program for patients 12 years and older and after having real-world experience with CASGEVY as an early commercial treatment center, I have seen firsthand the transformative impact this therapy has had on older patients with SCD or TDT. I am excited to hopefully be able to offer this option to my younger patients soon, early in life, before some of the most devastating impacts of these diseases begin," said Haydar Frangoul, M.D., M.S., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital, Member of Vertex’s SCD Program Steering Committee, and presenting author of the 5-11 years old CASGEVY data at ASH (Free ASH Whitepaper).

First presentation of data in children ages 5-11 years treated with CASGEVY

In children with SCD, 11 patients have been dosed with CASGEVY in the Phase 3 CLIMB-151 clinical study, and all (4/4) patients with sufficient follow-up achieved the primary endpoint of being free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12).
No patient experienced a VOC following infusion with CASGEVY, with the longest duration of VOC-free of approximately two years (range 3.2–24.1 months).
In children with TDT, 13 patients have been dosed with CASGEVY in the Phase 3 CLIMB-141 clinical study, and all (6/6) patients with sufficient follow-up achieved the primary endpoint of transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin (Hb) of at least 9 g/dL (TI12).
Following CASGEVY infusion, 12/13 are transfusion free, with the longest duration of transfusion free just under two years (range 2.3–22.5 months).
One patient died from pneumonia in the setting of multi-organ failure due to severe veno-occlusive disease related to the busulfan conditioning.
The safety profile of CASGEVY in younger patients is consistent with myeloablative conditioning and autologous transplant in both SCD and TDT, as established in clinical studies in older patients.
Consistent with studies in older patients, children treated with CASGEVY have durable increases in fetal hemoglobin (HbF) and stable allelic editing.
Longer-term data for people with SCD and TDT ages 12 years and older treated with CASGEVY

New longer-term data from the pivotal clinical studies of CASGEVY in people 12 years and older will also be presented at ASH (Free ASH Whitepaper). These data, as of April 2025, continue to demonstrate the transformative, durable clinical benefits that CASGEVY provides to people living with SCD or TDT. In SCD, 100% of patients (45/45) achieved VF12 in either CLIMB-121 or the long-term follow-up study CLIMB-131, with a mean duration of VOC-free for 35.3 months (range 12.9–67.7 months). In TDT, 98.2% (55/56) achieved TI12 in either CLIMB-111 or CLIMB-131 with a mean duration of transfusion independence of 41.4 months (range 13–72.3 months). The safety profile remained consistent with myeloablative conditioning and autologous transplant in both SCD and TDT.

About Sickle Cell Disease (SCD)
SCD is a debilitating, progressive and life-shortening disease. It is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or "sickled" red blood cells. The clinical hallmark of SCD is vaso-occlusive crises (VOCs), which are caused by blockages of blood vessels by sickled red blood cells and result in severe and debilitating pain that can happen anywhere in the body at any time. SCD requires a lifetime of treatment and results in a reduced life expectancy. In the U.S., the median age of death for patients living with SCD is approximately 45 years. SCD patients report health-related quality of life scores well below the general population, and the lifetime health care costs in the U.S. of managing SCD for patients with recurrent VOCs is estimated between $4 and $6 million.

About Transfusion-Dependent Beta Thalassemia (TDT)
TDT is a serious, life-threatening genetic disease. It requires frequent blood transfusions and iron chelation therapy throughout a person’s life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In the U.S., the median age of death for patients living with TDT is 37 years. TDT patients report health-related quality of life scores below the general population and the lifetime health care costs in the U.S. of managing TDT are estimated between $5 and $5.7 million.

About CASGEVY (exagamglogene autotemcel)
CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT.

The use of CASGEVY in children ages 5-11 years is investigational.

About the CLIMB Studies
The Phase 1/2/3 open-label studies, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12-35 years with TDT or with SCD and recurrent VOCs. Patients will be followed for approximately two years after CASGEVY infusion in these studies. CLIMB-141 and CLIMB-151 are ongoing Phase 3 open-label studies, designed to assess the safety and efficacy of a single dose of exagamglogene autotemcel in patients ages 2-11 years with TDT or with SCD and recurrent VOCs. Enrollment and dosing are complete for the 5-11-years-old cohort in both studies with the plan to extend to ages 2-4 years.

