Breakthrough Clinical Results
SCYNEXIS announced multiple presentations at the 12th Congress on Trends in Medical Mycology (TIMM-12) highlighting data on its second-generation antifungal drug candidate, SCY-247. The presentations showcase SCY-247's in vitro activity against various Candida species, including multidrug- and pandrug-resistant C. auris and Aspergillus species. Data demonstrates SCY-247's efficacy against echinocandin-resistant strains and its broad-spectrum antifungal activity. The company anticipates reporting Phase 1 SAD/MAD data for oral SCY-247 in Q3 2025.
Key Highlights
- SCY-247 demonstrates in vitro activity against C. auris strains, including echinocandin-resistant isolates.
- SCY-247 shows broad-spectrum antifungal activity against Candida species and Aspergillus species.
- Phase 1 SAD/MAD data for oral SCY-247 is anticipated in Q3 2025.
- Multiple presentations at TIMM-12 highlight SCY-247's potential to combat resistant fungal infections.
Incidence and Prevalence
Latest Estimates of Candida Infections Globally
Incidence and Prevalence
Recent studies provide important insights into the global burden of Candida infections. A 2024 study from a pediatric hematology clinic revealed Candida growth in 6.7% of blood cultures, while a 2023 study from Spain reported a prevalence of candidiasis of 14.6% based on data collected between 2000 and 2018.
In Latin America, a multi-center study across seven countries found an overall incidence of candidemia of 1.18 cases per 1,000 admissions, with Colombia showing the highest incidence and Chile the lowest. A 2019 Brazilian study focusing on children reported a higher incidence of 2.12 per 1000 admissions.
Species Distribution
The species distribution varies geographically. The 2024 study showed 43.2% were Candida parapsilosis complex, 29.7% were Candida albicans, and 8.1% were Candida haemulonii complex.
A 2021 Malaysian study examining candidemia cases from 2001-2018 found that among 1175 patients, C. parapsilosis was most common at 29.2%, followed by C. albicans (20.1%), and C. tropicalis (18.7%).
In Latin America, the distribution showed C. albicans (37.6%), C. parapsilosis (26.5%), and C. tropicalis (17.6%) as leading agents, with significant regional variation.
A 2014 study on type 1 diabetes patients found Candida species in 39% of vaginal swabs, with C. albicans being predominant (50%), followed by C. glabrata (36.6%).
Special Populations
Demographic patterns show that among 672 episodes of candidemia in Latin America, 44.2% occurred in children (23.7% younger than 1 year), 36.2% in adults between 19 and 60 years old, and 19.6% in elderly patients.
Recent studies have identified increased risk in specific populations. A 2024 study found that fibromyalgia patients had significantly higher odds ratios for candidal esophagitis (OR = 7.88) compared to the general population. Additionally, a 2018 study of sarcoidosis patients found that fungal infections accounted for 10 out of 38 severe infections observed after a median follow-up of 8 years.
Mortality and Outcomes
The mortality rate among patients with invasive candidiasis was reported as 35.1% in the 2024 pediatric hematology study. In the Latin American study, the overall 30-day survival for candidemia patients was 59.3%. The Brazilian pediatric study reported a global mortality rate from candidemia episodes of 28.31%.
Septic shock during candidemia episodes was associated with a relative risk-adjusted (RRa) of 2.77 for mortality.
Emerging Concerns
The emergence of pan-drug-resistant C. auris strains was noted in a 2021 review as a concerning development. However, antifungal susceptibility in the 2024 study showed over 90% sensitivity for most antifungals, with slightly lower rates for fluconazole (86.7%) and voriconazole (84.4%).
Current evidence indicates that pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis, with candidemia being the most frequently diagnosed invasive infection.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Candida Infections
Recent publications have revealed several promising mechanisms of action and therapeutic targets for treating Candida infections:
Targeting Cell Wall Components
The CaFKS1 subunit of 1,3-beta-glucan synthase, an essential enzyme that builds Candida cell walls, has emerged as a critical target. Machine learning models have achieved 96.72% accuracy in identifying active compounds against this target. Notably, several drugs including goserelin and icatibant (many being gonadotrophin-releasing hormone antagonists or agonists) demonstrated high activity against CaFKS1, with five of these predicted drugs experimentally confirmed to inhibit Candida.
Metabolic Pathway Inhibition
Fructose-1,6-bisphosphate aldolase (Fba1p) has been identified as a promising target for antifungal development. The rare fatty acid petroselinic acid (PeAc), isolated from plants of the Apiaceae family, effectively inhibits this enzyme. PeAc demonstrates broad activity against pathogenic fungi, shows synergistic effects with fluconazole, inhibits C. albicans hyphae and biofilm formation, and exhibits in vivo efficacy with low mammalian cell toxicity.
Mitochondrial Targeting
Mitochondrial components are being investigated as potential therapeutic targets due to their crucial roles in fungal viability and pathogenesis. Novel antifungal agents disrupt mitochondrial respiration, increase intracellular ATP, and generate reactive oxygen species. Additionally, the metal chaperone protein MtmA has been linked to antifungal resistance, as its repression leads to upregulation of multidrug resistance-associated transport genes and abnormal activation of the calcium signaling system.
Natural Product Derivatives
Traditional medicinal plants continue to show promise against Candida infections. The crude extract of Thalictrum rhynchocarpum root demonstrated superior activity against Candida albicans with a minimum inhibitory concentration of just 3.90 μg/mL, outperforming the reference drug clotrimazole. This activity is attributed to secondary metabolites including flavonoids, alkaloids, glycosides, phenols, saponins, steroids, and terpenoids.
Genetic Mechanisms of Resistance
Understanding resistance mechanisms has revealed that ERG11 gene mutations in azole-resistant C. tropicalis contribute significantly to antifungal resistance. This insight is particularly important as many Candida species including C. glabrata, C. parapsilosis complex, and C. tropicalis show reduced sensitivity to azole antifungals like itraconazole, fluconazole, and voriconazole.
Iron Acquisition Pathways
The FTR1 gene-encoded ferrous permease has been identified as necessary for host iron acquisition by fungi, making it a potential target for novel antifungal therapies. Novel epitope-based vaccines targeting the FTR1 protein show promise as potential therapeutics against virulent fungal species.
These emerging mechanisms of action represent significant advances in our understanding of Candida pathogenesis and offer promising avenues for developing more effective antifungal therapies to combat both invasive and non-invasive Candida infections.
Drug used in other indications
SCY-247 Clinical Trials Beyond Candida Infections
Based on the available information, I cannot provide specific details about clinical trials of SCY-247 for indications other than Candida infections. The context provided does not contain information about:
- Additional indications for which SCY-247 is being trialed
- Intervention models used in these trials
- Study designs for non-Candidiasis applications
- Clinical protocols for SCY-247 in other fungal infections
SCY-247 is an investigational antifungal agent, but the specific range of fungal pathogens it targets beyond Candida species is not detailed in the provided information. Similarly, there is no information about the mechanism of action that might explain its potential efficacy across multiple fungal infection types.
For comprehensive information about SCY-247's current clinical trial portfolio, including indications beyond Candida infections and their respective intervention models, consulting clinical trial registries such as ClinicalTrials.gov or contacting the drug developer directly would be advisable.
The development of broad-spectrum antifungal agents is an important area of research given the rising incidence of invasive fungal infections and increasing antifungal resistance. Novel agents with activity against multiple fungal pathogens represent significant therapeutic advances in this field.