NEW YORK (360Dx) – Avisa Pharma is developing a drug and device combination technology that can provide information on bacterial infections from a patient's exhaled breath. The test takes less than 10 minutes, detecting pathogen metabolites in breath after a patient inhales a tracer drug from a nebulizer, and the firm is currently focused on developing assays for pneumonia and Clostridium dificile.
Avisa was founded eight years ago in Santa Fe, New Mexico with core technology licensed from the University of New Mexico. The technology involves administering stable isotopes to patients that are metabolized by bacteria.
In the initial pneumonia application, called the AV BreathTest, the firm uses a nebulizer to deliver non-radioactive 13C-urea to a patient's lungs, which is in turn incorporated into 13CO2 generated by virulent urease-containing bacteria.
Exhaled carbon dioxide with the 13-isotope is detected with a milliwatt laser spectrometer-based detection platform, called AVISAR. The instrument also includes a touchscreen interface, nebulizer controller, and breath sampling pneumatics to rapidly measures isotopic ratios using near-infrared wavelength modulation spectroscopy, enabled by a patented, tunable semiconductor laser, according to the firm's website.
The core technology was initially described in a 2010 proof-of-concept PLoS One study, as it applied to M. tuberculosis detection in lab animals.
In an interview, Avisa CEO David Joseph noted that the product in development could be used to rule out urease-containing pathogens — such as S. aureus, P. aeruginosa, Klebsiella, and H. influenzae — which make up 15 percent of infections in the emergency department, and to help guide physicians to alter treatment course in order to prevent the overuse of broad-spectrum antibiotics. With a negative Avisa test, a patient could get a more narrow-spectrum antibiotic, or perhaps Tamiflu, or no treatment at all.
A 2016 study by researchers at UNM showed that the method was safe for patients with cystic fibrosis and that isotope ratios in CF patients with P. aeruginosa may be higher than control CF patients 10 min after inhalation of 13C-urea.
Furthermore, the technology can be adapted for early detection of pneumonia in patients on ventilators, Joseph said. Approximately 20 percent on a vent will get pneumonia, he said, and it has as high as 50 percent mortality in this population.
The device is the size of a laptop, Joseph said, and is also easy to use. It weighs approximately 4 kg, and its small size makes it potentially deployable in pointof-care settings.
Importantly, "It's not just a yes-or-no test, it is also quantitative," Joseph said. The test could be used for patients on a ventilator to find out if they are colonized with pneumonia-causing bacteria. "If we see colonization, a doctor can treat early, before they get full-blown ventilator-associated pneumonia," Joseph said. The 10-minute test can also be used to monitor effectiveness of pneumonia therapies.
The 13C urea method is similar to one used to detect H. pylori infections in a product from Exalenz Bioscience. In that test, patients swallow a solution that then is eventually metabolized by bacteria in the gut, which excrete isotope-containing CO2 that is measured with a breath test. Exalenz recently reported a doubling in product sales for its BreathID Hp urea breath test, due in part to new guidelines recommending non-invasive testing for some patients with suspected infections.
And other firms are also using breath-based biomarkers, including diagnostic tests measuring volatile organic compounds for lung and colon cancer from Owlstone Medical, a firm that recently closed a $50 million financing round. Researchers in Israel are developing a breath test that could be used for early detection of Parkinson's disease.
The AVISAR laser has now been granted patents in the US, Europe, China, and Japan, and Avisa was also issued IP in the US through its licensing agreement with UNM around the detection of C. diffinfections with the platform.
Future directions for Avisa include developing an assay using 13C-tyrosine that can be administered orally or intravenously, with exhalations indicating C. diff infection, particularly to predict relapse and determine antibiotic sensitivity by monitoring treatment response.
The firm is also pursuing a ventilator-acquired pneumonia test, as well as assays tailored to chronic obstructive pulmonary disease and cystic fibrosis. An Avisa-sponsored study by researchers at Temple University recently presented preliminary data at the American Thoracic Society annual conference showing reduced urease activity in the oral cavity of COPD patients who are active smokers, and that urease activity was negatively correlated with symptoms of breathlessness and wheezing.
The firm has raised approximately $14 million to day, Joseph said, and is commencing a $15 million Series B round this quarter. The funds will be used to complete additional manufacturing of the drug component and support its investigator-led studies for FDA submission of the combination product. Avisa plans to meet pre-submission guidelines in early 2019 and to initiate clinical trials in earnest beginning in 2020.