Madrigal Pharmaceuticals paid $25 million upfront and committed up to $1 billion to license ARO-PNPLA3 from Arrowhead Pharmaceuticals, adding another siRNA asset to a MASH portfolio that’s moving fast.
The asset targets the PNPLA3 I148M mutation, a genetic driver of MASH found in two copies in about 30% of patients. Phase 1 data showed it cut liver fat by up to 46% at 12 weeks, with effects appearing as early as six weeks and lasting through 24 weeks. Madrigal’s CMO framed it as complementary to Rezdiffra, the company’s partial agonist of the thyroid hormone receptor-beta that brought in $958.4 million last year and was the first FDA-approved MASH therapy, cleared in March 2024.
The $1 billion ceiling looks cheap against Madrigal’s February deal: $60 million upfront plus up to $4.4 billion to Suzhou Ribo Life Sciences for six siRNA candidates. In January, Madrigal paid Pfizer $50 million upfront for ervogastat, a DGAT-2 blocker in mid-stage development. Madrigal plans to test these assets in combination with Rezdiffra.
What does the buyer actually get? A Phase 2-ready candidate with a genetic rationale, a specific patient population covering roughly 30% of MASH cases, and a mechanism that complements rather than duplicates what Rezdiffra already does.
Madrigal is in talks with the FDA on a Phase 2 design for ARO-PNPLA3, but hasn’t set a start date.
Diana Kowalski