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CAMBRIDGE, Mass.–Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BCMs) today announced that it will present new preclinical data in an oral presentation at the 65^th Annual Meeting of the American Society of Hematology (ASH) taking place December 9-12, 2023, in San Diego, California. The research will describe the development of an ex vivo precision-engineered B Cell Medicine (BCM) that produces active and sustained levels of factor IX (FIX). The abstract is now available online in a special issue of the ASH official journal, Blood.

“We look forward to presenting our research at the ASH annual meeting, the pre-eminent global congress for scientific exchange in hematology,” said Dr. Rick Morgan, Chief Scientific Officer, Be Bio. “Our team of dedicated researchers is inspired by the potential of this bold new class of medicines.”

Details of the oral presentation are as follows:

Title: Development of an Ex Vivo Precision Gene Engineered B Cell Medicine That Produces Active and Sustained Levels of FIX for the Treatment of Hemophilia B
Session Name: 703 Cellular Immunotherapies: Basic and Translational: Novel Approaches for Next Generation Cellular Immunotherapies
Session Date: Sunday, December 10, 2023
Presentation Time: 9:30 AM PST
Room: San Diego Convention Center, Room 6A
Publication Number: 463

About Engineered B Cell Medicines – A New Class of Cellular Medicines
Imagine what could “Be?” In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs). BCMs have the potential to be durable, allogeneic, redosable and administered without toxic 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 cancer, rare diseases 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 by Longwood Fund and B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. 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. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page.

SAN DIEGO–(BUSINESS WIRE)–Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BCMs), will present preclinical data demonstrating that a BCM-derived biologic can deliver steady-state plasma concentrations of a bispecific T cell engager at clinically relevant doses for treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). Findings from the study, conducted jointly with researchers at Seattle Children’s Research Institute, will be presented during the Society for Immunotherapy of Cancer’s 38th Annual Meeting.

“These findings underscore the clinical potential of BCMs as an emerging platform for sustained delivery of antitumor biologics. Our platform enables production of a diverse set of therapeutic proteins, including those difficult to manufacture using traditional systems, and offers a promising approach for a new class of medicines with broad therapeutic utility,” said Dr. Rick Morgan, Chief Scientific Officer, Be Bio.

“Bispecific T cell engagers are highly effective in treating relapsed/refractory ALL; however, their short half-life requires continuous intravenous administration at high doses for four-week increments. This study demonstrates that engineered plasma cells can deliver a constant infusion of bispecific T cell engagers at a steady-state, clinically relevant plasma concentration, offering a potential therapeutic advance to decrease the burden of therapy for patients,” said Dr. Richard James, principal investigator at Seattle Children’s Research Institute.

The poster presentation details are as follows:

Bispecific T cell engagers, consisting of an anti-CD3 single-chain fragment variable (scFv) fused to an anti-tumor antigen scFv, are highly effective in the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). However, the short half-life of bispecific T cell engagers necessitates continuous intravenous administration at high doses for four weeks at a time. Given their ability to produce proteins at steady state, BCMs are particularly well-suited to overcome these pharmacokinetic shortcomings. To generate BCMs, B cells are engineered ex vivo to constitutively secrete transgenic biologics and then differentiated into plasma cells. These cells were chosen for their high antibody production capacity (thousands of Ig molecules/cell/sec) and ability to engraft without preconditioning, making them a highly attractive cell-based platform for continuous biologic delivery¹.

About the Study

To demonstrate proof-of-concept, a transgene coding for a bispecific anti-CD3:CD19 scFv was integrated into a safe-harbor locus of primary human B cells via targeted gene knock in. The engineered B cells were then differentiated into plasma cells ex vivo. Assessment of in vivo anti-tumor activity of these BCMs was conducted in NSG mice harboring a patient-derived CD19-expressing xenograft (PDx). Mice were inoculated with a luciferized B-ALL PDx line and autologous T cells were delivered after tumor transfer. Significant reduction in tumor burden (bioluminescent flux, area under the curve) was observed over the course of the 17-day study in the anti-CD3:CD19 scFv cohort compared to controls, which was in concordance with heightened in vivo T cell activation. The ~1000 pg/mL bispecific T cell engagers detected in mouse plasma demonstrated that a BCM-derived biologic can meet or even exceed the steady-state plasma concentrations achieved with clinically relevant blinatumomab doses².

