26 October 2018 - - US-based biopharmaceutical company Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) and US-based RNAi technology platform developer Dicerna Pharmaceuticals, Inc. (NASDAQ: DRNA) have forged a collaboration to discover and develop RNA interference therapies for complement-mediated diseases, 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 agreement provides Alexion with 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.

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 USD 22m, with Alexion making a concurrent USD 15m 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 USD 105m per target, plus sales milestones and mid-single to low-double digit royalties on future product sales.

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 (mRNAs) 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.

Additionally, RNAi-based therapeutic approaches hold the potential to offer more convenience for patients via infrequent subcutaneous dosing and a long duration of effect.

Dicerna's GalXC RNAi Technology Platform was invented by Dicerna, and aims to advance the development of next-generation RNAi-based therapies designed to silence disease-driving genes in the liver.

GalXC-based therapies are processed by the Dicer enzyme, which is the natural initiation point for RNAi within the human cell.

Using GalXC, Dicerna scientists attach N-acetylgalactosamine sugars directly to the extended region of the proprietary Dicer substrate short-interfering RNA (DsiRNA) molecules, yielding multiple conjugate delivery configurations that allow flexible and efficient conjugation to the targeting ligands while stabilizing the RNAi duplex.

Dicerna believes this stabilisation will enable subcutaneous delivery of RNAi therapies to hepatocytes in the liver, where they are designed to specifically bind to receptors on target cells, potentially leading to internalization and access to the RNAi machinery within the cells.

By using the Dicer enzyme as the entry point into RNAi, the GalXC approach seeks to optimize the activity of the RNAi pathway so that it operates in the most specific and potent fashion.

Compounds produced via GalXC are intended to be broadly applicable across multiple therapeutic areas, including rare diseases, viral infectious diseases, chronic liver diseases and cardiovascular diseases.

Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the discovery, development and commercialisation of life-changing therapies.

As a leader in complement biology and inhibition for more than 20 years, Alexion has developed and commercialises the first and only approved complement inhibitor to treat patients with paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia and lysosomal acid lipase deficiency (LAL-D).

In addition, the company is developing two late-stage therapies, including a second complement inhibitor and a copper-binding agent for Wilson disease.

Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, and metabolic disorders.