Activity of Eravacycline Against Anaerobic Bacteria from Europe Collected in 2013-14 IHMA Europe Sarl Phone: +44 (0) 1279 724929 I

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CONTACT: Presentation 784 Ian Morrissey Activity of Eravacycline Against Anaerobic Bacteria from Europe Collected in 2013-14 IHMA Europe Sarl Phone: +44 (0) 1279 724929 I. Morrissey1*, J. Sutcliffe2, M. Hackel3, S. Hawser1 Email: [email protected]

1IHMA Europe Sàrl, Epalinges, Switzerland; 2Tetraphase Pharmaceuticals, Watertown, USA; 3International Health Management Associates, Inc., Schaumburg, USA.

Revised Abstract Results Conclusions Background: Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class n Summary MIC data for eravacycline against anaerobic isolates where N ≥20 is shown in Table 1. Table 1. Summary MIC data for eravacycline against anaerobes Table 3. Summary MIC and susceptibility data for eravacycline and n Eravacycline demonstrated potent in vitro activity against anaerobic with broad-spectrum activity in development for the treatment of multidrug-resistant (MDR) infections. n Summary MIC and susceptibility data for eravacycline and comparators against Bacteroides comparators against Clostridium spp. (n=280), including clindamycin- Eravacycline has recently completed two Phase 3 studies for the treatment of complicated intra- (where N≥20) bacteria collected from Europe. spp. (n = 366), Clostridium spp. (n = 280) and Prevotella spp. (n = 179), including clindamycin- abdominal infections (cIAI) and complicated urinary tract infections (cUTI). The current study assessed resistant (n=88) and tetracycline-resistant (n=72) strains resistant and tetracycline-resistant strains, are shown in Tables 2 to 4. 0,& JPO n Importantly, the activity of eravacycline did not appear to be affected by the activity of eravacycline against 1,079 anaerobic bacteria collected from European hospitals in 2013- 0,& JPO n 2UJDQLVP 1 0,& 0,& 0LQ 0D[ resistance to tetracycline or clindamycin. MIC and MIC ranges for 2014. MIC90 values ranged from 0.03 - 2 µg/ml. 90 $QWLELRWLF %UHDNSRLQWV 6_,_5 6 , 5 0,& 0,& 0LQ 0D[ Methods: A total of 1,079 clinical anaerobic isolates from Europe were tested. MICs were determined n $OODQDHUREHV these sub-groups were similar to “wild-type” population MIC and MIC A comparison of the ratio of tigecycline versus eravacycline MICs for anaerobic isolates is $// ! ! 90 by agar dilution according to CLSI guidelines. Quality control testing was performed on each day of shown in Figure 2. $OO*UDPQHJDWLYHDQDHUREHV &OLQGDP\FLQ __! &OL5 ! ! ! ranges. testing as specified by the CLSI. $OO*UDPSRVLWLYHDQDHUREHV 7HW5 ! ! n These data along with data from the recently completed Phase 3 trials Results: Eravacycline results (in µg/ml) for all anaerobes combined and major species collected Bacteroides fragilis $// (UDYDF\FOLQH 1R%UHDNSRLQWV'HILQHG &OL5 (where N≥30) are shown in the following Table: Clostridium difficile will be used in determining the clinical breakpoints. 7HW5 Finegoldia magna n Figure 1. Country of origin (n,%) for the 1,079 anaerobic clinical $// Eravacycline had a lower MIC distribution than tigecycline or tetracy- 2UJDQLVP0,& JPO 1 0,& 0,& 0,1 0$; Clostridium perfringens isolates tested 0HURSHQHP __! &OL5 cline, with 23.5% of isolates having an eravacycline MIC 2-fold or more Bacteroides thetaiotaomicron 7HW5 $OODQDHUREHV lower than tigecycline. Prevotella bivia $// Bacteroides fragilis 0HWURQLGD]ROH __! &OL5 49, 5% 78,7% Parvimonas micra Belgium 7HW5 Clostridium difficile Peptostreptococcus anaerobius $// Finegoldia magna Bacteroides ovatus 3HQLFLOOLQ __! &OL5 139,13% CzechRepublic Bacteroides vulgatus 7HW5 Clostridium perfringens 142,13% References Peptoniphilus harei $// Bacteroides thetaiotaomicron 3LS7D] __! &OL5 1. CLSI, 2012. Methods for Antimicrobial Susceptibility Tests of Anaerobic Bacteria; Approved 92,8% Prevotella buccae France 7HW5 Standard—Eighth Edition. CLSI Document M11-A8. Clinical and Laboratory Standards Institute Prevotella bivia Clostridium innocuum $// (CLSI), Wayne, PA 19087-1898 USA. Parvimonas micra Prevotella melaninogenica 7HWUDF\FOLQH __! &OL5 Germany 2. CLSI, 2015. Performance Standards for Antimicrobial Susceptibility Testing; Informational Peptostreptococcus anaerobius 311,29% 7HW5 Supplement-Twenty-Second Edition M100-S25. Clinical and Laboratory Standards Institute 268,25% $// (CLSI), Wayne, PA 19087-1898 USA. Bacteroides ovatus 7LJHF\FOLQH __! &OL5 Hungary Bacteroidesvulgatus 7HW5 3. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf )'$EUHDNSRLQWVZHUHXVHGIRU7LJHF\FOLQH6,5SHUFHQWRILVRODWHVVXVFHSWLEOHLQWHUPHGLDWHRUUHVLVWDQWUHVSHFWLYHO\ Peptoniphilus harei Table 2. Summary MIC and susceptibility data for eravacycline and 3LS7D]SLSHUDFLOOLQWD]REDFWDP&OL5FOLQGDP\FLQUHVLVWDQW7HW5WHWUDF\FOLQHUHVLVWDQW Spain comparators against Bacteroides spp. (n=366), including clindamycin- Conclusions: Eravacycline demonstrated potent in vitro activity against anaerobic bacteria collected Table 4. Summary MIC and susceptibility data for eravacycline and from Europe. These data along with the data from the Phase 3 trials will be used in determining the resistant (n=125) and tetracycline-resistant (n=274) strains clinical breakpoints. Sweden comparators against Prevotella spp. (n=179), including clindamycin- 0,& JPO resistant (n=55) and tetracycline-resistant (n=81) strains $QWLELRWLF %UHDNSRLQWV 6_,_5 6 , 5 0,& 0,& 0LQ 0D[ $// ! 0,& JPO Introduction &HIR[LWLQ __! &OL5 ! $QWLELRWLF %UHDNSRLQWV 6_,_5 6 , 5 0,& 0,& 0LQ 0D[ Figure 2. Ratio of Tigecycline MIC and Eravacycline MIC for all 7HW5 ! $// $// ! ! &HIR[LWLQ __! &OL5 Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class with broad-spec- anaerobes combined 7HW5 &OLQGDP\FLQ __! &OL5 ! ! ! trum activity in development for the treatment of multidrug-resistant (MDR) infections, including those $// ! ! 7HW5 ! ! caused by MDR Gram-negative bacteria. Eravacycline was investigated in Phase 3 studies for the &OLQGDP\FLQ __! &OL5 ! ! ! $// treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections 7HW5 ! ! (UDYDF\FOLQH 1R%UHDNSRLQWV'HILQHG (cUTI). 70.0% &OL5 $// 63.6% 7HW5 (UDYDF\FOLQH 1R%UHDNSRLQWV'HILQHG &OL5 The current study assessed the activity of eravacycline against a collection of recent anaerobic clinical 60.0% $// 7HW5 isolates from Europe. 0HURSHQHP __! &OL5 $// 50.0% 7HW5 0HURSHQHP __! &OL5 $// 7HW5 isolates 40.0% 0HWURQLGD]ROH __! &OL5 $// of Methods 7HW5 0HWURQLGD]ROH __! &OL5 $// 7HW5 30.0% $// A total of 1,079 clinical anaerobic isolates from Europe (collected in 2013 and 2014) were tested. 3LS7D] __! &OL5 Country of origin is shown in Figure 1. 3LS7D] __! &OL5 20.0% 7HW5

