Boehringer returns to RNA for NASH in $2B deal with Ribo

03 Jan 2024
firstwordpharma.com
Phase 2License out/inPhase 1Oligonucleotide
It’s been just over six years since Boehringer signed a pair of deals to develop RNA-based therapeutics to treat non-alcoholic steatohepatitis (NASH), neither of which have resulted thus far in a clinical candidate. Now the pharma is revisiting the modality and disease match-up, thanks to a partnership announced Wednesday with Suzhou Ribo Life Science that’s potentially worth more than $2 billion in biobucks.
As part of the collaboration, which comprises multiple targets, the China-based biotech will use its small interfering RNA (siRNA) liver-targeting delivery technology, dubbed RIBO-GalSTA, to develop candidates.
Ribo received an undisclosed upfront payment, and is eligible for clinical, regulatory, and commercial milestones, plus tiered royalties, for an overall deal value greater than $2 billion.
No drug has yet been approved to treat NASH. While a series of pipeline failures have plagued the space, antisense oligonucleotide and RNA treatments are showing promise. For more, see Spotlight On: Mapping a recovering NASH landscape.
Boehringer’s NASH past
Boehringer first explored RNAi’s potential to treat NASH through November 2017 partnerships with MiNA Therapeutics and Dicerna Pharmaceuticals.
Both agreements had much smaller sticker prices than Wednesday’s deal with Ribo. The MiNA deal was valued at over €300 million; Dicerna was eligible to receive over $200 million between an upfront payment and milestones.
While Boehringer hasn’t given an update on its collaboration with MiNA, the drugmaker did select to develop an RNAi candidate from Dicerna in 2021. According to ClinicalTrials.gov, the compound, dubbed DCR-LIV2, has not yet entered clinical trials.
Boehringer’s current pipeline has one candidate in the clinic for NASH: Survodutide (BI 456906), a dual GLP1/GCGR agonist in-licensed from Zealand Pharma in 2011. The treatment is in Phase II testing for both NASH and obesity.
RNA frontrunners
At least two RNAi therapeutics have already reached Phase II testing for NASH: ALN-HSD from Alnylam Pharmaceuticals and Regeneron Pharmaceuticals, and GSK4532990 (ARO-HSD) from GSK and Arrowhead Pharmaceuticals.
GSK kicked off a Phase IIb trial in April 2023, for which Arrowhead received a $30 million milestone payment.
Alnylam and Regeneron began recruiting patients for their Phase II trial in February 2023, following promising Phase I results showing robust target knockdown and lower liver enzymes.
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