On September 16, 2019 Precision BioSciences, Inc. (Nasdaq: DTIL), a genome editing company dedicated to improving life through the application of its pioneering, proprietary ARCUS platform, reported the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for PBCAR20A, the Company’s second off-the-shelf chimeric antigen receptor (CAR) T cell therapy program (Press release, Precision Biosciences, SEP 16, 2019, View Source [SID1234539541]). Wholly owned by Precision, PBCAR20A is an allogeneic anti-CD20 CAR T therapy candidate in development for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). The company plans to initiate a Phase 1/2a clinical trial in the fourth quarter of 2019, with initial data expected in 2020. The study will include patients with NHL, of which a subset will have the diagnosis of mantle cell lymphoma (MCL). Precision BioSciences has received Orphan Drug Designation for MCL and plans to pursue this indication.
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"FDA clearance to begin clinical trials with our anti-CD20 off-the-shelf CAR T therapy candidate is a significant milestone for Precision. Closely following the initiation earlier this year of our first clinical trial with the anti-CD19 allogeneic CAR T therapy candidate PBCAR0191, today’s announcement demonstrates our ability to advance multiple product candidates in parallel into the clinic, leveraging the unique capabilities of our ARCUS genome editing platform, CAR T development approach and a highly differentiated manufacturing process developed in house," commented Matt Kane, Chief Executive Officer and Co-Founder of Precision BioSciences. "I am delighted that our team continues to deliver ahead of expectations."
David Thomson, Chief Development Officer of Precision, said, "In preclinical disease models, PBCAR20A has demonstrated potent in vivo clearance of CD20+ tumor cells and overall tumor volume reduction. Furthermore, we did not observe any evidence of graft-versus-host disease in strict preclinical models. It is our hope that PBCAR20A will provide a new allogeneic CAR T therapy option with the benefits of reliable, off-the-shelf access and optimized cellular activity to patients living with NHL or CLL/SLL, where a significant need for new treatment options remains. Receiving orphan drug designation from the FDA for MCL means that we have a special opportunity to serve those patients previously treated for the MCL form of NHL, who have a poor prognosis with currently available treatments."
PBCAR20A will be Precision’s second off-the-shelf CAR T therapy candidate to enter the clinic, following PBCAR0191, an off-the-shelf anti-CD19 CAR T therapy candidate currently being evaluated in adult patients with relapsed or refractory (R/R) NHL or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL). Precision initiated dosing of subjects in a Phase 1/2a clinical trial of PBCAR0191 in April 2019, which continues to progress as planned; the company expects to present interim data from this trial at a scientific conference no later than the first quarter of 2020.
With the IND acceptance and expected upcoming clinical trial initiation for PBCAR20A, Precision’s clinical-stage portfolio of off-the-shelf CAR T therapy candidates for B-cell malignancies continues to grow. In the United States, B-cell malignancies account for 85 percent of all NHL cases, and CLL and SLL represent 25 to 30 percent of leukemias. While front-line treatments provide benefit to more than half of newly diagnosed NHL patients, at least a third of those who do benefit will become refractory, achieve only partial remission or relapse after remission. In addition, patients with CLL have seen limited success with autologous CAR T cell therapies, which is commonly ascribed to T cell exhaustion associated with this malignancy. Administration of healthy donor T cells via allogeneic CAR T cell therapy has the potential to overcome current challenges in CLL treatment, increase access to care in NHL and overcome treatment resistance due to CD19 loss. In addition, allogeneic CAR T therapy presents the possibility for combination treatment options by targeting both CD19 and CD20, which may help overcome resistance mechanisms in some patients.
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. 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.
About the PBCAR20A Clinical Trial
PBCAR20A will be evaluated in a Phase 1/2a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation and dose-expansion clinical trial in adult NHL, CLL, and SLL patients. The trial will be conducted at multiple U.S. sites. For more information on the trial, visit www.clinicaltrials.gov, study identifier number NCT04030195.