Capella

We reported updated data from our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. Data were presented at the 53rd Congress of the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) in Vienna, Austria, held May 21-24, 2016.  Results showed that administration of ALN-CC5 in healthy volunteers (N=44) achieved up to 99% knockdown of serum C5 and a mean maximum of 86% serum hemolysis inhibition in the highest dose group, with mean levels consistently greater than 80% inhibition through the 13 weeks of treatment. Results also showed a mean maximum CH50 inhibition of 99.6% and maximum inhibition up to 100% relative to baseline.   The effects of ALN-CC5 were found to be highly durable, with C5 knockdown clamped at over 90% for more than six months following a single dose. C5 knockdown and complement inhibition results support the potential for a once-quarterly dosing regimen when used in combination with the monoclonal antibody, eculizumab. Importantly, ALN-CC5 was shown to be generally well tolerated, with no serious adverse events and no drug-related discontinuations to date. All adverse events were mild or moderate in severity. [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ERA-EDTA_CC5_Ph-1_052216.pdf" type="(880 KB PDF)"]View the presentation[/spotlight-link]

We reported results from our ongoing Phase 2 open-label extension (OLE) study with patisiran at the 68th Annual Meeting of the American Academy of Neurology (AAN), held April 15 – 21, 2016 in Vancouver, British Columbia, Canada.  Complete 18-month data (N=27) from the study provided continued evidence that patisiran has the potential to halt neuropathy progression in patients with hATTR-PN (also known as familial amyloidotic polyneuropathy, or FAP), showing a mean 0.8-point decrease in mNIS+7, which compares favorably to an estimated increase in mNIS+7 of 22 to 26 points at 18 months based upon analysis of historical data sets in untreated hATTR-PN patients with similar baseline neurologic impairment. Patisiran administration was also associated with a statistically significant, approximately 77% median improvement in nerve fiber density as read histologically in a blinded manner from distal thigh sweat gland biopsy samples.

We’re announcing the addition of a new program to our genetic medicines pipeline, ALN-F12, an investigational RNAi therapeutic targeting F12 for the treatment of Hereditary Angioedema (HAE). Pre-clinical data for ALN-F12 were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual meeting, held March 4-7, 2016. HAE is a genetic disorder characterized by episodes of severe swelling in various parts of the body, including the face, hands, feet, gastrointestinal tract, and airways. It is caused by a defect in the C1-inhibitor gene that results in poor control of contact pathway activation and excessive bradykinin generation. Elevated levels of bradykinin increase vascular permeability, ultimately causing the episodic swelling attacks that are characteristic of HAE. The F12 gene encodes Factor XII (FXII), which is at the top of the contact pathway cascade. Pre-clinical data showed that administration of ALN-F12 resulted in dose-dependent reduction of vascular permeability in two different mouse models of bradykinin-driven vascular leakage, demonstrating that suppression of F12 mRNA has the potential to mitigate excess bradykinin stimulation. Further, in non-human primates, a single subcutaneous dose of ALN-F12 at 3 mg/kg resulted in potent and durable knockdown of serum FXII of greater than 85 percent, with knockdown of over 50 percent sustained out to three months following administration. [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-F12_AAAAI_030716.pdf" type="(480 KB PDF)"]View the poster[/spotlight-link]

On Monday, January 11, 2016, John Maraganore presented an updated company overview at the 34th Annual J.P. Morgan Healthcare Conference in San Francisco. You may access the presentation below. [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALNY-JPMORGAN-2016-FINAL_011116.pdf" type="(6 MB PDF)"]View the J.P. Morgan Conference deck[/spotlight-link]  ...

On December 10, 2015, we hosted our third consecutive R&D Day in New York City. Alnylam management and key opinion leaders discussed our most advanced clinical programs, reviewing all the latest data and providing guidance on development plans for the ATTR amyloidosis programs, fitusiran (ALN-AT3), ALN-CC5, ALN-AS1, and ALN-PCSsc. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=946453" type=" "]Read our press release[/spotlight-link][spotlight-link icon="podcast" href="http://edge.media-server.com/m/p/fy9m5tbr" type=" "] Access the replay[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/RD-Day-2015_Full-Day.pdf" type="(14.5 MB PDF)"] View the complete presentation[/spotlight-link]

