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TUESDAY, JUNE 9
12:00 - 2:00 pm Registration for RNAi for Therapeutic Indications and RNAi for Target Identification and Validation Conferences
Moderator: Bob D. Brown, Ph.D., Senior Vice President, Research, Dicerna Pharmaceuticals Corp.
Participants:
Arthur M. Krieg, M.D., Chief Scientific Officer, Research Technology Center, Pfizer Inc.
Elena Feinstein, M.D., Chief Scientific Officer, Quark Pharmaceuticals Inc.
Klaus Giese, Ph.D., Chief Scientific Officer, Silence Therapeutics PLC
Thomas Singer D.A.B.T. Global Head of Non-Clinical Safety, F. Hoffmann-La Roche AG
3:35 Sponsored Presentation (Opportunity Available)
3:50 Networking Refreshment Break Poster and Exhibit Viewing
Participants:
Kathleen M. Williams, Ph.D, J.D., Intellectual Property Attorney, Partner, Edwards Angell Palmer & Dodge LLP
Rochelle K. Seide, Ph.D., Senior Counsel, Schwegman, Lundberg & Woessner, P.A.
Steven L. Highlander, Ph.D., Partner, Intellectual Property, Fulbright & Jaworski LLP
5:45 End of Day
WEDNESDAY, JUNE 10
7:00 am – 4:00 pm Registration Open
7:00- 8:00 am Facilitated Break-Out Discussion Groups and Continental Breakfast
8:15 Chairperson’s Remarks
Christina Rondinone, Ph.D., Director, Research, Metabolic Diseases, Hoffmann-La Roche Inc.
8:20 Development of an RNAi Therapeutic for Colon Polyposis
Johannes Fruehauf M.D., Ph.D., Vice President, Research, Cequent Pharmaceuticals Inc.
Indications in the gastrointestinal tract (GIT) pose particular challenges to the delivery of therapeutic RNAi. Cequent’s lead candidate CEQ508 is a nonpathogenic E.Coli equipped to produce and deliver shRNA against beta-catenin for the indication of Familial Adenomatous Polyposis. Treatment leads to the silencing of beta-catenin in the epithelial cells of the mucosa, this has been shown to result in reduction of polyp formation and polyp dysplasia in a mouse model of polyposis. Extensive toxicology testing performed in rodents and non-human primates has demonstrated the efficacy and safety of this technology and Cequent is planning to initiate Phase I testing for Familial Polyposis in late-2009.
8:50 Development of SNALP Formulated siRNA-Based Drugs
Ian MacLachlan, Ph.D., Chief Scientific Officer, Tekmira Pharmaceuticals Inc.
Using stabilized nucleic acid lipid particles (SNALP), a modular lipid nanoparticle siRNA delivery platform, Tekmira has confirmed siRNA mediated RNA interference in several preclinical models of oncology, infectious, and metabolic disease. SNALPs are expected to enter Phase I clinical trials in the first half of 2009.
9:20 Atu027, a Liposomal siRNA Formulation Targeting PKN3, Inhibits Cancer Progression
Klaus Giese, Ph.D., Chief Scientific Officer, Silence Therapeutics plc
We show that systemic administration of Atu027 by repeated bolus injections or infusions in mice, rats, and non-human primates results in specific, RNAi-mediated silencing of PKN3 expression. We demonstrate efficacy of Atu027 in orthotopic mouse models for prostate and pancreas cancer with significant inhibition of tumor growth and lymph node metastasis formation. A prospective, open label, single-centre, dose finding Phase I study with Atu027 in subjects with advanced solid tumours will commence in 2009.
9:50 Networking Coffee Break Poster and Exhibit Viewing
10:45 Delivery of shRNA and Other Anti-HIV RNAs by Autologous Transplantation of Lentivirus-Transduced CD34+ Cells: A Feasibility Trial
John Zaia, M.D., Chairman, Department of Virology and Director of the
General Clinical Research Center, Beckman Research Institute, City of Hope
A lentivirus encoding three anti-HIV RNAs was used for the first time in a clinical trial. The problems and approaches to design of such a vector, the large-scale packaging of a lentivirus encoding inhibitory packaging elements, and the issue of manufacture and release testing of the final cell product will be discussed. The study has completed enrollment and the study status will be updated at the time of the presentation.
11:15 Bringing up CALAA-01: The First Nanoparticle-Formulated siRNA for Cancer in the Clinic
Helen F. Chuang, Ph.D., Vice President of Research and Business Development, Calando Pharmaceuticals, Inc.
A lentivirus encoding three anti-HIV RNAs was used for the first time in a clinical trial. The problems and approaches to design of such a vector, the large-scale packaging of a lentivirus encoding inhibitory packaging elements, and the issue of manufacture and release testing of the final cell product will be discussed. The study has completed enrollment and the study status will be updated at the time of the presentation.
11:45 Non-Invasive siRNA Therapeutics for Treatment of Eye, Inner Ear, and Lung Pathologies
Elena Feinstein, M.D., Ph.D., Chief Scientific Officer, Quark Pharmaceuticals Inc.
