Arno Therapeutics Demonstrates AR-12 Has Potent Antiviral Activity Against Drug-Resistant HIV Strains

Flemington-based Arno Therapeutics, Inc., a clinical stage biopharmaceutical company primarily focused on the development of therapeutics for cancer and other life threatening diseases, today announced data demonstrating that AR-12 has potent in vitro antiviral activity against HIV-1, HIV-2 and drug-resistant HIV-1. Results were presented today in a poster presentation during the 15th European AIDS Conference, which is hosted by the European AIDS Clinical Society (EACS) and being held October 21-24 in Barcelona, Spain.

Results of the in vitro studies demonstrated that AR-12 inhibits HIV-1, HIV-2 and six drug resistant HIV-1 strains with 50 percent inhibitory concentrations (IC50) in the range of 240-1016 nM (nanomolar) and moderate cytotoxicity (5532 nM). The IC50s were found in this study to be consistent with the IC50s observed against other viral pathogens including Influenza A, Chikungunya, Ebola, Lassa and others.

Previous studies have demonstrated AR-12 down regulates the host cell chaperone machinery, including GRP78, HSP70, HSP90 and HSP27. GRP78 is a critical chaperone protein, whose inhibition results in the up-regulation of PERK, inducing autophagy and facilitating the clearing of intracellular viruses and/or phagocytized unfolded proteins.

Interfering with the host chaperone proteins in cells infected with viruses is thought to prevent the proper folding of viral proteins and efficient viral assembly.

These findings suggest that AR-12 inhibits HIV through a mechanism of action different from other inhibitors currently on the market, encompassing the major classes of HIV drugs currently available. These preclinical investigations confirmed that host cell targeting by AR-12 may be an effective approach to inhibit the replication of HIV at low concentrations that can be achieved in the clinical setting with an oral tablet formulation.

Findings from the study, titled “AR-12, a Novel First in Class Host Cell Targeting Therapeutic Candidate with Potent Activity Against HIV Multidrug Resistant Strains in vitro” (Poster PE6/4; Abstract #1094), will be presented by Arno Chief Development Officer Stefan Proniuk, Ph.D. during a Poster Session at the conference starting on Thursday, October 22 at 12:00 p.m. CEST.

Stefan Proniuk, Ph.D., Chief Development Officer of Arno Therapeutics, commented, “These findings indicate that AR-12’s novel antiviral mechanism of action offers a new promising approach to potentially circumvent existing resistance mechanisms, enhance existing HIV treatments through combination therapies and to potentially address co-infections with other viral pathogens. The results demonstrated in these in vitro studies in HIV strains are consistent with the broad spectrum antiviral activity findings we have shown in other viruses, including Ebola, Nipah, Lassa, Marburg, Junin, Tacaribe, Yellow Fever, Hepatitis C, Epstein Barr, Venezuelan equine encephalitis, Chikungunya and Influenza (H1N1, H3N2), which collectively provide insight into the depth of AR-12’s anti-viral capabilities.”

Alexander Zukiwski, M.D., Chief Executive Officer of Arno Therapeutics, added, “We are pleased with the findings from these in vitro studies which further support AR-12 as a potential versatile and effective antiviral compound. Based on these results, we plan to initiate a SAD/MAD study to assess the safety of single dose and multiple doses of a new optimized formulation of AR-12.”

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