On November 10, 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 financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, Precision Biosciences, NOV 10, 2021, View Source [SID1234595116]).
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"Precision is dedicated to delivering on the vast potential of ARCUS gene editing for best-in-class cell and gene therapeutics. In addition to significant research and development progress this past quarter, we signed strategic license and development agreements that we believe are accelerating certain in vivo program timelines to the clinic and providing us with important optionality for future product development efforts," said Michael Amoroso, Chief Executive Officer at Precision BioSciences.
"During our in vivo gene editing event in September, we showcased data supporting ARCUS’ differentiating capabilities for gene knockout, gene insertion and gene repair, and mitochondrial DNA gene editing. We also outlined an in vivo gene editing clinical development strategy designed to advance three investigational new drug (IND) or clinical trial applications (CTA) over the next three years. In addition, we continue to actively recruit patients for our ongoing clinical studies with PBCAR0191, PBCAR19B, and PBCAR269A while monitoring for safety, overall response rate, and durability of response. We look forward to sharing updated data on the PBCAR0191 program during two oral presentations at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) conference," Mr. Amoroso continued.
Recent Developments and Upcoming Milestones:
Allogeneic CAR T Portfolio: Precision BioSciences has treated more than 100 patients with PBCAR T cells across its clinical CAR T programs. Precision’s 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 potentially deleterious off target editing effects and preserve cell health and viability.
PBCAR0191: Precision continues to enroll patients in its Phase 1/2a study of PBCAR0191, targeting CD19 for the treatment of Relapsed/Refractory (R/R) non-Hodgkin lymphoma (NHL) or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL). New interim data for PBCAR0191 will be presented at the upcoming 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Oral presentations will be delivered by Bijal Shah, M.D., from Moffitt Cancer Center and Nitin Jain, M.D., from The University of Texas MD Anderson Cancer Center on Saturday, December 11, 2021 and Monday, December 13, 2021, respectively. Precision will host a webcast on Saturday, December 11, 2021 to provide a CAR T portfolio update.
PBCAR19B: In July 2021, Precision announced that the first patient was dosed in its Phase 1 clinical study of PBCAR19B, the Company’s anti-CD19 immune-evading stealth cell candidate for the treatment of R/R NHL. PBCAR19B is being administered at flat dose levels starting at 2.7 × 108 CAR T cells per patient, the same as Dose Level 3 for PBCAR0191. Precision expects to provide an initial study update in 2022.
PBCAR269A: PBCAR269A is an investigational allogenic CAR T immunotherapy targeting B-cell maturation antigen (BCMA) for the treatment of R/R multiple myeloma. Precision continues to enroll patients in the combination arm of its Phase 1/2a study of evaluating PBCAR269A with nirogacestat, a gamma secretase inhibitor developed by SpringWorks Therapeutics. Precision expects to provide an interim update on the monotherapy arm of the study during its conference webcast on December 11, 2021.
PBCAR20A: PBCAR20A is an investigational allogeneic CAR T cell immunotherapy targeting CD20 for the treatment of R/R NHL in a heterogeneous population who were all previously treated with anti-CD20 monoclonal antibodies. Treatment with PBCAR20A did not result in compelling response rates in a Phase 1/2a clinical study. While this study provided important information regarding allogeneic CAR T dosing and lymphodepletion regimens, Precision has decided to focus its clinical efforts in R/R lymphoma on CD19 targeting programs, as CD19 is a more robust antigenic target in R/R heterogeneous NHL populations. Precision will not continue development of PBCAR20A. All subjects enrolled in the study and evaluated for treatment with PBCAR20A had acceptable tolerability with no graft versus host disease, no Grade ≥ 3 cytokine release syndrome, and no Grade ≥ 3 neurotoxicity (ICANS).
Tiziana: In September 2021, Precision signed an exclusive license agreement to evaluate Tiziana’s foralumab, a fully human anti-CD3 monoclonal antibody, as a lymphodepleting agent in conjunction with Precision’s allogeneic CAR T cells for the potential treatment of cancers. This agreement reflects Precision’s ongoing pursuit of a best-in-class allogeneic CAR T cell therapy.
