Ornithine Carbamoyltransferase Deficiency Disease

Kostaive® anticipated to launch in Japan this year ARCT-032 remains on track for Phase 1b interim data in Q2 ARCT-810 remains on track for Phase 2 interim data by the end of Q2 ARCT-2138 (Quadrivalent LUNAR-FLU) Phase 1 study for seasonal influenza vaccine initiated New STARR® vaccine discovery programs initiated for Lyme Disease and Gonorrhea Cash runway extended to Q1 2027 Investor conference call at 4:30 p.m. ET today SAN DIEGO--(BUSINESS WIRE)-- Arcturus Therapeutics Holdings Inc. (the “Company”, “Arcturus”, Nasdaq: ARCT), a global messenger RNA medicines company focused on the development of infectious disease vaccines and opportunities within liver and respiratory rare diseases, today announced its financial results for the fourth quarter ended December 31, 2023, and provided corporate updates. “I am excited about the continued pipeline progress and efforts toward commercialization achieved by Arcturus in 2023,” said Joseph Payne, President & CEO of Arcturus Therapeutics. “Alongside our global vaccine partner CSL Seqirus and their COVID vaccine partner in Japan, Meiji, Kostaive® was granted historic approval as the world’s first self-amplifying mRNA (sa-mRNA) product. Recently released clinical trial data, demonstrated Kostaive® induced a stronger, broader, and more durable immune response compared to an approved conventional mRNA vaccine.” Mr. Payne continued: “We are especially pleased to announce the U.S. FDA and the European Commission recently granted Orphan Drug Designation for ARCT-032, an inhaled mRNA therapeutic candidate for individuals with cystic fibrosis. These regulatory designations will help advance ARCT-032 to become a potential treatment for the segment of the CF population who are not candidates for any of the currently approved drugs for this disease.” Andy Sassine, Chief Financial Officer of Arcturus said, “I am pleased to announce the cash runway was extended to the first quarter 2027 due to disciplined cost management and progression of the CSL collaboration. This is the second sequential quarter our runway was extended without including any contributions from Kostaive® revenues or commercial milestones.” Recent Corporate Highlights In February 2024, the Company announced new COVID-19 sa-mRNA results in collaboration with CSL, demonstrating a longer duration of immunity compared to conventional COVID-19 mRNA vaccine booster. Short communication follows previously published data in The Lancet Infectious Diseases in December 2023. The randomized, double-blind, active-controlled study, conducted at 11 sites in Japan assessed the immunogenicity of Kostaive® and Comirnaty® at one, three- and six-months post-booster. The new analysis extends the time of observation of immune response from 3 months to 6 months post booster dose, demonstrating an advantage in antibody persistence of Kostaive® over Comirnaty against both the original Wuhan strain and the Omicron BA.4/5 variant. The superior immune response of Kostaive® in terms of magnitude and duration of antibody persistence was achieved with one sixth the dose of Comirnaty (5 μg vs 30 μg). In November, Japan's Ministry of Health, Labor and Welfare (MHLW) granted approval for Kostaive®, a self-amplifying mRNA COVID-19 vaccine for primary vaccination and booster for adults 18 years and older. This marks the first marketing approval milestone for CSL and Arcturus since signing the Collaboration and License agreement in November 2022. The approval is based on positive clinical data from several Kostaive® studies, including a 16,000 subject efficacy study performed in Vietnam as well as a Phase 3 COVID-19 booster trial, which achieved higher immunogenicity results and a favorable safety pro to a standard mRNA COVID-19 vaccine comparator. The study results have been published in The Lancet Infectious Diseases. Kostaive® is anticipated to launch in Japan this year. In January 2024, the Company, under its collaboration with CSL, initiated a Phase 1 dose-finding study for ARCT-2138 (Quadrivalent LUNAR-FLU) seasonal influenza vaccine in healthy young and older adults. The Company continues to advance the development of ARCT-810, an mRNA therapeutic candidate for ornithine transcarbamylase (OTC) deficiency. ARCT-810 Phase 1b single ascending dose study in the U.S. has completed enrollment and dosing of all cohorts (N = 16 patients). ARCT-810 Phase 2 study in UK and Europe is