AstraZeneca has closed a global development and commercialisation agreement with Ionis Pharmaceuticals, Inc. (Ionis) for eplontersen, formerly known as IONIS-TTR-LRX.

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

Under the terms of the agreement, the upfront payment from AstraZeneca to Ionis is $200 million. AstraZeneca will make additional conditional payments of up to $485 million following regulatory approvals. It will also pay up to $2.9 billion 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.

The transaction will be funded with cash and is expected to be neutral to Core earnings in 2021. It will be accounted for as an intangible asset acquisition, recognised initially at the upfront amount, with any potential future milestone payments capitalised into the intangible asset as they are recognised.

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 does not impact AstraZeneca’s financial guidance for 2021.

Eplontersen is a ligand-conjugated antisense (LICA) investigational medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease.

Cardiomyopathy and polyneuropathy due to ATTR are caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium and peripheral nerves, respectively. In patients with ATTR, both the mutant and wild type TTR protein builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death. Worldwide, there are an estimated 300,000 - 500,000 patients with amyloid transthyretin cardiomyopathy (ATTR-CM) and 10,000 - 40,000 patients with amyloid transthyretin polyneuropathy (ATTR-PN).

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in oncology, rare diseases, and biopharmaceuticals, including cardiovascular, renal & metabolism, and respiratory & immunology.