On November 6, 2019 Precision BioSciences, Inc. (Nasdaq: DTIL), a genome editing company dedicated to improving life through the application of its pioneering, proprietary ARCUS platform, reported that initial results from the ongoing Phase 1/2a trial of its lead investigational off-the-shelf (allogeneic) chimeric antigen receptor (CAR) T cell therapy candidate, PBCAR0191, will be presented during the 61st Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando, Florida, December 7-10, 2019 (Press release, Precision Biosciences, NOV 6, 2019, View Source [SID1234550485]).
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PBCAR0191 is Precision’s first allogeneic CAR T therapy candidate in clinical trials and targets the well characterized cancer cell surface protein CD19. It is being developed in collaboration with Servier, an international pharmaceutical company. The Phase 1/2a trial includes adult patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL). The abstract outlining initial data from patients treated with PBCAR0191 at Dose Level 1 is available on the ASH (Free ASH Whitepaper) conference website (View Source). This trial is ongoing and updated results, including from patients treated at Dose Level 2, will be presented at the ASH (Free ASH Whitepaper) Annual Meeting on December 9, 2019 starting at 6:00 p.m. ET.
"We are excited to share initial clinical data from Precision’s PBCAR0191 program at ASH (Free ASH Whitepaper), which we believe demonstrate the potential of our differentiated approach to the development of allogeneic CAR T therapies," said Chris Heery, MD, Chief Medical Officer of Precision BioSciences. "These data bring the reality of a true off-the-shelf CAR T therapy a step closer for patients in need of new and improved treatment options. We remain committed to the wider goal of improving access to cellular therapies for patients with advanced NHL and ALL, and we are optimistic, based on these initial findings, that we may be able to help meet this need. While preliminary and from a limited number of patients, the safety profile, in vivo cell expansion and early evidence of clinical activity we have demonstrated at our lowest dose level with PBCAR0191 in the absence of biologic lymphodepletion is very encouraging. We look forward to sharing updated results from patients treated at Dose Levels 1 and 2 at ASH (Free ASH Whitepaper)."
Investigator Update & Webcast Information
Precision will host a live webcast of an investigator update event during the ASH (Free ASH Whitepaper) Annual Meeting to discuss the presented data, beginning at 8:15 p.m. ET on Monday, December 9, 2019. To access the webcast, please visit the "Events & Presentations" page within the Investors & Media section of the Precision BioSciences website at View Source A replay of the webcast will be available on the Precision website for 30 days following the call.
First Clinical Data from Precision’s PBCAR0191 Program
Title: Initial findings of the Phase 1 trial of PBCAR0191
Presenter: Bijal Shah, MD, Moffitt Cancer Center
Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies
Poster/Presentation Number: Poster III
Date and Time: December 9, 2019, 6:00-8:00 p.m. ET
Location: Orange County Convention Center, Hall B
PBCAR0191 is Precision’s first allogeneic CAR T therapy candidate in clinical trials. This presentation will include initial data from the Phase 1 portion of the ongoing Phase 1/2a trial of PBCAR0191, which is designed to assess safety, identify an optimal dose of PBCAR0191 and evaluate preliminary clinical activity in patients with R/R NHL and B-ALL. The trial is a 3+3 dose escalation study (at dose levels of 3×105, 1×106, and 3×106 CAR T+ cells/kg); in each of the three dose levels up to six patients may be enrolled in each of the two cohorts (NHL and B-ALL). Lymphodepletion is achieved using fludarabine 30mg/m2/day and cyclophosphamide 500mg/m2/day.
Data in the abstract include results as of the data cutoff date of August 1, 2019 for three patients with advanced NHL treated at Dose Level 1, one with mantle cell lymphoma (MCL) and two with diffuse large B cell lymphoma (DLBCL). No significant toxicity was observed, including no serious adverse events and no dose-limiting toxicities. All patients had a minimum follow-up of 28 days (median 60 days).
Findings indicate preliminary evidence of cell-mediated anti-tumor activity, which will be evaluated more fully at subsequent dose levels. Two of the three patients experienced an objective tumor response by Lugano criteria, at day 14 and day 28, respectively. Both patients progressed due to new lesions (on day 28 and day 60, respectively). The third patient, who had previously progressed following treatment with axicabtagene ciloleucel (Yescarta), an approved anti-CD19 autologous CAR T therapy, had not met the definition of response, but had shown evidence of central necrosis, decreased tumor size, and decreased PET-avidity at day 28, in the context of post-infusion tumor site pain and mild CRS symptoms.
Peripheral blood analysis for CAR T cell expansion has identified preliminary evidence of cell expansion.
This trial is ongoing and updated results, including from patients treated at Dose Level 2, will be shared at the ASH (Free ASH Whitepaper) conference.
Precision’s Off-The-Shelf 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 by improving access to care through a well-tolerated lymphodepletion regimen. Precision carefully selects high-quality T cells derived from healthy donors as starting material, then utilizes its unique 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.