What is the work you’re leading at Be Bio as CEO and Director?
We are pioneering a groundbreaking new class of in vivo biologics, engineered B Cell Medicines (BCMs). Using CRISPR/Cas9-based precision genome editing, BCMs leverage the biosynthetic machinery of human B cells to produce therapeutic proteins in vivo. They are exceptionally versatile, and we’ve successfully engineered BCMs to produce active peptides, enzymes, bispecifics, engagers, fusion proteins, and monoclonal antibodies (IgG, IgA, and IgM).
Our lead programs aim to establish new standards of care for genetic disease by delivering yearly protein replacement for patients with Hemophilia B (BE-101, in clinical development) and Hypophosphatasia (BE-102, in late preclinical development). Beyond these programs, we’re developing allogeneic BCMs to amplify the breadth, scale, and global impact of this transformative platform across genetic disease and other therapeutic areas.
What gap in treatment or current hurdle of existing therapies does an engineered B cell approach mitigate?
We believe B Cell medicines represent the potential to replace ex vivo therapeutic proteins produced by non-human cells with in vivo therapeutic proteins generated by engineered human B cells. BCMs function as in vivo factories, continuously producing a therapeutic protein, versus traditional cancer cell therapies such as CAR-T in which the cell itself acts as the effector or "weapon" against disease.
BCMs are engineered ex vivo to produce the desired target protein, and, once infused home to / engraft in the bone marrow. There, they continuously secrete therapeutics with human post-translational modifications at constant levels for a year or more – re-dosably, titratably, and without the need for preconditioning.
Why are B cell medicines so attractive as a modality?
BCMs for immuno-oncology are designed to leverage B cell attributes to address the challenges faced by the immuno-oncology field, including variable efficacy, tumor heterogeneity, and the complexities of targeted delivery. They can deploy an allogeneic format with a molecular kill switch to enable tunable durability in an off-the-shelf product.
As natural components of the immune system, B cells offer unique advantages. While most current therapeutic monoclonal antibodies are IgG, we have engineered B cells to secrete IgA and IgM monoclonal antibodies. IgAs are particularly effective at targeting specific sites of action, including intracellular targets. IgMs, with their pentameric structure, provide significantly enhanced antigen-binding capabilities.
How are you improving upon existing therapies?
Our lead program, BE-101, is designed to secrete Factor IX at constant levels for a year or more. In contrast, recombinant Factor IX therapies require life-long infusions every 1-2 weeks due to short protein half-lives. Liver-directed AAV gene therapies result in variable outcomes that cannot be adjusted because they cannot be re-dosed or titrated. In the case of children, AAV gene therapies are unsuitable for pediatric patients since, as the child grows, they cannot be re-dosed or titrated to meet increased demand for factor.
BE-102 leverages yearly dosing at constant levels in conjunction with BCMs’ ability to produce complex proteins, such as a complex enzyme/IgG4 Fc fusion protein with a bone-targeting tag. This could provide patients with a treatment other than the only available current therapy for hypophosphatasia, which requires 3-6 painful injections a week and is only used in severe cases. It could also provide a new treatment for hypophosphatasia patients with no therapeutic option.
What are the challenges you’re facing in developing engineered B cell therapies, and how are you navigating those challenges?
A key challenge is balancing innovation with scalability and manufacturability. BCMs must meet rigorous quality standards while remaining feasible for clinical and commercial scale production.
We’re also navigating a regulatory landscape with a new class, working closely with agencies to establish appropriate frameworks for safety and efficacy. Tackling complex scientific and translational hurdles head-on, from optimizing genome editing in B cells to ensuring consistent engraftment and therapeutic protein expression, is central to our mission.
Above all, we stay focused on delivering meaningful, long-term impact for patients, addressing future challenges like accessibility, affordability, and durability.
What is the future for BCMs?
We have only begun to scratch the surface of the innovative potential of BCMs for immuno-oncology. First, we have demonstrated in vivo proof-of-concept with a BCM-produced CD19/CD3 T cell engager. It showed robust tumor control and elimination in a patient-derived xenograft murine model of Acute Lymphoblastic Leukemia – all from a single infusion of BCMs.
Beyond antibody secretion, B cells play critical roles in antigen presentation, interaction with T cells to amplify anti-tumor responses. BCMs can also be targeted to locations such as tumors, bone, and the central nervous system (CNS). These combined capabilities position BCMs as a versatile platform for helping to address the unique challenges of immuno-oncology applications.
What keeps you passionate about this field?
The extraordinary moment we’re living in fuels my passion. Advances we could only dream of a decade ago are now within reach, and we have the tools to solve problems that were once thought unsolvable. I am particularly driven by the belief that B Cell Medicines have the potential to be one of the most broadly impactful contributions to medicine of my generation. Being part of this groundbreaking work – pioneering a new class of medicines and pushing the boundaries of what’s possible – is what keeps me inspired and motivated every single day.
Like so many, my life story includes chapters in which people I loved faced life-limiting illnesses and turned to medicine for answers, which profoundly shaped my experience of the urgency and importance of translating science into medicines that matter. As you strive to make a difference in increasingly impactful ways, you’ll not only experience the deep satisfaction of pushing the edge of science and medicine, but you’ll also find that career growth, success, and fulfillment naturally follow – often in ways more profound than you may have imagined.
What was a piece of career advice that helped you during your career that you would pass on to young people, particularly young women, entering careers in science?
I’d offer three “first principles:”
- Work on things that matter
- Be known as someone who gets things done
- Know that you are enough
It’s easy to believe that career success will happen when you have all the answers, prove your worth, and learn to avoid mistakes. But that day doesn’t ever really come, especially not for those of us pushing the frontiers of science and medicine.
What can come is a day when your focus shifts from what you aren’t yet/ can’t yet/ don’t yet, to what you are/ can/ do. That shift is powerful – energy once spent on “becoming” is instead channeled into “being” who you already are and throwing your whole self “all-in” to help your team make a difference for the patients whose lives depend on your work.
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