On December 11, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company using its ARCUS genome editing platform to develop allogeneic CAR T and in vivo gene editing therapies, reported program updates across its allogeneic CAR T cell therapy pipeline, including updated data for its Phase 1/2a clinical study of PBCAR0191 with enhanced lymphodepletion (eLD)1 presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Precision Biosciences, DEC 11, 2021, View Source [SID1234596818]).

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"Precision’s clinical stage CAR T pipeline continues to generate promising data in lymphoma patients. We have recently observed a potential signal in patients who have relapsed following auto CAR T therapy and responded to treatment with PBCAR0191. This is a growing population of patients with the greatest need for new treatment options, and PBCAR0191 has the potential to be a first-in-class allogeneic CAR T product for this patient population," said Michael Amoroso, Chief Executive Officer of Precision BioSciences. "In parallel, we are continuing to advance PBCAR19B, our immune evading stealth cell candidate, in a relapsed and/or refractory (R/R) patient population with non-Hodgkin’s lymphoma (NHL), in pursuit of a potential best-in-class CD19 targeting allogeneic product candidate."

First-in-Class Approach: PBCAR0191

The updated data from the PBCAR0191 Phase 1/2a study included 22 (17 NHL, 5 B-ALL) heavily pre-treated R/R subjects with predominantly advanced or aggressive B-cell malignancies who were evaluable as of November 16, 2021. Evaluable subjects received a median 5 lines of prior treatment, including 27% (6/22) who previously received a CD19-directed autologous CAR T.

For patients that received treatment of PBCAR0191 following eLD as of November 16, 2021:

PBCAR0191 showed no ≥ Grade 3 cytokine release syndrome (CRS), one Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) with resolution to ≤ Grade 2 in 72 hours, no evidence of graft versus host disease and one infectious death at Day 54 deemed possibly related to treatment2
PBCAR0191 yielded an overall response rate of 73% and a complete response rate of 59% using a 3 x 106 cells/kg cell dose
Four responders among the 17 evaluable NHL subjects reached Day 180 durability assessment
Most notably, a potential signal for PBCAR0191 was observed among six subjects that previously received an autologous CAR T:

100% of these patients responded and 66% experienced a complete response at ≥ Day 28
More than half of these patients had a longer duration of response on PBCAR0191 than with the prior autologous CAR T treatment
"Today, there are no FDA approved therapeutics for lymphoma patients who have relapsed following auto-CAR T therapy. PBCAR0191 has the potential to be developed as a salvage treatment for this growing population with high unmet need, and we are actively enrolling additional patients in this relapse setting to further validate this observed activity," said Bijal Shah, M.D., Associate Professor, Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute.

Best-in-Class Approach: PBCAR19B Immune Evading Stealth Cell

The Phase 1 clinical study of PBCAR19B is actively enrolling subjects with R/R NHL. Flat doses of PBCAR19B CAR T cells following standard lymphodepletion (sLD)3 are administered starting at Dose Level 1 (2.7 × 108 CAR T cells). The company has dosed the first three subjects at Dose Level 1.

"In parallel to our development with PBCAR0191, we are continuing to enroll patients in the PBCAR19B clinical trial and expect to share initial results for this program in mid-2022," said Alan List M.D., Chief Medical Officer of Precision BioSciences. "Unique attributes of ARCUS designed to make complex gene edits in a single step may allow PBCAR19B to achieve a best-in-class allogeneic product profile to potentially displace CD19 directed autologous CAR T."

PBCAR19B is a novel immune-evading stealth cell candidate employing a single-gene edit to knock-down beta-2 microglobulin designed for evading T cell rejection, while also inserting an HLA-E transgene to further evade rejection from natural killer cells. Precision BioSciences’ CAR T cells are the only allogeneic CAR T cells in human clinical trials made with a single gene editing step designed to specifically avoid the potentially deleterious effects of making multiple edits to T cells.

PBCAR269A Phase 1/2a Program Update

PBCAR269A is an investigational allogeneic CAR T immunotherapy targeting B-cell maturation antigen for the treatment of R/R multiple myeloma. The following has been observed among 14 patients that have been evaluated for clinical activity and safety across four dose levels of PBCAR269A4 monotherapy following sLD:

No Grade ≥ 3 CRS or ICANS
Dose-dependent increase in PBCAR269A peak expansion
Overall, PBCAR269A monotherapy response observed in the Phase 1/2a trial was not comparable with autologous CAR T profiles. Therefore, Precision is continuing to enroll subjects with PBCAR269A in combination with nirogacestat, a gamma secretase inhibitor developed by SpringWorks Therapeutics, in pursuit of a potential therapeutic index comparable with or better than autologous CAR T. Initial clinical data from the combination cohort is expected to be presented in mid-2022.

The Company’s balance of cash and cash equivalents was approximately $152 million as of November 30, 2021. The Company continues to expect that existing cash and cash equivalents, expected operational receipts, and available credit will be sufficient to fund its operating expenses and capital expenditure requirements into 2023.

Company-Hosted Webcast and Conference Call Information

Precision will host a conference call and webcast today, Saturday, December 11, 2021 at 7:30 PM ET. This event is not an official program of the ASH (Free ASH Whitepaper) annual meeting. The dial-in conference call numbers for domestic and international callers are (866) 996-7202 and (270) 215-9609, respectively. The conference ID number for the call is 1178837. Participants may access the live webcast, and accompanying presentation materials, as well as the archived webcast on Precision’s website in the Investors section under Events & Presentations: View Source