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Item 1. Business

2026-03-03 compared with 2025-03-06 · 541 added, 543 removed, 1112 unchanged (49% of the section changed)

We are a messenger RNA medicines company focused on the development of infectious disease vaccines and opportunities within liver and respiratory rare diseases.

We developed the world’s first approved self-amplifying messenger RNA (sa-mRNA) vaccine, KOSTAIVE ® (“KOSTAIVE”).

KOSTAIVE achieved approval in Japan in 2023 as a vaccine against COVID-19.

Sales of KOSTAIVE began in Japan in October 2024, marking our transition to a commercial stage company.

We have several key platform technologies that we leverage to develop and advance a pipeline of mRNA-based vaccines and therapeutics for infectious diseases and for rare genetic disorders with significant unmet medical needs.

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 believe we are among the world leaders in both areas.

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 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 therapeutics to disease-relevant target tissues.

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.

The approval of KOSTAIVE in Japan was a significant milestone which validates our LUNAR and STARR platforms, as well as sa-mRNA more generally as a meaningful modality.

Finally, we 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.

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 Seqirus, Inc.

(“CSL Seqirus”), a part of CSL Limited and one of the world’s leading influenza vaccine providers, on the development and commercialization of mRNA vaccines for COVID-19, influenza and certain other infectious diseases.

We made significant progress in 2024.

Commercial sales of KOSTAIVE began in October 2024 in Japan by Meiji Seika Pharma (“Meiji”), CSL Seqirus’ exclusive partner in Japan, marking the first commercial sales of an Arcturus-developed product.

In February 2025, we received approval of KOSTAIVE from the European Commission (EC), which provided further validation of our platform by another significant regulatory authority.

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.

We initiated dosing in a Phase 1 clinical trial of a novel seasonal influenza sa-mRNA vaccine candidate under our collaboration with CSL Seqirus in January 2024.

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

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”).

In our OTC program, we completed dosing of eight subjects in August 2024 in a Phase 2 double-blind multiple-dose study of ARCT-810.

In the second quarter of 2024, we expanded the Phase 2 clinical program of ARCT-810 with an open-label, multiple-dose study which initiated dosing in December 2024.

ARCT-810 has received Orphan Drug Designation from the FDA and Orphan Medicinal Product Designation from the European Medicines Agency (the “EMA”) for treatment of OTC deficiency, as well as Fast Track Designation and Rare Pediatric Disease Designation from the FDA.

In our CF program, we initiated dosing in December 2024 in a Phase 2 multiple ascending dose study of ARCT-032 designed to identify a safe and effective dose in people with Class I (null) CFTR mutations and other CF patients who do not benefit from CFTR modulators.

In July 2024, we completed dosing and follow-up visits for seven participants in a safety and tolerability Phase 1b clinical study in New Zealand of ARCT-032 in adults with CF.

ARCT-032 has received Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA for the treatment of CF, and Rare Pediatric Disease Designation from the FDA.

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 potentially be useful for identification and development of additional products for our portfolio.

Also, with our sourcing partners, we manufactured cGMP (current good manufacturing practices) batches yielding significant quantities of clinical trial materials for global studies of our candidates, and with our collaborator, CSL Seqirus, we have established commercial production processes for the COVID-19 vaccine program.

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

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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, from which all proteins necessary for life are encoded.

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.

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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;

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

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

• 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”));

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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 acids delivery vehicle seeks to protect the nucleic acid from degradation prior to cell entry and to release the nucleic acid payload inside the cell.

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.

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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, termed ATX, with over 300 to date.

Our 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.

We continue to expand our library of proprietary synthetic lipids, known as ATX, to over 300 to date.

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.

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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 within host cells which may provide protective immunity against infectious pathogens.

We have clinically shown that the combination of LUNAR and STARR technology can result in lower dose requirements with superior immune response and sustained protein expression compared to conventional RNA-based vaccines, which may enable production of greater volumes of vaccine doses more quickly.

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.

(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

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

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.

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 6 th 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.

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.

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

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).

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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 has 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 the 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 three other infectious diseases and global non-exclusive rights to pandemic pathogens.

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 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 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.

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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 initiated in January 2024 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.

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

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Our COVID-19 vaccine candidate, KOSTAIVE, is based on our STARR (self-amplifying mRNA) technology platform and our LUNAR platform.

It was designed to promote immune responses to the spike protein of the SARS-CoV-2 virus, the critical part of the virus that allows infection to occur.

KOSTAIVE is the brand name approved in Japan and Europe for ARCT-154, which is the version of the sa-mRNA COVID-19 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 the vaccine.

