Refractory Neuroblastoma

TAIPEI and SAN DIEGO, Sept. 13, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that its new drug Silmitasertib (CX-4945) was granted a rare pediatric disease designation (RPDD) by US FDA for the treatment of neuroblastoma. This is the recognition obtained again after Silmitasertib (CX-4945) received RPDD in medulloblastoma from the FDA in July 2020, demonstrating the great potential of Silmitasertib (CX-4945) in the development of treatments for rare pediatric cancers. Silmitasertib is a first-in-class small molecule drug that targets the CK2 protein and acts as a CK2 inhibitor that exhibited antitumor activity in pre-clinical study of neuroblastoma. The RPD designation will qualify the drug for the priority review voucher (PRV) program meant to encourage development of novel therapies for rare pediatric diseases. Silmitasetib has previously granted 1 RPD and 3 orphan drug designations (ODD) by the FDA. "The RPD designation offers sponsors the additional incentive by requesting priority review vouchers (PRVs) for their future marketing applications, and this approach encourages the drug development for the treatment of rare pediatric diseases," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. Neuroblastoma, an embryonic tumor of the peripheral sympathetic nervous system, is the third most common pediatric cancer and the most common cancer in infants. It is mostly diagnosed in infancy at an average of 1 to 2 years old. There are an estimated 700 to 800 new cases of neuroblastoma each year in the United States. While low and intermediate-risk neuroblastoma have a very high rate of survival, high-risk neuroblastoma has a 5-year survival rate of about 50%, and it has a high likelihood of recurrence even with intense multimodal treatments. There is currently no standard treatment for patients with relapsed/refractory neuroblastoma. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Study is the first to identify malignant cells responsible for relapse in high-risk neuroblastoma PHILADELPHIA, Aug. 15, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) announced a significant breakthrough in understanding chemotherapy resistance in high-risk neuroblastoma, a common and potentially deadly childhood cancer arising within the peripheral nervous system. The study marks the first time that researchers identified malignant cells responsible for relapse in neuroblastoma and offers insights for potential new therapeutic targets. The findings were published recently in the journal Cancer Discovery. In the United States, about 800 new cases of neuroblastoma are diagnosed each year, more often in boys. The average age of diagnosis is about 18 months but occasionally the disease is seen in teens and young adults. Neuroblastoma has a high mortality rate and despite extensive studies, the malignant cells responsible for relapse were not well understood until this research. This study is part of research conducted by the Human Tumor Atlas Network (HTAN), a National Cancer Institute (NCI) Moonshot initiative led by Kai Tan, PhD, an investigator in the Center for Childhood Cancer Research at CHOP, and a multi-institutional NCI Program Project Grant (PPG) focused on neuroblastoma and led by John M. Maris, MD, a study co-author and pediatric oncologist at CHOP. "This study is a major step forward in identifying why neuroblastoma is so difficult to cure," said Maris, who also holds the Giulio D'Angio Chair in Neuroblastoma Research. "Targeting specific cells and pathways responsible for relapse empowers us to chart a new path forward, allowing us to develop potentially safe and effective treatments for children and families battling this aggressive cancer." The CHOP research team employed advanced single nucleus RNA sequencing (snRNA-seq) and bulk whole genome sequencing techniques to analyze the genetic and transcriptional profiles of tumor samples from 20 pediatric patients with high-risk neuroblastoma who were treated between 2007 and 2022. The samples included matched diagnostic biopsies and definitive surgery specimens obtained after several cycles of induction chemotherapy. "HTAN played a crucial role in generating the powerful multi-omics dataset that led to the hypothesis we tested in this paper," said Tan, who is also a professor in the Department of Pediatrics at CHOP and spearheads CHOP's participation in the HTAN. "It supports the broader application of the identified therapeutic targets and resistance mechanisms in high-risk neuroblastoma." The investigators discovered and validated the fact that neuroblastoma can evade chemotherapy by becoming dormant and not constantly multiplying—a major hallmark