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Background Existing antifungal agents are active against many common fungal pathogens; however, breakthrough fungal infections occur and often involve less frequently encountered yeast and mould isolates. These rarer isolates tend to exhibit diminished susceptibility to current agents. Manogepix (MGX, APX001A) is a novel inhibitor of the fungal Gwt1 enzyme. The prodrug (fosmanogepix), is being evaluated in Phase 2 clinical trials for invasive candidiasis/candidemia, Candida auris infections, and invasive aspergillosis. In this study, we evaluated the in vitro activity of MGX and comparators against 2,669 clinical fungal isolates collected worldwide (2018-2019) and stratified by infection type. Methods Fungal isolates were collected from medical centers located in North America (34 sites; 42.3%), Europe (30 sites; 37.9%), Asia-Pacific (11 sites; 12.3%), and Latin America (7 sites; 7.6%). Isolates were collected from bloodstream infections (BSI; 51.7%), pneumonia in hospitalized patients (PIHP; 21.1%), skin and skin structure infections (SSSI; 5.5%), urinary tract infections (UTI; 2.3%), intraabdominal infections (IAI; 1.9%), and other infection types (17.5%). Results MGX demonstrated potent in vitro activity against 1,887 Candida spp. isolates from BSI, PIHP, SSSI, and all infection types (MIC50/90, 0.008/0.03-0.06 mg/L) outperforming all comparator agents (Table). Similarly, MGX was equally active against 578 Aspergillus spp. isolates (MEC50/90, 0.015/0.03 mg/L), regardless of infection type. MGX was active against Cryptococcus neoformans var. grubii isolates from BSI and ALL infection types with MIC50/90 values of 0.5/2 mg/L. Scedosporium spp. isolates from PIHP and all infection types were inhibited by low concentrations of MGX (MEC50/90, 0.03/0.03 mg/L). Table 1 Conclusion MGX demonstrated potent antifungal activity against Candida spp., Aspergillus spp., C. neoformans var. grubii, and non-Aspergillus moulds, including Scedosporium spp. isolates. Notable activity was seen against C. auris, echinocandin-resistant Candida spp., azole-resistant Aspergillus, and Scedosporium spp. isolates. Further clinical development of fosmanogepix in difficult-to-treat resistant fungal infections is warranted. Disclosures Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Shawn A. Messer, PhD, Amplyx Pharmaceuticals (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support) Beth A. Schaefer, n/a, Amplyx Pharmaceuticals (Research Grant or Support) Paul Bien, MS, Amplyx Pharmaceuticals (Employee) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck &amp; Co, Inc. (Research Grant or Support)Merck &amp; Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

1260. Activity of Manogepix (APX001A) against 2,669 Fungal Isolates from the SENTRY Surveillance Program (2018-2019) Stratified by Infection Type