RXi Pharmaceuticals Announces Positive Results with RXI-109 in the Eyes of Cynomolgus Monkeys as Part of a Dose Range Finding Study

MARLBOROUGH, Mass., May 2, 2014 -- RXi Pharmaceuticals Corporation (RXII), a biotechnology company focused on discovering, developing and commercializing innovative therapies addressing major unmet medical needs using RNA-targeted technologies, today announced results from the assessment of connective tissue growth factor (CTGF) protein levels following intravitreal injection, of RXI‑109 in the eyes of cynomolgus monkeys, as part of a dose-range finding study to build the Company's ophthalmology franchise.

CTGF protein levels were determined by immunohistochemistry methods seven days following injection and quantified by digital image analysis of stained slides. Intravitreal administration of RXI‑109 resulted in a reduction of CTGF protein levels in a dose-dependent manner in the retina. Whole eye sections were collected in this study and the Company was also able to determine CTGF protein levels in the cornea, and noted that these protein levels were also reduced in a dose-dependent manner in the cornea tissue.   

"These remarkable results constitute a major boost to the value of our newly formed ophthalmology franchise," said Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. He added that, "Not only do these data confirm that RXI‑109 lowers CTGF protein levels in a dose dependent manner in the retina of non-human primates, but it also demonstrates that, with an intravitreal injection of RXI‑109, sufficient compound migrates to the cornea to lower CTGF protein levels in that eye tissue as well. This finding opens up an avenue to possibly develop topical forms of RXI‑109 to combat corneal scarring which often occurs secondary to trauma or infection and can lead to visual impairment, including blindness."

About Retinal Scarring

Retinal scarring is the development of scar tissue on the retina as a result of injury or as a consequence of disease. During injury many critical cellular pathways become active including proliferation, adhesion, migration, angiogenesis and scar tissue remodeling. CTGF modulates signals from a wide range of factors in the cell and in this way impacts some of these critical cellular pathways. Overproduction of CTGF is implicated in fibrotic disease and scarring in many tissues including the retina. Specifically, CTGF has been found to be upregulated in proliferative vitreoretinopathy membranes of both human and rabbit (He, Chen et al., 2008) and has been shown to be expressed by Müller cells and RPE cells, two cell types that undergo proliferation in the presence of injury and contribute to retinal scarring.

About Corneal Scarring

The cornea is a transparent tissue at the front of the eye that plays two key roles in the health of the eye. First, it provides a physical barrier to protect the inner eye from environmental factors. Second, the cornea is instrumental in directing incoming light to the lens and retina. Scarring of the cornea resulting from injury, disease, or vision correction surgery can have a dramatic impact on vision. In some cases, a corneal transplant may be needed. Importantly, CTGF expression levels have been found to be increased during corneal wound healing in rat corneas and in human corneal fibroblasts and it has been proposed that a reduction of CTGF may be an important step towards reducing corneal scarring (Blalock et al., 2003).

About RXI-109

RXI-109 is an sd-rxRNA® that targets the mRNA of connective tissue growth factor (CTGF), a gene known to modulate fibrosis and scar formation. RXI-109 is initially being developed to reduce or inhibit scar formation in the skin following surgery.  The first clinical trials with RXI‑109 (RXI‑109‑1201 and RXI‑109‑1202) showed excellent safety and tolerability, with ascending single and multiple doses respectively, as well as dose dependent effects on the CTGF protein and on the mRNA that controls production of this protein.

Two Phase 2 clinical trials are currently underway to evaluate the effectiveness and safety of RXI‑109 on the outcome of scar revision surgeries performed on hypertrophic scars resulting from lower abdominal surgeries (RXI‑109‑1301) and to evaluate the effectiveness and safety RXI‑109 in healthy subjects who undergo an elective surgical excision of two similarly sized and placed keloids (RXI‑109‑1401).

About RXi Pharmaceuticals Corporation

RXi Pharmaceuticals Corporation (RXII) is a biotechnology company focused on discovering, developing and commercializing innovative therapies based on its proprietary, self-delivering RNAi (sd-rxRNA®) platform. Therapeutics that use RNA interference, or "RNAi," have great promise because of their ability to down-regulate the expression of specific genes that may be over-expressed in disease conditions. Building on the pioneering work of scientific founder and Nobel Laureate Dr. Craig Mello, a member of the RXi Scientific Advisory Board, RXi's first RNAi product candidate, RXI‑109, entered into human clinical trials in June 2012 and is currently conducting Phase 2 clinical trials.  RXI‑109 targets connective tissue growth factor (CTGF) to reduce dermal scarring (fibrosis). RXi's sd‑rxRNA oligonucleotides are designed for therapeutic use and have drug-like properties, such as high potency, target specificity, serum stability, reduced immune response activation, and efficient cellular uptake. These hybrid oligonucleotide molecules combine the beneficial properties of conventional RNAi and antisense technologies.  This allows sd‑rxRNAs to achieve efficient cellular uptake and potent, long-lasting intracellular activity. For more information, please visit www.rxipharma.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about future expectations, planned and future development of RXi Pharmaceuticals Corporation's products and technologies. Forward-looking statements about expectations and development plans of RXi's products involve significant risks, and uncertainties: risks that RXi may not be able to successfully develop its candidates, or that development of RNAi-based therapeutics may be delayed or not proceed as planned, or that we may not develop any RNAi-based product; risks that the development process for our product candidates may be delayed, risks related to development and commercialization of products by our competitors, risks related to our ability to control timing and terms of collaborations with third parties, and the possibility that other companies or organizations may assert patent rights preventing us from developing our products. Actual results may differ from those contemplated by these forward-looking statements. RXi does not undertake to update forward-looking statements to reflect a change in its views, events or circumstances that occur after the date of this release.

References

He, S., Y. Chen, et al. "Connective tissue growth factor as a mediator of intraocular fibrosis." Invest Ophthalmol Vis Sci 2008; (9): 4078-88.

Blalock, T.D., M. R. Duncan, et al. "Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy." Invest Ophthalmol Vis Sci 2003; 44 (5): 1879-87.

Contacts

RXi Pharmaceuticals Corporation
Tamara McGrillen, 508-929-3646
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