Boehringer Ingelheim and Suzhou Ribo Life Science subsidiary Ribocure Pharmaceuticals (Ribo) have partnered to develop treatments for nonalcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH).
Under the agreement, Ribo will receive an upfront payment, success-based milestones, and tiered royalties, with a total deal value exceeding $2 billion. The partnership combines Ribo's expertise in small interfering RNA (siRNA) therapeutics with Boehringer's mission to address cardiovascular, renal and metabolic diseases.
NASH, affecting over 440 million individuals globally, currently has no approved treatments. The condition leads to the formation of scar tissue over time, often progressing to severe complications like liver cirrhosis, liver failure, or liver cancer. Ribo's RIBO-GalSTAR platform facilitates the creation of RNAi therapeutics targeting disease-causing genes in hepatocytes, potentially addressing previously inaccessible drug targets.
SiRNA therapeutics work by being recognized as small double-stranded RNAs entering cells. Once inside, they interact with the enzyme dicer to create siRNA. These siRNA fragments join the RNA-induced silencing complex, dividing into sense and antisense strands. The antisense strand then targets mRNA, causing its degradation and triggering RNA interference (RNAi), effectively suppressing gene expression. This mechanism underscores the therapeutic promise of siRNA across various medical conditions.
Last year, Agios Pharmaceuticals entered an exclusive worldwide license agreement with Alnylam Pharmaceuticals, acquiring the rights to develop and commercialize Alnylam's preclinical siRNA targeting TMPRSS6 for potential treatment of polycythemia vera. Alnylam received an upfront payment of $17.5 million, and has the potential for up to $130 million in future milestone payments and royalties. The siRNA candidate demonstrates promise in modifying disease with low off-target activity and a favorable safety profile, highlighting its potential as an infrequent dosing regimen.