Proposal for revision of rezafungin

CLSI 24-hr broth MIC QC range for

C. parapsilosis ATCC 22019

For presentation to the CLSI Subcommittee

on Antifungal Susceptibility Tests

January 25, 2020

Jeff Locke, PhD

Background

• Rezafungin (previously CD101) is a once-weekly dosed echinocandin

• Structurally most similar to anidulafungin
• In vitro spectrum/potency in line with 3 approved echinocandins
• Ph3 clinical trials:
 ReSTORE - treatment of candidemia and invasive candidiasis
 ReSPECT - prevention of infections caused by Candida, Aspergillus, and
Pneumocystis spp. in allogenic blood and marrow transplant patients
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Rezafungin CLSI M23 Tier 2 studies

• Micromyx coordinated Tier 2 studies for rezafungin broth and disk (5 µg) formats
• QC ranges were tentatively accepted at CLSI antifungal subcommittee meetings

Format QC strain QC range Reference

0.25 – 1 µg/mL (24 hr)

C. parapsilosis ATCC 22019 January 2018 CLSI
BMD 0.25 – 2 µg/mL (48 hr)
Subcommittee on AFST
(M27-Ed4) 0.015 – 0.125 µg/mL (24 hr)
C. krusei ATCC 6258 (Dallas, TX)
0.015 – 0.125 µg/mL (48 hr)
C. krusei ATCC 6258 14 – 20 mm
Disk C. parapsilosis ATCC 22019 9 – 16 mm January 2019 CLSI
diffusion Subcommittee on AFST
(M44-A3) C. albicans ATCC 90028 13 – 20 mm (St. Augustine, FL)
C. tropicalis ATCC 750 14 – 20 mm

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 Rezafungin broth Tier 2 study data summary
C. parapsilosis ATCC 22019 C. krusei ATCC 6258

24 hr

48 hr

(C. Pillar, Micromyx, 2018) 4

 Original 24-hour Tier 2 C. parapsilosis 9-lab dataset

• No impact of media lot on rezafungin MIC values

• 48.5% shoulder at 1 µg/mL
• Rangefinder: 0.25 - 1 µg/mL

(C. Pillar, Micromyx, 2018) 5

 Summary of real-world rezafungin 24-hour QC data
• Real-world QC data:
 4 external labs
 7 years of data collection
 13 total studies
 4 plate types
 9+ rezafungin lots
 13+ media lots
 Comparator agent QC in
range for each study cited
 362 MIC values/QC strain

• Existing C. krusei QC range is supported with <1% out of QC

• C. parapsilosis, however, is out of QC in 13% of tests
• (Cidara internal data - not shown - generated in 14+ plate types and numerous drug
and media lots are consistent with these external MIC trends for both QC strains)
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Analysis of real-world rezafungin MIC data

87% of MIC values fall

within existing QC range

Rangefinder expansion
from initial QC range

• Rangefinder supports expansion of QC range to include 2 µg/mL

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Analysis of Tier 2 and real-world MIC data

• Combined data lead to Rangefinder expansion including 2 µg/mL

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 Tier 2, real-world, and combined data summary

Tier 2 Real-world Combined

360 360 360

320 320 320

280 280 280

Frequency (n)

Frequency (n)

Frequency (n)
240 240 240

200 200 200

160 160 160

120 120 120

80 80 80

40 40 40

0 0 0
0.06 0.125 0.25 0.5 1 2 4 8 0.06 0.125 0.25 0.5 1 2 4 8 0.06 0.125 0.25 0.5 1 2 4 8
MIC (µg/mL) MIC (µg/mL) MIC (µg/mL) 9
Rezafungin CLSI QC range modification request

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