On March 26, 2025 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for high unmet need diseases, reported financial results for the fourth quarter and fiscal year ended December 31, 2024, and provided a business update (Press release, Precision Biosciences, MAR 26, 2025, View Source [SID1234651466]).
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"2024 was a transformational year for Precision BioSciences as we solidified ourselves as a leading in vivo gene editing company, and we now have clinical data from two differentiated ARCUS based programs. Our focus on operational excellence was exemplified by PBGENE-HBV, our lead in vivo gene editing program for chronic Hepatitis B, where we in parallel filed and received approval for three Clinical Trial Applications (CTA) in three markets with world class clinical capabilities," said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences. "Building on that momentum, and consistent with our pursuit of globalizing the ELIMINATE-B trial, Precision has recently received Investigational New Drug (IND) clearance by the U.S. Food and Drug Administration. PBGENE-HBV is the first-ever investigational in vivo gene editing therapy cleared to enter clinical trials for the treatment of chronic Hepatitis B in the U.S. and globally."
"In 2025, our steadfast focus remains on continued clinical execution as we work to deliver on the promise of our ARCUS gene editing technology through robust clinical data," continued Mr. Amoroso. "The recent reported clinical experience for PBGENE-HBV focused on viral editing and elimination of replicating cccDNA and integrated HBV DNA in Hepatitis B, an extremely large patient population, adds to the compelling clinical validation of the ARCUS platform observed in severe OTC deficiency, a rare and extremely dire disease. In January, our partner iECURE announced news from the OTC-HOPE study, where first-in-human data demonstrated a complete clinical response in severe neonatal OTC deficiency using an ARCUS nuclease for in vivo gene insertion. We look forward to building on this clinical momentum throughout 2025."
Wholly Owned Portfolio
PBGENE-HBV (Viral Elimination Program): PBGENE-HBV is Precision’s wholly owned in vivo gene editing program under investigation in a global first-in-human clinical trial, which is designed to potentially cure chronic Hepatitis B infection. Currently, it is estimated that approximately 300 million people worldwide are afflicted with chronic Hepatitis B. Unlike all other downstream targeting modalities, which offer low likelihood of achieving a cure, PBGENE-HBV is the first and only potentially curative gene editing program to enter the clinic that is specifically designed to eliminate cccDNA and inactivate integrated HBV DNA. The ELIMINATE-B trial is designed to investigate PBGENE-HBV at multiple ascending dose levels with three dose administrations per dose level in patients afflicted with chronic Hepatitis B who are HBeAg-negative.
Precision received IND and CTA approvals for its Phase 1 ELIMINATE-B trial in the United States, Moldova, Hong Kong, and New Zealand.
Mr. Amoroso added, "We have already completed dosing of the first patient cohort establishing both safety and early efficacy for PBGENE-HBV at the lowest dose level in the Phase 1 clinical trial and have commenced subsequent administrations. These operational milestones are a tremendous step forward for Precision BioSciences, and we look forward to accelerating patient access to the study by initiating the trial in the U.S. and later expanding to the U.K. Clinical data updates will continue to be shared throughout 2025 at meaningful timepoints."
The Company dosed the first patient in December 2024 and has completed dosing the low-dose cohort (N= 3 patients) with the first dose administration of PBGENE-HBV. The participants treated in cohort 1 possessed different baseline characteristics: age of infection, duration of infection and level of Hepatitis B surface antigen (HBsAg).
The study is primarily designed to test the safety of three dose administrations of PBGENE-HBV. In the first cohort, all three patients dosed with the first dose administration of PBGENE-HBV have completed the initial safety evaluation period. PBGENE-HBV was well-tolerated and none of the patients experienced a Grade ≥2 treatment-related adverse event or serious adverse event.
