– Cryopreserved, Post-thaw CAR T Cell Composition and Effective CAR T Cell Dose are Predictive for Response to Treatment with Azer-cel
– Peak CAR T Expansion, a Key Determinant of Durable Response, Strongly Correlated with Effective CAR T Dose
DURHAM, NC, USA I December 10, 2022 I Precision BioSciences (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS®-based ex vivo allogeneic CAR T and in vivo gene editing therapies, today presented a novel, product-attributes analysis of its lead CD19 allogeneic CAR T candidate, Azercabtagene Zapreleucel (azer-cel; PBCAR0191) that shows a relationship between CAR T cell composition and effective cell dose with pharmacokinetics, pharmacodynamics, and clinical outcomes. Data from this analysis, Effective Cell Dose and Functional Attributes of Azercabtagene Zapreleucel (azer-cel; PBCAR0191) Associated with Allogeneic CAR T-Cell Safety and Efficacy in Patients with Relapsed/Refractory B-Cell Lymphoma, were presented today during a poster session at the American Society of Hematology Annual Meeting.
“Autologous CAR T therapy remains one of the most promising approaches in the treatment of hematological malignancies. However, 30-60% of high-grade non-Hodgkin Lymphoma (NHL) patients relapse after treatment and, for up a proportion of patients, an effective autologous product cannot be manufacturedi,” said Caron A. Jacobson, M.D., azer-cel clinical trial investigator and Medical Director for the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute. “Unlike autologous CAR T cell therapy, all allogeneic CAR T products are cryopreserved, which may alter the effective dose and composition of the post-thaw product. In this analysis, azer-cel cellular attributes were interrogated in the post-thaw product for possible relationship to in vivo pharmacokinetics, pharmacodynamics, and clinical outcomes for 44 subjects with NHL across multiple azer-cel dose levels and lymphodepletion regimens. The analysis found that CAR T expansion, a key determinant of durable response, strongly correlated with non-apoptotic CAR T cell dose.”
Azer-cel is an investigational allogeneic anti-CD19 CAR T candidate currently in a Phase 1/2a clinical trial of adult subjects with relapsed or refractory NHL, who relapsed following treatment with an autologous CAR T.
“This is the first analysis of an allogeneic anti-CD19 CAR T product to examine the relationships between allogeneic CAR T cell composition, cell dose, and lymphodepletion with pharmacokinetics, pharmacodynamics, and clinical outcomes,” said Alan List, M.D., Chief Medical Officer, Precision BioSciences. “These results indicate that the post-thaw CAR T product composition drives in vivo cell expansion potential and CAR T-related adverse events. We are continuing to use this information in real time, applying optimizations across our first- and second-generation allogeneic CAR T platforms with the goal of improving those attributes and characteristics that drive predictability, reliability, and performance of CAR T cell therapy.”
The analysis also showed that CD4:CD8 ratio strongly correlated with in vivo CD4+ CAR T cell expansion. Similar to data reported in autologous CAR T studies, differentiated CD4+ CAR T cell dose correlated with Grade 3 or greater neurotoxicity. This was particularly observed in a subset of patients that were both CAR T relapsed and conditioned with an intensified lymphodepletion treatment regimen.
About Precision BioSciences, Inc.
Precision BioSciences, Inc. is a clinical stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform. ARCUS is a highly precise and versatile genome editing platform that was designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the company’s pipeline consists of multiple ex vivo “off-the-shelf” CAR T immunotherapy clinical candidates and several in vivo gene editing candidates designed to cure genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com.
i Gena Kanas, Wenzhen Ge, Ruben G. W. Quek, Katie Keeven, Knar Nersesyan & Jon E. Arnason (2022) Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020–2025, Leukemia & Lymphoma, 63:1, 54-63, DOI: 10.1080/10428194.2021.1975188
SOURCE: Precision BioSciences
Post Views: 17
– Cryopreserved, Post-thaw CAR T Cell Composition and Effective CAR T Cell Dose are Predictive for Response to Treatment with Azer-cel
– Peak CAR T Expansion, a Key Determinant of Durable Response, Strongly Correlated with Effective CAR T Dose
DURHAM, NC, USA I December 10, 2022 I Precision BioSciences (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS®-based ex vivo allogeneic CAR T and in vivo gene editing therapies, today presented a novel, product-attributes analysis of its lead CD19 allogeneic CAR T candidate, Azercabtagene Zapreleucel (azer-cel; PBCAR0191) that shows a relationship between CAR T cell composition and effective cell dose with pharmacokinetics, pharmacodynamics, and clinical outcomes. Data from this analysis, Effective Cell Dose and Functional Attributes of Azercabtagene Zapreleucel (azer-cel; PBCAR0191) Associated with Allogeneic CAR T-Cell Safety and Efficacy in Patients with Relapsed/Refractory B-Cell Lymphoma, were presented today during a poster session at the American Society of Hematology Annual Meeting.
“Autologous CAR T therapy remains one of the most promising approaches in the treatment of hematological malignancies. However, 30-60% of high-grade non-Hodgkin Lymphoma (NHL) patients relapse after treatment and, for up a proportion of patients, an effective autologous product cannot be manufacturedi,” said Caron A. Jacobson, M.D., azer-cel clinical trial investigator and Medical Director for the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute. “Unlike autologous CAR T cell therapy, all allogeneic CAR T products are cryopreserved, which may alter the effective dose and composition of the post-thaw product. In this analysis, azer-cel cellular attributes were interrogated in the post-thaw product for possible relationship to in vivo pharmacokinetics, pharmacodynamics, and clinical outcomes for 44 subjects with NHL across multiple azer-cel dose levels and lymphodepletion regimens. The analysis found that CAR T expansion, a key determinant of durable response, strongly correlated with non-apoptotic CAR T cell dose.”
Azer-cel is an investigational allogeneic anti-CD19 CAR T candidate currently in a Phase 1/2a clinical trial of adult subjects with relapsed or refractory NHL, who relapsed following treatment with an autologous CAR T.
“This is the first analysis of an allogeneic anti-CD19 CAR T product to examine the relationships between allogeneic CAR T cell composition, cell dose, and lymphodepletion with pharmacokinetics, pharmacodynamics, and clinical outcomes,” said Alan List, M.D., Chief Medical Officer, Precision BioSciences. “These results indicate that the post-thaw CAR T product composition drives in vivo cell expansion potential and CAR T-related adverse events. We are continuing to use this information in real time, applying optimizations across our first- and second-generation allogeneic CAR T platforms with the goal of improving those attributes and characteristics that drive predictability, reliability, and performance of CAR T cell therapy.”
The analysis also showed that CD4:CD8 ratio strongly correlated with in vivo CD4+ CAR T cell expansion. Similar to data reported in autologous CAR T studies, differentiated CD4+ CAR T cell dose correlated with Grade 3 or greater neurotoxicity. This was particularly observed in a subset of patients that were both CAR T relapsed and conditioned with an intensified lymphodepletion treatment regimen.
About Precision BioSciences, Inc.
Precision BioSciences, Inc. is a clinical stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform. ARCUS is a highly precise and versatile genome editing platform that was designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the company’s pipeline consists of multiple ex vivo “off-the-shelf” CAR T immunotherapy clinical candidates and several in vivo gene editing candidates designed to cure genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com.
i Gena Kanas, Wenzhen Ge, Ruben G. W. Quek, Katie Keeven, Knar Nersesyan & Jon E. Arnason (2022) Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020–2025, Leukemia & Lymphoma, 63:1, 54-63, DOI: 10.1080/10428194.2021.1975188
SOURCE: Precision BioSciences
Post Views: 17
