Benzinga | Jun 4, 2021 07:08AM EDT

Precision Biosciences Highlights Progress On 2 Strategies Designed To Optimize Durability of Allogeneic CAR T Therapy in R/R Non-Hodgkin Lymphoma

Company Reports Updated Phase 1/2a Interim Study Results for 12 R/R Non-Hodgkin Lymphoma Patients who Received PBCAR0191 CAR T Cells Following Enhanced Lymphodepletion (eLD)

- Median Interval of 1 Day from Enrollment to Start of Lymphodepletion

- Single Dose of PBCAR0191 with eLD Yielded Overall Response Rate (ORR) of 75% and Complete Response Rate (CR) of 50% at Day ? 28 in Heavily Pretreated Patients with a Median and Mean of ~7 Prior Lines of Therapy

- 56% (5/9) of Responding Patients Remained Progression Free; 44% (4/9) of Responding Patients Showed Ongoing Responses > 4 Months; Assessment for Durability of Response is Ongoing

Company Showcases Preclinical Data Demonstrating that PBCAR19B Evaded Rejection by T-Cells and Natural Killer Cells

- PBCAR19B Stealth Cell Phase 1 Trial Open for Enrollment

Company to Host Webcast Today at 8:00 a.m. ET to Discuss Updated Study Results

DURHAM, N.C.--(BUSINESS WIRE)-- Precision BioSciences Inc. (NASDAQ:DTIL), a clinical stage biotechnology company developing allogeneic CAR T and in vivo gene correction therapies with its ARCUS(r) genome editing platform, today announced encouraging progress on two strategies designed to optimize the durability of allogeneic CAR T therapy in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). The Company reported updated interim results from its Phase 1/2a study of PBCAR0191, the Company's investigational, off-the-shelf, allogeneic CAR T cell therapy targeting CD19. As of May 21, 2021, 12 patients with R/R NHL were enrolled and evaluated for response to PBCAR0191 with enhanced lymphodepletion (eLD). The Company also reported preclinical data demonstrating the potential mechanism by which its investigational immune evading stealth cell, PBCAR19B, may avoid rejection by T cells and natural killer (NK) cells.

"These interim results in heavily pretreated R/R NHL patients illustrate the potential for PBCAR0191 to recognize and target CD19 positive cancer cells and suggest that enhanced lymphodepletion may be a strategy to help suppress host immune rejection. We're encouraged by the high initial response rates and look forward to monitoring the responses for evidence of long-term durability," said Alan List, MD, Chief Medical Officer of Precision BioSciences. "In addition, our PBCAR19B Phase 1 study is open for enrollment, and we believe this candidate has the potential to build on the encouraging clinical responses we've seen with PBCAR0191 to date and reduce the need for prolonged immunosuppression."

As of May 21, 2021, 18 subjects in the Phase 1/2a study of PBCAR0191 with R/R NHL completed Day 28 evaluation and received either eLD1 (n=12) or standard lymphodepletion2 (sLD; n=6) with Dose Level 33 of PBCAR0191.

Efficacy

* Use of eLD mitigated PBCAR0191 rejection and markedly increased peak cell expansion (~72x) and area under the curve (AUC) (~59x), each as compared to sLD.

* A single dose of PBCAR0191 cells following eLD yielded clinical responses in the majority of patients, with overall response rates (ORR) and complete response (CR) rates of 75% and 50%, respectively at Day ? 28.

* Five of nine responding patients (56%) who received PBCAR0191 cells following eLD remained progression-free, including 4/9 evaluable subjects with responses lasting > 4 months. Assessment of duration of response is on-going.

* Median interval from confirmation of eligibility to start of LD was 1 day, reinforcing the potential feasibility for rapid delivery of off-the-shelf, allogeneic, cellular therapy for high-risk patients.

All eLD CD19-CAR T Prior AutoDay ? 28 Evaluation Subjects Nai:ve CAR (n=12) (n=8) (n=4)*

Overall Response Rate (ORR) n 9 (75%) 6 (75%) 3 (75%)(%)

Complete Response (CR) n (%) 6 (50%) 4 (50%) 2 (50%)

* Three of four responding patients had prior auto-SCT and auto CD19 CAR treatment.

Safety and Tolerability

As of May 21, 2021, PBCAR0191 with eLD continued to show acceptable tolerability without evidence of graft versus host disease (GvHD) and with a similar frequency of immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) compared to patients who received sLD. Infections occurred more frequently when PBCAR0191 was dosed following eLD.

Adverse Event Max Grade sLD eLD (n=6) (n=12)

Grade 1 or Grade 3 (50%) 7 (58%)CRS 2(Cytokine release syndrome) Grade 3 or higher 0 0

ICANS Grade 1 or Grade 2 (33%) 3 (25%)(Immune effector cell-associated 2neurotoxicity) Grade 3 or higher 0 1 (8%)

GvHD 0 0(Graft versus host disease)

Grade 3 or higher 0 2 (17%)Neutropenia Grade 3+ at Day 0 2 (17%) 28

Grade 1 or Grade 0 1 (8%)Infection 2

Grade 3 or higher 0 3 (25%)

Three treatment emergent deaths without disease progression occurred, including two cases of infection and one case of cardiac arrest after a choking incident. Two of these patients were in ongoing complete responses at time of death. Only one death, as previously reported on December 4, 2020 was assessed by the investigator as possibly related to study treatment.

Demographics for Enrolled R/R NHL Patients (PBCAR0191 with eLD)

* Over 80% of subjects had advanced and aggressive lymphomas.

* 75% had stage III/IV disease.

* Subjects had received a median of seven lines of therapy prior to study enrollment.

* 33% of subjects had prior CD19-directed CAR therapy.

PBCAR19B Immune Evading Stealth Cell

PBCAR19B is designed to extend persistence of allogeneic CAR T cells by evading rejection by the immune system of the patient. In preclinical studies, the anti-CD19 PBCAR19B stealth cell exhibited substantial resistance to rejection mediated by both allo-reactive T cell and NK cells, suggesting the potential utility of this approach.

In January 2021, Precision announced that the U.S. Food and Drug Administration accepted its investigational new drug application to evaluate the safety and clinical activity of PBCAR19B in patients with R/R NHL. Initial clinical trial sites have been selected for the Phase 1 study that is now open for enrollment. PBCAR19B will be evaluated at increasing flat dose levels beginning at 2.7 x 108 cells using sLD with the ability to dose up to 8.1 x 108 cells. Of note, the first dose level is approximately equivalent to Dose Level 3 in the PBCAR0191 trial.