BrainChild Bio, Inc. is moving forward with the clinical development of BCB-276, an autologous CAR T-cell therapy targeting the B7-H3 immune checkpoint, for the treatment of diffuse intrinsic pontine glioma (DIPG), a devastating pediatric brain tumor with no approved treatments. This decision follows a positive meeting with the U.S. Food and Drug Administration (FDA) and leverages data from a Phase 1 trial published in Nature Medicine.
The company plans to initiate a single pivotal registration trial to expedite the submission of a Biologics License Application (BLA) for BCB-276 in children and young adults with DIPG. The FDA's alignment on proceeding directly to a multi-center Phase 2 pivotal clinical trial is based on promising preliminary safety and efficacy data from a Phase 1 clinical trial conducted by Seattle Children’s using SCRI-CARB7H3(s), the research cell product from which BCB-276 was derived.
Phase 1 Data Supports BCB-276 Development
The Phase 1 trial, BrainChild-03, conducted by Seattle Children’s, involved repetitive intracerebroventricular (ICV) dosing of the B7-H3 targeted CAR T therapy, SCRI-CARB7h3(s), in children with recurrent/refractory CNS tumors and DIPG. A subset of 21 DIPG patients were analyzed, including 12 who began CAR T treatment after disease progression and 9 who began treatment before progression.
Preliminary safety analyses showed that repetitive ICV dosing of the B7-H3 targeted CAR T therapy, up to 10x107 cells, was well-tolerated as an outpatient regimen and without lymphodepleting chemotherapy. Efficacy analyses revealed a median time from diagnosis to death for all 21 patients of 19.8 months. Notably, three patients who began CAR T treatment prior to disease progression remained alive at 44.6 months, 45.6 months, and 52.5 months from diagnosis.
According to BrainChild Bio, these preliminary data suggest a meaningful improvement in overall survival for DIPG patients compared to the current standard of care, which is limited to palliative focal radiation therapy and has a median survival time from diagnosis of 8-11 months.
Addressing Unmet Needs in DIPG Treatment
DIPG is a primary high-grade brain tumor that arises in the pons and is uniformly fatal, affecting 200-300 children per year in the U.S., primarily between the ages of 5 and 10. The limitations of current treatments are due to the tumor's location in the brainstem, its infiltrative growth, and the blood-brain barrier.
BrainChild Bio believes that locoregional delivery of targeted CAR T-cells directly into the cerebrospinal fluid via ICV dosing can overcome these barriers. This approach allows for extensive exposure of the pons to the CAR T-cells, enabling them to directly access the tumor bed. Repetitive infusions can replenish the tumor bed, potentially leading to more durable efficacy, while the intact blood-brain barrier minimizes off-target toxicities.
Future Directions
"We are very pleased to have a solid path forward for our clinical development of BCB-276 in DIPG, enabling us to continue our progress for children and families struggling with this devastating brain cancer that currently has no approved treatments," said Michael Jensen, MD, Founder and Chief Scientific Officer of BrainChild Bio. The company anticipates initiating the BCB-276 pivotal trial by the end of 2025.
