Quark siRNAs Examined Alone and in Combination with Chemotherapy

Fremont, CA October 13, 2008 – Quark Pharmaceuticals, Inc., a development-stage pharmaceutical company discovering and developing novel RNA interference (RNAi)-based therapeutics, today announced that the journal Cancer Research published results on efficacy of siRNA targeting its proprietary target gene against non-small cell lung cancer (NSCLC) in the edition dated October 1, 2008. The paper, entitled “RNAi-Mediated Silencing of Nuclear Factor Erythroid-2–Related Factor 2 Gene Expression in Non–Small Cell Lung Cancer Inhibits Tumor Growth and Increases Efficacy of Chemotherapy,” reports on research performed in collaboration with Professor Shyam Biswal of the Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University. The results provide a basis for a potential new drug candidate to be added to Quark’s pipeline.
The study examined efficacy of RNAi-mediated reduction of Nuclear Factor Erythroid-2–Related Factor 2 (Nrf2) expression in vitro and in in vivo mouse NSCLC xenograft models alone or in combination with chemotherapy. The results show that RNAi-mediated reduction of Nrf2 expression generates reactive oxygen species, suppresses tumor growth, and increases sensitivity to chemotherapeutic drug–induced cell death.
Elena Feinstein, M.D., Ph.D., Chief Scientific Officer of Quark Pharmaceuticals, said, “Nrf2 appears in our IP portfolio as a novel drug target for cancer treatment. Discovery of the target’s role in cancer was made years ago, using our proprietary functional high throughput drug target discovery method, BiFAR™, when we looked for genes whose inhibition could sensitize cancer cells to apoptosis. Since then, much progress has been made to study the concept of Nrf2 inhibition for cancer treatment by the scientific community. One of the major contributors in this field is Prof. Biswal from Johns Hopkins University with whom we have established a very productive collaboration. The results of the present study reconfirm our interest in the target and provide for new product opportunities within our expanding siRNA product pipeline. Quark has the deepest clinical-stage pipeline of siRNAs under development, with efficacy studies completed for several compounds, many stemming from our internal gene discovery programs, and ongoing research efforts to further broaden our range of siRNA product candidates.”
Professor Shyam Biswal of the Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, principal investigator of the study said, “RNAi-mediated reduction of Nrf2 expression represents a potential breakthrough for treating non-small cell lung cancer. Suppression of Nrf2 effectively inhibited tumor growth and increased sensitivity to chemotherapeutic drug-induced cell death in the study. It is critical that we establish new and effective therapies for NSCLC, which is intrinsically resistant and generally nonresponsive to initial chemotherapy, and commonly leads to acquired resistance even as therapies become increasingly sophisticated. We are encouraged by Quark’s continued evaluation and development of therapeutics that target Nrf2 to inhibit tumor growth and circumvent chemoresistance.”
Quark Pharmaceuticals has recently announced QPI-1007, its first drug candidate to utilize a novel siRNA structure developed by Quark with freedom to operate in the siRNA intellectual property space. QPI-1007 is currently being evaluated in advanced IND-enabling preclinical studies as a neuroprotective agent for eye diseases.


About Quark Pharmaceuticals, Inc.

Quark Pharmaceuticals, Inc. is a development-stage pharmaceutical company engaged in discovering and developing novel therapeutic RNAi drug candidates. Quark has a fully integrated drug development platform that spans therapeutic target identification to drug development. Quark’s RNAi technology includes novel siRNA structures and chemistry providing Quark with freedom to operate in the siRNA intellectual property arena, as well as the ability for non-invasive delivery of siRNA to target tissues including the eye, ear, kidney, lung, spinal cord and brain.
PF-4523655 (RTP801i-14), currently in Phase II clinical trials, is a synthetic, chemically modified, siRNA molecule to inhibit the expression of the gene RTP801 discovered by Quark through the gene discovery platform BiFAR. PF-4523655 is licensed to Pfizer. In addition, Quark’s current clinical pipeline includes AKIi-5, developed by Quark for the prevention of acute kidney injury (AKI) following major cardiac surgery, currently in Phase I/IIa clinical trials via systemic delivery and DGFi, about to start phase I/II for prevention of delayed graft function in kidney transplantation. Based on publicly available information, Quark believes AKIi-5 was the first siRNA administered systemically in a human clinical study.
In addition, Quark has a broad pipeline of siRNA drug candidates based on novel structures developed internally. The Company expects to utilize the structures to develop additional RNAi drug candidates.
Quark is headquartered in Fremont, California and operates research and development facilities in Boulder, Colorado and Ness-Ziona, Israel. Additional information is available at www.quarkpharma.com