enrolling up to 24 adolescents and adults with OTC deficiency. The ongoing study is evaluating two dose levels and includes up to six (6) bi-weekly administrations for each participant. The Company expects to share Phase 2 interim data by the end of Q2. In November 2023, Arcturus received Orphan Drug Designation from the U.S. FDA for ARCT-032, for the treatment of Cystic Fibrosis. In February 2024, Arcturus was granted Orphan Medicinal Product Designation from the European Commission for ARCT-032. ARCT-032 remains on track for Phase 1b interim data in Q2 2024. Based on the clinical and regulatory validation of LUNAR® and STARR® technologies provided by the approval of Kostaive® in Japan, the Company has initiated new vaccine discovery programs for Lyme Disease and Gonorrhea. Financial Results for the Year Ended December 31, 2023 Revenues in conjunction with collaborations and grants: Arcturus’ primary sources of revenues were from license fees, consulting and related technology transfer fees, reservation fees and collaborative payments received from research and development arrangements with pharmaceutical and biotechnology partners. For the year ended December 31, 2023, we reported revenue of $169.9 million compared with $206.0 million for the year ended December 31, 2022. Revenue recognized from CSL in 2023 was $157.4 million which slightly increased by $3.0 million compared to 2022. We made significant progress with the BARDA grant agreement that led to an increase in revenue of $8.8 million. The majority of the annual decrease in revenue was driven by the discontinuation of our collaboration agreements with Vinbiocare and Janssen. For the three months ended December 31, 2023, revenue recognized was $34.0 million compared with $160.3 million for the three months ended December 31, 2022. The $200.0 million up front payment for the execution of the CSL collaboration drove the majority of the revenue recognition during the three months ended December 31, 2022. Operating expenses: Total operating expenses for the year ended December 31, 2023, were $245.0 million compared with $193.8 million for the year ended December 31, 2022. For the three months ended December 31, 2023, operating expenses were $49.1 million compared with $38.8 million for the three months ended December 31, 2022. Research and Development Expenses: Research and development expenses consist primarily of external manufacturing costs, in-vivo research studies and clinical trials performed by contract research organizations, clinical and regulatory consultants, personnel related expenses, facility related expenses and laboratory supplies. Research and development expenses were $192.1 million for the year ended December 31, 2023, compared with $147.8 million for the year ended December 31, 2022. The increase in research and development expenses were primarily driven by the CSL and BARDA programs as well as our internal OTC and Cystic Fibrosis programs. Additionally, we have increased investments in early stage and discovery technologies. The Company initiated preclinical research related to its Lyme Disease and Gonorrhea vaccine discovery programs. Research and development expenses were $36.6 million for the three months ended December 31, 2023, compared with $27.0 million for the three months ended December 31, 2022. This increase was due to higher professional and personnel-related expenses as well as lower contra research and development expense from grants. General and Administrative Expenses: General and administrative expenses primarily consist of salaries and related benefits for our executive, administrative, legal and accounting functions and professional service fees for legal and accounting services as well as other general and administrative expenses. For the year ended December 31, 2023, general and administrative expenses were $52.9 million compared with $46.1 million for the year ended December 31, 2022. The annual increase was primarily due to personnel expenses as a result of increased headcount and salaries, travel and consulting expenses. Additionally, we incurred higher rent expenses associated with the new headquarters facility. General and administrative expenses were $12.5 million for the three months ended December 31, 2023, compared with $11.8 million for the three months ended December 31, 2022. The slight increase was due to personnel-related expenses. Net Loss: For the year ended December 31, 2023, we