Be Biopharma unveils promising preclinical data for BE-102 B cell therapy targeting hypophosphatasia

In a notable advancement for genetic bone disorder therapies, Be Biopharma Inc. has presented new preclinical data for BE-102, its lead B Cell Medicine (BCM) targeting Hypophosphatasia (HPP). Announced during the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting on May 17, the findings highlight a single intravenous administration of BE-102 delivering sustained in vivo secretion of active alkaline phosphatase (ALP) for over 175 days. This achievement marks a significant stride in the search for durable, less burdensome therapies for patients affected by this debilitating and under-addressed rare disease.

What is Hypophosphatasia and Why is BE-102 a Potential Game-Changer?

Hypophosphatasia is a rare inherited metabolic disorder characterized by loss-of-function mutations in the ALPL gene, leading to deficient activity of ALP, a critical enzyme for bone mineralization and metabolic balance. This deficiency results in the accumulation of inorganic pyrophosphate (PPi), an inhibitor of bone mineralization, causing a wide range of clinical complications, including skeletal deformities, fractures, and premature tooth loss. Severe forms of HPP present in infancy or childhood, and the disease burden persists throughout life.

Current treatment options are limited to enzyme replacement therapy (ERT), which is only approved for select early-onset forms and requires lifelong, frequent injections. In contrast, BE-102 introduces a novel paradigm—long-acting, re-dosable cellular therapy derived from engineered human B cells capable of continuously secreting active ALP.

How Does BE-102 Work and What Makes It Unique?

BE-102 is designed using Be Biopharma’s proprietary BCM platform, leveraging precision CRISPR/Cas9 genome editing to insert a functional copy of the ALPL gene into the CCR5 safe harbor locus of primary human B cells. The modified B cells are then expanded and differentiated in culture into ALP-secreting B lymphocyte lineage cells, forming the basis of a therapeutic infusion. Notably, this process does not require toxic pre-conditioning, unlike some other cell-based therapies.

Once administered intravenously, BE-102 delivers a continuous supply of therapeutic ALP. According to data from immune-deficient NOG-hIL6 mouse models, BE-102 maintained durable ALP secretion for more than six months, highlighting the therapy’s potential for disease-modifying effects with fewer interventions compared to current ERT regimens.

What Did the Preclinical Data Reveal About BE-102’s Efficacy and Safety?

The data presented at ASGCT included both in vitro and in vivo findings supporting BE-102’s biological activity and favorable safety profile. In vitro, the engineered B cells secreted enzymatically active ALP capable of overcoming PPi-mediated inhibition of calcium deposition, a surrogate marker of bone mineralization potential. This evidence supports the therapeutic rationale for BE-102’s application in HPP, where PPi accumulation disrupts normal bone formation.

In vivo experiments demonstrated long-term engraftment and ALP production in mouse models, with no adverse events reported in multiple pharmacological studies. The absence of toxicity combined with sustained enzyme activity builds a compelling case for the therapy’s progression into clinical trials. According to Be Biopharma’s Chief Scientific Officer Rick Morgan, the findings validate the durability and re-dosability potential of the company’s B cell medicine platform, which could circumvent limitations inherent in ERT.

What Makes Engineered B Cell Medicines a New Frontier in Cell Therapy?

Engineered B Cell Medicines, or BCMs, represent a new class of therapeutic modalities that reprogram the body’s own protein factories—B lymphocytes—to produce targeted biologics over extended periods. Unlike traditional gene or cell therapies that often require myeloablative conditioning or immunosuppression, BCMs aim to function in a more natural and sustainable manner. Each engineered B cell is capable of producing thousands of protein molecules per second and may persist in the body for years, theoretically enabling prolonged therapeutic benefit from a single dose.

In the context of HPP, this means replacing deficient ALP not by intermittent injections but by leveraging the body’s own immune machinery to supply the missing enzyme continuously. Be Biopharma’s platform has shown flexibility in protein payload design and insertion strategies, enabling broader application across diseases involving enzyme deficiencies or protein-based pathologies.

When Could BE-102 Enter Human Trials and What’s Next for Be Biopharma?

With BE-102 now demonstrating preclinical proof-of-concept, Be Biopharma is advancing toward filing an Investigational New Drug (IND) application. The company is currently assembling a comprehensive preclinical package to support its request to begin first-in-human clinical trials. These studies will be designed to assess safety, tolerability, engraftment dynamics, and preliminary signals of efficacy in individuals with confirmed ALPL mutations and clinical HPP manifestations.

If the IND is cleared, BE-102 could become the first B Cell Medicine evaluated in patients with a rare bone disorder, marking a significant milestone for Be Biopharma’s broader ambitions. The company is concurrently exploring additional BCM candidates targeting other rare genetic diseases and immune-mediated disorders, indicating a platform strategy that could disrupt conventional biologics and gene therapy paradigms.

How Are Investors and the Rare Disease Community Responding?

Though Be Biopharma remains a private entity and does not publicly disclose investor sentiment, its continued scientific visibility at major conferences such as ASGCT signals increasing recognition within the biotech innovation ecosystem. The unmet need in HPP is well-documented, and stakeholders in the rare disease space—from clinicians to patient advocacy groups—are actively monitoring advances that offer durable, less invasive alternatives to ERT.

Investor interest in cell therapy platforms has remained strong despite volatility in the biotech sector, with attention increasingly shifting toward differentiated modalities like BCMs that blend the scalability of biologics with the precision of genetic medicine. If BE-102 enters clinical development and maintains its current preclinical profile, it could attract significant strategic or institutional backing to support further pipeline expansion.

What Are the Broader Implications of This Development in Biotech Medicine?

The successful translation of BCM technology into a disease-modifying therapy for HPP could signal a wider shift in how protein replacement therapies are conceived, developed, and delivered. Rather than exogenous protein infusions requiring chronic administration, cellular factories inside the patient’s own immune system may offer a more sustainable, patient-friendly alternative. Moreover, the precision afforded by CRISPR-based genome insertion into safe harbor loci raises the possibility of treating diseases previously considered unsuitable for traditional gene therapy.

With BE-102 at the forefront, Be Biopharma has positioned itself as a leading innovator in the emerging field of B cell engineering. Its pipeline progress will be closely watched as the biotech industry continues to evolve toward platforms that emphasize durability, safety, and modular adaptability.

As the field anticipates the IND submission for BE-102, attention will now shift to how this first-in-class B Cell Medicine performs in the clinic and whether it can redefine standards of care for patients living with severe, chronic, and underserved genetic diseases like Hypophosphatasia.