ALG-010133

Aligos Therapeutics is laying off workers and focusing its resources on drug candidates for NASH and Covid-19, a move that comes after clinical trial setbacks in the past year to two hepatitis B programs. The layoffs announced after market close Wednesday will trim Aligos’s staff by about 10%. At the end of the third quarter of 2022, South San Francisco-based Aligos reported having 89 full-time employees, including 72 who work in R&D. But the company said attrition and targeted hiring means the overall headcount reduction is about 25% since last January. That’s when the company stopped development of drug candidate ALG-010133 in chronic hepatitis B infection after Phase 1 results failed to show enough activity at the projected efficacious dose. Two months later, the biotech stopped work on ALG-020572 after signs of liver toxicity were observed in a Phase 1 test. Both failed hepatitis B drugs were antisense oligonucleotides. The Aligos programs for non-alcoholic steatohepatitis (NASH) and Covid-19 are small molecules. The NASH drug candidate, ALG-055009, is designed to bind to and activate thyroid hormone receptor beta (THR-β), an approach intended to reduce liver fat and lead to improvement in the tissues and cells of the organ. Other biotechs are developing NASH drugs that hit this target. Madrigal Pharmaceuticals reported positive Phase 3 data in December that it said pave the way for a planned FDA regulatory submission for its drug candidate this year. Viking Therapeutics said Wednesday that a Phase 2b study for its NASH drug candidate has completed enrollment and preliminary data are expected in the second quarter of this year. Aligos said its NASH drug will complete Phase 1 testing in the first half of this year; a filing to commence Phase 2 testing could be submitted by the end of the year. Aligos’s antiviral research is focused on ALG-097558, a protease inhibitor with potential applications addressing multiple coronaviruses including SAS-CoV-2. The company says one advantage of its antiviral candidate is that it does not need dosing with ritonavir, a booster. Pfizer’s Covid-19 antiviral, Paxlovid, is indicated for use with ritonavir, which means a patient needs to take additional pills. Pardes Biosciences is also developing a Covid-19 antiviral that would not require dosing with ritonavir. The Pardes antiviral candidate, PBI-0451, is expected to post Phase 2 data in the first quarter of this year. Aligos said it expects to complete a Phase 1 test in healthy volunteers in the second half of this year, which would enable it to start a Phase 2 study by the end of the year. Despite its previous failures in hepatitis B, Aligos is not abandoning the indication. ALG-000184, a small molecule, has reached a Phase 1b dose-ranging study in chronic hepatitis B patients. Aligos said it expects to present data from cohorts in the study at scientific conferences throughout the year. A small-interfering RNA drug candidate called ALG-125755 is also in development for hepatitis B. Aligos said that it will continue to develop this candidate in a Phase 1 single-ascending dose study and present data at scientific conferences this year. The pipeline reprioritization leaves intact a Merck collaboration developing oligonucleotide drugs for NASH. The alliance spans two programs, both of which are in the discovery stage. “With such a diverse clinical portfolio, including four drug candidates in or near the clinic, as well as maintaining a strong discovery engine, where we continue to support multiple research collaborations, we determined that Aligos would be best positioned to achieve its business objectives by taking action now to streamline operations, reprioritize its portfolio, and implement certain cost-saving measures, including a reduction in force,” Aligos CEO Lawrence Blatt said in a prepared statement.