reported a net loss of approximately $26.6 million, or ($1.00) per diluted share, compared with net income of $9.3 million, or $0.35 per diluted share for the year ended December 31, 2022. For the three months ended December 31, 2023, we reported a net loss of approximately $8.6 million or ($0.32) per diluted share, compared with net income of $117.4 million or $4.33 per diluted share for the three months ended December 31, 2022. Cash Position and Balance Sheet: Cash, cash equivalents and restricted cash were $348.9 million at December 31, 2023, and $394.0 million at December 31, 2022. We have achieved a total of approximately $396.0 million in upfront payments and milestones from CSL as of December 31, 2023. We expect to continue to receive future milestone payments from CSL that will support the ongoing development of the covid and flu programs and three additional vaccine programs by CSL. The expected cash runway extends at least three years based on the current pipeline and programs. Earnings Call: Thursday, March 7, 2024 @ 4:30 pm ET Domestic: 1-877-407-0784 International: 1-201-689-8560 Conference ID: 13744044 Webcast: Link About Arcturus Therapeutics Founded in 2013 and based in San Diego, California, Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT) is a global 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 the first self-amplifying messenger RNA (sa-mRNA) COVID vaccine (Kostaive®) 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 deficiency and cystic fibrosis, 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 400 patents and patent applications in the U.S., Europe, Japan, China, and other countries). For more information, visit . 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 strategy, future operations, the likelihood of success of the Company’s pipeline (including ARCT-032 and ARCT-810) and partnered programs (including the COVID-19 and flu programs partnered with CSL Seqirus), the likelihood that preclinical or clinical data will be predictive of future clinical results, including that the results from Kostaive® (or ARCT-154) will be predictive of results for updated versions of the vaccine, the potential commercial launch of Kostaive®, the continued advancement ARCT-032 or its potential as a treatment for any of the CF population, the continued advancement of ARCT-810, the anticipated timing and sharing of clinical data including for the Company’s ARCT810 Phase 2 study and the ARCT-032 Phase 1b study, the continued efforts for our vaccine discovery programs for lyme disease or gonorrhea, the potential of the Company’s platform technology to be meaningfully differentiated from other technologies, the continued progress of the LUNAR-FLU program, the ability to enroll participants in clinical studies including the Company’s ARCT-810 and ARCT-032 programs, the likelihood and timing of commercial activities for the Company’s LUNAR-COVID program, the likelihood that a patent will issue from any patent application, the likelihood or timing of collection of accounts receivables including expected payments from CSL, its current cash position and expected cash burn and runway, 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 . 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. Trademark Acknowledgements The Arcturus logo and other trademarks of Arcturus appearing in this announcement, including LUNAR® and STARR®, are the property of Arcturus. All other trademarks, services marks, and trade names in this announcement are the property of their respective owners. ARCTURUS THERAPEUTICS HOLDINGS INC. AND ITS SUBSIDIARIES CONSOLIDATED BALANCE SHEETS As of December 31, (in thousands, except par value information) 2023 2022 Assets (unaudited) Current assets: Cash and cash equivalents $ 292,005 $ 391,883 Restricted cash 55,000 — Accounts receivable 32,064 2,764 Prepaid expenses and other current assets 7,521 8,686 Total current assets 386,590 403,333 Property and equipment, net 12,427 12,415 Operating lease right-of-use asset, net 28,500 32,545 Non-current restricted cash 1,885 2,094 Total assets $ 429,402 $ 450,387 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 5,279 $ 7,449 Accrued liabilities 31,881 30,232 Current portion of long-term debt — 60,655 Deferred revenue 41,695 28,648 Total current liabilities 78,855 126,984 Deferred revenue, net of current portion 42,496 20,071 Operating lease liability, net of current portion 25,907 30,216 Other non-current