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From New Mechanisms to New Standards of Care Corporate Presentation - - PowerPoint PPT Presentation

From New Mechanisms to New Standards of Care Corporate Presentation August 2019 Forward-Looking Statements Statements in this presentation, other than statements of historical fact, constitute forward-looking statements within the meaning of


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SLIDE 1

From New Mechanisms to New Standards of Care

Corporate Presentation August 2019

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SLIDE 2

Forward-Looking Statements

Statements in this presentation, other than statements of historical fact, constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements regarding Summit’s clinical trials supporting the safety and efficacy of its product candidates and the potential novelty of such product candidates as treatments for disease, plans and objectives for preclinical studies, clinical trials, product development and regulatory filings, Summit’s collaboration with Eurofarma Laboratorios SA, Summit’s award from BARDA, Summit’s Discuva Platform, strategies, future performance, expectations, assumptions, financial condition, liquidity and capital resources. These forward-looking statements may be preceded by, followed by or otherwise include the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions. Actual results or events may differ materially from those expressed or implied in any forward-looking statements due to various factors, including the risks and uncertainties inherent in clinical trials and product development and commercialization, such as the uncertainty in results of clinical trials for product candidates, the uncertainty of whether the preliminary results from a clinical trial will be predictive of final results of that trial or whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, the risk of failure of the third parties upon whom Summit relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk that any third-party collaborator, including Eurofarma, terminates or fails to meet its obligations to Summit, the risk of the ability of BARDA to terminate

  • ur contract for convenience at any time, the risk that Summit’s discovery and development platform may not identify new potential drug

development candidates, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials and the timing, cost and design

  • f future clinical trials and research activities, the timing of expected filings with the FDA or other regulatory agencies; and the other risks and

uncertainties described in Summit’s public filings with the Securities and Exchange Commission. Summit may not actually achieve the plans, intentions or expectations disclosed in its forward-looking statements, and you should not place undue reliance on its forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Summit disclaims any intent or obligation to revise or update these forward-looking statements, except as required by applicable law.

August 2019 Company presentation 2

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SLIDE 3

Urgent Need for New Antibiotics Provides Major Opportunity

August 2019 Company presentation 3

Poor patient outcomes and increasing resistance with existing classes of antibiotics

THE CHALLENGE THE SUMMIT SOLUTION

Recent launches have disappointed Focus on differentiation

  • No new classes of antibiotics: incremental

changes fail to combat emerging drug resistance

  • Failure to address clear unmet patient needs
  • No compelling medical evidence: non-

inferiority trials don’t show clear patient benefit

  • No economic data to justify use of premium

priced treatments over cheap generics

  • Develop new classes of antibiotics with

distinctive features and benefits

  • Target the infection or pathogen to restore

health

  • Address measurable unmet medical need
  • Show superiority in patient outcomes to

establish compelling use case

  • Demonstrate value of new antibiotics

through economic data

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SLIDE 4

Summit’s Approach: Innovation for the Patient

August 2019 Company presentation 4

Translating novel science into differentiated products delivered to the patient

DISCOVER

  • New classes of antibiotics
  • Distinctive features and benefits
  • Targeted spectrum preserves microbiomes
  • Less prone to rapid resistance development

DEVELOP

  • Clinical trial designs to test for unmet need
  • Outcomes show superiority over standard of care
  • Health economic measures demonstrate value of

improved outcomes

COMMERCIALIZE

  • Patients offered solution to unmet need
  • Physicians have data to switch therapy
  • Payors have data showing economic value
  • Strong stewardship case to use new drugs

PATIENT UNMET NEED

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SLIDE 5

Our New Mechanism Antibiotic Pipeline

August 2019 Company presentation

CDI (Ridinilazole)1 Gonorrhea (SMT-571) Enterobacteriaceae (DDS-04 Series)

Phase 1 Phase 2 Phase 3 Discovery Preclinical Threat Status

5

  • 1. We own worldwide rights to ridinilazole, outside of certain Latin American countries and Caribbean islands.

