In 2015, EXUMA initiated ambitious efforts to discover platform technologies that could enable
cell and gene therapies to deliver their full potential to patients.
EXUMA’s Platforms may Enhance the Efficacy, Safety or Durability of CAR-T Products Without Requiring Chemotherapy
Rapid Cell Product Manufacturing Process
rPOC SC Treatment
Chemotherapy Free CAR-T
Vascular Access
Lentivector + PBMC Incubation
& Automated Cell Processing
1 day
Vialing and
Cryopreservation
LVLL + PBMC
Rapid release
testing
Ready for
Administration
Subcutaneous
injection
LVLL + PBMC
Tertiary lymphoid structure
forms at SC injection site
CAR-T cells distribute
from the lymphatics
CAR-T cells engage
their target
rPOC SC Platform
rPOC SC is enabled by EXUMA’s CD3 LV and FITNESS DRIVER technologies
A PBMC formulation manufactured with CD3-targeted LV is administered subcutaneously. A synthetic lymph node forms at the injection site from which CAR-T cells mature, expand, and distribute to sites of disease. Our global team is pioneering this novel autologous treatment for autoimmune diseases and cancer, aiming to make cell therapy more accessible to patients.
- PBMC’s are incubated with CD3-Targeted LV
- FITNESS DRIVER, CAR, and cell removal epitope are expressed on CD3+ T cells
- FITNESS DRIVER supports all in vivo expansion without the need for lymphodepleting chemotherapy
T Cell Targeted
Lentivector (LV)
Injection
LV
LV activates, enters,
and transduces CD3
lymphocytes
CAR-T cells enter
the circulation
CAR-T cells engage
their target
GCAR Platform
In vivo CAR therapy enabled with the CD3-Targeted lentivector and FITNESS DRIVER that uses existing lymph nodes for CAR-T expansion.
- CD3-Targeted LV formulated for injection
- FITNESS DRIVER enabled all in vivo expansion & optimal persistence & cytotoxicity
- Safety and efficacy of the unique cell phenotype
Technologies
Our Technologies Enable the Development of Better Medicines without the Limitations of Cell Therapy
LV
CD3-Targeted LV
CD3-Targeted lentivector binds, activates and enters CD3+ lymphocytes.
- No cell purification steps
- Short 4-hour incubation with vector and leukopac material
- No ex vivo culture/expansion
- Reduced manufacturing time, cost, and complexity
LV T cell activation causes a primary expansion of the CAR-T cells in vivo, prior to their subsequent CAR-engagement driven expansion.
FITNESS DRIVER
Identified from a massively parallel (~7 million), knock-in, gain-of-function screen of intracellular signaling domains (native and non-native to T cells).
- Produces a unique favorable effector cell phenotype (T & NK) optimized for persistence and cytotoxicity
- Enables chemotherapy-free (cytokine-independent) proliferation
- Compact, multi-unit, semi-synthetic signaling construct
- All in vivo expansion shortens cell processing time and produces a stemlike effector cell phenotype
Tumor Metabolism Regulated CARs
Expands the universe of targets beyond blood cancer antigens.
- Addresses exposure dependent risk of on-target, off-tumor toxicity
- Reversibly exploits metabolically distinct characteristics within the tumor microenvironment for binding selectivity
- Improves the therapeutic index, permitting increased exposure in the setting of “over-expressed” tumor associated antigens
- Technology is portable across EXUMA’s cell therapy technology portfolio (CCT3, rPOC, GCAR)
Synthetic CAR Ligands
Synthetic CAR Ligands (SCL) are non-CAR target epitope constructs encoded by mRNA.
- Provides antigen independent CAR stimulation for PK modulation (Cmax, AUC, durability)
- Potential to support in vivo expansion with lower T cell doses
- Eliminate the cost, complexity, and toxicity of repeated lymphodepletion required for CAR-T re-dosing
