Precision BioSciences, Inc. (Nasdaq: DTIL) is proud to announce its impressive accomplishments in 2022 and outline its plans for 2023. The clinical-stage gene editing company is developing ARCUS®-based ex vivo allogeneic CAR T and in vivo gene editing therapies, and is looking forward to pushing the boundaries of what’s possible in the world of gene therapy. In the upcoming year, Precision BioSciences is dedicated to advancing its clinical development and research milestones, and is excited to continue its mission of improving human health through its cutting-edge gene editing technology.
In 2022, Precision BioSciences took major strides in advancing our corporate priorities, strengthening the company and making great headway in our clinical programs and research pipeline. We signed a premium collaboration with Novartis for a new in vivo gene editing system to treat sickle cell disease and beta thalassemia, and added $125 million to our balance sheet to secure the company and extend our cash runway. Moreover, we released the first non-human primate proof of concept data that supports continued development of our HBV in vivo gene editing program and made significant progress with our partnered programs with Lilly and Novartis involving complex gene edits such as excision and gene insertion.
At the end of 2020, we saw tremendous progress on our allogeneic CAR T programs from a clinical, manufacturing, and regulatory standpoint. Our Phase 1b clinical study of azercabtagene zapreleucel (azer-cel; PBCAR0191) yielded an impressive 100% overall response rate, with 73% of patients achieving a complete response to treatment.1 We also optimized our allogeneic CAR T manufacturing process, resulting in improved product attributes that we believe are associated with enhanced efficacy and safety. Finally, we had positive feedback from the FDA, suggesting alignment with our proposed CMC plan for azer-cel, our lead clinical candidate.
Today, Precision announced its key priorities and planned upcoming milestones for 2023, including:
Progress azer-cel to decision point for Phase 2 trial
We are progressing with azer-cel towards a decision point for Phase 2 trials in NHL patients who have relapsed after receiving autologous CAR T treatments. To determine the most effective dosing schedule before moving forward, we must first complete the Phase 1b cohort for azer-cel. We are also in the process of completing the Phase 1 dose escalation for PBCAR19B in the earlier line NHL setting. To keep stakeholders informed of the progress, we plan to present a CAR T clinical update in the first quarter of 2023, based on patient accrual and follow-up.
Advance wholly owned PBGENE-HBV in vivo program to final clinical candidate enabling target CTA and/or IND filing in 2024.
ARCUS has made an amazing breakthrough in the treatment of Hepatitis B Virus (HBV). Using its highly-targeted and optimized specificity lipid nanoparticle (LNP) delivery system, ARCUS nucleases achieved an impressive 85% degradation of HBV cccDNA and a durable 77% reduction of HBV S-antigen expression in primary human hepatocytes (PHH). Furthermore, the system completely prevented any detectable chromosomal translocations in the PHH model. Even more remarkable, the same delivery system achieved a 96% sustained reduction of HBV S-antigen in mice, further demonstrating its efficiency and efficacy. The Company will be presenting further evidence of the success of ARCUS nucleases at a scientific conference in 2023.
Advance first ARCUS in vivo gene editing program to clinical readiness.
Researchers from the University of Pennsylvania’s Gene Therapy Program are partnering with iECURE to explore an innovative ARCUS-mediated gene insertion approach for treating neonatal onset ornithine transcarbamylase (OTC) deficiency. Non-human primate studies have demonstrated sustained gene insertion of a therapeutic OTC transgene one-year post-dosing in newborns and infants with remarkable efficiency. With the goal of filing a CTA and/or IND in the second half of 2023, this groundbreaking treatment may offer a promising solution for those suffering from OTC deficiency.
Progress key partnered programs toward IND, including Duchenne muscular dystrophy and sickle cell disease.
ARCUS technology is revolutionizing the field of genetic engineering. By partnering with Novartis and Lilly, ARCUS has demonstrated its versatility for complex editing and gene insertion in various tissues, including muscle and hematopoietic stem cells. Our joint teams are making remarkable progress towards preclinical objectives, pushing the boundaries of gene editing and changing the way we approach genetic engineering.
Extend cash runway
At the close of 2022, Precision estimates to have amassed a remarkable $190 million in cash and cash equivalents. Even more promising, the Company is confident that its existing funds, along with future operational receipts and available credit, will be enough to sustain its operations and capital expenditure requirements until 2025.
In Vivo Gene Editing Strategy Update:
Strategic prioritization is underway at Precision to identify the diseases with the highest unmet need in the ever-evolving regulatory and competitive gene editing landscape. This exercise, announced during the Company’s third quarter earnings, will help to optimize Precision’s in vivo research pipeline.
