Wave Rides Coattails of Ionis, Strikes CNS Deal with Takeda

Today, Wave announced the licensing of their (stereopure) antisense technology to Japanese Big Pharma Takeda for their application in the central nervous system (CNS).  In return for $110M in upfront cash, a $60M equity investment and other biobuck goodies, Takeda receives an option to co-develop/commercialize ASO candidates for the treatment of Huntington’s Disease (HD), Amyotrophic Lateral Sclerosis (ALS), and type III Spinocerebellar Ataxia (SCA3).  Takeda also receives opt-in right to additional preclinical programs.

This deal has clearly been driven by the outstanding data gathered by rival Ionis and its corporate partner Biogen in applying phosphorothioate antisense chemistry for diseases of the CNS.  This not only includes the remarkable efficacy and commercial success seen with splice-skipping oligo Spinraza for spinal muscular atrophy (SMA), but also preclinical knockdown and biodistribution data from many other CNS programs. 

Also of note, Ionis and Roche disclosed last December statistically significant knockdown of huntingtin in people with HD, the same indication as Wave’s lead neurology program which has entered clinical development.  Important additional color for the Ionis HD candidate, especially relating to the actual depth of target knockdown is to be presented  at the upcoming CHDI conference at the end of this month.

To wit, the efficacy of exon skipper Spinraza relied on gain-of-function where minor (say 20%) target engagement may already translate into significant clinical benefit.  Most other programs, however, aim at inhibiting a disease-causing molecule from being made.  Here, you may want more like something of the order of 50%+ target engagement. 

Another wrinkle is that the target cells in the CNS will differ from indication to indication whilst antisense efficacy is not homogeneous throughout the CNS, so the SMA and HD program data will not have de-risked all the indications.   

Nevertheless, it is crystal clear that phoshorothioate oligos hold tremendous value for the many diseases of the CNS of high unmet medical need for which the industry is more and more relying on gene-targeted approaches after years of failures with small molecules.  And kudos to Wave for retaining substantial commercial value to the licensed programs.  

So thank you, Ionis, for making it exceptionally easy for them!