Pipeline

Overview
HEPLISAV
Asthma
Autoimmunity / Inflammation

Pipeline :: Autoimmunity / Inflammation

Dynavax has pioneered a new approach to therapies for multiple autoimmune and inflammatory diseases including lupus, psoriasis, and rheumatoid arthritis. Our technology consists of oligonucleotide-based immunoregulatory sequences (IRSs) that inhibit Toll-like Receptors (TLRs) 7, 8, and/or 9. TLRs are key receptors of the innate immune system that can induce strong inflammatory responses.

Our TLR inhibitors have demonstrated a highly targeted effect on key immune cells and pathways that play a role in multiple autoimmune and inflammatory diseases. In contrast, most currently marketed and pipeline products are broadly immunosuppressive with variable efficacy and substantial toxicity.

Under our worldwide strategic alliance with GlaxoSmithKline (GSK), established in 2008, we are developing DV1179, a bifunctional inhibitor of TLR7 and TLR9. In a 2010 article published in NATURE, Dynavax scientists showed that activation of the innate immune system by TLR7 and TLR9 can cause glucocorticoid resistance in lupus patients. This resistance was reversed by Dynavax's novel TLR7/TLR9 inhibitors in both human blood cells and in vivo animal models of lupus.

In October 2011, based on novel preclinical data, we announced the expansion of our alliance with GSK to include TLR8 as a new target. The activation of TLR8 in myeloid cells yields the production of multiple pro-inflammatory cytokines, including tumor necrosis factors (TNFs), IL-1, IL-6 and IL-12. We will evaluate the hypothesis that inhibition of TLR8 could prevent the inflammatory cascade initiated by these cytokines in many autoimmune conditions.

Under the terms of our alliance, GSK can exercise its exclusive option to license each program upon achievement of certain events, and we are eligible to receive option exercise payments. We are also eligible to receive tiered, up to double-digit royalties on sales and have retained an option to co-develop and co-promote one product.

Complementary to our research in the GSK programs, Dynavax is working to characterize the role of phosphoinositide 3-kinase (PI3K) in preclinical models of skin autoimmune inflammation. Scientists at Dynavax have shown that PI3K is required for the production of type I interferon (IFN) by plasmacytoid dendritic cells (PDCs) in response to TLR7 or TLR9 stimulation. Additionally, chronic activation of PDCs and the resulting IFN has been shown to play a role in skin autoimmune inflammation, making PI3K an attractive target for intervention in skin diseases such as psoriasis, cutaneous lupus, and dermatomyositis.

In September 2011, Dynavax received a two-year Small Business Innovation Research grant (SBIR) for our work on PI3K, awarded by the National Institute of Allergy and Infectious Diseases.

Clinical Results

In 2011, we initiated the first human clinical trial with DV1179 in healthy volunteers. DV1179 was shown to be well-tolerated in this Phase 1 trial, and, subsequently, in late 2011, we initiated a proof-of-mechanism clinical study of DV1179 in systemic lupus erythematosus (SLE) patients.

Commercial Opportunity

Over 20 million individuals in the U.S. and Europe have autoimmune diseases such as lupus, psoriasis, and rheumatoid arthritis. Key biologic drugs used to treat these conditions generate over $15 billion in worldwide sales each year.