Idera Pharma (IDRA) Announces Presentation of Positive 3GA Data at OTS Meeting
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Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced the presentations of new pre-clinical data on the mechanism of action supporting selective targeting of single point mutations. Also, data was presented on 3GA targeting the NLRP3 gene for the treatment of inflammatory disorders.
“The understanding we have gained of the mechanism of action of 3GA is providing insights into the increased potency and specificity of its gene silencing. This data has illustrated to us a way in which 3GA could be used to target point mutations,” stated Sudhir Agrawal, D. Phil., President of Research at Idera Pharmaceuticals. “We are continuing to employ 3GA technology to target multiple genes, including NLPR3, with a goal of prioritizing a candidate for clinical development.”
In the oral presentation, entitled “Selective Targeting of Point Mutations by Third Generation Antisense Oligonucleotides,” Reina Improgo, Ph.D., Research Scientist of Idera’s Discovery Team presented an overview of the novel mechanism of action of 3GA technology. These preclinical studies were conducted both in cell-based assays as well as in vivo models. The novel mechanism of action of 3GA leads to excision of the targeted RNA in the central region. Insertion of a single mismatch led to significant loss of gene-silencing activity. Based on this data, 3GAs were designed to target single point mutations. These proof-of-concept studies were conducted using two targets, the BRAF V600E and MYD88 L265P mutations. The 3GA targeted to BRAF V600E showed mutation-specific inhibition, whereas a 3GA targeted to wild type BRAF showed minimal activity. Similarly, 3GA targeted to MYD88 L265P showed mutation-specific inhibition, and had insignificant impact on wild type MYD88 expression. Based on the specificity in targeting RNA the data indicates that 3GA could be used to successfully treat diseases that require allele-specificity.
Additionally, Fugang Zhu, Ph.D. and Wayne Jiang, M.D., Ph.D., scientists from Idera’s Discovery Team, presented a poster entitled, “Third generation antisense (3GA) targeting NLRP3 for the treatment of inflammatory disorders.” In the presentation, they showed that 3GA targeting NLRP3 led to the suppression of the NLRP3 mRNA and protein and inhibition of the downstream cascade, including IL-1β and IL-18. The data also demonstrated that 3GA targeting of NLRP3 resulted in marked improvement in disease-associated parameters in both interstitial cystitis and uveitis preclinical models.
These presentations are currently available on Idera’s website at http://www.iderapharma.com/our-approach/key-publications/.
Previously the company has announced the identification of NLRP3 (NOD-like receptor family, pyrin domain containing protein 3) and DUX4 (Double Homeobox 4) as initial gene targets to advance into IND-enabling activities, which will occur throughout 2016. Potential disease indications related to these targets include, but are not limited to, interstitial cystitis, lupus nephritis, uveitis and facioscapulohumeral muscular dystrophy (FSHD). The Company is currently conducting clinical, regulatory and commercial analysis activities and conducting IND-enabling studies with the plan to enter the clinic in 2017 for the first clinical development program. In addition to these activities, over the first half of 2016, Idera generated 3GA compounds for a series of additional gene targets. These will enable the Company to continue to expand both its future pipeline opportunities for internal development as well as its opportunities for partnerships in areas outside of Idera’s focus. Additionally, Idera is party to a collaboration and license agreement with GSK to research, develop and commercialize compounds from its 3GA technology for the treatment of undisclosed, selected renal targets.
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