In addition to safety, the ELIMINATE-B protocol is designed to assess the efficacy for three dose administrations at each dose level, with the goal to maximize cumulative viral editing to achieve undetectable levels of HBsAg ultimately enabling patients to stop taking lifelong nucleos(t)ide analog therapy. PBGENE-HBV demonstrated a substantial reduction in HBsAg in two of the three participants following the first administration at the lowest dose. Initial clinical data in the first cohort of patients was consistent with the HBsAg reductions observed in preclinical non-human primate models.
"Given PBGENE-HBV’s novel modality, these data suggest that PBGENE-HBV appears to be working by its intended mechanism of eliminating the source of viral replication in cccDNA while inactivating integrated disease," said Cassie Gorsuch, PhD, Chief Scientific Officer of Precision BioSciences.
With a well-tolerated safety profile and early antiviral activity established after the first administration at dose level 1, Precision expects to complete subsequent administrations in all cohort 1 patients while in parallel expanding to the next higher dose cohorts. The Company plans to provide ongoing updates on the full low-dose cohort, including multiple dose administrations, and data at higher dose levels throughout 2025.
Supporting the ELIMINATE-B clinical study design, Precision presented new preclinical safety and efficacy data at the Global Hepatitis Summit (GHS) on March 21, 2025, showcasing the rationale for administering up to three repeat doses in clinic to safely increase cumulative viral editing and optimize the therapeutic index of PBGENE-HBV for patients with chronic Hepatitis B. The data shared at GHS was supported by definitive preclinical safety and toxicology studies conducted by Precision.
PBGENE-3243 (Mutant Mitochondrial DNA Elimination Program): PBGENE-3243 is a first-of-its-kind potential treatment for m.3243-associated mitochondrial disease that is designed to specifically target and eliminate mutant m.3243G mitochondrial DNA, thereby eliminating the root cause of the disease. Currently, there are no cures for m.3243-associated mitochondrial disease, which affects approximately 20,000 people in the U.S. alone and an even larger prevalent population globally. PBGENE-3243 is designed to alleviate muscular myopathy symptoms, providing a significant quality of life and functional improvement for patients.
The high specificity of ARCUS nucleases enables editing and elimination of mutant mitochondrial DNA while allowing wild-type (normal) mitochondrial DNA to repopulate, thus improving cellular function. Unlike CRISPR/Cas, base editors, and prime editors that require a guide RNA, ARCUS single-component nucleases are able to penetrate the mitochondrial membranes and target mutant mitochondrial DNA. In 2025, Precision plans to present new data for PBGENE-3243 while advancing the program toward a CTA and/or IND.
Wholly Owned Portfolio – Under Assessment
In July 2024, Precision regained the rights for three programs, including its PBGENE-DMD, PBGENE-LIVER, and PBGENE-CNS programs; the following of which are being assessed for either internal development and/or development through new partners.
PBGENE-DMD (Muscle Targeted Excision Program): New preclinical, in vivo efficacy data using the clinical construct, PBGENE-DMD, was presented at the 2025 Muscular Dystrophy Association Clinical and Scientific Conference on March 19, 2025. The oral presentation highlighted significant functional dystrophin protein production across heart, diaphragm and skeletal muscles at levels expected to provide therapeutic benefit. In a humanized DMD-diseased mouse model, PBGENE-DMD demonstrated long-term functional improvement over multiple time points, including achieving 93% of the maximal force output observed in healthy control mice. Importantly, PBGENE-DMD demonstrated the ability to edit Pax7+ cells, a marker for satellite muscle stem cells which are the precursor cells to new muscle cell formation and a potential predictor of durable functional benefit. These in vivo efficacy results further support the therapeutic potential of an ARCUS gene editing approach for the treatment of DMD and ongoing development in clinical trials.
PBGENE-CNS (CNS Targeted Excision Program): Precision expects to publicly present preclinical data on PBGENE-CNS for the first time at a scientific conference in 2025.
