Arcturus Therapeutics Holdings Inc. (ARCT) Business

Item 1. Business

Overview

We are a messenger RNA medicines company focused on the development of liver and respiratory rare disease therapeutics. We have ongoing Phase 2 clinical studies for our RNA therapeutic candidates to potentially treat ornithine transcarbamylase (OTC) deficiency and cystic fibrosis (CF).

We developed the world’s first approved self-amplifying messenger RNA (sa-mRNA) vaccine, KOSTAIVE® (“KOSTAIVE”), which we have partnered with Seqirus, Inc. (“CSL Seqirus”), a part of CSL Limited. KOSTAIVE has achieved approval in Japan, the European Union and the United Kingdom as a vaccine against COVID-19, and sales of KOSTAIVE began in Japan in October 2024.

We have several key platform technologies that we leverage to develop and advance a pipeline of mRNA-based therapeutics for rare genetic disorders with significant unmet medical needs and vaccines for infectious diseases. Current mRNA medicines have two critical components: the messenger RNA (“mRNA”) constructs and the lipid nanoparticles (“LNP”) which help deliver the mRNA to disease-relevant target tissues. We have extensive expertise in the design and optimization of mRNA constructs, including with respect to a type of mRNA technology known as self-amplifying mRNA (sa-mRNA). Our proprietary self-amplifying mRNA technology platform, or STARR® (“STARR”), has been demonstrated to induce a robust, longer-lasting and broader humoral immune response at lower dose levels than conventional mRNA-based vaccines. Our proprietary LNP delivery system, LUNAR® (“LUNAR”), is intended to address the major hurdle in RNA drug development, namely the effective and safe delivery of RNA to disease-relevant target tissues. LUNAR may enable multiple nucleic acid medicines. We also have significant expertise and valuable know-how in the development and scalability of complex and robust manufacturing processes required to deliver the next generation of nucleic acid medicines.

Our internal pipeline includes RNA therapeutic candidates to potentially treat ornithine transcarbamylase (OTC) deficiency and cystic fibrosis (CF), both rare diseases. In our vaccine program, we have partnered with CSL Seqirus, one of the world’s leading influenza vaccine providers, on the development and commercialization of mRNA vaccines for COVID-19, influenza and three other infectious diseases. In CSL Limited’s half-year results presented on February 11, 2026, CSL Limited reported an accounting write-down of approximately $430 million attributable to our collaboration agreement with CSL Seqirus, citing declining COVID-19 disease burden and more onerous U.S. regulatory requirements.

In our CF program, we enrolled and completed dosing in the three initially planned cohorts of our Phase 2 multiple ascending dose study of ARCT-032, confirming the safety and tolerability of ARCT-032 dosed daily for four weeks. This study was initiated in December 2024 and was designed to identify a safe and effective dose regimen in those with Class I (null) CFTR mutations and people with CF who do not benefit from CFTR modulators. In the study, six CF adults with Class I CFTR mutations inhaled 10 mg doses of ARCT-032 daily over 28 days. Interim results released in October 2025 demonstrated that the treatment was generally safe and well tolerated. Treatment-related adverse events (AEs) that were identified in the single-dose Phase 1 study were also observed in some participants for the first few doses but ceased with continued dosing. Bronchospasm has not been reported in this study thus far, neither with nor without albuterol pretreatment. One serious adverse event (SAE) occurred in a participant after the end of the dosing period. The safety review committee found no convincing evidence that the SAE is related to ARCT-032 and approved the study to proceed. We intend to initiate a 12-week safety and preliminary efficacy study in up to 20 CF participants in the first half of 2026, after the third cohort completes treatment. ARCT-032 has received Orphan Drug Designation by the U.S. Food and Drug Administration (the “FDA”) and Orphan Medicinal Product Designation by the European Medicines Agency (the “EMA”) for the treatment of CF, and Rare Pediatric Disease Designation from the FDA.

KOSTAIVE is the brand name approved in Japan and Europe for ARCT-154, which is the version of the sa-mRNA COVID vaccine encoding the ancestral strain of SARS-CoV-2, and also for updated variant-specific versions of this vaccine. We may use KOSTAIVE or the specific internally generated name, such as ARCT-154, ARCT-2301 and ARCT-2303, to identify a version of the vaccine.

In our OTC program, we have continued to conduct a Phase 2 double-blind multiple-dose study of ARCT-810. Five patients with OTC deficiency have now completed dosing, and a sixth patient has initiated dosing. A type C meeting with the FDA to discuss our plans for a proposed future pediatric study under the RDEP (Rare Disease

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Evidence Principles) is scheduled for the first half of 2026. ARCT-810 has received Orphan Drug Designation from the FDA and Orphan Medicinal Product Designation from the EMA for treatment of OTC deficiency, as well as Fast Track Designation and Rare Pediatric Disease Designation from the FDA.

Commercial sales of KOSTAIVE began in October 2024 in Japan by Meiji Seika Pharma, Ltd. (“Meiji”), CSL Seqirus’ exclusive partner in Japan, marking the first commercial sales of an Arcturus-developed product. In September 2025, Meiji launched a new presentation of KOSTAIVE in Japan. The product is a 2-dose vial lyophilized presentation incorporating the updated XEC variant strain. Approval for offshore manufacturing of the 2-dose vial lyophilized presentation was granted by Japan in August 2025, followed by approval for onshore manufacturing in January 2026. KOSTAIVE was approved by the European Commission (EC) in February 2025 and by the United Kingdom in January 2026, providing further validation of our platform by additional significant regulatory authorities.

In December 2024, we initiated dosing of an sa-mRNA vaccine candidate against pandemic avian influenza (bird flu) in a Phase 1 trial funded by the Biomedical Advanced Research and Development Authority (“BARDA”). The study results were received in the second half of 2025, indicating a favorable tolerability and safety profile and the ability to induce a robust and durable humoral immune response in young and older adults.

We also improved our platform technologies and advanced our early-stage research activities and manufacturing process development and operations. We conducted exploratory platform development activities, including the evaluation of genome editing, and new targeting approaches, where our LUNAR and STARR platforms could be useful for identification and development of additional products for our portfolio.

Nucleic Acid Medicines and an Introduction to Arcturus’ Platform Technologies

Nucleic Acid Medicines

Nucleic acid medicines have the potential to treat diseases caused by genetic mutations, including diseases that cannot be treated by conventional drugs, such as small molecules and biologics. Some of these medicines function by providing the means for producing a deficient yet vital protein in vivo. Within a cell, DNA carries the blueprint, in the form of genes, which encode critical proteins necessary for life. Each gene’s code is transcribed into a nucleic acid molecule called mRNA, which informs the cell’s own machinery how to organize amino acid building blocks to make one or more proteins needed for normal biological function.

Nucleic acid therapeutics represent a significant advancement in targeted medicines and several of these therapeutics are being developed by public and private companies. The general objectives of these therapies include:

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to introduce a gene product (e.g., mRNA or DNA) that encodes for a functional protein to replace an absent or defective protein;

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to restore a functional protein by genomic DNA editing of the corresponding gene or RNA editing resulting in the correction of the mRNA sequence;

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to reduce the amount of a target protein in a patient by binding to and destroying the associated target mRNA (antisense DNA or small interfering RNA (“siRNA”)); and

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to express proteins from viruses or unique proteins only found in cancer and not in non-cancerous cells resulting in the induction of protective immunity against specific viral pathogens or immune mediated elimination of cancer cells.

Brief Introduction to our LUNAR and STARR Technology Platforms

LUNAR®

A key challenge for nucleic acid medicines is the safe and effective delivery of the nucleic acid molecule into cells. In addition to enabling uptake of the medicine into cells, the nucleic acid delivery vehicle seeks to protect the nucleic acid from degradation prior to cell entry and to release the nucleic acid payload inside the cell. Arcturus has developed a novel lipid-mediated delivery system called LUNAR. LUNAR is comprised of a mixture of biodegradable synthetic lipids and naturally occurring lipids. Lipids are molecules that contain hydrocarbons and make up the building blocks of the structure and function of living cells. Examples of lipids include fats, oils, waxes and phospholipids. LUNAR is designed to address technical challenges facing the delivery of nucleic acid medicines into cells. We continue to expand our library of proprietary synthetic lipids, known as ATX, to over 300 to date. Our

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preclinical studies have shown that formulations can be customized for the indication and target cell type of interest, and we have also demonstrated that our proprietary formulation process is scalable and reproducible. Our LUNAR platform is described in more detail below.

STARR®

Our STARR technology is our proprietary self-amplifying mRNA (or sa-mRNA) technology platform. When combined with a delivery system, such as our lipid-mediated delivery system LUNAR, the STARR technology has the potential to generate a protective immune response or drive therapeutic protein expression to prevent against or treat a variety of diseases. Self-amplifying RNA-based prophylactic vaccines developed with STARR trigger rapid and prolonged antigen expression in host cells, which may provide protective immunity against infectious pathogens. We have shown in clinical trials that combining LUNAR and STARR technologies can reduce dose requirements, deliver a superior immune response, and sustain protein expression compared with conventional RNA-based vaccines, potentially enabling faster production of larger volumes of vaccine doses.

Our Pipeline

Therapeutics

Vaccines

(i) Commercialized in Japan; approved by the European Commission and the United Kingdom

Rare Disease Program

The Orphan Drug Act of 1983 (the “Orphan Drug Act”) defines a rare disease as a disease affecting fewer than 200,000 individuals in the United States. According to the National Institutes of Health (“NIH”), there are approximately 10,000 such diseases that, together, affect nearly 30 million people in the United States. The European Union (the “EU”) defines a rare disease as having a prevalence of fewer than five in 10,000 people. Collectively, these disorders affect between 6% and 7% of the population in the developed world.

There is a pressing need for new medicines for rare diseases as few of the 10,000 known rare diseases have approved treatments. Biopharmaceutical industry researchers are making great progress in the fight against some rare diseases as innovative science has opened new opportunities. More than 770 medicines have been approved by the FDA since the enactment of the Orphan Drug Act and more than 800 medicines are currently in clinical development. Despite recent progress, there is more work to be done to overcome the scientific, operational, and financial challenges that arise.

We believe our technology should provide an excellent platform to address genetically inherited rare diseases. Specifically, we are focusing on developing medicines to treat people with rare respiratory and liver diseases who currently have limited or no treatment options.

Rare Disease Program - LUNAR-CF (Cystic Fibrosis)

The LUNAR-CF program addresses cystic fibrosis (CF) lung disease, a progressive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. ARCT-032, our lead development candidate for the treatment of CF, uses our LUNAR platform to deliver a codon-optimized CFTR mRNA into airway epithelial cells. This allows airway cells to produce functional human CFTR protein using native translational machinery and protein trafficking pathways which could result in the treatment of the underlying defect

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that causes CF lung disease, regardless of the specific mutation. The Cystic Fibrosis Foundation (the “CFF”) has partnered with us to support the development of this therapy. ARCT-032 represents the first LUNAR-based mRNA therapeutic delivered by the inhaled route, offering direct delivery to the affected airways to restore functional CFTR.

