CAMBRIDGE, Mass. — Be Biopharma, a clinical-stage biotech company developing engineered B cell medicines, has unveiled new preclinical findings demonstrating the potential of its investigational therapy, BE-102, to treat Hypophosphatasia (HPP), a rare genetic disorder affecting bone mineralization.
The data, presented during an oral session at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting on May 17, showed that a single administration of BE-102 resulted in continuous in vivo secretion of active alkaline phosphatase (ALP) for over six months. Importantly, no safety concerns were observed in long-term pharmacology studies.
HPP is caused by mutations in the ALPL gene that lead to insufficient ALP activity, which is critical for healthy bone development. Current treatments, including enzyme replacement therapy (ERT), require frequent and lifelong injections and are only approved for early-onset forms of the disease. BE-102 is being developed to provide a longer-lasting, more flexible alternative.
“Our preclinical studies demonstrate that a single dose of BE-102 enables sustained secretion of active ALP, offering a potentially transformative approach to treating HPP,” said Rick Morgan, Chief Scientific Officer at Be Biopharma. “This could significantly reduce the treatment burden for patients, without the need for pre-conditioning.”
BE-102 is engineered from primary human B cells using CRISPR/Cas9 technology, which introduces a functional copy of the ALPL gene into a genomic “safe harbor” site. These modified cells are then expanded and differentiated to produce ALP-secreting B lymphocytes.
In mouse models, BE-102 showed long-term engraftment and continuous ALP production for more than 175 days following a single intravenous dose. Additional in vitro data confirmed the biological activity of the secreted enzyme, including its ability to counteract calcium inhibition caused by inorganic pyrophosphate (PPi), a key pathological factor in HPP.
The results support BE-102’s potential as a disease-modifying therapy with flexible dosing capabilities. Be Biopharma plans to continue preclinical studies and prepare for an investigational new drug (IND) application to initiate human clinical trials.
