- ALLO-329 Induces Deep, Transient Depletion of CD19+ B Cells and CD70+ T Cells, and Reduction in IgG and IgM without Lymphodepletion in Humanized Murine Models
- Proprietary Dagger® Technology Enables ALLO-329 to Overcome Rejection and Expand the Presence of Alloreactive T Cells
- Presented Data Demonstrates that ALLO-329 Could Be Effective in Treating Autoimmune Diseases with Reduced or No Lymphodepleting Chemotherapy
- ALLO-329 Investigational New Drug (IND) Submission Planned for Q1 2025
SOUTH SAN FRANCISCO, CA, USA I November 18, 2024 I Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer and autoimmune disease, today announced preclinical data for ALLO-329, an investigational allogeneic CD19/CD70 dual CAR T cell therapy being evaluated as a treatment for autoimmune diseases. The data, presented at the American College of Rheumatology (ACR) Convergence 2024, demonstrate the potential of ALLO-329 to specifically address key challenges associated with current autologous CAR T cell therapies in development for patients with autoimmune disease and highlights the promise of an allogeneic CAR T to reset the immune system.
ALLO-329 is the first CAR T designed to target both CD19+ B-cells and CD70+ activated T cells. Targeting of B cells has been shown to induce durable, treatment-free remissions in patients with certain autoimmune diseases. CD70 is expressed in activated T cells, which have been implicated in immune responses, including in autoimmunity. Simultaneous elimination of CD70+ T cells may enhance the therapeutic benefit and expand the list of addressable indications.
CD70+ activated T cells also include alloreactive T-cells – the patient’s cells that would attack and reject an allogeneic CAR-T. ALLO-329 is designed to effectively eliminate alloreactive T-cells and render ALLO-329 resistant to rejection. Incorporation of Dagger® technology into ALLO-329 is intended to reduce or eliminate lymphodepletion prior to cell infusion.
“The CAR T space for autoimmune disease is highly competitive, with many approaches focusing only on isolated aspects of autoimmune pathogenesis,” said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. “What sets ALLO-329 apart is its ability to target a greater spectrum of immune dysfunction, addressing both B cells and activated T-cells involved in the disease process, potentially improving disease outcomes with reduced or even no lymphodepletion. Coupled with its “off-the-shelf” accessibility, ALLO-329 has the potential to meet the substantial needs of a broad patient population. These preclinical findings reinforce our excitement as we move this therapy toward clinical development across multiple autoimmune conditions.”
Key findings from the preclinical evaluation of ALLO-329 include:
- High CAR expression and cytotoxic activity: ALLO-329 produced through site-specific integration of a dual CAR construct into the TRAC locus demonstrated robust CAR expression and specific cytotoxic activity against both CD19+ B cells and CD70+ T cells in vitro and in vivo.
- Resistance to rejection: In mixed lymphocyte reaction (MLR) assays, ALLO-329 successfully eliminated CD70+ alloreactive T cells, demonstrating resistance to rejection and enhanced persistence compared to CD19 CAR T cells.
- B cell depletion and antibody reduction: ALLO-329 effectively eradicated B cells derived from healthy donors and patients with systemic lupus erythematosus (SLE) in vitro and in vivo, leading to a reduction in IgG and IgM production.
- Potential to eliminate lymphodepletion: In humanized pre-clinical models, ALLO-329 demonstrated engraftment, B cell depletion, and expansion even without lymphodepletion.
- Manufacturability: CRISPR-mediated, T-cell receptor alpha (TRAC) site-specific transgene integration leads to a highly consistent, dual CAR T-expressing product.
Based on these promising preclinical results, the Company plans to file an investigational new drug (IND) application with the FDA in the first quarter of 2025 and expects to have proof-of-concept by year-end 2025.
About ALLO-329
ALLO-329 is a CD19/CD70 dual AlloCAR T™ investigational product being developed for the treatment of autoimmune diseases. ALLO-329 utilizes CRISPR-based site-specific integration for dual CAR expression. This approach targets both CD19+ B cells and CD70+ T cells, which play a role in autoimmune disease pathogenesis. Additionally, ALLO-329 incorporates Allogene’s clinically validated Dagger® technology, designed to reduce or eliminate the need for lymphodepletion, a pre-treatment regimen that may be a significant barrier to CAR T cell therapy adoption in autoimmune indications.
About Allogene Therapeutics
Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on X and LinkedIn.
