AstraZeneca Will Validate siRNA Delivery Technology For MDRNA In Shanghai Innovation Center

SHANGHAI - Bothell, Washington-headquartered MDRNA announced recently that the company will collaborate with AstraZeneca to validate MDRNA's small interfering RNA (siRNA) technology for systemic delivery in hepatocellular carcinoma, one of the company's preclinical oncology programs.

The research work will be conducted in AstraZeneca's Innovation Center China, located at Zhangjiang Hi-tech Park, a pharmaceutical R&D hub in Shanghai that has attracted global players including Roche, GlaxoSmithKline, Pfizer, Novartis, and Eli Lilly, along with leading contract research organizations Wuxi PharmaTech and Charles River Laboratories.

Nastech Pharmaceutical changed its name to MDRNA June 10, 2008, divested its intranasal program and declared a new focus on research, development and delivery of its RNA interference work (Also see "Renamed Nastech Turns To RNAi" - Pink Sheet, 11 Jun, 2008.).

"AstraZeneca's ICC is evaluating MDRNA's MRNA-046 compound and MDRNA's DiLA2 delivery system with AstraZeneca siRNAs in their oncology models. Our mutual goal is to establish a basis for a larger, long-term R&D collaboration," June Ameen, MDRNA's vice president of corporate development, told PharmAsia News.

Delivery Is The Holy Grail In RNAi Therapeutics

"MDRNA's DiLA2 delivery system enables MDRNA to tailor the charge, linker length and acyl chain characteristics to improve the delivery of the liposomes to target tissues of interest," Ameen said.

"In vivo studies have demonstrated effective delivery in models of metabolic disease, cancer and other diseases. DiLA2-based liposomes are well tolerated for repeat dose and systemic and local administration," Ameen added.

MDRNA is also utilizing condensing peptides to form peptide-siRNA nanoparticles to further increase the efficiency of its DiLA2 delivery system.

"In addition, the platform is designed to permit attachment of peptides and other targeting molecules for delivery to a variety of tissues, and thus provide for a diverse therapeutic portfolio," Ameen said.

The company paid $46 million April 1 to acquire Cequent Pharmaceutical to strength its research work force on delivery systems for RNAi-based therapeutics.

Bladder Cancer Could Be The First IND For MDRNA

The first IND from MDRNA could be for non-muscle invasive bladder cancer, according to Chief Scientific Officer Barry Polisky. "Defining the clinical developmental pathway for this indication is critical and forms the basis for all our current IND activities," Polisky said during a March 23 earnings call.

MRNA-046 targets survivin, a protein involved in cell division and inhibition of apoptosis, and the company reports significant inhibition of tumor growth in mice.

MDRNA uses a DiLA2-based formulation to encapsulate survivin and Polo-like kinase 1, a protein involved in cell mitosis and tumor progression, and deliver them directly to the bladder.

At an equivalent total dose, tumor bioluminescence with a combination approach was roughly 30 percent lower when compared to a single UsiRNA, according to the company.

"We'll continue to drive on with bladder cancer and liver cancer at this point, as it is our emphasis on moving bladder cancer into an IND [and] is a significant effort for the company," CEO Michael French said during the earnings call.

"MDRNA's plan is to take the bladder cancer program into early clinical studies and identify a partner or a buyer. However, we are open to discussions with a potential partner at any time," Ameen told PharmAsia News.

Pursuing More Partnerships With MNCs

The collaboration with AstraZeneca is the third agreement with a large pharmaceutical company in the past nine months. However the company declined to disclose the names of two earlier partners.

"We can say they are focused on the capabilities of MDRNA's RNAi drug discovery platform and on working with our world-class research team," Ameen said.

According to Ameen, the company is talking with its early collaborative partners as well as with other major pharmaceutical companies regarding larger R&D collaboration.

Last February, Roche obtained a non-exclusive license to a portion of MDRNA's technology platform for the development of RNAi-based therapeutics.

RNAi accounted for 5 percent of Roche's R&D work in 2008 (Also see "China Leads Pharmaceutical Growth In 2009: Asia Pharma R&D Leaders" - Scrip, 4 Mar, 2010.).

- Dai Jialing ([email protected])