ARCUS Platform
At the ESGCT 31st Annual Congress in October 2024, Precision presented preclinical data highlighting ARCUS’s capability for high-efficiency gene editing to achieve a range of gene editing outcomes, including specific base correction, insertions, and the replacement of large segments of DNA within the genome via homology-directed repair (HDR). The presentation also discussed how the ARCUS approach may provide broader therapeutic applicability and address significantly more diseases through gene insertion and repair than other gene editing modalities which primarily target gene deletion or knock out.
Partnered Programs
iECURE-OTC (Gene Insertion Program): Led by iECURE, ECUR-506 is an ARCUS-mediated in vivo gene editing program currently in a first-in-human Phase 1/2 trial (OTC-HOPE) evaluating ECUR-506 as a potential treatment for neonatal onset ornithine transcarbamylase (OTC) deficiency. In January 2025, iECURE reported clinical efficacy and safety data in the first patient dosed showing a complete clinical response from three months post exposure to the end of study at six months post exposure, as demonstrated by the removal of standard of care ammonia scavenger medicines, an absence of hyperammonemic crises, and normalization of protein intake to age-appropriate levels. ECUR-506 was generally well tolerated with no significant clinical safety concerns apart from asymptomatic transaminitis experienced at four weeks. The asymptomatic transaminitis was managed with a short course of immunosuppressive therapy and resolved within four weeks. Twelve weeks after a single dose of ECUR-506, ammonia scavenger medication was discontinued and mean daily protein intake was increased to age-appropriate levels.
The OTC-HOPE study is ongoing in the United Kingdom, the United States, Australia, and Spain, and iECURE expects to finish enrollment in 2025 and provide complete data for the program in the first half of 2026.
PBGENE-NVS (Gene Insertion Program): Precision continues to advance its gene editing program with Novartis to develop a custom ARCUS nuclease for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia. The collaborative intent is to insert, in vivo, a therapeutic transgene as a potential one-time transformative treatment administered directly to the patient to overcome disparities in patient access to treatment with other therapeutic technologies, including those that are targeting an ex vivo gene editing approach.
Corporate Updates
Strengthened Senior Leadership Team: In January 2025, Precision announced the appointments of Cindy Atwell as Chief Development and Business Officer, and Dr. Cassie Gorsuch, PhD as Chief Scientific Officer, significantly strengthening the Company’s research and development capabilities to support clinical execution for its lead PBGENE-HBV program and advancement of other programs towards the clinic.
Business Updates – Monetization of CAR T Investments:
Equity Investment as Part of 2024 Deal with TG Therapeutics:
In January 2025, Precision received a deferred cash payment of $2.5 million as an equity investment in Precision’s common stock at $11.33 per share, a 100% premium to the then 30-day VWAP prior to purchase. This stock purchase by TG Therapeutics followed receipt of $7.5 million in February 2024 upon closing of the agreement with TG Therapeutics to develop azercabtagene zapreleucel (azer-cel) for autoimmune disorders.
In January 2025, TG Therapeutics announced its intention to enroll participants into the Phase 1 azer-cel trial in autoimmune disease, beginning with primary progressive Multiple Sclerosis in 2025. Upon the achievement of certain near-term clinical milestones, Precision will receive an additional $7.5 million payment in cash and the purchase of Precision common stock by TG Therapeutics at a 100% premium to the then current 30-day VWAP.
Quarter Ended December 31, 2024 Financial Results:
Cash, Cash Equivalents, and Restricted Cash: As of December 31, 2024, Precision had approximately $108.5 million in cash, cash equivalents, and restricted cash. The Company expects that existing cash and cash equivalents, upfront and potential near-term cash from CAR T transactions, along with expected operational receipts, continued fiscal and operating discipline, and availability of Precision’s at-the-market (ATM) facility are expected to extend Precision’s cash runway into the second half of 2026. Based on its expected cash runway, Precision believes it is sufficiently capitalized to operate the two wholly owned programs to Phase 1 data readouts.