There are close to 40,000 children and adults living with CF in the United States (and an estimated 105,000 people have been diagnosed with CF across 94 countries). CF can affect people of every racial and ethnic group. Approximately 800 people are newly diagnosed with CF each year in the United States. CF is caused by more than 2,000 known mutations in the CFTR gene. These mutations have been grouped into several different classes based on the mechanism by which they cause reduction in the production and/or function of the CFTR protein. When CFTR is absent or defective, the airway surfaces become dehydrated and coated with a layer of thick mucus that clogs the airways, causing difficulty breathing and often resulting in chronic infections, exaggerated inflammation, structural airway damage, and other serious complications in the lungs. CF is a multi-system disease that may also affect the pancreas, intestines, liver, sinuses, reproductive tract, and sweat glands. The median predicted survival of CF patients has dramatically improved since the introduction of highly effective CFTR modulators, and is approximately 65 years for those born between 2020-2024 in the United States. However, for those people with CF who are not eligible or otherwise cannot take modulators, the predicted survival remains much lower, and the cause of most of the mortality and morbidity is due to the lung disease.

Current non-curative therapies for CF lung disease are directed towards treating symptoms and preventing the progression of the disease. These treatments include aerosolized mucolytics, antibiotics, and airway clearance techniques that are time-consuming and represent a significant treatment burden for people with CF. Many CF patients ultimately suffer from a critical decline in lung function and require lung transplants.

The FDA has approved several CFTR modulator therapies (Kalydeco®, Orkambi®, Symdeko®, Trikafta®, and Alyftrek®) that assist certain classes of abnormal CFTR protein to reach the cell membrane and/or increase functional ion channel activity. The CFTR modulators, while effective in many patients, are mutation-specific and therefore are not effective in all persons with CF. Other treatments are required to target Class I mutations (no CFTR produced; approximately 10% of CF cases worldwide), and people who are intolerant or have poor response to CFTR modulator therapies. We are initially focusing ARCT-032 on these groups of patients, as they currently have the highest unmet need for CF therapies.

ARCT-032 has received Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA. The FDA also granted Rare Pediatric Disease Designation for ARCT-032. The Rare Pediatric Disease Designation is designed to recognize rare pediatric diseases in which the serious or life-threatening manifestations primarily affect patients from birth to 18 years of age. With this designation, if ARCT-032 achieves approval for a pediatric indication in the original rare pediatric disease product application in the United States, Arcturus (or the sponsor of ARCT-032) is eligible to receive a voucher for priority review of a subsequent marketing application for a different product.

In 2023, we successfully completed a safety and tolerability Phase 1 single ascending dose study of ARCT-032 (LUNAR-CF), our mRNA therapeutic candidate for CF. Thirty-two healthy participants (eight subjects in each of four dose cohorts) received a single inhaled dose of ARCT-032. Subsequently, seven CF adults received two administrations of ARCT-032 separated by two days in a Phase 1b study extension.

In the Phase 1/1b clinical study, ARCT-032 was generally safe and well tolerated in both the healthy volunteers and the participants with CF. Of the seven total CF participants in the Phase 1b study, six were being treated with CFTR modulators while one subject had Class I mutations that do not benefit from modulator therapy. No serious or severe adverse events (SAEs) were observed, and the safety profile was similar between healthy volunteers and CF participants. Mild, transient events of elevated temperature or feeling hot accompanied by other nonspecific symptoms were observed at dose levels that are higher than those planned for the Phase 2 study. In the CF subjects, lung function measured over eight days did not demonstrate a discernable pattern or safety concern after two doses of ARCT-032. Preliminary findings from the study were presented at the European CF Society Conference in June 2024 in Glasgow, Scotland, and at the North American CF Conference in September 2024 in Boston, MA.

In December 2024, we initiated dosing in our ARCT-032 Phase 2 multiple ascending dose study designed to identify a safe and effective dose in Class I (null) and other CF participants who do not benefit from CFTR modulators. This study is supported by safety and tolerability data collected in healthy volunteers (N = 32) and the

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two-administration Phase 1b study in CF adults. The initial three dose cohorts are fully enrolled, with each participant in the Phase 2 CF study (NCT06747858) receiving daily treatments of ARCT-032 over a period of 28 days.

On October 21, 2025, we announced interim results from the ongoing Phase 2 clinical trial of ARCT-032 for CF. In the second cohort of the study, six Class I CF adults received inhaled 10 mg doses of ARCT-032 daily over 28 days. High-resolution computed tomography (HRCT) lung scans analyzed using FDA 510(k)-cleared AI technology, revealed reductions in mucus burden in four of six Class I CF participants. The treatment was generally safe and well tolerated. Bronchospasm was not reported in these participants, either with or without pretreatment with a bronchodilator. Treatment related AEs that were identified in the single-dose Phase 1 study were also observed in some participants for the first few doses but ceased with continued dosing. One SAE occurred in a participant after the end of the dosing period. The safety review committee found no convincing evidence that the SAE was related to ARCT-032 and approved the study to proceed. The third cohort is ongoing and has enrolled four subjects to determine if there is a different response at 15 mg daily over 28 days and if ARCT-032 continues to be generally safe and well tolerated. A fourth cohort is planned to begin enrollment of up to 20 adults with CF to explore safety, tolerability, and efficacy of ARCT-032 administered for 12 weeks.

In December 2025, we published our preclinical data of the ARCT-032 study. This study demonstrates that LUNAR lipid nanoparticles effectively deliver human CFTR mRNA to airway epithelia, restoring chloride channel function and mucociliary clearance in primary human cystic fibrosis cells and a ferret model of the disease.

Rare Disease Program – ARCT-810 (LUNAR-OTC)

The LUNAR-OTC development program addresses ornithine transcarbamylase (OTC) deficiency, a rare, life-threatening, genetic disease caused by mutations in the OTC gene that lead to dysfunctional or deficient OTC.

OTC deficiency is the most common of the urea cycle disorders, a group of inherited metabolic disorders that are associated with reduced ability to eliminate ammonia from the body. There are over 5,000 people with OTC deficiency in the United States, and the prevalence is approximately one in 14,000 to one in 77,000 people worldwide. Ammonia is a toxic waste product produced from the breakdown of protein. OTC is a critical enzyme in the urea cycle, which takes place in liver cells and converts ammonia to harmless urea which is eliminated by the kidneys. In patients with OTC deficiency, ammonia accumulates in the blood and is toxic to the brain and liver. Symptoms of high ammonia levels include vomiting, headaches, coma and death. OTC deficiency can cause developmental problems, seizures and death in newborn babies. As an X-linked disorder, OTC deficiency tends to be more severe in males, though female carriers are often affected. Patients with less severe symptoms may present later in life, as adults. Currently no cure exists for OTC deficiency apart from liver transplant; however, this treatment comes with significant risks and complications such as organ rejection, and transplant recipients must take immunosuppressant drugs for the rest of their lives. Current standard of care for OTC deficiency is a low-protein diet, dietary supplements, and nitrogen scavengers to try to prevent accumulation of ammonia. Life-threatening episodes of high ammonia levels can still occur, requiring treatment with dialysis or hemofiltration. These treatments do not address the underlying cause of disease, and there remains a high unmet need for an effective treatment.

Our LUNAR-OTC development candidate, ARCT-810, uses our LUNAR platform to deliver normal OTC mRNA into liver cells which then produce normal functioning OTC with possible disease-modifying effects. Our LUNAR-OTC approach has the potential to treat the underlying defect that causes the debilitating symptoms of OTC deficiency, rather than mitigating symptoms by sequestering ammonia. We have retained worldwide development and commercialization rights to ARCT-810.

LUNAR-OTC has received Orphan Drug Designation from the FDA and Orphan Medicinal Product Designation from the EMA for treatment of OTC deficiency. ARCT-810 was also granted Fast Track Designation in and Rare Pediatric Disease Designation (RPDD). Fast Track Designation is designated to facilitate development and expedite review of new therapeutics intended to treat serious or life-threatening conditions that demonstrate the potential to address important unmet medical needs. Rare Pediatric Disease Designation is designed to recognize rare pediatric diseases in which the serious or life-threatening manifestations primarily affect patients from birth to 18 years of age. Due to such designation, if ARCT-810 achieves approval for a pediatric indication in the original rare pediatric disease product application in the United States, Arcturus (or the sponsor of ARCT-810) is eligible to receive a voucher for priority review of a subsequent marketing application for a different product.

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Preclinical data in OTC-deficient murine models demonstrated that dosing of LUNAR-OTC results in robust OTC protein expression and activity, thereby improving ureagenesis, reducing plasma ammonia, and increasing survival.

A Phase 1 double-blind, placebo-controlled, dose-escalation study of ARCT-810 in healthy volunteers, completed in November 2020, and demonstrated favorable safety, tolerability and PK profiles.

A single ascending dose, placebo-controlled Phase 1b study in 16 stable mild OTC-deficient adults was completed in the United States in September 2023. The trial assessed safety, tolerability, and pharmacokinetics of a single dose of ARCT-810, and exploratory biomarkers of drug activity. ARCT-810 was generally safe and well tolerated at doses ranging from 0.1- 0.5mg/kg and no serious or severe adverse events were observed. Sporadic infusion-related reactions (IRRs) were managed with symptomatic treatment and appeared to be less frequent with slower infusion rates. In plasma, ARCT-810 mRNA could be detected for up to four weeks, while ionizable lipid was no longer measurable after 48 hours, indicating rapid degradation of the lipid nanoparticle that was utilized to deliver ARCT-810 mRNA. Study results were presented at the Society for Inherited Metabolic Disorders meeting in Charlotte, North Carolina in April 2024 and at the annual symposium for the Society for the Study of Inborn Errors of Metabolism in Porto, Portugal in August 2024.

A Phase 2 double-blind study of ARCT-810 in stable OTC-deficient adolescents and adults in the European Union and the United Kingdom completed dosing of eight subjects in August 2024 at the 0.3 mg/kg dose level. The participants in this group were randomized 3:1 to receive six doses of ARCT-810 or placebo administered every 14 days. Study results were presented at the 6th International Symposium on Urea Cycle Disorders, Kyoto, Japan and International Congress of Inborn Errors of Metabolism, Kyoto, Japan in September, 2025.

In the second quarter of 2024, we expanded the Phase 2 clinical program of ARCT-810 to the U.S. with an open-label, multiple-dose study to evaluate pharmacodynamics and safety in adult and adolescent patients requiring clinical management for OTC-deficiency. The first OTC deficient participant receiving 0.5 mg/kg ARCT-810 initiated dosing in December 2024 in the United States. Each participant is expected to receive five intravenous infusions administered over two months.

On June 30, 2025, we announced positive multiple dosing data of ARCT-810 from two Phase 2 studies: (i) a completed placebo-controlled study in Europe that randomized eight participants to ARCT-810 0.3 mg/kg or placebo; and (ii) an open-label multiple ascending dose study in the U.S., with interim data from the initial three completed participants. Both studies evaluate safety and pharmacodynamics in adult and adolescent patients requiring clinical management for OTC-deficiency. We continue to enroll participants in the U.S. study. Each participant in the U.S. study is expected to receive five intravenous infusions administered over two months.

