ARCT-810 Overview - Arcturus is a commercial mRNA medicines company with a pipeline of multiple therapeutic candidates in advanced clinical trial development[7] - ARCT-810 aims to restore OTC enzyme function, potentially preventing neurological damage and the need for liver transplantation in Ornithine Transcarbamylase (OTC) Deficiency patients[9] - ARCT-810 has received Orphan Drug Designation (FDA), Orphan Medicinal Product Designation (EMA), Fast Track Designation (FDA), and Rare Pediatric Disease Designation (FDA)[14, 15, 16, 17] Clinical Trial Results - European Phase 2 study (N = 8; 6 ARCT-810 / 2 placebo) is completed, and the U S Phase 2 study (N = 3 completed to date) is ongoing[20] - Combined analysis of both Phase 2 studies showed mean glutamine levels decreased significantly (N = 8, p-value = 0 0055)[25] - In the Phase 2 Open-label U S Study, mean glutamine levels decreased significantly (N = 3, p-value = 0 004), with all subjects achieving normal levels after three administrations[28] - Interim Phase 2 data from the U S Open Label Study (N = 3) showed a mean RUF (relative ureagenesis function) increase of +14 7% from baseline to 28 days post-fifth dose, from 29 0% (SD 9 1%) to 43 7% (SD 21 7%), which is statistically significant (p-value = 0 026)[31] Safety and Tolerability - ARCT-810 was generally safe and well-tolerated in Phase 2 studies at all tested dose levels, comprising 40 participants to date, including 20 OTC deficient participants[34, 35] KOL Insights - Glutamine rises earlier than ammonia in OTC deficiency and has lower variability, making it a reliable indicator of urea cycle stress[47] - 15N-Ureagenesis assay directly reflects cycle function, providing a clear readout of therapeutic efficacy[47]

Summary of Arcturus Therapeutics KOL Presentation on ARCT-810 Phase II Interim Data for OTC Deficiency Company Overview - **Company**: Arcturus Therapeutics - **Headquarters**: San Diego - **Focus**: mRNA medicines, specifically targeting rare liver diseases like ornithine transcarbamylase (OTC) deficiency [5][6] Industry Context - **Industry**: Biotechnology, specifically in the development of mRNA therapeutics for rare diseases - **Condition**: OTC deficiency is the most common urea cycle disorder with significant unmet medical needs [6][7] Key Points from the Presentation 1. **ARCT-810 Overview**: - ARCT-810 is an mRNA therapeutic designed to replace dysfunctional OTC enzymes, improving urea cycle activity, detoxifying ammonia, and potentially eliminating the need for liver transplants [6][7][8] - It utilizes Arcturus' proprietary lunar delivery platform for effective delivery to hepatocytes [7] 2. **Regulatory Designations**: - ARCT-810 has received multiple designations: orphan drug designation, orphan medicinal product designation, fast track designation, and rare pediatric disease designation [8] 3. **Phase II Study Design**: - Two Phase II studies were conducted: one in the US and one in Europe, focusing on safety, tolerability, and biomarker assessments [11][12] - The US study enrolled patients with more severe disease, while the European study included patients with stable disease [12] 4. **Biomarker Results**: - **Plasma Glutamine**: - In the European study, mean glutamine levels decreased from high to normal during treatment and began to rise again after four weeks post-treatment [13][14] - In the US study, glutamine levels normalized after three doses and remained normal for approximately twenty days [14] - **Ureagenesis Function**: - The new N15 assay showed significant increases in relative ureagenesis function (RUF) post-treatment, with a mean increase of 14.7% [16][17] - Two subjects achieved RUF levels above 50%, indicating clinically meaningful improvements [17] - **Ammonia Levels**: - Ammonia levels remained stable and within normal ranges after treatment, supporting the favorable glutamine and ureagenesis data [18] 5. **Safety Profile**: - The safety database included 40 participants, indicating that ARCT-810 was generally safe and well-tolerated [19] - No serious infusion-related reactions were reported, and adverse events were manageable [19][20] 6. **Next Steps**: - Arcturus plans to complete the ongoing Phase II US study and engage with regulatory agencies for a multi-biomarker driven pivotal trial [68][69] Additional Insights - **Clinical Implications**: - The KOLs emphasized the importance of normalizing