Cardio-Metabolic Disease

Alnylam and The Medicines Company reported positive initial results from the ongoing Phase 1 clinical trial with ALN-PCSsc, an investigational RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia.  Subcutaneous administration of ALN-PCSsc resulted in an up to 83% lowering of LDL-C, with an up to 64 ± 5% mean maximum reduction, comparable to published results for anti-PCSK9 monoclonal antibodies (Zhang XL., et al., BMC Med, 2015).  Similar reductions in LDL-C were seen in patients on and off concomitant statin therapy.  The effects of ALN-PCSsc were highly durable, with clinically significant and clamped reductions in LDL-C maintained for over 140 days, supportive of a once-quarterly and possibly bi-annual subcutaneous dose regimen. Maximal lowering effects on LDL-C were consistently achieved at a dose of 300 mg associated with a low injection volume of 1.5 mL. Importantly, ALN-PCSsc was generally well tolerated with no clinically significant adverse events to date. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=929318" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-PCSsc-Phase-1_Poster_08302015.pdf" type="(0.4 MB PDF)"]View the poster[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-PCSsc-Phase-1_Presentation_08302015.pdf" type="(1.7 MB PDF)"]View the presentation[/spotlight-link]

On December 12, we hosted an R&D Day in New York City. Alnylam management and key opinion leaders discussed the latest progress as well as plans for the future development of our RNAi therapeutics pipeline. At this event, we announced our pipeline growth strategy for development and commercialization of RNAi therapeutics across three Strategic Therapeutic Areas (STArs): Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease. [spotlight-link icon="podcast" href="http://edge.media-server.com/m/p/njherf95" type=" "] Listen to the webcast replay[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/MASTER-RD-DAY-DECK_Capella.pdf" type="(12.3 MB PDF)"] View the complete presentation[/spotlight-link]

We presented pre-clinical data from our investigational RNAi therapeutic programs toward genetically validated targets in development for the treatment of cardiovascular metabolic diseases, including: ALN-PCSsc targeting PCSK9 for the treatment of hypercholesterolemia; ALN-AC3 targeting apolipoprotein C3 (apoC3) for the treatment of hypertriglyceridemia; and ALN-ANG targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia.  The data, presented at the American Heart Association (AHA) Scientific Sessions 2014, included new pre-clinical multi-dose data in non-human primates (NHPs) with over six months of dosing for ALN-PCSsc, showing robust and clamped knockdown of PCSK9 of up to 92% and reductions in LDL-C of up to 77% with a once-monthly subcutaneous dosing regimen.  These studies confirm the potential for a once-monthly, and possibly once-quarterly, low volume subcutaneous dose regimen, thus highlighting the emerging profile of our ESC-GalNAc conjugate delivery technology. We believe that ALN-PCSsc represents an innovative, differentiated, and well-validated approach for the treatment of hypercholesterolemia. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=883469" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/CardioMetabolic_AHA_Poster_111714.pdf" type="(1.1 MB PDF)"] View our poster[/spotlight-link]

We announced a new program, ALN-AGT, an RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertensive disorders of pregnancy (HDP), including preeclampsia. Pre-clinical data were presented at the American Heart Association’s High Blood Pressure Research 2014 Scientific Sessions, held September 9 – 12, 2014, in San Francisco. Data from experiments in an established rat model of preeclampsia demonstrated that an RNAi therapeutic targeting AGT ameliorates the clinical sequelae of preeclampsia and improves outcomes for the fetus.  This treatment approach has the potential for selective delivery to the pregnant mother without fetal drug exposure, as our study confirmed undetectable siRNA levels in the fetus. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=870551" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-AGT_HBPR_presentation_09112014.pdf" type="(1.3 MB PDF)"] View our presentation[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-AGT_HBPR_poster_09112014.pdf" type="(1.3 MB PDF)"] View our poster[/spotlight-link]

We have presented new pre-clinical data from our growing pipeline of RNAi therapeutics for the treatment of cardiovascular metabolic disease, including ALN-PCSsc targeting PCSK9 for the treatment of hypercholesterolemia, and a newly named program, ALN-AC3 targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia.  The data were presented in an oral presentation at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) 2014 Scientific Sessions held May 1-3, 2014 in Toronto, Ontario. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=844592" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALNY-CardioMetabolicPrograms-ATVB-May2014.pdf" type="(1.3 MB PDF)"] View our presentation [/spotlight-link]

We presented new pre-clinical data with RNAi therapeutic programs for cardiovascular disease: ALN-PCSsc, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; and ALN-ANG, an RNAi therapeutic targeting ANGPTL3 for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia. These data were presented at the American Heart Association (AHA) Scientific Sessions held November 16 – 20, 2013 in Dallas, Texas. The data showed that subcutaneous administration of ALN-PCSsc led to an up to 95% knockdown of plasma PCSK9 and an up to 67% reduction of low density lipoprotein cholesterol (LDL-C) – in the absence of statin co-administration. In addition, new results for ALN-ANG demonstrated a greater than 95% reduction of triglycerides and greater than 85% reduction of LDL-C in a rodent model of mixed hyperlipidemia. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=807877" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALNY-AHAposterByPanel-Nov2013.pdf" type="(1.1 MB PDF)"] View our poster [/spotlight-link]

Yesterday, scientists presented positive results from our Phase I clinical trial of ALN-PCS at the American Heart Association’s Arteriosclerosis, Thrombosis and Vascular Biology 2012 Scientific Sessions held in Chicago. Results showed that administration of a single dose of ALN-PCS, in the absence of concomitant lipid-lowering agents such as statins, resulted in statistically significant and durable reductions of PCSK9 plasma levels of up to 84% and lowering of LDL-C of up to 50%. [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-PCS-PhaseI-ATVB-April20-2012.pdf" type="(572 KB PDF)"]View our  presentation[/spotlight-link] [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=734310" type="(572 KB PDF)"]Read our press release[/spotlight-link]

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