Arcturus Therapeutics (ARCT) Earnings Call zu Q3 2026: Wichtige klinische Meilensteine

Wichtigste Erkenntnisse

• Arcturus Therapeutics meldete für das dritte Quartal 2026 einen Umsatz von 18,3 Millionen US-Dollar, verglichen mit 17,2 Millionen US-Dollar im Vorjahreszeitraum. Dies spiegelt vor allem eine Kündigungszahlung von CSL Seqirus in Höhe von 12 Millionen US-Dollar sowie die Erfassung verbliebener abgegrenzter Umsätze wider.
• Der Nettoverlust im dritten Quartal verringerte sich auf 7,4 Millionen US-Dollar bzw. 0,26 US-Dollar je Aktie, nach 13,4 Millionen US-Dollar bzw. 0,49 US-Dollar je Aktie im dritten Quartal 2025. Die F&E-Aufwendungen sanken von 23,3 Millionen auf 17,0 Millionen US-Dollar.
• Die flüssigen Mittel beliefen sich zum 30. September 2026 auf 184,8 Millionen US-Dollar. Das Management geht davon aus, dass die Liquiditätsreichweite bis Ende 2028 reicht.
• Das Unternehmen rechnet damit, die Rekrutierung für die Phase-2-Studie zu ARCT-032 bei Mukoviszidose bis Ende 2026 abzuschließen und den vollständigen Datensatz für Kohorte 4 im zweiten Quartal 2027 vorzulegen. Vorläufige Eckdaten (Top-Line-Daten) werden noch vor der vollständigen Präsentation erwartet.
• Die Phase-2-Dosierung von ARCT-2601 ist für das erste Quartal 2027 geplant, wobei Top-Line-Daten in der zweiten Jahreshälfte 2027 erwartet werden. Der Wirkstoffkandidat basiert auf LUNAR 2.0, das bei nicht-menschlichen Primaten eine 38-mal höhere Wirkstärke als die ursprüngliche LUNAR-Formulierung aufwies.
• Das Management plant die Einreichung eines IND-Antrags für das PKU-Programm in der zweiten Jahreshälfte 2027, während COSTAVE in Japan für die Saison 2026–2027 weiterhin kommerziell vertrieben wird.

Wichtigste Finanzdaten

Geschäfts- und operative Entwicklung

ARCT-032-Programm bei Mukoviszidose

In Kohorte 4 der Phase-2-Studie wird inhaliertes ARCT-032 in einer Dosierung von 10 mg einmal täglich über 12 Wochen bei bis zu 20 Erwachsenen untersucht, primär Patienten mit Klasse-1-Mukoviszidose. Die Rekrutierung beschleunigte sich nach Eröffnung zusätzlicher Studienzentren in Israel und der Türkei.

Nach Angaben des Managements haben einige Patienten das gesamte zwölfwöchige Regime abgeschlossen. Das Unternehmen verzeichnete keine schweren Sicherheitsereignisse, die das Drug Safety Monitoring Committee dazu veranlasst hätten, die Fortführung einzuschränken oder das Programm zu stoppen. Anders als bei konkurrierenden Programmen, die im Earnings Call erörtert wurden, waren bei Arcturus weder die tägliche Gabe systemischer Steroide noch eine tägliche Verabreichung in der Klinik erforderlich.

In der Studie werden der prozentuale Sollwert der FEV1, der Lungen-Clearance-Index, Parameter der Lebensqualität sowie hochauflösende CT-Aufnahmen untersucht. Die REACH-Verlaufsbeobachtungsstudie der CF Foundation könnte vorbehaltlich behördlicher Abstimmungen das Design von Phase 3 unterstützen und die Abhängigkeit von einer größeren Placebogruppe verringern.

ARCT-2601 und LUNAR 2.0

ARCT-2601 ist der erste therapeutische Kandidat, der die Verabreichungsplattform LUNAR 2.0 nutzt. Bei nicht-menschlichen Primaten erzielte die Plattform eine 38-fach höhere Wirkstärke gegenüber der ursprünglichen LUNAR-Formulierung, die bei ARCT-810 zum Einsatz kam.

In die geplante Phase-2-Studie sollen Patienten ab 12 Jahren mit Ornithin-Transcarbamylase-Mangel aufgenommen werden. Das Management beabsichtigt, bis zu sechs Probanden zu rekrutieren und Patienten zu priorisieren, deren Ammoniak- und Glutaminspiegel trotz aktueller Standardversorgung im oberen Bereich bleiben.

Das Unternehmen geht davon aus, dass der Datensatz zu ARCT-2601 zusammen mit den Ergebnissen zu ARCT-810 in einem End-of-Phase-2-Treffen mit der FDA bewertet wird, um das Design einer potenziellen Phase 3 zu unterstützen. Die Phase-2-Daten zu ARCT-810 zeigten bei 0,3 mg/kg und 0,5 mg/kg eine Senkung oder Stabilisierung des Nüchtern-Ammoniaks sowie niedrigere Glutaminwerte.

Pipeline-Erweiterung und Impfstoffe

Arcturus entwickelt eine mit LUNAR 2.0 formulierte mRNA-Therapie gegen Phenylketonurie, die darauf ausgelegt ist, die funktionelle PAH-Aktivität wiederherzustellen und den Phenylalanin-Stoffwechsel zu verbessern. Das Management plant, nach der Kandidatenauswahl und weiteren Studien zu Wirkungsdauer und Wirkstärke zusätzliche präklinische Ergebnisse bekannt zu geben.

