Ornithine Carbamoyltransferase Deficiency Disease

DURHAM, N.C.--(BUSINESS WIRE)--May 1, 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, including gene elimination, gene insertion, and gene excision programs, today announced that five abstracts detailing Precision’s wholly owned or partnered programs have been accepted for presentation at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting being held May 13-17, 2025, in New Orleans, Louisiana. "We are pleased to present new data at ASGCT from multiple programs across our in vivo gene editing pipeline, highlighting the potentially unmatched breadth and therapeutic potential of our ARCUS gene editing technology,” said Michael Amoroso, President and Chief Executive Officer at Precision BioSciences. “Clinically, we have made progress advancing our lead program, PBGENE-HBV, which is a novel gene editing approach being evaluated in a first-in-human study for chronic hepatitis B, and we look forward to sharing initial safety data from the first two dose cohorts at ASGCT. Additionally, we continue to be excited by the promising clinical results generated thus far by our partner iECURE for ECUR-506 in OTC deficiency, which utilizes an ARCUS nuclease and will also be presenting data at this conference." “We are also excited to share promising preclinical results from two muscle programs, PBGENE-3243 program for m.3243-associated mitochondrial disease and PBGENE-DMD for the treatment of Duchenne Muscular Dystrophy (DMD),” Mr. Amoroso continued. “Collectively, these presentations highlight the progress we are making with ARCUS by deploying a variety of gene edit types, including gene elimination, gene insertion and gene excision across a range of complex genetic diseases as we seek to develop durable, curative treatments for patients." Clinical Program Presentations: Title: Initial Safety Data From ELIMINATE-B, the First Clinical Trial of a Gene Editing Treatment for Chronic Hepatitis B Oral Presentation Session: Gene Therapy Trials - In-Vivo Gene Therapy Modification Date and Time: Friday, May 16, 2025, 4:00 PM CT Location: Room 393-396 Title: ARCUS in vivo OTC, Large Gene Insertion (clinical stage partnered program) Oral Presentation Session: Advances in Genome Editing: Novel Large DNA Insertion Technologies and Their Potential Towards Curative Therapies Date and Time: Wednesday, May 14, 2025, 8:00 AM CT Location: NOLA Theater B Preclinical Program Presentations: Title: Excision of the C9orf72 Hexanucleotide Repeat Expansion Using a Dual-ARCUS Gene Editing Approach Reduces Neurotoxic RNA Foci and Dipeptides in an In Vivo Model of ALS Poster Session: Poster Reception Date and Time: Tuesday, May 13, 2025, 6:00 PM - 7:30 PM CT Location: Poster Hall I2 Title: Systemic Delivery of a Mitochondria-Targeting ARCUS Gene Editing Nuclease by AAV Eliminates Mutant Mitochondrial DNA, Demonstrating Therapeutically Meaningful Heteroplasmy Shifts In Vivo Oral Presentation Session: Gene Editing: New Tools and Technology Advances Date and Time: Wednesday, May 14, 2025, 3:45 PM CT Location: NOLA Theater A Title: ARCUS-Mediated Gene Editing Excision of Exons 45-55 of the Human Dystrophin Gene using PBGENE-DMD Leads to Functional Dystrophin Protein and Durable Restoration of Skeletal Muscle-Function In Vivo for the Treatment of Duchenne Muscular Dystrophy Poster Session: Poster Reception Date and Time: Wednesday, May 14, 2025, 5:30 PM - 7:00 PM CT Location: Poster Hall I2 The abstracts are now publicly accessible through the ASGCT website here. About Precision BioSciences, Inc. Precision BioSciences, Inc. is a clinical stage gene editing company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform that differs from other technologies in the way it cuts, its smaller size, and its simpler structure. Key capabilities and differentiating characteristics may enable ARCUS nucleases to drive more intended, defined therapeutic outcomes. Using ARCUS, the Company’s pipeline is comprised of in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com. The ARCUS® platform is being used to develop in vivo gene editing therapies for sophisticated gene edits, including gene insertion (inserting DNA into gene to cause expression/add function), elimination (removing a genome e.g. viral DNA or mutant mitochondrial DNA), and excision (removing a large portion of a defective gene by delivering two ARCUS nucleases in a single AAV such as in the DMD program). Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the therapeutic potential of ARCUS compared to other gene editing technologies; clinical development and expected safety, efficacy and benefit of our wholly owned gene editing product candidates PBGENE-HBV, PBGENE-DMD, PBGENE-3243, and PBGENE-CNS programs and those being advanced by our collaborators and partners including ECUR-506; our gene editing approaches including editing efficiency, and the suitability of ARCUS nucleases for gene insertion, gene elimination and gene excision and differentiation from other gene editing approaches; the expected timing of regulatory processes and clinical operations for our wholly-owned and partnered product candidates, including filings, studies, enrollment and clinical data; the translatability of preclinical data to development of durable, curative treatments for patients; the initial safety and antiviral activity observed in the ELIMINATE-B clinical trial; plans