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Development of an Inhibitory Oligonucleotide for the Treatment of Lupus

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AI066483-01A1
Agency Tracking Number: AI066483
Amount: $207,278.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: PHS2006-2
Timeline
Solicitation Year: 2006
Award Year: 2006
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
DYNAVAX TECHNOLOGIES CORPORATION 2929 7TH ST, STE 100
BERKELEY, CA 94710
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 ROBERT COFFMAN
 (510) 665-7224
 RCOFFMAN@DVAX.COM
Business Contact
 DINO DINA
Phone: (510) 848-5100
Email: DDINA@DVAX.COM
Research Institution
N/A
Abstract

DESCRIPTION (provided by applicant): Systemic lupus erythematosis (SLE) is a complex autoimmune disease that affects multiple organ systems and affects preferentially young to middle-aged women. It has proven difficult to treat and the few effective therapies often have serious side effects. Recent research has identified a chronic elevation of interferon-a (IFN-a), produced primarily by a rare cell-type called the plasmacytoid dendritic cell, as an important factor in the pathogenesis of SLE. Raised serum levels of IFN-a have been observed in a proportion of SLE patients and correlate with both disease activity. Most patients have elevated expression of a characteristic group of IFN-a-inducible genes. We have developed a novel family of compounds that specifically inhibit the activation and production of IFN-a by plasmacytoid dendritic cells. The compounds, which we call immunoregulatory sequences (IRS), are short oligodeoxynucleotides with specific sequence motifs that inhibit signaling through Toll like receptors 7 and 9. These important innate immune receptors mediate signaling from the two major types of IFN-a inducers in SLE, viruses and immune complexes containing RNA or DNA. Thus, IRS are able to block the major stimuli for IFN-a in SLE without causing broad-based immunosuppression. The goal of this Phase I proposal is to complete the initial steps of preclinical of development of our lead compound, IRS 954, as a therapeutic agent for the treatment of SLE. These include production and evaluation of modified forms with enhanced resistance to degradation (Aim 1), pharmacokinetic and pharmacodynamic evaluations of IRS 954 and stabilized modifications (Aim 2) and an initial evaluation of the normal mouse responses to the chronic treatment with the most stable form of the molecule. Successful completion of these aims will enable us to choose the appropriate entity to take forward into an IND-enabling clinical development program. (Brief description) Systemic lupus erythematosis is a serious autoimmune disease affecting over 1 million people in the U.S., primarily women. Current treatments for this disease have serious side effects, however recent discoveries suggest new methods of treatment that may be safer and more effective. We propose to develop a novel drug that specifically inhibits Interferon-alpha, a key factor in the disease.

* Information listed above is at the time of submission. *

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