CAMBRIDGE, Mass.--(BUSINESS WIRE)--Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of engineered B Cell Medicines (BCMs), today announced the presentation of preclinical data demonstrating the transformative power of BCMs to produce active alkaline phosphatase (ALP), highlighting BCMs as a potential treatment for Hypophosphatasia (HPP). Researchers coupled CRISPR/Cas9 precision gene engineering and artificial intelligence-guided protein design to modify primary human B cells to express ALP, an enzyme deficient in people living with HPP. The findings were presented during poster presentations at the American Society for Bone and Mineral Research (ASBMR) 2024 Annual Meeting (Thursday September 26th through Saturday, September 28th).
HPP is a rare genetic disease caused by loss of function mutations in the ALPL gene which leads to deficient ALP activity. People living with HPP can experience wide-ranging systemic complications, with impaired bone mineralization, such as rickets/osteomalacia, as the major clinical hallmark of disease. The only approved therapy for HPP is an enzyme replacement therapy, asfotase alfa, which requires multiple injections every week and is approved only for use in patients with pediatric-onset forms of HPP.
“This study builds on data presented earlier this year, demonstrating the ability of BCMs to produce sustained active levels of ALP in vivo,” said Rick Morgan, Chief Scientific Officer. “Our ALP-BCM is designed to address key unmet medical needs in HPP, delivering constant levels of active ALP, with a medicine that has the potential for once-yearly administration, does not require pre-conditioning, and can be re-dosed as necessary. These positive preclinical data support the potential of an ALP-BCM as a first-in-class medicine for people living with HPP.”
In this study, primary human B cells were expanded and precision engineered by CRISPR/Cas9 genome editing with AAV-mediated homology directed repair (HDR) to insert an ALP gene expression cassette into various loci, including CCR5 (a safe harbor locus). Guided by an artificial intelligence-based ALP protein structure design engine, protein constructs were optimized for activity and stability of ALP-Fc fusion proteins. Engineered BCMs secreted active ALP proteins (ALP-BCM) and demonstrated phenotypic correction in an in vitro bone mineralization model. Notably, ALP-BCMs engrafted in an immunodeficient mouse model and produced sustained levels of active ALP. These data underscore the potential of ALP-BCMs to address a significant unmet medical need as a potential HPP treatment. No adverse effects were observed during the in vivo study.
About Engineered B Cell Medicines – A New Class of Cellular Medicines
The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, and over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable, and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.
About Be Biopharma
Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page.