Calico Life Sciences Announces that Fosigotifator (ABBV-CLS-7262) for Vanishing White Matter Disease has been Selected for the FDA START Pilot Program

SOUTH SAN FRANCISCO, Calif., June 7, 2024 /PRNewswire/ -- 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 that its investigational eIF2B activator fosigotifator (ABBV-CLS-7262) has been accepted into the U.S. Food and Drug Administration (FDA) Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program. Fosigotifator is being developed by Calico and AbbVie pursuant to their 2014 collaboration as a potential treatment for Vanishing White Matter (VWM) disease.

FDA's Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) initiated the START Pilot Program to help further accelerate the development of novel drug and biological products for rare diseases. Selected participants will be able to obtain frequent advice and enhanced communication with FDA review staff to address program-specific development issues, including, but not limited, to clinical study design, choice of control group, and fine-tuning the choice of patient population.

"Calico is honored that fosigotifator has been selected by CDER as one of three candidates for the FDA's innovative START Pilot Program. The inclusion of fosigotifator underscores the potential of this investigational therapy in addressing the unmet needs of individuals and families affected by Vanishing White Matter Disease," said Arthur D. Levinson, Ph.D., founder and CEO of Calico. "We applaud the FDA's dedication to advancing treatments for rare diseases and are committed to working closely with the Agency to accelerate the development of fosigotifator for those living with this devastating condition."

VWM disease is an ultra-rare progressive leukoencephalopathy – a disease of the brain's white matter – caused by variations in any of the five subunits of an essential enzyme in cells called eIF2B. VWM variations in eIF2B cause a reduction in its enzymatic activity that may lead to chronic activation of the integrated stress response (ISR). The ISR plays a critical role in protein homeostasis and organismal resilience, both of which are implicated in the biology of aging.

In VWM, chronic activation of the ISR in the brain causes the white matter to degenerate. Individuals with VWM disease commonly have symptoms such as impaired muscle movement, cognitive decline, seizures, and have a shortened lifespan. While symptoms often begin to appear between ages 2 and 6, the disease can present at any age. The disease course is chronic and progressive, and stressors such as fever, infection, and mild head trauma may cause episodes of rapid deterioration. There is currently no cure and no treatment approved for VWM disease.

About Fosigotifator (ABBV-CLS-7262)
Fosigotifator targets eIF2B, a guanine nucleotide exchange factor that is essential for protein synthesis and a key regulator of the ISR. In preclinical studies in a mouse model of VWM, fosigotifator blunted the persistent ISR in the brain and spinal cord, primarily in cell types that are known to be severely affected by the human form of VWM, and corrected coordination and movement problems in these mice.

Calico and AbbVie are currently conducting a Phase 1b/2 trial of fosigotifator to evaluate the safety, tolerability, and pharmacokinetics of fosigotifator in participants diagnosed with VWM disease. This study is the first time an eIF2B activator has been administered to people with VWM disease. For more information on study NCT05757141, please visit: www.clinicaltrials.gov.

Fosigotifator is also being investigated as a potential treatment for people with amyotrophic lateral sclerosis (ALS) in two ongoing studies.

Fosigotifator is an investigational drug not yet approved for use in any country.

About Calico
Calico (Calico Life Sciences LLC) is an Alphabet-founded research and development company whose mission is to harness advanced technologies to increase our understanding of the biology that controls lifespan. 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. Follow @calico on LinkedIn, X (formerly Twitter), and YouTube.

SOURCE Calico Life Sciences LLC