ESKAPE Program Gonorrhea (Target #2)

A portfolio created with assistance: BARDA, CARB-X, Innovate UK & Wellcome Trust Urgent (CDC) Urgent / High (CDC / WHO) Urgent / High (CDC / WHO) Urgent / High (CDC / WHO) Urgent / High (CDC / WHO) Discuva Platform

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SLIDE 6

About C. difficile Infection (CDI)

August 2019 Company presentation 1. Decision Resources, 2015 2. New England Journal of Medicine, 2015

>1.0m cases per year in US and EU1, 29,000 deaths per year in the US2 Initial treatment fails to cure or sustain cures in around a third

  • f cases

Failure likely connected to impact on microbiome of standard of care

6

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SLIDE 7

Ridinilazole Designed to be Patient-Friendly

August 2019 Company presentation 7

Clear differentiation in Phase 2 trial supports new standard of care potential

Initiated global Phase 3 clinical trials Feb. 2019 Expect top-line data H2 2021 With positive results, expect NDA filing 2022

 60% reduction in recurrences, the key unmet need  Superiority over standard of care vancomycin in sustained cures  Discharged from hospital earlier

Cured CDI and sustained cures

  • ver 40 days

 Treatment preserved microbiome and allowed good bacteria to recover  Well-tolerated, as treatment targeted to gut

Gut-friendly

 Resolved diarrhea earlier  Significantly reduced pain/discomfort  Significantly reduced anxiety/depression

Improved physical & mental effects of CDI

Source: CoDIFy Phase 2 clinical trial

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SLIDE 8

Aiming for Dominant Position in Front-Line Treatment

August 2019 Company presentation 8

  • A more effective treatment option
  • High cure rate with low recurrence
  • Well tolerated with preservation of the microbiome
  • A more effective treatment option
  • Statistical superiority over vancomycin, the standard of care
  • High cure rates with low recurrence
  • Premium pricing supported by total cost of care savings
  • Fewer expensive recurrences
  • Fewer readmissions help meet CMS targets

Goal of Phase 3 clinical trials is to show clear benefits of ridinilazole

Compelling data to support potential switch to front-line use of ridinilazole PATIENT

~$3,000- $6,100

ESTIMATED SAVINGS OF PER PATIENT IN THE US1

PHYSICIAN PAYOR

  • 1. Range based on management estimates of potential savings of front-line treatment reducing CDI recurrence derived from

Ghantoji et al., J Hosp. Infect 2010; Duberke et al., Infect Control Hosp Epidemiol 2014; Zhang et al., CID 2018; Zilderberg et al., Medicine 2017; Desai et al., BMC Infect Dis 2016. Relevant studies identified in PubMed search July 2019, with reported/derived recurrence costs adjusted to 2023 pricing using US CPI for years to 2018 and assumed 2% inflation 2019-2023 rate to 15%

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SLIDE 9

Ridinilazole: Significant Commercial Potential in CDI

Estimated cost savings per US patient with first incidence treated, if recurrence rate was reduced by absolute 15%2

August 2019 Company presentation 9

~450,000

US PATIENTS TREATED ANNUALLY FOR 1st CDI INCIDENCE

25%

APPROXIMATELY

HAVE A RECURRENCE. RISK RISES TO 45% FOR SECOND, 65% FOR THIRD

~$1.4-2.7B

Total potential cost savings to US healthcare system supports premium pricing

COST OF RECURRENCE IN US HOSPITALS1

$11,400 -

~$3,000-6,100

  • 1. Range from Ghantoji et al., J Hosp. Infect 2010; Duberke et al., Infect Control Hosp Epidemiol 2014; Zhang et al., CID 2018;

Zilderberg et al., Medicine 2017; Desai et al., BMC Infect Dis 2016. Relevant studies identified in PubMed search July 2019, with reported/derived recurrence costs adjusted to 2023 pricing using US CPI for years to 2018 and assumed 2% inflation 2019-2023 rate to 15%; 2. Based on management estimates of potential savings of front-line treatment reducing CDI recurrence

$23,200

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SLIDE 10

Ridinilazole has a Highly Targeted Spectrum of Activity

August 2019 Company presentation

ANTIBIOTIC MIC90 µg/mL Bacteria Ridinilazole Vancomycin Metronidazole Fidaxomicin Clostridium difficile

0.25 4 2 0.5

Bifidobacterium spp.

>512 1 128 0.125

Eggerthella lenta

>512 4 0.5 ≤0.03

Various Gram positive rods

>512 4 2 128

Finegoldia magna

64 0.5 1 2

Peptostreptococcus anaerobius

64 0.5 1 ≤0.03

Staphylococcus aureus

>512 1 >512 16

Enterococcus faecalis

>512 4 >512 8

Enterococcus faecium

128 0.5 >512 128

Streptococcus spp.