liabilities 497 2,804 Total liabilities 147,755 180,075 Stockholders’ equity: Common stock: $0.001 par value; 60,000 shares authorized; issued and outstanding shares were 26,828 at December 31, 2023 and 26,555 at December 31, 2022 27 27 Additional paid-in capital 646,352 608,426 Accumulated deficit (364,732 ) (338,141 ) Total stockholders’ equity 281,647 270,312 Total liabilities and stockholders’ equity $ 429,402 $ 450,387 ARCTURUS THERAPEUTICS HOLDINGS INC. AND ITS SUBSIDIARIES CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (LOSS) Year Ended December 31, (in thousands, except per share data) 2023 2022 2021 Revenue: (unaudited) Collaboration revenue $ 160,882 $ 205,755 $ 12,359 Grant revenue 9,051 244 — Total revenue 169,933 205,999 12,359 Operating expenses: Research and development, net 192,133 147,751 173,760 General and administrative 52,871 46,071 41,451 Total operating expenses 245,004 193,822 215,211 (Loss) income from operations (75,071 ) 12,177 (202,852 ) (Loss) gain from equity-method investment — (515 ) 515 (Loss) gain from foreign currency (229 ) (598 ) 584 Finance income (expense), net 16,591 (420 ) (1,921 ) Gain on debt extinguishment 33,953 — — Net (loss) income before income taxes (24,756 ) 10,644 (203,674 ) Provision for income taxes 1,835 1,295 — Net (loss) income $ (26,591 ) $ 9,349 $ (203,674 ) (Loss) earnings per share: Basic $ (1.00 ) $ 0.35 $ (7.74 ) Diluted $ (1.00 ) $ 0.35 $ (7.74 ) Weighted-average shares used in calculation of (loss) earnings per share: Basic 26,628 26,445 26,317 Diluted 26,628 27,093 26,317 Comprehensive (loss) income: Net (loss) income $ (26,591 ) $ 9,349 $ (203,674 ) Comprehensive (loss) income: $ (26,591 ) $ 9,349 $ (203,674 ) ARCTURUS THERAPEUTICS HOLDINGS INC. AND ITS SUBSIDIARIES CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (LOSS) (UNAUDITED) Three Months Ended December 31, September 30, (in thousands, except per share data) 2023 2022 2023 Revenue: Collaboration revenue $ 28,212 $ 160,049 $ 43,376 Grant revenue 5,777 244 1,764 Total revenue 33,989 160,293 45,140 Operating expenses: Research and development, net 36,620 26,981 51,077 General and administrative 12,507 11,860 13,377 Total operating expenses 49,127 38,841 64,454 Income (loss) from operations (15,138 ) 121,452 (19,314 ) (Loss) gain from foreign currency (54 ) (3,835 ) 4 Finance expense, net 6,881 1,025 3,981 Net (loss) income before income taxes (8,311 ) 118,642 (15,329 ) Provision for income taxes 262 1,295 893 Net (loss) income $ (8,573 ) $ 117,347 $ (16,222 ) (Loss) earnings per share: Basic $ (0.32 ) $ 4.43 $ (0.61 ) Diluted $ (0.32 ) $ 4.33 $ (0.61 ) Weighted-average shares used in calculation of (loss) earnings per share: Basic 26,628 26,508 26,574 Diluted 26,628 27,080 26,574 Comprehensive (loss) income: Net (loss) income $ (8,573 ) $ 117,347 $ (16,222 ) Comprehensive (loss) income $ (8,573 ) $ 117,347 $ (16,222 )

PHILADELPHIA--( BUSINESS WIRE )-- iECURE , Inc., a gene editing company focused on the development of mutation-agnostic in vivo gene insertion, or knock-in, editing therapies for the treatment of liver disorders with significant unmet need, announced today approval from the U.K. Medicines & Healthcare products Regulatory Agency (MHRA) of the company’s Clinical Trial Authorisation application (CTA) to expand the OTC-HOPE study into the U.K. The OTC-HOPE study is investigating ECUR-506, an investigational gene editing-based therapy, for the treatment of Ornithine Transcarbamylase (OTC) deficiency in infants. The CTA approval by the MHRA follows the previous approval to begin the OTC-HOPE study by the Australian Therapeutic Goods Administration (TGA). “ECUR-506 is the first ever clinical meganuclease-based in vivo gene insertion program, and as we continue progressing ECUR-506 towards first-in-human dosing, we are assured by the confidence instilled in this program by both the MHRA and the TGA,” said Joe Truitt, Chief Executive Officer of iECURE. “Throughout 2024, we will continue to be in close contact with other regulatory bodies as we seek to expand the OTC-HOPE study into additional geographies. We are in the process of ensuring sites are prepared to enroll patients and anticipate site initiations in the upcoming months.” The OTC-HOPE study is a Phase 1/2 first-in-human study in newborn males with genetically confirmed neonatal onset OTC deficiency. It is designed primarily to assess the safety and tolerability of up to two dose levels of ECUR-506 