Eplontersen, which uses Ionis’ advanced Ligand-Conjugated Antisense (LICA) technology, is designed to treat transthyretin (TTR) amyloidosis (ATTR). In patients with ATTR, the TTR protein builds up in body tissues, interfering with their normal functions and ultimately causing death.

The companies will jointly commercialize eplontersen in the US, while AstraZeneca will commercialize the therapy in the rest of the world, excluding Latin America.

"We believe that bringing together Ionis' industry-leading experience in RNA-targeted therapeutics and deep knowledge of the TTR amyloidosis market with AstraZeneca's global scale and leadership in cardiovascular drug development and commercialization will enable faster and deeper market penetration for the benefit of patients," said Ionis CEO Brett P. Monia. "In addition to being the best strategy to maximize patient and shareholder value for eplontersen, this agreement also represents a key step in bolstering our commercial organization as we prepare to launch multiple products."

Under the terms of the deal, the Anglo-Swedish pharma is paying Ionis $200 million cash and will make additional conditional payments of up to $485 million following regulatory approvals. AstraZeneca will also pay up to $2.9 billion on sales-related milestones, plus royalties.

Hereditary ATTR amyloidosis (hATTR) with polyneuropathy is expected to be the first indication for which the companies will seek regulatory approval for eplontersen, potentially filing a a new drug application with the US Food and Drug Administration by the end of 2022.

Library access for Ovid

In separate news, AstraZeneca has agreed to license its library of pre-clinical candidates for treating epilepsy to US biopharma Ovid Therapeutics. The agreement includes early-stage small molecules that target KCC2, which is thought to be important in controlling seizures.

Ovid will pay $5 million upfront to AstraZeneca along with transferring $7.5 million in shares of its common stock. AstraZeneca, which is retaining first negotiation rights to opt-in for a strategic collaboration with Ovid, is also eligible to receive payments on clinical development milestones of up to $8 million, and on regulatory milestones of up to $45 million, while commercial milestones could reach $150 million.

Ovid’s lead candidate OV350 is designed to directly target and activate KCC2 and has shown encouraging in-vitro and in-vivo proof of concept in resistant forms of epilepsy. According to the New York-based firm, OV350 also has potential to be developed for multiple epilepsies and other central nervous system indications, including neurodevelopmental and neurodegenerative diseases.

“The KCC2 transporter is an exciting and novel target that we believe holds great promise in treating epilepsies,” said Ovid chairman and CEO Jeremy Levin. “The compounds are a natural fit for our franchise dedicated to small molecule epilepsy medicines, and they follow our track record of successful partnering with large pharmaceutical companies.”

AstraZeneca developed KCC2 transporter molecules in partnership with Tufts Laboratory for Basic and Translational Neuroscience Research.

Author: Elaine Burridge, Freelance Journalist