Pipeline
Strike is building a pipeline of first in class in vivo CAR-M candidates for autoimmune disease and cancer, as well as a next generation in vivo CAR-T program that is developed in collaboration with AbClon Inc. under a Eurostars grant.
LNP-based in vivo CAR therapy constitutes an off-the-shelf alternative to autologous CAR therapies, such as the approved CAR-T treatments. It holds the potential to be equally effective without the need for lengthy and costly personalized production and without the need for chemotherapy-induced ymphodepletion. Moreover, the effect is transient, which reduces potential safety concerns and allows for repeated administration and titration of its pharmacodynamic effects. Our LNP-based platform enables selective delivery to defined immune cell populations with low risk of immunogenicity while the site-directed antibody conjugation results in high efficacy.
In vivo CAR-M for autoimmune disease and cancer
Strike develops first in class in vivo CAR-M therapies based on targeted LNPs that deliver CAR mRNA to monocytes. When the monocytes express the CAR on its cell membrane it leaves the blood stream and is transformed into a macrophage that infiltrates inflamed tissues. Specifically, the programs aim at generating CAR-Ms that target either autoreactive T cells or regulatory T cells for autoimmunity and cancer, respectively. While monocytes and macrophages are natural phagocytes and can be transiently reprogrammed using naked LNPs, our targeting technology allows a more than 10-fold increase in uptake and expression, thus increasing efficacy and reducing potential off-target toxicity.
The LNP-based in vivo CAR-M is targeted to surface receptors on circulating monocytes. The complex is taken up and the mRNA translated into a T-cell targeting CAR on the cell membrane.
Our lead program is an in vivo CAR-M that depletes autoreactive T cells and that is intended for the treatment of T-cell dependent autoimmune disease, including rheumatoid arthritis and spondyloarthritis.
A second in vivo CAR-M program targets tumor infiltrating regulatory T cells and aims at augmenting the effect of cancer immunotherapies for the treatment of solid tumors.
The CAR-M cell distributes into inflamed tissues and attacks autoreactive T-cell or regulatory T cells.
In vivo CAR-T for autoimmune disease and cancer
StAb19 is a B-cell targeting in vivo CAR-T developed in collaboration with AbClon Inc under a Eurostars grant. It is based on a CD3-targeting antibody and a novel CD19 CAR binding to a unique epitope and optimized for fast off-rate to prolong CAR-T activation. The CD19 CAR mRNA is thus delivered to T cells that are subsequently reprogrammed to in vivo CAR-Ts targeting B-cells.
The candidate is intended for treatment of B-cell dependent autoimmune disease and B-cell malignancies. Autoreactive B cells play a key role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE).
StAb19 is based on an LNP carrying mRNA for an anti-CD19 CAR and a Bispecific antibody that binds to the LNP and to CD3. The antibody will deliver the LNP-cargo to T-cells inside the body, which will take up the mRNA and start expressing anti-CD19 CARs. The T cells are thus reprogrammed to seek out and kill CD19-expressing B cells.