Calico Life Sciences Announces Fosigotifator Granted Breakthrough Therapy Designation by the U.S. FDA for the Treatment of Vanishing White Matter Disease

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Jun 23, 2026, 08:00 ET

SOUTH SAN FRANCISCO, Calif., June 23, 2026 /PRNewswire/ -- Calico Life Sciences LLC (Calico), a clinical-stage biotechnology organization focused on aging and age-related diseases and founded by Alphabet Inc. and Arthur D. Levinson, today announced that the U.S. Food and Drug Administration (FDA) granted fosigotifator Breakthrough Therapy Designation (BTD) for the treatment of Vanishing White Matter (VWM) disease. Fosigotifator, an investigational eIF2B activator, is currently in a Phase 1b/2 clinical trial evaluating its safety, tolerability, pharmacokinetics, and exploratory efficacy following administration in adult, pediatric, and infant subjects with VWM disease.

"Patients and families affected by Vanishing White Matter disease face a relentlessly progressive condition with no approved treatments or cure," said Arthur D. Levinson, Ph.D., CEO of Calico. "Receiving Breakthrough Therapy Designation is an important milestone that, alongside our preliminary clinical data, supports the continued development of fosigotifator as a potential treatment for this disease. We are encouraged to see our research into eIF2B and the Integrated Stress Response translating into early evidence that may provide a meaningful advance for these patients."

The FDA grants BTD designation to a drug intended to treat a serious or life-threatening disease or condition. This designation is based on preliminary clinical evidence indicating the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed in early clinical development.¹ This latest regulatory achievement follows the prior selection of fosigotifator for the Support for clinical Trials Advancing Rare disease Therapeutics (START) program—an FDA initiative focused on accelerating the development of novel treatments for rare diseases.

About VWM
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 enzymatic activity that leads 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.²

In VWM, chronic activation of the ISR in the brain causes the white matter to degenerate. Individuals with VWM disease commonly experience symptoms such as impaired movements, 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.³

About Fosigotifator
Developed by Calico, fosigotifator targets eIF2B, a translation initiation factor that is essential for protein synthesis and a key regulator of the ISR. Calico is investigating fosigotifator as a potential regulator of the ISR. In preclinical studies in animal models, fosigotifator directly targets eIF2B and increases the activity of elF2B complexes carrying VWM-associated pathogenic variations. In these preclinical models, fosigotifator has demonstrated the ability to decrease the ISR in the brain and spinal cord in disease models that carry VWM variations and has been shown to improve coordination and movement problems, as well as extend lifespan.⁴ It is hypothesized that if proper function of the elF2B protein complex can be restored, brain white matter damage and loss may be prevented in people with VWM.

Calico's Phase 1b/2 trial (NCT05757141) of fosigotifator is the first time an eIF2B activator has been administered to people living with VWM disease.

Fosigotifator is an investigational drug and has not been approved by any regulatory authority.

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. Follow @calico on LinkedIn, X, and YouTube.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements include, but are not limited to, statements regarding the potential benefits, safety, and efficacy of fosigotifator; the expected timing, design, and results of clinical trials; the potential for fosigotifator to receive regulatory approval; and the expected impact of fosigotifator on patients with VWM disease. These statements involve risks and uncertainties that could cause actual results to differ materially from those expressed or implied, including risks related to drug development and clinical trials, regulatory review processes, and other factors. Calico undertakes no obligation to update these forward-looking statements.