Efficient siRNA delivery to target cells remains the main challenge in the field of siRNA therapeutics. It turns out that siRNA delivered topically to the eye, inner ear or lungs (including tumors residing in the lungs) can efficiently reach its target cells, exert target gene knockdown and pharmacological effect.
Sponsored by
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12:15 pm Conception of Circular Interfering RNA and Production’s Strategy
Guillaume Plane, Ph.D., CEO, MitoProd SA
Interfering RNAs represent a powerful tool for the Pharmaceutical Industry. The discovering of the basic mechanism of RNA Interference was made by Andrew Fire and Craig Mello, who won the Nobel Prize in Medicine in 2006. Indeed, the stability, quality, in vivo efficiency, and delivery of these molecules represent major challenges for their development. Basically, by circularizing the primary transcript and thus removing extremities, MitoProd brings an innovative solution to face most of these challenges. In association with MitoProd innovative technology for RNA manufacturing, based on the fermentation of Saccharomyces cerevisiae yeast, Circular Interfering RNAs (ciRNA®s) offer some major advantages for the development of siRNA-based drugs.
12:30 pm Presentation 1 (Opportunity Available) or Lunch on Your Own
1:00 Session Break
1:45 Chairperson’s Remarks
Arthur M. Krieg, M.D., Chief Scientific Officer, Research Technology Center, Pfizer Inc.
1:50 Understanding the Immune Effects of RNA
Arthur M. Krieg, M.D., Chief Scientific Officer, Research Technology Center, Pfizer Inc.
Natural or synthetic RNA can stimulate several innate immune receptors, resulting in distinct patterns of cytokine and cellular responses. This innate immune activation can protect against infectious challenge, and induce tumor rejection. Distinguishing immune stimulatory effects of RNAi from a true RNAi mechanism of action can be difficult, but is important in the therapeutic development of RNAi.
2:20 Non-Clinical Safety Assessment of siRNA-Based Therapeutics
Thomas Singer, D.A.B.T., Global Head of Non-Clinical Safety, F. Hoffmann-La Roche AG
siRNA-based therapeutics represent a new class of molecules in addition to small molecules and biologicals. They offer the unique opportunity to target virtually any gene of the human genome leading to a significant extension of therapeutic opportunities. However, there are no guidelines addressing siRNA safety yet and there is little information available in the public domain. It is assumed that the safety assessment of siRNAs is more complex as with classical drugs because the delivery vehicle and the double stranded RNA trigger independent responses such as immune system or transcriptome interference. Strategies to address these interactions will be presented together with a panel of standard assays we consider important to enable siRNAs to enter clinical development.
2:50 Networking Refreshment Break (Last Chance for Poster and Exhibit Viewing)
3:30 Optimization of shRNA Features for Targeting Hepatitis C Virus
Qing Ge, Ph.D., Director, Viral Therapeutics, Somagenics Inc.
Short hairpin RNAs (shRNAs) targeting the highly conserved internal ribosome entry site (IRES) of HCV were designed and tested for their capabilities to silence gene expression. Comparison of shRNA and siRNA of the same sequence showed that shRNAs are of similar or greater potency than the corresponding siRNAs. No type I interferon-induction and cytotoxicity was found with lead shRNAs. The results indicate that shRNAs, delivered as chemically synthesized, may be effective agents for the control of HCV.
4:00 siRNA-Based Topical Microbicides Targeting Sexually Transmitted Diseases
Deborah Palliser, Ph.D., Assistant Professor, Albert Einstein College of Medicine
Sexually transmitted diseases (STD), such as HSV-2 infect 20% people in the U.S. and cause significant morbidity. There is no cure for HSV-2 and STDs are also cofactors for HIV transmission. We have used siRNAs specific for HSV-2 virus and host cellular receptors to assess whether siRNAs could be used as a component in a microbicide that targets HSV-2 and here I will present our findings.
4:30 Developing Multi-Targeted siRNA Therapeutics for Treatment of Critical Human Diseases
Patrick Y. Lu, Ph.D., President and CEO, Sirnaomics, Inc.
Using siRNA cocktail to silence multiple disease genes is truly realizing the advantage of small interfering RNA (siRNA)-based drugs. We have developed a set of siRNA cocktails using proprietary algorithm and “Tri-Blocker™” platform, delivered with optimized nanoparticle formulations locally and systemically for treatment of various human diseases.
5:00 U1 Adaptors: A Novel Gene Silencing Technology
Mark Behlke, M.D., Ph.D., Chief Scientific Officer, Integrated DNA Technologies
U1 Adaptors represent a novel gene silencing method where a bi-functional synthetic oligonucleotide recruits action of the U1 snRNP complex in the terminal exon of a targeted gene. Tethering of U1 snRNP inhibits 3’ end processing (polyA tail addition) leading to degradation of that RNA species within the nucleus. Adaptors and siRNAs work via different mechanisms of action at different sub-cellular locations; the methods can be combined to increase the level of knockdown achieved using lower doses of both reagents.
5:30 Close of RNAi for Therapeutic Indication Conference