Alexion and Dicerna Collaborate on RNAi Therapies for Complement-Mediated Diseases

Rare Daily Staff

Alexion Pharmaceuticals and Dicerna Pharmaceuticals entered into a collaboration to discover and develop RNA interference therapies for complement-mediated diseases that provides Dicerna with $37 million in upfront payments and investment.

Alexion will receive exclusive worldwide licenses as well as development and commercial rights for two of Dicerna’s preclinical, subcutaneously delivered GalXC RNAi molecules and an exclusive option for other preclinical GalXC RNAi molecules for two additional targets within the complement pathway.

RNA interference is a biologic process in which certain double-stranded RNA molecules inhibit the expression of disease-causing genes by destroying the messenger RNAs of those genes. It reflects a new approach in the development of specific and powerful therapies. Rather than targeting and binding to proteins to inhibit their activity, RNAi exerts its effects one step earlier in the gene silencing process by targeting the mRNA, the instruction set that directs the building of the protein.

By attaching to this instruction set, RNAi is believed to have the ability to attack any target, including disease-causing genes that are beyond the reach of conventional antibody and small-molecule modalities. The companies said an RNAi-based approach to blocking the production of complement pathway factors offers the potential to inhibit the uncontrolled complement activation that leads to many diseases. The complement system is part of the immune system and can play a role in immunological and inflammatory conditions.

“With Soliris, Alexion has demonstrated the transformative impact of complement inhibition on multiple serious and debilitating diseases,” said John Orloff, executive vice president and head of research & development at Alexion. “This collaboration provides the opportunity to continue building on our more than two decades of complement expertise using Dicerna’s proprietary GalXC RNAi technology platform, which provides a potentially promising new way of inhibiting the uncontrolled complement activation that we know plays a significant role in many devastating diseases.”

Under the terms of the agreement, Alexion and Dicerna will collaborate on the discovery and development of subcutaneously delivered GalXC RNAi molecules directed to two complement pathway targets for the treatment of complement-mediated diseases. In addition, Alexion will have the right to exercise options, for additional payment, for two additional GalXC RNAi molecules directed to complement pathway targets.

Dicerna will lead the joint discovery and research efforts through the preclinical stage, and Alexion will lead development efforts beginning with Phase 1 studies. The agreement provides Alexion with exclusive worldwide licenses and commercial rights to the GalXC RNAi molecules developed in the collaboration.

Dicerna will receive an immediate upfront payment of $22 million, with Alexion making a concurrent $15 million equity investment in Dicerna at a premium to market as of the collaboration effective date. The collaboration also provides for potential additional development and approval-related milestone payments of up to $105 million per target, plus sales milestones and mid-single to low-double digit royalties on future product sales.

“Dicerna’s proprietary GalXC technology is designed to silence the expression of disease-driving genes in a way that is highly specific, generally well tolerated, and allows for convenient, infrequent subcutaneous administration,” said Douglas Fambrough, president and CEO of Dicerna. “Having recently demonstrated clinical proof-of-concept for DCR-PHXC, our lead program for the treatment of primary hyperoxaluria, we are eager to expand and advance our pipeline of innovative GalXC therapies, including both proprietary and partnered programs.”

October 24, 2018
Photo: Douglas Fambrough, president and CEO of Dicerna