Percenatge 15.2% 7HW5 11.8% $// ! Minimum inhibitory concentration (MIC) endpoints were determined by agar dilution under anaerobic $// ! 7HWUDF\FOLQH __! &OL5 ! conditions according to CLSI guidelines (1). 10.0% 7.0% 7HWUDF\FOLQH __! &OL5 1.1% 1.1% 7HW5 ! Quality control testing was performed each day of testing as specified by the CLSI using B. fragilis 0.1% 0.2% 7HW5 ! 0.0% $// $// ATCC 25285, B. thetaiotamicron ATCC 29741 and C. difficile ATCC 700057, as required. 0.12 0.25 0.5 1 2 4 8 16 7LJHF\FOLQH __! &OL5 7LJHF\FOLQH __! &OL5 Acknowledgement Antibiotic susceptibility was determined using CLSI 2015 breakpoints (2), with the exception of tigecy- RatioofTigecyclineMIC/EravacyclineMIC 7HW5 7HW5 cline where FDA breakpoints were used (3). )'$EUHDNSRLQWVZHUHXVHGIRU7LJHF\FOLQH6,5SHUFHQWRILVRODWHVVXVFHSWLEOHLQWHUPHGLDWHRUUHVLVWDQWUHVSHFWLYHO\ )'$EUHDNSRLQWVZHUHXVHGIRU7LJHF\FOLQH6,5SHUFHQWRILVRODWHVVXVFHSWLEOHLQWHUPHGLDWHRUUHVLVWDQWUHVSHFWLYHO\ This study was supported by a research grant from Tetraphase Pharmaceuticals 3LS7D]SLSHUDFLOOLQWD]REDFWDP&OL5FOLQGDP\FLQUHVLVWDQW7HW5WHWUDF\FOLQHUHVLVWDQW 3LS7D]SLSHUDFLOOLQWD]REDFWDP&OL5FOLQGDP\FLQUHVLVWDQW7HW5WHWUDF\FOLQHUHVLVWDQW

Presented at IDWeek, October 7 - 11, 2015, San Diego, CA, USA