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Arrowhead Receives Notice of Patent Allowance for New Protease Sensitive Masking Chemistry for DPC siRNA Delivery System
PASADENA, Calif. — February 28, 2013 — Arrowhead Research Corporation, a targeted therapeutics company, today announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office for U.S. Patent Application Number 13/336,028 entitled, “In Vivo Polynucleotide Delivery Conjugates Having Enzyme Sensitive Linkages.” This new IP expands the Dynamic Polyconjugate (DPC) platform, broadly protecting Arrowhead's next generation DPC polymer masking technology. Using this masking technology, DPCs can be engineered for long circulation times and improved tissue-targeting characteristics. In addition, hepatocyte-targeted DPCs formulated using this new masking technology have shown to be highly potent upon subcutaneous administration. The company has previously reported target gene knockdown of 99% in monkeys after a single subcutaneous injection of 1 mg/kg, with >80% knockdown for 3 months. Additional data will be reported at upcoming scientific conferences and through peer-reviewed publications.
“This patent protects a new masking chemistry that broadens the reach of DPC-enabled RNAi therapeutics. It enables efficient subcutaneous delivery of siRNA and opens up new therapeutic area targets including oncology,” said Dr. Chris Anzalone, President and CEO of Arrowhead. “Arrowhead scientists continue to discover innovative solutions for siRNA delivery and we look forward to providing updates on how these technologies are being deployed to create new drug candidates.”
ir.arrowheadresearch.com/releasedetail.cfm?ReleaseID=841010
Arrowhead Extends Lead as ISIS Pharmaceuticals Goes Back to Drawing Board
During the Q&A session of the recent quarterly conference call, ISIS Pharmaceuticals revealed a setback in its HBV program. The compound that had entered the clinic last year has been shelved in favor of finding a more potent GalNAc-based version of ISIS-HBVRx. It is likely that this decision has been driven by competitive considerations as well as the dilemma presented by rapidly progressing technology platforms: at what point do I settle on a development candidate?
Competition and technology improvements
We may never find out about the knockdown results from the clinical studies, if such data has indeed been gathered. However, based on the presentation on ISIS-HBVRx at EASL 2014 in April, the generation 2.0 (2’ MOE gapmer) compound did not appear to have particularly impressive potency in the rodent models (ED50 for HBsAg knockdown in transgenic HBV mice of ~5mg/kg).
Especially in light of Regulus’ spectacular GalNAc-based results in HCV last month, it should have been an easy decision to terminate a compound that would have struggled to achieve 80% knockdown in Man in favor of a much more potent compound. The combination of the gen 2.5 cET chemistry and GalNAc are predicted to increase potency by 10-50 fold, giving the RNAi competition a good run for their money.
As a result of that decision, the first-in-class lead of Arrowhead Research has significantly widened with ARC520 now being the only compound in active clinical development. Tekmira’s candidate should be next with an IND expected in the coming months. Meanwhile Alnylam’s candidate appears to exist only in the form of press releases and ISIS with partner GSK have now gone back to the drawing board.
So yes, Arrowhead, get that subQ and especially much more potent single molecule DPC backup ready. There is still time for it.
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