Mallinckrodt strikes $20M RNAi pact with Silence Therapeutics

Mallinckrodt is handing over $20 million upfront in its deal with Silence Therapeutics but is promising more than $2 billion down the line. (Pixabay)

Mallinckrodt has jumped into RNA interference (RNAi) medicine, teaming up with Silence Therapeutics to develop a program aimed at the complement cascade, a group of proteins that help antibodies and other immune cells fight off pathogens and that play a part in promoting inflammation. 

The duo will work on drugs that silence—or inhibit—these proteins, starting with SLN500, an early-stage program for complement-mediated diseases, Mallinckrodt said in a statement Thursday. It picks up an exclusive worldwide license for the drug as well as the chance to license up to two more complement drugs later on.

London-based Silence will carry out preclinical and clinical work for the programs through the end of phase 1, at which point Mallinckrodt will take over clinical development and, eventually, commercialization. 

Mallinckrodt is handing over $20 million upfront but is promising more than $2 billion down the line. The backloaded deal offers $10 million in research milestones for each program Mallinckrodt takes forward and up to $663 million in clinical, regulatory and commercial milestones for SLN500. If Mallinckrodt pulls the trigger on more programs, Silence could net another $703 million in milestones for each asset. 

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"We are very excited by the significant potential offered by Silence's RNAi technology to meet the needs of underserved patients in a number of serious and critical conditions, and we look forward to collaborating with them to advance development of complement-targeted assets as new therapeutic options," said Mallinckrodt Chief Scientific Officer Steven Romano, M.D., in the statement. 

The duo didn’t specify which diseases they are targeting, noting only that complement activation underpins many diseases including autoimmune diseases. 

"The increasing number of clinical conditions and pathologies that involve the complement system has generated significant interest in the development of therapeutic options to inhibit complement activation, which holds great promise in treating a range of diseases,” said David Horn Solomon, M.D., CEO of Silence Therapeutics. 

Mallinckrodt’s entry into complement-targeted drugs comes 12 years after the FDA cleared the first complement inhibitor, Alexion Pharmaceuticals' Soliris, for the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH). Alexion followed up with Ultomiris, an improved, long-acting version of the drug that earned approval in 2018.

For its next act, Alexion is looking beyond PNH, picking up a pair of preclinical RNAi therapies from Dicerna Pharmaceuticals last October that block production of complement pathway factors and securing the option to buy Dutch biotech Complement Pharma. Alexion and Complement are working on a C6 complement inhibitor for neurodegenerative diseases.