following intravenous administration of a single dose. Secondary objectives are to assess the pharmacokinetics and efficacy of ECUR-506. In addition, exploratory endpoints will assess disease-specific biologic markers, developmental milestones and quality of life. “OTC deficiency is a serious inherited metabolic disorder and in most severe cases, liver transplant is required,” said Gabriel M. Cohn, MD, Chief Medical Officer of iECURE. “ECUR-506, if approved, offers hope to families afflicted by this life-threatening condition as an alternative treatment approach. Through gene editing, we believe ECUR-506 can enable these children to durably produce functional OTC enzyme thereby providing lasting clinical benefit and eliminating the need for liver transplant and the lifelong immunosuppressive treatments required to prevent organ rejection.” About ECUR-506 iECURE’s approach to gene editing for its initial programs, including OTC deficiency, relies on the delivery of two adeno-associated virus (AAV) capsids, each carrying different payloads. ECUR-506 comprises two vectors, an ARCUS® nuclease vector targeting gene editing in the well-characterized PCSK9 gene locus and a donor vector that inserts the desired functional OTC gene. iECURE has licensed the ARCUS nuclease for ECUR-506 from Precision BioSciences. 1 The cut in the PCSK9 site serves as the insertion site for the OTC gene, providing a potential path to permanent expression of a healthy gene. ECUR-506 is being studied in the OTC-HOPE study, the first clinical meganuclease-based in vivo gene insertion program. About the OTC-HOPE Study The OTC-HOPE study is a Phase 1/2 first-in-human clinical trial of ECUR-506 in baby boys with genetically confirmed OTC deficiency and will test up to two dose levels of ECUR-506. The study is enrolling baby boys aged 24 hours to seven months who are diagnosed with severe neonatal onset OTC deficiency and meet certain other criteria. The primary objective is to assess the safety and tolerability of intravenous administration of a single dose of ECUR-506. It will also assess the pharmacokinetics and efficacy of ECUR-506 administration and the potential effects of ECUR-506 on disease-specific biologic markers, developmental milestones and quality of life. About iECURE iECURE is a clinical-stage gene editing company focused on developing therapies that utilize mutation-agnostic in vivo gene insertion, or knock-in, editing for the treatment of liver disorders with significant unmet need. We believe our approach has the potential to replace and restore the function of a dysfunctional gene, regardless of mutation, by knocking-in a healthy copy of that gene to offer durable gene expression and long-term, potentially curative, therapeutic benefit. Our management team has extensive experience in executing global orphan drug and gene therapy clinical trials and successfully commercializing multiple products. We intend to leverage our team’s core strength in research and development strategy to identify what we believe to be the most suitable target and modality for our product candidates to address particular liver diseases. We are collaborating with the University of Pennsylvania’s Gene Therapy Program (GTP) led by James M. Wilson, M.D., Ph.D., to utilize GTP’s world-class translational expertise and infrastructure, which has helped generate our initial pipeline of potential product candidates. For more information, visit https://iecure.com and follow on LinkedIn . About Precision BioSciences & ARCUS ® Precision BioSciences, Inc. is an advanced gene editing company dedicated to improving life (Nasdaq: DTIL) with its novel and proprietary ARCUS® genome editing platform that is designed to differ 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, Precision’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, visit www.precisionbiosciences.com . Penn’s Financial Disclosure The University of Pennsylvania (Penn) and Dr. Wilson each hold equity interests in iECURE. Penn also receives significant sponsored research support from iECURE, and both Penn and Dr. Wilson stand to benefit from licensing revenues received from iECURE based on successful technology development and commercialization of the technologies licensed from Penn. Dr. Wilson serves as Chief Scientific Advisor for iECURE. [1] iECURE has licensed the ARCUS® nuclease from Precision BioSciences for four gene insertion programs including OTC, CTLN1 and PKU.