The approval 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, all as further described below, are significant milestones in the advancement of our vaccines franchise.

The recent approval of KOSTAIVE (ARCT-154 version) by the EMA in January 2025 provides further validation of our platform by another significant regulatory authority, in addition to expanding the potential commercialization of KOSTAIVE.

During 2024, several important publications were released relating to our studies, which are summarized below.

• In May 2024, Nature Communications published results from the 19,000 subject study performed in Vietnam, with results demonstrating that two 5µg doses of ARCT-154 were well-tolerated, immunogenic and provided significant protection against multiple strains of COVID-19.

This publication relates to the study described below – “ Pivotal Phase 1/2/3 Study in Vietnam” .

• In November 2024, npj Vaccines, a Nature Portfolio journal, published the results of Phase 3c of the pivotal Phase 1/2/3 study in Vietnam, demonstrating higher immune response and protective efficacy of ARCT-154 compared to an approved adenovirus-vector COVID-19 vaccine (DOI:

10.1038/s41541-024-01017-5).

• In October 2024, Lancet Infectious Diseases published the follow-up article ‘12-month persistence of immune responses to self-amplifying mRNA COVID-19 vaccines:

ARCT-154 versus BNT162b2 vaccine’ (https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00615-7/fulltext), which confirmed a better neutralizing immune response against a panel of SARS-CoV-2 strains in pre-immunized Japanese adults boosted with ARCT-154 compared with the conventional mRNA vaccine, BNT162b2, which persisted up to 12 months post-vaccination, including in those age 50 years and older.

This publication relates to the study described below – “ Phase 3 Study of Bivalent Version of KOSTAIVE (COVID-19 Vaccine) Candidate in Japan ”.

Approval of KOSTAIVE in Japan

KOSTAIVE (ARCT-154 version) received marketing authorization approval in November 2023 from the Japanese Ministry of Health, Labour and Welfare for use as a primary immunization and booster in Japan for adults 18 years and older.

The approval was based on positive clinical data from several ARCT-154 studies, including a 19,000-participant efficacy, safety and immunogenicity study performed in Vietnam, as well as a Phase 3 booster study in Japan.

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.

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, and clinical evidence supporting the safety and immunogenicity of KOSTAIVE (bivalent, BA.4/5 and ancestral strain).

In January 2025, CSL Seqirus’ partner Meiji announced that it received approval for a partial amendment to the manufacturing and marketing approval of KOSTAIVE to include manufacturing sites in Japan.

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

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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

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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 or are conducting the studies described below.

Pivotal Phase 1/2/3 Study in Vietnam

During 2021, we entered into a collaboration with Vinbiocare Biotechnology Joint Stock Company (“Vinbiocare”), a member company of the Vingroup Joint Stock Company (Vingroup) group of companies.

As part of a collaboration with Vinbiocare, ARCT-154, our next-generation, self-amplifying mRNA-based vaccine for COVID-19, was advanced into a Phase 1/2/3 study in Vietnam, funded and sponsored by Vinbiocare (the “Vinbiocare Study”).

The trial was randomized, observer-blinded, placebo and active-controlled, and intended to assess the safety, immunogenicity, and efficacy of ARCT-154.

The Phase 3 arm of the Phase 1/2/3 study was initiated in September 2021.

The study enrolled over 19,000 adult subjects in Vietnam, including individuals with medical conditions, putting them at higher risk of severe complications of COVID-19.

The Phase 3b placebo-controlled efficacy portion of the study enrolled over 16,000 participants.

The study demonstrated that a 2-dose vaccination series with 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 ancestral SARS-CoV-2 strain and induced a cross-neutralizing immune response against new emergent variants.

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

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 were used as a basis for vaccine licensure in Japan and the European Union.

In August 2023, we submitted the primary manuscript with efficacy, immunogenicity and safety results of the pivotal Phase 1/2/3 clinical study of ARCT-154 in Vietnam ( https://www.nature.com/articles/s41467-024-47905-1 ).

Later, we published the results of Phase 3c part of the study, comparing the immunogenicity and efficacy of ARCT-154 and licensed adenoviral vector vaccine ChAdOx-1S, demonstrating higher immunogenicity and relative vaccine efficacy (19.8% (95% CI:

4.0–33.0)) of ARCT-154 compared to ChAdOx-1S ( https://pmc.ncbi.nlm.nih.gov/articles/PMC11585660/ ).

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

Meiji sponsored a randomized, multicenter, Phase 3, observer-blind, active-controlled comparative study to evaluate the safety and immunogenicity of a booster dose of ARCT-154 and to evaluate the non-inferiority of ARCT-154 over COMIRNATY® (Monovalent, Original strain).