Die Übernahme von MyNeo brachte KI-basierte Kompetenzen im Antigendesign, bei der mRNA-Optimierung sowie bei der Target-Identifizierung ein. Nach Angaben des Managements könnte die Technologie strategische Kooperationen in der Onkologie unterstützen; gleichzeitig wurde betont, dass Arcturus weiterhin auf die Umsetzung seiner mRNA-Therapeutika-Pipeline fokussiert bleibe.

COSTAVE, der selbstamplifizierende mRNA-COVID-Impfstoff des Unternehmens, wird in Japan weiterhin über Meiji kommerziell vertrieben. Zudem schloss Arcturus die Übertragung der Zulassungsinhaberrechte in der Europäischen Union und im Vereinigten Königreich von CSL Seqirus ab. Für die USA bekräftigte das Management, nach einem Partner zu suchen.

Ausblick der Unternehmensführung

• Abschluss der Rekrutierung für Kohorte 4 der Phase-2-Studie zu ARCT-032 bis Ende 2026.
• Veröffentlichung von Top-Line-Daten zu ARCT-032 vor der geplanten vollständigen Phase-2-Präsentation im zweiten Quartal 2027.
• Beginn der Phase-2-Dosierung von ARCT-2601 im ersten Quartal 2027.
• Meldung von Top-Line-Daten zu ARCT-2601 in der zweiten Jahreshälfte 2027.
• Einreichung eines IND-Antrags für das LUNAR-2.0-PKU-Programm in der zweiten Jahreshälfte 2027.
• Wahrung der Liquiditätsreichweite bis Ende 2028 auf Basis der aktuellen Pläne.
• Prüfung von Vermarktungsaktivitäten für COSTAVE in Europa und im Vereinigten Königreich im Jahr 2027 bei gleichzeitiger Suche nach einem US-Partner.

Risiken und Beobachtungspunkte

• Der genaue Zeitplan für die Veröffentlichung der Top-Line-Daten zu ARCT-032 und die Go/No-Go-Entscheidung zu Phase 3 wurde nicht näher spezifiziert, außer dass dies vor der vollständigen Datenpräsentation im zweiten Quartal 2027 geschehen soll.
• Das Management rechnet mit potenziellen Gesprächen mit der FDA zu ARCT-032 in der zweiten Jahreshälfte 2027, stufte einen Beginn von Phase 3 bis Ende Dezember 2027 jedoch als spekulativ ein.
• Die klinische Übertragbarkeit der bei nicht-menschlichen Primaten beobachteten 38-fachen Wirkstärkesteigerung von LUNAR 2.0 auf Patienten ist bislang unbestätigt.
• Der erste Datensatz zu ARCT-2601 wird voraussichtlich nicht mehr als sechs Probanden umfassen, weshalb die Konsistenz der Biomarker und die Vergleichbarkeit mit ARCT-810 wichtige Aspekte darstellen.
• Die Nutzung des REACH-Datensatzes der CF Foundation als Verlaufsbeobachtungskontrolle hängt von der Datenverfügbarkeit und Gesprächen mit der FDA ab.

Wichtigste Punkte aus der Fragerunde der Analysten

• Datensatz zu ARCT-032: Das Management bestätigte, dass die vollständige Präsentation rund 20 Probanden aus Kohorte 4 umfassen dürfte, die 12 Wochen lang täglich mit 10 mg behandelt wurden. Die Top-Line-Ergebnisse werden vor der vollständigen Präsentation im zweiten Quartal 2027 veröffentlicht.
• Zwölfwöchiges Wirksamkeitsfenster: Chief Medical Officer Alan Cohen erklärte, dass 12 Wochen ausreichen sollten, um ein klinisches Signal bei Spirometrie, Lungen-Clearance-Index, Lebensqualitätsparametern und Bildgebung zu erkennen.
• Sicherheit von ARCT-032: Nach Angaben des Unternehmens haben Patienten die 12 Wochen abgeschlossen; es traten keine schwerwiegenden Sicherheitsereignisse auf, die zu Studienbeschränkungen oder einem Abbruch führten. Der Zugang zu Wirksamkeitsdaten bleibt beschränkt, um eine Beeinflussung der Studiendurchführung zu vermeiden.
• Endpunkte bei OTC-Mangel: Das Management geht davon aus, dass die Senkung oder Stabilisierung von Ammoniak und Glutamin auch bei künftigen behördlichen Gesprächen und der Phase-3-Planung zentrale Wirksamkeitsmaße bleiben werden.
• Regulatorischer Weg für ARCT-2601: Zwei Typ-C-Meetings mit der FDA lieferten wichtige Erkenntnisse für das Programm und die Entwicklung von LUNAR 2.0. Die abschließenden GLP-Toxikologiearbeiten wurden in den IND-Antrag eingearbeitet.
• COSTAVE-Strategie: Arcturus plant, im Jahr 2027 Vermarktungschancen in Europa und im Vereinigten Königreich auszuloten, und sieht einen Partner weiterhin als bevorzugten Weg für den US-Markt an.

Vollständiges Transkript der Telefonkonferenz

Vollständiges Transkript der Telefonkonferenz

Ausführungen des Managements

Operator

Hello and welcome, everyone joining today's Arcturus Therapeutics third quarter 2026 earnings call.

[Operator Instructions]

Please note this call is being recorded.