Each patient will be asked to participate in the ongoing long-term, open-label study, CLIMB-131. CLIMB-131 is designed to evaluate the long-term safety and efficacy of CASGEVY in patients with up to 15 years of follow up after CASGEVY infusion.

Next steps for CASGEVY in children ages 5-11 years
Enrollment and dosing are complete for the 5-11 years cohort in both studies. Vertex expects to initiate global regulatory filings for this age group, including a supplemental Biologics License Application (sBLA) in the U.S., in the first half of next year. Vertex recently received a Commissioner’s National Priority Voucher for CASGEVY in the 5-11 years age group from the U.S. Food and Drug Administration to accelerate the review of the sBLA once submitted. Products under the program will be subject to a 1–2-month review clock from the start of FDA’s review and will also benefit from enhanced communication opportunities with the agency.

U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY

WHAT IS CASGEVY?

CASGEVY is a one-time therapy used to treat people ages 12 years and older with:

sickle cell disease (SCD) who have frequent vaso-occlusive crises or VOCs
beta thalassemia (β-thalassemia) who need regular blood transfusions
CASGEVY is made specifically for each patient, using the patient’s own edited blood stem cells, and increases the production of a special type of hemoglobin called hemoglobin F (fetal hemoglobin or HbF). Having more HbF increases overall hemoglobin levels and has been shown to improve the production and function of red blood cells. This can eliminate VOCs in people with sickle cell disease and eliminate the need for regular blood transfusions in people with beta thalassemia.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about CASGEVY?

After treatment with CASGEVY, you will have fewer blood cells for a while until CASGEVY takes hold (engrafts) into your bone marrow. This includes low levels of platelets (cells that usually help the blood to clot) and white blood cells (cells that usually fight infections). Your doctor will monitor this and give you treatment as required. The doctor will tell you when blood cell levels return to safe levels.

Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of platelet cells:
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of white blood cells:
fever
chills
infections
You may experience side effects associated with other medicines administered as part of the treatment regimen for CASGEVY. Talk to your physician regarding those possible side effects. Your healthcare provider may give you other medicines to treat your side effects.

How will I receive CASGEVY?

Your healthcare provider will give you other medicines, including a conditioning medicine, as part of your treatment with CASGEVY. It’s important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

After receiving the conditioning medicine, it may not be possible for you to become pregnant or father a child. You should discuss options for fertility preservation with your healthcare provider before treatment.

STEP 1: Before CASGEVY treatment, a doctor will give you mobilization medicine(s). This medicine moves blood stem cells from your bone marrow into the blood stream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.

During this step rescue cells are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated just in case there is a problem in the treatment process. If CASGEVY cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in the body, these rescue cells will be given back to you. If you are given rescue cells, you will not have any treatment benefit from CASGEVY.

STEP 2: After they are collected, your blood stem cells will be sent to the manufacturing site where they are used to make CASGEVY. It may take up to 6 months from the time your cells are collected to manufacture and test CASGEVY before it is sent back to your healthcare provider.

STEP 3: Shortly before your stem cell transplant, your healthcare provider will give you a conditioning medicine for a few days in hospital. This will prepare you for treatment by clearing cells from the bone marrow, so they can be replaced with the modified cells in CASGEVY. After you are given this medicine, your blood cell levels will fall to very low levels. You will stay in the hospital for this step and remain in the hospital until after the infusion with CASGEVY.

STEP 4: One or more vials of CASGEVY will be given into a vein (intravenous infusion) over a short period of time.

After the CASGEVY infusion, you will stay in hospital so that your healthcare provider can closely monitor your recovery. This can take 4-6 weeks, but times can vary. Your healthcare provider will decide when you can go home.

What should I avoid after receiving CASGEVY?

Do not donate blood, organs, tissues, or cells at any time in the future
What are the possible or reasonably likely side effects of CASGEVY?

The most common side effects of CASGEVY include:

Low levels of platelet cells, which may reduce the ability of blood to clot and may cause bleeding
Low levels of white blood cells, which may make you more susceptible to infection
Your healthcare provider will test your blood to check for low levels of blood cells (including platelets and white blood cells). Tell your healthcare provider right away if you get any of the following symptoms:

fever
chills
infections
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
These are not all the possible side effects of CASGEVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of CASGEVY

Talk to your healthcare provider about any health concerns.

Please see full Prescribing Information including Patient Information for CASGEVY.

(Press release, Vertex Pharmaceuticals, DEC 6, 2025, View Source [SID1234661228])