WHITEFISH, MT / June 9th , 2014 / RNA therapeutics have been growing in popularity over the past couple years with the FDA approval of ISIS Pharmaceuticals’ (ISIS) and Sanofi SA’s (SNY) Kynamro(R) as the first antisense drug to reach the market and Alnylam Pharmaceuticals’ (ALNY) successes in late-stage clinical trials utilizing RNA interference ("RNAi") in its so-called 5×15 clinical pipeline.
Unfortunately, both of these approaches have drawbacks when it comes to clinical efficacy. Traditional antisense compounds have favorable tissue distribution and cellular uptake, but don’t have the intracellular potency of RNAi compounds. On the other side, the structure of traditional RNAi compounds result in poor tissue distribution and cellular uptake relative to antisense technologies.
In this article, we’ll take a look at a company that has bridged the divide between antisense and RNAi by taking the best of both worlds.
Best of Both Worlds
RXi Pharmaceuticals Corp. (RXII) has developed a unique platform, known as sd-rxRNA, that bridges the gap between antisense and RNAi. The technology has a single-stranded phosphorothioate region, a short duplex region, and contains a variety of nuclease-stabilizing and lipophilic chemical modifiers. These features provide both efficiency cellular uptake and long-lasting intracellular activity.
Figure 1 – Tissue Uptake & Distribution – Source: RXi Pharmaceuticals Corp.
The efficient cellular uptake is observed both in vitro and in vivo in tissues including the skin, retina, lung, spinal cord, and liver (Figure 1). Since tissue distribution is defined by the administration route and pharmacokinetic properties, efficient uptake of sd-rxRNA could be possible in any tissue as long as the administration route permits local delivery of the compound.
With the ability to improve tissue distribution and cellular uptake across multiple tissue types, the platform could address most if not all RNA-targetable indications, ranging from rare genetic disorders to cancers. The company has already built a sizeable pipeline in areas like dermal scarring, PVR, macular degeneration, retinoblastoma, and other conditions (see Figure 2).
Figure 2 – RXi Pharma Clinical Pipeline – Source: RXi Pharmaceuticals Corp.
RXi Pharmaceutical’s initial proof-of-concept is its RXI-109 compound for the treatment of dermal scarring following planned surgeries. By reducing the expression of CTGF, a regulator of biological pathways involved with fibrosis and scar formation, RXI-109 is expected to significantly reduce serious scarring following a variety of different types of surgery.
RXi Pharmaceuticals President and CEO, Dr. Geert Cauwenbergh, commented in a July 2013 press release discussing the company’s second Phase 1 study (RXI-109-1202), results, "These results show that multiple intradermal injections of RXI-109 are well tolerated … results from this second study demonstrate the mRNA for CTGF in the incisions is reduced in a dose-dependent manner by RXI-109 as compared to placebo."
In May 2014, the company also announced positive results from its assessment of CTGF protein levels following an intravitreal injection of RXI-109 in the eyes of cynomolgus monkeys. This dose-range finding study, which is part of the initial steps to build the company’s growing ophthalmology franchise, also demonstrates the ability of the sd-rxRNA compounds to penetrate ocular tissues.
RXi Pharmaceuticals has announced that it received a Notice of Allowance from the U.S. Patent & Trademark Office for sd-rxRNA in late May 2014. Broadly covering both the composition and methods used by the platform technology, the patent protects the company’s approach of integrating drug-like properties in RNAi compounds until the patent expires in 2029.
"This key patent is what differentiates RXi’s technology platform from the competition," said Dr. Cauwenbergh. "It provides us with a powerful advantage to deliver our RNAi compounds without delivery vehicles, which are commonly used with other siRNA compounds in clinical development. The use of our proprietary sd-rxRNA technology platform may lead to improved tolerability and thereby potentially broadening of the therapeutic window for these compounds."
The patent also adds to the company’s extensive patent portfolio that provides multiple layers of intellectual property protection for the rxRNA and sd-rxRNA platforms, as well as for innovations in RNA delivery technologies. The complete portfolio includes RNAi compound designs, oligonucleotide technologies, sequences for multiple therapeutic target genes, and therapeutic methods in treating diseases.
RXi Pharmaceuticals’ stock has moved off of its highs from earlier this year, but its underlying platform technology and clinical pipeline remain robust. With key patents issued on its sd-rxRNA platform, the company is well positioned to continue developing RXI-109 as a proof-of-concept. The platform could become significantly more valuable with a successful drug under its belt over the coming years.
In particular, the company’s sd-rxRNA platform could be licensed to third party drug companies interested in joint ventures pursuing other diseases and conditions. Shareholders could benefit from the wider scope of conditions covered, diversified pipeline of opportunities, and ultimately potential royalty revenue. These factors make the stock worth a second look for biotechnology investors.
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SOURCE: Emerging Growth LLC