It is now my pleasure to turn the meeting over to Neda Safarsadeh, Vice President, Head of Investor Relations, Public Relations and Marketing. Please go ahead.

Neda Safarzadeh

Thank you, operator. Good afternoon and welcome to Arcturus Therapeutics' quarterly financial update and pipeline progress call. Today's call will be led by Joe Payne, our President and CEO, and Dennis Mulroy, our Chief Financial Officer. Dr. Pad Chivukula, our CSO and COO, and Dr. Alan Cohen, our Chief Medical Officer, will join them for the Q&A session.

Before we begin, I would like to remind everyone that the statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by this statement.

Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factors section in our most recent Form 10-K and in subsequent filings with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made. Arcturus specifically disclaims any obligation to update such statements. And with that, I will now turn the call over to Joe.

Joseph Payne

Thank you, Neda. Good afternoon, everyone, and thank you for joining us today. The third quarter was an important period for Arcturus as we continue to advance our key clinical programs, introduced our next-generation LUNAR 2.0 delivery platform, and expanded our pipeline of mRNA therapeutics.

I'd like to begin with our liver therapeutics franchise, where we believe we are entering an exciting new phase of development. In September, we presented encouraging Phase 2 data from ARCT-810 in patients with ornithine transcarbamylase, or OTC, deficiency. At the 0.3 and 0.5 milligram per kilogram dose levels, ARCT-810 demonstrated meaningful biomarker activity, reducing and/or maintaining first morning fasting ammonia within the normal range, including during increased protein intake, and reducing glutamine levels in all participants, with the 0.5 milligram per kilogram dose achieving mean glutamine concentrations within the normal range during treatment and was generally safe and well-tolerated.

These results provide important clinical validation of our mRNA approach to liver therapeutics and contributed to the development of our next-generation OTC program called ARCT-2601. ARCT-2601 is particularly significant for Arcturus because it is the first mRNA therapeutic candidate utilizing our new LUNAR 2.0 delivery technology. Non-human primate models have consistently demonstrated strong translational predictivity for lipid nanoparticle-formulated RNA therapeutics.

This is well documented. And in non-human primates, we can measure human ornithine transcarbamylase expression. In this non-human primate model, we demonstrated a 38-fold improvement in potency using LUNAR 2.0 compared to the original LUNAR formulation that we used in ARCT-810. We believe this substantial improvement in delivery efficiency has the potential to enable lower and less frequent dosing and potentially broaden the range of diseases we can address with our mRNA therapeutics.

We shared the LUNAR 2.0 data with the FDA. Following favorable FDA feedback and clarity on the regulatory pathway from our Type C meeting in June, we now plan to initiate Phase 2 dosing of ARCT-2601 next quarter. The amended protocol will evaluate patients with OTC age 12 and older, and we expect top-line data in the second half of 2027. Central to our thesis is safe and effective delivery of mRNA.

We work in the field of RNA therapeutics where delivery is everything. And so you can understand why we are looking forward to seeing this first potential clinical top-line data for ARCT-2601, as this is the first opportunity to confirm how the 38-fold improvement we observed in non-human primates translates into patients.

Beyond OTC deficiency, LUNAR 2.0 is enabling us to expand our liver therapeutics pipeline into additional genetic diseases, including phenylketonuria, or PKU, and gout. For PKU, we are developing an investigational LUNAR 2.0-formulated mRNA therapy designed to enable the liver to produce functional PAH. This is the enzyme that is deficient in patients with PKU. Our objective is to restore PAH activity, improve phenylalanine metabolism, and ultimately address the underlying cause of the disease. We currently plan to submit an IND for this program in the second half of 2027.

Turning now to our respiratory franchise, we continue to make progress with ARCT-032 in CF. Enrollment in Cohort 4 of the Phase 2 study has accelerated as we have activated additional clinical sites in Israel and Turkey. We expect enrollment to be completed by year-end, with full Cohort 4 data planned for presentation in the second quarter of 2027. Cohort 4 is evaluating 10 mg of ARCT-032 administered by inhalation for 12 weeks in up to 20 adults with cystic fibrosis, primarily Class 1 CF subjects.

We are also pleased with the continued support of Thermo Fisher Scientific for the ARCT-032 program. Under our collaboration, a decision to advance ARCT-032 into Phase 3 would trigger significant contributions from Thermo Fisher, with that decision expected when top-line data is available before our planned Phase 2 full data presentation. With the ongoing bolus of patients enrolling in Turkey and Israel, the data generated from these patients may be included to inform that decision. Thermo Fisher receives regular updates in accordance with our agreement, and per the agreement, the decision to advance ARCT-032 into Phase 3 remains under Arcturus' control.

During the quarter, we also continued to strengthen our broader technology capabilities and AI infrastructure. We completed the acquisition of MyNeo, adding AI-driven capabilities in antigen design, mRNA optimization, and target identification. We believe integrating these capabilities with our existing mRNA design and delivery expertise can accelerate pipeline development and create additional strategic opportunities, including oncology, given MyNeo's 7 years of experience expertly designing neoantigens.

On the vaccine side of our business, COSTAVE, our self-amplifying mRNA COVID vaccine, continues to be commercialized in Japan through our partner Meiji for the 2026-2027 season. We also successfully completed the transfer of the marketing authorization holder rights for COSTAVE in both the European Union and the United Kingdom from CSL Seqirus to Arcturus. These transfers are an important step as we move toward executing commercial objectives for COSTAVE in 2027.