diet and reducing the need for ammonia scavengers as key success metrics for OTC therapies [78][80] - mRNA therapies are viewed as a potential alternative to liver transplants, especially for severe cases [100][101] - **Comparison with Other Therapies**: - ARCT-810 is positioned as a more effective solution compared to existing ammonia scavengers, which do not restore urea cycle function [87][88] Conclusion - The interim data for ARCT-810 demonstrates promising results in reducing glutamine levels and improving urea cycle function, with a favorable safety profile. The company is poised to advance its clinical development and regulatory strategy to address the significant unmet needs in OTC deficiency treatment [67][68]

Core Viewpoint - Arcturus Therapeutics (ARCT) has seen a 7.5% increase in share price over the past four weeks, closing at $12.81, with analysts suggesting a potential upside of 371.4% based on a mean price target of $60.38 [1][12]. Price Targets and Analyst Estimates - The mean price target is derived from eight short-term estimates, with a standard deviation of $33.97, indicating variability among analysts [2]. - The lowest price target of $32 suggests a 149.8% increase, while the highest target of $140 indicates a potential surge of 992.9% [2]. - A low standard deviation among price targets suggests a strong consensus among analysts regarding the stock's price direction [9]. Earnings Estimates and Analyst Agreement - Analysts show strong agreement in revising earnings estimates upward, which is a positive indicator for potential stock upside [4][11]. - The Zacks Consensus Estimate for the current year has increased by 42.1% over the past month, with four estimates rising and no negative revisions [12]. - ARCT holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate factors [13]. Caution on Price Targets - While price targets are a common metric for investors, relying solely on them can be misleading, as they often do not accurately predict stock price movements [3][7][10]. - Analysts may set overly optimistic price targets due to business incentives, which can inflate expectations [8].

Core Viewpoint - Arcturus Therapeutics (ARCT) shows significant upside potential based on Wall Street analysts' short-term price targets, with a mean target of $65.43 indicating a 503.6% increase from the current price of $10.84 [1] Price Targets and Estimates - The mean estimate consists of seven short-term price targets with a standard deviation of $34.14, indicating variability among analysts. The lowest estimate of $44 suggests a 305.9% increase, while the highest estimate predicts a surge of 1191.5% to $140 [2] - A low standard deviation in price targets indicates a high degree of agreement among analysts regarding the stock's price movement direction and magnitude [9] Earnings Estimates and Analyst Sentiment - Analysts are optimistic about ARCT's earnings prospects, as indicated by a positive trend in earnings estimate revisions. The Zacks Consensus Estimate for the current year has increased by 28.3% over the last 30 days, with four estimates moving higher and no negative revisions [11][12] - ARCT holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates, suggesting a strong potential upside in the near term [13] Caution on Price Targets - While the consensus price target is a commonly referenced metric, relying solely on it for investment decisions may not be prudent due to historical inaccuracies in analysts' price targets [3][7][10] - Analysts often set optimistic price targets influenced by business relationships, which can lead to inflated expectations [8]

分组1 - Arcturus Therapeutics reported a quarterly loss of $0.52 per share, significantly better than the Zacks Consensus Estimate of a loss of $1.58, representing an earnings surprise of 67.09% [1] - The company posted revenues of $29.38 million for the quarter ended March 2025, exceeding the Zacks Consensus Estimate by 3.10%, but down from $38.01 million year-over-year [2] - Over the last four quarters, Arcturus has surpassed consensus EPS estimates three times and topped revenue estimates twice [2] 分组2 - The stock has underperformed, losing about 35.3% since the beginning of the year, compared to a decline of 3.8% in the S&P 500 [3] - The current consensus EPS estimate for the upcoming quarter is -$1.77 on revenues of $21.84 million, and for the current fiscal year, it is -$6.44 on revenues of $96.5 million [7] - The Zacks Industry Rank for Medical - Biomedical and Genetics is in the top 34% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8]

