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• Publication Demonstrates Engraftment of 20% of Infused Cells without Preconditioning with Consistent Distribution Upon Redosing
• Manuscript Published in the Molecular Therapy Journal

CAMBRIDGE, Mass. February 6, 2025 – Be Biopharma, Inc. (“Be Bio”), a clinical-stage company pioneering the discovery and development of engineered B Cell Medicines (BCMs), today announced the publication in the journal Molecular Therapy of a manuscript highlighting first-of-its-kind preclinical research from a collaboration study showing homing and engraftment of ex-vivo-generated plasma cells in non-human primates (NHPs) with intact immune systems.  The study highlights the ability of these plasma cells to engraft in NHPs without preconditioning, validating a crucial aspect of the BCM platform designed to develop innovative programs with best-in-class profiles. The study was funded and conducted through a collaborative research and development agreement with the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

The publication, entitled “In vivo tracking of ex vivo generated ⁸⁹Zr-oxine labeled plasma cells by PET in a non-human primate model”, summarizes a study designed to evaluate engraftment without preconditioning of ex vivo expanded NHP plasma cells. Plasma cells are terminally differentiated B cells which can live for decades and have the capacity to secrete extremely high levels of protein. In the study, B cells from two NHPs were collected, expanded 10-15 fold ex vivo, and differentiated into antibody-secreting plasma cells. Using radioactive labeling and PET/CT imaging to track the cells after infusion, researchers found that 20% of the cells engrafted into the plasma cell niche by 24 hours and high-resolution imaging of the bone marrow compartment showed cellular distribution comparable to human bone marrow. A second infusion in one of the subjects showed remarkably similar distribution patterns to the first infusion, suggesting the feasibility of predicable re-dosing.

“These findings demonstrate the incredible potential of engineered B cells as a therapeutic platform and validate engraftment without preconditioning, a key pillar of our platform,” said Richard Morgan, Ph.D., Chief Scientific Officer, Be Biopharma. “Our successful tracking and monitoring of these cells in non-human primates marks a crucial step toward developing B cell medicines that could potentially treat genetic disorders, metabolic diseases, and cancer. The safety profile and ability to perform repeated infusions are particularly encouraging and support our continued development of this innovative approach.”

A phase 1/2 clinical trial, the BeCoMe-9 trial, has been initiated for Be Bio’s lead program, BE-101, in people with Hemophilia B, and Be Bio expects to initiate clinical development for BE-102 for the treatment of hypophosphatasia during 2026.

To read the published article, please visit
https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(24)00842-6

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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, and is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Nextech, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others to re-imagine medicine based on the power of Engineered B cells. For more information, please visit us at Be.Bio and our LinkedIn page.

Investor Contact:
ir@be.bio

Media Contact:
media@be.bio

• BeCoMe-9 Trial Poster: Highlights ongoing Phase 1/2 trial evaluating BE-101, a first-in-class B cell medicine (BCM) designed to sustain Factor IX levels in adults with Hemophilia B.

• Oral Presentation: Showcased breadth and versatility of ex-vivo precision gene-engineered BCM platform across genetic disease and oncology

CAMBRIDGE, Mass. December 8, 2024 – Be Biopharma, Inc. (“Be Bio”), a clinical-stage company pioneering engineered B Cell Medicines (BCMs), today announced two key updates at the 66th ASH Annual Meeting in San Diego, CA. These updates include a Trial in Progress poster detailing the BeCoMe-9 clinical trial and an oral presentation highlighting the potential of Be Bio’s BCM platform to create innovative programs with best-in-class profiles.

The Trial in Progress poster highlights the design of Be Bio’s BeCoMe-9 clinical trial, evaluating BE-101 in patients with Hemophilia B. BE-101, the Company’s lead clinical program, is an autologous BCM therapy engineered to express human factor IX (hFIX). This innovative therapy aims to offer a transformative new therapeutic option by delivering sustained hFIX levels, addressing the needs in patients with hemophilia B, a bleeding disorder affecting approximately 40,000 people globally. Despite advancements, many people living with hemophilia B continue to experience regular bleeding events that can lead to chronic pain and irreversible joint damage. BE-101 is designed to provide long-lasting FIX protection using the patient’s own B cells, with the flexibility to be titratable and redosable as needed. The BeCoMe-9 first-in-human Phase 1/2 trial is actively enrolling patients and aims to achieve clinical proof of concept for both BE-101 and the BCM platform. BE-101 has been granted Orphan Drug and Fast Track Designations by the FDA, underscoring its potential to address important unmet needs.

