Therapeutics

BIIB100

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Overview

Name: BIIB100
Synonyms: KPT-350
Therapy Type: Small Molecule (timeline)
Target Type: Inflammation (timeline), Other (timeline)
Condition(s): Amyotrophic Lateral Sclerosis
U.S. FDA Status: Amyotrophic Lateral Sclerosis (Discontinued)
Company: Biogen

Background

BIIB100 is an inhibitor of Exportin 1 (XPO1), a protein that mediates export of many proteins and RNA from the cell nucleus. Abnormal movement of proteins and RNA molecules in and out of the nucleus plays a role in neurodegenerative and other diseases.

In preclinical work, this compound showed broad neuroprotective action in animal and cell models of multiple sclerosis, traumatic brain injury, and Huntington’s disease (Haines et al., 2015; Tajiri et al., 2016; Grima et al., 2017; Cantu et al., 2020). A related compound protected against motor neuron death in a C9ORF72-ALS model (Zhang et al., 2015). BIIB100 is orally available and crosses into the brain in animals.

Biogen purchased development rights to this compound from Karyopharm in 2018, and began development for ALS. Karyopharm has another XPO1 inhibitor approved for the treatment of blood cancers.

Findings

In May 2019, Biogen began a Phase 1 study to evaluate the safety and tolerability of single doses of BIIB100 in adults with ALS. The study enrolled 49 participants at 10 sites across the U.S., who received one of six single ascending doses or placebo, against a primary outcome of adverse events. The study, which also evaluated pharmacokinetics, was completed in June 2021.

In a June 2022 SEC filing, Karyopharm disclosed that Biogen had terminated the development agreement.

For details on the BIIB100 trial, see clinicaltrials.gov.

Last Updated: 28 Jul 2022

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References

Paper Citations

  1. Haines JD, Herbin O, de la Hera B, Vidaurre OG, Moy GA, Sun Q, Fung HY, Albrecht S, Alexandropoulos K, McCauley D, Chook YM, Kuhlmann T, Kidd GJ, Shacham S, Casaccia P. Nuclear export inhibitors avert progression in preclinical models of inflammatory demyelination. Nat Neurosci. 2015 Apr;18(4):511-20. Epub 2015 Feb 23 PubMed.
  2. Tajiri N, De La Peña I, Acosta SA, Kaneko Y, Tamir S, Landesman Y, Carlson R, Shacham S, Borlongan CV. A Nuclear Attack on Traumatic Brain Injury: Sequestration of Cell Death in the Nucleus. CNS Neurosci Ther. 2016 Apr;22(4):306-15. Epub 2016 Feb 4 PubMed.
  3. Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K, Ochaba J, Geater C, Morozko E, Stocksdale J, Glatzer JC, Pham JT, Ahmed I, Peng Q, Wadhwa H, Pletnikova O, Troncoso JC, Duan W, Snyder SH, Ranum LP, Thompson LM, Lloyd TE, Ross CA, Rothstein JD. Mutant Huntingtin Disrupts the Nuclear Pore Complex. Neuron. 2017 Apr 5;94(1):93-107.e6. PubMed.
  4. Cantu D, Croker D, Shacham S, Tamir S, Dulla C. In vivo KPT-350 treatment decreases cortical hyperexcitability following traumatic brain injury. Brain Inj. 2020 Sep 18;34(11):1489-1496. Epub 2020 Aug 27 PubMed.
  5. Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, Gupta S, Thomas MA, Hong I, Chiu SL, Huganir RL, Ostrow LW, Matunis MJ, Wang J, Sattler R, Lloyd TE, Rothstein JD. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature. 2015 Sep 3;525(7567):56-61. Epub 2015 Aug 26 PubMed.

External Citations

  1. SEC filing
  2. clinicaltrials.gov

Further Reading

No Available Further Reading