Summary of Aligos Therapeutics Conference Call Company Overview - **Company**: Aligos Therapeutics (NasdaqCM:ALGS) - **Focus**: Development of therapies for liver and viral diseases, specifically targeting chronic hepatitis B virus (HBV) and metabolic dysfunction-associated steatohepatitis (MASH) [1][2] Key Points on Chronic Hepatitis B Virus (HBV) - **Prevalence**: HBV is the largest chronic viral infection globally, affecting approximately three times more people than HIV [3] - **Current Treatments**: Standard care involves nucleoside and nucleotide analogs, which block virus replication but do not eliminate the long-lived cccDNA form of the virus [3][4] - **Clinical Outcomes**: A study in Taiwan showed that after five years of treatment with nucleoside analogs, 4% of patients developed liver cancer, and 5% experienced liver decompensation [4] - **Need for Better Therapies**: Deep and rapid suppression of HBV is essential to prevent liver disease and cancer, highlighting the limitations of current therapies [5] PEVI/PHOSCOVIR Development - **Lead Program**: PEVI is a next-generation capsid assembly modulator designed to treat chronic HBV [2] - **Mechanism of Action**: PEVI blocks the encapsulation of pre-genomic RNA and reduces cccDNA levels, which is a significant advancement over first-generation capsid assembly modulators [10][11] - **Clinical Data**: In a 96-week study, 100% of E antigen negative patients achieved HBV DNA levels below 10 international units, compared to only 20% in traditional treatments [16][22] - **Resistance**: PEVI has shown effectiveness against resistant variants of HBV, which is a significant advantage over previous treatments that led to drug resistance [17][18] B Supreme Phase II Study - **Study Design**: The B Supreme study will compare PEVI with nucleoside analogs in both E positive and E negative patient populations, focusing on achieving HBV DNA levels below 10 [21][22] - **Endpoints**: The study will measure antigen reductions and cccDNA levels, with paired biopsies to assess integration events related to HBV lifecycle [24][26] - **Regulatory Approval**: The study has received approval from regulatory agencies in 14 countries, indicating broad acceptance of its design [19][24] Future Milestones and Commercial Opportunity - **Upcoming Data**: Key data from the B Supreme study will be presented at the AASLD meeting, including post-treatment effects and interim analyses [46][47] - **Market Opportunity**: With 94% of HBV patients needing better chronic suppressive therapy, PEVI is positioned to become the standard of care, potentially increasing the rate of functional cures in combination therapies [39][42][44] MASH and ALG-055009 Development - **Overview**: ALG-055009 is a thyroid hormone receptor beta agonist aimed at treating MASH, showing improved potency and reduced side effects compared to existing therapies [50][52] - **Clinical Results**: In Phase IIa studies, ALG-055009 demonstrated a 46% reduction in liver fat, outperforming similar drugs [54] - **Partnership Discussions**: Aligos is in discussions with potential partners for ALG-055009, aiming to leverage its capabilities in cardiometabolic diseases [56] Conclusion - Aligos Therapeutics is advancing innovative therapies for HBV and MASH, with promising clinical data and a clear regulatory pathway for its lead programs. The company is well-positioned to address significant unmet needs in these areas, with a focus on improving patient outcomes and reducing healthcare costs associated with liver diseases [57][58]

ARC-520 Tolerability and Mechanism - ARC-520 has been very well tolerated in 84 humans with single doses, showing no serious or severe adverse events or discontinuations due to AEs[15, 16] - Chimpanzee studies showed that ARC-520 leads to deep HBsAg reduction, with HBeAg(+) chimps showing a mean peak knockdown of 99% (2 log) and HBeAg(-) chimps showing 81% (0.7 log)[17] - The DPC platform is potent and consistent, de-risking ARC-520 and future candidates built on the same DPC, with HBeAg knockdown in HBeAg(+) patients reaching 92% (1.2 log) mean max KD and 98% (1.7 log) max KD after a single 4mg/kg dose[19] ARC-520 Efficacy and Target Population - ARC-520 achieved a 99% (1.9 log) maximum knockdown of HBsAg after a single dose, the highest ever reported in a human using RNAi[20] - In NUC-naïve HBeAg(+) patients, ARC-520 administration resulted in a mean max HBsAg knockdown of 1.05 log, with a maximum knockdown of 99% (1.9 log) through Day 15[21] - In the US, 95% of estimated CHB patients are NUC-naïve, with approximately 50% estimated to be HBeAg(+), making them an important target population for ARC-520[25] - In Western Europe, 90% of estimated CHB patients are NUC-naïve, with approximately 33% estimated to be HBeAg(+)[25] Integrated DNA and ARC-521 - Integrated DNA becomes an increasingly important source of HBsAg as cccDNA is reduced, influencing the response to ARC-520[19] - Two HBeAg neg chimps treated with siRNA targeting integrated DNA showed a mean nadir of HBsAg reduction of 99.8% after switching from ARC-520, representing an additional 2 log decline[77] - The company nominated an additional candidate, ARC-521, optimized to include integrant KD, with an IND or equivalent expected by mid-year 2016[29, 30]