- Insertion of a functional OTC gene through ARCUS in vivo gene editing may provide lasting clinical benefit for children with OTC deficiency who are in dire need for effective treatments - CTA approval for ECUR-506 in the United Kingdom provides further regulatory support for Precision BioSciences’ ARCUS in vivo gene editing platform DURHAM, N.C.--(BUSINESS WIRE)-- Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS® platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene insertion, excision, and elimination, today announced that its partner iECURE has received approval from the U.K. Medicines & Healthcare products Regulatory Agency (MHRA) for the company’s Clinical Trial Authorization (CTA) application to expand the Phase 1/2 OTC-HOPE study evaluating ECUR-506 into the U.K. The OTC-HOPE study is investigating ECUR-506, incorporating an ARCUS nuclease, for the treatment of Ornithine Transcarbamylase (OTC) deficiency in infants. The CTA approval by the MHRA follows the previous approval to begin the OTC-HOPE study by the Australian Therapeutic Goods Administration (TGA). In 2021, Precision licensed to iECURE an ARCUS nuclease that inserts a functional copy of the OTC gene for treatment of OTC deficiency. “Congratulations to iECURE for bringing the first gene editing approach into clinical investigation for patients with OTC deficiency. Approval from the MHRA to expand iECURE’s OTC-HOPE Phase 1/2 study represents yet another milestone, which both advances our partner’s work to potentially revolutionize the treatment of OTC deficiency in infants while validating the differentiated ability of ARCUS to efficiently insert genes and restore function,” said Michael Amoroso, Chief Executive Officer of Precision BioSciences. “To that end, we view progression through multiple regulatory agencies around the world as important proof-points for ARCUS that reflects our broader strategy to leverage ARCUS with select development partners as we continue to advance our wholly owned hepatitis B program toward an investigational new drug (IND) application and/or CTA filing in 2024.” OTC deficiency, the most common urea cycle disorder, is an inherited metabolic disorder caused by a genetic defect in a liver enzyme responsible for the detoxification of ammonia. Individuals with OTC deficiency can build up excessive levels of ammonia in their blood potentially resulting in devastating consequences, including irreversible neurological damage, coma, and death. The severe form of the condition emerges shortly after birth and is more common in boys than girls. The only corrective treatment for early onset severe OTC deficiency is a liver transplant. Currently available medical therapies do not correct the disease and do not eliminate the risk of life-threatening symptoms or crises. About Precision BioSciences, Inc. Precision BioSciences, Inc. is an advanced 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, Precision’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. About ECUR-506 iECURE’s approach to gene editing for its initial programs, including OTC deficiency, relies on the delivery of two adeno-associated virus (AAV) capsids, each carrying different payloads. ECUR-506 comprises two vectors, an ARCUS® nuclease vector targeting gene editing in the well-characterized PCSK9 gene locus and a donor vector that inserts the desired functional OTC gene. iECURE has licensed the ARCUS nuclease for ECUR-506 from Precision BioSciences. The cut in the PCSK9 site serves as the insertion site for the OTC gene, providing a potential path to permanent expression of a healthy gene. About the OTC-HOPE Study The OTC-HOPE study is a Phase 1/2 first-in-human clinical trial of ECUR-506 in baby boys with genetically confirmed OTC deficiency and will test up to two dose levels of ECUR-506. The study is enrolling baby boys aged 24 hours to seven months who are diagnosed with severe neonatal onset OTC deficiency and meet certain other criteria. The primary objective is to assess the safety and tolerability of intravenous administration of a single dose of ECUR-506. It will also assess the pharmacokinetics and efficacy of ECUR-506 administration and the potential effects of ECUR-506 on disease-specific biologic markers, developmental milestones and quality of life. About iECURE iECURE is a clinical-stage gene editing company focused on developing therapies that utilize mutation-agnostic in vivo gene insertion, or knock-in, editing for the treatment of liver disorders with significant unmet need. We believe our approach has the potential to replace and restore the function of a dysfunctional gene, regardless of mutation, by knocking-in a healthy copy of that gene to offer durable gene expression and long-term, potentially curative, therapeutic benefit. Our management team has extensive experience in executing global orphan drug and gene therapy clinical trials and successfully commercializing multiple products. We intend to leverage our team’s core strength in research and development strategy to identify what we believe to be the most suitable target and modality for our product candidates to address particular liver diseases. We are collaborating with the University of Pennsylvania’s Gene Therapy Program (GTP) led by James M. Wilson, M.D., Ph.D., to utilize GTP’s world-class translational expertise and infrastructure, which has helped generate our initial pipeline of potential product candidates. For more information, visit and follow on LinkedIn. 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’ product candidates and gene editing approaches including editing efficiency; the suitability of ARCUS nucleases for gene insertion and other gene editing approaches; the expected timing of regulatory processes; expectations about our and our partners’ operational initiatives and strategy; and anticipated timing of clinical data. In some cases, you can identify forward-looking statements by terms such as “aim,” “anticipate,” “approach,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “goal,” “intend,” “look,” “may,” “mission,” “plan,” “possible,” “potential,” “predict,” “project,” “pursue,” “should,” “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 or field trials; potential manufacturing problems associated with the development or commercialization of any of our product candidates; our ability to obtain an adequate supply of T cells from qualified donors; 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 the COVID-19 pandemic and variants thereof, or 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 Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2023, 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 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.