Be Biopharma

Advancing our science with bold humanity

rbracey

by

CAMBRIDGE, Mass.–Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BeCMs), today announced that Chief Executive Officer Joanne Smith-Farrell, Ph.D., will present at the annual Cell & Gene Meeting on the Mesa to be held October 10-12 in Carlsbad, California, and livestreamed globally.

Details regarding the Be Biopharma presentation at the conference are as follows:

Event: 2023 Cell & Gene Meeting on the Mesa

Presentation: About B Cells: A New Class of Cellular Medicines

Date: October 11, 2023

Time: 4:15-6:00pm PT

Location: Park Hyatt Aviara Resort, 7100 Aviara Resort Dr., Carlsbad, California 92011

Dr. Smith-Farrell will also participate on October 12 in an interactive discussion about resourcing strategies to support advancing innovation while meeting the practical and economic considerations of R&D.

Organized by the Alliance for Regenerative Medicine, the Cell & Gene Meeting on the Mesa is a three-day conference featuring more than 120 dedicated company presentations by leading public and private companies, highlighting technical and clinical achievements over the past 12 months in the areas of cell therapy, gene therapy, gene editing, tissue engineering, and broader regenerative medicine technologies, as well as over 100 panelists and featured speakers.

Virtual attendance is available, which includes a livestream of the Be Biopharma presentation and the ability to view all conference sessions on-demand. Please visit https://meetingonthemesa.com for full information including registration. Complimentary attendance at this event is available for credentialed investors and members of the media only. Investors should contact Savannah Bryant at sbryant@alliancerm.org and interested media should contact Stephen Majors at smajors@alliancerm.org.

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.

by

CAMBRIDGE, Mass. — Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BeCMs), today announced that Chief Executive Officer, Joanne Smith-Farrell, Ph.D., will present at the Jefferies Healthcare Conference being held in New York, NY, June 7-9, 2023. Company management will also be available for one-on-one meetings.

Presentation Details:

  • Thursday, June 8, 2023
  • 9:30-9:55 a.m. EST
  • Track 3

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.

by

Findings Presented at Late-Breaking Oral Session at American Society of Gene & Cell Therapy 26th Annual Meeting

 

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

Contacts

Be Bio Investor and Media:
Stephanie Fagan
ir@be.bio
media@be.bio

by

Preclinical Research Shows B Cell Medicines Durably Produce Functional Biologics and Engraft without Preconditioning

Platform Modularity Drives Creation of B Cell Medicines Across Multiple Diseases

CAMBRIDGE, Mass.–(BUSINESS WIRE)– Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BeCMs), will present preclinical research today showing the precise genome engineering of human B cells to express diverse therapeutic proteins using the company’s proprietary platform. The findings will be presented during an oral session at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting at 2:15-2:30 p.m. PST with additional data in poster presentation 1453 on Friday, May 19th from 12:00-2:00 p.m. PST.

Plasma cells are terminally differentiated B cells, which can live for decades1 and have the capacity to secrete extremely high levels of protein2 making them attractive for the sustained delivery of biologics to treat a wide range of diseases. However, it has historically been challenging to genetically engineer B cells efficiently, precisely, and in a manner that could produce proteins at therapeutic levels over long durations. Leveraging the convergence of advanced gene editing, deep insights into B cell biology and cell therapy technologies, Be Bio has designed a versatile CRISPR/Cas9 engineering platform capable of delivering a gene of interest via homology-directed repair (HDR) to produce stable BeCMs.

“In a short two years, Be Bio has validated key concepts of our B cell medicine platform including editing precision and efficiency, reproducible engraftment, and durable functional protein expression with the goal of creating a new class of cellular medicines with broad therapeutic utility,” said Dr. Rick Morgan, Chief Scientific Officer, Be Bio. “B cell medicines have the potential to transform the lives of patients – they can be redosed when required, delivered autologously and allogeneically, and can be administered without preconditioning – offering distinct advantages over other advanced therapies.”

Be Bio Platform Attributes

Engineering Precision and Efficiency:

Depending on the desired therapeutic protein expression level, the platform can target gene insertions to safe harbor sites as well as sites transcriptionally active in B cells. Across transgenes, targeting a transcriptionally active B cell site can enable up to a tenfold increase in protein secretion compared to insertion at the CCR5 safe harbor site. In addition, precisely targeted integration significantly reduces the risk of random gene insertion.

Using optimized cell culture and engineering conditions, the platform achieves gene knockouts with greater than 90% efficiency, stable gene insertion via precise HDR with up to 60% efficiency as measured by digital droplet PCR, and multiplexed expression of two genes with efficiencies above 20% as measured by flow cytometry.

Durable and Functional Protein Expression:

We observed the robustness of the platform through the expression of multiple therapeutic proteins such as Factor IX (FIX) for hemophilia B, acid sphingomyelinase (ASM) for Niemann-Pick Diseases (NPD) and an anti-CD19/CD3 bispecific T cell engager for acute lymphoblastic leukemia (ALL).

In each of two donors, FIX was detected in mouse plasma and lasted for greater than 18 weeks post BeCM transfer demonstrating persistence. In a separate experiment, BeCM-secreted ASM corrected the disease phenotype in NPD (SMPD1) gene knock-out cells.