Financial Data and Key Metrics Changes - For Q1 2025, revenues were $29.4 million, down from $38 million in Q1 2024, primarily due to lower development milestone revenues from the CSL collaboration as the COVID vaccine transitions to commercialization [19][20] - Research and development expenses decreased to $34.9 million from $53.6 million year-over-year, driven by lower manufacturing costs, with expectations for further declines in the second half of fiscal year 2025 [20][21] - General and administrative expenses were $11.3 million, down from $14.9 million in the same period last year, attributed to reduced share-based compensation costs [21] - The net loss for Q1 2025 was approximately $14.1 million, or $0.52 per diluted share, compared to a net loss of $3 million, or $1 per diluted share, in Q1 2024 [21] Business Line Data and Key Metrics Changes - The mRNA therapeutics pipeline is being prioritized, with significant focus on the CF and OTC programs, while the COVID vaccine program is transitioning to commercialization [11][18] - The ARCT032 program for cystic fibrosis is in Phase II, with enrollment expected to complete by the end of 2025, and interim data anticipated in mid-2025 [7][10] - The ARCT810 program for OTC deficiency is also in Phase II, with interim data expected in Q2 2025 [8][10] Market Data and Key Metrics Changes - The company received an initial milestone payment from CSL related to the EU approval of the COVID vaccine, with further payments anticipated as the program progresses [11][19] - The company is preparing for a Marketing Authorization Application in the UK in Q2 2025 and a BLA filing in the US in Q3 2025 [12] Company Strategy and Development Direction - The company has made a strategic decision to focus resources on mRNA therapeutics, particularly CF and OTC programs, due to current market conditions and regulatory uncertainties [18][19] - The STAR self-amplifying mRNA platform continues to receive positive feedback from publications, enhancing the company's position in the market [12][14] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming clinical data from the CF and OTC programs, highlighting the potential for significant advancements in treatment options [22][23] - The company remains committed to maintaining a strong financial position, with a cash runway extended into 2028, allowing for the achievement of near-term milestones [21][22] Other Important Information - The company is utilizing a newly developed 15N ureogenesis assay to monitor the effects of ARCT810 in clinical development, which is expected to provide valuable data [10][18] - Long-term data from the COVID vaccine trial suggests a favorable safety profile, with no reports of myocarditis or pericarditis [14] Q&A Session Summary Question: Can you provide more details on the changes made to extend the cash runway and potential incoming cash flows? - Management indicated that tough decisions were made regarding cost reductions and focusing on critical programs, which contributed to extending the cash runway [27][28] Question: What milestones should we expect related to the UK and US approvals for the COVID vaccine? - There are no milestones associated with the UK or US approvals; however, a milestone is anticipated with the first US revenues from the COVID vaccine, expected in 2028 [30][31] Question: What is the expected size of the initial interim cohort for ARCT032 and the bar for success? - The interim data set is expected to include 6 to 9 subjects, with a bar for success set at a 3% improvement in lung function [35][36] Question: How does ARCT032 differ from competitor programs in terms of tolerability? - The company highlighted its exclusive LUNAR lipid nanoparticle delivery technology and the high purity of its mRNA constructs as key differentiators [42][43] Question: What are the expected biomarkers for the OTC program? - Management confirmed that glutamine, orotic acid, and other biomarkers will be measured to assess the effectiveness of the treatment [86][87]