We also recently published the results of our Phase 1 study for our self-amplifying mRNA pandemic influenza vaccine in Nature Communications. The study demonstrated immunological benefits compared with standard of care, a favorable safety profile, and the potential for a single-dose pandemic response. Taken together, we believe these developments in our vaccine enterprise demonstrate the breadth of our mRNA platform and the evolution of Arcturus.

We now have important programs progressing across respiratory and liver therapeutics, a next-generation delivery technology with LUNAR 2.0, an expanding pipeline in genetic diseases, additional AI-enabled discovery capabilities through MyNeo, and a commercial vaccine platform led with COSTAVE. Looking ahead, we have several important milestones approaching. We expect to complete enrollment in the ARCT-032 Phase 2 study by year-end, present the full Phase 2 CF data in the second quarter of 2027, initiate Phase 2 dosing of ARCT-2601 in the first quarter of 2027, and report top-line ARCT-2601 data in the second half of 2027.

Our focus remains on disciplined execution and advancing the programs where we believe our technology can deliver meaningful differentiation in patients and long-term value for shareholders. With that, I'll turn the call over to Dennis to review our third quarter financial results.

Dennis Mulroy

Thanks, Joe, and good afternoon, everyone. Our press release issued earlier today includes financial statements for the three and nine months ended September 30, 2026, and provides a summary and analysis of year-over-year performance. We also reference our Form 10-Q for more details on our financial performance.

Cash and cash equivalents were $184.8 million as of September 30, 2026, and $230.9 million on December 31, 2025, for a decrease of $46.1 million during the first nine months of 2026. The decrease was primarily driven by cash used for ongoing clinical development activities, including the continued advancement of the company's cystic fibrosis and OTC deficiency programs, partially offset by a $12 million payment received from CSL Seqirus under the termination and settlement agreement.

Revenue was $18.3 million and $23.3 million for the three and nine months ended September 30, 2026, compared to $17.2 million and $74.8 million in the comparable periods last year. The increase in revenue for the three-month period was primarily driven by the recognition of the $12 million termination payment and the remaining deferred revenue upon termination of the CSL Seqirus collaboration, after which the company regained strategic control of COSTAVE and its broader vaccine portfolios, partially offset by lower grant revenue. The decrease for the nine-month period was primarily attributable to revenue recognized under the CSL Seqirus collaboration prior to the termination and lower BARDA grant revenue.

Research and development expenses were $17 million and $56 million for the three and nine months ended September 30, 2026, compared to $23.3 million and $87.7 million for the corresponding periods in 2025. The decreases were primarily driven by reduced clinical activity and manufacturing activities, particularly across the LUNAR COVID and BARDA programs, together with lower personnel and facility costs, as the company continues to advance its highest priority programs while maintaining a disciplined approach to capital allocation.

General and administrative expenses were $10.5 million and $30.9 million for the three and nine months ended September 30, 2026, compared with $10.4 million and $32.1 million in the comparable period last year. Overall, general and administrative expenses remained relatively consistent for the quarter, and the year-to-date decrease was primarily driven by lower payroll and benefit costs and lower share-based compensation expense, all resulting from lower headcount and partially offset by increased legal and professional fees.

Net loss was $7.4 million and $58.2 million for the three and nine months ended September 30, 2026, or a net loss per share of $0.26 and $2.05, compared to a net loss of $13.4 million and $36.7 million for the three and nine months ended September 30, 2025, or a net loss per share of $0.49 and $1.35 per share.

We continue to prioritize disciplined investment in the programs and technologies that we believe will create the greatest long-term value. We're excited with the recent acquisition of MyNeo and working with their talented team as we incorporate their strong expertise in our future strategic relationships. We continue to maintain a strong balance sheet and a cash runway of over two years through year-end 2028, allowing the company to reach important clinical and regulatory milestones in our mRNA therapeutic pipeline. With that, I'll pass the call back to Joe.

Joseph Payne

Thank you, Dennis. As you can hear, Arcturus is entering an important period with multiple potential value-creating data milestones across our pipeline with a strong balance sheet and a disciplined approach to capital allocation. So with that, operator, we're ready to take questions.

Operator

[Operator Instructions]

We will take our first question from Lili Nsongo with Leerink Partners. Please go ahead.

Fragen und Antworten

Lili Nsongo

Maybe a couple of questions related to the cystic fibrosis program. Can you remind us how many patients have been dosed to date? And I know you mentioned that you expect completion of dosing by year-end 2026, and I think the target enrollment was 20 patients. But in terms of the go/no-go decision along with top-line data, should we expect that to be a minimum of 12 weeks after the completion of the cohort, or do you plan on presenting maybe a smaller dataset first?

Joseph Payne

Thanks, Lili, for the questions. First of all, the cohort size remains consistent. It's approximately 20 people and up to 20 subjects, primarily Class 1 CF individuals. A lot of these have been coming out of Israel and Turkey, and we highlighted that. We haven't disclosed exactly the number that we've recruited to date, but we have shared our confidence in completing that enrollment by year-end.

With respect to the data presentation, this is intended to be a full dataset of all approximately 20 of these subjects when we complete enrollment of the entire fourth cohort. So it'll be a fulsome dataset that we've guided now in Q2.

Lili Nsongo

And sorry, and just to confirm, it will also be a full dataset for the top-line data that will guide the go/no-go decision?

