Ann: Retina Target Engagement Confirmed in Large Eye, page-61

Biogen has reported primary endpoint failure in its Phase 3 trial of tofersen in adults with ALS associated with a SOD1 mutation. Biogen had licensed the antisense therapy from Ionis, which is considered to be the world leader in antisense drug development. Ionis stock fell to a 5 year low on yesterday’s news.

Although a reduction in SOD1 protein was seen, along with “trends favoring tofersen…. across multiple secondary and exploratory measures of biologic activity and clinical function”, the drug failed to demonstrate improvement in functional status compared with placebo. Four severe neurological events were also seen in the drug arm.

Evaluate opined that the failure was a major blow to Ionis and its antisense approach more broadly, especially following another recent Ionis antisense failure. In March this year, Roche abandoned a pivotal trial of the Ionis out-licensed tominersen in Huntington’s, citing problems with the drug's risk/benefit profile.

Difficulty in achieving efficient delivery to organs and tissues other than the liver, as well as off-target effects, have been major obstacles preventing a more widespread adoption of antisense oligonucleotide therapeutics.

PYC aims to demonstrate that its novel CPP-PMO approach can address the delivery challenge faced by antisense therapeutics, getting more drug, more safely, into more types of tissues.

https://www.reuters.com/business/he...company-says-data-are-encouraging-2021-10-17/

https://www.fiercebiotech.com/biotech/biogen-s-als-drug-has-failed-phase-3-will-fda-approve-anyway

https://www.evaluate.com/vantage/articles/news/trial-results/ana-2021-ionis-rocked-tofersen-flop

https://www.nature.com/articles/s41573-020-0075-7