>512 1 >512 128

Bacteroides fragilis

>512 64 2 >512

Bacteroides ovatus

>512 256 2 >512

Bacteroides thetaiotaomicron

>512 128 2 >512

Bacteroides vulgatus

>512 128 1 >512

Parabacteroides spp.

>512 128 2 >512

Fusobacterium nucleatum

64 512 0.25 >512

Fusobacterium spp.

>512 >512 0.5 >512

Prevotella spp.

>512 512 1 >512

Veillonella spp.

>512 >512 2 256

Lactobacilus spp.

>512 >512 >512 >512

10 MIC90 value: the minimum concentration of the antibiotic at which 90% of the microbial activity is inhibited Source: Goldstein et al: Antimicrob Agents Chemother. 2013, 57: 4872–4876

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SLIDE 11

Ridinilazole Highly Preserving of Patients’ Microbiomes Compared to Vancomycin in Phase 2 Clinical Trial

Cladograms Showing Changes in Relative Abundance of Microbiome Following 10 Days Dosing

August 2019 Company presentation

RIDINILAZOLE VANCOMYCIN Increased relative abundance

Source: Thorpe et al., PLOS ONE, 2018

Reduced relative abundance

11

  • C. difficile
  • C. difficile
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SLIDE 12

Ridinilazole: Statistical Superiority Over Vancomycin in Phase 2 CoDIFy Trial in Sustained Clinical Response (SCR)

August 2019 Company presentation

25 50 75 100 Vancomycin Ridinilazole

Cure at End of Treatment

25 50 75 100 Vancomycin Ridinilazole

Recurrence 30 Days Post Treatment

25 50 75 100 Vancomycin Ridinilazole

Sustained Clinical Response (SCR)

Δ 24.3 66.7% 42.4%

77.8% 69.7% 14.3% 34.8%

(90% CI 3.1–39.1)

Primary analysis conducted on the mITT group; n=36 in ridinilazole arm and n=33 in vancomycin arm

Source: Vickers et al, Lancet ID, 2017 12

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SLIDE 13

Ri-CoDIFy: Landmark Clinical Program

Top line data expected in H2 2021

August 2019 Company presentation 13

Aiming for clear differentiation to support switch from current therapies

Primary endpoint: sustained clinical response (SCR) that measures cure and recurrence 30 days post treatment Test for superiority compared to vancomycin Key secondary endpoint: cure at end of treatment

ECONOMIC DATA SUPERIORITY TRIALS MICROBIOME

Range of outcome measures incorporated into trial design including readmission rates and length of hospital stay Show preservation of healthy gut microbiome, key in reducing rates of recurrence Aim to show ridinilazole is better at sustaining patient cures Inclusion of health economic measures to support commercialization Comprehensive analysis

  • f impact of ridinilazole on

the microbiome

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SLIDE 14

Phase 3 Clinical Trials Powered to Test for Superiority in SCR

August 2019 Company presentation 14

 Test for superiority; >95% power, 2-sided test, 5% significance level  Assumes 55% SCR rate for vancomycin & a 15% improvement with ridinilazole  Consistent trend on SCR to 60 and 90 days post end of treatment (EOT) required

Primary endpoint: SCR

 Test for non-inferiority; 90% power, 1-sided test, 2.5% significance level  Established non-inferiority margin of 10%  Assumes conservative 80% cure rate for vancomycin and ridinilazole

Important secondary endpoint: clinical cure at assessment of cure

z

1 2

Group

340 340

N

Ridinilazole Vancomycin

Agent

200mg BID for 10 days 125mg QID for 10 days

Regimen

Trial Design

Two global Phase 3 trials of near identical design to the successful Phase 2 proof of concept trial

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SLIDE 15

Ridinilazole: Commercialization Strategy

August 2019 Company presentation 15

Delivering clinical and economic evidence at launch to position ridinilazole as front-line agent. Done by achieving the following goals:

 Demonstrating superiority over current standard of care vancomycin on a clinically meaningful endpoint (SCR) that assesses the unmet medical need of reducing CDI recurrence  Could result in regulatory approval for:

Differentiated label

Treatment of CDI and reducing the recurrence of CDI

 Justifies premium price for ridinilazole

  • ver current standard of care

Demonstrating economic benefits

  • f reduced recurrence

 Quality metrics requiring healthcare facilities to minimize readmissions  Increasing awareness of the importance

  • f the microbiome

 Stewardship: CDI specific therapy replacing inappropriate vancomycin use

Capitalizing on favorable environment

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SLIDE 16

New Science

Discovering new mechanism antibiotics with our Discuva Platform

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SLIDE 17

Discuva Platform: Enabling Optimized Candidate Selection

August 2019 Company presentation

Discuva Platform uses transposon-mediated mutagenesis to allow exquisite control over bacterial genomes to enable selection of antibiotics with:

New mechanisms

  • f action

Targeted spectrums of activity Low propensities for resistance

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We advance those new mechanism candidates where a major commercial opportunity exists and we believe we can show significant advantages over the current standard of care

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SLIDE 18

Proprietary Libraries Cover Major Unmet Needs and Enable Potential Pipeline Expansion

August 2019 Company presentation 18

Gram positive Gram negative

  • P. aeruginosa
  • E. coli
  • N. gonorrhoeae
  • K. pneumoniae
  • A. baumannii

CDC Urgent / WHO Critical Threats

  • S. aureus
  • E. faecium
  • E. faecalis

CDC Serious Threats / Other ESKAPE Pathogens

  • S. pneumoniae
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SLIDE 19

1.4m cases in US & EU 78m worldwide1

  • N. Gonorrhoeae

has consistently developed resistance to known classes

  • f antibiotics

Clinicians are using the last CDC recommended treatment option; no new treatment

  • ptions available

About Gonorrhea

August 2019 Company presentation 19

  • 1. World Health Organization, July 2017 press release
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SLIDE 20

SMT-571: Potential Front-Line Treatment for Gonorrhea

 Novel mechanism, targeted spectrum  Potent in vitro activity against over 200 clinical isolates, including numerous multi- and extensively drug resistant strains  Low propensity for resistance development  Demonstrated in vivo activity and

  • ral bioavailability

 Potential to replace inappropriate use of ceftriaxone  Discovered and optimized using Discuva Platform

August 2019 Company presentation 20

Addressing the emergence of extensively- and multi-drug resistant gonorrhea

Currently in IND-enabling studies

Resistance of gonococcal isolates to antibiotics Africa Americas E Med. Europe SE Asia W Pac Total Countries (%) reporting resistance/ decreased susceptibility Ceftriaxone and/or Cefixime Countries 9 16 3 27 6 16 77 ≥5% 1 15 4 6 26 51 (66%) <5% 2 6 8 1 8 25 Full Susceptibility 6 10 3 4 1 2 26 Azithromycin Countries 3 7 1 26 6 15 58 ≥5% 3 2 21 1 2 29 47 (81%) <5% 4 3 4 7 18 Full susceptibility 1 1 2 1 6 11 Ciprofloxacin Countries 8 16 1 26 6 15 72 >90% 1 1 3 4 5 14 70 (97%) ≥5% 6 14 23 2 7 52 <5% 1 3 4 Full susceptibility 2 2

Source: Wi et al, Plos Medicine, 2017

SMT-571 designed to address the unmet need

When resistance rates reach ≥5% globally, the next treatment option is recommended

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SLIDE 21

Gram-negative family of bacteria, includes E. coli, K. pneumoniae More than 1m cases1 in US across three infection sites: lung, bloodstream, urinary tract Approaching crisis, with growing cases of resistance to last resort antibiotics

About Enterobacteriaceae

August 2019 Company presentation 21

  • 1. Summit estimate based on Flores-Morales, 2015
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SLIDE 22

DDS-04 Series: Targeting Enterobacteriaceae Infections

 Enterobacteriaceae specific targeting through LolCDE  In vivo proof of concept established  Exposure observed across key infection sites in vivo  Low propensity for resistance  No cross resistance to other major antibiotic classes  Could replace reliance on antibiotics w/toxicity concerns  Discovered and optimized using Discuva Platform

August 2019 Company presentation 22

Potential to treat three major infection sites: bloodstream, lungs and urinary tract

Currently in lead optimization

Sources: (a) Sader et al, JAC, 2018; (b) Cilloniz et al, Int J Mol Sci, 2016; (c) NHSN 2014; (d) Magill, NEJM, 2018; (e) Flores-Mireles et al, Nat Rev Microbiol, 2015; (f) Wagenlehner et al., WJU, 2012; (g) Magill et al, NEJM 2014; (h) Koningstein et al, PLOS One, 2014. CDDEP Resistance Map 2017.

