Regulus present advancements in microRNA platform at Oligonucleotide Therapeutics Society meeting

Regulus Therapeutics Inc. announced today that advancements from its leading microRNA platform and product pipeline were presented at the "6^th Annual Meeting of the Oligonucleotide Therapeutics Society" held October 20 - 23, 2010 in Dana Point, California. Regulus and its collaborators presented new data on characteristics for anti-miR design, including oligonucleotide length and chemical modifications. Longer microRNA inhibitors (15 to 23 bases) were significantly more potent and efficacious in vitro and in vivo than shorter anti-miRs (8 bases) that only target the seed region of a microRNA.

“6th Annual Meeting of the Oligonucleotide Therapeutics Society”

"microRNAs as drug targets represent an entirely new untapped pool of therapeutically relevant opportunities," said Hubert Chen, M.D., Vice President Translational Medicine of Regulus. "Regulus is developing a new class of high impact medicines using a mature therapeutic platform based on technology that has been developed over 20 years and tested in greater than 5,000 human subjects. Data presented at the Oligonucleotide Therapeutics Society meeting further demonstrate the leading position of Regulus in the field microRNA therapeutic design, discovery, and development."

In a talk titled "targeting microRNAs for therapeutics" Regulus and collaborators from the Hanover Medical School, Germany and the Technische Univeristat Munchen showed the importance of oligonucleotide length in the design of anti-miRs. In an established murine cardiac model of fibrosis, different length anti-miRs targeting the microRNA miR-21 were tested for effectiveness and therapeutic efficacy. Longer anti-miR-21 (22 bases) was more efficacious and potent than shorter anti-miR-21 that target only the seed region (8 bases) as shown by their impact on target gene expression and in vivo heart size and function.

In a poster titled "short seed-matched anti-miRs modulate microRNA, but have poor potency and suboptimal pharmacokinetic properties" Regulus scientists presented additional data on optimal anti-miR design for therapeutic use. Longer anti-miRs targeting the microRNAs miR-122 and let7a were shown to be more potent than shorter anti-miRs that target only the seed region. Longer anti-miRs to miR-122 were more effective than shorter anti-miRs as measured by target gene derepression and impact on cholesterol levels (anti-miR-122 has been shown to reduce levels of LDL cholesterol). Similarly, longer anti-miRs to let-7a were more effective than shorter anti-miRs as measured by target gene derepression and in vivo diabetes end points (anti-let-7a has been shown to impact levels of glucose in animal models of diabetes). Further, pharmacokinetic analysis demonstrated that the long anti-miRs have higher tissue accumulation than short anti-miRs, suggesting greater therapeutic utility for full-length anti-miRs.

In a talk titled "microRNA-146a is a significant break on autoimmunity myeloproliferation and cancer in mice" Regulus scientists and collaborators from California Institute of Technology presented data that microRNA-146 is upregulated in activated immune cells and is a key regulator of inflammation.

In a poster titled "tale of a tumor suppressor microRNA: miR-34a as a paradigm," Regulus scientists present a characterization of the effects of introducing miR-34a into hepatocellular carcinoma cells with an emphasis on the effects in the p53 pathway.

Regulus, in an alliance with GlaxoSmithKline, presented a poster titled "inhibition of microRNA function in macrophages by anti-miRs" demonstrating delivery of anti-miRs to macrophages and showed functional target engagement as measured by derepression of seed-matched transcripts.

In total, the data presented at OTS by Regulus and its collaborators demonstrate the therapeutic potential of modulating microRNAs in many disease areas. Regulus continues to advance several programs into the clinic, including its miR-122 and miR-21 programs, by indentifying potent and efficacious anti-miR inhibitors.