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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 January 2020 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 January 2020

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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.

January 2020 Company presentation 2

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SLIDE 3

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

January 2020 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

3

Bedaquiline

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SLIDE 4

The Summit Opportunity

January 2020 Company presentation 4

NEW CLASSES OF ANTIBIOTICS WITH DISTINCTIVE FEATURES AND BENEFITS

Targeted to infection/pathogen to work in harmony with the microbiome

VALUE TO PATIENTS, PHYSICIANS AND PAYORS DEMONSTRATED IN DEVELOPMENT

Economic outcomes data gathered in clinical trials Superiority clinical trials

LARGE INDICATIONS WITH MEASURABLE UNMET NEEDS

Enterobacteriaceae >1 million cases per year in US

  • C. difficile infection ~1 million cases

per year in US and Europe Gonorrhea ~1.4 million cases per year in US and Europe

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SLIDE 5

Our New Mechanism Antibiotic Pipeline

January 2020 Company presentation

CDI (Ridinilazole)1 Gonorrhea (Target #1) 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)

January 2020 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

Importance of the Microbiome in CDI

January 2020 Company presentation 7

Low CDI risk Low CDI risk Normal microbiome

Adapted from Rupnik et al., Nat. Rev. 2009

Normal microbiome Patients being treated for CDI

NO ANTIBIOTIC NO ANTIBIOTIC

CDI RISK

Microbiome disrupted

BROAD-SPECTRUM ANTIBIOTIC NO ANTIBIOTIC

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SLIDE 8

Increasing Risk of CDI Recurrence Associated with Broad-Spectrum Treatments

January 2020

20 40 60 80 3rd Infection 2nd Infection 1st Infection

Risk of Disease Recurrence (%)

Risk: ~25% Risk: ~45% Risk: ~65%

Increasing Risk of Recurrence

Source: Kelly, Clinical Microbiology & Infection, 2012

Each additional episode of CDI associated with increased morbidity and mortality and increased healthcare cost Recurrent CDI associated with increased microbiome damage Mainstay therapies are broad-spectrum antibiotics that drive microbiome damage

Company presentation 8

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SLIDE 9

Current CDI Treatments Damage the Gut Microbiome

November 6-7, 2019

  • C. diff Foundation

ANTIBIOTIC MIC90 µg/mL

Bacteria Vancomycin Metronidazole Fidaxomicin Bifidobacterium spp.

1 128 0.125

Eggerthella lenta

4 0.5 ≤0.03

Various Gram positive rods

4 2 128

Finegoldia magna

0.5 1 2

Peptostreptococcus anaerobius

0.5 1 ≤0.03

Staphylococcus aureus

1 >512 16

Enterococcus faecalis

4 >512 8

Enterococcus faecium

0.5 >512 128

Streptococcus spp.

1 >512 128

Bacteroides fragilis

64 2 >512

Bacteroides ovatus

256 2 >512

Bacteroides thetaiotaomicron

128 2 >512

Bacteroides vulgatus

128 1 >512

Parabacteroides spp.

128 2 >512

Fusobacterium nucleatum

512 0.25 >512

Fusobacterium spp.

>512 0.5 >512

Prevotella spp.

512 1 >512

Veillonella spp.

>512 2 256

Lactobacilus spp.

>512 >512 >512

9 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

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SLIDE 10

Microbiome Plays an Important Role in Bile Salt Metabolism (the Metabolome) to Protect Against C. difficile Infection

November 6-7, 2019

  • C. diff Foundation

10

Cholesterol Taurocholate Glycocholate Cholate Deoxycholate Liver Gut microbiota-mediated bile salts transformation Glycine Taurine Bile salt hydrolase 7-Dehydroxylase Taurocholate Glycocholate

Gut

  • C. diff spore germination

Vegetative cell growth

Conjugated bile salts Primary bile salts Secondary bile salts

+ + +

  • Adapted from Ridlon et al., Gut Microbes 2016

and Winston and Theriot, Anaerobe, 2016

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SLIDE 11

Microbiome Damage Results in Imbalance of Bile Salts that Favor C. difficile Growth

