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Science

A novel and structurally distinct triterpenoid glucan synthase inhibitor to treat various fungal infections

SCY-078 represents a new chemical class of triterpenoid glucan synthase inhibitors designed to block an established target in infectious fungi by interfering with the assembly of the fungal cell wall and preventing the growth of medically important fungal species. SCY-078, prepared by chemical modification of enfumafungin, is the lead clinical candidate identified from this platform technology and is being developed as a new intravenous (IV) and oral agent for the treatment of several fungal infections, including life-threatening invasive fungal infections caused by Candida and Aspergillus species. SCY-078 is an inhibitor of fungal 1,3 – β -glucan and synthesis and shows antifungal activity against a wide range of clinically important fungi, including those that are resistant to azole drugs such as fluconazole.

To date, more than 300 subjects and patients have received SCY-078 either orally, intravenously or by an IV–oral step-down. SCY-078 was generally well-tolerated in several human Phase 1 studies at clinically relevant dose levels. The most commonly reported adverse events after oral administration were gastrointestinal (GI) events (i.e., nausea, diarrhea, vomiting), typically transient, mild or moderate and not leading to discontinuation. The most commonly reported adverse events after IV administration of SCY-078 were local reactions at the site of infusion of SCY-078, observed only at the highest doses and highest concentrations in a Phase 1 study.

SCYNEXIS is using its platform of enfumafungin derivatives and expertise to discover new compounds for the treatment of systemic and cutaneous fungal infections affecting humans.

About Invasive Fungal Infections

Hospital acquired fungal infections are an increasing problem for the healthcare system, with Candida and Aspergillus species being responsible for approximately 85% of all invasive fungal infections in the United States and Europe. Infections caused by Candida rank as the fourth most common hospital-acquired bloodstream infection in the United States and result in mortality rates of 20-40% depending on the immune status of the patient.

The Centers for Disease Control and Prevention (CDC) recently classified a new multi-drug resistant pathogen, Candida auris, as an emerging serious global health threat. Preclinical results in the first systematic study of Candida auris, published in Antimicrobial Agents and Chemotherapy, showed that SCY-078 effective in vitro against C. auris and confirmed SCY-078’s differentiated activity compared to currently available antifungal drugs.

In the study, researchers at Case Western University evaluated the activity of SCY-078 and ten currently available antifungal agents against 16 different C. auris isolates to determine their susceptibility and several virulence factors that allow Candida species to grow and thus cause human infection. While most of the assessed strains of C. auris proved to be resistant to multiple drugs tested, SCY-078 showed potent activity against all strains at concentrations indicative of potential clinically-relevant effect. Additionally, results showed that SCY-078 reduced biofilms and biofilm metabolic activity at all concentrations tested, which is relevant considering that C. auris infections have been frequently associated with intravenous catheter use.

About Glucan Synthesis

The formation of glucan polymers is critical for fungal growth and inhibition of this process by the echinocandin class of drugs, e.g Cancidas®, is a clinically validated approach to antifungal therapy. However, echinocandins can only be administered parenterally, often requiring prolonged hospitalization for patients.

About Vulvovaginal Candidiasis

We are also developing SCY-078 as a treatment for vulvovaginal candidiasis (VVC), commonly known as a "yeast infection." VVC is caused by Candida albicans. An estimated 75% of women of reproductive age will have at least one episode of VVC during their lifetime and 40-45% will experience two or more episodes. As many as 7-9% of these patients suffer from recurrent VVC, or at least four episodes during a 12-month period. There are currently no products approved for recurrent VVC.