20 40 60 80 100 China Greece India Italy Russia Turkey US

  • E. coli carbapenem
  • K. pneumoniae carbapenem
  • E. coli cephalosporin
  • K. pneumoniae cephalosporin

Percent of resistant isolates

DDS-04 series designed to address unmet need

Pneumonia/LRT Bloodstream

Healthcare Associated Infection

861,000 313,000

EU Incidence

250,000 249,000

US Incidence

27-30 a,b 19-20 c,d

% Enterobacteriaceae

Urinary Tract 888,000 562,000 62-75 e-h

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SLIDE 23

Planned Upcoming Milestones & Newsflow

August 2019 Company presentation

2022 2021 2019 2020

23

  • Initiated Phase 3

trial for ridinilazole

  • H2 2021: expect

topline Phase 3 data for ridinilazole

  • 2022: with positive

Phase 3 results, expect to file NDA for FDA approval of ridinilazole

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SLIDE 24

Antibiotic Experience at Summit

David Roblin, MD, President of R&D Previous antibiotic experience at Pfizer and Bayer Richard Vickers, PhD, CSO Discovered ridinilazole Dave Powell, PhD, SVP, Research Previous antibiotic experience at GSK Nawaz Khan, VP, Anti-infectives Discovery Discovered SMT-571 Clive Mason, Senior Director, Platform Discovery Discovered SMT-571 Frank Armstrong, MD, Chairman Previous antibiotic experience at AstraZeneca and Bayer

August 2019 Company presentation

Brought 8 antibiotics to market

24

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SLIDE 25

Summary Financials

August 2019 Company presentation

Key Items Amount

Nasdaq Share Price (Aug. 1, 2019): $1.36 Issued Share Capital O/S(1): 32.1M Market Cap (Aug. 1, 2019): $44M Cash Balance (Apr 30, 2019)(2): $36.9M Debt (Apr 30, 2019): $0

SYMBOL: SMMT SYMBOL: SUMM

(1) Based on total Ordinary Shares outstanding; Ordinary Shares outstanding as of Apr 30, 2019, were 160.5 million; one ADS is equivalent to five Ordinary Shares (2) Assumes an exchange rate of $1.303 to £1.00 25

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SLIDE 26

Contact Details

investors@summitplc.com Twitter: @summitplc 136a Eastern Avenue Milton Park Oxfordshire UK One Broadway Cambridge Massachusetts US

August 2019 Company presentation 26

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SLIDE 27

Past Commercial Success Associated with Innovation

1920s-1980s

  • Multiple novel mechanisms & classes
  • Multiple examples of significant commercial

success

  • Ciprofloxacin; azithromycin; ceftriaxone
  • Resistance not clinical issue

August 2019 Company presentation

Penicillin Aminoglycosides, Bacitracin Nitrofurans Tetracyclines Macrolides Quinolones Glycopeptides, Nitroimidazoles, Streptogramins Trimethoprim Oxazolidinones Sulfonamides Polymyxins, Phenicols Cephalosporins Pleuromutilins Cycloserine, Novobiocin Rifamycins Fosfomycin Mupirocin Carbapenems Monobactams

Adapted from ReAct Group 2015

1920s 1980s 1970s 1960s 1950s 1940s 1930s 2010s 2000s 1990s YEAR ANTIBIOTIC CLASS DISCOVERED

Since 1990

  • Few new mechanisms; only

incremental benefits

  • Niche market positioning with

low commercial return

  • Resistance is a clinical issue

Lipopeptides

27

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SLIDE 28

Ridinilazole is the Only Novel Late Stage Antibiotic

August 2019 Company presentation 28

Drug name Company Phase Drug Class Ceftobiprole Basilea 3/ Marketed (ex-US) Cephalosporin Plazomicin Achaogen Marketed (US) Aminoglycoside Eravacycline Tetraphase Marketed (US) Tetracycline Omadacycline Paratek Marketed (US) Tetracycline Iclaprim Motif Bio CRL received 2,4 diaminopyrimidine Lefamulin Nabriva Pre-reg Pleuromutilin Fusidic acid Melinta 3 Fusidane WCK771/WCK2349 Wockhardt 3 Fluoroquinolone Cefilavancin Theravance 3 Glycopeptide beta lactam Contezolid MicuRx 3 Oxazolidinone Sulopenem Iterum 3 Carbapenem SPR994 Spero 3 Carbapenem Imipenem & relebactam Merck 3 Carbapenem/BLI Cefiderocol Shionogi 3 Cephalosporin Cefepime & AAI101 Allecra 3 Cephalosporin/BLI Cefepime & tazobactam Wockhardt 3 Cephalosporin/BLI EXT2514SUL Entasis 3 BLI Ridinilazole Summit 3 Novel; C. difficile specific

Source: Pew Trust