Deidentified human PBMCs were acquired under informed consent from the Fred Hutch Specimen Processing and Research Cell Bank (protocol #3942).

No toxicities were identified in this study.

About Engineered B Cell Medicines – A New Class of Cellular Medicines

Imagine what could “Be?” In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs). BCMs have the potential to be durable, allogeneic, redosable and administered without toxic 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 cancer, rare diseases 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 by Longwood Fund and B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. 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. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page.

References:

1. Hung KL, Meitlis I, Hale M, Chen C, Singh S, Jackson SW, Miao CH, Khan IF, Rawlings DJ, James RG. Engineering Protein-Secreting Plasma Cells by Homology-Directed Repair in Primary Human B Cells. Mol. Ther. 2018; 26:456-467.
2. Franquiz MJ and Short NJ. Blinatumomab for the Treatment of Adult B-Cell Acute Lymphoblastic Leukemia: Toward a New Era of Targeted Immunotherapy. Biologics. 2020; 14: 23–34.

CAMBRIDGE, Mass., Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BeCMs), will present first-of-its-kind preclinical research today from a collaboration study showing homing and engraftment of B cells in non-human primates (NHPs) with intact immune systems. The findings will be presented during a late-breaking oral presentation at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting from 9:30-9:45 a.m. PST. 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 study was designed to evaluate engraftment without preconditioning of ex vivo expanded NHP plasma cells. Plasma cells are terminally differentiated B cells which can live for decades¹ and have the capacity to secrete extremely high levels of protein². In two NHPs, B cells were collected, expanded, and differentiated into plasma cells. The resulting cells were radiolabeled and directly infused into the NHPs and tracked by PET imaging. Rapid homing (within one hour) and engraftment to plasma cell niches in the bone marrow and spleen were observed with a consistent signal over a six-day period. Radiolabeled cells were also observed in the liver. Greater than 20% of the total cells dosed engrafted into the plasma cell niche by day one and high-resolution imaging of the bone marrow compartment showed cellular distribution comparable to human bone marrow. No toxicities in the study were identified.

“NHP engraftment without preconditioning validates a key pillar of the Be Bio platform and broadens the potential clinical utility of engineered B cell medicines for patients where preconditioning toxicities are unacceptable or outweigh therapeutic benefit,” said Dr. Rick Morgan, Chief Scientific Officer, Be Bio. “Be Bio’s stable engineering platform for the expression of diverse therapeutic proteins by engineered B cells represents a promising approach for a new class of medicines with broad therapeutic utility.”

“NHPs with intact immune systems have close similarities to humans and can model autologous and allogeneic cell therapy treatment,” said Dr. David Young, Staff Clinician, Translational Stem Cell Biology Branch, NHLBI. “Our results show for the first time that ex vivo expanded plasma cells distribute to the bone marrow and spleen in patterns comparable to human sites of active blood cell formation.”

In the next phase of the study, long-term engraftment without preconditioning and tracking of BeCMs are planned in NHPs with intact immune systems.

Study Design

Peripheral blood B cells were collected and purified from two adult rhesus monkeys (12 and 10 years old) and expanded over eight days in a defined serum-free culture to yield ≥10-fold expansion (measured by live cell count) with a final viability of ≥80% (measured by percent of live cells). Differentiation to plasma cells was demonstrated by loss of CD20 (protein found in B cells) along with antibody class switching (>75% Immunoglobulin G producing cells). The plasma cell product was radiolabeled with zirconium-89-oxine and intravenously infused. Imaging was performed using high sensitivity PET/CT tracking of the BeCMs. PET/CT images were acquired at 15 minutes, one hour and then one, three and six-days post-infusion.

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 B Cells – A New Class of Cellular Medicines

Imagine what could “Be?” In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BeCMs). BeCMs have the potential to be durable, allogeneic, redosable and administered without toxic conditioning. The promise of BeCMs 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 (BeCMs) to dramatically improve the lives of patients who are living with cancer, rare diseases 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 by Longwood Fund and B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. 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. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page.

¹ Landsverk et al (2017) J Exp Med
² Hibi and Dosch (1986) J Immunol; Eyer et al (2017) Nat Biotech