The U.S. Food and Drug Administration has approved Myrio Therapeutics' Investigational New Drug application for PHOX2B PC-CAR T, enabling the first human trials of a novel chimeric antigen receptor T-cell therapy targeting neuroblastoma. The approval, granted on May 7, 2025, represents a significant milestone in pediatric oncology and validates Myrio's innovative approach to solid tumor immunotherapy.
Breakthrough Technology Targets Previously Inaccessible Protein
The therapy targets PHOX2B, a functionally relevant protein identified in neuroblastoma cells by Prof. John Maris at a leading children's hospital in Philadelphia. Using Myrio's proprietary Retained Display (ReD™) technology, researchers developed a highly specific binder to the PHOX2B peptide-major histocompatibility complex (p-HLA) target.
Unlike conventional binders that target a single HLA allotype, Myrio's binder can recognize the peptide across multiple HLA allotypes—a phenomenon called "breaking HLA restriction." This breakthrough capability offers the potential to treat a broader population of patients using the same immunotherapy, addressing a key limitation in current CAR-T approaches for solid tumors.
The groundbreaking approach was detailed in a Nature publication titled "Targeting of intracellular oncoproteins with peptide-centric CARs" in November 2023, demonstrating the scientific rigor behind the development.
Addressing Critical Unmet Medical Need
Neuroblastoma represents the most common tumor of the sympathetic nervous system, accounting for 97% of such cases, and is the most common malignancy of infancy with a median age of diagnosis of 17 months. The annual incidence in the United States is approximately 800 cases, representing 15% of pediatric cancer-related deaths.
"The current treatment options for patients with high-risk neuroblastoma are associated with low response rates and significant toxicities and the development of new treatment options is desperately needed," said Prof. Maris. "This investigational immunotherapy has the potential to be a major advance for patients suffering from this devastating disease."
Despite overall increases in five-year event-free survival rates, these improvements have come at the cost of significant life-threatening treatment-related side effects. Subgroup analysis reveals a stark contrast between high cure rates for benign low-risk forms and minimal improvement in high-risk groups, highlighting the urgent need for novel therapeutic approaches.
Clinical Trial Design and Timeline
The Phase 1 clinical trial, entitled "PHOX2B Peptide-Centric Chimeric Antigen Receptor Autologous T cells (PHOX2B PC-CAR T) for Relapsed Neuroblastoma," will be conducted under Prof. Maris's leadership. The first patient enrollment is anticipated for mid-2025, marking a critical transition from preclinical development to human testing.
This represents the first time a Myrio-developed binder will enter human trials, serving as a major validation of the company's technology platform focused on developing bispecific binders to Human Leukocyte Antigens for solid tumor treatment.
Platform Technology with Broader Implications
Myrio's ReD™ platform facilitates the discovery of stable, human single-chain variable fragment (scFv) binders against peptides presented on solid cancer cell surfaces by the HLA complex. These binders demonstrate utility in both bispecific T-cell engager and CAR-T formats to direct cytotoxicity against peptide-HLA specific target tumor cells.
Dr. Graeme Wald, CEO of Myrio Therapeutics, described the approval as "a major step forward for Myrio" and "the culmination of many years of work at Myrio in developing bispecific binders to Human Leukocyte Antigens for the treatment of solid tumours."
The technology's potential extends beyond neuroblastoma, as the platform can theoretically target any intracellular oncoprotein presented on the cell surface through HLA complexes, opening new avenues for treating previously "undruggable" targets in solid tumors.