to provide ongoing updates on the PBGENE-HBV study; anticipated timing of clinical data; clinical efficacy and safety data in the OTC-HOPE clinical trial; ability of an ARCUS nuclease to eliminate mutant mitochondrial DNA and achieve therapeutically meaningful heteroplasmy shifts in vivo; the therapeutic potential of PBGENE-DMD and advancement through preclinical studies; and the potential of proof of concept for ARCUS-mediated excision of the C9orf72 gene HRE and further development of PBGENE-CNS for ALS. In some cases, you can identify forward-looking statements by terms such as “aim,” “anticipate,” “appear,” “approach,” “believe,” “contemplate,” “could,” “designed,” “encouraged”, “estimate,” “expect,” “goal,” “intend,” “look,” “may,” “mission,” “plan,” “possible,” “potential,” “predict,” “project,” “promising,” “pursue,” “should,” “strive,” “suggest,” “target,” “will,” “would,” or the negative thereof and similar words and expressions. Forward-looking statements are based on management’s current expectations, beliefs and assumptions and on information currently available to us. These statements are neither promises nor guarantees, but involve number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to: our ability to become profitable; our ability to procure sufficient funding to advance our programs; risks associated with raising additional capital and requirements under our current debt instruments and effects of restrictions thereunder; our operating expenses and our ability to predict what those expenses will be; our limited operating history; the success of our programs and product candidates in which we expend our resources; our limited ability or inability to assess the safety and efficacy of our product candidates; our dependence on our ARCUS technology; the initiation, cost, timing, progress, achievement of milestones and results of research and development activities, preclinical studies and clinical trials; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, and biotechnology fields; our or our collaborators’ ability to identify, develop and commercialize product candidates; potential product liability lawsuits and penalties against us or our collaborators related to our technology and our product candidates; the U.S. and foreign regulatory landscape applicable to our and our collaborators’ development of product candidates; our or our collaborators’ or other licensees’ ability to advance product candidates into, and successfully design, implement and complete, clinical or field trials; potential manufacturing problems associated with the development or commercialization of any of our product candidates; delays or difficulties in our and our collaborators’ ability to enroll patients; changes in interim “top-line” and initial data that we announce or publish; if our product candidates do not work as intended or cause undesirable side effects; risks associated with applicable healthcare, data protection, privacy and security regulations and our compliance therewith; our ability to obtain orphan drug designation or fast track designation for our product candidates or to realize the expected benefits of these designations; our or our collaborators’ ability to obtain and maintain regulatory approval of our product candidates, and any related restrictions, limitations and/or warnings in the label of an approved product candidate; the rate and degree of market acceptance of any of our product candidates; our ability to effectively manage the growth of our operations; our ability to attract, retain, and motivate executives and personnel; effects of system failures and security breaches; insurance expenses and exposure to uninsured liabilities; effects of tax rules; effects of any pandemic, epidemic, or outbreak of an infectious disease; the success of our existing collaboration agreements, and our ability to enter into new collaboration arrangements; our current and future relationships with and reliance on third parties including suppliers and manufacturers; our ability to obtain and maintain intellectual property protection for our technology and any of our product candidates; potential litigation relating to infringement or misappropriation of intellectual property rights; effects of natural and manmade disasters, public health emergencies and other natural catastrophic events; effects of sustained inflation, supply chain disruptions and major central bank policy actions; market and economic conditions; risks related to ownership of our common stock, including fluctuations in our stock price; our ability to meet the requirements of and maintain listing of our common stock on NASDAQ or other public stock exchanges; and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the annual period ended December 31, 2024, as any such factors may be updated from time to time in our other filings with the SEC, which are accessible on the SEC’s website at www.sec.gov and the Investors page of our website under SEC Filings at investor.precisionbiosciences.com. All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we have no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. View source version on businesswire.com: https://www.businesswire.com/news/home/20250501903476/en/ Investor and Media Contact: Naresh Tanna Vice President of Investor Relations naresh.tanna@precisionbiosciences.com Source: Precision BioSciences, Inc.

