BrainChild Bio, Inc., a clinical-stage biotechnology company, announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to its investigational B7-H3 targeting autologous CAR T-cell therapy for the treatment of diffuse intrinsic pontine glioma (DIPG), a uniformly fatal pediatric brain tumor.
The designation was based on promising overall survival benefit observed in patients with brain tumors treated with an autologous B7-H3 CAR T-cell therapy in the BrainChild-03 Phase 1 trial (NCT04185038). This trial was conducted by BrainChild Bio's academic partner, Seattle Children's, with results recently published in Nature Medicine.
"Breakthrough Therapy designation gives us the possibility to accelerate the development path for BCB-276 as a CAR T-cell therapy that can potentially transform the treatment of DIPG," stated Michael Jensen, MD, Founder and Chief Scientific Officer of BrainChild Bio. "This designation is a major milestone for the children and families afflicted with these devastating brain tumors and represents a new paradigm for treating CNS brain tumors in children and adults, including a large number of patients suffering with glioblastomas and brain metastases."
The FDA grants Breakthrough Therapy designation to investigational medicines that demonstrate potential to treat a serious or life-threatening condition and show preliminary clinical evidence of substantial improvement over available therapies. This designation provides early and more frequent interactions with the FDA, eligibility for rolling submission, and priority review of the marketing application.
Dr. Jeff Sperring, Chief Executive Officer of Seattle Children's, commented on the significance of this development: "This designation is an important milestone for Seattle Children's and demonstrates our continued momentum in pediatric brain cancer research. We harness the power of research to bring potential cures to kids faster, and we're excited by the early promise shown by our work with BrainChild Bio to advance a potential CAR T therapy."
Understanding DIPG and the Treatment Approach
DIPG is a primary high-grade brain tumor that arises in the pons and affects approximately 300 children per year in the United States. The majority of diagnoses occur in children between 5 and 10 years of age. Current standard-of-care treatment is limited to palliative focal radiation therapy, resulting in a median overall survival of only about 11 months from diagnosis.
Several barriers have historically prevented effective treatment of DIPG, including:
- The tumor's location in the brainstem
- Infiltrative growth throughout normal brainstem functional anatomy
- The blood-brain barrier remaining relatively intact during tumor progression
BrainChild Bio's approach aims to overcome these barriers through locoregional delivery of appropriately targeted CAR T-cells directly into the cerebrospinal fluid via intracerebroventricular (ICV) dosing with an indwelling reservoir-catheter device. This delivery method enables:
- Extensive exposure of the pons to cerebrospinal fluid flow from the ventricular system
- Direct access of CAR T-cells to the tumor bed
- Repetitive infusions to replenish the tumor bed for potentially more durable efficacy
- Minimized on-target, off-tumor toxicities from systemic exposure
Clinical Development Plans
BrainChild Bio is preparing to advance BCB-276 in a Phase 2 multi-center, pivotal registration trial to support a potential Biologics License Application (BLA) to the FDA for the treatment of children and young adults with DIPG. This clinical plan is based on alignment between BrainChild Bio and FDA at a Type B meeting in late 2024.
About BrainChild Bio's Technology Platform
BrainChild Bio was launched out of Seattle Children's Therapeutics program and founded on the work of Dr. Michael Jensen, a pioneer in the cancer immunotherapy field and previous Chief Therapeutics Officer at Seattle Children's.
The company is advancing a next-generation CAR T-cell therapy platform for tumors of the central nervous system that integrates several innovative technologies:
- Multiplex targeting and enhanced potency controls
- Multiple targets in a single CAR T-cell therapy
- Novel transgenes to increase potency
- Delivery technology for durable efficacy
- Streamlined CAR T-cell design and manufacturing
BCB-276, the company's lead drug candidate, is an autologous CAR T-cell therapy that targets the immune checkpoint B7-H3. While initially focused on pediatric indications, BrainChild Bio plans to expand into adult CNS tumors, specifically glioblastoma and brain metastasis.
This breakthrough designation represents a significant step forward in addressing the critical unmet need for effective treatments for DIPG and potentially other CNS tumors, offering new hope to patients and families affected by these devastating diseases.