SOURCE: Allogene Therapeutics
Post Views: 102
- ALLO-329 Induces Deep, Transient Depletion of CD19+ B Cells and CD70+ T Cells, and Reduction in IgG and IgM without Lymphodepletion in Humanized Murine Models
- Proprietary Dagger® Technology Enables ALLO-329 to Overcome Rejection and Expand the Presence of Alloreactive T Cells
- Presented Data Demonstrates that ALLO-329 Could Be Effective in Treating Autoimmune Diseases with Reduced or No Lymphodepleting Chemotherapy
- ALLO-329 Investigational New Drug (IND) Submission Planned for Q1 2025
SOUTH SAN FRANCISCO, CA, USA I November 18, 2024 I Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer and autoimmune disease, today announced preclinical data for ALLO-329, an investigational allogeneic CD19/CD70 dual CAR T cell therapy being evaluated as a treatment for autoimmune diseases. The data, presented at the American College of Rheumatology (ACR) Convergence 2024, demonstrate the potential of ALLO-329 to specifically address key challenges associated with current autologous CAR T cell therapies in development for patients with autoimmune disease and highlights the promise of an allogeneic CAR T to reset the immune system.
ALLO-329 is the first CAR T designed to target both CD19+ B-cells and CD70+ activated T cells. Targeting of B cells has been shown to induce durable, treatment-free remissions in patients with certain autoimmune diseases. CD70 is expressed in activated T cells, which have been implicated in immune responses, including in autoimmunity. Simultaneous elimination of CD70+ T cells may enhance the therapeutic benefit and expand the list of addressable indications.
CD70+ activated T cells also include alloreactive T-cells – the patient’s cells that would attack and reject an allogeneic CAR-T. ALLO-329 is designed to effectively eliminate alloreactive T-cells and render ALLO-329 resistant to rejection. Incorporation of Dagger® technology into ALLO-329 is intended to reduce or eliminate lymphodepletion prior to cell infusion.
“The CAR T space for autoimmune disease is highly competitive, with many approaches focusing only on isolated aspects of autoimmune pathogenesis,” said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. “What sets ALLO-329 apart is its ability to target a greater spectrum of immune dysfunction, addressing both B cells and activated T-cells involved in the disease process, potentially improving disease outcomes with reduced or even no lymphodepletion. Coupled with its “off-the-shelf” accessibility, ALLO-329 has the potential to meet the substantial needs of a broad patient population. These preclinical findings reinforce our excitement as we move this therapy toward clinical development across multiple autoimmune conditions.”
Key findings from the preclinical evaluation of ALLO-329 include:
- High CAR expression and cytotoxic activity: ALLO-329 produced through site-specific integration of a dual CAR construct into the TRAC locus demonstrated robust CAR expression and specific cytotoxic activity against both CD19+ B cells and CD70+ T cells in vitro and in vivo.
- Resistance to rejection: In mixed lymphocyte reaction (MLR) assays, ALLO-329 successfully eliminated CD70+ alloreactive T cells, demonstrating resistance to rejection and enhanced persistence compared to CD19 CAR T cells.
- B cell depletion and antibody reduction: ALLO-329 effectively eradicated B cells derived from healthy donors and patients with systemic lupus erythematosus (SLE) in vitro and in vivo, leading to a reduction in IgG and IgM production.
- Potential to eliminate lymphodepletion: In humanized pre-clinical models, ALLO-329 demonstrated engraftment, B cell depletion, and expansion even without lymphodepletion.
- Manufacturability: CRISPR-mediated, T-cell receptor alpha (TRAC) site-specific transgene integration leads to a highly consistent, dual CAR T-expressing product.
Based on these promising preclinical results, the Company plans to file an investigational new drug (IND) application with the FDA in the first quarter of 2025 and expects to have proof-of-concept by year-end 2025.
About ALLO-329
ALLO-329 is a CD19/CD70 dual AlloCAR T™ investigational product being developed for the treatment of autoimmune diseases. ALLO-329 utilizes CRISPR-based site-specific integration for dual CAR expression. This approach targets both CD19+ B cells and CD70+ T cells, which play a role in autoimmune disease pathogenesis. Additionally, ALLO-329 incorporates Allogene’s clinically validated Dagger® technology, designed to reduce or eliminate the need for lymphodepletion, a pre-treatment regimen that may be a significant barrier to CAR T cell therapy adoption in autoimmune indications.
About Allogene Therapeutics
Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on X and LinkedIn.
SOURCE: Allogene Therapeutics
Post Views: 102
