Platform: Dicer Substrate technology and Dicer substrate siRNA (DsiRNA) molecules
Partnerships: Kyowa Hakko Kirin in a deal worth up to $1.4 billion; Ipsen
Therapeutic opportunities: Oncology, endocrinology, immunology and inflammation
RNAi technologies initially made headlines when it was reported that they could help silence the genes that create cancer. That promise didn't pay off because of limitations in the first generation of the drugs to home in on disease targets in patients.
Watertown, MA-based Dicerna believes that its approach will help overcome these issues through its proprietary Dicer Substrate Technology platform and its Dicer Substrate short interfering RNA molecules (DsiRNA).
Dicerna's DsiRNA molecules are 25 or more base pairs in length, slightly longer than other companies' short interfering RNAs (siRNAs), and are processed by the Dicer enzyme. This difference provides for an earlier entry into the gene-silencing pathway, increasing the potency and duration of the silencing cascade.
Dicerna's DsiRNAs can be locked onto antibodies, peptides and lipid-based particles, enhancing their delivery potential. The company hit a significant milestone in mid-December 2011 when it announced that its first DsiRNA candidate selected for development would be for oncology as part of its January 2010 deal with the Japanese company Kyowa Hakko Kirin.
The candidate demonstrated in vivo efficacy in a tumor model for a highly aggressive and difficult-to-treat form of cancer and provided complete tumor regression when delivered by Kyowa's drug-delivery system. The current chemical standard of care achieved only an expected slowing of the tumor growth rate.
"Dicerna has now shown excellent preclinical efficacy in multiple solid tumor models, validating our delivery system, our DsiRNA technology and the importance of heretofore undruggable targets in oncology," CEO Douglas Fambrough told FierceBiotech. "We look forward to testing our DsiRNAs in human clinical trials as quickly as possible." Dicerna expects to file an IND for the chosen KHK therapy late next year.
The company also has a deal with the French company Ipsen for oncology and endocrinology. It is developing conjugates of DsiRNA molecules and Ipsen's peptide-targeting vectors.
The next-generation RNA platforms offer hope for an RNAi arena that suffered the setback of Swiss drug giant Roche's exit announced in November 2010. A comeback for RNAi will likely depend on companies like Dicerna and Alnylam ($ALNY) offering impressive data from human trials.