The Precision team, in collaboration with its partners, has made tremendous progress in preclinical studies in 2022. Their discoveries have been invaluable in validating the unique features of the ARCUS platform, such as safety, on-target editing, gene insertion, complex gene edits, and compatibility with viral and non-viral delivery. We are thrilled about the ARCUS platform and are committed to taking the first ARCUS in vivo gene editing program into the clinic as soon as possible. Derek Jantz, Ph.D., Chief Scientific Officer, is highly optimistic about Precision’s advancements in this area.
Our HBV program continues to be a major focus for us, and we are still on track to submit a CTA and/or IND by 2024. We are excited to keep the public apprised of our progress as we move closer to our goal. In addition, our partner iECURE has already made great strides in their first gene insertion program, and a CTA filing for neonatal onset OTC deficiency is being planned for submission later this year.
The Company is making strategic choices to prioritize areas of research where ARCUS technology can have the most powerful and far-reaching effect. While the Company is still exploring gene knock-out programs, the data points to prioritizing complex edits (like HBV and DMD) and gene insertion (such as with the Company’s OTC program) as the way forward. With these prioritization efforts, the Company is ensuring that ARCUS technology can be utilized to its fullest potential.
Precision remains deeply committed to aiding patients with cardiovascular diseases and has recently made the decision to no longer pursue PBGENE-PCSK9 for familial hypercholesterolemia (FH) in partnership with iECURE. However, PCSK9 for FH remains a wholly-owned program and Precision is actively monitoring the regulatory landscape for potential cardiovascular disease indications to prioritize for its pipeline. In mid-2023, Precision will host an R&D Day to provide a detailed plan for development of its in vivo pipeline, including research milestones.
In 2022, work on the PBGENE-PH1 program advanced as anticipated, and Precision now has clinical applicants ready to move onto the following phase of IND enabling studies. Taking into account Precision’s new prioritized focus, as well as the constantly changing treatment pattern for PH1, the Company has decided to look for a partner in the kidney disease area to further develop PBGENE-PH1, rather than continuing to develop it alone.
At Precision, we are thrilled to explore the potential of our in vivo gene editing pipeline. We look forward to discussing our prioritization, learnings from ARCUS, and further steps at our 2023 R&D Day. Join us as we unlock the possibilities of precision gene editing!
About Precision BioSciences, Inc.
Precision BioSciences, Inc. is revolutionizing the way we improve life with its novel and proprietary ARCUS® genome editing platform. This highly precise and versatile genome editing platform has been designed with safety, delivery, and control in mind, allowing Precision BioSciences to develop a powerful pipeline of ex vivo “off-the-shelf” CAR T immunotherapy clinical candidates and several in vivo gene editing candidates. These treatments are designed to cure genetic and infectious diseases where no adequate treatments exist, and open up a world of possibilities for patients in need.
At Cytovia Therapeutics, we are dedicated to making forward-looking advancements in our research, clinical development and regulatory review of our product candidates. We anticipate providing updates on our CAR T and in vivo gene editing programs, as well as communicating with regulators, in the near future. We are confident that our product candidates and programs can deliver powerful efficacy and benefits to those that need it most. Additionally, we are committed to operational initiatives and our business strategy, which we believe will help us achieve key milestones and additional collaborations. Finally, we are confident that our financial resources are sufficient to fund our operating expenses and capital expenditure requirements.
Precision Biosciences is focused on developing innovative genome-editing products, but there are a number of risks and uncertainties that could derail our plans. Our ability to become profitable, our operating expenses and our ability to predict them, our limited operating history, the success of our programs and product candidates, and our limited ability to assess the safety and efficacy of our product candidates all pose potential risks and uncertainties. We must also contend with the success of other genome-editing technologies, competition in the genome editing, biopharmaceutical, and biotechnology fields, and the ever-changing U.S. and foreign regulatory landscape. Additionally, we rely on our ARCUS technology, and must navigate the public perception about genome editing technology and its applications. All of these factors, and more, could have a material impact on our business, so we must remain vigilant in order to stay ahead of potential challenges.
As we look ahead, our outlook is promising. We are committed to making every effort to ensure our continued success, and we are confident that our forward-looking statements will reflect this. We are constantly striving to improve and refine our strategies, and we are dedicated to keeping our stakeholders up to date on all the latest developments. Our goal is to create a bright future for all involved, and we will do all we can to make this a reality.
Financial Disclosure Advisory
The Company has released preliminary, unaudited financial results for the year ended December 31, 2022. However, these figures may yet change as the Company’s internal control over financial reporting and audit of the financial statements is still in progress. Once these procedures are complete, the Company will be able to provide a full and accurate account of its financial performance for the year ended December 31, 2022.