A Linear Mixed-Effects Model (LMM) was applied as an exploratory analysis to the Phase 2 glutamine and ureagenesis data. LMM is suitable for analyses of small, rare disease trial datasets. In the Phase 2 randomized European study, glutamine levels in patients who received multiple doses of ARCT-810 significantly (p-value = 0.016; LMM) decreased during the dosing period. In the Phase 2 open-label U.S. study, interim analysis of the first three participants showed a sustained and significant (p-value = 0.004; LMM) decrease in glutamine from baseline, reaching normal levels after the first three doses. In the combined analysis of both Phase 2 studies, significantly (p-value = 0.0055; LMM) decreased glutamine levels were observed. The ongoing U.S. Phase 2 open-label study uses a modified and improved 15N-ureagenesis assay (Allegri et al., 2025). The assay measures relative ureagenesis function (RUF) against a normal range established from healthy controls. The assay is not impacted by ammonia scavengers, has low intraindividual variability, and can distinguish between symptomatic and asymptomatic OTC deficient patients. In the first three participants in the ongoing Phase 2 open-label study, RUF statistically (p-value = 0.026, LMM) increased at all post treatment evaluations from a baseline of 29.0% (SD; 9.1%) to 43.7% (SD; 21.7%) at 28 days post-fifth dose. These results suggest a progressive increase of functional OTC enzymes in the liver with continued administrations of ARCT-810. Two of the three participants achieved RUF 50% indicating a clinically meaningful improvement in urea cycle flux.

A type C meeting with the FDA to discuss our plans for a proposed future pediatric study under the RDEP (Rare Disease Evidence Principles) is scheduled for the first half of 2026.

Vaccine Programs

According to the National Foundation for Infectious Diseases, over 50,000 people die each year due to vaccine-preventable diseases and related complications in the United States alone (Centers for Medicare and

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Medicaid Services, 2018; Walter et al., 2016). Influenza and pneumonia cases approach this number of deaths each year and more than one million individuals in the United States have died of COVID since the beginning of the COVID-19 pandemic (Centers for Disease Control and Prevention). The Department of Health and Human Services estimated that 330,000 lives were saved in the United States due to COVID-19 vaccination in 2021 alone. Outbreaks of new infectious diseases, and the rise of variants to existing viruses, create demand for new and novel approaches to producing vaccines in a more cost-effective and quicker manner.

The COVID-19 pandemic highlighted the efficacy, safety, and rapidity in which nucleic acid medicines can be used to vaccinate vulnerable populations, and our vaccine program has continued to progress. In 2020, we initiated development of our first self-amplifying mRNA vaccine candidate to protect against COVID-19. In December 2022, we entered into a Collaboration and License Agreement (“CSL Collaboration Agreement”) with CSL Seqirus, a part of CSL Limited and one of the world’s leading influenza vaccine providers, for the global exclusive rights to research, develop, manufacture and commercialize self-amplifying mRNA vaccines against COVID-19, influenza and up to three other infectious diseases and global non-exclusive rights to pandemic pathogens. The CSL Collaboration Agreement combines CSL Seqirus’ established global vaccine commercial and manufacturing infrastructure with Arcturus’ manufacturing expertise and innovative STARR self-amplifying mRNA vaccine and LUNAR delivery platform technologies. For a more comprehensive discussion of the CSL Collaboration Agreement, please see Item 1 “Business” – “Revenue and Collaboration Arrangements and Other Material Agreements” – “CSL Seqirus.”

In November 2023, ARCT-154 (KOSTAIVE) became the world’s first approved self-amplifying RNA vaccine following Japan’s approval of ARCT-154 for primary immunization and as a booster dose against COVID-19. In September 2024, Japan’s Ministry of Health, Labor and Welfare (MHLW) granted approval and authorization for an updated version of KOSTAIVE, targeted to protect against the JN.1 lineage of Omicron subvariants for adults 18 years of age and older. CSL Seqirus’ exclusive partner in Japan, Meiji, began distributing the updated vaccine in Japan in October 2024, marking the world’s first commercially available sa-mRNA COVID-19 vaccine for adults 18 and older. The approval was based on manufacturing data demonstrating the quality and consistency of the vaccine product, non-clinical immunogenicity data against JN.1 lineage of Omicron subvariants of KOSTAIVE (JN.1), and clinical evidence supporting the safety and immunogenicity of KOSTAIVE (bivalent, BA.4/5 and ancestral strain).

In our influenza vaccine franchise, a Phase 1 clinical trial of our seasonal influenza candidate was conducted in 2024-2025 under our collaboration with CSL Seqirus, and a BARDA-funded Phase 1 clinical trial of our H5N1 pandemic flu candidate was initiated in December 2024 and is ongoing.

KOSTAIVE® and COVID-19 Vaccine Program

Coronaviruses are a family of viruses that can lead to respiratory illness. Three viruses in this family have emerged in the past twenty years: Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV), and Severe Acute Respiratory Syndrome 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic. Throughout the pandemic, there have been surges of infections as protective health measures have waxed and waned. Uncontrolled viral spread has led to billions of cases worldwide and the selection of viral variants that are more contagious, pathogenic, or both. Since late 2021, infections have been dominated by subvariants of the Omicron strain, which continue to displace previous circulating strains by evading immunity and spreading more efficiently, resulting in an increased risk of breakthrough infection among the vaccinated. Vaccines that induce robust and durable immunity against current and emerging variants of concern (“VOCs”) can help to reduce the infection and disease burden for both the public and the health care systems globally.

Our COVID-19 vaccine candidate, KOSTAIVE, is based on our STARR (self-amplifying mRNA) technology platform and our LUNAR platform. It was designed to elicit immune responses against the SARS-CoV-2 spike protein, the critical component that enables viral entry.

KOSTAIVE is the brand name approved in Japan and Europe for ARCT-154, the version of the sa-mRNA COVID-19 vaccine encoding the ancestral strain of SARS-CoV-2, as well as for updated variant-specific versions of this vaccine. We may use KOSTAIVE or internally generated names, such as ARCT-154, ARCT-2301, and ARCT-2303, to identify vaccines targeting specific SARS-CoV-2 variants.

The licensure of KOSTAIVE in Japan in 2023, followed by the approval of an updated version of KOSTAIVE (JN.1 Omicron subvariant) and initiation of commercial sales in Japan in 2024 are significant milestones in the advancement of our vaccine franchise. The approval of KOSTAIVE by the EMA in January 2025 and by the United

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Kingdom (the UK Medicines and Healthcare Products Regulatory Agency (MHRA)) in January 2026 provided further validation of our platform by other major regulatory authorities.

On September 5, 2025, the week prior to the planned Biologics License Application (“BLA”) submission related to KOSTAIVE, the U.S. Food and Drug Administration (the “FDA”) requested that the submission of the BLA filing be delayed due to the FDA’s expectation of providing additional advice. On October 14, 2025, the FDA informed us that, although the FDA had previously agreed that our proposed data package could support a single-dose indication, upon further consideration it found that additional data from a clinical endpoint efficacy study will be needed to align with the current COVID-19 vaccine regulatory framework requirements published in The New England Journal of Medicine in May 2025. On September 26, 2025, Meiji Holdings Co., Ltd. announced that its subsidiary, Meiji, launched a new composition of KOSTAIVE®, a self-amplifying mRNA vaccine against COVID-19. The product targets the SARS-CoV-2 Omicron sub lineage JN.1 variant XEC. In non-clinical studies, it induced neutralizing antibodies not only against Omicron JN.1 and XEC, but also against LP.8.1 and the currently circulating variants XFG and NB.1.8.1. The formulation is lyophilized and supplied as a two-dose vial, with one vial per carton.

In 2025, several important manuscripts related to our studies were published, which are summarized below.

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In April 2025, we published a comprehensive analysis of safety data for KOSTAIVE®, with a 12-month follow-up from the pivotal clinical study in Vietnam (NCT05012943), which had 17,582 participants who received at least one dose of the study vaccine. The study confirmed the favorable reactogenicity profile of the vaccine. Acceptable tolerability of KOSTAIVE (ARCT-154) was also observed in older participants and individuals who are at risk of severe consequences of COVID-19 due to underlying medical conditions. Long-term follow-up has not revealed any safety concerns, with no reports of myocarditis or pericarditis. No serious consequences occurred in several pregnancies reported after vaccination. Long-term data from this large trial suggest that KOSTAIVE is safe and well-tolerated.

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In April 2025, our Japanese partner, Meiji, published an analysis characterizing the distribution and clearance of KOSTAIVE (ARCT-154) encoded spike protein and non-structural proteins nsP1, nsP2, nsP3 and nsP4 in the lymph nodes and injection-site muscle in mice following a single vaccination. The study showed the encoded spike protein reached its highest level approximately three days after vaccination and quickly disappeared from the injection site muscle. The spike protein levels also peaked at an early time point in the lymph nodes, it remained detectable 28 days after the vaccination and disappeared by 44 days after the vaccination. Expression of nsP1, nsP2 and nsP4 was observed in the injected muscle and/or the lymph nodes for up to 15 days post-vaccination. The data indicates that the extended expression of spike proteins in lymph nodes may be responsible for the induction of higher and prolonged levels of neutralizing antibodies. The study also confirmed that the self-replication is limited over time.

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In July 2025, we published the manuscript ‘Immunogenicity of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, in different booster settings where we summarized extensive clinical data and concluded that KOSTAIVE (ARCT-154), administered as a homologous or heterologous booster after previous COVID-19 vaccination or natural exposure, provides robust, broad and durable immune responses against SARS-CoV-2 viruses.

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In July 2025, a researcher from Tokyo University, Japan, published the manuscript ‘A second-generation, self-amplifying COVID-19 Vaccine: World’s first approval and distribution in the Japanese market with vaccine hesitancy. The manuscript positions KOSTAIVE as a second-generation mRNA vaccine, differentiating it based on effective dose, durability, and breadth of immune response, and summarizes experience from the first year of routine use of the vaccine in Japan.

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In August 2025, the manuscript ‘Immunogenicity and Safety of Self-Amplifying mRNA COVID-19 Vaccine (ARCT-2303), With or Without Co-Administration of Seasonal Inactivated Influenza Vaccine in Adults: a Phase 3, Randomised, Controlled, Observer-blind, Multicentre Study’ was accepted by eClinicalMedicine. The manuscript presents the results of a recent pivotal Phase 3 clinical study and concludes that KOSTAIVE (ARCT-2303; XBB.1.5 strain) induces a robust immune response against the SARS-CoV-2 vaccine variant and can be co-administered with licensed influenza vaccines in adults, without affecting the safety or immunogenicity of either vaccine.

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In December 2025, in collaboration with the McNamara Lab at Harvard, we presented the manuscript ‘Sustained Humoral Activation through self-amplifying mRNA Vaccination Enhances Longitudinal Antibody Function in a Phase III Trial. The authors applied a system serology approach to analyze post-vaccination serum samples from participants who received KOSTAIVE (ARCT-154) and a conventional mRNA vaccine (BNT162B2, Comirnaty). The study demonstrated that ARCT-154 elicited a unique antibody response defined by a sustained, activating profile to the vaccine-encoded Spike protein and a broad spectrum of drifted Spikes. Notably, activating FcγRIIIA-binding antibodies showed sustained stimulation in the ARCT-154-treatment arm, which translated into enhanced natural killer (NK) cell activation.

Commercialization of KOSTAIVE in Japan

Meiji has launched in Japan the two-dose vial of KOSTAIVE updated for the JN.1 variant XEC, following receipt of approval, in August 2025, from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). KOSTAIVE first received marketing authorization approval in Japan in 2023 for use as a primary immunization and booster in Japan for adults 18 years and older. The updated versions were approved and commercialized in the 2024-2025 and 2025-2026 seasons.

In January 2025, CSL Seqirus’ partner Meiji received approval for a partial amendment to the manufacturing and marketing approval of KOSTAIVE to include manufacturing sites in Japan. With this approval, Meiji and ARCALIS, Inc., Arcturus’ manufacturing joint venture in Japan, have been added as manufacturing sites. As a result, KOSTAIVE, with active pharmaceutical ingredients manufactured at such sites, may be shipped for commercial use in Japan.