SAN DIEGO --(BUSINESS WIRE)--Apr. 10, 2025-- Arcturus Therapeutics Holdings Inc. (the “Company”, “Arcturus”, Nasdaq: ARCT), a commercial messenger RNA medicine company focused on the development of infectious disease vaccines and opportunities within liver and respiratory rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for the self-amplifying mRNA (sa-mRNA) vaccine candidate, ARCT-2304, designed for active immunization to protect against disease caused by influenza A H5N1 subtype contained in the vaccine. This designation recognizes the potential of ARCT-2304 as an innovative approach to address unmet medical needs for the prevention of disease caused by pandemic influenza A virus H5N1, a significant global health risk. The Phase 1 clinical study initiated in November 2024 . Fast Track Designation from the FDA is granted to vaccines intended to prevent serious conditions caused by infectious disease. The designation is designed to expedite the development and review process, providing several benefits, including enhanced communication with the FDA and eligibility for priority review, and the possibility of a rolling review. “We are pleased to receive Fast Track Designation from the FDA for ARCT-2304,” said Joseph Payne , President and CEO of Arcturus Therapeutics . “We remain steadfast in our commitment to the U.S. government to develop safe and effective STARR® next-generation mRNA vaccines to protect U.S. citizens from future pandemic threats. This designation from the FDA is an important step forward in our mission to provide protective solutions for global health crises.” This project has been supported in whole with federal funds from the Department of Health and Human Services ; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50122C0007. About ARCT-2304 (LUNAR-H5N1) ARCT-2304, also known as LUNAR-H5N1, is a STARR® sa-mRNA vaccine candidate formulated with Arcturus proprietary LUNAR® delivery technology. The sa-mRNA vaccine candidate is designed to make many copies of mRNA within the host cell after intramuscular injection to achieve enhanced expression of haemagglutinin (HA) and neuraminidase (NA) antigens, thereby enabling lower doses than conventional mRNA vaccines. Utilizing a sa-mRNA-based platform for pandemic influenza vaccine development offers further options for meeting domestic vaccine manufacturing surge capacity goals. The technology may make vaccines available much sooner than egg- and cell-based technologies. The lyophilized vaccine formulation is stable in refrigerators, thereby simplifying cold-chain storage and reducing distribution risks. About Arcturus Founded in 2013 and based in San Diego, California , Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT) is a commercial mRNA medicines and vaccines company with enabling technologies: (i) LUNAR® lipid-mediated delivery, (ii) STARR® mRNA technology (sa-mRNA) and (iii) mRNA drug substance along with drug product manufacturing expertise. Arcturus developed KOSTAIVE®, the first self-amplifying messenger RNA (sa-mRNA) COVID vaccine in the world to be approved. Arcturus has an ongoing global collaboration for innovative mRNA vaccines with CSL Seqirus, and a joint venture in Japan , ARCALIS , focused on the manufacture of mRNA vaccines and therapeutics. Arcturus’ pipeline includes RNA therapeutic candidates to potentially treat ornithine transcarbamylase (OTC) deficiency and cystic fibrosis (CF), along with its partnered mRNA vaccine programs for SARS-CoV-2 (COVID-19) and influenza. Arcturus’ versatile RNA therapeutics platforms can be applied toward multiple types of nucleic acid medicines including messenger RNA, small interfering RNA, circular RNA, antisense RNA, self-amplifying RNA, DNA, and gene editing therapeutics. Arcturus' technologies are covered by its extensive patent portfolio (over 500 patents and patent applications in the U.S. , Europe , Japan , China , and other countries). For more information, visit www.ArcturusRx.com. In addition, please connect with us on Twitter and LinkedIn. Forward Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact included in this press release, are forward-looking statements, including those regarding the likelihood of success (including safety and efficacy) of ARCT-2304, the likelihood of ARCT-2304 attaining approval or addressing unmet medical needs, the continued development of ARCT-2304, the continued involvement and support of BARDA, and the impact of general business and economic conditions. Arcturus may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in any forward-looking statements such as the foregoing and you should not place undue reliance on such forward-looking statements. These statements are only current predictions or expectations, and are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels of activity, performance or achievements to be materially different from those anticipated by the forward-looking statements, including those discussed under the heading "Risk Factors" in Arcturus’ most recent Annual Report on Form 10-K, and in subsequent filings with, or submissions to, the SEC , which are available on the SEC’s website at www.sec.gov. Except as otherwise required by law, Arcturus disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. View source version on businesswire.com: https://www.businesswire.com/news/home/20250410338815/en/ Arcturus Therapeutics Public Relations & Investor Relations Neda Safarzadeh VP, Head of IR/PR/Marketing (858) 900-2682 IR@ArcturusRx.com Source: Arcturus Therapeutics Holdings Inc.

