While few drug developers are focused on multi-drug resistant invasive fungal infections, San Diego-based Cidara Therapeutics is in the thick of the fight with its Phase III lead antifungal rezafungin.
Candida auris fungi.
While few drug developers are focused on multi-drug resistant invasive fungal infections, San Diego-based Cidara Therapeutics is in the thick of the fight with its Phase III lead antifungal rezafungin.
Cidara’s Rezafungin is a novel antifungal echinocandin being developed as a once-weekly therapy for the prevention of invasive fungal infections caused by the most common fungal pathogens, Candida, Aspergillus and Pneumocystis. Each year, approximately 97,000 Americans die from hospital-related invasive fungal infections. Of those, approximately 90 percent of all reported fungal related deaths result from a few common fungi, including the three aforementioned ones. Currently, there is no single agent approved in the United States for the prevention of infections from each of these fungi. Current prophylaxis regimens require multiple antifungals, including azole drugs and Bactrim. Some of these are associated with known drug-drug interactions as well as safety and tolerability issues.
Recently, Candida auris, a dangerous fungal infection that can be fatal and is highly resistant to many anti-fungals, was discovered at Mount Sinai Hospital in New York. After a patient infected with the fungus expired, hospital officials discovered that his room was covered in the fungus spores as it had spread from him. That incident set alarm bells buzzing across the healthcare industry.
Cidara Chief Executive Officer Jeff Stein told BioSpace that rezafungin has shown potency against Candida auris, as well as a broader range of Candida strains. Each of the strains of candida has a high mortality rate, Stein said. Those rates could rise alongside the growing number of people who are immune compromised.
“Autoimmune disease is on the upswing and people are taking new drugs to treat them. By virtue of their mechanism of action, the immune response is being suppressed. The number of individuals who are susceptible is growing,” Stein said in an exclusive interview with BioSpace.
To respond to that threat, Cidara has initiated a Phase III trial in Candidemia, the fourth most common cause of nosocomial bloodstream infections, and invasive candidiasis, a serious fungal infection that can affect the blood, heart, brain, eyes, bones and other parts of the body. The study was launched in October and Stein said the company anticipates a readout of the data in the first half of 2020. In addition to the Phase III study, the company anticipates readout of a second Phase II study for the same indications in July. The second study is expected to bolster the safety database in order to meet FDA regulations, Stein said.
One of the keys to rezafungin’s potential success is its design. While rezafungin is in the echinocandin class, Stein said it’s different from other like drugs in that it only has to be dosed intravenously once per week. Other drugs in the same class tend to degrade more rapidly, which requires additional dosing. Rezafungin does not seem to have that issue, which means it’s safer and has greater efficacy. Because the drug can be “front-loaded” in a patient, Stein said rezafungin can actually shorten the hospital stay of patients who may come down with one of these infections.
In addition to Cidara’s anti-fungal asset, the company is also developing an antiviral conjugate called CB-012, part of its Cloudbreak program, that Stein said could be a transformational approach. It’s not a vaccine or traditional drug. CB-012 borrows from bispecific immunotherapy treatment being used in cancer patients, Stein said. Cidara’s therapy attack influenza through a dual mechanism: The antiviral agent neutralizes the influenza virus directly, while the human antibody fragment engages a patient’s immune system to accelerate elimination of the pathogen. The approach is designed to improve on, and combine, the preventive effects of vaccination with an antiviral drug’s capability to treat flu illness, Stein said. In short, it’s a drug with a single subcutaneous injection for universal treatment of the flu. Stein said CB-012 could be “the holy grail” of flu treatment.
“This is very exciting. A single injection could provide protection for a year,” Stein said.
As Cidara moves forward with both is CB-012 program and rezafungin, Stein said the company will look to forge partnership agreements for both assets. While he would not provide specifics on any companies Cidara may have flirted with, Stein said that data presented earlier this month at the 29th European Congress of Clinical Microbiology and Infectious Diseases “accelerated the discussions.”
“These are exciting times to work on these programs,” Stein said.
