Summary of Aligos Therapeutics Conference Call Company Overview - **Company**: Aligos Therapeutics - **Industry**: Biotechnology, focusing on liver and viral diseases - **Mission**: To improve patient outcomes by developing best-in-class therapies for chronic hepatitis B virus (HBV) infection and metabolic dysfunction-associated steatohepatitis (MASH) [1][34] Key Drug: ALG-000184 - **Type**: Capsid assembly modulator for HBV - **Discovery**: Originated from research by Professor Raymond Schinazi at Emory University, known for developing several antiviral drugs [3][4] - **Mechanism of Action**: - Binds to HBV core protein, preventing encapsulation of pregenomic RNA, thus blocking DNA production [4][16] - Evokes a secondary mechanism that reduces CCC DNA, a long-lived viral reservoir [6][17] - **Pharmacokinetics**: - Improved from 5% to 80% oral bioavailability [5] - Demonstrated significant reductions in HBV DNA and surface antigens in clinical studies [6][7] Clinical Data and Efficacy - **Phase 1B Study**: - 96-week data showed no emergence of drug resistance, allowing for potential monotherapy [10][11] - Achieved 100% of E antigen negative patients below 10 international units of HBV DNA at week 48, compared to historical data of around 20% for standard treatments [21][22] - **Endpoints**: - Primary endpoint for monotherapy is chronic suppression of HBV DNA [18][19] - Importance of achieving below 10 international units for better long-term outcomes, including reduced liver cancer progression [20][22] Future Development: B Supreme Study - **Design**: Ongoing phase 2 study comparing ALG-000184 with TDF in both E positive and E negative patients [24][25] - **Goals**: - Superiority in HBV DNA endpoints and antigen reductions [27][28] - Paired biopsies to quantify integration events and CCC DNA levels [28] Competitive Landscape - **Positioning**: ALG-000184 aims to become the standard of care for chronic HBV suppression and a backbone for functional cure regimens [30][31] - **Antisense Oligonucleotide Program**: Aligos is developing its own ASO program to complement ALG-000184, enhancing potential treatment options [31] Other Drug: ALG-055009 for MASH - **Mechanism**: Targets metabolic dysfunction in liver disease, showing significant fat reduction in phase 2A studies [36][37] - **Combination Potential**: Compatible with GLP-1 therapies, enhancing fat reduction and weight loss [38][39] Upcoming Milestones - **2025-2027 Timeline**: - Final data from the 96-week study of ALG-000184 to be presented at AASLD [41] - Interim readout from the B Supreme study in 2026 [41] - Partnership announcement for ALG-055009 expected early next year [42] Conclusion - Aligos Therapeutics is positioned to address significant unmet needs in the treatment of HBV and MASH, with promising clinical data and a robust pipeline aimed at improving patient outcomes in these areas [40][43]

Financial Data and Key Metrics Changes - The company ended the second quarter with $355 million in cash, cash equivalents, and marketable securities, expected to fund operations through mid-2028 [42] - Total revenue for the quarter was $13.8 million, driven by collaborations with ACADIA and Biogen, with expectations for revenue from Biogen to increase [43] - The net loss for the quarter was $23.5 million, or $0.40 per share, slightly improved from the prior year despite a $6.9 million year-over-year increase in operating expenses [43] Business Line Data and Key Metrics Changes - The Phase III EMPORER study for Dravet syndrome is underway, with the first patient dosed and strong enrollment anticipated due to high awareness and urgent patient need [5][21] - The company has advanced STK002 into Phase I clinical development for autosomal dominant optic atrophy (ADOA), indicating a growing pipeline [7][35] Market Data and Key Metrics Changes - The collaboration with Biogen enhances the company's ability to deliver zurivanersen globally and strengthens its balance sheet [8] - The company estimates approximately 13,000 patients currently living with ADOA across key geographies, indicating a significant market opportunity [38] Company Strategy and Development Direction - The key priority remains the development of zurivanersen for Dravet syndrome, aiming to deliver a disease-modifying medicine [4] - The company is focused on establishing internal capabilities and enhancing leadership to support growth and value creation [9] - The strategic collaboration with Biogen is expected to provide global expertise in commercializing high-value disease-modifying medicines [8] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the long-term potential of