- Announced first in vivo clinical validation for ARCUS gene editing across two distinct programs including wholly owned PBGENE-HBV and partnered program ECUR-506 - - Commenced Phase 1 ELIMINATE-B clinical trial for PBGENE-HBV, the first gene editing technology studied for Hepatitis B, in fourth quarter of 2024 - - Demonstrated PGENE-HBV was safe and well tolerated with substantial antiviral activity measured by reduction of Hepatitis B surface antigen after only one administration at lowest dose level; Subsequent doses of PBGENE-HBV to follow with data expected throughout 2025 - - Announced complete clinical response in first infant dosed by partner iECURE in ongoing Phase 1/2 clinical trial in Ornithine Transcarbamylase (OTC) Deficiency - - Anticipated cash runway into the second half of 2026 is expected to enable achievement of key Phase 1 clinical inflection points across both wholly owned in vivo gene editing programs - DURHAM, N.C. --(BUSINESS WIRE)--Mar. 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, today announced financial results for the fourth quarter and fiscal year ended December 31, 2024 , and provided a business update. “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. Revenues: Total revenues for the quarter ended December 31, 2024 , were $0.6 million , as compared to $7.0 million for the quarter ended December 31, 2023 . The decrease of $6.4 million in revenue during the quarter ended December 31, 2024 was primarily the result of a decrease in the revenue recognized under the Prevail agreement following conclusion of the collaboration in April 2024 as well as a decrease in revenue recognized under the Novartis Agreement as Precision nears completion of its pre-clinical workplan. Research and Development Expenses: Research and development expenses were $15.9 million for the quarter ended December 31, 2024 , as compared to $13.4 million for the quarter ended December 31, 2023 . The increase of $2.5 million was primarily due to increases in program costs, in particular PBGENE-HBV costs as it entered clinical trials, partially offset by decreases in outsourced research and development costs and licensing fees. General and Administrative Expenses: General and administrative expenses were $9.6 million for the quarter ended December 31, 2024 , as compared to $8.5 million for the quarter ended December 31, 2023 . The increase of $1.1 million was primarily due to an increase in employee-related expenses and share-based compensation expense. Net Loss from Continuing Operations: Net loss from continuing operations was $17.8 million for the quarter ended December 31, 2024 , as compared to $13.4 million for the quarter ended December 31, 2023 . Net Loss: Net loss was $17.8 million , or $(2.22) per share (basic and diluted) for the quarter ended December 31, 2024 . Net loss was $16.3 million , or $(4.06) per share (basic and diluted) for the quarter ended December 31, 2023 . Fiscal Year 2024 Financial Results: Revenues: Total revenues for the year ended December 31, 2024 were $68.7 million , as compared to $48.7 million for the year ended December 31, 2023 . The increase of $20.0 million in revenue during the year ended December 31, 2024 was primarily the result of an increase in revenue recognized under the Prevail agreement as well as new license agreements with TG Therapeutics and Caribou Biosciences in the year ended December 31, 2024 . These increases were partially offset by a decrease in revenue recognized under the Novartis Agreement as Precision nears completion of its pre-clinical workplan. Research and Development Expenses: Research and development expenses were $59.6 million for the year ended December 31, 2024 , as compared to $53.4 million for the year ended December 31, 2023 . The increase of $6.2 million was primarily due to increases in program costs, in particular PBGENE-HBV program costs as the program advanced towards the clinic, partially offset by decreases in platform development and early-stage research expenses. General and Administrative Expenses: General and administrative expenses were $35.3 million for the year ended December 31, 2024 , as compared to $39.1 million for the year ended December 31, 2023 . The decrease of $3.8 million was primarily a result of operational discipline and lower headcount. Net Income from Continuing Operations: Net income from continuing operations was $7.2 million for the year ended December 31, 2024 , as compared to a net loss from continuing operations of $42.5 million for the year ended December 31, 2023 . Net Income: Net income was $7.2 million , or $1.05 per share basic and $1.04 per share diluted for the year ended December 31, 2024 . Net loss was $61.3 million , or $(15.96) per share (basic and diluted) for the year ended December 31, 2023 . Shares: Basic and