- |||||||||| fosmanogepix (APX001) / Amplyx Pharma, APX001 / 3SBio, Apexigen
Biomarker, Clinical, Journal: Galactomannan is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis. (Pubmed Central) - Sep 1, 2020
In a murine invasive pulmonary aspergillosis model, fosmanogepix or posaconazole treatment resulted in a ∼6-7 log reduction in conidial equivalents (CE)/g lung tissue after 96 h versus placebo. Changes in GM levels in BAL and serum mirrored reductions in lung CE with significant decreases seen after 96 h or 72 h for fosmanogepix or posaconazole, respectively (P <0.02).
- |||||||||| fosmanogepix (APX001) / Amplyx Pharma, APX001 / 3SBio, Apexigen
Preclinical, Journal: Synthesis of analogs of the Gwt1 inhibitor manogepix (APX001A) and in vitro evaluation against Cryptococcus spp. (Pubmed Central) - Aug 12, 2020
Several compounds demonstrated significantly (8- to 32-fold) improved antifungal activity against both Cryptococcus neoformans and C. gattii as compared to manogepix. Further in vitro characterization identified three analogs with a similar preliminary safety and in vitro profile to manogepix and superior activity against Cryptococcus spp.
- |||||||||| fluconazole / Generic mfg.
Preclinical, Journal: In Vitro Activity of APX001A (Manogepix) and Comparator Agents against 1,706 Fungal Isolates Collected During an International Surveillance Program (2017). (Pubmed Central) - Jun 10, 2020
isolates; corresponding anidulafungin, micafungin, and fluconazole MIC values were 16- to 64-fold higher...Aspergillus isolates (>98%) exhibited a wild-type phenotype for the mold-active triazoles (itraconazole, posaconazole, and voriconazole)...The extended spectrum of APX001A was also notable for its potency against many less common, yet antifungal-resistant strains. Further studies are in progress to evaluate the clinical utility of the methyl phosphate prodrug, APX001, in difficult-to-treat resistant fungal infections.
- |||||||||| fosmanogepix (APX001) / Amplyx Pharma, APX001 / 3SBio, Apexigen
Preclinical, Journal: APX001 is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis. (Pubmed Central) - Jan 29, 2020
The observed survival and tissue clearance were comparable to a clinically relevant posaconazole dose. These results warrant the continued development of APX001 as a broad spectrum, first in class treatment for invasive fungal infections.
- |||||||||| fluconazole / Generic mfg., fosmanogepix (APX001) / Amplyx Pharma, APX001 / 3SBio, Apexigen
Journal: APX001 and Other Gwt1 inhibitor Prodrugs are Effective in Experimental Coccidioides immitis Pneumonia. (Pubmed Central) - Jan 29, 2020
In a survival experiment, both APX001 and APX2097-treated mice survived significantly longer than control and fluconazole treated mice. APX001 and other members of this new class of antifungal agents may offer great promise as effective therapies for coccidioidomycosis.
- |||||||||| fluconazole / Generic Mfg., fosmanogepix (APX001) / Amplyx Pharmaceuticals, APX001 / 3SBio, Apexigen
Preclinical, Journal: In vitro and in vivo Evaluation of APX001A/APX001 and other Gwt1 inhibitors against Cryptococcus. (Pubmed Central) - Oct 18, 2019
In a CM model, APX001 and fluconazole each, alone, reduced log colony forming units (CFU)/g brain (0.78 and 1.04, respectively), whereas the combination resulted in a reduction of 3.52 log CFU/g brain.Efficacy as measured by a reduction in brain and lung fungal burden was also observed for another Gwt1 inhibitor prodrug, APX2096, where dose dependent reductions in fungal burden ranged between 5.91 and 1.79 log CFU/g lung and between 7.00 and 0.92 log CFU/g brain, representing near or complete sterilization of lung and brain tissue at the higher doses. These data support further clinical evaluation of this new class of antifungal agents for CM.
- |||||||||| fluconazole / Generic Mfg.
Preclinical, Journal: APX001A in vitro activity against contemporary blood isolates and C. auris determined by the EUCAST reference method. (Pubmed Central) - Oct 2, 2019
APX001A is the active moiety of the first-in-class drug candidate APX001...EUCAST E.Def 7.3.1 susceptibility testing included APX001A, amphotericin B, anidulafungin, micafungin, fluconazole, and voriconazole...A correlation was observed between APX001A and fluconazole MICs across all species except C. guilliermondii and C. auris, and when comparing high and low fluconazole MIC isolates of C. albicans, C. dubliniensis, C. glabrata, C. tropicalis and C. aurisAPX001A showed promising in vitro activity against most Candida and other yeast species including C. auris when compared to five comparators. WT-ULs were suggested for the common species and a new and un-explained correlation to fluconazole susceptibility was observed.
- |||||||||| Clinical, Journal: Drugs in Clinical Development for Fungal Infections. (Pubmed Central) - Apr 5, 2019
We also discuss two glucan synthesis inhibitors: CD101, an echinocandin with an increased half-life, and SCY-078 with oral bioavailability and increased activity against echinocandin-resistant isolates...Two novel classes of antifungal drugs are also described: glycosylphosphatidylinositol inhibitors, and the leading drug APX001, which disrupt the integrity of the fungal wall; and the orotomides, inhibitors of pyrimidine synthesis with the leading drug F901318. Finally, a chitin synthesis inhibitor and progress on human monoclonal antifungal antibodies are discussed.
- |||||||||| fosmanogepix (APX001) / Amplyx Pharma, APX001 / 3SBio, Apexigen
APX001 protects immunosuppressed mice from scedosporiosis (Arena 2) - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_4064;
APX001 protected immunosuppressed mice from scedosporiosis due to S. apiospermum. Continued investigation of APX001 as a novel antifungal agent against scedosporiosis is warranted.
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