Fosigotifator (ABBV-CLS-7262) is an eIF2B activator that targets a key regulator of the highly conserved integrated stress response pathway. Inhibition of this pathway has therapeutic potential in a number of neurodegenerative diseases, such as ALS, Parkinson’s disease and traumatic brain injury.

On March 28, 2023, Calico announced that fosigotifator would be part of the HEALEY ALS Platform Trial, which is designed to evaluate multiple investigational products simultaneously, thus accelerating the development of effective and breakthrough treatments for people living with ALS. Trial enrollment was completed on April 11, 2024.

On January 6, 2025, Calico disclosed that fosigotifator did not meet the study’s primary endpoint of disease progression or key secondary endpoints, including health-related quality-of-life. There were hints of “slower deterioration in [muscle strength in] both upper and lower extremities in the exploratory high dose treatment group compared to placebo. In addition, there was a potential signal towards slowing respiratory functional decline as measured by the slow vital capacity (SVC) in the participants taking the exploratory high dose.”

In the same announcement, a Calico official said that they “remain committed to investigating the potential of fosigotifator as a much needed treatment option for people living with ALS and for other disorders, including vanishing white matter disease and major depressive disorder which each test different scientific hypotheses.”

On the same day, Denali Therapeutics announced that its own eIF2B activator DNL343 had also failed in the HEALEY ALS trial.