Approval of KOSTAIVE (ARCT-154) in Europe

In February 2025, the European Commission granted marketing authorization for KOSTAIVE (ARCT-154) for individuals 18 years of age and older. The European Commission approval follows a positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) of the EMA on December 12, 2024. The centralized marketing authorization of KOSTAIVE provided by the EC is valid in all 27 European Union (EU) member states and 3 additional European Economic Area (EEA) countries summarized here: Austria, Belgium, Bulgaria, Croatia, Republic of Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, The Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain and Sweden.

KOSTAIVE BLA Submission

On September 5, 2025, the week prior to the planned Biologics License Application (“BLA”) submission related to KOSTAIVE, the FDA requested that the submission of the BLA filing be delayed due to the FDA’s expectation of providing additional advice. On October 14, 2025, the FDA informed us that, although the FDA had previously agreed that our proposed data package could support a single-dose indication, upon further consideration it finds that additional data from a clinical endpoint efficacy study will be needed to align with the current COVID-19 vaccine regulatory framework requirements published in The New England Journal of Medicine in May 2025. The FDA's sudden changes to regulatory requirements for COVID-19 vaccines have indefinitely delayed the U.S. BLA filing for KOSTAIVE.

Approval of KOSTAIVE (ARCT-154) in United Kingdom

In January 2026, the UK Medicines and Healthcare products Regulatory Agency (MHRA) under the International Recognition Procedure (IRP) granted marketing authorization for KOSTAIVE for individuals 18 years and older.

Clinical Studies of KOSTAIVE (COVID-19 vaccine)

In connection with the development of KOSTAIVE, we have conducted seven clinical studies, including four pivotal studies described below.

Pivotal Phase 1/2/3 Efficacy, Safety, and Immunogenicity Study of KOSTAIVE (ARCT-154) in Vietnam (NCT05012943)

This randomized, observer-blinded, placebo-controlled, and active-controlled study enrolled more than 19,000 adult individuals across multiple sites in Vietnam and demonstrated that a 2-dose vaccination series with

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ARCT-154 induced protection in the seronegative population against heterologous SARS-CoV-2 variants (mainly Delta) with vaccine efficacy of 56.6% (48.7–63.3) for COVID-19 of any severity and 95.3% (80.5–98.9) for severe COVID-19. The vaccine was immunogenic against the ancestral SARS-CoV-2 strain and induced a cross-neutralizing immune response against new emergent variants. The vaccine was well tolerated, and safety analysis did not identify specific safety concerns. The study results served as the basis for vaccine licensure in Japan, the European Union, and the UK.

The results were broadly published and presented in multiple international forums.

The study was conducted in collaboration with Vinbiocare Biotechnology Joint Stock Company (“Vinbiocare”), a member of the Vingroup Joint Stock Company (Vingroup) group, and was sponsored by Vinbiocare.

Pivotal Phase 3 Non-Inferiority Study of KOSTAIVE (ARCT-154) in Japan (jRCT 2071220080).

This Meiji-sponsored, randomized, multicenter, observer-blind, active-controlled study evaluating the safety and immunogenicity of a booster dose of ARCT-154 and assessing its non-inferiority to COMIRNATY® (Monovalent, Original strain). The study demonstrated immunological non-inferiority of KOSTAIVE versus COMIRNATY for the ancestral SARS-CoV-2 strain and immunological superiority for the epidemiologically dominant Omicron BA.4/5 variant. KOSTAIVE also demonstrated a more durable humoral immune response up to 12 months post-booster dose. Overall, the study results support the favorable benefit/risk profile of the ARCT-154 vaccine when administered as a booster dose in adults who previously received other mRNA COVID-19 vaccines.

The study results were publicly disclosed in April 2024.

Pivotal Phase 3 Study of Bivalent Version of KOSTAIVE (ARCT-2301) in Japan (jRCT2031230340)

This Meiji-sponsored study of a bivalent version of KOSTAIVE (ancestral strain and Omicron BA.4/5) to further support immunogenicity and safety data for the self-amplifying mRNA platform and facilitate the timely release of future seasonal updates of our COVID-19 vaccine against evolving variants of concern. As with the monovalent vaccine, the bivalent sa-mRNA formulation demonstrated superior immunogenicity compared with the conventional bivalent mRNA vaccine COMIRNATY, with a higher immune response persisting up to six months after a booster dose, and broader variant coverage, supporting the robustness of the sa-mRNA vaccine platform for future vaccine strain updates.

The study results were published in March 2025.

Pivotal Phase 3 Co-administration Study of KOSTAIVE (ARCT-2303) and Seasonal Influenza Vaccines (NCT06279871).

This CSL- and Arcturus-funded randomized, observer-blind, placebo-controlled, phase 3 study aimed to generate additional immunogenicity and safety data in multiple ethnicities to support regulatory filings in the U.S. and globally. The study also assessed the co-administration of the ARCT-2303 vaccine with the age-appropriate seasonal influenza vaccines. The study results demonstrated robust immunogenicity of the XBB1.5-containing vaccine and support the concomitant administration of KOSTAIVE with licensed non-adjuvanted and adjuvanted influenza vaccines in both young and older adults. The safety and reactogenicity of co-administered vaccines were comparable to those of standalone administration. No safety concerns were raised based on the study results.

COVID-19 Vaccine Product Format

The product format of KOSTAIVE that began commercialization in Japan in October 2024 is a lyophilized product presentation. The stability and cold chain characteristics of KOSTAIVE in a lyophilized format compares favorably to frozen liquid format, and our ongoing development of proprietary manufacturing technology has led to significant increases in refrigerated and ambient temperature shelf-lives for both lyophilized and liquid drug products.

Seasonal Flu Collaboration Program

LUNAR-FLU (Seasonal Influenza)

Influenza is estimated to cause one billion infections globally every year and hundreds of thousands of deaths, especially in the elderly and individuals with underlying medical conditions. In many regions, influenza is seasonal, with infections peaking during November through April in the Northern Hemisphere and May through September in

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the Southern Hemisphere. Year-round surveillance by the World Health Organization (“WHO”) in collaboration with various national health agencies informs WHO recommendations on the strains of influenza most likely to spread during the upcoming influenza season. National health agencies (such as the FDA) then make the final decision of which strains should be covered by vaccines licensed in their country.

Our LUNAR-FLU (seasonal) program, partnered with CSL Seqirus, has the objective of producing a safe and effective seasonal influenza vaccine candidate with significant advantages over the traditional egg-based inactivated quadrivalent vaccine. Inaccurate predictions of circulating influenza strains as well as mutations due to adaptation in egg-grown vaccines can substantially reduce efficacy on a year-to-year basis. We believe the ability of mRNA platforms to nimbly adapt to new viral strains should help improve efficacy. In addition, we do not expect mRNA vaccines to face the challenge from mutations common to egg-grown vaccines.

LUNAR-FLU has been designed to leverage our expertise in both our LUNAR lipid delivery platform and STARR self-amplifying mRNA technology. These technologies have been shown to deliver effective protection against COVID-19 and has been optimized to elicit robust immunogenicity with acceptable reactogenicity at a lower dose than conventional mRNA vaccines, with the objective of creating a highly effective influenza vaccine for use in general and high-risk populations. We conducted a Phase 1 study of ARCT-2138, a sa-mRNA seasonal influenza vaccine candidate encoding haemagglutinin (HA) and neuraminidase (NA) of four seasonal influenza strains as recommended by the World Health Organization (WHO). Overall, the study showed the potential of a self-amplifying mRNA vaccine, encoding eight antigens, to induce an immune response in both young and older adults with a dose as low as 2 μg, and was tolerable across a dose range of 2 to 20 μg.

Pandemic Avian Influenza Program (H5N1 Influenza)

Our LUNAR-H5N1 program continues to progress under the award from BARDA that we obtained in 2022 to advance through Phase 1 a vaccine to protect against disease caused by H5N1 highly-pathogenic avian influenza. H5N1 influenza is a significant concern in animal health. To date, H5N1 flu has affected over 10,000 wild birds, nearly a thousand dairy cows, and over 130 million poultry. Elevated H5N1 infections in animals have led to increasing numbers of human infections including two confirmed severe cases in the United States and one death. Most of the confirmed human infections are due to exposure of U.S. dairy and poultry workers to infected dairy cows and poultry. We are working diligently with our partners, BARDA and CSL Seqirus, to clinically validate our low-dose STARR mRNA technology for H5N1 to assist towards pandemic preparedness.

In April 2025, the FDA granted Fast Track Designation for ARCT-2304. 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. Fast Track Designation from the FDA is granted to vaccines intended to prevent serious conditions caused by infectious diseases. The designation is designed to expedite the development and review process, providing several benefits, including enhanced communication with the FDA, eligibility for priority review, and the possibility of a rolling review.

Our Phase 1 study of ARCT-2304, an sa-mRNA pandemic influenza A/H5N1 vaccine candidate, released interim results in September 2025. The study objectives were to evaluate the safety and tolerability of the vaccine and to characterize the immune response across three dose levels in 132 young adults (18-59 years of age) and 80 older adults (60-80 years of age). ARCT-2304 induced a humoral immune response after a single dose (as measured by microneutralization and enzyme-linked lectin anti-neuraminidase assays) in all tested dose levels. Administering a second dose of ARCT-2304 further increases immune responses. The magnitude of the anti-HA response was higher after an 8-week interval than after a 4-week interval in both young and older adults. ARCT-2304 in dose levels 5 and 12 µg (2 doses administered 4 or 8 weeks apart) and 1.5 µg (2 doses administered 8 weeks apart) induces a hemagglutinin-specific immune response similar to or higher than that after the MF59-adjuvanted pandemic vaccine (in both young and older adults). Immunogenicity monitoring up to eight months after the first vaccination confirmed high antibody persistence and substantial durability of vaccine-induced immunity. No safety or tolerability concerns were raised from available data.

Platform Technologies and R&D Programs

We have four key proprietary platform technologies:

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lipid-mediated delivery (LUNAR®)

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mRNA and protein design

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•
self-amplifying mRNA (STARR®)

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manufacturing and formulation for mRNA medicines

LUNAR (Lipid-Mediated Delivery) Platform

Our LUNAR lipid-mediated delivery technology includes a diverse, growing library of over 300 proprietary lipids that we are rationally designing to be versatile, while maximizing efficacy and improving tolerability of a diverse selection of nucleic acids, refining the LNPs to target specific cell types, and determining the most favorable routes of administration. A key feature of our LUNAR lipids is their biodegradability, decreasing the undesired effects caused by lipid accumulation that are associated with tolerability issues present in other lipid-mediated RNA medicine delivery platforms. Our team continues to advance our LUNAR lipid formulated nucleic acid platform in a scalable and highly reproducible manner, reducing the costs of goods for the therapies in our pipeline.

In addition to our LUNAR lipid-mediated delivery technology, we believe we have created innovative, proprietary advancements in producing mRNA medicines, including improvements that increase purity, scalability, efficiency in production times, and adaptability to different mRNA modification strategies. We strive to use these proprietary innovations to benefit each mRNA medicine in our pipeline.

We continue to invest in and improve our LUNAR lipid-mediated delivery of mRNA with continuous improvements in our mRNA and sa-mRNA platforms in conjunction with improvements in our next generation proprietary lipids to improve targeting, efficacy and safety profiles for both our vaccine and therapeutic protein platforms. This investment has led to key innovations ensuring that our LUNAR formulated drug product candidates have optimal characteristics for therapeutic use, which we believe sets us apart from other nucleic acid therapeutics and lipid-mediated delivery platforms. As such, we consider ourselves a leader in the research and development of mRNA therapeutics for multiple indications.

