Be Biopharma reports positive preclinical data for BE-102 in hypophosphatasia

Be Biopharma, Inc. has reported new preclinical data for its lead engineered B cell medicine candidate, BE-102, developed for the treatment of hypophosphatasia (HPP). Presented at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), the results show a single administration of BE-102 delivered sustained secretion of active alkaline phosphatase (ALP) for more than 175 days in vivo, with no related safety concerns observed in long-term pharmacology studies. The findings mark a potentially transformative step in the management of HPP, a rare genetic disorder for which current treatments remain limited and burdensome.

What Is BE-102 and How Does It Work?

BE-102 is an investigational, first-in-class engineered B cell medicine designed to address the underlying cause of hypophosphatasia: mutations in the ALPL gene that impair ALP activity. Unlike conventional enzyme replacement therapies (ERTs), which require frequent and lifelong injections, BE-102 is delivered as a single infusion and is designed to secrete ALP continuously over time.

The drug candidate is manufactured from primary human B cells. Be Biopharma uses CRISPR/Cas9 genome editing combined with AAV-mediated gene insertion to embed the human ALPL gene into the CCR5 locus — a genomic safe harbor. Following genetic engineering, these modified B cells are expanded and differentiated into a lineage capable of long-term ALP secretion. According to the company, this approach eliminates the need for pre-conditioning and allows titration and repeat dosing as required.

What Did the Preclinical Data Show?

At ASGCT 2025, Be Biopharma presented both in vivo and in vitro preclinical data. In immune-deficient NOG-hIL6 mice, a single intravenous dose of BE-102 resulted in the engraftment of engineered B cells and continuous in vivo ALP production for over six months. Importantly, no BE-102–related adverse events were observed, indicating a favourable safety profile thus far.

In vitro studies further demonstrated that ALP secreted by BE-102 effectively neutralized inorganic pyrophosphate (PPi), a substrate that accumulates in HPP patients and inhibits bone mineralization. By degrading PPi, BE-102 enables calcium deposition, a key physiological process impaired in HPP.

Rick Morgan, Chief Scientific Officer at Be Biopharma, stated that these findings demonstrate the potential for BE-102 to overcome key limitations of ERT, including its short half-life and the need for frequent administration. He also emphasized the non-requirement of pre-conditioning, which broadens its usability across different patient populations.

Why Is Hypophosphatasia a Target for B Cell Therapy?

Hypophosphatasia is an ultra-rare inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene, which encodes the tissue-nonspecific isoenzyme of ALP. The disease results in insufficient bone and dental mineralization, along with systemic complications such as muscle weakness, respiratory issues, and seizures in severe cases. Currently, the only approved treatment — asfotase alfa (Strensiq®) — is an ERT requiring frequent injections and is approved only for certain pediatric-onset forms of the disease.

This limited therapeutic scope and the burdensome administration schedule have created a significant unmet need. BE-102 aims to address this by enabling durable ALP secretion from within the body via engineered B cells, potentially reducing or eliminating the need for continuous exogenous enzyme infusions.

The disease-modifying potential of B cell therapy lies in its capacity for persistent protein production. B cells naturally produce thousands of protein molecules per second and can persist in the body for decades. By harnessing this biology, Be Biopharma’s platform enables stable, long-term expression of therapeutic proteins such as ALP — a paradigm-shifting approach in rare metabolic disorders.

What’s Next for Be Biopharma’s Pipeline?

Be Biopharma has confirmed that BE-102 has been selected as a development candidate. The company is currently compiling a robust preclinical data package in anticipation of submitting an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA). A first-in-human clinical trial in patients with HPP is expected to follow, although timelines have not been publicly disclosed.

According to the company’s pipeline strategy, the goal is to advance BE-102 toward becoming a disease-modifying therapy capable of re-setting the standard of care in HPP. Additional nonclinical work is ongoing to validate biodistribution, scalability, and long-term safety across multiple species before regulatory filing.

Be Biopharma’s broader platform — focused on Engineered B Cell Medicines (BCMs) — continues to gain traction. Beyond HPP, the company is exploring indications including hemophilia B and certain cancers. Backed by a strong syndicate of institutional and strategic investors, including Bristol Myers Squibb, Takeda Ventures, and RA Capital Management, Be Biopharma is positioning itself at the forefront of next-generation cell therapies.

The preclinical results presented at ASGCT mark a milestone in the evolution of cell-based therapies beyond traditional CAR-T and stem cell platforms. By demonstrating six months of sustained enzyme production from a single infusion, BE-102 exemplifies the potential of B cell–based delivery systems to address chronic and genetic diseases that have long relied on repeat dosing of biologics.

Investor sentiment around engineered cell therapy platforms remains cautiously optimistic. While clinical translation remains the ultimate test, the platform’s modular design and non-reliance on conditioning regimens offer commercial and clinical advantages that could appeal to both regulators and payors. The absence of adverse findings in the animal studies also supports a favourable risk-benefit profile entering the IND stage.

Should the IND be approved, BE-102 will join a small but growing class of engineered cell therapies aiming to treat enzyme deficiency disorders with a durable, one-and-done approach. Be Biopharma’s scientific leadership, combined with early institutional support and high-profile conference visibility, positions it well to draw continued attention from the biotech investment community and rare disease advocacy groups.