This New Jersey Biotech is Tackling the Rise of Concerning Fungal Infections

“Last of Us” fans take note – while there isn’t a fungi-fueled zombie apocalypse in sight, some fungi do pose a serious threat to human health.

By Alex Keown
February 14, 2023

A mutated version of the cordyceps fungus, able to withstand higher temperatures, is capable of jumping from the insect world to humans. Seeking to propagate itself, the parasitic fungus takes over the minds of people and rapidly spreads, causing a global zombie apocalypse.

That’s the premise of the new HBO series “The Last of Us,” based on the 2013 video game of the same name. The show uses the known capabilities of the fungus, commonly known as “zombie ant fungus“, and follows the “what if” scenario to drive the story. While the concept is rooted in science, mycologists and infectious disease experts note the premise is out of the realm of probability.

“There are millions of different species of fungi. They don’t like high temperature growth. The mammalian body temperature isn’t conducive to fungi. That gives us a big, big advantage over fungal infections,” explained Dr. John Perfect, a Duke University mycologist.

Perfect noted the majority of fungal infections most people will have to deal with are those that cause athlete’s foot or yeast infections. These types of infections are readily treated with various antifungal therapeutics. Still, there are some fungal infections that pose a serious health concern, particularly to those who have a compromised immune system, he said.

“A lot of the organisms won’t infect a normal host if their immune system is normal. But, we do have a lot of immune-compromised people. And in them, the mortality rate of some of these infections can be around 40%,” Perfect said.

A growing concern, and potential solutions

In October 2022, the World Health Organization released its first-ever list of fungal pathogens that pose a major threat to public health. Among those are Candida auris, Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, which is the type of fungus Perfect primarily works with. Not only are these fungi a global health concern, the WHO noted they are resistant to treatment with only four classes of antifungal medicines currently available, and few candidates in the clinical pipeline.

This is largely due to the complex nature of developing effective antifungal treatments. David Angulo, President and Chief Executive Officer of Jersey City-based SCYNEXIS, said the complexity is related to the cellular nature of fungi, which are more closely related to human cells than other infectious agents such as bacteria. Because fungi share many of the same features as human cells, researchers have to figure out a target that will kill the fungi without damaging us.

“Developing an antifungal is much more tricky than an antibacterial,” he noted.

The difficulty in developing effective therapies is concerning to global health officials, especially as these pathogens develop resistance to our current arsenal of treatments. The SCYNEXIS team is developing its antifungal therapeutic Ibrexafungerp, the first new class of antifungal medication in 20 years, against many of these concerning fungi and has already won approval for the treatment of recurrent vulvovaginal candidiasis, a common fungal infection in women. The antifungal drug is sold under the brand name Brexafemme.

Most fungal infections in people are superficial in nature – an infection on the skin, nails or mucosal areas. However, there are systemic fungal infections that go into deep tissues and can have the capacity to destroy those tissues, Angulo said.

Fungi that can cause systemic infections are frightening enough on their own without the fictionalized version of cordyceps. Angulo, who remarked that he enjoyed the first two episodes of “The Last of Us” pointed to the growing concern of fungal infections such as aspergillosis, which are showing signs of resistance to currently-available antifungals. Another deadly fungal disease is mucormycosis, which has also shown significant antifungal resistance.

“Resistance to antifungal medications is on the rise,” he said.

The SCYNEXIS team believes Ibrexafungerp has a role to play in treating systemic fungal infections. Ibrexafungerp, a triterpenoid antifungal, is being evaluated in multiple Phase III programs for severe fungal infections such as C. auris, which can cause serious and, sometimes fatal, blood infections in people. The fungus, which causes infections with high mortality, is frequently resistant to many antifungal medications, Angulo said. He also noted that it belongs to the most common group of fungi that causes systemic infections.

“It’s a very common cause of infection. It affects very vulnerable populations and has been shown to be passed from people to people very easily. That’s uncommon for most candida infections,” Angulo said.

Many patients ultimately infected with C. auris have undergone blood transfusions or various transplant procedures. The vast majority of systemic infections are hospital-acquired, Angulo said.

In 2019, Mount Sinai Hospital in New York was at the center of a C. auris infection. Following the death of a patient infected by the fungus, hospital officials discovered the room where the patient was housed was covered in the fungus spores that had spread from him. According to the New York Times report highlighting concerns about C. auris, hospital officials said specialized cleaning equipment had to be brought in to clear the spores from where they attached. Additionally, many floor and ceiling tiles had to be removed before the room could be used again.

SCYNEXIS anticipates Phase III data later this year from trials assessing Ibrexafungerp against C. auris. Interim data showed patients infected with C. auris saw a significant response from Ibrexafungerp treatment, Angulo said. If the data continues to show efficacy, SCYNEXIS intends to seek regulatory approval.

And that will be welcome news for treating physicians who are looking for new treatment modalities.

“Fungal infections aren’t going to go away,” Perfect said. “Broad-spectrum antibiotics don’t impact the fungi and we’re still frequently seeing outbreaks of fungal infections. We need more effective agents… more potent drugs.”