Aligos hacks off 2nd hep B med since January after 'unexpected' reaction in 4 patients

Aligos Therapeutics is axing a second med from its pipeline after four recipients of the company’s treatment for chronic hepatitis B fell ill, including one who was hospitalized.

Four patients in the phase 1 trial testing ALG-020572 experienced increased levels of alanine aminotransferase, an enzyme found in the liver and kidney that can signal liver damage when spiking, the company said in a Tuesday announcement.

The serious adverse events occurred after dosing in the first cohort of the trial. One of the patients was briefly hospitalized but has since been discharged. Aligos said the reactions were unexpected based on nonclinical studies and dose safety data from healthy volunteers. Symptoms for all four patients are improving, and Aligos pledged to continue to follow up with them. 

As a result of the serious adverse events, the company elected to discontinue development of the treatment, an antisense oligonucleotide meant to reduce hepatitis B surface antigen levels. 

This is the second discontinuation Aligos has announced since the start of the year, prompting the company to pivot its pipeline to focus on small molecules. Investors seemed to shrug off the latest setback, as shares stayed stable around 1% up to $2.88. That was not the case when the discontinuation of a hepatitis B antiviral was revealed back in January, causing shares to halve from $10.61 to $4.61.

The Bay Area-based biotech called it quits on the hepatitis B antiviral after it was found ineffective at the highest dose. With Tuesday’s news, the company has effectively halved its potential therapies for hepatitis B since the start of the year. 

“Although this is undeniably a setback, our team remains committed to developing drug candidates with the potential to improve the lives of patients living with viral and liver diseases,” said Aligos CEO Lawrence Blatt, Ph.D. 

Now, Aligos will turn to the early small-molecule therapies to salvage its pipeline, including a phase 1 capsid assembly modulator to treat hepatitis B that works by limiting viral replication. Another early-phase candidate is a thyroid hormone receptor inhibitor to treat nonalcoholic steatohepatitis, or NASH.

Aligos is continuing to develop two NASH candidates with Merck. Upfront payments weren’t disclosed when the partnership was announced (and subsequently expanded), but Aligos stands to gain up to $460 million for each target should they hit future milestones. 

Even with the discontinuation, Aligos’ available cash runaway remains unchanged from earlier in the month, when executives reported enough money to last into the first half of 2024. The company now says it will reinvest savings from ALG-020572 into the remaining pipeline.