RNAi Roundup #4
Jul16

RNAi Roundup #4

While everyone was focused on Avandia & Qnexa, a spate of RNAi-related news slipped past us: --Tekmira Pharmaceuticals scored a major contract through the U.S. Department of Defense’s Transformational Medical Technologies program. The biotech will use its lipid nanoparticle technology to deliver siRNA tailored to treat the Ebola virua. Tekmira could snag up to $34.7 million over the next three years to help bring the Ebola virus candidate through an investigational new drug filing and a Phase I clinical trial. If the government decides to extend the contract beyond Phase I, Tekmira is eligible for up to $140 million in funding. The contract comes a few months after Tekmira and the U.S. Army Medical Research Institute of Infectious Diseases published an article in The Lancet showing its lipid nanoparticle could protect non-human primates against the Ebola virus. --Nitto Denko of Japan and Fremont, Calif.-based Quark Pharmaceuticals will jointly develop RNAi-based drugs to treat fibrotic diseases. The companies will use Quark’s RNAi technology and patent fortress, and Nitto Denko’s drug delivery technology. Terms weren’t disclosed, but the companies say they “have an initial budget of double-digit million US dollars” with the goal of filing their first investigational new drug application with FDA by early 2012. Nitto, which has expertise in polymeric formulations, says it picked Quark because of the chemical modification it had made to the siRNA that have eliminated worries over an immune response from the therapeutic. --AstraZeneca has extended its siRNA research pact with Silence Therapeutics by one year. The companies have worked together since 2007 on finding five novel siRNA therapeutic molecules for oncology and respiratory diseases. The duo forged a separate pact around siRNA delivery in April. --The NIH has awarded RXi Pharmaceuticals a small business innovation research grant (SBIR) worth $600,000 to support the pre-clinical development of RNAi-based therapeutics. NIH has seen a surge in applications for SBIR grants amid a tougher financing climate for biotechs. RXi is eligible for an additional $1 million per year for up to three years during the second phase of the SBIR’s program. --Alnylam Pharmaceuticals has dosed its first patient in a Phase I clinical trial of ALN-TTR01, a systemically-delivered RNAi therapeutic for the treatment of transthyretin (TTR)-mediated amyloidosis, a rare, inherited disease in which a mutation in the TTR gene causes the build up of the toxic protein in the several tissues in the body. This study is designed to test the safety of the drug and show whether the drug is impacting TTR levels in the...

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Exploding Microbubbles, RNAi, and RXi
Jun04

Exploding Microbubbles, RNAi, and RXi

The Haystack saw a press release yesterday out of Worcester, Mass.-based RNAi therapeutic firm RXi Pharmaceuticals that was intriguing. The company has signed a pact with Royal Philips Electronics to explore “image-guided therapy concepts based on RNAi.” What the heck does that mean? We were curious so we reached out to RXi for a primer, which turned into a bit of an update on where the company has come in the last year. Before we get into translating the mouthful of techno-speak from Philips and RXi, a few words to explain RXi’s delivery approach. Most folks in the RNAi therapeutics world are focused on encapsulating the siRNA in a lipid nanoparticle or polymer-based system: the formulation (in theory) guides the drug to its target cell and, once inside, releases its therapeutic payload. Check out our article on siRNA delivery for more details on the challenges and current limitations of that strategy. RXi is working on “self delivery” technology, which it bought from Boulder, Co.-based Advirna. As the company’s CSO (and Advirna co-founder) Anastasia Khvorova told me yesterday, the company is combining oligonucleotides, short single-stranded strings of nucleic acids, with small bits of double-stranded siRNA. RXi makes hydrophobic modifications to that hybrid molecule that stabilize the structure and allow it to be taken up by the cell of interest. They wind up with a large complex that has been tricked out to behave like a small molecule. So what does Philips bring to the table? RXi hopes to improve the potency of its self-delivery RNAi molecules using Philips’ formulation technology, which traps drugs inside “microbubbles” that are sensitive to ultrasound pulses. After a drug is dosed, it travels to the tissue of interest and an ultrasound pulse is applied, causing the bubbles to explode and the drug to be released. It all sounds rather futuristic, but RXi thinks it could significantly improve the potency of its molecules by one-to-two orders of magnitude. “Our RNAi molecules are very good at getting into cells once they’re kind of in the proximity, whereas their technology helps us get into the right organs,” RXi’s CEO Noah Beerman says. It’s cool stuff, but will it work? It remains to be seen, but it’s nice that some outside-the-box thinking is getting play in the RNAi arena. As mentioned, many companies continue to beat the lipid nanoparticle drum, but that technology has yet to work across a wide range of diseases. The need for chemistry and engineering to step in and come up with some innovative approaches to RNAi delivery is great. It’s worth noting that all this shiny new technology is a bit of a departure...

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