In addition, in vitro and in vivo anti-tumor activity was observed. Potent in vitro anti-tumor activity was shown when supernatant from bispecific T cell engager-producing BeCMs directed primary human T cells to kill Raji tumor cells (CD19+). In a study conducted by Be Bio’s scientific co-founders and collaborators from the Seattle Children’s Research Institute, engineered B cells produced bispecific T cell engagers in vivo that mediated T cell activation and showed anti-tumor efficacy in a patient-derived xenograft mouse model3.

Rapid Screening:

To supplement adeno-associated virus (AAV) vector-mediated HDR, a rapid plasmid-based screening protocol was developed. The plasmid-based platform efficiently identifies the appropriate parameters for the secretion of a given protein of interest in primary B cells enabling rapid development from idea to prototype. The screening protocol assesses gene and protein design parameters for optimal transgene expression levels.

Engraftment without Preconditioning:

Rapid homing (within one day) and engraftment without preconditioning were shown in two models. In immunodeficient (NOG-hIL6) mice, BeCMs engrafted and persisted for greater than 100 days. In non-human primates with intact immune systems, BeCMs administered by intravenous infusion homed to and engrafted in the bone marrow and spleen.

These fundamental platform attributes overcome historical challenges for scalable and effective B cell engineering. The platform has the potential to transform the power of B cells into the development of autologous and allogeneic B cell medicines and unlock a pipeline of product candidates for broad and meaningful therapeutic utility in rare disease, cancer and beyond.

# # #

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
3 Hill et al (2023, May 16-19) Human Plasma Cells Engineered to Produce Bi-Specific T cell Engagers Show In Vivo Anti-Tumor Efficacy [Conference Abstract]. American Society of Gene & Cell Therapy 26 Annual Meeting.

Contacts

Investors and Media:
Stephanie Fagan
ir@be.bio
media@be.bio

by

Data Selected for Oral Presentation from Late-Breaking Abstract from NIH-Partnered Study Showing Engraftment without Preconditioning in Non-Human Primates

Engineered B Cells Demonstrate In Vivo Anti-Tumor Efficacy with Bi-specific T Cell Engagers

Additional Studies Demonstrate Precise Engineering and Expression of Multiple Therapeutic Proteins

CAMBRIDGE, Mass. May 2, 2023 – Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BeCMs), announced that it will present new data from preclinical research and collaboration programs at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting taking place May 16-20, 2023, in Los Angeles, Calif.

A late-breaking abstract was selected for oral presentation from Be Bio’s collaboration study with the National Heart, Lung, and Blood Institute, National Institutes of Health in which homing and engraftment of plasma cells were observed from peripheral B cells without preconditioning in immune competent non-human primates. In a separate oral presentation, the precise engineering of B cells using Be Bio’s proprietary engineering platform will be featured. Additionally, a poster presentation will show the stable expression and continuous secretion of therapeutic proteins in vitro and in vivo. Finally, Be Bio’s scientific co-founders and collaborators from the Seattle Children’s Research Institute will present findings in which engineered B cells produced Bi-specific T cell engagers that mediated T cell activation and showed in vivo anti-tumor efficacy in a patient-derived xenograft model.

“Data from our preclinical research programs support the ability of Be Bio’s platform to unlock the power of B cells as the basis for a prolific and versatile product engine,” said Dr. Rick Morgan, Chief Scientific Officer, Be Bio. “We are inspired by the potential to transform patient lives with B cell medicines as we progress our lead candidate towards an investigational new drug application and advance our novel pipeline programs in rare disease and oncology.”

Details of the presentations are as follows:

  • Abstract 575, Poster Presentation: Human Plasma Cells Engineered to Produce Bi-Specific T Cell Engagers Show In Vivo Anti-Tumor Efficacy

         Presenter: Tyler Hill, MSTP, Seattle Children’s Research Institute

         Session Date/Time/Location: Wednesday, May 17, 12:00- 2:00 p.m. PT, Exhibit Hall A

  • Abstract 119, Oral Presentation: Precise CRISPR/Cas9 Genome Engineering of Primary Human B Cells Enables a New Class of Cellular Medicines Designed for Sustained Delivery of Therapeutic Biologics

         Presenter: Dr. Anja Hohmann, Senior Director, Cell Engineering, Be Bio

         Session Date/Time/Location: Thursday, May 18, 2:15 – 2:30 p.m. PT, Concourse Hall 152 & 153

  • Late Breaking Abstracts 1, Oral Presentation: Rhesus Antibody Secreting Cells Differentiated Ex Vivo from B Cells Engraft without Preconditioning in an Autologous Host and Represent a Novel Modality for Cell and Gene Therapy

          Presenter: Dr. David Young, National Heart, Lung, and Blood Institute, National Institutes of                   Health

          Session Date/Time/Location: Friday, May 19, 9:30 – 9:45 a.m. PT, Room 515 AB

  • Abstract 1453, Poster Presentation: Development of an Ex Vivo Gene Engineered B Cell Medicine Platform with Precision, Modularity, and Broad Therapeutic Utility

          Presenter: Dr. Hanlan Liu, Senior Vice President, Rare & Early Pipeline Research, Be Bio

          Session Date/Time/Location: Friday, May 19, 12:00 – 2:00 p.m. PT, Exhibit Hall A

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.

Investor and Media Contact:

Stephanie Fagan

ir@be.bio

media@be.bio