DV281 is a novel investigational TLR9 agonist designed specifically for focused delivery to primary lung tumors and lung metastases. DV281 is similar in biological activity and mechanism of action to SD-101, but has been optimized for administration as an aerosol. Clinical and preclinical studies with SD-101 have demonstrated the advantage of localized delivery of TLR9 agonists to the tumor site; however, the strategy of focused intratumoral injection used in our SD-101 program is not practical for lung tumors. An alternate strategy for focused delivery to lung tumors would be direct administration to the lung by inhalation.
Dynavax pioneered the development of an inhaled TLR9 agonist for asthma. This oligonucleotide, AZD1419, was developed in partnership with AstraZeneca and is currently being evaluated in a phase 2 clinical trial in asthma patients. Based on this experience, Dynavax is developing a novel TLR9 agonist, DV281, formulated for delivery to lung cancer patients as an inhaled aerosol.
Studies in preclinical animal models of lung cancer show that this direct delivery of DV281 to tumor-bearing lungs results in induction of interferons and cytokines and infiltration of T cells, responses similar to those observed after intratumoral injection of SD-101. Animal models also demonstrate clear synergy of inhaled DV281 with anti-PD-1 antibodies in reducing tumor burden and generating a systemic and durable anti-tumor response. Inhibitors of the PD-1/PD-L1 pathway have become the standard treatment for patients with the most common form of lung cancer and Dynavax will focus clinical development on combinations of DV281 and a PD-1 inhibitor. Inhaled DV281, delivered by a nebulizer, is expected to enter clinical trials for non-small cell lung carcinoma (NSCLC), in combination with anti-PD-1 therapy, in 2017.