diluted weighted-average common shares outstanding the year ended December 31, 2024 were 6,832,982 and 6,883,911, respectively, compared to 3,841,405 (basic and diluted) for the year ended December 31, 2023 . Precision BioSciences had 8,202,715 shares outstanding as of December 31, 2024 . As of March 20, 2025 , Precision BioSciences had 10,481,931 shares outstanding, including 921,243 shares sold on March 19, 2025 , at the market. About Precision BioSciences, Inc. Precision BioSciences, Inc. is a clinical stage gene editing company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform that differs from other technologies in the way it cuts, its smaller size, and its simpler structure. Key capabilities and differentiating characteristics may enable ARCUS nucleases to drive more intended, defined therapeutic outcomes. Using ARCUS, the Company’s pipeline is comprised of in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences , please visit www.precisionbiosciences.com. The ARCUS® platform is being used to develop in vivo gene editing therapies for sophisticated gene edits, including gene insertion (inserting DNA into gene to cause expression/add function), elimination (removing a genome e.g. viral DNA or mutant mitochondrial DNA), and excision (removing a large portion of a defective gene by delivering two ARCUS nucleases in a single AAV). Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the clinical development and expected safety, efficacy and benefit of our and our partners’ and licensees’ product candidates and gene editing approaches including editing efficiency, and the suitability of ARCUS nucleases for gene insertion, gene elimination and gene excision and differentiation from other gene editing approaches; the expected timing of regulatory processes and clinical operations (including filings, studies, enrollment and clinical data for PBGENE-HBV, PBGENE-3243 and iECURE OTC); the design of PBGENE-HBV to directly eliminate cccDNA and inactivate integrated HBV DNA with high specificity, potentially leading to functional cures; clinical data suggesting that PBGENE-HBV appears to be working by its intended mechanism of eliminating the source of viral replication in cccDNA while inactivating integrated disease; plans to provide ongoing updates on the full low-dose cohort for the PBGENE-HBV study, including multiple dose administrations, and data at higher dose levels throughout 2025; the ability of ARCUS single-component nucleases to penetrate the mitochondrial membranes; 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; plans to present new data for PBGENE-3243 in 2025 while advancing the program toward a CTA and/or IND; the ability of PBGENE-DMD to provide 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; the ability of PBGENE to edit satellite muscle stem cells, a potential predictor of durable functional benefit; the translation of results in preclinical studies of ARCUS nucleases to clinical studies in humans; expectations about our and our partners’ operational initiatives, strategies, and further development of our programs; expectations and updates around our partnerships and collaborations and our ability to enter into new collaborations, license agreements or other arrangements; our expected cash runway and available credit; the sufficiency of our cash runway extending into the second half of 2026 and realizing Phase 1 clinical data for multiple in vivo gene editing programs; expectations about achievement of key milestones and receipt of any milestone, royalty, or other payments; expectations regarding our liquidity and capital resources; and anticipated timing of clinical data . In some cases, you can identify forward-looking statements by terms such as “aim,” “anticipate,” “appear,” “approach,” “believe,” “contemplate,” “could,” “designed,” “estimate,” “expect,” “goal,” “intend,” “look,” “may,” “mission,” “plan,” “possible,” “potential,” “predict,” “project,” “pursue,” “should,” “strive,” “suggest,” “target,” “will,” “would,” or the negative thereof and similar words and expressions. Forward-looking statements are based on management’s current expectations, beliefs and assumptions and on information currently available to us. These statements are neither promises nor guarantees, and involve a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to, our ability to become profitable; our ability to procure sufficient funding to advance our programs; risks associated with our capital requirements, anticipated cash runway, requirements under our current debt instruments and effects of restrictions thereunder, including our ability to raise additional capital due to market conditions and/or our market capitalization; our operating expenses and our ability to predict what those expenses will be; our limited operating