Danyelza (naxitamab-gqgk) / Y-mAbs Therap, Takeda, SciClone, Nobelpharma, INPHARMUS - LARVOL DELTA

The combination of naxitamab with or without sintilimab (anti-PD-1) for the treatment of refractory/progressive neuroblastoma: A prospective, non-randomized, multicenter trial. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06013618 The abstract will be released to the public on May 22, 2025 at 4:00 PM"

Clinical • Neuroblastoma • Oncology • Solid Tumor

Irinotecan, temozolomide and naxitamab plus GM-CSF (HITS) and naxitamab plus GM-CSF and ifosfamide, carboplatin, etoposide (NICE) for patients with relapsed or refractory high-risk neuroblastoma: A single center, open-label phase 2 clinical trial. (ASCO 2025) - "Clinical Trial Registration Number: EudraCT 2020-000538-17 The abstract will be released to the public on May 22, 2025 at 4:00 PM"

Clinical • P2 data • Neuroblastoma • Oncology • Solid Tumor • CSF2

Y-mAbs Reports First Quarter 2025 Financial Results and Recent Corporate Developments (GlobeNewswire) - "Total revenues for the quarter ended March 31, 2025 were $20.9 million, which was a 5% increase over the $19.9 million of total revenues for the quarter ended March 31, 2024, primarily driven by a $6.7 million increase in Ex-U.S. DANYELZA revenue, partially offset by a $5.2 million decrease in U.S. DANYELZA revenue and $0.5 million decrease related to license revenue recognized in the three months ended March 31, 2024....The Company’s Ex-U.S. DANYELZA net product revenues for the quarter ended March 31, 2025 were $7.5 million, representing an increase of $6.7 million from the same period in 2024."

Sales • Neuroblastoma

Safety of Naxitamab+GM-CSF in Combination With Induction Chemotherapy in High-Risk Neuroblastoma (ASPHO 2025) - "No new safety concerns have emerged: The safety profile of naxitamab when combined with induction chemotherapy was found to be manageable and acceptable."

Clinical • Combination therapy • Cardiovascular • Hypertension • Hypotension • Neuroblastoma • Pain • Pulmonary Disease • Solid Tumor • CSF2

111In/225Ac-Naxitamab: Theranostic anti-GD2 antibody in the management of Osteosarcoma - in-vitro evaluation (SNMMI 2025) - "The radiolabeling yield of 111In-Naxitamab was 99%; therefore, no further purification was needed. The specific activity was 27.75 MBq/nmol. The radiolabeling yield for 225Ac-Naxitamab was 30-40%, and after purification with a PD-10 column, radiochemical purity was 99%."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Y-mAbs Announces Update to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Neuroblastoma to Include Naxitamab-gqgk (DANYELZA) (GlobeNewswire) - "Y-mAbs Therapeutics, Inc...announced that naxitamab-gqgk (DANYELZA) is recommended by the National Comprehensive Cancer Network ('NCCN') Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a NCCN Category 2A treatment option for high-risk neuroblastoma."

NCCN guideline • Neuroblastoma

Dinutuximab BetaVersus Naxitamab in the Treatment of Relapsed/Refractory Neuroblastoma - Matching-Adjusted Indirect Treatment Comparison and Economic Evaluation in Mexico (ISPOR 2025) - "Compared to naxitamab, dinutuximab beta improves survival in patients with relapsed/refractory neuroblastoma and is cost-saving in the health care system in Mexico."

HEOR • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • MYCN

Dinutuximab Beta Versus Naxitamab in the Treatment of Relapsed/ Refractory Neuroblastoma – Matching-Adjusted Indirect Treatment Comparison and Economic Evaluation in the Private Health Insurance System in Brazil (ISPOR 2025) - "Compared to naxitamab, dinutuximab beta improves survival in patients with relapsed/refractory neuroblastoma and is cost-saving in private health insurance system in Brazil."

HEOR • Reimbursement • US reimbursement • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • MYCN

A first-in-human phase 1, multicenter, open-label study of M3554, a novel anti-GD2 antibody-drug conjugate (ADC), in patients with advanced solid tumors (AACR 2025) - P1 | "GD2 is a clinically validated target in pediatric neuroblastoma; however, currently approved anti-GD2 antibody treatments, such as dinutuximab and naxitamab, have been associated with severe adverse events (AEs) of pain, likely due to Fcγ receptor-mediated immune activation via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The study is currently recruiting and aims to enroll 52 patients in the dose escalation phase and 110 patients in the dose expansion phase (STS, n=80; GBM, n=30), across different global sites including, Japan, Belgium, France, and the US. Clinical trial information: NCT06641908."