We continue to conduct exploratory platform development activities, including the evaluation of genome editing, and new targeting approaches, where our LUNAR and STARR platforms could potentially be useful for identification and development of additional products for our portfolio.

Key Attributes of Our LUNAR Lipid-Mediated Delivery Technology

We have designed our LUNAR lipid-mediated delivery platform to address major challenges with nucleic acid medicine delivery, including transfection efficiency, adverse immune reactions and liver damage.

LUNAR is a multi-component, lipid-mediated drug delivery system that utilizes our proprietary lipids, called ATX lipids. Each of our ATX lipids contains an ionizable head group and a biodegradable lipid backbone. The head group is a key chemical component of the ATX lipid, making it pH-sensitive and providing it distinct advantages as a component of our LUNAR lipid formulation. At acidic pH, ATX lipids are positively charged, facilitating interaction with the negatively charged nucleic acid, thereby enabling LUNAR particle formation. At physiological pH (e.g., pH 7.4), the ATX lipids within the LUNAR formulations are neutrally charged, reducing the toxicity often seen with permanently positively charged lipid-mediated delivery technology. Upon uptake into a cell by endocytosis (a process that forms a cellular structure called an endosome around the LUNAR formulated nucleic acid therapeutic), the head group again becomes positively charged due to the low pH of the endosome, disrupting the endosome and the LUNAR particle, resulting in release of the nucleic acid therapeutic into the cell where it is translated to produce a therapeutic protein.

The disruption of the LUNAR particle also releases the components of the formulation into the cell, where the ATX lipid is degraded by enzymes called esterases in the cell allowing for the lipids to be cleared from the cell. We designed the ATX lipid to be rapidly biodegradable by engineering chemical structural components, called esters, into the ATX backbone that are sensitive to esterases. This degradation prevents ATX lipids from accumulating inside the cell and causing toxicity.

Biodegradable, highly optimized for each cell type

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LUNAR-platform development

The development of our LUNAR platform is focused on continuous innovation and advancement in the following areas:

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Design, manufacture and incorporate novel ATX lipids into formulations to enrich our library of proprietary ATX lipids for target cell/tissue specificity, improved tolerability and translatability to larger species;

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Develop, optimize and innovate manufacturing processes for LUNAR formulations to ensure RNA encapsulation across compositions and scales;

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Develop stabilization strategies (e.g. lyophilized presentation) for LUNAR formulations to mitigate the need for frozen storage and to extend shelf-life; and

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Continually optimize and innovate LUNAR screening paradigm to enable rigorous selection of ATX lipids for various therapeutic programs and routes of administration.

Through the above efforts, our versatile LUNAR platform continues to drive internal and partner programs.

ATX Lipid Design and In Vivo Screening Process

As mentioned above, we have generated a growing library of more than 300 proprietary ATX lipids. ATX lipids are rationally designed to fit different applications and vary depending on the target cell type and route of administration. We perform extensive formulation screening for each nucleic acid therapeutic candidate to determine the optimal ATX lipid to be used and the appropriate excipient composition (LUNAR composition) for the nucleic acid therapeutic candidate, the desired route of administration, and target cell type.

The design of ATX lipids is an iterative process based on in vivo protein expression and tolerability results from previous ATX lipid candidates. To date, we have developed seven generations of ATX lipids. New ATX lipids are chemically synthesized and used to package mRNAs expressing a secreted protein. The ATX lipid formulated RNAs must meet specific chemical and biophysical acceptance criteria before being tested for biological activity. RNA formulations meeting all acceptance criteria are first screened for protein expression in mice. Active candidates are further verified by evaluating protein expression in non-human primates. Active candidates are then tested for tolerability and preliminary tissue clearance rates following administration. Active ATX lipid candidates demonstrating high levels of protein expression and equivalent or improved tissue clearance rates are then assigned to a specific disease target for development of therapeutic applications. The following results are from an in vivo mRNA expression study which identified three new highly active LUNAR lipids with regard to protein expression in non-human primates compared to the positive control.

Expression of Human EPO in Mice 6 hours After IV Administration (Figure 1)

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Mouse Liver Clearance of LUNAR Lipids 48 hours After IV Administration (Figure 2)

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Expression of Human EPO in Non-Human Primates 6 Hours After IV Administration (Figure 3)

Figure 1: mice were injected intravenously with 4 different ATX lipid formulations containing mRNA expressing human erythropoietin (hEPO). The ATX lipids that were screened were C9G, C9H, C9I and B2G at 0.1 mg/kg and 0.3 mg/kg RNA doses. ATX lipid B2G formulation is a positive control to which expressions from the other formulations are compared. Mice were bled 6 hours after injection and assayed for hEPO, a secreted protein.

Figure 2: shows the clearance of the ATX lipids from the mouse liver 48 hours after administration of 0.1mg/kg and 0.3 mg/kg RNA doses. C9G, C9H and C9I yielded much higher expression levels of hEPO than B2G, the positive control for both doses tested. It also shows that the residual amount of C9G and C9I were below the limit of detection and the residual amount of C9H was at least 10-fold less than the remaining amount of B2G at the 0.1 mg/kg RNA dose and at least two-fold less than the residual amount of B2G at the higher RNA dose.

Figure 3: C9G and C9I formulations were tested for EPO expression in non-human primates at a single dose and assayed for secreted hEPO in the blood six hours after IV administration. Both C9G and C9I yielded significantly higher expression levels than the positive control, B2G further confirming the superior performance of the new LUNAR formulations. Hence, this lipid screen identified three LUNAR lipids that yielded greater RNA expression in mice and two LUNAR lipids in NHPs and were rapidly cleared from the liver within 48 hours after administration. This demonstrated the ability to design and execute LUNAR formulations using our advanced generation lipids with many-fold higher protein expression and ready biodegradability.

Lung Targeting

Aerosol capabilities have been developed for the CF program using our proprietary lipid nanoparticle delivery platform, LUNAR. Characterization and optimization of the aerosolized LUNAR formulations in targeting airway epithelium have been achieved in rodent (mice, rat) and nonrodent models (ferret, NHP) as depicted in the image using a reporter mRNA encapsulated in LUNAR. We expect that the validation attained for the inhaled LUNAR platform in the CF program will serve as a translatable approach to support other respiratory approaches where targeting airway epithelium is needed.

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LUNAR delivery to airway epithelium demonstrated in vivo across species (rodents, ferrets, NHPs).

LUNAR Safety and Tolerability (i.v. administration)

As part of the screening method for our proprietary lipids, we conduct an initial lipid tolerability screen in Balb/C and C57Bl/6 mice strains to ascertain the initial maximum tolerated dose in rodent species(s). LUNAR formulations encapsulating hEPO mRNA with different ATX lipids are intravenously administered to these mouse strains at three and five mg/kg doses and monitored for clinical signs. Blood was drawn at six and 48 hours after LUNAR administration and assayed for both liver functions and cytokine elevations. Liver function changes are determined by measuring for any increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes in the blood. A significant increase in these enzymes (i.e., above five times the normal range) indicates a negative effect on liver function. The results show that many of the LUNAR formulations that were tested are tolerable up to three mg/kg in both strains of mice for LUNAR formulations containing DSPC. Moreover, there is an even greater improvement in tolerability of up to five mg/kg when the helper lipid is PCA57. Thus, with these innovations we believe that we have substantially improved both the potency and tolerability of our LUNAR platform.

Our Proprietary mRNA and Protein Design Technology

The mRNA programs in our pipeline benefit from our in-house expertise in protein and mRNA design, which helps us address many of the known challenges that face the viability of mRNA therapeutics today. We have identified several design elements of mRNA compounds that provide improved translation (the process of making protein based on the instructions/codes in the mRNA) of our mRNA therapeutics, including untranslated regions derived from species that have not previously been combined with human mRNA sequences. This platform technology is applicable to many different human mRNA sequences that we are currently investigating in our discovery efforts. We are able to engineer human protein sequences to increase the half-life of the proteins produced by our mRNA therapies and can more efficiently direct specific types of proteins to certain cellular structures of interest. These innovations are broadly applicable to several programs that are part of our mRNA discovery efforts.

In addition to these platform technologies, we have developed a proprietary tool to aid our team in the efficient design and development of new mRNA drug candidates. Our mRNA Design Suite is a cloud-based software suite with a collection of proprietary bioinformatic algorithms aimed at achieving highly improved potency of a drug substance through optimization of mRNA sequences. The algorithms were developed in house through the integration of experimentally validated optimization processes. Through multi-layered in silico quality control pipelines, mRNA Design Suite promptly generates high-quality and error-free sequences accompanied by various statistics. Additionally, mRNA Design Suite seamlessly interacts with our plasmid/mRNA production database to accelerate the process from mRNA design to gene synthesis, cloning, and mRNA production.

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Our STARR mRNA Technology

Our distinct and proprietary self-amplifying mRNA (sa-mRNA) platform technology (STARR) incorporates proprietary design algorithms that optimize sa-mRNA to enhance expression of the applicable antigen while minimizing structures that could inhibit expression. The replicase, an RNA-dependent RNA polymerase, is encoded upstream of the antigen of interest and functions to increase the duration of antigen/transgene expression compared to conventional mRNA (Figure 6). When combined with LUNAR delivery, STARR has demonstrated reduced dose requirements and more durable, superior immune responses compared with conventional mRNA vaccines in preclinical studies and clinical trials.

Figure 6: The luciferase expression from an optimized sa-mRNA, STARR Technology (Green), a non-optimized sa-mRNA (Blue) and the conventional RNA (Purple). The STARR Technology was shown to yield at least a 30-fold greater expression level than conventional RNA. The STARR Technology also demonstrated a longer duration of expression compared to the conventional RNA and also the non-optimized self-amplifying RNA.

Our Proprietary Manufacturing Technology

We continue to innovate and improve our capabilities to manufacture nucleic acid medicines with high standards of quality, efficiency, and in compliance with Good Manufacturing Practices and its analogous regulations outside the U.S. Our technologies work to improve every aspect of the drug product manufacturing process from design to filling and packaging. Nucleic acid manufacturing relies on the confluence of complex technologies in the chemical and biological sciences that require extreme precision in their execution. Consequently, the nucleic acid medicines industry has faced many challenges across all steps of the manufacturing process, most notably the ability to scale processes to produce batches of adequate size while continuing to meet product specifications. Notable capabilities include:

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mRNA Drug Substance Manufacturing – We have developed the ability to manufacture mRNA drug substance with high product yield and exceptional product purity. In addition, we have developed reliable and efficient testing methodologies for characterizing mRNA drug substance. We continue to innovate in this area to further improve the cost, yield, purity and stability of mRNA drug substance.

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Drug Product Formulation – The formulation of mRNA drug substance with our LUNAR delivery platform is essential to achieving effective in vivo delivery and translation of the mRNA. We have developed advanced processes and know-how that enable us to manufacture lipid-encapsulated compounds at large volumes to help ensure that lipid-encapsulated compounds that meet key product specifications, including purity, particle size, concentration, stability, and percent encapsulation, in both liquid and lyophilized product formats. The continued advancement of these capabilities is an important focus of our platform development.