November 6-7, 2019

  • C. diff Foundation

11

Cholesterol Taurocholate Glycocholate Cholate Deoxycholate Liver Glycine Taurine Taurocholate Glycocholate

Gut

  • C. diff spore germination

Vegetative cell growth

Conjugated bile salts Primary bile salts Secondary bile salts

+ + +

  • Bile salt hydrolase

Adapted from Ridlon et al., Gut Microbes 2016 and Winston and Theriot, Anaerobe, 2016

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SLIDE 12

Ridinilazole Designed to be Patient-Friendly

January 2020 Company presentation 12

Clear Phase 2 trial differentiation 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 compared to VAN

Source: CoDIFy Phase 2 clinical trial

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SLIDE 13

Ridinilazole has a Highly Targeted Spectrum of Activity

January 2020 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

13 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 14

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

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

January 2020 Company presentation

RIDINILAZOLE VANCOMYCIN Increased relative abundance

Source: Thorpe et al., PLOS ONE, 2018

Reduced relative abundance

14

  • C. difficile
  • C. difficile
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SLIDE 15

Ridinilazole is Preserving of Patients’ Metabolome in Phase 2 CoDIFy Trial

November 6-7, 2019

Primary Bile Acids Conjugated Primary Bile Acids Secondary Bile Acids Conjugated Secondary Bile Acids

Vancomycin Ridinilazole Healthy Day D1 D10 D25 D40 D1 D10 D25 D40 100% 75% 50% 25% 0% Percentage

Following ridinilazole treatment, there is normalization of bile acid composition

  • C. diff Foundation

15

Source: X. Qian et al., ID Week 2019

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SLIDE 16

Ridinilazole: Similar Cure Rates to Vancomycin in Phase 2 CoDIFy Trial

January 2020 Company presentation

25 50 75 100

Vancomycin Ridinilazole Cure at End of Treatment 77.8% 69.7%

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 16

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SLIDE 17

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

January 2020 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 17

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SLIDE 18

Short and Long-Term Improvements Seen in Patient Quality of Life in Phase 2 CoDIFy Trial

  • Patients’ quality of life assessed during the course of the study using the EQ-5D
  • 5 domain questionnaire assessing patients’ welfare

November 6-7, 2019

  • C. diff Foundation

18

EQ-5D-3L – Pain/Discomfort EQ-5D-3L – Anxiety/Depression Proportion of Patients Reporting Problem (%)

Ridinilazole Vancomycin

Proportion of Patients Reporting Problem (%)

10 20 30 40 50 60 70 80 Baseline Day 5 Day 10 (EOT) Day 12 (AOC) Day 40 10 20 30 40 50 60 Baseline Day 5 Day 10 (EOT)Day 12 (AOC) Day 40

Source: S. Paul et al., ID Week 2019

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SLIDE 19

Ri-CoDIFy: Landmark Clinical Program

Top line data expected in H2 2021

January 2020 Company presentation 19

Aiming for clear differentiation to support switch from current therapies

ECONOMIC DATA SUPERIORITY TRIALS MICROBIOME Aim to show ridinilazole is better than vancomycin at sustaining patient cures Inclusion of health economic measures to support commercialization Comprehensive analysis of impact of ridinilazole on the microbiome

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SLIDE 20

Phase 3 Clinical Trials Designed to Evaluate Clinical and Economic Evidence

January 2020

Primary Endpoint

  • SCR to 30 days after end of therapy (EOT)
  • Test for superiority (>95% power)

Important Secondary Endpoint

  • Clinical cure at AOC
  • Test for non-inferiority (90% power)

Secondary & Exploratory Endpoints

  • SCR rates to 60 and 90 days post EOT
  • Impact on microbiome/metabolome
  • Safety and tolerability

