The Medicines Company Presents Clinical Data Analyses for Inclisiran at 87th European Atherosclerosis Society Congress - Seite 3

Data from the combined analysis of ORION-1 and ORION-7 were presented on May 27 during an e-poster session at the 87^th EAS Congress (abstract #EAS19-0576, Efficacy, Safety and Pharmacokinetics of Inclisiran by Renal Function, Kallend et al).

ORION-2

ORION-2 results presented at EAS showed that HoFH patients (N=4) who received inclisiran sodium 300 mg met the primary efficacy endpoint of durable LDL-C lowering up to day 180 and all patients achieved reductions in PCSK9 and apolipoprotein B. The effects were similar to those of anti-PCSK9 monoclonal antibody medicines in this patient population, but without the need to increase the treatment dose. Secondary endpoints of reductions in PCSK9 and apolipoprotein B from baseline to day 90 and day 180 were also achieved. Inclisiran was reported to be well-tolerated, with no drug-related adverse events. A larger Phase 3 study of inclisiran in HoFH (ORION-5) is ongoing.

ORION-2 (N=4) is a Phase 2 pilot study to assess the safety, tolerability and efficacy a single dose of inclisiran sodium 300 mg in participants with genetically confirmed HoFH. The primary endpoint is percentage change in LDL-C from baseline to day 90 and day 180.

Data from ORION-2 were presented on May 27 during a late-breaking abstract session at the 87^th EAS Congress (abstract #EAS19-1122, Inclisiran Durability Lowers LDL-C and PCSK9 Expression in Subjects with Homozygous Familial Hypercholesterolaemia: The ORION-2 Pilot Study, Raal et al).

About Inclisiran

Inclisiran, the first cholesterol-lowering therapy in the siRNA class, is The Medicines Company’s investigational therapy in Phase 3 clinical development to evaluate its ability to lower low-density lipoprotein cholesterol (also known as LDL-C or bad cholesterol) through twice-a-year dosing. As a siRNA, inclisiran directly targets messenger RNA and harnesses one of the body’s powerful natural mechanisms, RNA interference, to prevent production of the PCSK9 protein at its source in the liver and facilitate removal of LDL-C from the bloodstream. In Phase 2 studies, inclisiran provided clinically significant LDL-C reductions greater than 50 percent in addition to the effects of statins and/or ezetimibe, and LDL-C reductions were sustained throughout the six-month dosing interval. Inclisiran is not yet approved for use by the FDA or any other regulatory authority. The Medicines Company obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement with Alnylam Pharmaceuticals.