Roche-Backed Poseida's Non-Viral Allogeneic CAR-T Therapy P-BCMA-ALLO1 Shows 100% ORR in Subgroup of Relapsed/Refractory Multiple Myeloma Patients

December 13, 2023 / eMedClub News /--Recently,Poseida TherapeuticsAnnounced its collaboration with Roche (Roche) Co-developed allogeneicCAR-TTherapyP-BCMA-ALLO1Clinical1Positive Early Efficacy and Safety Results from Phase Trials，This therapy is used to treat recurrence./Refractory Multiple Myeloma (RRMM) Patient.

These data come from 33 heavily pretreated patients who were followed up for at least 4 weeks, with a median of 7 prior treatment lines. Among them, 11 received 500mg/m.2Or 1000mg/m2A cyclophosphamide preconditioning regimen was administered, followed by the injection of 2 million study treatment cells. The remaining patients received 300 mg/m² of cyclophosphamide prior to P-BCMA-ALLO1 treatment. Analysis showed that in patients who underwent intensive pre-treatment with adequate lymphodepletion,The objective response rate (ORR) for patients treated with CAR-T therapy P-BCMA-ALLO1 was 82% (n=9/11), with deep clinical responses.Patients pretreated with cyclophosphamide show better expansion and persistence of CAR-T cells.In previously untreatedBCMATargeted BispecificTCell Engager Antibody Therapy PatientsORRThen it is100%。

Poseida also conducted cell kinetic analyses on two patients showing high levels of CAR-T cell expansion. These studies demonstrated that the cells remained measurable in the peripheral blood of one patient for at least four weeks and persisted and remained measurable in the bone marrow of another patient for at least six weeks. Additionally, after administration,The infused cells in these two patients proliferated and differentiated, producing a population richer in effector T cells, including subsets of cytotoxic T cells.。

The therapy demonstrated favorable safety and reliability profiles, with no graft-versus-host disease (GvHD) or dose-limiting toxicity observed in all intention-to-treat (ITT) patients. The incidence of cytokine release syndrome (CRS) and neurotoxicity was low (both ≤ grade 2).

Poseida Therapeutics President Kristin Yarema said in a statement, "These findings are 'The first known publicly available dataset provides clear clinical evidence for the hypothesis that TSCM cells are an ideal cell type for allogeneic CAR-T.”。

Poseida's research products aim to address the limitations of other CAR-T therapies, including response duration, the ability to treat solid tumors, and safety issues. According to Poseida's official website, the company’s CAR-T cells differ from typical CAR-T cells as they do not contain the scFv structure, but insteadComposed of fully human Centyrin domains, engineered based on its proprietary piggyBac non-viral gene delivery system to generate a high proportion of stem cell memory T cells (Tscm).。Tscm cells are the only long-lived T cells with self-renewal capabilities, able to differentiate into the entire T cell subset, thereby triggering an effector response against cancer, potentially making candidate drugs more effective, less toxic, and more durable.Data show that TSCM cells can survive for years after CAR-T treatment, potentially providing long-lasting anti-tumor protection.

From the perspective of current technology, the main method for producing CAR-T therapy is virus-based, which has limitations in delivering genetic material and potential safety risks. AndThe piggyBac DNA system delivers CAR molecules to T cells without using viruses and can carry more genetic material.. This is expected to bring about CAR-T therapies with lower costs and shorter production times, addressing the current bottleneck.To explore the iterative updates of CAR-T therapy technology, the 2024 IBI EXPO Biotech Innovation Conference has specially set up the 6th Tumor Immunotherapy and Cell Therapy Technology Seminar, gathering industry experts in the field of cell therapy to jointly explore future development directions!

(Guests for participation and speeches are being recruited simultaneously~)

The non-viral piggyBac DNA modification system can produce better CAR-T therapy, with the following additional features:

➤Large loading capacity: The cargo capacity of piggyBac may be 20 times that of lentiviral vectors, which can effectively deliver large genes, including the possibility of various CAR or TCR molecules;

➤Reduce Risk: Compared with viral vector systems, non-viral vector systems reduce the risk of mutagenesis and tumorigenesis;

➤Stable and Efficient: This technology provides high gene insertion efficiency and stable transgenic expression;

➤Production Advantages: Can be produced in a shorter time, with manufacturing costs lower than the viral method.

On October 17, 2023, TriArm Therapeutics (Stardust Bio) announced its non-viral rapid preparationFIT-CD19 CAR-T Immunotherapy for the Treatment of Non-Hodgkin's Lymphoma Receives FDA Approval for IND Application, officially entering the clinical trial stage. The rapid preparation speed and low preparation cost of FIT-CD19 CAR-T make this treatment more likely to be extended to a wider range of medical needs.

Precigen Presented PRGN-3005, a Non-Viral Multi-Gene CAR-T Therapy, at ASCO 2023: Phase 1/1b Clinical Trial Data Show Safety and Efficacy in Patients with Advanced Platinum-Resistant Ovarian Cancer. PRGN-3005 UltraCAR-TUtilizing Precigen's advanced Sleeping Beauty transposon system to co-express antigen-specific CAR, specifically targeting tumor cells, membrane-bound interleukin-15 (mbIL15) enhances in vivo expansion and persistence, combined with a termination switch for precise elimination of CAR-T cells.Advanced non-viral multi-gene delivery system and overnight dispersion manufacturing process, which do not require ex vivo activation and expansion of T cells,Autologous CAR-T cells can be reinfused into patients within just one day after gene transfer, reducing the waiting time for autologous CAR-T therapy.May address the major limitations of current T-cell therapies. At the same timeBy addressing the suppressive tumor microenvironment through a novel mechanism of intrinsic checkpoint blockade, eliminating the need for complex and costly gene-editing technologies.`, which is expected to reduce the treatment price of CAR-T, truly making CAR-T therapy "accessible to ordinary households."`

On September 17, 2022, the clinical trial application for "Targeted CD19 Non-viral PD1 Site-specific Integrated CAR-T Cell Injection" by Shanghai Bangyao Biotech has been accepted by the CDE. BRL-201 utilizes theNon-viral targeted integration CAR-T technology can insert the CAR sequence into a specific site of the T-cell genome without using a viral vector, achieving stable CAR integration and endogenous gene regulation in one step. It has the advantages of low production cost, short preparation time, and high product uniformity, avoiding the risk of tumorigenicity caused by random insertion.It is worth mentioning that this isThe world's first targeted CD19 non-viral PD1 site-integrated CAR-T product.

On August 31, 2022, the IIT data of BRL-201 was published in the top journal Nature, showing that:The complete response rate (CR) reached 87.5%, and the objective response rate (ORR) was 100%.; The longest cancer-free survival period exceeds 2 years, and the patient is currently still in a state of complete disease remission. In terms of safety, no CAR-T-related neurotoxicity or cytokine release syndrome above grade 2 was observed in all 8 patients.