Chemistry:Fosigotifator
Fosigotifator is an experimental small-molecule related to ISRIB that activates the eukaryotic initiation factor eIF2; it was licensed by Calico from University of California, San Francisco and partnered with AbbVie.[1][2][3] Abbvie and Calico ran clinical trials to determine if the drug can treat amyotrophic lateral sclerosis (ALS)[4][5][6] and major depressive disorder.[1] A formulation of fosigotifator, as its monosodium phosphate salt mixed with tromethamine, is known as ABBV-CLS-7262. Fosigotifator has been patented by AbbVie and Calico as a prodrug for modulation of the integrated stress response pathway.[7]
In January 2025 Abbvie and Calico announced that the drug had failed a Phase 2/3 trial in ALS; in November 2025 Abbvie ended its partnership with Calico.[1]
References
- ↑ 1.0 1.1 1.2 "Fosigotifator". 21 Nov 2025. https://www.alzforum.org/therapeutics/fosigotifator.
- ↑ Masson, Gabrielle (13 November 2025). "AbbVie to end Calico collab, lays off researchers: Stat" (in en). www.fiercebiotech.com. https://www.fiercebiotech.com/biotech/abbvie-cuts-ties-calico-100-scientists-after-11-year-partnership.
- ↑ "Fosigotifator - AbbVie/Calico - AdisInsight". https://adisinsight.springer.com/drugs/800064446.
- ↑ Arnold, F. J.; Nguyen, A. D.; Bedlack, R. S.; Bennett, C. L.; La Spada, A. R. (1 August 2023). "Intercellular transmission of pathogenic proteins in ALS: Exploring the pathogenic wave". Neurobiology of Disease 184. doi:10.1016/j.nbd.2023.106218. ISSN 0969-9961. PMID 37394036.
- ↑ Martinez-Gonzalez, Loreto; Martinez, Ana (1 February 2023). "Emerging clinical investigational drugs for the treatment of amyotrophic lateral sclerosis" (in en). Expert Opinion on Investigational Drugs 32 (2): 141–160. doi:10.1080/13543784.2023.2178416. ISSN 1354-3784. PMID 36762798.
- ↑ Cho, William; Jeong, Anna; Malik, Paul; Boiser, Joey; Huang, Xiu; Rosebraugh, Matthew (25 April 2023). "A Phase 1 First-in-human Study to Investigate the Safety, Tolerability and Food Effect of ABBV-CLS-7262 (P6-4.002)" (in en). Neurology 100 (17 Supplement 2): 4188. doi:10.1212/WNL.0000000000203810. ISSN 0028-3878.
- ↑ "Prodrug Modulators of the Integrated Stress Pathway" WO patent 2020077217, published 2020-04-16
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