Novel mechanism for a new generation

CAMBRIDGE, Mass. & EXTON, Pa.—In August, at the Cold Springs Harbor Laboratory Conference on Regulatory & Non-Coding RNAs, Idera Pharmaceuticals Inc., a biopharmaceutical company focused on discovering, developing and commercializing novel nucleic acid-based therapeutics for oncology and rare diseases, announced the presentation of new preclinical data that it says demonstrates the novel gene-silencing mechanism of action of the third-generation antisense (3GA) technology platform.

In the presentation, entitled “Precise excision of targeted RNA by third-generation antisense (3GA) oligonucleotides,” Idera scientists presented data indicating that gene-silencing by 3GAs led to excision sites in the targeted mRNA in the region similar to that observed with siRNA—these excision products are different from those observed with earlier generations of antisense, according to Idera.

The presentation also provided a demonstration of 3GA’s specificity by showing that the incorporation of a mismatch at the region of excision led to the loss of gene-silencing activity. Based on these studies, the company is also conducting studies to further the potential applications of 3GAs in targeting diseases caused by point mutations; data from those studies is expected to be presented in the second half of 2016.

“Our in-depth understanding from our pioneering work in antisense technology along with our insights into the interaction of nucleic acids with Toll-like receptors has allowed us to design this very unique technology platform to fully realize the potential of antisense technology,” said Dr. Sudhir Agrawal, president of research at Idera Pharmaceuticals. “We are continuing to conduct preclinical studies with multiple 3GA candidates in house and with our collaborators, with a goal of advancing this technology to clinical development.”

In other Idera news, the company in late September presented initial clinical data from its ongoing Phase 1/2 clinical trial of intratumoral IMO-2125, a Toll-like receptor 9 agonist, with these early results indicating that IMO-2125 demonstrates promising clinical activity and is being well tolerated in a patient population with minimal options and low expectation of clinical response with ipilimumab treatment alone.

“We have completed extensive preclinical work in a broad scope of tumor types to test the hypothesis of intratumoral administration of IMO-2125 inducing a meaningful effect on the tumor microenvironment and potentiating local and systemic tumor regression in patients. This work gave us confidence to test the ability of IMO-2125, beginning with this current study in PD-1 refractory metastatic melanoma patients,” stated Vincent Milano, Idera’s CEO.