2043. In Vitro Activity of Manogepix Against 2,810 Fungal Isolates from the SENTRY Surveillance Program (2020-2021) Stratified by Infection Type

Abstract

Abstract Background Manogepix is a new antifungal with a novel mechanism of action and potent in vitro activity against Candida (except C. krusei), Aspergillus, and rare mold isolates. The manogepix prodrug fosmanogepix is in Phase 2 development for the treatment of invasive mold infections caused by Aspergillus and rare molds (NCT04240886) and has completed Phase 2 studies for candidemia (NCT03604705) and C. auris (NCT04148287) infections. We evaluated the in vitro activity of manogepix and comparators against 2,810 geographically diverse fungal isolates collected in the SENTRY Surveillance Program during 2020-2021 and stratified them by infection type. Methods Antifungal susceptibility testing of manogepix and comparator agents was conducted according to CLSI M27 (2017) and M38 (2017) guidelines. Fungal surveillance isolates were collected from medical centers located in North America (30 sites; 37.9%), Europe (30 sites; 38.4%), Asia-Pacific (11 sites; 14.7%), and Latin America (6 sites; 9.0%). Infection sites included bloodstream infections (BSI; 48.3%), pneumonia in hospitalized patients (PIHP; 19.9%), skin and skin structure infections (SSSI; 7.8%), urinary tract infections (UTI; 3.1%), intra-abdominal infections (IAI; 1.6%), and other infection types (19.3%). Results Manogepix demonstrated potent in vitro activity against Candida spp. isolates (MIC50/90, 0.004-0.03/0.008-0.06 mg/L) regardless of infection type (Table). Similarly, manogepix was highly active against 534 Aspergillus spp. isolates (MEC50/90, 0.015/0.03 mg/L). Manogepix was active against 53 Cryptococcus neoformans var. grubii (MIC50/90, 0.25/1 mg/L), 19 Fusarium spp. (MEC50/90, 0.015/0.06 mg/L), 12 Lomentospora prolificans (MEC50/90, 0.03/0.06 mg/L), and 17 Scedosporium spp. isolates (MEC50/90, 0.06/0.12 mg/L). Conclusion Manogepix showed potent in vitro activity against Candida spp., Aspergillus spp., C. neoformans var. grubii, and rare molds, including Fusarium spp., L. prolificans, and Scedosporium spp. isolates. Notable activity was also demonstrated by manogepix against C. auris isolates. Further clinical development of fosmanogepix in difficult-to-treat, resistant fungal infections is warranted. Disclosures Michael D. Huband, BS, AbbVie: Grant/Research Support|Melinta: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.