In Vivo Gene Editing Portfolio:
Accelerated Research & Development Strategy: At the Company’s in vivo gene editing R&D event on September 9, 2021, Precision outlined its clinical development strategy and plans to accelerate three programs to human clinical trials: familial hypercholesterolemia (FH) as early as 2022, primary hyperoxaluria type 1 (PH1) in 2023, and chronic hepatitis B virus (HBV) in 2024. The event featured preclinical data differentiating the precision, safety and versatility of ARCUS, including the first presentation of ARCUS-mediated gene insertion in non-human primates (NHPs) and mitochondrial DNA gene editing. Specific program updates featured the following:
PBGENE-PCSK9 & iECURE Collaboration: In August 2021, Precision signed a license and collaboration agreement with iECURE, a mutation-agnostic in vivo gene editing company co-founded by James M. Wilson, M.D., Ph.D. Under the agreement, iECURE will advance Precision’s wholly-owned PBGENE-PCSK9 candidate into a Phase 1 study in FH, with a CTA filing expected as early as 2022. iECURE will also use Precision’s PCSK9-directed ARCUS nuclease to develop four other pre-specified gene insertion therapies for rare genetic diseases, including ornithine transcarbamylase (OTC) deficiency (iECURE-OTC), phenylketonuria (iECURE-PKU) and two other programs focused on liver diseases. Precision received an equity stake in iECURE and is eligible to receive milestone and mid-single digit to low double digit royalty payments on sales of iECURE products developed with ARCUS.
PBGENE-PH1: Preclinical research continues to progress for Precision’s wholly-owned in vivo gene editing program applying ARCUS to knock out the HAO1 gene as a potential one-time treatment for PH1. In September 2021, Precision presented NHP data showing on average, a 98.0% reduction in HAO1 mRNA and a 97.9% reduction in the encoded protein after a single administration of an AAV vector encoding ARCUS. Precision has initiated IND-enabling activities and expects to submit an IND/CTA in 2023 for PBGENE-PH1 delivered by lipid nanoparticle.
PBGENE-HBV: Precision’s gene editing program for chronic HBV applies ARCUS to knock out persistent closed circular DNA (cccDNA) and potentially reduce viral persistence. Previously reported preclinical data has shown that ARCUS efficiently targeted and degraded HBV cccDNA in HBV-infected primary human hepatocytes and reduced expression of HBV S-antigen (HBsAg) by as much as 95%. Similar levels of HBsAg reduction were observed in a newly developed mouse model of HBV infection following administration of ARCUS mRNA using lipid nanoparticle delivery. Precision expects to submit an IND/CTA in 2024.
Lilly In Vivo Gene Editing Programs: Programs announced as part of the research and development agreement with Lilly, including Duchenne muscular dystrophy (PBGENE-DMD), a liver-directed target (PBGENE-LLY2) and a CNS-directed target (PBGENE-LLY3) continue to progress.
Corporate:
Executive Leadership: In September 2021, Michael Amoroso was appointed President and Chief Executive Officer and a member of Precision’s Board of Directors, both effective October 15, 2021. Mr. Amoroso joined Precision from Abeona Therapeutics, where he served most recently as Chief Executive Officer. He succeeded Matt Kane, Co-Founder, President, and Chief Executive Officer who is serving as an advisor to the Company.
Board Appointments: On November 8, 2021, Sam Wadsworth, Ph.D., Chief Scientific Officer at Ultragenyx Gene Therapy, an operating unit of Ultragenyx Pharmaceutical Inc., and Shari Lisa Piré, J.D., Chief Legal & Sustainability Officer at Plume Design were appointed to the Company’s Board of Directors. Together Dr. Wadsworth and Ms. Piré add significant cell and gene therapy drug development and strategic business growth experience.
Elo Life Systems:
Corporate Structure: In January 2021, Precision BioSciences disclosed its intention to spinout Elo Life Systems, a wholly-owned subsidiary of Precision. Precision continues to explore strategic options and expects to complete any such spinout, sale or other treatment of Elo in 2021.
Quarter Ended September 30, 2021 Financial Results
Cash and Cash Equivalents: As of September 30, 2021, Precision had approximately $160.5 million in cash and cash equivalents. The Company expects 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.
Revenues: Total revenues for the third quarter ended September 30, 2021 were $24.0 million, as compared to $7.4 million for the same period in 2020. The increase of $16.6 million in revenue during the three months ended September 30, 2021 was primarily the result of an $17.9 million in revenue recognized under the iECURE agreement as the agreement was executed in August 2021. In the third quarter of 2021, the Company also recognized $4.9 million in revenue under the Lilly Agreement, as work commenced in 2021. These increases in revenue were partially offset by a $7.0 million decrease in revenue recognized under the Servier Agreement compared to the third quarter of 2020, as the performance obligation was deemed fully satisfied upon the execution of the Program Purchase Agreement in April 2021.
Research and Development Expenses: Research and development expenses were $25.9 million for the quarter ended September 30, 2021, as compared to $24.9 million for the same period in 2020.
General and Administrative Expenses: General and administrative expenses were $9.6 million for the quarter ended September 30, 2021, as compared to $8.5 million for the same period in 2020. The increase was primarily due to costs required to meet our growing infrastructure needs, including an increase of $1.2 million in general and administrative employee-related costs.
Net Loss: Net loss was $11.3 million, or $(0.19) per share (basic and diluted), for the quarter ended September 30, 2021, as compared to a net loss of $26.0 million, or $(0.50) per share (basic and diluted), for the same period in 2020.