P-1205. <i>In vitro</i> activity of EL219 (SF001) and amphotericin B agents against a collection of <i>Candida</i> and <i>Aspergillus</i> isolates collected in 2024

Abstract Background EL219 is a novel polyene antifungal drug (formerly known as SF001) currently in preparation for Phase 2 clinical trials (Elion Therapeutics). Through synthetic modifications to amphotericin B, EL219 was designed to improve antifungal activity while reducing the potential for toxicity. This international surveillance study reports on the in vitro activity of EL219 and amphotericin B tested against contemporary Candida and Aspergillus clinical isolates. Methods 130 Candida and 265 Aspergillus isolates were collected in 2024 from 73 medical centers worldwide including: USA (n=118, 25 centers), Europe (n=190, 17 countries), Asia-Pacific (n=75, 6 countries), and Latin America (n=12, 5 countries). Isolates were tested for susceptibility by CLSI broth microdilution methods. MIC results for comparator agents were interpreted per CLSI guidelines. Results EL219 was active against all Aspergillus species with MIC90 values ranging from 0.25-1 µg/mL; A. fumigatus (n=157; MIC50/90, 0.5/1 µg/mL), A. flavus species complex (sc) (n=32; MIC50/90, 0.5/0.5 µg/mL), A. niger sc (n=57; MIC50/90, 0.25/0.25 µg/mL), other Aspergillus species (n=19; MIC50/90, 0.5/1 µg/mL). EL219 was more active in vitro than amphotericin B against all Aspergillus species groups whose MIC90 values ranged from 0.5-4 µg/mL. EL219 was also active against all Candida species with MIC90 values ranging from 0.25-1 µg/mL; C. albicans (n=36; MIC50/90, 0.12/0.25 µg/mL), C. auris (n=31; MIC50/90, 0.25/1 µg/mL), C. glabrata (n=28; MIC50/90, 0.12/0.25 µg/mL), C. parapsilosis (n=16; MIC50/90, 0.12/0.25 µg/mL), and other Candida species (n=19; MIC50/90, 0.12/0.25 µg/mL). EL219 was more active in vitro than amphotericin B against all Candida species groups whose MIC90 values ranged from 1-2 µg/mL. Conclusion EL219 was active against prevalent Aspergillus and Candida clinical isolates causing invasive mycoses recovered in 2024. EL219 was often 4- to 8-fold more active than amphotericin B when comparing MIC50/90 values. These results further support the continued development of EL219. Disclosures Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support