Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Alnylam Scientists Present Pre-clinical Data with ALN-CC5, an RNAi Therapeutic

Published: Friday, June 21, 2013
Last Updated: Friday, June 21, 2013
Bookmark and Share
New research demonstrates potent, dose-dependent, and durable silencing of serum C5 for the treatment of complement-mediated diseases.

Alnylam Pharmaceuticals, Inc. announced that it has presented new pre-clinical data with ALN-CC5, an RNAi therapeutic targeting complement component C5. These data were presented at the 6th International Conference on Complement Therapeutics being held June 18 - 23, 2013 in Kos, Greece. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in serious, life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, amongst others. C5 is a genetically and clinically validated target; loss of function human mutations are associated with an attenuated immune defense against certain infections and intravenously administered anti-C5 monoclonal antibody therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. In a presentation titled “Development of an RNAi Therapeutic Silencing the C5 Component of Complement,” Alnylam scientists presented pre-clinical results showing potent, dose-dependent, and durable RNAi-mediated knockdown of serum C5 and inhibition of complement-mediated hemolytic activity of approximately 90% with a subcutaneously administered RNAi therapeutic. Alnylam believes that ALN-CC5 – part of the company’s “Alnylam 5x15” product strategy – represents a novel approach for the treatment of complement-mediated diseases; the company expects to nominate a development candidate for clinical advancement in late 2013.

“C5 is a genetically and clinically validated target that exemplifies the potential of Alnylam’s ‘5x15’ product strategy for innovative new medicines. First, C5 is predominantly expressed in liver, where we have established clinical activity and tolerability for RNAi therapeutics. In addition, our clinical development plan for an RNAi therapeutic targeting C5 will be facilitated by serum biomarkers in Phase I trials and a relatively streamlined and focused path for advanced development,” said Rachel Meyers, Ph.D., Vice President, Research and RNAi Lead Development at Alnylam. “Indeed, we believe that a subcutaneously administered RNAi therapeutic targeting C5 could represent an important advance for the treatment of a broad range of complement-mediated diseases.”

New data presented at the scientific meeting showed that a GalNAc-siRNA conjugate targeting the C5 mRNA resulted in potent, dose-dependent, and durable silencing of C5 liver mRNA, knockdown of C5 serum protein levels, and inhibition of complement-mediated hemolysis activity. Specifically, a prototype GalNAc-siRNA conjugate targeting C5 showed a single dose ED50 for C5 knockdown of approximately 0.6 mg/kg in rodent models. In multi-dose experiments, subcutaneous administration of the GalNAc-siRNA conjugate resulted in approximately 90% knockdown of serum C5 levels at doses of ≥1.25 mg/kg. Additional multi-dose experiments showed that the current lead candidate siRNA could achieve an approximately 90% inhibition of complement-mediated hemolytic activity in the rat at subcutaneous doses of 5 mg/kg; these effects were rapid, dose-dependent, and durable for weeks after cessation of treatment. The company is performing additional optimization of the GalNAc-siRNA conjugate lead molecule and expects to nominate its ALN-CC5 development candidate in late 2013.

“The complement system plays a central role in immunity as part of host defense. However, dysregulation of this pathway can lead to life-threatening complications in a wide range of human diseases including PNH, aHUS, myasthenia gravis, neuromyelitis optica, amongst others,” said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Alnylam. “We are excited about these pre-clinical data showing potent, dose-dependent, and durable knockdown of serum C5 with about 90% inhibition of hemolysis activity using a subcutaneously administered RNAi therapeutic. We believe that if these results can extend in the clinical setting, they could represent a very promising therapeutic strategy and new treatment option for patients with complement-mediated diseases.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,100+ scientific posters on ePosters
  • More Than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Alnylam Elects Amy Schulman to its Board of Directors
Appointment of industry leader brings broad strategic, commercial, and legal experience to board.
Saturday, July 05, 2014
Alnylam Announces USPTO Issues Patent Covering RNAi Therapeutics
New '277 McSwiggen patent includes broad, sequence-independent claims for chemically modified siRNAs targeting the HBV genome.
Saturday, June 14, 2014
Alnylam Presents New Pre-Clinical Data with Development Candidate for ALN-CC5
Company on track to file IND application in late 2014 and now guides to report initial clinical results in mid-2015.
Thursday, June 12, 2014
Alnylam Initiates Phase II Clinical Trial with ALN-TTRsc
Company expects to present data in late 2014, and start pivotal phase III trial with ALN-TTRsc in TTR cardiac amyloidosis in late 2014.
Monday, December 30, 2013
Alnylam Presents New Pre-clinical Data on ALN-AT3
New results demonstrate an expanded therapeutic index for AT knockdown and complete correction of aPTT in models of hemophilia.
Tuesday, December 10, 2013
Alnylam Files CTA to Initiate a Phase I Study for ALN-AT3
Company expects to initiate phase I study in early 2014 with interim data from hemophilia subjects by year-end 2014.
Friday, November 01, 2013
Alnylam Reports Positive ALN-TTR02 Clinical Data
Results of clinical study demonstrate rapid, dose-dependent, durable, and specific knockdown of TTR, the disease-causing protein in TTR-mediated Amyloidosis (ATTR).
Tuesday, July 24, 2012
Alnylam and Collaborators Publish New Pre-clinical Results
New paper published in blood shows potent and selective induction of liver erythropoietin through silencing of EglN genes.
Wednesday, June 13, 2012
Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
Grant Supports Project To Develop Simple Test To Screen For Cervical Cancer
UCLA Engineering announces funding from Bill and Melinda Gates Foundation.
Injecting New Life into Old Antibiotics
A new fully synthetic way to make a class of antibiotics called macrolides from simple building blocks is set to open up a new front in the fight against antimicrobial drug resistance.
Insight into Bacterial Resilience and Antibiotic Targets
Variant of CRISPR technology paired with computerized imaging reveals essential gene networks in bacteria.
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Alzheimer’s Protein Serves as Natural Antibiotic
Alzheimer's-associated amyloid plaques may be part of natural process to trap microbes, findings suggest new therapeutic strategies.
Slime Mold Reveals Clues to Immune Cells’ Directional Abilities
Study from UC San Diego identifies a protein involved in the directional ability of a slime mold.
How Do You Kill A Malaria Parasite?
Drexel University scientists have discovered an unusual mechanism for how two new antimalarial drugs operate: They give the parasite’s skin a boost in cholesterol, making it unable to traverse the narrow labyrinths of the human bloodstream. The drugs also seem to trick the parasite into reproducing prematurely.
Illuminating Hidden Gene Regulators
New super-resolution technique visualizes important role of short-lived enzyme clusters.
Supressing Intenstinal Analphylaxis in Peanut Allergy
Study from National Jewish Health shows that blockade of histamine receptors suppresses intestinal anaphylaxis in peanut allergy.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,100+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!