We reported new data from our Phase 1 study with the newly named fitusiran (ALN-AT3), an investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders. Interim results – presented at the American Society of Hematology (ASH) 2015 Annual Meeting, held December 5 – 8, 2015 – showed that monthly, subcutaneous administration of fitusiran achieved potent and dose-dependent lowering of AT of up to 88% in patients with hemophilia. This AT lowering was associated with statistically significant increases in thrombin generation and an 85% reduction in estimated median annualized bleeding rates (ABR) in all evaluable cohorts. The observed bleeding rates are comparable to those reported for prophylactic intravenous infusions of replacement factors in patients with hemophilia. Fitusiran was found to be generally well tolerated to date, including no thromboembolic events or clinically significant increases in D-dimer, a biomarker of excessive clot formation. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=945893" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ASH-2015_fitusiran_010715.pdf" type="(1.0 MB PDF)"]View the fitusiran Phase 1 presentation[/spotlight-link]

We reported new data from our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. Data were presented at the American Society of Hematology (ASH) 2015 Annual Meeting, held December 5 – 8, 2015.  Results showed that administration of ALN-CC5 achieved up to 99% knockdown of serum C5 and up to 98% inhibition of serum hemolytic activity, an assay for complement activity.  Further, ALN-CC5 administration resulted in low levels of residual C5, which – based on comparisons from separate studies – were at or below the estimated levels of free C5 observed at therapeutic doses of eculizumab, an approved anti-C5 monoclonal antibody. The effects were also found to be highly durable, with C5 knockdown and complement inhibition results supporting a once monthly and possibly a once quarterly subcutaneous dose regimen.  Importantly, ALN-CC5 was shown to be generally well tolerated, with no clinically significant, drug-related adverse events to date. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=945752" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ASH-2015_CC5_Hill_Poster_010615.pdf" type="(0.6 MB PDF)"]View the poster[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ASH-2015_CC5_Hill_Presentation_010615.pdf" type="(1.3 MB PDF)"]View the presentation[/spotlight-link]

We presented new pre-clinical data with ALN-HBV, an investigational RNAi therapeutic targeting the Hepatitis B Virus (HBV) genome for the treatment of HBV infection. The ALN-HBV siRNA targets a highly conserved site across genotypes A-J, mapping to the X open reading frame, which is downstream from the most prevalent integration hotspot targeted by siRNAs from other developers. ALN-HBV is thus expected to achieve potent knockdown of HBV surface antigen (HBsAg) expressed by both covalently closed circular DNA (cccDNA) and integrated HBV DNA. Pre-clinical study results in rodent HBV models showed that subcutaneous administration of ALN-HBV led to potent and durable knockdown of HBsAg. Single doses of ALN-HBV in mice resulted in an up to 3.6 log10 and a mean of 1.6 log10 reduction of HBsAg 15 days after a single dose. Further, multiple doses of ALN-HBV in rats showed highly durable knockdown, with effects lasting up to 4 months following three weekly doses of ALN-HBV at 3 mg/kg. In addition, ALN-HBV was generally well tolerated in all rodent models. [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-HBV_AASLD_111515.pdf" type="(1.3 MB PDF)"]View the presentation[/spotlight-link]  

Alnylam and The Medicines Company reported updated positive results from the ongoing Phase 1 clinical trial with ALN-PCSsc, an investigational RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia.  We had previously reported that subcutaneous administration of ALN-PCSsc resulted in an up to 83 percent lowering of LDL-C, with an up to 64 ± 5 percent mean maximum reduction. In new results, the effects of ALN-PCSsc were also found to be highly durable, with clinically significant and clamped reductions in LDL-C that now confirm the potential for a bi-annual subcutaneous dose regimen. An up to 53 percent maximal and 47 percent least squares mean reduction in LDL-C was achieved at day 180 after a single, low volume injection. In addition, ALN-PCSsc was shown to reduce a number of atherogenic lipids, including lipoprotein (a), and total cholesterol, which are associated with increased risk of cardiovascular disease. Importantly, ALN-PCSsc was generally well tolerated with no clinically significant drug-related adverse events to date. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=942203" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/AHA_PCS-Ph-1_111115.pdf" type="(1.1 MB PDF)"]View the presentation[/spotlight-link]

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