Financial Data and Key Metrics Changes - For Q1 2025, revenues were $29.4 million, down from $38 million in Q1 2024, primarily due to lower development milestone revenues from the CSL collaboration as the COVID vaccine transitions to commercialization [17][18] - Research and development expenses decreased to $34.9 million from $53.6 million year-over-year, driven by lower manufacturing costs, partially offset by increased costs for CF and OTC programs [18][19] - General and administrative expenses were $11.3 million, down from $14.9 million in the same period last year, mainly due to reduced share-based compensation costs [19][20] - The net loss for Q1 2025 was approximately $14.1 million, or $0.52 per diluted share, compared to a net loss of $3 million, or $1 per diluted share, in Q1 2024 [20] Business Line Data and Key Metrics Changes - The mRNA therapeutics pipeline is being prioritized, with significant focus on CF and OTC programs, while the COVID vaccine program is transitioning to commercialization [10][16] - The company expects to complete Phase II enrollment for ARCT032 by the end of 2025 and provide interim data for the first two cohorts in mid-2025 [6][9] - The ARCT-810 program for OTC deficiency is also progressing, with interim data expected in Q2 2025 [7][9] Market Data and Key Metrics Changes - The company received an initial milestone payment from CSL related to the EU approval of the COVID vaccine, Costave, and anticipates further milestone payments as the program progresses [10][17] - The company is preparing for a Marketing Authorization Application (MAA) filing in the UK in Q2 2025 and a U.S. BLA filing in Q3 2025 [11] Company Strategy and Development Direction - The company has made a strategic decision to focus resources on mRNA therapeutics, particularly CF and OTC programs, due to current market conditions and regulatory uncertainties [10][16] - The STAR self-amplifying mRNA platform continues to receive positive feedback from publications, enhancing the company's position in the market [11][13] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming clinical data from CF and OTC programs, indicating a strong cash runway extending into 2028 [21] - The company remains committed to advancing its therapeutic programs and believes that the science will support its regulatory interactions [100] Other Important Information - The company has received FDA Fast Track designation for ARCT2304, its mRNA vaccine candidate for pandemic influenza A [14] - The 15N Ureogenesis Assay is expected to provide important data for monitoring the effect of ARCT-810 in clinical development [9][108] Q&A Session Summary Question: Can you provide more details on extending the cash runway and potential cash flows? - Management indicated that focusing on critical programs and making cost reductions contributed to extending the cash runway, with a conservative approach to cash burn forecasts [26][27] Question: What milestones should we expect related to UK and U.S. approvals for the COVID vaccine? - There are no milestones associated with UK or U.S. approvals; however, a milestone is anticipated with the first U.S. revenues from Costave, expected in 2028 [31][60] Question: What is the expected size of the interim cohort for ARCT032? - The interim data set is expected to include 6 to 9 subjects, with a bar for success set at a 3% improvement in lung function [36][37] Question: How does ARCT032 differ from competitor programs? - The key differentiators include the exclusive LUNAR lipid nanoparticle delivery technology and the high purity of the mRNA construct, which may enhance safety and tolerability [44][45] Question: What are the thresholds for FEV1 improvement in the CF program? - A 3% improvement in FEV1 is considered a significant threshold, with higher improvements potentially allowing for smaller Phase III trial sizes [86][87] Question: Will other biomarkers be measured in the OTC program? - In addition to glutamine, orotic acid and other amino acids will also be measured as part of the biomarker strategy [88][89]

