South San Francisco, CA, January 6, 2025 – Calico Life Sciences LLC (Calico), a biotechnology organization focused on the biology of aging and age-related diseases, and founded by Alphabet and Arthur D. Levinson, Ph.D., today announced initial topline results from Regimen F of the HEALEY ALS Platform Trial evaluating fosigotifator (ABBV-CLS-7262) in adults with amyotrophic lateral sclerosis (ALS). Fosigotifator is a eukaryotic initiation factor 2B (eIF2B) activator in development by Calico in collaboration with AbbVie for the treatment of ALS and other disorders of the central nervous system.
The fosigotifator regimen did not meet the study’s primary endpoint of disease progression (a combined analysis of function and mortality) for either the primary or the exploratory high dose. Key secondary endpoints based on the Revised ALS Functional Rating Scale (ALSFRS-R), respiratory function, and health-related quality-of-life, were also not statistically different from placebo groups for the primary dose. Of note, endpoints of muscle strength, as measured by hand-held dynamometry (HHD) appeared to be different between the exploratory high dose and placebo groups, with slower deterioration 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. Further analyses on the observed HHD signal and biomarker data are ongoing and will be presented at an upcoming medical meeting.
“Although these results were disappointing, the study has yielded important insights into fosigotifator’s potential bioactivity in people with ALS that supports further investigation,” said Bill Cho, M.D., Head of Clinical Sciences at Calico. “We are grateful to the participants and our collaborators who have made this trial possible. We 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.”
Overall, fosigotifator was found to be safe and well-tolerated, with results showing that treatment-emergent adverse events were similar among all treatment groups.
The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital Press Release here.
About ALS
ALS is a progressive, fatal neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to the gradual degeneration of motor neurons and resulting in muscle weakness, loss of mobility, and eventually, impaired respiratory function, often culminating in paralysis.
In ALS, the aggregation and mislocalization of TDP-43 (transactive response DNA-binding protein 43 kDa) protein are thought to contribute to nerve cell damage and stress. eIF2B, a key component of the Integrated Stress Response (ISR) pathway, plays a vital role in maintaining cellular homeostasis under stress conditions. By activating eIF2B, fosigotifator could attenuate the ISR pathway and restore normal protein production in stressed nerve cells, potentially slowing the progression of ALS.
The HEALEY ALS Platform Trial is a patient-centric clinical trial designed in collaboration with the Northeast ALS Consortium (NEALS) to accelerate the development of breakthrough treatments for persons with ALS by testing multiple drugs (regimens) at the same time with efficient use of patient, scientific, and operational resources. So far, seven regimens have been included in the trial and more regimens will become available soon, with the goal of adding approximately three regimens per year. Data derived from the trial, if positive, could be used to support the potential approval of an investigational medication. Moreover, results from the trial, even when negative, can advance current knowledge related to the mechanisms underlying ALS and aid in the development of new biomarkers, laying the foundation for new avenues of scientific inquiry.
About Calico
Calico (Calico Life Sciences LLC) is an Alphabet-founded research and development company whose mission is to harness advanced technologies and model systems to increase our understanding of the biology that controls human aging. Calico will use that knowledge to devise interventions that enable people to lead longer and healthier lives. To learn more about Calico, visit www.calicolabs.com.