Be Biopharma, Inc. ("Be Bio"), a clinical-stage biotechnology company developing engineered B Cell Medicines (BCMs), will present new nonclinical data for its BE-102 program at the upcoming American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting in New Orleans, May 13-17, 2025.
The company's oral presentation will showcase promising results for BE-102, a novel B cell therapy being developed as a potential treatment for hypophosphatasia (HPP), a rare genetic disorder characterized by deficient bone mineralization due to mutations in the ALPL gene.
Novel B Cell Therapy Shows Promise for Hypophosphatasia Treatment
HPP is caused by a deficiency in tissue-nonspecific alkaline phosphatase (TNSALP) activity resulting from pathogenic mutations in the ALPL gene. This deficiency leads to multi-systemic clinical complications, most notably deficient bone mineralization.
Currently, enzyme replacement therapy (ERT) is the only approved treatment for HPP, but it comes with significant limitations. ERT requires frequent lifelong injections, is only available for perinatal/infantile- and juvenile-onset forms of HPP, and is associated with common side effects that can significantly impact patients' quality of life.
BE-102 was specifically developed to address these limitations. The therapy is manufactured from primary human B cells through a process of isolation, activation, and precision engineering using CRISPR/Cas9 technology. This is followed by AAV-mediated delivery of a DNA donor template for the insertion of the human ALPL gene into the CCR5 locus, which serves as a safe harbor within the genome.
Dr. Hanlan Liu, Ph.D., MBA, SVP and Head of Late Research and NCD at Be Biopharma, will present the data on May 17, 2025, as part of the B-Cell and Solid Organ Therapies session.
"Our nonclinical data demonstrates that BE-102 has the potential to be a disease-modifying therapy for people with HPP by providing long-lasting active TNSALP, with the flexibility to be titratable and redosable as needed," said Dr. Liu in a company statement.
Compelling Preclinical Evidence
In vitro pharmacology results have demonstrated that BE-102 secretes active TNSALP, which is capable of rescuing calcium deposits inhibited by inorganic pyrophosphate (PPi), a substrate that accumulates in people with HPP.
Further in vivo studies conducted in immune-deficient NOG-hIL6 mice confirmed long-term engraftment and continuous production of active TNSALP following a single intravenous administration of BE-102.
These findings establish nonclinical proof-of-concept that BE-102 could potentially serve as a disease-modifying therapy for HPP patients by providing sustained levels of active TNSALP, with the added benefits of being titratable and redosable when necessary.
Advancing Allogeneic Cell Therapy Approaches
In addition to the BE-102 presentation, Be Biopharma will also present a poster highlighting their approach to developing allogeneic off-the-shelf B Cell Medicines. The poster, presented by Dr. Xuqing Zhang, Ph.D., Director of Immunology at Be Biopharma, will be displayed during the Tuesday Poster Reception on May 13, 2025.
The research explores allogeneic shielding strategies using precise CRISPR/Cas9 genome engineering of primary human B cells. Both in vitro and in vivo assays were used to determine the potential of BCMs as an allogeneic off-the-shelf cell therapy without additional engineering and ways to enhance hypoimmunogenicity via genome engineering.
The data demonstrates that BCMs are "immunologically stealthy" and can be further engineered to evade host immune responses. This opens the possibility of developing off-the-shelf cellular therapies without HLA matching, potentially allowing for broader patient access.
Engineered B Cell Medicines: A New Therapeutic Frontier
Be Biopharma is pioneering a new class of cellular medicines based on engineered B cells. B cells naturally produce thousands of proteins per cell per second at constant levels over decades, making them ideal candidates for therapeutic protein production.
Through precision genome editing, B cells can be engineered to produce specific therapeutic proteins of interest. These Engineered B Cell Medicines (BCMs) have 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," explained a company representative.
Founded in October 2020, Be Biopharma is backed by prominent investors including ARCH Venture Partners, Atlas Venture, RA Capital Management, Bristol Myers Squibb, and Takeda Ventures, among others. The company aims to improve the lives of patients living with genetic diseases, cancer, and other serious conditions through its innovative cell therapy approach.
The upcoming presentations at ASGCT represent significant milestones in the company's development of its B cell therapy platform and highlight the potential of this novel therapeutic approach to address unmet medical needs in rare genetic disorders like hypophosphatasia.
