RXi Pharmaceuticals Still Confident About Outstanding 2010 Goals

A week or so ago, I had the opportunity to talk by phone to the CEO and CSO of RXi Pharmaceuticals, Noah Beerman and Anastasia Khvorova respectively, about the company's scientific and business development strategy. Overall, they were quite upbeat about the prospect of turning around the perception of a company aimlessly wandering around in early technology development and increase shareholder value by finally moving their technology into the clinic and raise the promised non-dilutive capital. Specifically, they did not flinch when asked about their belief whether they were still on track to achieve their outstanding 2010 goals: the selection of their first development candidate (anti-scarring) for which an IND would be expected in 2011, and establishing their first major partnership.

Painfully aware that RXi has a history of promising lucrative partnerships, not one of which has yet to come to fruition, I specifically wanted to confirm that the stated partnership goal is yet to be reached and is not accounted for by the recent string of deals where RXi evaluates whether its self-delivering siRNAs ('sd-rxRNA') have utility in conjunction with technologies provided by partners small and large. While definitely the right approach to explore the wider potential of sd-rxRNAs (note that they have 6-12 month milestone goals), these deals lack the traditional upfront monies and royalties/milestones which would make a world of a difference in limiting shareholder dilution until the company’s own product candidates will allow it to raise capital on the risk-averse financial markets on favourable terms. And yes, Noah Beerman left no doubt that the company has no intention of letting the technology development deals serve as a substitute for that partnership goal.

Yet the exact nature of such a deal was left an open question. It seems that the company is still debating internally about issues such as whether such a deal ought to involve its strategic areas or its core focus areas in ocular and dermal disease. I can understand if a potential partner wanted to benefit from the company’s technology for ocular disease in particular, but that RXi might feel that it should get a better valuation for that at a later point. On the other hand, with self-delivering rxRNAs having potential for direct and localized RNAi applications beyond their core focus areas, such as in certain cancers (e.g. cervical, bladder, breast, maybe liver), respiratory disease, and disorders of the CNS, there could be demand for the technology in non-focus areas, too. This would be mutually beneficial, since these investments would help develop sd-rxRNAs in areas, many of which very attractive financially, for which RXi with its 32 employees and less than $10M in cash realistically wouldn’t have the resources to pursue on its own and the potential value of which would eventually have to be written down. Accordingly, it seemed that CNS and oncology could indeed be high-traffic areas for partnership discussions.

Do I believe that RXi’s sd-rxRNAs have the potential to form the basis for a decent Big Pharma deal (what follows in the next two paragraphs are my speculations only, not management’s guidance)? Based on conference presentations and the company’s patent application for the technology, I do believe that it has such value simply because unformulated siRNAs should eventually occupy a niche in RNAi Therapeutics and RXi can be considered a, if not the emerging leader in this area. Alnylam (of cholesterol-siRNA conjugate fame), naturally, and Dharmacon (Accell siRNAs) can probably be considered the two closest competitors. While Alnylam seemed to have the early lead in the area (2004 Nature and 2007 Nature biotech papers), it is not clear to me what their current stage of the technology is. It seems like the comparative data slightly favors sd-rxRNAs, but in order to command favourable economics, one has to assume that RXi has now amassed, through sheer focus and some siRNA chemistry genius of Dr Khvorova, such a toolbox of diverse chemistries and know-how in designing potent sd-rxRNAs such that candidates with IC50 potencies in the low nanomolar range can be found routinely in passive tissue culture uptake studies, instead of the 500nM-10uM potencies commonly observed with first-generation lipophilic-siRNA conjugates. In this regard, I am concerned that the patent applications that provide RNAi trigger screening examples for a number of genes, do not support that. However, RXi may have chosen, for trade secret purposes, not to provide the best mode in the patent application, but modes of applications sufficiently advanced to get patents issued.

If the technology has indeed advanced over what is publicly available and a deal were to involve the core area of ocular disease, I could imagine a drug discovery deal in which RXi gives away a handful of targets in return for ~$20M in upfront plus the usual milestones and royalties. If CNS or oncology, a deal involving a similar number of drug candidates with a $10M upfront plus an equity investment at a premium would appear reasonable.

As we concluded the talk, I had to ask about how to interpret parent company CytRx' aggressive selling of RXi stock, very disconcerting indeed given the already depressed share price (RXII) at which some of these purchases happened, a financial position by CytRx that does not appear too distressed and the fact that the CEO of CytRx, Mr. Steven Kriegsman, sits on RXi’s Board of Directors. It was apparent that this must be a question that RXi is often asked, and while Noah Beerman did not want to speak on behalf of CytRx, he told me to listen to Mr. Kriegsman’s own words on the RXi stock issue. So I did. What Mr. Kriegsman said in conference presentations (paraphrasing now) is that isn’t it nice to be able to use RXi as a piggy bank, but isn’t it also nice at the same time to be still the largest owner of RXII shares (~17% of outstanding) in case that RXII goes up for a change. Since RXi has strictly served CytRx as a piggy bank thus far, RXi shareholders will hope that the rest of the comments were not but some empty words.