In our efforts to improve these and other capabilities, we use qualified scale down models to optimize operating conditions for each manufacturing step for both drug substance and drug product. Optimized conditions identified by these small-scale models are applied to the cGMP manufacturing processes. This manufacturing development process is also utilized for evaluating potential additives that improve drug substance and drug product quality and efficacy, improve manufacturing efficiency and reduce manufacturing costs. Some of the major accomplishments that have been achieved using this manufacturing development process are increased drug

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substance yield, reduction in drug substance impurities, increased manufacturing efficiency, and extended refrigerated and ambient temperature shelf life.

Discovery Programs

The versatile nature of our platform technologies may allow for a broad spectrum of nucleic acid medicines. We have conducted, and will continue to conduct, efforts to explore potential new drugs through our discovery and enabling technologies programs, though we are prioritizing our later stage programs.

Discovery Programs – HPV

Arcturus is advancing the development of a post-exposure HPV therapeutic vaccine candidate. Although prophylactic HPV vaccinations have substantially lowered the incidence of cervical cancer in developed countries, cervical cancer is still the fourth leading cause of cancer in women globally with the vast majority (approximately 90%) of cases in countries that have not yet widely adopted prophylactic HPV vaccinations and other cervical cancer prevention strategies, including screening and treatment. Cervical cancer typically develops years after initial HPV exposure due to a failure to clear the virus and the integration of viral oncogenes. A therapeutic vaccine which induces T-cell responses targeting the integrated HPV genes in precancerous cells could help prevent precancer and cancer in those already exposed to HPV. The Gates Foundation awarded Arcturus a grant of $3.9 million in November 2024 to support the development of such a therapeutic HPV vaccine through the clinical candidate nomination stage.

Enabling Technologies

Enabling Technologies – Cancer vaccines

Our LUNAR Cancer vaccine discovery efforts are aimed at developing an immunotherapy against a tumor via activated T-cells. We contemplate that the vaccine would encode an antigen(s) that would be specifically presented by (or associated with) a tumor, such that the vaccination would elicit T cell responses that recognize and attack the tumor. We have applied our learnings from our more-advanced LUNAR-COVID-19 vaccine program to establish both STARR (self-amplifying) and conventional mRNA platforms for immuno-oncology therapy.

In a preclinical study, our proof of concept (POC) vaccine encoding AH1 antigen of gp70 protein which is highly expressed on the surface of mouse colorectal carcinoma cell line CT26 has demonstrated clear effectiveness in a syngeneic mouse model of a colorectal CT26 cell line. With intramuscular administration of the STARR vaccine (two doses of 10 ug), treated with a checkpoint inhibitor (CPI), anti-PD1/PDL1 antibody, led to a substantial reduction of tumor growth in comparison to the CPI treatment by itself (Panel A). Moreover, the same level of efficacy was achieved with a single administration of a 0.2 ug dose of the STARR vaccine.

With various LUNAR formulations, conventional mRNA vaccine expressing the AH1 antigen also demonstrated a robust T cell response (Panel B) and reduction of tumor growth with anti-PD1/PDL1 treatment in the syngeneic mouse model. We believe that these POC results from the two platforms might lead to applicability to various types of cancer with flexibility in dosing regimens.

Our efforts to date have focused on the selection of neoantigens, and other common tumor-specific antigens encoded in the cancer vaccines. Common tumor antigens can be shared among patients, and therefore target broader patient populations, whereas a neoantigen vaccine would be a personalized vaccine specific for an individual patient. Additional advancements of the LUNAR Cancer Vaccine program include the improvement of antigen cassette designs, STARR RNA elements, and immune modulator molecules, all of which can significantly enhance T cell responses.

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Figure 7: Antitumor activity and T cell response by Arcturus cancer vaccines. A. STARR vaccine expressing a tumor antigen led to a significant reduction of the tumor growth rate of a colorectal cancer cell line, CT26. B. T cell responses elicited by conventional mRNA cancer vaccine by various LUNAR formulations.

Along with these platform improvements, we sought to understand how T cell responses induced by conventional mRNA, which have shown great promise in recent personalized cancer vaccine trials, differ from T cell responses induced by our STARR platform, especially after multiple vaccinations. We compared T cell responses in mice vaccinated with either sa-mRNA (STARR) encoding 13 epitopes known to generate responses in C57BL/6 mice to those in mice vaccinated with a conventional (N1-psuedouridine modified) mRNA encoding those same epitopes. All vaccines were formulated with our LUNAR lipids. Each mouse received a series of five vaccinations with an interval of two weeks between vaccinations (Figure 8A). We found that even after five vaccinations, mice vaccinated with sa-mRNA showed more than twice the CD8+ T cell response compared to mice vaccinated with conventional mRNA vaccine (Figure 8B).

Because sa-mRNA technology allows for extended duration of antigen expression, the possibility of T cell exhaustion after multiple vaccinations was a concern. We assessed the levels of CD8+ T cells expression PD-1 or Lag-3, well characterized exhaustion markers, and found significantly lower levels of exhaustion markers in mice vaccinated with sa-mRNA compared to conventional mRNA (Figure 8C). We hypothesize that the additional innate immune stimulation from the replicase intermediates may be responsible for the reduction in exhaustion makers. CD8+ memory subsets were also analyzed. While we expected to see increases in CD8+ T cell memory subsets overall, we observed that we saw an increase in the important T cell effector (Tem) subsets at the expense of T central memory (Tcm) in sa-mRNA vaccinated mice after 5 vaccinations (Figure 8D). The generation of Tem cells is an important prognostic indicator of vaccine efficacy in cancer vaccination. Lastly, we wanted to verify that T cells induced by multiple vaccinations with sa-mRNA were functional, so we assessed the levels of granzyme B, an important cytotoxic effector molecule, in CD8 T cells before and after stimulation. Prior to stimulation sa-mRNA vaccinated mice had significantly higher granzyme B compared to conventional mRNA vaccinated mice. After peptide stimulation, T cells from sa-mRNA vaccinated mice showed increased degranulation (as indicated by levels of CD107a, a degranulation marker) compared to T cells from conventional mRNA vaccinated mice (Figure 8E). Altogether, our data indicate that our STARR platform not only delivers a higher magnitude of epitope-specific responses compared to conventional mRNA, but that the T cell response induced by the STARR platform is better suited for clinical efficacy even after multiple vaccinations by inducing highly functional and cytotoxic T cells with the relevant memory markers (Tem).

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Figure 8: CD8 T cell responses after multiple vaccinations with sa-mRNA (STARR) vaccines and conventional mRNA vaccines formulated with LUNAR lipids. (A) Design of sa-mRNA vaccine encoding 13 H-2b restricted T cell epitopes (top). The conventional mRNA vaccine used the same epitope cassette. C57Bl/6 mice were vaccinated 5 times (two-week interval between vaccinations) and spleens were collected two weeks after the last vaccination (bottom). (B) Epitope specific responses to encoded epitopes were higher in sa-mRNA vaccinated mice compared to conventional mRNA vaccinated mice after 5 vaccinations. (C) The T cell exhaustion markers PD-1 and Lag-3 were assessed and lower levels of PD-1 and PD-1/Lag3 were observed on CD8+ T cells from sa-mRNA vaccinated mice. (D) Naïve (CD62L+CD44-), T central memory (Tcm; CD62L+CD44+), and T effector memory (Tem; CD62L-CD44+) were assessed in all mouse groups. sa-mRNA vaccinated mice showed the highest levels of Tem cells, an important prognostic indicator of vaccine efficacy. (E) CD8+ T cells were also assessed for granzyme B levels and surface levels of the degranulation marker, CD107A, before (top) and after (bottom) simulation with the encoded peptides. Prior to stimulation, sa-mRNA vaccinated mice had the highest levels of granzyme B. When stimulated, these cells lost granzyme B expression through degranulation, as indicated by the higher levels of CD107a, indicating functional degranulation of cytotoxic mediators was higher in sa-mRNA vaccinated mice compared to conventional mRNA vaccinated mice.

Enabling Technologies – Immuno-oncology

Cell-based therapies for hematologic malignancies using chimeric antigen receptor (CAR) T cells have made significant advances in the past decade. The success of CAR-T cells in immuno-oncology has led to a growing number of therapies utilizing other immune cell types engineered to express a variety of immunomodulatory molecules. Yet, despite their promise, extensive challenges still exist with this therapeutic approach. Some of the issues include toxicity, potential for insertional mutagenesis of the CAR construct, T cell malignancies, and an ex vivo manufacturing process that is complex, time consuming and costly. We believe that our LUNAR-I/O approach has the potential to ameliorate some of these issues. For example:

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1.
RNA-driven CAR expression in lymphocytes or immune cell types would be transient and therefore expected to have a lower side effect profile;

2.
There is no integration into the germline DNA allowing for co-delivery of multiple therapeutic molecules without the risk of insertional mutagenesis; and

3.
Generation of CAR-expressing cells by a process that is quicker and cheaper, particularly when targeting specific immune cell subtypes in vivo.

Our efforts to date have focused on targeting T lymphocytes in vivo with either CAR-mRNA or CAR-STARR (self-amplifying RNA) constructs in combination with other immunostimulatory molecules.

Supply and Manufacturing

Our supply and manufacturing strategies are focused on supporting the following:

1.
multiple pre-clinical and clinical pipeline candidates;

2.
late-stage clinical and commercial scale COVID vaccine products; and

3.
regional and global product demand.

We have built a global manufacturing footprint with our partners, including Aldevron, Catalent, Recipharm, Polymun and ARCALIS. With such collaborations, we have established an Integrated Global Supply Chain Network with our primary and secondary sourcing contract development & manufacturing organizations (CDMOs) based in the United States, EU and Asia for producing critical raw materials, drug substance, and packaged finished product.

We have manufactured and supplied gram quantities of drug substance, and have scaled-up and validated our finished drug products (COVID Vaccine) through our CDMOs for clinical studies, and commercial readiness. We continue to dedicate, resources to advance our sophisticated manufacturing know-how, including formulation of lipid nanoparticles, which improves manufacturing efficiency and capacity.

We believe we have established sufficient manufacturing capacity through our CDMOs to meet our current internal research, development, and potential commercial needs, as well as our obligations under existing agreements with our partners. Additionally, we continue to evaluate relationships with additional suppliers to increase overall capacity and diversify our supply chain.

Revenue and Collaboration Arrangements and Other Material Agreements

In addition to our internal programs, we have collaborated or partnered with other parties on discovery, development, manufacturing or other efforts based on our proprietary platform technologies. Among other collaboration arrangements,

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we have a collaboration with CSL Seqirus for vaccines against SARS-CoV-2 (COVID-19), influenza and three other infectious diseases;

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we have received funding from the CFF to support our LUNAR-CF development program; and

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we have a contract with BARDA to support the development of a low-dose pandemic influenza candidate based on our proprietary self-amplifying messenger RNA-based vaccine platform.

CSL Seqirus

In November 2022, we entered into the CSL Collaboration Agreement with CSL Seqirus for the global exclusive rights to research, develop, manufacture and commercialize self-amplifying mRNA vaccines. The CSL Collaboration Agreement became effective on December 8, 2022, following clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

Under the CSL Collaboration Agreement, CSL Seqirus receives global exclusive rights to our technology for vaccines against SARS-CoV-2 (COVID-19), influenza and three other infectious diseases. Specifically, the collaboration agreement grants CSL Seqirus a license to our STARR mRNA technology and LUNAR lipid-mediated delivery, as well as mRNA drug substance and drug product manufacturing expertise. CSL has also been granted global non-exclusive rights in the field of pandemic preparedness (i.e., pathogens identified as priority diseases by the WHO), with the right to convert to an exclusive license.