Clinical • Metastases • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), the NCCN Drugs & Biologics Compendium (NCCN Compendium), the NCCN Radiation Therapy Compendium, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC) for Neuroblastoma, Version 1.2025. (NCCN)

NCCN guideline • Neuroblastoma

Porous Fe/Cu Nanoreactor with Dual Insurance Design for Precision Chemotherapy and Chemodynamic Therapy. (PubMed, Adv Healthc Mater) - "In this study, a porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) is developed for co-loading with the humanized 3F8 anti-GD2 disialoganglioside antibody (3F8) and the novel pyridazinone-based chemotherapeutic agent (IMB), forming a nanoreactor (3F8@FeCuNPs@IMB) for targeted chemotherapy and CDT...Furthermore, FeCuNPs act as peroxidase-like (POD) and glutathione oxidase-like (GSHOX) enzymes, catalyzing hydroxyl radical (•OH) generation and depleting excess GSH, enhancing CDT. The results in vitro and in vivo indicate that the dual insurance designed 3F8@FeCuNPs@IMB offers a promising prospect for a targeted, precise, and effective combination of chemotherapy and CDT against melanoma."

Journal • Reimbursement • US reimbursement • Melanoma • Oncology • Solid Tumor

A phase II trial of Naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in first complete remission. (PubMed, Clin Cancer Res) - P2 | "Naxitamab+GM-CSF is a good option to consolidate 1st CR of HR-NB patients, including those who did not undergo ASCT. Efforts to prevent CNS relapse are warranted."

Journal • P2 data • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • CSF2 • MYCN

Y-mAbs Reports Fourth Quarter 2024 Financial Results and Recent Corporate Developments (GlobeNewswire) - "The Company’s U.S. DANYELZA net product revenues for the quarter and year ended December 31, 2024 were $16.8 and $66.0 million, representing decreases of 12% and 3%, respectively, from the same periods in 2023. The decline in the U.S. DANYELZA net product revenues was driven by an unfavorable price mix for the quarter and year ended December 31, 2024, compared to 2023."

Sales • Neuroblastoma

Y-mAbs Announces Publication of Phase 2 Interim Results in Nature Communications (GlobeNewswire) - P2 | N=122 | NCT03363373 | Sponsor: Y-mAbs Therapeutics | "Y-mAbs Therapeutics, Inc...announced the publication of interim data from a Phase 2 clinical trial evaluating naxitamab with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with relapsed/refractory high-risk neuroblastoma in the journal Nature Communications. The primary endpoint in the prespecified interim analysis was overall response (per 2017 International Neuroblastoma Response Criteria). Overall response rate (ORR) was 50% (95% CI: 36-64%, N = 52), and CR and PR were observed in 38% and 12%, respectively. Among 26 responders (CR + PR) in the efficacy population, 58% had refractory disease, and 42% had relapsed disease. With the 95% CI lower limit for ORR exceeding 20%, the primary endpoint of overall response was met. Patients with evaluable bone disease had a 58% (29/50) bone compartment response (CR, 40%; PR, 18%). Bone marrow compartment response was 74% (17/23; CR, 74%)."

P2 data • Neuroblastoma

A phase II trial of Naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in first complete remission (Clin Cancer Res) - P2 | N=59 | NCT03033303 | "Fifty-nine HR-NB patients (53 stage 4, 6 stage 3) were enrolled 2/2017-7/2020. At 36 months, EFS/OS were 73%/93%, but 50/59 patients received post-protocol treatment (vaccine and/or DFMO). 6/18 relapses were isolated in the central nervous system (CNS). Longer time from diagnosis to enrollment was a significantly adverse prognostic factor (p=0.04). 21/59 patients took no isotretinoin. Treatment was tolerable allowing outpatient administration."

P2 data • Neuroblastoma

The anti-GD2 monoclonal antibody naxitamab plus GM-CSF for relapsed or refractory high-risk neuroblastoma: a phase 2 clinical trial. (PubMed, Nat Commun) - P2 | "Naxitamab-related Grade 3 adverse events included hypotension (58%) and pain (54%). Overall, naxitamab demonstrated clinically meaningful efficacy with manageable safety in patients with residual neuroblastoma in bone/BM."

Journal • P2 data • CNS Tumor • Hypotension • Neuroblastoma • Oncology • Orthopedics • Pain • Solid Tumor • CSF2

The anti-GD2 monoclonal antibody naxitamab plus GM-CSF for relapsed or refractory high-risk neuroblastoma: a phase 2 clinical trial (Nat Commun, Nature) - P2 | N=122 | NCT03363373 | Sponsor: Y-mAbs Therapeutics | "Among 26 responders (CR + PR) in the efficacy population (N = 52), 58% had refractory disease, and 42% had relapsed disease. Overall response rate (ORR) was 50% (95% CI: 36-64%), and CR and PR were observed in 38% and 12%, respectively. With the 95% CI lower limit for ORR exceeding 20%, the primary endpoint of overall response was met. Patients with evaluable bone disease had a 58% (29/50) bone compartment response (CR, 40%; PR, 18%). BM compartment response was 74% (17/23; CR, 74%). One-year overall survival and progression-free survival (secondary endpoints) were 93% (95% CI: 80-98%) and 35% (95% CI: 16-54%), respectively."

