Poseida’s vision is to create best-in-class gene engineering technologies – spanning gene insertion, gene editing, and delivery. This robust set of industry-leading tools lays the foundation for developing a safer, more durable, and more efficient suite of treatments.
Benefits in Cell Therapy
Generating CAR-T products with desirable high percentage of TSCM cells
- Preferentially favors stem cell memory T cells (TSCM) and works well in resting T cells for potentially improved tolerability and more durable responses
- Large cargo capacity enables multi-CAR products, addition of safety switch, and selection gene
Benefits in Gene Therapy
Integrates into DNA delivering stable long-term expression
- Ideal for use in dividing tissues like those in juvenile liver
- Highly efficient integration may allow reduced dosing and single treatment cures
- Large cargo for delivering larger genes
- Delivered using AAV + nanoparticle or in vivo electroporation
Our proprietary piggyBac DNA Modification system is at the heart of our novel approach to treatments. With its unique design, piggyBac efficiently delivers extensive genetic cargo into cells, creating solutions far beyond earlier-generation therapies.
- Activity in virtually any cell type with broad applicability
- Results in high expression levels
- Works in resting T Cells and has a preference for Tscm cells
- No practical cargo limitations
- Delivery to a variety of ex vivo and in vivo cells and tissues
piggyBac DNA Modification System
A majority of today’s CAR-T therapies are produced using viral-based manufacturing, which carries significant risks:
- Patient safety concerns
- Limited genetic cargo capacity
- Undesirable phenotype of the final product
The non-viral piggyBac platform delivers CAR molecule genes to T cells, which generates CAR-T products with a high percentage of TSCM cells, providing distinct advantages over a viral approach:
- Therapies with potentially more consistent and durable responses
- Less toxicity
- Lower manufacturing costs
- Shorter manufacturing timelines
Our high-precision Cas-CLOVER gene editing technology has shown great promise in pre-clinical studies with little-to-no off-target activity. In our initial CAR-T applications, Cas-CLOVER can efficiently make multiple edits and can edit resting T cells.
Cas-CLOVER is a proprietary obligate homodimer nuclease system comprising elements of the Type IIS restriction endonuclease, Clo051. Using this enzyme for genome cutting makes it fully dimeric, giving it precise site-specificity. Cas-CLOVER uses a Cas9 enzyme altered to be unable to cut DNA. The dCas9 acts only as a DNA binding protein when combined with an appropriate guide RNA.
Cas-CLOVER features the advantages of first-generation CRISPR:
- Ease of design
- Low cost
Poseida is a leading innovator in developing gene delivery systems. Scaling our pre-clinical pipeline in gene therapies, we have developed multiple gene delivery technology platforms. This includes both an AAV and a nanoparticle program enabling tools like PiggyBac and Cas-CLOVER to be used in vivo to address various genetic disease.
We match the right applications with the right delivery mechanism – enabling development of potentially more safe and effective gene therapies to fill critical unmet needs.
Gene Delivery Technology Platforms
Poseida’s science enables best-in-class CAR-T therapies that we believe will set new standards of excellence for this revolutionary treatment for cancer and beyond.
Not all T cells are created equally. Poseida has developed a differentiated CAR-T product composed primarily of the earliest-stage T cells, known as stem memory T cells (TSCM cells). TSCM cells are long-lived, self-renewing and multipotent, with the capacity to reconstitute the entire spectrum of T cell subsets, including TEFF cells. They have been shown in clinical trials to have the potential to survive for years after treatment, providing the potential for long-lived duration of response.
In a retrospective analysis of patients in our BCMA clinical trial who received CAR-T therapies, best responses were correlated with the percentage of TSCM cells occurring in the patient’s product prior to therapy.
T cells play a central role in immune response, moving through multiple stages of growth and maturation before they become the killer T cells, or T effector cells, that attack foreign pathogens and cancer cells. While these T effector cells can be engineered to efficiently kill cancer cells, they are short-lived — lasting only weeks to months. This means patients receiving today’s CAR-T therapies, which are largely comprised of modified T effector cells, have the potential to relapse unless their initial dose is capable of quickly eliminating every cancer cell in the body.
Because of their unique properties, TSCM cells are potentially safer and more effective than early-generation CAR-T products. We believe delivering a high percentage of TSCM cells will drive more gradual tumor killing, thereby inducing less inflammatory cytokine response and improving the tolerability profile of our CAR-T product candidates relative to those of existing CAR-T therapies. Conceptually, through these TSCM cells, we are able to deliver a predominantly self-renewing CAR-T “prodrug” that can engraft and produce unlimited T effector “drug,” an approach that potentially results in more potent activity and duration of response.