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The CSL Collaboration Agreement sets forth how the parties will collaborate to research and develop vaccine candidates. In the COVID-19 field, we undertake activities for certain regulatory filings for our leading self-amplifying mRNA vaccine candidate in COVID-19, ARCT-154, in the United States and Europe and for research and development activities of a next-generation COVID vaccine candidate. CSL Seqirus leads and is responsible for all other research and development in COVID-19, influenza and the other fields.

We received an up-front payment of $200.0 million, with the potential to receive development milestones totaling more than $1.3 billion if all products are registered in the licensed fields. We also are entitled to potentially receive up to $3.0 billion in commercial milestones based on “net sales” of vaccines in the various fields. In addition, we are entitled to receive a 40% share of net profits from COVID-19 vaccine sales and up to low double-digit royalties of annual net sales for vaccines against influenza, pandemic preparedness and three additional infectious diseases. Entitlement to all such payments is subject to the strict conditions, requirements, royalty reduction provisions and other limitations set forth in the CSL Collaboration Agreement.

Either party may terminate the CSL Collaboration Agreement on a field-by-field basis for material breach by the other party, following notice and opportunity to cure. CSL Seqirus may also terminate the collaboration agreement in its entirety or on a field-by-field basis for any reason or no reason whatsoever, with certain limitations. The CSL Collaboration Agreement may also be terminated by CSL Seqirus for safety reasons, clinical data nonviability, commercial nonviability and other specified reasons.

In March 2024, we entered into Amendment Number Two to the CSL Collaboration Agreement to reflect updates to the development program and other adjustments consistent with our prior disclosures regarding the Collaboration and License Agreement (“Amendment Number Two”). Amendment Number Two, among other things, adjusts (i) the development plans for certain product candidates, (ii) various development milestones related to such product candidates, (iii) provisions of the CSL Collaboration Agreement related to specific royalty payments, (iii) provisions of the CSL Collaboration Agreement related to distributors, and (iv) proprietary payment calculations related to the foregoing.

On May 30, 2025, we initiated an arbitration against CSL Seqirus before the International Chamber of Commerce, seeking payment of a milestone under the CSL Collaboration Agreement based on the European Commission’s grant of marketing authorization for a presentation of KOSTAIVE® in the European Union.

In CSL Limited’s half-year results presented on February 11, 2026, CSL Limited reported an accounting write-down of approximately $430 million attributable to our collaboration agreement with CSL Seqirus, citing declining COVID-19 disease burden and more onerous U.S. regulatory requirements.

Cystic Fibrosis Foundation Agreement

On May 16, 2017, pursuant to a Development Program Letter Agreement (as amended, the “CFF Agreement”) with the CFF, CFF agreed to award us funding for a development program to identify lead CFTR mRNA sequences and LUNAR formulations, demonstrate tolerability of LUNAR CFTR mRNA, and demonstrate translatability of aerosolized LUNAR. The award includes a grant of rights to CFF know-how to assist us to research, develop, commercialize, make or otherwise exploit a product. If the award results in a successful commercialized product, we will pay CFF (i) royalties on sales of the product up to a maximum of a single-digit multiple of the total award amount actually paid to us by CFF, and (ii) thereafter, a single-digit percentage of annual net sales. Further, in the event of a license, sale or other transfer of the product or our development program technology (including a change of control transaction), we will pay CFF a percentage of such license, sale or transfer payments actually received by us or our shareholders (subject to a royalty cap). On August 1, 2019, we entered into an amendment to the CFF Agreement. Pursuant to the amendment, (i) CFF will increase the amount it will award to advance LUNAR-CF, (ii) we will provide a certain amount of matching funds for remaining budgeted costs, and (iii) the related disbursement schedule from CFF to us was modified such that (a) a disbursement was made upon execution of the amendment, (b) an agreed upon amount will be disbursed to us within thirty days of the first day of each of January, April, July and October 2020, and (c) the last payment will be disbursed upon us invoicing CFF to meet good manufacturing practices and submitting an IND application. In January 2022, the parties signed an additional amendment for CFF to fund the development of a CF ferret model for application in the development of ARCT-032, our LUNAR-CF candidate.

On September 25, 2023, we entered into an additional amendment (the “Fourth Amendment”) to the CFF Agreement, pursuant to which we and CFF agreed to: (a) increase the Amount of Award (as defined in the CFF Agreement and applicable amendment) from CFF to advance LUNAR-CF by up to $9 million (for a total to date of

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up to approximately $25 million), and required Arcturus to provide $15 million in matching funds for remaining budgeted costs; (b) modify the existing rates and caps on royalties due to CFF under the CFF Agreement, including the addition of an option for Arcturus to reduce the royalty rate through a one-time payment; (c) modify the calculation of payments from Arcturus to CFF in the event of certain dispositions or licensing of cystic fibrosis or other pulmonary assets or of a change of control of Arcturus; and (d) make corresponding changes to exhibits, definitions and other provisions of the CFF Agreement.

BARDA

In August 2022, we entered into a cost reimbursement contract with the Biomedical Advanced Research and Development Authority (“BARDA”) of the U.S. Department of Health and Human Services to support the development of a low-dose pandemic influenza candidate based on our proprietary self-amplifying messenger RNA-based vaccine platform.

The contract is to support our non-clinical and pre-clinical development, early-stage clinical development through Phase 1, and associated drug product manufacturing, regulatory and quality-assurance activities over a period of three years. The contract provides for reimbursement by BARDA of Arcturus’ permitted costs incorporated into the contract, up to $63.2 million. The contract does not include the purchase of any pandemic influenza vaccine that eventually may be developed. The contract is terminable by BARDA at any time under specified circumstances, including for convenience.

This contract is part of BARDA’s ongoing efforts to bolster pandemic preparedness and response capabilities by investing in innovative medical counter-measures that can help prevent the medical consequences that result from outbreaks caused by pandemic influenza and emerging infectious diseases. In December 2024, we initiated a Phase 1 clinical trial for our H5N1 pandemic flu candidate that is supported by funding from BARDA.

ARCALIS Joint Venture

In April 2021, Arcturus and Axcelead, Inc., a company existing under the laws of Japan (“Axcelead”), formed a joint venture entity, named ARCALIS, Inc. (“ARCALIS”), which operates as a corporation under the laws of Japan. Axcelead is an integrated drug discovery solutions provider to the pharmaceutical industry in Japan, having succeeded to a portion of the drug discovery research department of Takeda Pharmaceutical Company Limited in 2017. The goal of ARCALIS is to be a contract development and manufacturing organization focused on mRNA manufacturing that would provide manufacturing services to us and also to third parties.

ARCALIS has constructed facilities for the manufacture of mRNA drug substance and mRNA-LNP liquid and lyophilized drug product financed largely by grants from the Japanese government.

In January 2025, Meiji Seika Pharma, along with ARCALIS, received Ministry of Health, Labour and Welfare (MHLW) approval for adding commercial manufacturing sites in Japan for KOSTAIVE. Domestically produced products with active pharmaceutical ingredients manufactured at ARCALIS’s Minami-soma facilities, and formulated at Meiji Seika Pharmatech, have been shipped for commercial use in Japan for the 2024-25 and 2025-26 seasons.

Legacy Arrangements

During our formative period, we entered into various collaboration, development and license agreements with larger parties in our industry, providing for the designation of targets for collaborative development using our platform technologies. Although, as we have previously reported, parties to these agreements, including Ultragenyx, continue to have exclusive rights to certain of these targets, other than as reported above, there has been no significant development activities under the programs.

Intellectual Property

Our business success depends in part on our ability to obtain and maintain intellectual property protection for our proprietary technologies, inventions and know-how, and on our ability to operate without infringing on the proprietary rights of others. We strive to protect our intellectual property through a combination of patents, trademarks, trade secrets, licensing agreements, invention assignment agreements and confidentiality agreements with employees, advisors, consultants and contractors.

We rely on continuing technological innovation to strengthen our proprietary position in the field of nucleic acid medicines. Therefore, we plan to continue to file patent applications in jurisdictions around the world as we

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discover and develop novel nucleic acid technology platforms and novel nucleic acid therapeutic candidates. We cannot guarantee that future applications will be issued.

Our Patent Portfolio

As of January 31, 2026, we own over 500 patents and pending patent applications. The claims of these patents and pending applications include compositions of matter, methods of use, manufacturing processes and drug product formulations. These claims cover the use of our core platform technologies including the use of LUNAR® and lipid components to deliver nucleic acids, specific nucleic acid modalities for treating disease, as well as our proprietary technology regarding the design, manufacture, and purification of nucleic acids for use in therapy. Claims also cover the composition of matter, formulation, and use of our therapeutic candidates to prevent and/or treat target diseases including OTC deficiency, CF, COVID-19 and Influenza. If issued, our patents are expected to expire between 2028 and 2046, without taking into account any possible patent term extensions.

Our patent portfolio is built upon a strategy of robust protection for our LUNAR and STARR® platforms as described below:

•
LUNAR – Our patent holdings continue to grow in scope and territory for our LUNAR platform with patents and patent applications directed to composition of matter including chemical structures for our growing library of proprietary lipids, manufacture of lipid nanoparticles (including lyophilization), and use of our LUNAR technology for nucleic acid delivery and drug delivery in more than 50 countries around the world.

•
STARR – In 2019, we began to develop our STARR platform which combines our proprietary LUNAR delivery systems with technologies that enable self-transcribing and self-amplifying RNA. As noted above, our robust LUNAR portfolio provides protection for delivery vehicles that can enable specific and effective delivery of STARR-based drug substances. As with our LUNAR portfolio, our patent holdings directed to our STARR platform have a broad geographical footprint. This portfolio is generally directed to specially designed RNA constructs, specific nucleotide and amino acid sequences, and lipid formulations comprising the same. We anticipate that further patents will be filed as we continue to innovate with respect to our STARR platform and that current applications covering these developments in our STARR platform, if granted, will last until 2046, not including any patent term extensions.

Patent Terms

The term of individual patents depends on the countries in which they are obtained. The patent term is 20 years from the earliest effective date of filing a non-provisional patent application in most of the countries in which we file.

Under the Drug Price Competition and Patent Term Restoration Act (also known as the Hatch-Waxman Act), U.S. patent holders can apply for a patent term extension to compensate for the patent term lost during the FDA regulatory review process. Patent extension is only available for patents covering FDA-approved drugs. The extension can be up to five years beyond the original expiration date of the patent and cannot extend a patent term for longer than 14 years from the date of product approval. Only one patent extension is granted per approved drug. Similar provisions may be available in foreign jurisdictions, including Europe. We intend to apply for patent term extensions where possible.

Trade Secrets

We have developed valuable trade secrets to protect our product candidates and proprietary processes, including trade secrets related to the design and optimization of nucleic acids, the design and optimization of lipid compositions for delivery of nucleic acids, manufacturing and formulation processes, and analytical techniques.

Certain Risks to Intellectual Property

Our commercial success also depends in part on our non-infringement of the patents or proprietary rights of third parties. For a more comprehensive discussion of the risks related to our intellectual property, please see Item 1A “Risk Factors” – “Risks Related to Our Intellectual Property.”

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The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States. Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions.

Our success depends in part on our ability to:

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preserve trade secrets;

•
prevent third parties from infringing upon our proprietary rights; and

•
operate our business without infringing the patents and proprietary rights of third parties, both in the United States and internationally.