P2 data • Neuroblastoma

The anti-GD2 monoclonal antibody naxitamab plus GM-CSF for relapsed or refractory high-risk neuroblastoma: a phase 2 clinical trial (Nat Commun, Nature) - P2 | N=122 | NCT03363373 | Sponsor: Y-mAbs Therapeutics | "Among 26 responders (CR + PR) in the efficacy population (N = 52), 58% had refractory disease, and 42% had relapsed disease. Overall response rate (ORR) was 50% (95% CI: 36-64%), and CR and PR were observed in 38% and 12%, respectively. With the 95% CI lower limit for ORR exceeding 20%, the primary endpoint of overall response was met. Patients with evaluable bone disease had a 58% (29/50) bone compartment response (CR, 40%; PR, 18%). BM compartment response was 74% (17/23; CR, 74%). One-year overall survival and progression-free survival (secondary endpoints) were 93% (95% CI: 80-98%) and 35% (95% CI: 16-54%), respectively."

P2 data • Neuroblastoma

New treatments, new challenges: Nephrotoxicity associated to Naxitamab in patients with high-risk neuroblastoma (IPNA 2025) - "Eight of them (32%) had potential confounding factors (previous chemotherapy, ibuprofen or radiotherapy). All patients received prior chemotherapy and 2 developing chronic renal damage (CKD stage 2 and 3). Conclusions Short-and long-term follow-up, the systematic performance of ABPM, and the use of early markers of renal damage, could lead to a more efficient management of complications derived from this new treatment"

Adverse events • Clinical • Cardiovascular • Chronic Kidney Disease • CNS Tumor • Hypertension • Nephrology • Neuroblastoma • Oncology • Renal Disease • Solid Tumor

Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • MYCN

Case Report: Successful treatment of metastatic retinoblastoma with CNS involvement with anti-GD2 immunotherapy, intrathecal topotecan and reduced systemic chemotherapy. (PubMed, Front Pediatr) - "We present two cases of bilateral, metastatic RB, managed with the anti-GD2 mAb naxitamab following reduced intensity myeloablative chemotherapy and autologous stem cell transplant (ASCT) with intrathecal topotecan for MDD detected in the CSF. The patients remain disease-free 10 and 9 years after initial diagnosis. While additional studies are needed, the results suggest anti-GD2 mAbs and CNS-directed chemotherapy may improve long-term outcomes and reduce cytotoxicity for high-risk patients with RB."

Journal • Bone Marrow Transplantation • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • Transplantation

Clinical observation of naxitamab in high-risk neuroblastoma in the real-world setting: a single-center, prospective, observational study (ChiCTR) - P4 | N=40 | Sponsor: Children’s hospital of Fudan university; Children’s hospital of Fudan university

New P4 trial • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

Y-mAbs Provides Strategic Business Update and 2025 Priorities (GlobeNewswire) - "Anticipated 2025 Milestones: Part A data from GD2-SADA Phase 1 trial (Trial 1001) expected to be presented in the second quarter of 2025; GD2-SADA optimization data expected to be presented in the second quarter of 2025; Expect to present updates with respect to reprioritized SADA PRIT pipeline, including new high-value target indications and timelines, in the second quarter of 2025; Expect to dose first patient in CD38-SADA Phase 1 trial (Trial 1201) in the first quarter of 2025; Potential for marketing approval of DANYELZA in new ex-U.S. market in 2025."

Non-US regulatory • P1 data • Pipeline update • Trial status • Melanoma • Neuroblastoma • Non-Hodgkin’s Lymphoma • Sarcoma • Small Cell Lung Cancer

Gemcitabine and Ex Vivo Expanded Allogenic Universal Donor, TGFβi Natural Killer (NK) Cells with or Without Naxitamab (Danyelza) for the Treatment of Patients with Metastatic, GD2 Expressing, HER2 Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=42 | Recruiting | Sponsor: Margaret Gatti-Mays | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • HER-2

GD2-targeted theranostics of neuroblastoma with [64Cu]Cu/[177Lu]Lu-hu3F8. (PubMed, Eur J Nucl Med Mol Imaging) - "This study demonstrated that 64Cu-/177Lu- labelled hu3F8 could noninvasively evaluate the GD2 expression and effectively inhibit tumour growth in NB tumour models. The excellent therapeutic efficacy of [177Lu]Lu-DOTA-hu3F8 may be helpful for the clinical translation of this GD2-targeted theranostics approach in GD2-positive tumours."

IO biomarker • Journal • CNS Tumor • Embryonal Tumor • Neuroblastoma • Oncology • Solid Tumor