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BrainChild Bio, Inc., a clinical-stage biotechnology company developing CAR T-cell therapies to treat tumours in the central nervous system (CNS), announced that the investigational B7-H3 targeting autologous CAR T-cell therapy has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the US Food and Drug Administration (FDA) for the treatment of diffuse intrinsic pontine glioma (DIPG), an incurable paediatric brain tumour.
The use of a regenerative medicine, specifically a CAR T-cell therapy, offers the potential to overcome barriers for other drug modalities to be effective in addressing DIPG, including the precarious location of the DIPG tumour in the brainstem, the infiltrative growth of the tumour throughout normal brainstem functional anatomy, and the blood brain barrier that remains intact during tumour progression. BrainChild Bio has designed BCB-276 to be administered by locoregional delivery of targeted CAR T-cells directly into the cerebrospinal fluid, permitting infused CAR T-cells to directly access the tumour bed, using an indwelling reservoir-catheter device.
This approach to administering an autologous B7-H3 CAR T-cell therapy has been successfully implemented and resulted in the promising overall survival benefit in patients with brain tumours observed in the BrainChild-03 phase 1 trial (NCT04185038), conducted by BrainChild Bio’s academic partner, Seattle Children’s Research Institute, and recently published in Nature Medicine.
“We are very pleased to now also receive RMAT designation, less than one month after being granted Breakthrough Therapy designation from FDA for our lead CAR T therapy, BCB-276, for the treatment of DIPG. Receiving designations from two independent reviews within FDA further validates the positive CAR-T clinical results achieved by our team to date and the urgent need for a treatment for DIPG,” stated Michael Jensen, MD, founder and chief scientific officer of BrainChild Bio. “Our team is keenly focused on initiating the pivotal phase 2 trial by the end of this year and look forward to continuing to work with the FDA on an accelerated path forward to bring potential new CAR-T treatments for CNS brain tumours in children and adults.”
FDA grants RMAT designation to investigational regenerative medicine therapies, including cell therapies, that are aimed at treating serious or life-threatening diseases have shown preliminary clinical evidence that the drug has the potential to address unmet medical needs for the disease. Investigational medicines with RMAT are provided intensive interactions with the FDA during the product candidate’s development process in addition to being eligible for rolling submission and priority review of the marketing application.
“It’s gratifying to see another important benchmark reached in our work to combat paediatric brain cancer,” said Dr. Jeff Sperring, chief executive officer at Seattle Children’s. “Our research is the foundation of progress to bring potential therapies to kids as fast as we can – and we’re excited about the possibilities afforded by this designation.”
BrainChild Bio is preparing to advance BCB-276 in a phase 2 multi-centre, 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.
Diffuse intrinsic pontine glioma (DIPG) is a primary high-grade brain tumour that arises in the pons and is uniformly fatal. DIPG affects approximately 300 children per year in the US with the majority of diagnoses made in children between 5 and 10 years of age. Current standard-of-care treatment remains limited to palliative focal radiation therapy which results in a median overall survival of only about 11 months from diagnosis. Barriers to effective therapies for DIPG include the precarious location of the tumour in the brainstem, the infiltrative growth of the tumour throughout normal brainstem functional anatomy, and the blood brain barrier that remains relatively intact during tumour progression preventing therapies from gaining access to the cancer.
The barriers to effective therapies for DIPG can be effectively overcome by the locoregional delivery of appropriately targeted CAR T-cells directly into the cerebrospinal fluid via intracerebroventricular (ICV) dosing with an indwelling reservoir-catheter device. This enables the potential for extensive exposure of the pons to cerebrospinal fluid flow from the ventricular system, thus permitting infused CAR T-cells to directly access the tumour bed. This also allows for repetitive infusions of CAR T-cells to replenish the tumour bed, offering the potential for more durable and sustained efficacy. Additionally, with the blood brain barrier intact, this therapeutic approach can also minimize any on-target, off-tumour toxicities resulting from systemic exposure of CAR T-cells.
BrainChild Bio, Inc., is a kids-first, clinical-stage biotechnology company harnessing the power of CAR T-cell technology to treat tumours in the central nervous system, prioritizing paediatric indications with plans to expand into adult CNS tumours, specifically Glioblastoma and brain metastasis.
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