Fosigotifator Selected for FDA START Pilot Program

Calico Life Sciences LLC, a biotechnology firm founded by Alphabet and Arthur D. Levinson, Ph.D., announced that their investigational drug fosigotifator (ABBV-CLS-7262) has been accepted into the U.S. FDA's START Pilot Program. This collaboration, initiated in 2014 between Calico and AbbVie, aims to develop fosigotifator as a treatment for Vanishing White Matter (VWM) disease.

The START Pilot Program, launched by the FDA's Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER), assists in accelerating the development of novel therapies for rare diseases. Selected candidates in the program receive frequent advice and enhanced communication with FDA review staff to address specific development issues such as clinical study design and patient population selection.

Arthur D. Levinson, Ph.D., founder and CEO of Calico, expressed honor in fosigotifator being chosen for the START Pilot Program, highlighting the therapy's potential to meet the needs of those impacted by VWM disease. Levinson praised the FDA's commitment to advancing treatments for rare diseases and emphasized Calico's dedication to collaborating with the agency to expedite fosigotifator's development.

VWM disease, a rare progressive condition affecting the brain's white matter, is caused by variations in the eIF2B enzyme subunits. These variations lead to reduced enzymatic activity and chronic activation of the integrated stress response (ISR), crucial for protein homeostasis and organismal resilience. Chronic ISR activation results in the degeneration of brain white matter, leading to symptoms such as impaired muscle movement, cognitive decline, seizures, and reduced lifespan. The disease often manifests between ages 2 and 6 but can appear at any age. VWM's course is chronic and progressive, with stressors like fever or mild head trauma causing rapid deterioration. Currently, there is no approved cure or treatment for VWM disease.

Fosigotifator targets eIF2B, a guanine nucleotide exchange factor essential for protein synthesis and a key ISR regulator. Preclinical studies in a mouse model of VWM demonstrated that fosigotifator mitigated persistent ISR in the brain and spinal cord, corrected coordination, and improved movement in affected mice. Calico and AbbVie are conducting a Phase 1b/2 trial to evaluate fosigotifator's safety, tolerability, and pharmacokinetics in VWM patients. This trial marks the first administration of an eIF2B activator to individuals with VWM disease.

Fosigotifator is also being explored as a potential treatment for amyotrophic lateral sclerosis (ALS) in ongoing studies. However, fosigotifator remains an investigational drug and is not yet approved for use in any country.

Calico Life Sciences LLC, established by Alphabet, focuses on understanding the biology of aging to develop interventions that promote longer and healthier lives. The company leverages advanced technologies to achieve its mission of extending human lifespan. More information about Calico can be found on their LinkedIn, X (formerly Twitter), and YouTube channels.