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]

Core Insights - Assembly Biosciences, Inc. announced positive topline results from a Phase 1b study of ABI-4334, demonstrating favorable safety, tolerability, and pharmacokinetics for once-daily oral dosing in chronic hepatitis B virus (HBV) infection [1][3][4] Efficacy and Safety - In the 400 mg cohort, mean plasma HBV DNA reductions of 3.2 logs IU/mL were observed over 28 days, consistent with the 150 mg cohort, indicating effective viral replication inhibition [1][2][10] - ABI-4334 showed a favorable safety profile with no serious adverse events reported, and only two grade three treatment-emergent lab abnormalities were noted, both of which resolved [8][9] Pharmacokinetics - The pharmacokinetic data indicated that ABI-4334 maintained exposure levels significantly above those required for potent antiviral activity and inhibition of cccDNA formation, supporting its once-daily dosing regimen [4][10] - Slightly higher than dose-proportional increases in clinical pharmacokinetic exposures were observed from the 150 mg to the 400 mg dose [10] Collaboration and Future Steps - The completion of the trial triggers an opt-in point for Gilead Sciences, Inc. to review the option data package for potential exclusive licensing of ABI-4334 for further development and commercialization [1][5] - Discussions regarding the next steps for ABI-4334 will be supported by the trial results as Gilead evaluates its options [3][5]