Joseph Payne

Yes, exactly. Well, the go/no-go decision, that is expected when top-line data is available, and that will be available before, likely, our planned Phase 2 full data presentation in Q2.

Operator

We will move next with Seamus Fernandez with Guggenheim Securities. Please go ahead.

Unknown Speaker

This is Evan Wang on for Seamus Fernandez. A clarification on cystic fibrosis: with the planned presentation in 2Q, is that referring to a medical meeting if you're talking about a separate top-line readout?

And then secondly, on the OTC program and 2601, curious if there is any more color you can provide on the design there, evaluation of 1 or 2 dose levels. And now that you've guided top-line data in the second half, is that a full dataset of 3 to 6 patients? If there's anything you can share there, thank you.

Joseph Payne

Sure. So we haven't disclosed the exact method of the presentation in Q2, but it will likely be at a conference, so stay tuned for that.

With respect to the 2601 dataset, yes, we want to make sure that we have sufficient data to give us some initial confidence in the proof of concept of 2601 so that we can share that data coupled with the ARCT-810 data at the EOP2 meeting after we collect that initial dataset. Now, Alan, are you available to comment further?

Alan Cohen

Yes, Joe, I'm on the call. Thank you. So just to align and reemphasize what Joe was just saying, as it relates to the 2601 dataset, the plan is to enroll upwards of 6 subjects, and the plan would be to have the full dataset in hand in combination with the 810 data so that we could present the totality of that data at an End of Phase 2 meeting with the FDA. And then based on that data and what we believe we've observed and achieved, use that to construct and design a Phase 3 program moving forward.

Unknown Speaker

If I could ask 1 follow-up on cystic fibrosis, just to clarify when top-line press release data may be then.

Joseph Payne

Top-line data, all we've indicated will be before—for CF, yes, the top-line data will be available prior to the full data presentation. Or were you talking about the OTC data?

Unknown Speaker

Yes, the CF data, yes.

Joseph Payne

The CF data, the top-line data will be before the full data presentation.

Unknown Speaker

Okay, thank you.

Operator

Thank you. Our next question comes from Yanan Xu with Wells Fargo. Please go ahead.

Kuan-Hung Lin

This is Kuan for Yanan. On the CF program, given that this is an open-label study, I assume the company is monitoring the data in real time. So can you share with us whether you remain confident that 12 weeks would be sufficient to capture consistent benefits across patients?

Joseph Payne

Yes, we're definitely confident that 12 weeks is sufficient. And with respect to limiting real-time access to the data, Alan, maybe you can comment on both of those questions.

Alan Cohen

Sure. So just to reemphasize Joe's response, we're confident that if there's going to be an ascertainable clinical signal, 12 weeks should be sufficient using clinically relevant measures such as changes in percent predicted FEV1 based on spirometry and changes in MBW via LCI, the Lung Clearance Index, as well as the 2 quality of life measures and the changes in HRCT over that 12-week period.

In terms of the fact that it's open label, we are spending a lot of time making sure that the only people that have access to that open-label data right now are the medical people, including myself. And the access to that is really primarily for safety monitoring, not efficacy monitoring at this time. We don't want to have that data inadvertently influence how we proceed with the study and how we collect the balance of the remaining dataset. So right now, and I can say that we have had patients make it through all 12 weeks at the current regimen of 10 mg once daily by inhalation. So we're confident that based on the data that we've collected thus far, we'll be able to continue to enroll and collect that data in its totality, ideally by the end of this calendar year.

Kuan-Hung Lin

That's super helpful. And 1 quick question on OTCD. So based on your interactions with FDA on 810 so far, do you think there is clarity on a potential pivotal endpoint for the OTCD program in general? And does 2601's preclinical data have any implication on the likelihood of success on that endpoint? Thank you.

Joseph Payne

Yes, with respect to the likelihood of success, obviously we are very optimistic in light of the 38-fold improvement we saw in primates, and that this will translate positively into human data. But with respect to the endpoint clarity on 2601, maybe you can elaborate, Alan.

Alan Cohen

Sure. If history serves as an appropriate reference point, we believe that it does. Given that the drugs that are currently approved for OTC deficiency focus on stabilizing and bringing down serum ammonia levels, we certainly know that the biomarkers that we have observed changes in that we believe are clinically relevant and important—both reductions in glutamine levels and reductions in ammonia levels—will undoubtedly be the focus area that the FDA will want to be able to see continued improvements and changes in over time.

As you'll recall also, we had patients that liberalized their dietary intake of protein. So we were also able to observe that in the context of patients taking in more protein, they were still able to have reductions and stabilization in their glutamine and ammonia levels through the balance of the dataset that we collected thus far. Those are going to be the focused areas of attention that we believe the agency will want to continue to see demarcations for clinical efficacy, and will undoubtedly serve as relevant primary and secondary endpoints for a Phase 3 study of this kind.

Kuan-Hung Lin

Thank you for all the color.

Operator

Thank you. Our next question comes from Miles Minter with William Blair. Please go ahead.

Myles Minter

First one's just on 2601. I think you've previously said that the patients you'd enroll in that cohort would have elevated ammonia levels at baseline. And I know the patients you've treated with 810 prior to that have had relatively controlled ammonia levels at baseline, so just wondering how that different patient population might change your expectations for data there. And then the second one, Joe, you mentioned oncology. I'd be remiss not to ask, are you going to become a personalized neoadjuvant vaccine company? Thanks.

