RXi Pharma claims ‘first place’ in RNAi

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WORCESTER, Mass.—RXi Pharmaceuticals Corp., which will soonbe spun-out by Cytrx Corp. to become an independent publicly traded company,has entered into an agreement with privately held TriLink Biotechnologies Inc.to exclusively license three RNAi chemistry technologies. These include apatented method of adding a peptide or other link to RNAi; novel RNAi-likechimeric RNA-DNA duplexes; and an undisclosed chemistry approach that haspotential to improve existing RNAi compounds, which have historically been bothunstable and somewhat nonspecific in vivo.

Although financial terms of the agreement are not beingdisclosed, it includes upfront and yearly minimum licensing payments, royaltiesof 1 percent or less from RXi to TriLink on sales of therapeutic productsdeveloped from the licensed technologies, and payments based on the achievementof certain clinical milestones.

"This licensed TriLink chemistry technology adds componentsto our expanding RNAi toolbox and can be integrated with our existingtechnology portfolio to create advanced proprietary RNAi compounds that haveshown certain potential advantages in terms of potency and otherpharmacological properties," says Dr. Tod Woolf, president and CEO of RXi. "Thelicensed technology was created by the TriLink chemists, who have beenrecognized leaders over the past decade in the design and manufacture ofadvanced RNA compounds."

Supporting Woolf's claim that RXi is "first in RNAi," thecompany lists a virtual Who's Who of RNAi researchers among its management teamand scientific advisory board, the chairman of which is 2006 Nobel Laureate Dr.Craig C. Mello, who received the honor as the co-discoverer of RNAi. Others onthe RXi team include Dr. Tariq M. Rana, inventor of fundamental technology forstabilizing RNAi and of RNAi nanotransporters; Dr. Greg Hannon, discoverer ofthe RNAi mechanism RNA-induced silencing complex (RISC) and short hairpin RNAi(shRNA); and Dr. Michael Czech, a leader in the application of RNAi to diabetesand obesity.

Finally, Dr. Woolf co-invented and commercialized StealthRNAi, a widely used second-generation RNAi research product. Mello was anadviser to Tod Woolf when the latter's company Sequitur, where Stealth RNAioriginated, was bought by Invitrogen.

Woolf believes that its licensed RNAi chemistries anddelivery technologies cover all therapeutic areas, and may potentially be usedto target any gene of therapeutic interest. Initially, RXi is pursuing researchin amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Some forms ofALS are caused by defects in a gene called SOD1. Early preclinical studies in amouse model of SOD1-mediated ALS, conducted by Rana and RXi advisor Dr.Zuoshang Xu at the University of Massachusetts Medical School, showed promisingresults using an RNAi therapeutic to selectively inhibit the SOD1 gene.

RXi is refining and extending this work and, if successful,the company intends to advance towards preclinical development. RXi alsointends to leverage its experience related to the delivery of RNAi compounds inthe central nervous system to explore development of RNAi-based treatments forneurodegenerative diseases other than ALS, including Alzheimer's disease andHuntington's disease for which no effective therapies are currently available.

Another area of active development is based on Greg Hannon'sshRNA, which are single-stranded RNA molecules of about 21-23 nucleotides whosemain function is downregulating gene expression.

A third area of emphasis is RIP140, a gene identified byCzech, which appears to act as a master regulator of metabolism. According toWoolf, studies have shown that inactivation of RIP140 may be able to convertfat cells from a fat storage to a fat burning mode.

For example, in studies using a mouse model for diabetes andobesity, turning off the expression of RIP140 results in mice that remain leanand non-diabetic even when maintained on a high-fat diet. RIP140 is a member ofa protein class that does not appear to be effectively treatable withtraditional small-molecule approaches; however, it may be treatable with anRNAi-based approach.RXi has acquired exclusive rights to develop RNAi compoundstargeting the RIP140 gene from the University of Massachusetts Medical Schooland The Imperial College of London.

With its eye on oncology, RXi is also actively seeking toleverage its technology platform by working with larger pharmaceutical andbiotechnology partners.

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