daretabart (hu1418K322A) / St. Jude Children's Research Hospital, Essential Pharma, Renaissance Pharma - LARVOL DELTA

Phase I Study of 131I-Metaiodobenzylguanidine With Dinutuximab ± Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy Trial. (PubMed, J Clin Oncol) - "MIBG combined with dinutuximab was well tolerated with encouraging antitumor activity. Vorinostat added to this combination may augment responses in this heavily pretreated patient population."

Journal • P1 data • Fatigue • Neuroblastoma • Oncology • Pneumonia • Solid Tumor

Aragen completes commercial-scale GMP manufacturing of Daretabart in 9 months (Indian Pharma Post) - "Aragen, a leading global Contract Research, Development, and Manufacturing Organization (CRDMO), has successfully completed the technology transfer and commercial-scale GMP manufacturing of the first batches of Renaissance Pharma’s lead candidate, Daretabart, within nine months....The rare pediatric cancer therapy is now being manufactured at commercial scale at Aragen’s biologics facility in Bengaluru, India, following development of the cell line and initial process at the company’s Morgan Hill, California site....The manufacturing suite is capable of producing 60–70 batches annually at the 2KL scale, with a turnaround time of four to five days per batch at full capacity."

Commercial • Neuroblastoma

SHINE: A Safety and Efficacy Study of hu14 in High-Risk Neuroblastoma Patients (clinicaltrials.gov) - P2/3 | N=144 | Recruiting | Sponsor: Renaissance Pharma Ltd.

New P2/3 trial • Neuroblastoma • Oncology • Solid Tumor

Efficacy and Safety of Anti-GD2 Monoclonal Antibodies Combined with GM-CSF in Relapsed and Refractory Neuroblastoma: A Systematic Review and Meta-analysis (AAN 2026) - "Results Thirteen studies (n = 2008) were included, evaluating hu14.18K322A (n = 172) and dinutuximab (n = 1836). Common adverse events included fever (31%), pain (42%), and hypotension (21%), with variable heterogeneity across studies. Conclusions Anti-GD2 combined with GM-CSF shows promising efficacy and tolerable toxicity in relapsed and refractory neuroblastoma, though further studies are needed to confirm consistency across treatment settings."

Retrospective data • Review • Hypotension • Neuroblastoma • Solid Tumor • CSF2

Therapy for Children With Advanced Stage Neuroblastoma (clinicaltrials.gov) - P2 | N=153 | Completed | Sponsor: St. Jude Children's Research Hospital | Active, not recruiting ➔ Completed

Trial completion • Neuroblastoma • Oncology • Solid Tumor • MYCN

Direct cytotoxicity of hu14.18K.322A in high-risk neuroblastoma (AACR 2024) - "Taken together, our findings suggest that hu14.18K322A induces direct cell cytotoxicity in a subset of high-risk Neuroblastoma and synergizes well with standard chemotherapy drugs. Furthermore, our research highlights the complex nature of signaling pathways involved in hu14-mediated cytotoxicity that can be harnessed towards targeted therapy."

Neuroblastoma • Oncology • Solid Tumor

KAT6A and B inhibition increases efficacy of differentiation and GD2 targeting immunotherapy in neuroblastoma (AACR 2025) - "Reflecting the epigenetic reprogramming of these tumor cells, we observed that expression of GD2, a cell surface glycosphingolipid that is a target of antibody-based and CAR T cell therapies in neuroblastoma, was induced on GD2low neuroblastoma cells by treatment with retinoic acid plus PF-9363 both in vitro and in vivo, leading to increased effectiveness of anti-GD2 CAR T cell therapy in neuroblastoma. These studies nominate KAT6A/B inhibition as a novel approach to enhance the effectiveness of differentiation and GD2-immunotherapy in neuroblastoma and may be relevant for other tumors of neuro-ectodermal origin."

Clinical • IO biomarker • Neuroblastoma • Oncology • Solid Tumor • GATA3 • HOXB6 • KAT6A • MYCN • PHOX2B

Renaissance Pharma Limited, an Essential Pharma company, secures FDA Fast Track Designation and IND clearance for Daretabart (hu1418K322A) in high-risk neuroblastoma (GlobeNewswire) - "FDA clearance of IND application enables initiation of the SHINE Phase II/III clinical trial in relapse and refractory patients with high-risk neuroblastoma; First commercial-scale GMP batch of Daretabart (hu1418K322A) successfully manufactured; Programme builds on positive Phase II data which demonstrated overall survival rate of 86.0%...The designation recognises the significant unmet medical need in HRNB and will support more frequent interactions with the FDA throughout development, as well as eligibility for accelerated and rolling review."