Joseph Payne

Sure, sure. How about if I address the cancer question first, and then Alan, you can talk about the elevated ammonia question for 2601.

Arcturus is focused on executing on our mRNA therapeutics pipeline. I want to make that clear. However, we do have technology and capabilities that can enable key players in the oncology space. With the recent acquisition of MyNeo, we now have capabilities of neoantigen design, and we have clearly a differentiated samRNA platform that is better at engaging T cells, for example, proven mRNA delivery and manufacturing.

So for these reasons, of course, we're always open to enabling key players in oncology, but I also want my message to be equivalently clear that we're focused on executing on our mRNA therapeutics pipeline this year. Alan, on to you.

Alan Cohen

Yes, and let me just try to elaborate on your question relevant to ammonia levels and glutamine levels in the study patient populations. Despite the best efforts by patients under their current standards of care, where they're significantly restricting their protein intake—and most, if not all of them, are on ammonia-binding agents like Revicti—despite their best efforts, more often than not, there are patients out there that are walking around with elevated ammonia levels on the high end of what would be considered the normal range, but as a result of that, don't feel well. They have mental cloudiness and fog, they have GI upset, they have headaches, et cetera.

What we're going to try to do in the 2601 study is, within the audience of patients that we have the pleasure of actually accessing for this trial, we're going to try to prioritize those patients whose ammonia levels and glutamine levels are running on the higher end so that the deltas can be as pronounced as possible.

But we recognize that right now, if we can just show continued reductions and stabilization of those levels, particularly as we go down in the age groups over time... The problem with the stable adults is just quality of life and functionality and their ability to just take in normal protein amounts during the day. For the kids, it's these unexpected spikes that they sometimes experience with very high ammonia levels, which cross the blood-brain barrier and cause irreversible neurological damage.

So as we go down in the age ranges from stable adults into adolescents into the younger kids, certainly the kinds of things we're going to be looking for and the stability of those changes over time will become increasingly important. But you're correct, we're going to be continuing to go into patients for whom, despite their best efforts, their baseline levels are running on the higher end of things so that we can ascertain stability and changes and reductions for both glutamine and ammonia over the study period.

Myles Minter

Thanks, guys. Thank you.

Operator

Our next question comes from Whitney Ijem with Canaccord. Please go ahead.

Whitney Ijem

Sorry to go back to this, but I did just want to try to triple clarify the CF data timing. So just to make sure I understood, is it that you've now said the go/no-go decision will be based on the top-line data that will be available before Q2? Previously, the go/no-go decision was expected for year-end, so does that imply that the top-line data is expected in the fourth quarter of this year? I just want to be really clear on that.

Joseph Payne

Yes, no. We've provided very clear goalposts here with the completion of enrollment at year-end and a full data presentation guidance for Q2. With respect to when the decision is expected, we have to recognize a couple of things: when is top-line data available and what does that include? We've already indicated that top-line data, by definition, is before our planned full data presentation. But the ongoing bolus of patients that we're enrolling in Turkey and Israel, that data generated from these patients may be included to inform that decision. It doesn't have to be, but it may be, and we just want to keep that above ground and open for everybody.

And so the timing of that data, we haven't guided the specifics, but when we have it, it provides us the opportunity to share and to provide that decision. The only new guidance that we've provided today is the data presentation timing, when the team was out at the bank conference season in September.

Whitney Ijem

Okay, got it. So the go/no-go decision might not happen before year-end, depending on that?

Joseph Payne

Yes, we have not indicated that. We heard feedback that they would like guidance on data presentation timing, and so that's what we've done.

Whitney Ijem

Okay, that makes sense. I just wanted to be clear on that. And then just my second question was on the plans for COSTAVE in the U.S. and Europe. I think there was language about moving towards commercialization next year. Is that something you plan to do on your own, or will you be seeking a partner? Thanks.

Joseph Payne

Yes, well, now that the marketing authorization holders have been shifted from CSL Seqirus to Arcturus, that provides us an opportunity to engage in additional commercial activities outside of Japan in 2027. With respect to the U.S., we've been consistent that we would pursue a partner in the U.S. region. But we've indicated that since the separation agreement with CSL, it provides us the opportunity to explore commercial activities next year in Europe and the United Kingdom, and now we have the opportunity to do so. That is correct.

Whitney Ijem

Got it. Thanks.

Joseph Payne

Thanks, Whitney.

Operator

We will move next with Adam Walsh with Roth Capital Partners. Please go ahead.

Adam Walsh

The first one is on the CF. If there is a go decision there, what would be the main hurdle to starting a Phase 3, and could that be done in 2027?

Joseph Payne

Yes, Alan can comment on that.

Alan Cohen

Yes, as Joe has just been laying out the timeline, let's just go through it real quick. We're going to enroll upwards of 20 patients in the U.S., Israel, and Turkey through the balance of this calendar year, so by the end of December. It's a 12-week study, and then we have to do data lock on last patient out and then analysis. And some of the endpoints that we're looking at, like high-resolution CT scans, take a little bit longer than things like spirometry. So we would want to have all that data in hand before we sit down with the agency to have a conversation about based on the data that we've seen and the access to the data that we intend to have available, if needed, from the CF Foundation from the REACH study, which is the normative dataset that you've heard us talk about, and that they're continuing to complete their dataset and analysis on as well.

