Poseida Therapeutics Inc (PSTX)

[jondoeuk]

Presentations at the American Society of Gene and Cell Therapy Annual Meeting;

Preclinical Evaluation of Combined Adeno-Associated Virus and Nanoparticle Delivery of piggyBac Transposon System for Durable Transgene Expression in the Growing Neonatal Murine Liver https://poseida.com/wp-content/uploads/2021/05/ASGCT-2021-In-vivo-gene-therapy-JJ_FINAL.pdf

In a preclinical study, Poseida evaluated concomitant delivery of recombinant adeno-associated virus (rAAV) vectors and novel nanoparticle (NP) vectors using its piggyBac and "Super" piggyBac (SPB) technologies in order to deliver transposon and transposase in a growing neonatal mouse model. Data demonstrated that the piggyBac DNA Delivery System was effective in using both rAAV and NP vectors to introduce edited genes into targeted hepatocyte genomes. Poseida also found that SPB, a hyperactive form of the transposase, produced stable vector integration into the hepatocyte genome for more than three months, compared to transpose alone. Similarly, delivery of a novel NP formulation using SPB produced efficient delivery of mRNA to the liver hepatocytes, with similarly high levels of durability in the transgene expression. Taken together, these preclinical findings suggest the potential of piggyBac and SPB technology for gene therapies that treat congenital liver disease in infants and young children.

P-BCMA-ALL01: A Fully Allogeneic Stem Cell Memory T Cell (TSCM) CAR-T Therapy Targeting BCMA for the Treatment of Multiple Myeloma Shows Potent Anti-Tumor Activity https://poseida.com/wp-content/uploads/2021/05/ASGCT-2021-P-BCMA-ALLO1-Poster-Max-Richter.pdf

P-BCMA-ALLO1 is Poseida's first fully allogenic product candidate targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. In in vitro and in vivo preclinical studies, P-BCMA-ALL01 showed effective, targeted cancer cell killing and cytokine secretion, with similar or superior performance in anti-tumor efficacy compared to an autologous CAR-T therapy. Inclusion of a proprietary "booster molecule" in the allogeneic manufacturing process further improved expansion of gene-edited cells and enabled production of hundreds of patient doses from a single manufacturing run, thereby reducing the manufacturing cost per dose into the same range as that of a monoclonal antibody.

Anti-c-kit CAR-T Cells Afford Effective Eradication of Human AML and Normal Hematopoietic Cells in a Preclinical Model of Safer Non-Genotoxic Stem Cell Transplant Conditioning https://poseida.com/wp-content/uploads/2021/05/ASGCT-2021-Poster-Deck-cKit-Nina-Timberlake.pdf

Poseida is investigating its anti-c-kit CAR-T program, which leverages its proprietary piggyBac DNA Delivery System in preclinical studies as a potentially safer precursor conditioning therapy to the transplantation of hematopoietic stem cells (HSC) for patients suffering from AML. The piggyBac delivery vectors under investigation include a transposon that generates pure CAR+ product as well as a safety switch that allows rapid clearance of the reactive CAR-T cells prior to donor transplant of hematopoietic stem cells. Preclinical data to be presented in the poster showed that the lead CAR-T cells that express the anti-c-kit binder (CAR 1) deplete up to 92% of human CD34+ stem and progenitor cells in bone marrow within 48 hours. Additionally, an enhanced anti-c-kit CAR-T product, CAR 2, killed an estimated >99% of leukemia cells, exceeding the killing ability of a single dose of 30 mg/kg dose of busulfan. These encouraging data suggest that stem cell-directed CAR-T cells may be a safer preconditioning regimen compared to the current standard of care and may expand access to treatment for acute myeloid leukemia patients needing HSC transplant.