Commercial • Fast track • IND • New P2/3 trial • Neuroblastoma

The Price of Survival: Global Inequities in Anti-GD2 Immunotherapy for Neuroblastoma. (PubMed, Pediatr Blood Cancer) - "Global access to anti-GD2 therapy is highly unequal. Strategic measures, including negotiations for reduced drug costs, research-based access, and WHO Essential Medicines List inclusion, could help address these disparities."

Journal • Neuroblastoma • Oncology • Solid Tumor

A pilot study of chemoimmunotherapy in the postconsolidation setting for high-risk neuroblastoma (ANBL19P1): A report from the Children's Oncology Group. (PubMed, Cancer) - "The administration of chemoimmunotherapy in the postconsolidation setting after tandem ASCT is feasible and tolerable. Future studies will be needed to define the population most likely to benefit from this augmented postconsolidation therapy."

Journal • Neuroblastoma • Oncology • Solid Tumor • Transplantation

A Phase II Study With a Safety Run-In of the Addition of N-803 to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Neuroblastoma • Oncology • Solid Tumor • CSF2

A Phase II Study With a Safety Run-In of the Addition of N-803 to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2 | N=54 | Not yet recruiting | Sponsor: St. Jude Children's Research Hospital | Initiation date: Jul 2025 ➔ Dec 2025

Trial initiation date • Neuroblastoma • Oncology • Solid Tumor • CSF2

A Phase II Study With a Safety Run-In of the Addition of N-803 to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2 | N=54 | Not yet recruiting | Sponsor: St. Jude Children's Research Hospital

New P2 trial • Neuroblastoma • Oncology • Solid Tumor • CSF2

Therapy for Children With Advanced Stage Neuroblastoma (clinicaltrials.gov) - P2 | N=153 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Dec 2024 ➔ Dec 2025

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

Survival Outcomes in Children with High-Risk Neuroblastoma Treated with Anti-GD2 Immunotherapy: A Single-Arm Systematic Review and Meta-Analysis (AAP-NCE 2024) - "Of these, 11 studies evaluated Dinutuximab, three studies evaluated Naxitamab, two studies hu14.18K322A, and two studies 3F8. This single-arm meta-analysis suggests that high-risk Neuroblastoma patients may benefit from anti-GD2 immunotherapy, with promising impacts on OS, PFS, and EFS."

Retrospective data • Review • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

Survival rates in high-risk neuroblastoma patients undergoing anti-GD2 immunotherapy: A single arm meta-analysis and systemic review (ESMO 2024) - "Among these, five studies assessed Dinutuximab; six assessed Dinutuximab beta; four investigated Naxitamab; two examined hu14.18K322A, and two evaluated 3F8. This single-arm meta-analysis suggests that high-risk Neuroblastoma patients may benefit from anti-GD2 immunotherapy, with promising impacts on OS, PFS, and EFS."

Retrospective data • Review • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • IL2

Hu14.18K.322A Causes Direct Cell Cytotoxicity and Synergizes with Induction Chemotherapy in High-Risk Neuroblastoma. (PubMed, Cancers (Basel)) - "In this study, we examined the direct cytotoxic effects of the humanized anti-GD2 antibody hu14.18K322A (hu14) on NB cell lines, by exploring the associated cell-death pathways...Our comprehensive investigation provides valuable insights into the multifaceted effects of hu14 on NB cells, shedding light on its direct cytotoxicity, cell-death pathways, and interactions with induction chemotherapy drugs. This study contributes to the evolving understanding of anti-GD2 antibody therapy and its potential synergies with conventional treatments in the context of NB."

Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

A pilot study of post-consolidation chemoimmunotherapy for high-risk neuroblastoma (ANBL19P1): A report from the Children's Oncology Group. (ASCO 2024) - P2 | "Therapy, administered every 28 days, consisted of temozolomide and irinotecan on Days 1-5, dinutuximab on Days 2-5, and sargramostim on Days 6-12 during Cycles 1-5; isotretinoin on Days 8-21 during Cycles 1-6... Administration of post-consolidation chemoimmunotherapy in pts who underwent tandem ASCT is tolerable and met pre-defined feasibility criteria. The impact of this approach on survival outcomes will be studied in a future COG trial."

