Poseida Therapeutics Presents Novel BCMA-Specific CAR-T Therapy at CAR-TCR Summit
- Category: DNA RNA and Cells
- Published on Wednesday, 06 September 2017 16:40
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SAN DIEGO, CA, USA I September 06, 2017 I Poseida Therapeutics Inc. (“Poseida”), a San Diego-based company translating best-in-class gene editing technologies into lifesaving cell therapies, today presented preclinical data on P-BCMA-101, the company’s BCMA-specific CAR-T drug candidate for the treatment of multiple myeloma, at the CAR-TCR Summit on T Cell Immunotherapies in Boston.
The presentation, given by Devon J. Shedlock, Ph.D., senior director of immuno-oncology at Poseida, expanded upon recent preclinical studies of P-BCMA-101 demonstrating potent and persistent anti-tumor activity, elimination of tumors following relapse without re-administration of drug and prolonged survival compared to other BCMA CAR-T agents in the same preclinical model. Poseida’s CAR-T modifications are engineered using its proprietary piggyBac™ non-viral gene delivery system and 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 stem cell memory T cell subtype (Tscm) even when starting with patient materials where Tscm is very rare. In contrast, competitor products typically report 0-20% Tscm cells. Recent studies show that Tscm cells may result in a CAR-T product that is more efficacious in patients.1
Poseida has now demonstrated that P-BCMA-101 can achieve 100% survival in an ultra-stringent p53 knockout mouse xenograft model developed at MD Anderson Cancer Center. These mice are implanted with a highly aggressive human myeloma cell line that has been genetically modified to knockout p53, a tumor suppressor protein involved in many types of cancer. This system accurately models the 30-50% of relapsed/refractory multiple myeloma patients whose tumor develops perturbations in the p53 pathway.2 Multiple myeloma tumors with p53 mutations are not fully responsive to any existing therapeutic on the market and these patients have an extremely poor prognosis.
Key findings include:
- Potent anti-tumor activity: P-BCMA-101 treatment typically reduced tumor burden to the limit of detection within 6 to 9 days. Conversely, all untreated controls succumbed to disease.
- Persistent and durable response: P-BCMA-101 expands and persists in treated mice, eliminated tumor following relapse and prolonged survival with all treated mice surviving to the end of the 90-day study.
- No T-cell exhaustion observed: P-BCMA-101 did not exhibit effects of CAR-mediated tonic signaling, a common cause of T-cell exhaustion that leads to poor durability. Tonic signaling is caused by oligomerization of unstable binding domains commonly seen with traditional single-chain variable fragment (scFv) CARs.
Poster presentations are available on the publications page of Poseida’s website at www.poseida.com/publications.
Poseida’s lead product candidate is a B-cell maturation antigen (BCMA)-specific CAR-T drug candidate (P-BCMA-101) for the treatment of patients with relapsed or refractory multiple myeloma. P-BCMA-101 employs a BCMA-specific Centyrin™ binding domain and is engineered using a non-viral gene delivery system called 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-BCMA-101 has demonstrated potent anti-tumor activity, persistent and durable response, significant T-cell memory, a high concentration of P-BCMA-101 modified T-cells and no T-cell exhaustion. A unique feature of P-BCMA-101 is its strong stem cell memory phenotype, which has shown in preclinical studies to lead to unprecedented durability of response without re-administration of treatment. Poseida expects to initiate a Phase 1 clinical study of P-BCMA-101 in 2017.
About Poseida Therapeutics, Inc.
Poseida Therapeutics is translating best-in-class gene editing technologies into lifesaving cell therapies. The company is developing CAR T-cell immunotherapies for multiple myeloma and other cancer types, as well as gene therapies for orphan diseases. Poseida has assembled a suite of industry-leading gene editing 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.
- Melenhorst J. et al. “Correlates of Response to CD19-directed CART Cell Therapy in Chronic Lymphocytic Leukemia.” 20th ASGCT Annual Meeting, 12 May 2017.
- Drach, J, et al. “Presence of a p53 Gene Deletion in Patients with Multiple Myeloma Predicts for Short Survival after Conventional-Dose Chemotherapy.” Blood, U.S. National Library of Medicine, 1 Aug 1998, www.ncbi.nlm.nih.gov/pubmed/9680348.
SOURCE: Poseida Therapeutics