We seek to protect our proprietary technology and processes, in part, by confidentiality and invention assignment agreements with our employees, consultants, scientific advisors and other contractors. These agreements may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our employees, consultants, scientific advisors or other contractors use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.

Product Approval and Government Regulation

Government authorities in the United States, at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing. Any product candidate that we develop must be authorized or approved by the FDA before it may be legally marketed in the United States and by the appropriate foreign regulatory agency before it may be legally marketed in foreign countries.

U.S. Drug Development Process

In the United States, the development, manufacturing, and marketing of human drugs and vaccines are subject to extensive regulation. The FDA regulates drugs under the Federal Food, Drug and Cosmetic Act (“FDCA”) and implementing regulations, and biological products, including vaccines, under provisions of the FDCA and the Public Health Service Act (“PHSA”). Drugs and vaccines are also subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. The process required by the FDA before a drug or biological product may be marketed in the United States generally involves the following:

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completion of nonclinical laboratory tests, animal studies and formulation and stability studies according to good laboratory practices (“GLP”) or other applicable regulations;

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submission to the FDA of an application for an IND, which must become effective before human clinical trials may begin;

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performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as current good clinical practices (“GCPs”) to establish the safety and efficacy of the proposed drug for its intended use;

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submission to the FDA of a new drug application (“NDA”) or biologics license application (“BLA”) for a new drug or biologics;

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satisfactory completion of FDA inspections of the manufacturing facility or facilities where the drug is produced to ensure compliance with the FDA’s current good manufacturing practice standards (“cGMP”), to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

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potential FDA inspection of the nonclinical and clinical trial sites that generated the data in support of the NDA or BLA; and

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FDA review and approval of the NDA or BLA.

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The lengthy process of seeking required approvals and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial resources and approvals are inherently uncertain.

Before testing any compounds with potential therapeutic value in humans, the drug candidate enters the preclinical study stage. Preclinical tests, also referred to as nonclinical studies, include discovery and target identification, in vitro testing to assess biological activity, mechanism of action, and potential toxicity, as well as animal studies to assess the potential safety, pharmacokinetics, and pharmacological activity of the drug candidate.

Clinical trials involve the administration of the drug candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s direct control. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

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Phase 1. The drug is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion. In the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing may be conducted in patients;

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Phase 2. The drug is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule; and

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Phase 3. Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the product and provide an adequate basis for product labeling. Generally, a well-controlled Phase 3 clinical trial is required by the FDA for approval of an NDA or BLA.

Post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication.

U.S. review and approval processes

The results of product development, nonclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an NDA or BLA requesting approval to market the product. The submission of an NDA or BLA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product. Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling. In addition, the FDA may require post marketing clinical trials, sometimes referred to as Phase 4 clinical trials, which are designed to further assess a product’s safety and effectiveness and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized.

Post-approval requirements

Approved products remain subject to ongoing FDA regulation, including requirements relating to manufacturing, labeling, promotion, adverse event reporting and periodic inspections. Failure to comply with applicable requirements may result in enforcement actions, including warning letters, fines, product recalls, suspension or withdrawal of approval, or other penalties.

Regulation in Europe and Other Regions

In addition to U.S. requirements, we must obtain regulatory approvals in foreign jurisdictions prior to conducting clinical trials or marketing products outside the United States. Regulatory requirements vary by country

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but generally involve processes comparable to those of the FDA, including review of clinical data, manufacturing information and product labeling.

Competition

Our Business in General

The RNA pipeline across the biopharma industry is expansive, with mostly early-stage assets. Published market reports indicate that there are 1,000+ RNA assets in development with approximately 90% in pre-clinical and Phase 1 studies RNA assets in development are across a broad therapeutic range making for a diffused therapeutic focus across the field.

Competition is intensifying in this space as both biotech and larger pharma companies invest more in RNA technology and RNA pipelines mature in three key areas: RNA platform development (targeted on build of RNA platform components and delivery), platform discovery (unlocking broader therapeutic applicability) and in technology-aided platform accelerators (accelerate RNA design, development, and production - to further leverage advantage of RNA versus traditional technologies). Pharmaceutical and biotechnology companies are heavily pursuing opportunities to build foundational platforms and to expand and accelerate RNA applications. As a result, we face competition at the technology platform and therapeutic indication levels from both large and small biopharmaceutical companies, academic institutions, governmental agencies and public and private research institutions.

Many of our competitors, including those with strategic partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Mergers and acquisitions, recently and into the future, may result in resource concentration among a potentially consolidated number of competitors.

Our success will be based in part upon our ability to identify, develop and manage a portfolio of product candidates that are safer and more effective than competing products in the treatment of our targeted patients. The commercial opportunity could be reduced or eliminated if competitors develop and commercialize products that are safer, more effective, are more convenient or are less expensive than any products we may develop in our respective areas. Our collaboration with CSL Seqirus may allow us to compete commercially on the world stage within the COVID and influenza markets.

We are aware of several other companies that are working to develop nucleic acid medicines, including gene therapy, gene editing, mRNA (including sa-mRNA), siRNA, and antisense therapeutics. Many of these companies, such as Genevant Sciences and Acuitas Therapeutics, are also developing nucleic acid delivery platforms which compete with LUNAR technology.

Below we have included what we believe to be the competitive landscape for certain of the medicines that we currently have in development.

Lung Franchise ARCT-032 (LUNAR-CF)

The lead candidate of our lung franchise is ARCT-032, an mRNA therapeutic candidate for cystic fibrosis based on our proprietary drug substance mRNA technology platform and our LUNAR lipid nanoparticle delivery platform has advanced into Phase 2 clinical development.

We are aware of product candidates of the following companies that we consider as competitors or future competitors to ARCT-032: Moderna/Vertex, Recode Therapeutics, Eloxx Pharmaceuticals, 4DMT, Spirovant, SalioGen, Splisense, Krystal Biotech, Sionna and Enterprise Therapeutics.

Liver Franchise ARCT-810 (LUNAR-OTC)

Our liver franchise has advanced into mid-stage clinical development with ARCT-810 in Phase 2 clinical development. Potential competitors include, but are not limited to, Ultragenyx and iECURE which are advancing a gene therapy program for OTC in clinical development. Additional companies working on therapies targeting people with OTC deficiency include, Bloomsbury Genetic Therapies and Moderna, which has a therapeutic candidate in pre-clinical development.

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LUNAR-COVID-19 Vaccine (KOSTAIVE®)

Our vaccine franchise is based on our self-amplifying STARR technology platform and our lipid nanoparticle delivery platform called LUNAR. This franchise has advanced into the market with the approval of KOSTAIVE® in Japan and geographic expansion is underway to other markets through our collaboration with CSL Seqirus. We consider the following companies with approved or late-stage clinical development vaccines as some of our competitors or future competitors to our partnered COVID-19 vaccine franchise: Pfizer/BioNTech, Moderna, and Sanofi/Novavax. Dozens of other companies are continuing to develop COVID-19 vaccines. However, the majority of these companies use conventional mRNA (not self-amplifying) and protein-based vaccine technology as the basis for their COVID-19 vaccines.

LUNAR-FLU Vaccine

We have partnered our influenza vaccine franchise with CSL Seqirus. We consider the following companies as some of the competitors or future competitors to our partnered LUNAR-Flu vaccine franchise: Pfizer, Moderna, Novavax, and Sanofi. The flu industry is evaluating a shift to utilizing mRNA-based platforms in addition to other non-egg based technologies and traditional (egg-based) technologies.

Multiple Areas

Of the competitors noted above, the following compete with us across multiple areas of our portfolio and/or aspects of our platform technologies:

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While we are the first and only company with an approved sa-mRNA vaccine in a major market, there are two other manufacturers with approved conventional mRNA-based vaccines, according to information published by the relevant companies:

o
BioNTech, in collaboration with Pfizer, has a marketed COVID-19 conventional mRNA vaccine, COMIRNATY®, available in multiple geographies, and is developing an mRNA flu vaccine and a COVID-19/flu combination vaccine, as well as latent virus and other vaccines of global public health interest in early development.

o
Moderna manufactures two other approved conventional mRNA-based COVID-19 vaccines, Spikevax® and mNEXSPIKE®, which are available in multiple geographies. Moderna’s pipeline includes both infectious disease and rare disease assets. From an infectious disease perspective, beyond Spikevax, Moderna is developing respiratory (e.g., seasonal flu, pandemic flu, COVID-19/flu combo, RSV, etc.), enteric (Norovius), bacterial (Lyme), latent (e.g., EBV, HSV, etc.), and other virus vaccine candidates ranging from Phase I to Phase III stages of development. Moderna’s rare disease pipeline includes intercellular therapeutics and inhaled therapeutics. Through the Moderna-Vertex collaboration, the mRNA-3692 / VX-522 asset for CF is in Phase I. Moderna’s mRNA-3139 asset is in preclinical development for OTC.

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The mRNA portfolio resulting from the GSK-CureVac collaboration focuses on vaccines in the prevention of influenza and COVID-19 viruses. Neither entity nor the collaboration has achieved health authority approval for flu and/or COVID-19 mRNA vaccine products. Both the flu and COVID-19 assets are in Phase 2 clinical development; the COVID-19/flu combo is in Phase 1. The GSK–CureVac collaboration is no longer a joint mRNA vaccine development partnership as it has been transformed into a licensing relationship where GSK owns and advances all the infectious‑disease mRNA vaccines originally co‑developed with CureVac.

•
Subsequently, BioNTech formally acquired CureVac in January 2026 BioNTech acquisition of CureVac consolidated ownership of the companies’ ongoing IP litigation.

Human Capital

As of December 31, 2025, we had approximately 111 employees, of which 106 were full-time and 5 were part-time. Additionally, we are supported by contractors and scientific consultants in most areas of the business. None of our employees are represented by a labor union or covered by a collective bargaining agreement. We consider relations with our employees to be good. Our ability to advance our research, development, manufacturing and commercialization activities depends largely on our ability to attract, retain and develop qualified personnel. We compete for talent in specialized and competitive markets and support our employees through professional

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development and training programs, and generally offer our employees competitive compensation and benefits, including base salary, annual incentive bonuses, equity-based compensation, healthcare and insurance benefits, retirement savings plans and generous paid time off and holidays.

Senior Leadership

On December 11, 2025, we and Andy Sassine, our former Chief Financial Officer and former member of the Board of Directors, mutually agreed to end his employment relationship in an amicable manner effective December 31, 2025. On December 12, 2025, Joe Roberts, our Controller, was appointed interim principal financial officer and interim principal accounting officer. We have initiated a comprehensive search for a new Chief Financial Officer.

Available Information

The Company was founded in 2013 as Arcturus Therapeutics, Inc., and we have maintained our principal executive offices in San Diego, California since that time. In November 2017, Alcobra Ltd., an Israeli limited company, merged with our company, changed its name to Arcturus Therapeutics Ltd. (“Arcturus Israel”), and commenced trading on Nasdaq under the symbol “ARCT.” On June 17, 2019, we redomiciled to the United States (the “Redomiciliation”) and changed our name to Arcturus Therapeutics Holdings Inc.

Our Internet address is www.arcturusrx.com. Our Annual Reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and proxy statements, and all amendments thereto, are available free of charge on our Internet website. These reports are posted on our website as soon as reasonably practicable after they are electronically filed with the SEC. The public may read and copy any materials that we file with the SEC electronically through the SEC website (www.sec.gov). The information contained on the SEC’s website is not incorporated by reference into this Annual Report on Form 10-K and should not be considered to be part thereof.