of cancer. Thus, these "non-cycling" cells are resistant to chemotherapy, which is designed to kill cells that are actively multiplying. These "persister cells" can hide in the body for months or even years and see a relapse when they later awaken. To validate their findings and enhance the analysis, the researchers leveraged independent post-induction chemotherapy data generated by other groups in the HTAN. By assessing the primary study's findings within the context of other datasets, the researchers ensured consistency and reliability in the transcriptional subtypes they identified. For example, researchers were able to study the expression level of the MYCN gene and its relationship to the transcriptional subtypes. This provided several insights into the biology of neuroblastoma and offered promising new therapies. As a result, Maris noted that the NCI-funded neuroblastoma PPG is actively pursuing research and that several immunotherapeutic strategies to eliminate persister cells are already being tested. "This research could have far-reaching implications beyond neuroblastoma, as it enhances our understanding of chemotherapy resistance mechanisms," said Liron Grossmann, MD, MSc, the study's lead author, who managed the research during his Hematology-Oncology fellowship at CHOP, and is currently a Senior Attending Physician at Sheba Medical Center in Israel. "We've gained invaluable insights that can inform new approaches for various cancers, potentially improving treatment outcomes and reducing relapse rates across a broad spectrum of malignancies." The study was supported by Human Tumor Atlas Network U2C CA233285 and the National Cancer Institute (NCI) grants R35 CA220500, P01 CA217959, and K08 CA266914. This work was also supported by the Sheba Medical Center Physician-Scientist Program, the Giulio D'Angio Endowed Chair, the Richard & Sheila Sanford Endowed Chair and the Patricia Brophy Endowed Chair. Grossmann et al. "Identification and characterization of chemotherapy resistant high-risk neuroblastoma persister cells." Cancer Discovery. Online July 31, 2024. DOI: 10.1158/2159-8290.CD-24-0046. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Jennifer Lee Children's Hospital of Philadelphia (267) 426-6084 [email protected] SOURCE Children's Hospital of Philadelphia

QARZIBA is indicated to treat high-risk neuroblastoma in patients aged 12 months and above. Credit: Kateryna Kon/Shutterstock. Ligand Pharmaceuticals has announced a definitive agreement for the acquisition of the complete outstanding shares of Austria-based biopharmaceutical company APEIRON Biologics in a $100m cash deal. The deal also includes future payments based on commercial and regulatory milestones. The strategic move will grant Ligand royalty rights to QARZIBA (dinutuximab beta), a treatment for high-risk neuroblastoma in patients aged 12 months and above. It is indicated for those who have responded to induction chemotherapy, undergone myeloablative therapy and stem cell transplantation, and with a history of relapsed or refractory neuroblastoma with or without residual disease. APEIRON co-developed QARZIBA, which received the European Medicines Agency approval in 2017. This therapy is currently available in more than 35 countries. See Also: How will a Labour government support the UK clinical trials industry? TLC-2716 by OrsoBio for Familial Hypercholesterolemia (Type II Hyperlipoproteinemia): Likelihood of Approval The company receives royalties on the product’s net sales outside mainland China from Recordati and within mainland China from BeiGene. Ligand will make further payments based on commercial and regulatory milestones, with potential payments up to $28m by either 2030 or 2034 on QARZIBA royalties exceeding preset thresholds. The agreement received unanimous approval from the board of directors of Ligand and the supervisory board of APEIRON. The acquisition will conclude in July 2024. Ligand is also investing $4m in invIOs Holding, an APEIRON spin-off, under a stock purchase agreement. This funding will support the research and development of three early-stage immuno-oncology assets. Ligand CEO Todd Davis stated: “The addition of QARZIBA to our commercial royalty portfolio further supports our growth strategy to invest in high-value medicines that deliver significant clinical value and generate predictable and long-term revenue streams for our investors. “QARZIBA is the only immunotherapy for high-risk neuroblastoma marketed across Europe and in other parts of the world. We believe this drug will be a meaningful contributor to our royalty revenue, which is now driven by a diversified portfolio of 12 key commercial-stage products.”