Alnylam Pharmaceuticals to present results on RNAi therapeutics at ACS National Meeting

Alnylam PharmaceuticalsAug 24 2010

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it will make a total of 16 oral presentations at the American Chemical Society (ACS) Fall 2010 240^th National Meeting & Exposition being held in Boston, Mass. from August 22-26, 2010. The main theme of this meeting is "Chemistry for Combating and Preventing Disease," and the presentations are being made at the Oligonucleotide Therapeutics Symposium organized by the Carbohydrate Division of ACS. Data being presented by Alnylam scientists at this meeting include new results on design, synthesis, and characterization of siRNAs, siRNA conjugates, and delivery formulations.

“Optimizing the LAL assay for detection of bacterial endotoxin in conjugated and formulated siRNAs”

"We are excited by the research being presented at this meeting, which together illustrate the very significant progress Alnylam scientists are making in the discovery and development of RNAi therapeutics. Certainly, these cumulative data demonstrate Alnylam's continued scientific leadership in the advancement of RNAi therapeutics as a new class of innovative medicines," said Muthiah Manoharan, Ph.D., Senior Vice President, Drug Discovery. "Some notable highlights from our presentations include results showing superior properties of canonical siRNAs compared with so-called 'dicer substrate' constructs, the application of 'click chemistry' approaches to the synthesis of siRNA conjugates, and the synthesis of novel cationic lipids for systemic delivery of siRNAs with lipid nanoparticles."

The oral presentations being given at the conference by Alnylam scientists include an overview by Dr. Manoharan summarizing the progress made in improving and optimizing the chemistry utilized in the discovery of siRNAs, siRNA conjugates, and lipid-based formulations. Further, several of the presentations describe the design, synthesis, and analytical characterization of siRNAs with optimized properties, including:

• "Solid-phase synthesis of 5'-di- and tri-phosphates and their modified analogs of DNA, RNA and chemically modified oligonucleotides," by Ivan Zlatev, Ph.D., Scientist;
• "Parallel high throughput synthesis of chemically modified 21-27mer siRNA sequences," by Satya Kuchimanchi, Ph.D., Associate Director, Small Scale Synthesis;
• "Novel method for the confirmation of siRNA sequence by LC-MS/MS," by Gary Lavine, Ph.D., Senior Scientist;
• "Evaluation of Canonical vs. Dicer-substrate siRNAs in vitro and in vivo," by Don Foster, Senior Research Associate; and,
• "Modulation of thermal stability can enhance the potency of siRNA," by Haripriya Addepalli, Research Associate.

Data are also being presented describing both lipid nanoparticle (LNP) and siRNA conjugation chemistry approaches for improved delivery of RNAi therapeutics including several new applications using "click chemistry" for the synthesis of novel materials:

• "Carbohydrate conjugation to siRNA for tissue-specific delivery," by G. Rajeev Kallanthottathil, Ph.D., Director, Drug Discovery;
• "Efficient synthesis of siRNA-folic acid conjugates," by Rajendra Pandey, Ph.D., Senior Scientist;
• "Synthesis and evaluation of bicyclic ketal-based cationic lipids for the delivery of siRNA via lipid nanoparticle delivery systems," by Muthusamy Jayaraman, Ph.D., Principal Scientist;
• "Synthesis of oligo spermine-containing oligonucleotides for siRNA delivery," by Shigeo Matsuda, Ph.D., Senior Scientist;
• "Conjugation strategies for RNAs using copper-catalyzed click chemistry," by Chang Geng Peng, Ph.D., Scientist;
• "Non-nucleoside building blocks for copper-assisted and copper-free click chemistry for synthesis of oligonucleotide conjugates," by K.N. Jayaprakash, Ph.D., Principal Scientist; and,
• "Solid-support immobilized, reusable Cu (I) catalyst for "click reactions" of oligonucleotides with ligands," by Laxman Eltepu, Ph.D., Scientist.

In addition, several presentations will focus on the chemistry, manufacturing, and control of siRNAs, related to their development as RNAi therapeutic products:

• "Development of a stability-indicating, ion-pair RP-HPLC method for separation and quantitative determination of two siRNA duplexes in a liposome," by Veeravagu Murugaiah, Ph.D., Principal Scientist;
• "Novel applications of aerosol-based detectors for the analysis of non-chromophore, multi-lipid, drug delivery vehicles," by William Zedalis, Principal Research Associate; and,
• "Optimizing the LAL assay for detection of bacterial endotoxin in conjugated and formulated siRNAs," by Mara Broberg, Research Associate.