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Sep 12, 2011

Silence and InteRNA Partner to Develop AtuPlex-Formulated Anticancer miRNAs

  • Silence Therapeutics and InteRNA Technologies inked a collaboration to develop anticancer miRNA therapeutics using Silence’s AtuPlex™ delivery system. Under terms of the deal, InteRNA will provide specific miRNA sequences, which Silence will formulate using the AtuPlex delivery system to develop multiple candidates. The firms will partner on in vitro and in vivo studies and selection of candidates for further development. Silence is eligible for up-front fees and staged research payments.

    Silence is focused on the discovery, development, and delivery of RNA interference (RNAi) therapeutics. The firm’s AtuPlex delivery platform is based on lipid components known as AtuFect that embed siRNA into multiple lipid bilayer structures. The resulting nanoparticle structure consists of the siRNA combined with a cationic lipid, fusiogenic lipid, and PEG. 

    Silence is currently exploiting the AtuPlex platform in house for the development of siRNA therapeutics. The deal with InteRNA will expand application of the technology to the delivery of a different class of oligonucleotides. “Functional delivery into target cells is one of the greatest challenges facing most nucleic acid therapies,” comments Thomas Christely, COO.

    InteRNA says the collaboration will provide a potential means to deliver its RNA-based therapeutic candidates via systemic administration. “AtuPlex may significantly contribute to the efficacy of several miRNA drug candidates in our pipeline that have shown to reduce tumor growth in vivo,” adds Roel Schaapveld, Ph.D., CEO.

    Silence has a number of in-house and partnered AtuPlex-formulated RNAi candidates in clinical trials. Lead in-house candidate, Atu027, is a liposomal siRNA formulation targeting PKN3, which is in Phase I development for the treatment of solid cancers. Lead partnered program, with Quark Pharmaceuticals and Pfizer, is PF-4523655, an AtuRNAi which Pfizer is taking through Phase II studies for the treatment of age-related macular degeneration (AMD) and diabetic retinopathy. PF-4523655 was originally developed through an ongoing RNAi therapeutics collaboration between Silence and Quark Pharmaceuticals, signed back in 2004, and focused on AtuRNAi lead compounds against RTP801. Pfizer in-licensed the lead product in 2006.  

    In a separate collaboration between Silence and Quark, the latter has negotiated nonexclusive rights to additional AtuRNAi compounds for development. The first RNAi therapeutic candidate to enter clinical trials from this collaboration is QPI-1002, an siRNA-based p53 temporary inhibitor that Quark is currently progressing through separate Phase II clinical trials for preventing acute kidney injury in cardiac surgery patients, and for the prevention of delayed graft function. In August 2010, Quark granted Novartis to obtain an exclusive worldwide license to develop and commercialize QPI-1002. 

    Silence in addition has ongoing siRNA-therapeutics collaborations in place with AstraZeneca and with Dainippon Sumitomo.

    Established in 2006, Dutch firm InteRNA Technologies is focused on the discovery and development of miRNA-based cancer therapeutics. The firm has exclusive access to a collection of miRNAs discovered by its scientific founders at the Hubrecht Institute in Utrecht. Validation of miRNA function in cancer is carried out through functional screens using a lentiviral-based miRNA expression library, which the firm says enables the identification of novel, druggable targets involved in the control signal transduction pathways and other control mechanisms known to play a role in cancer initiation, progression, and metastasis. 


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