On January 9, 2023 Precision BioSciences (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported on its significant accomplishments in 2022 and reported its corporate priorities and anticipated clinical development and research milestones for 2023 (Press release, Precision Biosciences, JAN 9, 2023, View Source [SID1234626093]).
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"In 2022, we advanced our corporate priorities strengthening the company and made significant progress with our clinical programs and research pipeline. We established a new, premium in vivo gene editing collaboration with Novartis focused on gene insertion for sickle cell disease and beta thalassemia, and we added $125 million to our balance sheet to fortify the company and extend our cash runway. We also published the first non-human primate proof of concept data supporting further development of our HBV in vivo gene editing program and made significant progress on our partnered programs with Lilly and Novartis involving complex gene edits such as excision and gene insertion," said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences.
"We made meaningful clinical, manufacturing and regulatory progress on our allogeneic CAR T programs. From a clinical perspective, in the latest cohort of our Phase 1b clinical study reported in mid-2022, azercabtagene zapreleucel (azer-cel; PBCAR0191) achieved a 100% overall response rate and 73% complete response to treatment.1 In addition, we implemented process optimizations for our allogeneic CAR T manufacturing process, significantly improving product attributes that we believe are correlated with improved efficacy and safety, and concluded the year with favorable FDA feedback signaling 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:
1. Progress azer-cel to decision point for Phase 2 trial in non-Hodgkin lymphoma (NHL) subjects who have relapsed following autologous CAR T treatment.
Complete Phase 1b cohort for azer-cel to determine final dosing schedule; request FDA clinical meeting pending data.
Complete Phase 1 dose escalation for PBCAR19B in the earlier line NHL setting.
Present CAR T clinical update in the first quarter of 2023, based on patient accrual and follow-up.
2. Advance wholly owned PBGENE-HBV in vivo program to final clinical candidate enabling target CTA and/or IND filing in 2024.
Data published in 2022 demonstrates that ARCUS efficiently targeted and degraded hepatitis B virus (HBV) cccDNA by 85% and durably reduced expression of HBV S-antigen by 77% in HBV-infected primary human hepatocytes (PHH). Importantly, optimized specificity of the ARCUS nuclease completely prevented detectable chromosomal translocations in the PHH model.
Using lipid nanoparticle (LNP) delivery, ARCUS nucleases showed high on-target editing and a robust decrease in viral DNA in both mouse and non-human primate models, along with 96% sustained reduction of HBV S-antigen in mice.
The Company plans to present additional data at a scientific conference in 2023.
3. Advance first ARCUS in vivo gene editing program to clinical readiness.
In partnership with iECURE, an ARCUS-mediated gene insertion approach is being pursued as a potential treatment for neonatal onset ornithine transcarbamylase (OTC) deficiency.
Non-human primate data presented by researchers from the University of Pennsylvania’s Gene Therapy Program demonstrated sustained gene insertion of a therapeutic OTC transgene one-year post-dosing in newborn and infant non-human primates with high efficiency.
iECURE targeting to file CTA and/or IND in second half of 2023.
4. Progress key partnered programs toward IND, including Duchenne muscular dystrophy and sickle cell disease.
Through partnerships with Novartis and Lilly, the versatility of ARCUS is highlighted for complex editing and gene insertion in diverse tissues, including muscle and hematopoietic stem cells.
Joint teams continue to make significant progress against preclinical objectives.
5. Extend cash runway.
Although it has not finalized its full financial results, Precision expects to report it had approximately $190 million in cash and cash equivalents as of December 31, 2022. The Company’s management also believes that, as of January 9, 2023, the Company’s existing cash and cash equivalents, expected operational receipts, and available credit will be sufficient to fund its operating expenses and capital expenditure requirements into 2025.
In Vivo Gene Editing Strategy Update:
The strategic prioritization exercise for Precision’s in vivo research pipeline, announced during the Company’s third quarter earnings, is ongoing to assess diseases with highest unmet need in an increasingly dynamic regulatory and competitive gene editing landscape.
"The Precision team, along with its partners, have generated an abundance of preclinical data in 2022 and had significant learnings," said Derek Jantz, Ph.D., Chief Scientific Officer. "The Precision team along with partners continue to validate unique features of the ARCUS platform with regards to safety, on-target editing, gene insertion, complex gene edits, and compatibility with viral and non-viral delivery. We remain very excited about Precision’s proprietary and foundational ARCUS platform and are steadfast about moving the first ARCUS in vivo gene editing program into the clinic as rapidly as possible."
"Our HBV program remains a top priority, and we are on track with our original goal of submitting a CTA and/or IND in 2024. We look forward to providing periodic updates on the team’s progress. In addition, in our partner’s hands at iECURE, operational progress has been made on a first gene insertion program and the CTA filing for neonatal onset OTC deficiency is planned for submission this year," said Dr. Jantz.
As a result of the ongoing prioritization, the Company is making trade-offs and further honing its focus on disease areas where the Company believes ARCUS, more than any other technology, can have the greatest and most profound impact. While the Company will continue to pursue gene knock-out programs opportunistically, the proof of concept data continues to lead toward prioritizing programs involving complex edits, as with the HBV and DMD programs, and gene insertion (adding a functional copy of a gene) as exemplified by our partnered OTC program.
While Precision remains committed to patients with cardiovascular diseases, it has made the decision to cease pursuit of PBGENE-PCSK9 for familial hypercholesterolemia (FH) with iECURE as its partner. PCSK9 for FH remains a wholly-owned program, and the Company is monitoring the regulatory landscape as it considers FH as well as several potential cardiovascular disease indications in its pipeline prioritization exercise. A more robust plan for development of Precision’s in vivo pipeline, including research milestones, will be outlined at an R&D Day in mid-2023.
Finally, work on the PBGENE-PH1 program progressed as planned in 2022. Precision has clinical candidates ready to proceed to the next stage of IND enabling studies. Based on Precision’s new prioritized focus as well as the evolving treatment paradigm for PH1, the Company has made the choice to look for a partner in the kidney disease arena for further development of PBGENE-PH1 and will no longer develop the program on its own.
"Precision has significant optionality with its in vivo gene editing pipeline and we look forward to discussing more about our prioritization, learnings with ARCUS, and next steps at the 2023 R&D Day," said Mr. Amoroso.