AstraZeneca has entered into a new global development and commercialization agreement with Ionis Pharmaceuticals, a Carlsbad, California-based company developing RNA-targeted therapies, for an antisense therapy, in a deal worth up to $3.6 billion ($200 million upfront, up to $485 million in conditional payments, and up to $2.9 billion in sales-related milestones).

The deal focuses on eplontersen, a ligand-conjugated antisense medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR). The drug is currently in Phase III development for amyloid transthyretin cardiomyopathy (ATTR-CM), a fatal condition that leads to progressive heart failure and death, and for hereditary amyloid transthyretin polyneuropathy (ATTR-PN), a disease that leads to peripheral nerve damage. Eplontersen is designed to reduce the production of TTR protein to treat both hereditary and non-hereditary forms of ATTR.

Hereditary ATTR-PN is expected to be the first indication for which the companies will seek regulatory approval for eplontersen, with the potential to file a new drug application with the US Food and Drug Administration by the end of 2022.

The companies will jointly develop and commercialize eplontersen in the US, and AstraZeneca will develop and commercialize it in the rest of the world, except in Latin America.

AstraZeneca will pay Ionis an upfront payment of $200 million and additional conditional payments of up to $485 million following regulatory approvals. It will also pay up to $2.9 billions of sales-related milestones based on sales thresholds between $500 million and $6 billion, plus royalties in the range of low double-digit to mid-twenties percentage depending on the region. The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions.

Ionis will continue to manufacture and supply eplontersen for the existing clinical studies and process qualification. AstraZeneca will be responsible for commercial supply, with transition timing to be agreed by both parties. AstraZeneca will book all sales generated under the agreement.

The transaction is expected to close in the fourth quarter of 2021, subject to customary closing conditions and regulatory clearances.

Source: AstraZeneca and Ionis Pharmaceuticals