The study completed enrollment in February 2023 with 828 participants, with half in the ARCT-154 group and half in a comparator group.

The study met all primary and secondary immunogenicity endpoints, including a secondary pre-defined superiority assessment over COMIRNATY (Omicron BA.4/5 strain).

Overall, the safety and immunogenicity results of the study support the favorable benefit/risk profile of the ARCT-154 vaccine when administered as a booster dose in adult individuals who previously received other mRNA COVID-19 vaccines.

In October 2024, Lancet Infectious Diseases published the follow-up article ‘12-month persistence of immune responses to self-amplifying mRNA COVID-19 vaccines:

ARCT-154 versus BNT162b2 vaccine’, which confirmed a better neutralizing immune response against a panel of SARS-CoV-2 strains in pre-immunized Japanese adults boosted with ARCT-154 compared with the conventional mRNA vaccine, BNT162b2, which persisted up to 12 months post-vaccination, including in those age 50 years and older.

Phase 3 Study of Bivalent Version of KOSTAIVE (COVID-19 Vaccine) Candidate in Japan

In September 2023, Meiji initiated a Phase 3 clinical study with ARCT-2301, a bivalent version of KOSTAIVE (ancestral strain and Omicron BA.4/5) to further support immunogenicity and safety data for our self-amplifying mRNA platform, which may facilitate the timely release of future seasonal updates of our COVID-19 vaccine against evolving variants of concern.

The study enrolled 930 healthy adults and individuals with comorbidities, who previously received three to five doses of mRNA COVID-19 vaccines, including the last booster at least three months prior to recruitment, and compared the investigational vaccine (ARCT-2301) and COMIRNATY (ancestral strain and BA.4/5) to evaluate safety and immunogenicity between observer-blind groups.

The bivalent vaccine met the primary study endpoint (non-inferiority).

Both the geometric mean titer (GMT) ratio and seroresponse rate (SRR) difference of neutralizing antibodies against SARS-CoV-2 (Omicron BA.4/5 and Wuhan strains) met pre-specified non-inferiority and superiority criteria versus COMIRNATY.

There were no causally-associated severe or serious adverse events with ARCT-2301.

As with the monovalent vaccine, the bivalent sa-mRNA formulation demonstrated superior immunogenicity over the conventional bivalent mRNA vaccine COMIRNATY, a higher immune response persisting up to six months after a booster dose, and improved breadth, supporting the robustness of the sa-mRNA vaccine platform for future vaccine strain updates.

The study results were presented at OPTIONS XII for the Control of Influenza conference in Brisbane, Australia, in September 2024.

Phase 3 Co-administration Study of KOSTAIVE (Monovalent XBB1.5) and Seasonal Influenza Vaccines

In March 2024, Arcturus and CSL Seqirus initiated a Phase 3 pivotal study with the ARCT-2303 candidate vaccine containing the XBB1.5 Omicron variant.

The study aimed to generate additional immunogenicity and safety data in multiple ethnicities to support regulatory filings in the U.S.

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 vaccine s.

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.

In addition, the study assessed the co-administration of the ARCT-2303 vaccine with the age-appropriate seasonal influenza vaccines.

Overall, 1,499 adults, including older adults, were recruited in the study in Australia, Costa Rica, Honduras and the Philippines.

The study results showed that all four primary study objectives and key secondary study objectives were met.

ARCT-2303 demonstrated a superior immune response compared to ARCT-154 as measured by neutralizing antibodies against Omicron XBB.1.5 in terms of GMT ratio and SRR difference.

Co-administration of ARCT-2303 and quadrivalent influenza vaccine (QIV;

Flucelvax, CSL) in adults 18-64 years old showed a noninferior immune response compared to standalone QIV.

Co-administration of ARCT-2303 and QIV also showed a noninferior immune response compared to standalone ARCT-2303.

Co-administration of ARCT-2303 and adjuvanted QIV (Fluad, CSL) in adults 65 years of age and above showed similar results for co-administered and separately administered groups.

The safety and reactogenicity of co-administered vaccines were comparable with standalone administration.

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.

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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.

In conjunction with our collaborator, CSL Seqirus, we are working to optimize KOSTAIVE’s formulation to better meet the needs of healthcare professionals and their patients.

Seasonal Flu Collaboration Program

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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 the Southern Hemisphere.

In many regions, influenza is seasonal, with infections peaking during November through April in the Northern Hemisphere and May through September in

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 U.S.