Right now, the likelihood would be that we would have a conversation with the agency in the second half of next year. And then the likelihood of starting a study, we could probably have a protocol written and ready to go, but the ability to start that by, let me say, late December, I think it would be speculative at this point to put a flag in the ground and say absolutely. But we would certainly want to move the program forward based on positive data in a population for whom standards of care are just simply not available.

So there's a sense of urgency for this patient population. I think the agency is consistent in that feeling, and the CF Foundation, of course, is advocating strongly for rapid, safe, thoughtful studies that can be done efficiently and quickly. So we would certainly do everything we can to try to get a study started as soon as possible. I think it would be a push to say absolutely end of 2027, but I certainly think that if it's feasible, we would go for it.

Adam Walsh

My second question is also on CF. You've talked a little bit about the safety and having the open-label trial, so you're able to see the safety data. You said previously that if there were any very serious adverse events, you would publicly disclose them, and you've also said that some patients have finished the full 12 weeks. That sounds pretty encouraging given the fact that competitor programs all failed on safety and tolerability. If you could just give some thoughts and color around where we stand on safety, that'd be helpful. Thank you.

Alan Cohen

Sure, of course. What you're referring to is the most recent mention by Vertex in a recent quarterly earnings report that they had stopped advancing their own messenger RNA LNP program, and I believe they clarified that it was largely for safety concerns. What we are aware of in that study was that in order to continue to conduct that trial, they were actually requiring things like systemic steroids on a daily basis in a population that has pancreatic insufficiency already and has problems with blood glucose levels. They were also using moderate-dose inhaled long-acting bronchodilators and inhaled corticosteroids on top of that.

Fortunately, we've not needed to do that in our protocol. We're just using a bronchodilator, which most of these patients use daily as part of their standard of care for airway clearance, and we only have them doing that for the first 2 weeks. And then if they don't need the additional pre-dosing before self-administration at home, they can stop it.

Also, the other programs were unable to proceed with home administration, and our understanding was that they were requiring towards the end of their program before they discontinued it that patients were needing to come in daily for administration in the clinic setting, which obviously would be incompatible with a drug that's inhaled and that needs to be administered on a daily basis.

Once again, we're not having those problems. So currently what I can say and what I will reiterate is that of the patient population that we've currently enrolled, we have patients that have successfully completed all 12 weeks. We also have not had any severe significant safety events which the Drug Safety Monitoring Committee would either put stipulations into our ability to advance it or would ask us to stop the program or we would need to discontinue it. We have not had any of those triggers or any of those events thus far. So what I can say is that we are continuing to successfully enroll this trial as planned, and we have interested patients across the globe, which we are actively continuing to screen and enroll with the hope of getting the full dataset in by end of calendar year. Hopefully that answers your question.

Adam Walsh

It does. That's very helpful color. Thank you.

Alan Cohen

Thanks, Adam.

Operator

Thank you. Our next question comes from Mayank Mamtani with B. Riley Securities. Please go ahead.

Mayank Mamtani

1 more, if I may, on 032. If you could clarify what proportion of already dosed patients or those who plan to enroll until year-end have already been at the 15 mg escalated, or is the entire 20-patient cohort now going to be at the 10 mg dose and we don't need de-escalation?

Joseph Payne

No, we anticipate the entire 20 subjects will be primarily Class 1 CF subjects, and all of them will have received 10 mg daily for the 12-week period.

Mayank Mamtani

Great. Thank you. And then, Alan, on the REACH study learnings, it's very important to know to any magnitude and consistency of what the annual FEV1 or LCI data you're learning from there. And there's an opportunity to use that as an external control versus doing a procedural control in this population as a Phase 3. I don't know how challenging that is.

Joseph Payne

With respect to the REACH study, I'll start there and pass the mic over to Alan. But we got a detailed update on the REACH study from the CF Foundation in October at the NACFC, and it was good to hear from them that there are hundreds of participants in this REACH study over a wide age span, and it includes multiple lung function parameters, FEV1 and LCI, which we're also collecting in the present study. So this was all very encouraging. But Alan, I'll turn the time over to you to elaborate further.

Alan Cohen

Yes, and in addition... So obviously, the REACH study is being run and is completely under the control of the folks at the CF Foundation and the academic physicians that are working with them who were kind enough to meet with us during the time of the NACFC meeting in Atlanta in October and at least give us an update as to how they're progressing.

Right now, what I can say is that they've done an excellent job, and there's been very high interest across the CF community to want to participate and contribute to this natural history study. And this was intended, as you know, to make a natural history database available, which doesn't exist in the literature, so that sponsors like ourselves could have access to it and use it when sitting down with the FDA to allow us to ideally do a smaller number of patient studies and use it as a potential natural history control so that the relationship of placebo versus active drug arm could be minimized. Also the number of patients could be minimized.

The CF Foundation is also working on novel approaches for statistical direction for how these studies might be able to be conducted, recognizing that there is really a relatively small patient population that can be accessed and that would be interested in participating in a Phase 3 study. So the good news is that they're progressing. The dataset looks to be useful, it will be supportive, and we hope to be able to have access to that in the second half of next year around the time that we would be planning engagement with the FDA with our End of Phase 2 data.

A lot of things are going to need to happen between now and then. But right now, we're continuing to coordinate and work in a collaborative way with the CF Foundation and the academics running that study so that if and when we need to have that information in hand to help us with our negotiations and discussions with the agency on steps moving forward, we will have it in our pocket so that we'll be able to reference it and use it to this end. Hopefully that gives you a little bit more color and flavor for the timing and the expectations and the hopes of what we plan to do with it, as well as other sponsors.