Health Economic Outcomes Endpoints

  • Include readmission rates, length of hospital stay

Global Studies

  • North & South America, Europe, Asia Pacific

Group Design for Each Trial Group N Agent Regimen 1 340 Ridinilazole 200mg BID10 days 2 340 Vancomycin 125mg QID 10 days

D1 Randomisation D10 EOT D100 EOS

Screening Treatment Follow-Up

Ridinilazole 200 mg BID Vancomycin 125 mg QID

// //

D12 (AOC): Key 2° Endpoint Clinical Response at the AOC Visit D40 (AOC): 1° Endpoint SCR to 30 days post EO T D70: 2° Endpoint SCR to 60 days post EO T D100 (EOS): 2° Endpoint SCR to 90 Days Post EO T

Company presentation 20

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SLIDE 21

Phase 3 Clinical Trials Powered to Test for Superiority in SCR

January 2020 Company presentation 21

 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

Key secondary endpoint: clinical cure at assessment of cure

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SLIDE 22

Aiming for Dominant Position in Front-Line Treatment

January 2020 Company presentation 22

  • 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

~$6,000

ESTIMATED SAVINGS OF PER PATIENT IN THE US1

PHYSICIAN PAYOR

1 - Costs adjusted to 2023 pricing using US CPI for years to 2018 and assumed 2% inflation 2019-2023, based on NNT of 6.7 associated with 15% recurrence delta and on front-line population per Lessa et al, 2015

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SLIDE 23

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

January 2020 Company presentation 23

  • 1. Summit estimate based on Flores-Morales, 2015
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SLIDE 24

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

January 2020 Company presentation 24

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 25

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

January 2020 Company presentation 25

  • 1. World Health Organization, July 2017 press release
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SLIDE 26

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

January 2020 Company presentation 26

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

Currently in lead

  • ptimization 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

Designed to address the unmet need

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

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SLIDE 27

Planned Upcoming Milestones & Newsflow

January 2020 Company presentation

2022 2021 2020

27

  • H1 2021: complete

Phase 3 recruitment

  • H2 2021: expect

topline Phase 3 data for ridinilazole

  • 2022: with positive

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

  • H1 2020: planned

Phase 3 sites active

  • H2 2020: 50%

enrollment complete in Phase 3 trials

  • 2020: pipeline

progress

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SLIDE 28

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

January 2020 Company presentation

Brought 8 antibiotics to market

28

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SLIDE 29

Summary Financials

January 2020 Company presentation

Key Items Amount

Nasdaq Share Price (Jan. 7, 2020): $1.50 Issued Share Capital O/S(1): 67.2M Market Cap (Jan. 7, 2020): $100M Cash Balance (Oct. 31, 2019)(2): $17.6M Pro-Forma Cash Balance (Oct. 31, 2019)(3) $66.9M Debt: $0

SYMBOL: SMMT

(1) Based on total Ordinary Shares outstanding; Ordinary Shares outstanding as of Dec. 31, 2019, were 335.9 million; one ADS is equivalent to five Ordinary Shares (2) Assumes an exchange rate of $1.2939 to £1.00 (3) Pro forma figure includes net proceeds of $49.3 million related to Summit’s placement that closed

  • Dec. 24, 2019.

29

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SLIDE 30

Contact Details

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

January 2020 Company presentation 30

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SLIDE 31

Avoidable Economic Burden

31

~$2.7B saving3

US Healthcare System, 2023

COST OF CDI RECURRENCE OVER ONE YEAR 2013 DATA Rodrigues et al.

~$34,000

~$40,000, 20231

What if ALL front-line patients receive an agent that reduces recurrence by 15%?

1 - Costs adjusted to 2023 pricing using US CPI for years to 2018 and assumed 2% inflation 2019-2023 2 - Based on NNT of 6.7 associated with 15% recurrence delta; 3 – Based on front-line population per Lessa et al, 2015

~$6,000 saving per treated patient2

Number Needed to Treat = 6.7

January 2020 Company presentation