Biogen takes nuclear option, terminating Karyopharm ALS pact after getting a look at phase 1 data

Biogen is jettisoning one of its three clinical-phase amyotrophic lateral sclerosis (ALS) candidates, kicking an oral nuclear export inhibitor back to Karyopharm Therapeutics.

The big biotech struck a deal to acquire the asset, called KPT-350, in 2018, paying $10 million upfront and committing to $207 million in milestones. It began a phase 1 trial in 49 adults with ALS the next year to set out to show whether reducing nucleoprotein export by inhibiting nuclear transport factor XPO1 can prevent the formation of neuronal cytoplasmic inclusions and thereby slow progression of sporadic ALS.

Work on the study ended in June 2021. On June 7, 2022, Biogen wrote to Karyopharm to terminate the agreement, with Karyopharm informing investors eight days later.

The news initially triggered a double-digit drop in Karyopharm’s share price, although by 7:30am ET the next day the stock had stabilized down around 4% at $4.35. Karyopharm’s prospects are more closely tied to its ability to maximize the value of its cancer drug selinexor, both in its approved indications and through further clinical development, but Biogen’s exit still deprives it of a potential source of income. 

Karyopharm was eligible to receive up to $142 million in development and regulatory milestones from Biogen, with the remaining $65 million tied to commercial landmarks. The termination shuts off the cash stream, although Karyopharm is still evaluating its “specified rights relating to the purchased assets upon the termination of the agreement.” 

For Biogen, the termination eliminates one of its three shots on goal against ALS. The antisense prospect tofersen is most advanced of the three ALS programs, but its failure to hit the primary endpoint in phase 3 has raised doubts about its chances, even as Biogen has made the case for the asset and engaged with regulators about the next steps.  

Biogen’s other clinical-phase ALS candidate is BIIB105, another antisense asset. BIIB105 is in a phase 1 clinical trial designed to assess its effect on two forms of ALS. The study has a primary completion date of 2026 on ClinicalTrials.gov.