Biopharma Tackles Antimicrobial-Resistant Fungi

Antimicrobial-resistance is becoming an increasingly serious issue in the public domain. Just a few weeks ago, the NY Times reported an outbreak of an antimicrobial-resistant fungus, Candida Auris, at Mount Sinai Hospital.

Marco Taglietti

Some companies, such as SCYNEXIS, however, have ventured into treating antimicrobial resistant fungi. In this interview, Marco Taglietti, CEO of SCYNEXIS, will discuss efforts to help advance fungal disease treatments.

Moe Alsumidaie: SCYNEXIS specializes in developing treatments for fungal infections, which do not get much media attention, despite the severity. Could you give us a global view on fungal infections and tell us about the vital work that SCYNEXIS is doing to combat them?

Marco Taglietti: Fungal infections are a neglected area of development, despite being potentially severe and life-threatening. A reason for negligence in this space is that most people associate fungal infections with non-threatening dermatologic conditions, such as athlete’s foot and toenail infections. SCYNEXIS is tackling the dangerous, severe fungal infections that have very few treatment options. For example, mortality rates of invasive fungal infections in immunocompromised patients, such as cancer patients receiving chemotherapy, is between 30-50%. The second group of infections that we are treating, mucocutaneous infections, are less frightening but severe and difficult to eradicate, like vulvovaginal, oropharyngeal or esophageal infections. Recently, we have had some excellent Phase 3 data showing the activity of our product in these refractory and difficult-to-treat fungal infections.

MA: There's much awareness of antimicrobial resistance in the world. Do fungal infections mimic bacterial infections, and can fungi morph and change to become resistant to current medications? How is SCYNEXIS addressing this problem?

MT: All pathogens will eventually develop a way to go around or “resist” anti-infectives. We can temporarily create treatments with new antibiotics and new antifungals, making it imperative to continue to look for new classes and products that can fight against strains that are becoming resistant. The product we are developing, Ibrexafungerp, is a new class of antifungal, which is exceedingly significant since there are only three other classes of antifungals. Fungi have evolved a way to be resistant to the other classes, but ours is an entirely new weapon. It's an antifungal against which these fungi are still sensitive. We believe that this product will be able to address many of the problems of resistance that we have with the other classes that are available today.

MA: How is this new antifungal class different from previous generation classes?

MT: Ibrexafungerp has an entirely different chemical structure with a different approach to destroying fungi. Fungi are surrounded by a hard shell made of glucan and chitin, and our product blocks the enzyme that produces glucan, causing the shell to break down. It is also important to note that Ibrexafungerp is a fungicidal, so it completely kills the fungi. Many other antifungals are fungistatic, which means they block the growth of the pathogen, but then rely on the immune system of the patient to kill it. This is where a fungicidal product can make a significant difference. Ibrexafungerp is also very versatile in the sense that it can be taken orally and that it can have a significant impact on many different types of resistant infections. Also, our product has demonstrated a very high level of safety since it targets the shell in fungal cells that do not exist in human cells. We have treated over 500 subjects with Ibrexafungerp and observed no systemic toxicity with only a small percentage of subjects reporting nausea and diarrhea.

MA: How is SCYNEXIS improving the efficiency of clinical trials in antifungal development?

MT: We have been conducting trials globally because fungal infections infect people around the world. We are currently holding trials in North America, South America, Europe, and Asia. One of those studies is a Phase 3 trial in patients with refractory, invasive fungal infections. These enrolled patients have not responded to any previous treatments or are not tolerant of currently available ones. Because this is a “salvage” setting, i.e., an environment where the patients have no other treatment options, we can test our product, showing that it can work where other products have failed. We recently released a press release announcing the first analysis of this study with very positive results.

MA: Where do you see this industry heading in the next six months, five years ten years, with these treatments?

MT: It may take 10-15 years for fungi to become resistant to treatments. For Ibrexafungerp, we plan to file the NDA in 2020 with potential approval in 2021. We expect that there will be no significant resistance to it for at least 10-15 years. Simply put, there are not enough drugs in development since only 2-3 companies are developing new antifungals. We are working very closely with fellow antifungal developers because we believe that there is room for all these products in the market. I hope that in 10-15 years from now we will have 5-6 different classes of antifungals instead of only 3. Our new class is still the most advanced, so it should be the next one introduced to the market.

Moe Alsumidaie, MBA, MSF is Chief Data Scientist at Annex Clinical,.