Financial Performance - Total revenue for Q1 2025 was $29.382 million, a decrease of 22.8% compared to $38.012 million in Q1 2024[16] - Collaboration revenue decreased to $25.477 million in Q1 2025 from $32.598 million in Q1 2024, representing a decline of 21.7%[16] - The net loss for Q1 2025 was $14.076 million, compared to a net loss of $26.817 million in Q1 2024, reflecting a 47.6% improvement[16] - Revenue for the three months ended March 31, 2025, was $29.4 million, a decrease of $8.6 million or 23% compared to $38.0 million in the same period of 2024[100][102] - Operating expenses decreased by 32% to $46.2 million for the three months ended March 31, 2025, down from $68.4 million in the same period of 2024[104] Cash and Assets - Cash and cash equivalents at the end of Q1 2025 were $216.948 million, down from $237.028 million at the end of 2024[14] - Total assets decreased to $331.785 million in Q1 2025 from $344.069 million at the end of 2024[14] - Cash and cash equivalents totaled $216.9 million as of March 31, 2025, down from $288.4 million as of March 31, 2024[54] - Cash and cash equivalents, including restricted cash, totaled $273.8 million as of March 31, 2025[114] Research and Development - Research and development expenses for Q1 2025 were $34.893 million, down 34.9% from $53.573 million in Q1 2024[16] - Total research and development expenses for the three months ended March 31, 2025, were $34.9 million, down from $53.6 million in the same period of 2024, reflecting a reduction of 34.9%[77] - The LUNAR-CF program for cystic fibrosis has progressed to a Phase 2 multiple ascending dose study, with dosing initiated in December 2024[101] - The FDA granted Fast Track Designation for ARCT-2304, recognizing its potential to address unmet medical needs for H5N1 influenza prevention[97] Collaboration and Milestones - The Company received a $200 million upfront payment from CSL Seqirus and is eligible for over $1.3 billion in development milestones and up to $3 billion in commercial milestones[38] - The Company achieved an initial $8 million milestone related to the CSL Collaboration Agreement in Q1 2025, along with a $7 million development milestone[38] - The company achieved approximately $488.1 million in total upfront payments and milestones from CSL Seqirus, including $15.0 million in the current quarter[114] - CSL Seqirus received exclusive global rights to develop mRNA vaccines, with an upfront payment of $200 million and potential milestones exceeding $1.3 billion[116] Financial Position and Liabilities - Total liabilities decreased to $98.026 million in Q1 2025 from $103.091 million at the end of 2024[14] - The company’s accumulated deficit increased to $462.883 million as of March 31, 2025, from $448.807 million at the end of 2024[14] - The remaining available funding from the BARDA grant, net of revenue earned, was $36.1 million as of March 31, 2025[49] - The remaining available funding from the BARDA Contract as of March 31, 2025, was $36.1 million, net of revenue earned[123] Internal Controls and Compliance - A material weakness in internal control over financial reporting was identified, specifically related to IT general controls affecting financial reporting processes[143] - The company plans ongoing remediation efforts to address the identified material weakness and strengthen the overall financial control environment[144] - The company is in the process of implementing remediation activities to strengthen ITGCs and controls related to accounting for collaboration arrangements, expecting completion in fiscal year 2025[146] - Management concluded that there were no changes in internal controls over financial reporting that materially affected the company during the periods covered by the Quarterly Report[147] Legal and Regulatory Matters - The company is subject to various legal proceedings and claims that arise in the ordinary course of business, which are inherently uncertain[150] - There have been no material changes from the risk factors described in the Annual Report on Form 10-K for the fiscal year ended December 31, 2024[151] - The company is committed to compliance with the Securities Exchange Act of 1934[164] Shareholder Information - The company reported a weighted-average share count of 27.107 million for Q1 2025, compared to 26.879 million for Q1 2024[16] - As of March 31, 2025, a total of 1,177,945 shares remain available for future issuance under the 2019 Omnibus Equity Incentive Plan[62] - As of March 31, 2025, the Company had 127,419 shares available for future issuance under the 2021 Inducement Equity Incentive Plan, which was reduced from an initial 1,000,000 shares[63] Debt and Financing Activities - The Company received $15 million in proceeds from debt financing during Q1 2025[21] - The Company drew down $15 million from its credit agreement with Wells Fargo in March 2025, which was repaid in April 2025[59] - Net cash provided by financing activities was $15.2 million for Q1 2025, compared to $2.2 million in Q1 2024, mainly due to $15 million in debt proceeds[132] - The company has pledged $55 million in cash as collateral under the Wells Fargo credit agreement[122]