Mayank Mamtani

Super helpful. And lastly, on 2601, has the GLP-tox study wrapped up internally, and what starting dose levels are you submitting as part of the protocol as you get ready to file the IND? That would be helpful. Thank you so much for taking the question.

Joseph Payne

With respect to 2601, we're preparing to file the IND here very shortly. We just have to include the final GLP-tox studies into that report and send it off. We've already indicated with clear guidance that we plan to initiate dosing in Q1 or next quarter for 2601. There are no other activities that we need to highlight. Pat, anything you want to add?

Padmanabh Chivukula

No. Again, the starting dose, we have not disclosed that, but it will be a dose that we previously tested.

Operator

Our next question comes from Thomas Shrader with BTIG. Please go ahead.

Thomas Shrader

Regarding 2601 dosing, 6 patients is not a lot. Do you feel like you have good agreement with the FDA? I assume you're going to try to crosswalk to the big 810 dataset. Do you have good agreement? You've had very positive interactions, it sounds like. Do you have good agreement on what you need to show, what you need to match, to say you understand those?

Joseph Payne

We had a pair of Type C meetings to discuss this program and a significant discussion on LUNAR 2.0 specifically, and we incorporated that into this IND filing. So yes, we have a high degree of confidence, but that's what the IND process is for, to formalize that. And once that's formally approved to proceed, then we can provide more details pertaining to the protocol.

With respect to our confidence on the small level of patients, this is a luxury that you have when you're utilizing a program that's potentially 38 times better, and that can be determined. It's not like 2 times better or 3 times better, where we have to power the study significantly. And it also takes into consideration that this is simply a reformulation of ARCT-810, and so that played a key role in making this a relatively smooth process. Did I address your question, Tom? I wanted to make sure.

Thomas Shrader

Yes, that makes sense. The falloff and stuff should all be the same. It's the same protein, it's only the starting levels.

1 quick vaccine question: a single-dose pandemic vaccine is pretty exciting, kind of what the world needs. Do you think there is still public money for something that has RNA in the title, or just any thoughts on how promising you could get a BARDA grant or something to move what seems on paper a fantastic vaccine?

Joseph Payne

Yes, although our focus is on mRNA therapeutics, we do acknowledge the non-dilutive money associated with business development type deals in the vaccine enterprise. And one of those types of deals that is more relevant is pandemic preparedness contracts and deals. Sitting on a technology that's ideal for the next pandemic and helping countries prepare for that is something that will continue to provide that opportunity to different countries going forward.

And you're spot on: self-amplifying mRNA, yet another example of a single administration to protect against pandemic bird flu. That's significant data that was quietly shared today, and hopefully it doesn't become relevant in the future, but it does showcase the breadth of our platform and the capability of self-amplifying mRNA not only in infectious disease vaccines, but also in oncology, which is a hotter topic now in the mRNA field.

Thomas Shrader

Totally agree. Thank you.

Joseph Payne

Thank you.

Operator

We will move next with Yale Jen with Laidlaw & Company. Please go ahead.

Yale Jen

I just want to go back to the earlier question regarding the natural history study by the CF Foundation. I understand that it is not completed yet, but at this time with the data you have already seen, as well as your knowledge about the current study you are conducting, putting those 2 together, does that increase your confidence for the potential success of ARCT-032 at this moment? And then I'll follow up.

Joseph Payne

Well, that's the entire purpose of the REACH study: to enable sponsors. The CF Foundation is trying to help companies like Arcturus get drugs approved for Class 1 CF. This is a completely untreated population, and we're first movers in this area, and they're trying to help us. The CF Foundation came up with this REACH study to help us for this purpose: to provide some sort of baseline control, a normative study on what happens to Class 1 subjects over time, a natural history-like study. So the short answer to your question is yes, this is going to very likely help us, especially if we're fortunate to advance this into a Phase 3 study, then it can be leveraged at that time even more so. So the short answer is yes.

Yale Jen

Okay, maybe 1 follow-up here, which is the PKU program that you have not talked too much about. Should we be able to see some preclinical data over the next period of time and start to let investors understand a little bit more about that program as well? Thanks.

Joseph Payne

We indicated today that we're guiding an IND filing for the PKU program in the second half. As part of that process, there's a copious amount of preclinical data that's included in the filing, and that will provide opportunities for us to share that. But Pat, do you want to provide some color?

Padmanabh Chivukula

Yes, again, a few weeks ago during the science day, I think we did present a little bit of data about our optimization process in chimera in terms of RNA design. Once we select the candidate, we will be doing a more thorough study, looking at duration, looking at potency, and at some point, yes, absolutely, we will be sharing that publicly as well.

Joseph Payne

And 1 thing I'd like to add: I'm glad you asked that question in closing because I just want to commend Pat and his team. It's not just innovations around the delivery technology, but extending the half-life and the durability of expression of the mRNA molecule as well. So there's a lot of innovation at Arcturus that we're very proud of, and I wish we had more time to highlight that on this call, so thank you for that question.

Yale Jen

Okay, great. Thanks.

Operator

There are no further questions in queue. I will now turn the meeting back to Joe for closing remarks.

Joseph Payne

Thanks, everyone, for participating on the call. Don't hesitate to reach out to our team for any remaining questions. We'll get back to you as soon as we can. Thanks again. Thank you.

Operator

This brings us to the end of today's meeting. We appreciate your time and participation.

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