Food and Drug Administration (“FDA”)) then make the final decision of which strains should be covered by vaccines licensed in their country.

Our LUNAR-FLU (seasonal) program, now exclusively licensed to 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.

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.

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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 take advantage of our expertise in both LUNAR lipid delivery systems and our STARR self-amplifying mRNA technology.

This platform has 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.

Working with CSL Seqirus, we generated a comprehensive non-clinical data package to support the initiation of the Phase 1 clinical trial with a novel influenza sa-mRNA vaccine candidate.

A Phase 1 dose-finding safety and immunogenicity study was initiated in January 2024 in Australia and is ongoing.

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, which is part of the CSL Collaboration Agreement, 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.

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.

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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.

The Phase 1 study of ARCT-2304, a self-amplifying mRNA (sa-mRNA) vaccine candidate, also known as LUNAR-H5N1, initiated dosing in December 2024.

The randomized placebo-controlled Phase 1 trial (NCT06602531) is being conducted at multiple sites in the U.S.

and designed to enroll approximately 200 healthy adults (120 participants 18-59 years old;

80 participants 60-80 years old).

The primary objective of this initial clinical trial is to evaluate safety and immune responses of three different dose levels and two different vaccination schedules of ARCT-2304 vaccine.

Immune responses are measured by hemagglutination inhibition (HAI), virus microneutralization (MN) and neuraminidase enzyme-linked lectin assays (ELLA).

The clinical study is fully funded by Biomedical Advanced Research and Development Authority (BARDA).

For a more comprehensive discussion of the funding award, please see Item 1 “Business” – “Revenue and Collaboration Arrangements and Other Material Agreements” – “BARDA.”

Preclinical Ferret Studies of ARCT-2304 (LUNAR-H5N1)

Several ferret challenge studies have been conducted to establish the efficacy of ARCT-2304, our clinical candidate for the LUNAR-pandFLU program.

ARCT-2304 vaccinated ferrets were challenged with the same influenza strain, H5N1 A/Indonesia/5/2005, encoded by the vaccine and protected all ferrets from lethal challenge.

Robust HAI and NI titers were observed after two doses of the vaccine and nasal titers in the days following challenge were lower than in either the unvaccinated ferrets (PBS) or ferrets vaccinated with an adjuvanted recombinant trimeric hemagglutinin (rHA).

Further, fewer signs of lung damage were observed in ARCT-2304 ferrets compared to either unvaccinated or rHA vaccinated ferrets.

In a separate experiment, ARCT-2304 vaccinated ferrets were challenged with an antigenically drifted strain from a different clade of H5N1, A/Vietnam/1203/2004.

ARCT-2304 vaccinated ferrets were compared to unvaccinated ferrets and to ferrets receiving an adjuvanted trimeric rHA vaccine encoding either the same strain as encoded by ARCT-2304 (A/Indonesia) or the challenge strain (A/Vietnam).

ARCT-2304 vaccinated ferrets were protected from death from this antigenically drifted strain.

While HAI and NI titers were lower against A/Vietnam than against A/Indonesia, ARCT-2304 vaccinated ferrets had the lowest nasal wash titers of any group and showed no signs of lung damage in contrast to unvaccinated ferrets and ferrets vaccinated with adjuvanted trimeric rHA protein.

A) Ferrets were vaccinated twice (day 0 & 28) with either ARCT-2304 (5µg) or an adjuvated (Addavax) recombinant trimeric HA protein (15µg) and challenged 3 weeks (day 49 post-vaccination) after the last vaccination with a lethal dose of the homologous H5N1 A/Indonesia/5/2005 strain.

All vaccinated ferrets survived infection while all unvaccinated (PBS) ferrets succumbed to the infection by day 7 post-infection.

ARCT-2304 ferrets had the highest HAI and NI titers among vaccinated groups both prior to and after challenge.

In addition, nasal wash titers were lowest in the ARCT-2138 vaccinated ferrets.

B) Ferrets were vaccinated twice (day 0 & 28) with either ARCT-2304 (5µg) or an adjuvated (Addavax) recombinant trimeric HA protein (15µg) encoding the same strain at ARCT-2304 (A/Indonesia) or the challenge strain (A/Vietnam) and challenged 4 weeks (day 56 post-vaccination) after the last vaccination with a lethal dose of H5N1 A/Vietnam/1203/2004 strain.

While lower HAI and NI titers were observed against the heterologous A/Vietnam strain, all vaccines elicited protection from lethal infection.

Similar to the heterologous challenge, however, the lowest nasal wash titers were observed in the ARCT-2304 vaccinated group.

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 – ARCT-810 (LUNAR-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.