Be Biopharma Reveals New Preclinical Data for B Cell Medicine for Hypophosphatasia Treatment

Be Biopharma, Inc. ("Be Bio"), a trailblazing company in the field of Engineered B Cell Medicines (BCMs), has recently unveiled promising results from their latest preclinical research. The study highlights the production of active tissue-nonspecific alkaline phosphatase (ALP) by a BCM, presenting BCMs as a potential therapeutic avenue for Hypophosphatasia (HPP). This significant research was showcased during a poster presentation at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting.

Hypophosphatasia is a rare genetic disorder resulting from loss-of-function mutations in the ALPL gene, leading to deficient ALP activity. Individuals with HPP suffer from various systemic complications, the most notable being impaired bone mineralization, manifesting as rickets or osteomalacia in severe cases. Currently, the only approved treatment for HPP is asfotase alfa, an enzyme replacement therapy that necessitates frequent injections each week and is limited to patients with pediatric-onset forms of the disease.

Be Bio's breakthrough study demonstrates the application of CRISPR/Cas9 precision gene engineering combined with artificial intelligence (AI)-guided protein design to modify primary human B cells. These engineered cells successfully produce ALP, the enzyme lacking in HPP sufferers. The advanced AI techniques were employed to optimize protein constructs for the activity and stability of ALP-Fc fusion proteins, leading to the secretion of active ALP proteins at significant levels.

According to Rick Morgan, Chief Scientific Officer of Be Bio, this study underscores the potential of BCMs when integrated with AI-guided protein design. He emphasizes that BCMs are capable of providing consistent and durable protein levels without preconditioning, are redosable, and hold promise across a variety of diseases, including offering a pioneering treatment for HPP.

The study involved expanding primary human B cells and using CRISPR/Cas9 genome editing along with AAV-mediated homology-directed repair to introduce an ALP gene expression cassette into various loci, including CCR5. The engineered B cells secreted active ALP proteins, demonstrating up to 200 ng/1e6 cells/24hr. Furthermore, robust in vitro phenotypic correction was observed using ALP-secreting BCMs in an osteoblast precursor mineralization model.

Engineered B Cell Medicines (BCMs) represent a novel class of cellular therapies. B cells are unique in their ability to produce thousands of proteins per cell each second, consistently over long periods. With advancements in precision genome editing, B cells can now be engineered to produce therapeutic proteins, heralding a new era in cellular medicine. BCMs have the potential to be durable, allogeneic, redosable, and administered without pre-conditioning, offering transformative possibilities across various therapeutic areas.

Be Biopharma, established in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., focuses on creating impactful treatments for conditions like Hemophilia B, genetic diseases, and cancer. Supported by investors including ARCH Venture Partners, Atlas Venture, RA Capital Management, and others, Be Bio has secured over $180 million in funding since its inception. This investment enables the company to innovate and develop B cell therapies, aiming to revolutionize medicine through the power of B cell technology.

In summary, Be Biopharma's recent preclinical research marks a significant stride in the development of BCMs for treating HPP, with potential applications extending to various other diseases. The integration of CRISPR/Cas9 gene engineering and AI-guided protein design holds promise for producing effective and durable therapeutic proteins, positioning BCMs as a revolutionary advancement in the field of cellular medicine.