Clinical • Bone Marrow Transplantation • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • Transplantation

Essential Pharma reaches agreement with AGC Biologics for late phase clinical manufacturing of its immunotherapy candidate for the treatment of high-risk neuroblastoma (GlobeNewswire) - "Essential Pharma...announced its rare disease business has signed a strategic agreement with AGC Biologics. As a leading global biopharmaceutical contract development and manufacturing organisation (CDMO), AGC Biologics will produce Hu1418K322A (Hu14.18), a humanised monoclonal antibody being developed for Essential Pharma for the treatment of high-risk neuroblastoma (HRNB). Under the agreement, AGC Biologics will support the process development, scale-up and manufacturing as Essential Pharma plans to commence clinical activities and ongoing regulatory agency interactions over the coming months."

Licensing / partnership • Neuroblastoma

Orphan Designation: Treatment of Neuroblastoma (FDA) - Date Designated: 04/08/2024

Orphan drug • Neuroblastoma

Essential Pharma acquires Renaissance Pharma Ltd with its clinical stage immunotherapy for the treatment of high-risk neuroblastoma (GlobeNewswire) - "Essential Pharma...announces that it has completed the acquisition of the entire issued share capital of Renaissance Pharma Ltd. Renaissance Pharma is a clinical stage pharmaceutical company focused on the development of life changing therapies in paediatric rare disease, with its lead asset being Hu14.18K322A (Hu14.18) - an immunotherapy currently in Phase II clinical development for the treatment of high-risk neuroblastoma (HRNB)....Essential Pharma will be responsible for clinical development and defining the optimal route for regulatory approval and eventual commercial launch of Hu14.18."

M&A • Neuroblastoma

Therapy for Children With Advanced Stage Neuroblastoma (clinicaltrials.gov) - P2 | N=153 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Dec 2023 ➔ Dec 2024

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

Renaissance Pharma launches today and announces the in-licensing of Hu14.18K322A (Hu14.18) from St. Jude Children’s Research Hospital for the treatment of High-Risk Neuroblastoma (GlobeNewswire) - "Renaissance Pharma Ltd...today launches and announces the signing of an exclusive license agreement with St. Jude Children’s Research Hospital ('St. Jude') for Hu14.18, a humanised antibody in development by St. Jude for the treatment of newly diagnosed high-risk neuroblastoma....Under the terms of the licensing agreement, Renaissance Pharma has secured exclusive development, manufacturing and commercialisation rights to US, Canada, Europe, China, Japan and Turkey."

Licensing / partnership • Neuroblastoma • Oncology • Solid Tumor

A multicenter cooperative group study of late effects after high-risk neuroblastoma: COG ALTE15N2—LEAHRN study. (ASCO 2023) - "ASCT conditioning included: Busulfan/Melphalan (BuMel) (18%), Carboplatin/Etoposide/Melphalan (CEM) (73%), Thiotepa/Cytoxan (19%), and total body irradiation (5%)...Use of carboplatin during ASCT was not assocoiated with increased ototoxicity risk for any category of cisplatin induction dose... The burden of late toxicity in HRNBL survivors is substantial. Anti-GD2 immunotherapy and isotretinoin do not appear to be associated with SMN, ototoxicity, growth failure, or RLD."

Clinical • Acute Myelogenous Leukemia • Cardiovascular • CNS Tumor • Congestive Heart Failure • Endocrine Disorders • Heart Failure • Hypertension • Infectious Disease • Neuroblastoma • Neuroendocrine Tumor • Oncology • Otorhinolaryngology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sarcoma • Solid Tumor • Transplantation

TREATMENT OF HIGH-RISK NEUROBLASTOMA USING DINUTUXIMAB CHEMOIMMUNOTHERAPY IN ALL CYCLES OF INDUCTION (ASPHO 2023) - P2 | "Background: The addition of an anti-GD2 monoclonal antibody (hu14.18K322A) to 6 cycles of Induction chemotherapy for the treatment of patients with high-risk neuroblastoma (HRNBL) led to an end of Induction (EOI) objective response rate (ORR; > partial response [PR]) of 93.8% in a single institution phase 2 clinical trial (NB2012, NCT01857934). The administration of DIN and GM-CSF to COG Induction for patients with HRNBL had an encouraging EOI ORR. A randomized phase 3 study of Induction chemoimmunotherapy is warranted."

CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • CSF2 • IL2