zurivanersen to modify the course of Dravet syndrome, supported by positive data from ongoing studies [7][31] - The company is committed to advancing zurivanersen to patients as quickly as possible, leveraging breakthrough therapy designation from the FDA [50][52] Other Important Information - The company has seen a favorable safety profile for zurivanersen, with no clinical manifestations associated with elevated CSF protein levels observed in patients [32][94] - The Vineland-three assessment is being used to measure changes in cognition and behavior in patients with Dravet syndrome, with significant improvements noted over time [28][30] Q&A Session Summary Question: Can you help us understand the potential for accelerated approval for zurivanersen? - Management confirmed that zurivanersen has breakthrough designation and they are collecting further data to discuss with the FDA in the second half of the year [50][52] Question: What is the magnitude of cognition and behavior improvements in the Vineland-three data? - Management noted that changes in cognition and behavior are clinically meaningful, with caregivers identifying even small improvements as significant [62][63] Question: Can you explain the data used to inform the powering assumptions for the Phase III EMPOR study? - Management indicated that data from previous studies and natural history studies were used to inform the powering assumptions, ensuring robust statistical significance [70][72] Question: Are there trends in seizure reduction and neurodevelopmental benefits among different age groups? - Management acknowledged variability in responses but emphasized the importance of treating younger patients to potentially change the course of their development [86][87] Question: Can you discuss the higher incidence of CSF protein elevations in the OLE study? - Management clarified that elevated CSF protein levels are a laboratory finding and have not been associated with clinical effects, supporting the safety profile for moving into Phase III [92][94] Question: What prompted the decision to explore STK-two in ADOA? - Management explained that a thorough evaluation of the opportunity in ADOA, including promising nonhuman primate data, led to the decision to pursue clinical studies [98][100]

Core Insights - Ultragenyx Pharmaceutical reported a second-quarter 2025 loss of $1.17 per share, which is an improvement from a loss of $1.52 per share in the same quarter last year and better than the Zacks Consensus Estimate of a loss of $1.27 [1][5] - Total revenues for the quarter reached $166.5 million, reflecting a 13% year-over-year increase, driven primarily by higher product sales, and surpassing the Zacks Consensus Estimate of $162 million [1][5] Revenue Breakdown - Crysvita generated total revenues of $120.4 million, up 6% year over year, with contributions of $79 million from North America, $35 million from Latin America and Turkey, and $7 million from Europe [3] - Mepsevii product revenues increased by 35% year over year to $8.3 million, while Dojolvi revenues rose 20% to $23.2 million due to new patient demand [4] - Evkeeza recorded sales of $14.6 million in the first quarter, showing significant growth as the drug continues to be launched in territories outside the United States [4] Financial Guidance - The company reaffirmed its 2025 financial guidance, expecting total revenues between $640 million and $670 million, which represents a growth of approximately 14-20% compared to 2024 [9] - Crysvita revenues are anticipated to be in the range of $460-$480 million, reflecting a year-over-year increase of 12-17%, while Dojolvi revenues are expected to be between $90 million and $100 million, up 2-14% year over year [9] Operating Expenses - Operating expenses for the quarter were $274.4 million, a 4% increase year over year, attributed to higher investments in late-stage pipeline programs and marketing costs for approved drugs [7] - Research and development expenses were $164.7 million (up 2%), selling, general and administrative expenses were $86.6 million (up 7%), and cost of sales was $23 million (up 8%) [7] Pipeline Updates - The FDA issued a complete response letter for Ultragenyx's biologics license application for UX111, requesting additional information related to manufacturing processes, which the company plans to address promptly [11][12] - The company is also developing GTX-102 for Angelman syndrome, which received Breakthrough Therapy designation, with data expected in the second half of 2026 [14] - Ultragenyx plans to submit a BLA for DTX401, a gene therapy for glycogen storage disease type Ia, in the fourth quarter of 2025 [15]