Arno Therapeutics’ AR-13 Shows Promise as Potential New Cystic Fibrosis Therapeutic Option for Serious Bacterial Infections

Arno Therapeutics’ AR-13 Shows Promise as Potential New Cystic Fibrosis Therapeutic Option for Serious Bacterial Infections

Flemington, New Jersey based clinical stage biopharmaceutical company Arno Therapeutics, Inc. has announced data from a preclinical study demonstrating that its drug candidate AR-13, an analogue of Arno’s AR-12 infectious disease compound portfolio, shows promise as a potential new therapeutic option for patients with cystic fibrosis (CF) who are acutely and chronically infected with Burkholderia cenocepacia and other antibiotic resistant organisms such as Pseudomonas aeruginosa.

A 2010 Open Access study published in the journal Clinical Microbiology and Infection entitled: “Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence” (Clin Microbiol Infect. 2010 Jul;16(7):821-30. doi: 10.1111/j.1469-0691.2010.03237.x), notes that Burkholderia cepacia complex (Bcc) bacteria have gained notoriety as cystic fibrosis pathogens because they are difficult to identify and treat, and also have the ability to spread between CF individuals. The study coauthors, Pavel Drevinek and E. Mahenthiralingam of the Charles University 2nd Medical School Paediatric Department in Prague, Czech Republic note that of the 17 formally named species within the complex, Burkholderia multivorans and Burkholderia cenocepacia dominate in CF and the Czech strain (ST-32), have spread epidemically within CF populations in Canada and Europe, and that with the wealth of molecular knowledge acquired in the last decade on B. cenocepacia strains, scientists are now in a much better position to develop strategies for the treatment of pathogenic colonization with Bcc and to answer key questions on pathogenesis concerning, for example, the factors that trigger the rapid clinical decline in CF patients.

The new AR-13 dataset from Arno, a company primarily focused on the development of therapeutics for cancer and other life threatening diseases, will be presented in a poster session during the upcoming 29th Annual North American Cystic Fibrosis (NACF) Conference, to be held October 8-10, 2015 at the Phoenix Convention Center in Phoenix, Arizona.

CFConferencePhoenix

The NACFC serves as a collaborative forum to advance research for the treatment and cure of CF, and is an ideal opportunity to receive state-of-the-art continuing medical education and learn about the latest products and services in CF care. The meeting’s educational elements over three days with more than 60 concurrent sessions will be targeted to physicians, nurses, research scientists, respiratory therapists, physical therapists, nutritionists, social workers, and pharmacists to share the latest research and advances in CF.

The content and faculty of the scientific program of educational sessions and approval of arrangements for hosted functions are the sole responsibility of the CF Foundation, the NACFC Program Planning Committee and the accredited provider.

NACF Conference Main Poster session Abstract #319 scheduled for Thursday, October 8; 11:50 a.m. – 1:50 p.m. MT, will present study data on AR-13 as a potential new therapeutic for reducing Burkholderia Cenocepacia burden in CF macrophages.

THP-1 monocyte cell line, human peripheral blood samples containing monocyte derived macrophages and neutrophils from patients with CF and blood samples from non-CF healthy controls were used for this preclinical study, results of which demonstrate that AR-13 in combination with broad-spectrum antibiotics has synergistic effects on reducing antibiotic-resistant B. cenocepacia burden in human CF macrophages. AR-13 alone also significantly reduces the CF pathogen Pseudomonas aeruginosa burden in CF neutrophils specifically, a 70% reduction in P. aeruginosa burden in CF neutrophils and 66% reduction in non-CF neutrophils using AR-13 alone.

KoppBBenjamin T. Kopp, MD, Assistant Professor, Department of Pediatrics at The Research Institute at Nationwide Children’s Hospital, comments in a release: “The NACFC Annual Meeting offers researchers and physicians a central opportunity to learn about and present new research and discoveries on cystic fibrosis (CF) one of the most debilitating genetic disorders for children for which there is no cure. These data are promising as they show AR-13 could possibly be used with antibiotics to reduce the antibiotic resistant pathogen burden present in human CF macrophages. Importantly, we found that CF and non-CF macrophages and neutrophils safely tolerated AR-13 in relatively high concentrations, with increased macrophage viability in CF compared to antibiotics alone. We are pleased to present these very compelling and interesting preclinical findings for AR-13.”

Arno Therapeutics Chief Executive Officer Alexander Zukiwski, MD adds, “AR-13 appears to exhibit unique autophagy induction properties that have benefit in reducing the burden of intracellular pathogens. The reported in vitro activity of AR-13 in macrophages from patients with cystic fibrosis infected with difficult-to-treat bacterial pathogens demonstrates the differential activity of this compound which is based on a common “backbone” of the same chemical series as AR-12. The broad potential for antimicrobial activity of the compound series is further supported by the activity observed against methicillin resistant staphylococcal aureus (MRSA) of the compound series as described in the literature. Although early, we believe this AR-13 data set holds substantial promise in treating antibiotic resistant bacteria in patients with CF. We look forward to evaluating AR-13 further as a potential therapeutic option for B. cenocepacia and P. aeruginosa infections in patients with CF for which there are limited effective treatments due to antibiotic resistance and defective host cells not being able to kill the bacteria.”

AR-13 is an analogue of AR-12 that is being evaluated as part of Arno’s AR-12 orally-available small molecule infectious disease product portfolio. Data reported previously demonstrated that AR-12’s mechanism of action may include host cell autophagy and inhibition induction of of a number of protein chaperones. AR-12 has completed Phase 1 clinical trials in patients with cancer, and has been granted two orphan drug designations in Europe for the treatment of cryptococcosis and tularaemia. In addition, Arno also owns rights to a broad portfolio of compounds in the “AR-12 series,” which have been demonstrated to have a broad spectrum antimicrobial activity. In addition, AR-12’s anti-viral activity against Ebola and other pathogens of biodefense interest is being evaluated under a Cooperative Research and Development Agreement (CRADA) Material Transfer Agreement with the US Army Medical Research Institute of Infectious Diseases (USAMRIID).

The Bethesda, Maryland based nonprofit donor-supported Cystic Fibrosis Foundation funds more CF research than any other organization, with nearly every CF drug available today having been made possible because of Foundation support.

The Foundation’s drug development model has been recognized by Harvard Business School and by publications such as Forbes, The New Yorker, and Bloomberg Businessweek. The Foundation funds and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease, and as one of the most efficient organizations of its kind and an accredited charity of the Better Business Bureau’s Wise Giving Alliance.

Sources:
Arno Therapeutics, Inc.
Centers for Disease Control and Prevention (CDC)
Clinical Microbiology and Infection
29th Annual North American Cystic Fibrosis (NACF) Conference
The Cystic Fibrosis Foundation

Image Credits:
Arno Therapeutics, Inc.
Nationwide Children’s Hospital

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