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Arcturus Therapeutics to Report Identification of LUNAR-HBV

Arcturus Therapeutics to Report Identification of LUNAR-HBV, a Potent Combination of Three UNA Oligomers Targeting All Hepatitis B Virus Genotypes at the AASLD Liver Meeting® 2016
SAN DIEGO, Oct 3, 2016 /PRNewswire/ -- Arcturus Therapeutics, Inc. ("Arcturus" or the "Company"), a leading RNA medicines company, announced today that preclinical data for a multi-siRNA treatment of Chronic Hepatitis B Virus (HBV), developed in collaboration with Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, will be presented in a poster at The Liver Meeting, the 67th Annual Meeting of the American Association for the Study of Liver Disease (AASLD) being held November 11-15, 2016, in Boston.

The presentation identifies a potent combination of three UNA (Unlocked Nucleomonomer Agent) oligomers that targets all HBV transcripts and covers all known HBV sequences – the most comprehensive HBV genotype coverage reported for a single drug product to date. The combination demonstrated excellent efficacy in mouse models of HBV infection using Lipid-enabled and Unlocked Nucleomonomer Agent RNA (LUNAR™), a novel biodegradable nanoparticle delivery technology with a favorable safety profile.

"Arcturus is delighted to present HBV preclinical data, developed in collaboration with Janssen, at the AASLD Liver meeting 2016," said Joseph E. Payne, Arcturus' President & Chief Executive Officer. "Based on the potent reduction of Hepatitis B surface antigen, and the observed safety profile, LUNAR-HBV has the potential to be part of a new generation of HBV therapies."

The poster presentation "LUNAR-HBV, a UNA Oligomer Combination for the Treatment of Chronic Hepatitis B Virus Infection" will be presented by Christine Esau, Ph.D., Director of Translational Biology on November 14, 2016, between 12:30 p.m. – 2:00 p.m. EST. Authors: Christine Esau, Pattraranee Limphong, Kiyoshi Tachikawa, James McSwiggen, Wendy Taylor, Michael Figa, Priya Karmali, David Smith, Tse-l Lin, Leonid Beigelman, and Pad Chivukula.

"Arcturus' novel RNA therapeutics treatment for HBV, LUNAR-HBV, has shown potent anti-HBV activity in HBV-infected human hepatocytes and in mouse models of HBV infection," said Pad Chivukula, Ph.D., Arcturus' Chief Scientific Officer. "The combination of three UNA oligomers also has the potential to minimize viral resistance and we are enthusiastic about the attributes of UNA chemistry and of the LUNAR delivery platform as we advance this program with our partners."

About Arcturus Therapeutics, Inc.  

Founded in 2013 and based in San Diego, Arcturus Therapeutics, Inc. is an RNA medicines company with enabling technologies — UNA Oligomer™ chemistry and LUNAR™ nanoparticle delivery. Arcturus' versatile RNA therapeutics platform can be applied toward all types of RNA medicines including small interfering RNA, messenger RNA, antisense RNA, microRNA and gene editing therapeutics. The company owns LUNAR™ nanoparticle delivery and unlocked nucleomonomer agent (UNA) technology including UNA Oligomers™, which are covered by its patent portfolio (77 patents and patent applications, issued in the U.S., Europe, Japan and other countries). Arcturus' proprietary UNA technology can be used to target any gene in the human genome, as well as viral genes, and other species for therapeutic purposes. The Company's commitment to the development of novel RNA therapeutics has led to collaborations and license agreements with Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, and Ultragenyx Pharmaceutical, Inc. For more information, visit www.ArcturusRx.com.

5 Responses
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Hi Sorte, thanks for this good news. We need more of this, but most importantly, the sooner they develop the drugs the better for all of us. In the meantime we live with increasing hope because, i think, hope itself is a good medicine.
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It is interesting that this company has licensed programs with Arbutus and Arrowhead, according to its website.
yes, I've noticed the same
seems that RNA medicines is the future of medicine, is there any disease cured by it already ?
I don't know any. Remember, RNAi was abandoned by most several years ago.
Avatar universal
All those ™ signs make my head spin. Is this basically from the same cloth as Arrowhead, Tekmira, Benitec et al.?
Avatar universal
There are two parts to RNAi technology. The first part is the load - the short piece of RNA that targets the relevant mRNA. This part should be fairly standard to do. The second part is the delivery platform - how to deliver the load to the target organ. This part is very proprietary, where all the™ signs are appropriate.
I am still hoping someone will design a load that will knock down HBcAg.
As mentioned before, i think the current construct are already reducing the core expression as well. It is just very hard to measure that effect. If lucky they will reduce core expression between 90 and 99%. This in itself will not lead to a substantial reduction of virion production,
so that technology may be just the part of the future drug combo, but not the drug to cure standalone ?
I would be very surprised if iRNA treatment by itself for a limited time could be applied and lead to a permanent, treatment free, hbsag seroconversion.
Avatar universal
According to AASLD2016, Abstract 1865, Arbutus has indeed developed a new type of RNAi that seems to specifically targets HBcAg. Sure would be interesting to see how it performs in human.
"Here we describe a second-generation RNA interference (RNAi) therapeutic comprised of 3 small
interfering RNAs (siRNAs) directly targeting multiple loci of hepatitis B viral transcripts, enabling inhibition of HBV replication and suppression of all viral antigens. Like ARB-1467, which is currently in Phase 2 clinical trials with chronic HBV patients, ARB-1740 can inhibit HBsAg production even from integrated HBV and utilizes lipid nanoparticle (LNP) technology to deliver siRNA to the infected liver. In vivo, ARB-1740 is up to 10-fold more potent than ARB-1467, resulting in 2.5 log10 serum HBsAg reduction at 7 days after a single 0.3 mg/
kg dose in a hydrodynamic injection mouse model of HBV. Duration of activity was also improved with resolution to  35 days. Its antiviral drug activities also included inhibition of serum HBVDNA (2.9 log10) and HBeAg (> 2 log10) as well as hepatic HBsAg (1.5 log10), HBV DNA (1.5 log10) and HBV RNA (>1 log10). ARB-1740 has demonstrated pan-genotypic activity with sub-nanomolar in vitro EC50 potencies against extracellular HBV relaxed circular DNA and HBsAg across 12 clinical isolates representing 4 genotypes (A-D), including 5 NUC-resistant
strains. In summary, in vivo modeling of ARB-1740, a second-generation RNAi therapeutic with pan-genotypic activity and a well-understood mechanism of action, has demonstrated that it is more effective than previous therapeutic agents for reduction of HBsAg and other HBV viral markers in both the peripheral blood and liver."
It seems they have changed the target location so that it blocks integrated hbv expression as well. Similar to arc 521. They say it inhibits all viral antigens,  will therefore include the core antigen, but I do not see that it is specific for the core from this abstract.  Certainly sounds very interesting and one hopes that they move to human testing soon.
Yes, you are right - I got carried away when I saw three 3 new triggers and a measured reduction in HBeAg, thinking that HBcAg is targeted. Capsid inhibitors also target HBcAg, so a trigger that targets HBcAg may give us an answer how useful this approach is.
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