BrainChild Bio to Advance BCB-276 CAR T-cell Therapy for Pediatric Brain Tumors

BrainChild Bio, Inc., an innovative biotechnology firm, is making significant strides in the development of CAR T-cell therapies targeting tumors in the central nervous system (CNS). The company recently unveiled its plan to advance BCB-276, an autologous CAR T-cell therapy aimed at the immune checkpoint B7-H3, specifically for treating diffuse intrinsic pontine glioma (DIPG), a devastating and currently incurable pediatric brain tumor.

The company's primary objective is to accelerate the development of BCB-276 through a pivotal registration trial. The aim is to expedite the submission of a Biologics License Application, focusing on children and young adults affected by DIPG. This clinical strategy emerged from a meeting with the U.S. Food and Drug Administration (FDA), where they received the green light to proceed directly to a multi-center Phase 2 pivotal clinical trial. This accelerated path is based on promising preliminary safety and efficacy data from a Phase 1 clinical trial on SCRI-CARB7H3(s), the research product that leads to BCB-276. The findings from this trial were recently published in Nature Medicine.

BrainChild Bio's founder and Chief Scientific Officer, Dr. Michael Jensen, expressed optimism about the progress, stating that the clinical development plan provides a clear path to address the critical needs of children and families dealing with DIPG. The company is keen on collaborating with the FDA to generate the necessary data for a successful Investigational New Drug (IND) submission, with the goal of initiating the pivotal trial for BCB-276 by the end of 2025.

Seattle Children’s initiated a Phase 1 clinical trial named BrainChild-03, focusing on a single-center, dose-escalation study of repetitive intracerebroventricular (ICV) dosing of B7-H3 targeted CAR T therapy. This trial involves children with recurrent or refractory CNS tumors, including DIPG. The clinical data from 21 DIPG patients revealed that 12 received CAR T treatment post-disease progression, while nine began treatment prior to progression. The treatments showed favorable safety profiles, with repetitive ICV dosing tolerable without the need for lymphodepleting chemotherapy. The initial efficacy analysis showed that the median survival time from diagnosis for all treated patients was 19.8 months. Notably, three patients who began CAR T treatment before disease progression survived 44.6, 45.6, and 52.5 months from diagnosis. These results suggest a significant improvement in overall survival compared to the current standard treatment, which offers a median survival time of just 8-11 months.

Dr. Jeff Sperring, CEO of Seattle Children’s, highlighted the momentum of CAR T-cell research and clinical trials for pediatric brain cancer. He noted that the advancements at Seattle Children’s, as showcased in Nature Medicine, are driving progress in CAR T therapy for DIPG. The innovation model at Seattle Children’s is designed to accelerate the development of potential cures, and the partnership with BrainChild Bio is a testament to these efforts.

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive brain tumor that forms in the pons and is almost always fatal. Affecting 200-300 children annually in the U.S., most diagnoses occur in children aged 5 to 10. Current treatments are limited to palliative radiation therapy, providing a median survival of 8-11 months. The tumor's location, infiltrative nature, and intact blood-brain barrier pose significant challenges to treatment. However, targeted CAR T-cell therapies delivered through intracerebroventricular dosing present a promising approach. This method allows CAR T-cells to directly target the tumor while minimizing systemic side effects, potentially leading to more durable and effective treatment outcomes.

BrainChild Bio is at the forefront of leveraging CAR T-cell technology to combat CNS tumors, focusing on pediatric cases and expanding into adult brain cancers like glioblastoma. Their innovative platform integrates synthetic technologies to enhance efficacy and efficiency, with BCB-276 serving as their leading therapeutic candidate.