The companies will develop therapies that target the complement cascade, a group of proteins known to play a role in autoimmune diseases.
Two U.K. pharma companies, Mallinckrodt Pharmaceuticals and Silence Therapeutics plc, have teamed up to develop RNA interference therapeutics that are designed to inhibit the complement cascade, a group of proteins that are involved in the immune system and that play a role in the development of inflammation.
The proteins of the complement cascade are recognized for their role in contributing to the pathogenesis of many diseases, including autoimmune diseases and Mallinckrodt is aiming to exploit Silence’s expertise in RNAi to develop therapies. Silence’s proprietary technology is a highly specific and modular platform designed to inhibit or ‘silence’ the expression of disease-causing genes.
Mallinckrodt will obtain an exclusive license to Silence’s C33 complement asset, SLN500, with options to license up to two additional complement-targeted assets in Silence’s preclinical complement-directed RNAi development program. Silence will be responsible for preclinical activities, as well as driving the assets through the end of Phase I. Once that stage is complete, Mallinckrodt will take over clinical development and the responsibility for potential commercialization.
The financial terms of the deal are heavily loaded on the back end for Silence. Under terms of the deal, Mallinckrodt provided Silence with an upfront payment of $20 million for the collaboration. Mallinckrodt also made a $5 million equity investment in Silence. Additionally, Silence can receive up to $10 million in research milestones for SLN500 and for each optioned asset, in addition to funding for Phase 1 clinical development. Silence will be responsible for funding preclinical activities. In all, Silence can earn up to $100 million in milestone payments for SLN500, as well as commercial milestone payments of up to $563 million, the companies said. If Mallinckrodt opts to license other assets, Silence could receive up to $703 million in similar clinical, regulatory, and commercial milestone payments per asset, the companies said. If all three assets make it through commercialization, Silence could earn about $2 billion off the deal.
David Horn Solomon, president and chief executive officer of Silence Therapeutics, said the increasing number of diseases and conditions associated with 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.” He said the collaboration between Silence and Mallinckrodt will leverage the expertise of both companies in developing therapies that can transform the lives of patients.
Mallinckrodt Chief Scientific Officer Steven Romano said they are excited about the potential Silence’s RNAi technology has in the development of therapies for underserved patients who face a number of critical conditions. Romano said the deal provides an opportunity to develop “complement-targeted assets as new therapeutic options” that can benefit those patients.
The two companies will form a joint steering committee to guide the development program.
For Mallinckrodt, the deal with Silence comes a day after the company announced it was halting a Phase II trial assessing a therapeutic for the treatment of amyotrophic lateral sclerosis (ALS). The trial was halted after the study’s Independent Data and Safety Monitoring Board raised concerns over a higher number of patients developing pneumonia who were using the company’s investigational treatment. The midstage study dubbed PENNANT was examining the safety and efficacy of Mallinckrodt’s Acthar Gel (repository corticotropin injection) as a potential treatment for ALS.
