Arno explores new class of antimicrobial drugs

Work includes possible biodefense and public health applications for compound known as AR-12

Zack Anchors
Register for free to listen to this article
Listen with Speechify
FLEMINGTON, N.J.—Arno Therapeutics, a clinical-stage biopharmaceutical company, is marking several milestones in its effort to develop a compound with the potential to be first in a new class of antimicrobial drugs. Among the most significant of these developments was the designation of orphan drug status for AR-12 in Europe and the release of new data supporting the development of the molecule as a host-directed antiviral drug.
“We believe this molecule offers the potential for broad antiviral activity,” Alex Zukiwski, CEO of Arno Therapeutics, tells DDNews. “Our efforts right now through preclinical research are focused on gaining knowledge about where we might have the biggest therapeutic impact.”
In addition to Arno’s recent release of new data regarding AR-12’s potential as a host-directed antiviral drug and its new designation as an orphan drug, Arno has also released new data showing the drug’s potential against multiple hemorrhagic fevers and launched a research collaboration with medical research arms of the U.S. Army.
Zukiwski says the recent data from preclinical research positions AR-12 to have great potential to address a wide range of unmet medical needs. “Overall, the studies demonstrate the unique ability of AR-12 to inhibit key host chaperone proteins and potentially circumvent certain antiviral drug resistance mechanisms,” he says. “Furthermore, established safety from an Investigational New Drug-enabling toxicology program and a previous Phase 1 study position the compound for potentially rapid development as an antimicrobial agent.”
AR-12 is an orally available small molecule that has completed Phase 1 clinical trials in patients with cancer and preclinical research that revealed the molecule’s potential as an antimicrobial agent in various infectious diseases.
Arno's release of new data comes just weeks after AR-12 was granted two Orphan Drug Designations in Europe for the treatment of cryptococcosis, an infectious disease of the lungs caused by the fungus Cryptococcus neoformans, and tularaemia, an infection which can be spread from animals to humans that is caused by the bacterium Francisella tularensis.
The orphan designation was awarded based on data from preclinical models for each condition. In Arno’s application regarding cryptococcosis, results of an animal model evaluating AR-12 showed a reduction in brain fungal burden in combination with fluconazole, an antifungal medication. In the application regarding tularaemia, results of an animal model evaluating AR-12 showed improved survival in combination with gentamicin.
The special status in Europe allows Arno a 10-year period of marketing exclusivity in the EU after product approval, along with protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
Arno presented findings of preclinical studies of AR-12 at the 28th Annual International Conference on Antiviral Research in Rome. The studies demonstrated potent antiviral activity against several viruses, including Influenza A, Tacaribe virus and the hemorrhagic fever viruses including Ebola, Lassa, Marburg, Nipah and Junin.
The findings suggest that the antiviral activity of AR-12 is based on host-cell target modulation, with AR-12 having the ability to essentially hijack critical chaperone proteins by down-regulating and inhibiting them. “Viruses basically hijack the cell machinery to make the proteins and various other components of virus, including copies of RNA and DNA and all the virus’ structural and non-structural components,” Zukiwski tells DDNews. “There are a number of the new agents that are effective at treating viral infections by going after the viral RNA delivery. AR-12, on the other hand, basically looks at interfering with the host mechanisms that are involved in the production, replication and assembly of viruses. This makes it a very unique target.”
Arno’s efforts to explore the potential of AR-12 also received a boost from a new cooperative research and development agreement with the U.S. Army Medical Research Institute of Infectious Diseases. The partnership provides a framework for the two organizations to further evaluate the anti-viral activity of AR-12 and various analogous molecules against Ebola and other viruses that are considered to be relevant to the nation’s biodefense.
Yet another milestone for AR-12 came with the publication of in-vitro data for the molecule generated by the Viral Special Pathogens Branch of the U.S. Centers for Disease Control and Prevention. The data, published online in the journal Antiviral Research, demonstrated AR-12’s activity against the Ebola, Marburg, Lassa and Nipah hemorrhagic fever viruses.
“The concentrations of AR-12 which demonstrated activity against these four hemorrhagic fever viruses were approximately 10 percent of the plasma concentration achieved in a previous Phase 1 oncology study of AR-12,” said Zukiwski. “These data, along with antiviral data from other sources, provide rationale for further in-vitro and in-vivo evaluation of AR-12 against a number of viral pathogens.”
Zukiwski tells DDNews that Arno’s next steps regarding AR-12 involve continuing its preclinical studies and determining in which areas the molecule is most likely to have the most significant therapeutic impact. “We’re trying to understand where the highest likelihood of success will be in all the areas where the molecule could have an impact,” he says. “We have limited resources as a small company, so we have to be smart in how we focus our resources.”

Zack Anchors

Subscribe to Newsletter
Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

March 2024 Issue Front Cover

Latest Issue  

• Volume 20 • Issue 2 • March 2024

March 2024

March 2024 Issue