RXi Pharmaceuticals Announces Publication in Nature of Positive Pre-clinical Data Demonstrating that Oral Administration of RNAi Therapeutics Effectiv

RXi Pharmaceuticals announced the publication of an article in the journal Nature that presents new pre-clinical data demonstrating that low dose (20 μg/kg) oral administration of RNAi therapeutics resulted in a significant reduction of a systemic inflammatory response in an established mouse model of inflammation

WORCESTER, MA, USA | April 30, 2009 | RXi Pharmaceuticals Corporation (Nasdaq: RXII), a biopharmaceutical company pursuing the development and commercialization of proprietary therapeutics based on RNA interference (RNAi), today announced the publication of an article in the journal Nature that presents new pre-clinical data demonstrating that low dose (20 μg/kg) oral administration of RNAi therapeutics resulted in a significant reduction of a systemic inflammatory response in an established mouse model of inflammation.

This important work on oral delivery of RNAi compounds was published by Michael Czech, Ph.D., co-founder of, and Scientific Advisor to, RXi Pharmaceuticals and Professor and Chair of Molecular Medicine and Professor of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School (UMMS) (Aouadi, et al, Nature, Vol. 458 (7242), pp. 1180-1184). RXi Pharmaceuticals has the exclusive worldwide rights to certain patent applications claiming aspects of the technology behind the oral delivery of RNAi therapeutics upon which this work was based under a license agreement entered with UMMS in October 2008.

Commenting on today’s news, Tod Woolf, Ph.D., President and Chief Executive Officer of RXi Pharmaceuticals, noted, “Oral administration of RNAi therapeutics using this particular technology is a major scientific breakthrough that was not previously thought practical. As a result of the publication of Dr. Czech’s data in Nature, one of the premier scientific journals, it now appears that this method may constitute a significant advance in RNAi delivery. This new orally available, low dose RNAi therapy may be able to control many severe inflammatory diseases without the need for more invasive types of administration such as injection, which is the current standard of care for approved non-RNAi therapeutics. We believe that oral RNAi therapeutics, if successfully developed, could address the multi-billion dollar markets of rheumatoid arthritis, Crohn’s disease, atherosclerosis, inflammatory bowel disease and diabetes. As a result, this new technology provides many potential scientific and commercial opportunities for RXi Pharmaceuticals, and we are focusing our resources on this exciting therapeutic area.”

In the published work, which was funded by UMMS and the National Institutes of Health, oral delivery of micron sized RNAi encapsulation vehicles made of beta 1,3 D glucan (called “GeRPs”) target macrophages in the gut that then migrate to tissues throughout the body. Gene silencing of the cytokine TNF-alpha or the protein kinase MAP4K4 that controls TNF-alpha expression was observed in isolated immune cells of treated mice, as compared to controls, after oral administration of the respective GeRP-encapsulated RNAi compound. Silencing of the MAP4K4 target gene mRNA level was observed in macrophages isolated from spleen, liver and lung tissues. Additional experiments featured in the publication showed that the gene silencing with this technology and delivery of unmodified siRNAs lasted about eight days following the termination of oral administration.

The data presented in Nature shows that the GeRPs efficiently target immune cells and that efficient gene silencing can be observed specifically in macrophages. In addition, the work revealed that MAP4K4 is a novel mediator of cytokine expression, providing an opportunity to use this target to attenuate the inflammatory response in human diseases.

Michael Czech, Ph.D., noted, “Macrophages are key cells which orchestrate immune responses in man. Our collaboration with Gary Ostroff, Ph.D., Professor of Molecular Medicine, and my colleague here at UMMS, has led to encouraging results that show oral delivery of RNAi compounds is feasible for reducing inflammatory gene expression in these cell types. We are very excited about this technology and the potential to move it forward in collaboration with RXi Pharmaceuticals.”

Earlier this year, a collaboration between RXi Pharmaceuticals and the UMMS research team received funding from a Massachusetts Life Sciences Center Cooperative Research Grant to further develop this technology. The three-year grant of up to $250,000 per year, which is part of the state’s $1 billion, 10-year life-science initiative, will help fund the use of RXi Pharmaceutical’s rxRNA™ compounds to advance the progress of oral administration of RNAi therapeutics.

RXi Pharmaceuticals has an agreement with UMMS whereby UMMS has granted RXi an exclusive license to certain patent applications to this technology and co-exclusive options to other underlying technology. UMMS and inventors of this intellectual property may receive developmental milestones and/or royalty payments pursuant to the agreement.

The journal article can be accessed on-line at www.nature.com.

About GeRPs

The GeRP delivery system uses hollow, porous, micron-sized shells filled with RNAi compounds that may be taken up by M (microfold) cells in the intestinal wall and are then transferred to the underlying GALT (gut associated lymphatic tissue) where they are then taken up by macrophages and other phagocytic cell types. The RNAi compounds are presumed to be released into the cytoplasm of the macrophage where they will start silencing genes by an RNAi mechanism, while the macrophages traffic throughout the body. The GeRP delivery system appears to be 5 to 250 times more potent than previous generally known methods used for systemic delivery of RNAi therapeutics by intravenous injection. The loading capacity of the shells would also potentially allow co-delivery of RNAi, DNA, protein and small molecule combinations.

About RXi Pharmaceuticals Corporation

RXi Pharmaceuticals is a discovery-stage biopharmaceutical company pursuing the development and potential commercialization of proprietary therapeutics based on RNA interference (RNAi) for the treatment of human diseases. RXi has a comprehensive RNAi platform that includes both RNAi compounds and delivery methods. RXi Pharmaceuticals’ rxRNA™ compounds are distinct from the siRNA compounds used by many other companies developing RNAi therapeutics and are very active and potent (10-100pM activity in cell culture) based on the company’s internal research, in addition to being nuclease resistant and readily manufactured. RXi Pharmaceuticals believes it is well positioned to compete successfully in the RNAi-based therapeutics market with its accomplished scientific advisors, including Dr. Craig Mello, recipient of the 2006 Nobel Prize for his co-discovery of RNAi; a management team that is experienced in developing RNAi products; and a strong early intellectual property position in RNAi chemistry and delivery. www.rxipharma.com.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $193 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu.

SOURCE: RXi Pharmaceuticals

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