On July 1, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company developing allogeneic CAR T and in vivo gene correction therapies with its ARCUS genome editing platform, reported that the first patient has been dosed in its Phase 1 clinical trial with PBCAR19B, an immune evading allogeneic CAR T stealth cell candidate for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) (Press release, Precision Biosciences, JUL 1, 2021, View Source [SID1234584536]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to have dosed the first patient in our Phase 1 trial of PBCAR19B, a next-generation, CD19-targeted candidate incorporating our immune evading stealth cell technology. This is our fourth CAR T program in the clinic, demonstrating the modularity of ARCUS for allogeneic CAR T therapies," said Alan List, M.D., Chief Medical Officer of Precision BioSciences. "Moreover, we believe that our ARCUS-edited stealth cell technology holds the potential to safely improve the persistence of allogeneic CAR T cells without the need for prolonged immunosuppression, which may ultimately lead to deeper and more durable responses for patients."

The Phase 1 study will be a non-randomized, open-label, single-dose, dose-escalation and dose-expansion study designed to evaluate the safety and clinical activity of PBCAR19B at flat dose levels beginning at 2.7 × 108 with the ability to dose up to 8.1 × 108 CAR T cells per patient, following standard lymphodepletion1 in patients with R/R NHL. The first dose level of PBCAR19B is comparable to dose level 3 of the PBCAR0191 CAR T. The primary objective of the study is to identify the maximum tolerated dose and any dose-limiting toxicities. Clinical trial material for this study is generated at the Company’s in-house Manufacturing Center for Advanced Therapeutics (MCAT) in Durham, North Carolina.

About PBCAR19B (Clinical Trials Study Identifier: NCT04649112)
PBCAR19B is a next-generation, immune evading stealth cell candidate for patients with CD19-positive malignancies such as R/R NHL. PBCAR19B is designed to improve the expansion and persistence of allogeneic CAR T cells following infusion by reducing rejection by T cells and NK cells. In addition to the CAR gene, the PBCAR19B stealth cell vector carries a short hairpin RNA that suppresses expression of beta-2 microglobulin, a component of Class I Major Histocompatibility Complex (MHC) molecules found on the cell surface. Reducing or knocking-down Class I MHC expression on allogeneic CAR T cells has been shown to reduce CAR T cell killing by cytotoxic T cells. The PBCAR19B vector also carries an HLA-E gene intended to reduce rejection of CAR T cells by NK cells that can be stimulated as a result of reduced MHC molecule expression on the cell surface.

About Precision’s Allogeneic CAR T Platform
Precision is advancing a pipeline of cell-phenotype optimized allogeneic CAR T therapies, leveraging fully scaled, proprietary manufacturing processes. The platform is designed to maximize the number of patients who can potentially benefit from CAR T therapy. Precision carefully selects high-quality T cells derived from healthy donors as starting material, then uses its ARCUS genome editing technology to modify the cells via a single-step engineering process. By inserting the CAR gene at the T cell receptor (TCR) locus, this process knocks in the CAR while knocking out the TCR, creating a consistent product that can be reliably and rapidly manufactured and is designed to prevent graft-versus-host disease. Precision optimizes its CAR T therapy candidates for immune cell expansion in the body by maintaining a high proportion of naïve and central memory CAR T cells throughout the manufacturing process and in the final product.