history; the progression and success of our programs and product candidates in which we expend our resources; our limited ability or inability to assess the safety and efficacy of our product candidates; the risk that other genome-editing technologies may provide significant advantages over our ARCUS technology; our dependence on our ARCUS technology; the initiation, cost, timing, progress, achievement of milestones and results of research and development activities and preclinical and clinical studies, including clinical trial and investigational new drug applications; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, and biotechnology fields; our or our collaborators’ or other licensees’ ability to identify, develop and commercialize product candidates; pending and potential product liability lawsuits and penalties against us or our collaborators or other licensees related to our technology and our product candidates; the U.S. and foreign regulatory landscape applicable to our and our collaborators’ or other licensees’ development of product candidates; our or our collaborators’ or other licensees’ ability to advance product candidates into, and successfully design, implement and complete, clinical trials; potential manufacturing problems associated with the development or commercialization of any of our product candidates; delays or difficulties in our and our collaborators’ and other licensees’ ability to enroll patients; changes in interim “top-line” and initial data that we announce or publish; if our product candidates do not work as intended or cause undesirable side effects; risks associated with applicable healthcare, data protection, privacy and security regulations and our compliance therewith; our or our licensees’ ability to obtain orphan drug designation or fast track designation for our product candidates or to realize the expected benefits of these designations; our or our collaborators’ or other licensees’ ability to obtain and maintain regulatory approval of our product candidates, and any related restrictions, limitations and/or warnings in the label of an approved product candidate; the rate and degree of market acceptance of any of our product candidates; our ability to effectively manage the growth of our operations; our ability to attract, retain, and motivate executives and personnel; effects of system failures and security breaches; insurance expenses and exposure to uninsured liabilities; effects of tax rules; effects of any pandemic, epidemic, or outbreak of an infectious disease; the success of our existing collaboration and other license agreements, and our ability to enter into new collaboration arrangements; our current and future relationships with and reliance on third parties including suppliers and manufacturers; our ability to obtain and maintain intellectual property protection for our technology and any of our product candidates; potential litigation relating to infringement or misappropriation of intellectual property rights; effects of natural and manmade disasters, public health emergencies and other natural catastrophic events; effects of sustained inflation, supply chain disruptions and major central bank policy actions; market and economic conditions; risks related to ownership of our common stock, including fluctuations in our stock price; our ability to meet the requirements of and maintain listing of our common stock on Nasdaq or other public stock exchanges; and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024 , as any such factors may be updated from time to time in our other filings with the SEC , which are accessible on the SEC’s website at www.sec.gov and the Investors page of our website under SEC Filings at investor.precisionbiosciences.com. All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we have no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. 2024 2023 $ 638 $ 7,038 15,907 13,389 9,577 8,539 25,484 21,928 (24,846 ) (14,890 ) (972 ) (871 ) (659 ) 1,603 7,812 — (392 ) (579 ) 1,494 1,827 (182 ) (524 ) 7,101 1,456 $ (17,745 ) $ (13,434 ) — (2,855 ) $ (17,745 ) $ (16,289 ) $ (2.22 ) $ (4.06 ) 7,999,288 4,010,067 2024 2023 $ 68,696 $ 48,727 59,559 53,375 35,299 39,088 94,858 92,463 (26,162 ) (43,736 ) (1,084 ) (4,931 ) 258 1,145 29,610 — (1,782 ) (2,230 ) 6,763 7,686 (436 ) (461 ) 33,329 1,209 $ 7,167 $ (42,527 ) — (18,792 ) $ 7,167 $ (61,319 ) $ 1.05 $ (15.96 ) $ 1.04 $ (15.96 ) 6,832,982 3,841,405 6,883,911 3,841,405 $ 108,468 $ 116,678 80,009 86,372 136,388 159,781 79,995 140,920 $ 56,393 $ 18,861 8,202,715 4,164,038 View source version on businesswire.com: https://www.businesswire.com/news/home/20250326544666/en/ Investor and Media Contact: Naresh Tanna Vice President, Investor Relations Naresh.Tanna@precisionbiosciences.com Source: Precision BioSciences, Inc.