“This year marks a pivotal milestone for Be Bio as we have transitioned into a clinical stage company, advancing our groundbreaking science into lead programs that aim to deliver new therapeutic options for patients in need,” said Joanne Smith-Farrell, PhD, Chief Executive Officer of Be Bio. “In 2025, the BeCoMe-9 trial is poised to generate clinical proof of concept for BE-101, advancing this critical program for patients while demonstrating the transformative potential of our B Cell Medicine platform.”

The BeCoMe-9 study is designed to evaluate the safety and clinical activity of a single IV dose of BE-101 in adults with moderately severe or severe Hemophilia B. The study consists of two parts. Part 1 employs an ascending-dose design, enabling the stepwise evaluation of increasing dose levels to determine a safe and effective dose. Once this dose is identified, Part 2 will add a cohort to confirm and further characterize the safety and activity of BE-101 at the selected dose along with a cohort to include adolescents. Details of the poster presentation are as follows:

Abstract Title: BeCoMe–9: A Phase 1/2 Dose Escalation and Expansion Study of BE-101 for the Treatment of Adults with Moderately Severe or Severe Hemophilia B
Session Name: 322. Hemophilia A and B: Clinical and Epidemiological: Poster II
Publication Number: 2593.1
Date: Sunday, December 8, 2024
Time: 6:00 PM – 8:00 PM PT
Session Room: San Diego Convention Center, Halls G-H

Be Bio’s oral presentation on December 7 highlighted the versatility of BCMs in delivering therapeutic biologics for diverse patient populations and diseases. BCMs are designed to produce constant levels of therapeutic proteins in a durable, redosable, and titratable manner, all without the need for preconditioning. The presentation highlighted data from the Company’s two lead candidates, BE-101, a clinical-stage BCM engineered to express hFIX as a potential new treatment for Hemophilia B, and BE-102, a development candidate engineered to express tissue nonspecific alkaline phosphatase (ALP) as a potential treatment option for hypophosphatasia (HPP). The presentation also included data from a BCM prototype engineered to express an anti-CD3:CD19 scFv bispecific T cell engager, which demonstrated a significant reduction in tumor burden in a patient-derived xenograft model of acute lymphoblastic leukemia.

“These data reinforce the capabilities of our versatile B cell engineering platform to develop novel BCMs that express therapeutically relevant proteins,” said Rick Morgan, Ph.D., Chief Scientific Officer, Be Biopharma. “Our BCM platform offers transformative potential to improve the delivery of therapeutic biologics across a wide spectrum of genetic diseases, cancers and other therapeutic areas.”

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, 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, titratable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across diverse protein classes, patient populations and therapeutic areas.

About BE-101

BE-101 is a first-in-class engineered B Cell Medicine (BCM) designed to treat Hemophilia B by inserting the human Factor IX (FIX) gene into primary human B cells, enabling continuous expression of active FIX. BE-101 offers the potential for sustained therapeutic FIX activity levels with a single infusion, with the flexibility to be titrated and/or re-dosed, and without the need for preconditioning. By maintaining sustained and constant therapeutic FIX activity levels while reducing dosing frequency required by current FIX replacement regimens, BE-101 could alleviate the considerable infusion burden faced by people with Hemophilia B while potentially lowering annualized bleeding rates and FIX usage. The US FDA cleared the BE-101 IND in May of 2024, and has granted the program Fast Track and Orphan Designations. The Phase 1/2 BeCoMe-9 Trial is open for enrollment and further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06611436.

About Be Biopharma

Be Biopharma (“Be Bio”) is clinical-stage company pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B, other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, Be Bio’s team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborates to create a bold new class of cell therapies. Be Bio was founded in October 2020, 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. For more information, please visit us at Be.Bio and our LinkedIn page.

Investor Contact:
ir@be.bio

Media Contact:
media@be.bio