P-PSMA-101 was evaluated in two distinctive models of prostate cancer in immune deficient mice. The first utilized an androgen-sensitive human prostate adenocarcinoma cell line, called LNCaP, administered subcutaneously as a solid tumor. The second evaluated anti-tumor efficacy in a bone metastasis model using an androgen insensitive human prostate cell line called PC3.hPSMA. Both studies also compared P-PSMA-101 with a version of a traditional single-chain variable fragment (scFv)-based anti-PSMA CAR-T (J591) that has been tested clinically.
"In addition to decreasing the tumor burden below detectable levels, P-PSMA-101 persisted in the peripheral blood with greater than 70% of T-cells exhibiting a Tscm phenotype," said Eric Ostertag, M.D., Ph.D., founder and CEO at Poseida. "We are encouraged that P-PSMA-101 anti-tumor potency against PC3, a cell line engineered to express human PSMA, was seen at a dose three times lower than a comparable anti-PSMA CAR-T binder in clinical development. Furthermore, P-PSMA-101 reduced LNCaP tumor, a naturally PSMA-expressing cell line, to below the limit of detection whereas J591 did not significantly control tumor burden. These findings in a solid tumor model are consistent with the finding we've seen with our anti-BCMA program in hematologic cancers."
Poseida's CAR-T modifications are engineered using its proprietary piggyBac™ non-viral gene delivery system and fully-human Centyrin™ binding domain, which enables a streamlined and scalable manufacturing process that does not employ viruses, cytokines or magnetic beads and consistently produces high concentrations of modified T-cells necessary to treat patients. This process yields an exceptionally high percentage (>70%) of the highly desirable Tscm phenotype, an early memory population that correlates with complete responses in CD19 CAR-T cell clinical trials. In contrast, competitor products typically report 0-20% Tscm cells.
Key findings include:
Similar unprecedented efficacy was seen in preclinical models with Poseida's lead therapeutic, P-BCMA-101, an autologous CAR-T therapy for multiple myeloma, which is also comprised of predominantly stem cell memory T-cells and is currently being tested in a Phase I clinical trial.
The presentation titled "PSMA-specific CARTyrin T-Stem Cell Memory Therapy Eliminates Solid Tumor in Subcutaneous Prostate Cancer Model" by Jenessa B. Smith, Ph.D., Research Scientist at Poseida, takes place today December 5, 2017, from 10:30 a.m. -12:30 p.m. ET at the American Association for Cancer Research Prostate Cancer: Advances in Basic, Translational, and Clinical Research meeting in Orlando, Florida.
P-PSMA-101 is a CAR-T immunotherapy designed to supercharge a patient's own T-cells to safely and effectively eliminate tumor cells carrying prostate-specific membrane antigen (PSMA), which is expressed on the majority of prostate cancer cells. P-PSMA-101 employs a PSMA-specific Centyrin™ binding domain and is engineered using a non-viral gene delivery system called the piggyBac™ DNA Modification System, which leverages the technology's capability to deliver 30 times more cargo than traditional virus-based CAR-T cell modification systems. P-PSMA-101 has demonstrated potent anti-tumor activity, persistent and durable response, significant T stem cell memory, a high concentration of P-PSMA-101 modified T-cells and no T-cell exhaustion. A unique feature of P-PSMA-101 and other Poseida CAR-T products is their exceptionally high percentage of stem cell memory T-cells, which has been shown in preclinical studies to lead to unprecedented durability of response without re-administration of treatment.
About Poseida Therapeutics Inc.
Poseida Therapeutics is translating best-in-class gene engineering technologies into lifesaving cell therapies. The company is developing CAR-T cell immunotherapies for multiple myeloma, prostate and other cancer types, as well as gene therapies for orphan diseases. P-BCMA-101 is Poseida's lead CAR-T therapy currently in Phase 1 clinical development for the treatment of multiple myeloma. Poseida has assembled a suite of industry-leading gene engineering technologies, including the piggyBac™ DNA Modification System, XTN™ TALEN and NextGEN™ CRISPR site-specific nucleases, and Footprint-Free™ Gene Editing (FFGE). For more information, visit www.poseida.com.
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