Financial Performance - Revenues for Q1 2025 were $29.4 million, down from $38.0 million in Q1 2024, primarily due to lower milestone revenues from the CSL collaboration[5] - The net loss for Q1 2025 was approximately $14.1 million, or ($0.52) per diluted share, compared to a net loss of $26.8 million, or ($1.00) per diluted share in Q1 2024[9] - Total revenue for Q1 2025 was $29.382 million, a decrease of 22.7% from $38.012 million in Q4 2024[18] - Collaboration revenue decreased to $25.477 million in Q1 2025 from $32.598 million in Q4 2024, representing a decline of 21.7%[18] - Grant revenue for Q1 2025 was $3.905 million, down from $5.414 million in Q4 2024, a decrease of 28.0%[18] - Net loss for Q1 2025 was $14.076 million, an improvement from a net loss of $26.817 million in Q4 2024[18] - Net loss per share for Q1 2025 was $0.52, compared to $1.00 in Q4 2024[18] - Comprehensive loss for Q1 2025 was $14.076 million, consistent with the net loss[18] Operating Expenses - Total operating expenses decreased to $46.2 million in Q1 2025 from $68.4 million in Q1 2024[6] - General and administrative expenses were $11.3 million in Q1 2025, compared to $14.9 million in Q1 2024, attributed to reduced share-based compensation costs[8] - Total operating expenses were $46.208 million in Q1 2025, down 32.5% from $68.424 million in Q4 2024[18] - Research and development expenses were $34.9 million in Q1 2025, down from $53.6 million in the same period last year, driven by lower manufacturing costs[7] - Research and development expenses decreased to $34.893 million in Q1 2025 from $53.573 million in Q4 2024, a reduction of 34.8%[18] Cash and Financial Position - Cash, cash equivalents, and restricted cash totaled $273.8 million as of March 31, 2025, down from $293.9 million on December 31, 2024[10] - The cash runway is expected to extend into 2028 following the re-allocation of resources to the therapeutics pipeline[2] - The company reported a net finance income of $2.771 million in Q1 2025, down from $4.016 million in Q4 2024[18] Clinical Development - Enrollment in the Phase 2 cystic fibrosis study (ARCT-032) is expected to be completed by year-end 2025, with interim data anticipated in mid-2025[3] - The company received initial milestone payment from CSL related to the EU approval of KOSTAIVE®, a self-amplifying mRNA COVID-19 vaccine[4] - The company expects to file for regulatory approval of KOSTAIVE in the UK in Q2 2025 and in the US in Q3 2025[4] Shareholder Information - Weighted-average shares outstanding increased to 27.107 million in Q1 2025 from 26.879 million in Q4 2024[18]

Core Viewpoint - The market anticipates a year-over-year decline in earnings for Arcturus Therapeutics despite an increase in revenues, with the actual results being crucial for stock price movement [1][2]. Earnings Expectations - Arcturus Therapeutics is expected to report a quarterly loss of $1.13 per share, reflecting a year-over-year change of -13% [3]. - Revenues are projected to be $38.08 million, which is a slight increase of 0.2% from the previous year [3]. Estimate Revisions - The consensus EPS estimate has been revised down by 5% over the last 30 days, indicating a bearish sentiment among analysts [4]. - The Most Accurate Estimate for Arcturus is lower than the Zacks Consensus Estimate, resulting in an Earnings ESP of -9.49% [10][11]. Earnings Surprise Prediction - The Zacks Earnings ESP model suggests that a positive or negative reading indicates the likely deviation of actual earnings from the consensus estimate, with a strong predictive power for positive readings [6][7]. - Stocks with a positive Earnings ESP and a Zacks Rank of 1, 2, or 3 have historically shown a nearly 70% chance of a positive surprise [8]. Historical Performance - In the last reported quarter, Arcturus was expected to post a loss of $0.34 per share but instead reported a loss of $1.11, resulting in a surprise of -226.47% [12]. - Over the past four quarters, Arcturus has beaten consensus EPS estimates three times [13]. Conclusion - Arcturus Therapeutics does not appear to be a strong candidate for an earnings beat based on current estimates and rankings, suggesting caution for investors [16].