Arrowhead Secures $25M Upfront, $975M Milestones in $1B SiRNA Asset Deal

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Madrigal Pharmaceuticals gained global rights to Arrowhead’s ARO-PNPLA3 siRNA asset under a licence agreement worth up to $1 billion, including a $25 million upfront payment, $975 million in milestones and royalties on sales. ARO-PNPLA3 showed Phase I results with up to 46% liver fat reduction maintained through 24 weeks.

1. Arrowhead Licenses ARO-PNPLA3 to Madrigal

Arrowhead Pharmaceuticals has granted Madrigal Pharmaceuticals exclusive global rights to its siRNA candidate ARO-PNPLA3 for treating metabolic dysfunction-associated steatohepatitis. Madrigal will handle development, manufacturing and commercialization under the agreement.

2. Deal Terms and Financial Commitments

The licensing deal includes a $25 million upfront payment and up to $975 million in milestone payments tied to clinical, regulatory and commercial milestones, plus royalties on future sales if approved. This agreement represents a potential $1 billion value to Arrowhead.

3. Clinical Profile of ARO-PNPLA3

ARO-PNPLA3 targets the PNPLA3 I148M genetic variant and demonstrated up to 46% liver fat reduction in MAFLD patients during a Phase I trial, with sustained efficacy at 24 weeks. Approximately one-third of patients with moderate to advanced fibrosis carry two copies of this variant.

4. Strategic Impact on Pipeline and Finances

This transaction provides Arrowhead with non-dilutive capital and shifts development risk to Madrigal, allowing Arrowhead to prioritize its RNAi pipeline. The upfront and milestone payments bolster cash reserves and support ongoing research programs.

Sources

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