From New Mechanisms to New Standards of Care...Quinolones. Glycopeptides, Nitroimidazoles, Streptogramins. Trimethoprim. Oxazolidinones. Sulfonamides. Polymyxins, Phenicols. Cephalosporins

From New Mechanismsto New Standards of CareCorporate PresentationJanuary 2020

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 our 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 of 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 2020Company presentation2

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 2020Company presentation

Penicillin

Aminoglycosides, Bacitracin

Nitrofurans

Tetracyclines

Macrolides

Quinolones

Glycopeptides, Nitroimidazoles, Streptogramins

Trimethoprim

Oxazolidinones

Sulfonamides

Polymyxins, PhenicolsCephalosporins

Pleuromutilins

Cycloserine, NovobiocinRifamycins

FosfomycinMupirocin

Carbapenems

Monobactams

Adapted from ReAct Group 2015

1920s 1980s1970s1960s1950s1940s1930s 2010s2000s1990s

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

The Summit Opportunity


NEW CLASSES OF ANTIBIOTICS WITHDISTINCTIVE FEATURES AND BENEFITS

Targeted to infection/pathogen to workin harmony with the microbiome

VALUE TO PATIENTS, PHYSICIANS AND PAYORS DEMONSTRATED IN DEVELOPMENT

Economic outcomes data gathered in clinical trialsSuperiority 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

Our New Mechanism Antibiotic Pipeline


CDI(Ridinilazole)1

Gonorrhea(Target #1)

Enterobacteriaceae (DDS-04 Series)

Phase 1 Phase 2 Phase 3Discovery Preclinical Threat Status

51. 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)




Discuva Platform

About C. difficile Infection (CDI)

January 2020Company 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 of cases

Failure likely connected to impact on microbiome of standard of care

6

Importance of the Microbiome in CDI


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

CDIRISK

Microbiome disrupted

BROAD-SPECTRUMANTIBIOTIC

NO ANTIBIOTIC

Increasing Risk of CDI Recurrence Associated with Broad-Spectrum Treatments

January 2020

0 20 40 60 80

3rdInfection

2ndInfection

1stInfection

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 damageMainstay therapies are broad-spectrum antibiotics that drive microbiome damage

Company presentation

8

Current CDI Treatments Damage the Gut Microbiome

November 6-7, 2019C. diff Foundation

ANTIBIOTIC MIC90 µg/mLBacteria 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

9MIC90 value: the minimum concentration of the antibiotic at which 90% of the microbial activity is inhibitedSource: Goldstein et al: Antimicrob Agents Chemother. 2013

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

November 6-7, 2019C. diff Foundation10

Cholesterol

Taurocholate

GlycocholateCholate Deoxycholate

Liver

Gut microbiota-mediated bile salts transformation

Glycine

Taurine

Bile salt hydrolase 7-DehydroxylaseTaurocholate

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

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

November 6-7, 2019C. diff Foundation11

Cholesterol

Taurocholate

GlycocholateCholate 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

Ridinilazole Designed to be Patient-Friendly


Clear Phase 2 trial differentiation supports new standard of care potential

Initiated global Phase 3 clinical trials Feb. 2019Expect top-line data H2 2021With 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 over 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

Ridinilazole has a Highly Targeted Spectrum of Activity


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

13MIC90 value: the minimum concentration of the antibiotic at which 90% of the microbial activity is inhibitedSource: Goldstein et al: Antimicrob Agents Chemother. 2013, 57: 4872–4876

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


RIDINILAZOLE VANCOMYCIN

Increased relative abundance

Source: Thorpe et al., PLOS ONE, 2018

Reduced relative abundance

14

C. difficile

C. difficile

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

November 6-7, 2019

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

Vancomycin Ridinilazole Healthy

DayD1 D10 D25 D40 D1 D10 D25 D40

100%

75%

50%

25%

0%

Perc

enta

ge

Following ridinilazole treatment, there is normalization of bile acid composition

C. diff Foundation

15Source: X. Qian et al., ID Week 2019

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


0 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 armSource: Vickers et al, Lancet ID, 2017

16

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


0 25 50 75 100

Vancomycin

Ridinilazole

Cure at End of Treatment

0 25 50 75 100

Vancomycin

Ridinilazole

Recurrence 30 Days Post Treatment

0

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 armSource: Vickers et al, Lancet ID, 2017

17

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

Prop

ortio

n of

Pat

ient

s R

epor

ting

Prob

lem

(%)

Ridinilazole Vancomycin

Prop

ortio

n of

Pat

ient

s R

epor

ting

Prob

lem

(%)

0

10

20

30

40

50

60

70

80

Baseline Day 5 Day 10 (EOT) Day 12(AOC)

Day 400

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

Ri-CoDIFy: Landmark Clinical Program

Top line data expected in H2 2021


Aiming for clear differentiation to support switch from current therapies

ECONOMIC DATASUPERIORITY 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

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 TrialGroup N Agent Regimen

1 340 Ridinilazole 200mgBID10 days

2 340 Vancomycin 125mg QID 10 days

D1Randomisation

D10EOT

D100EOS

Screening Treatment Follow-Up

Ridinilazole200 mg BID

Vancomycin125 mg QID

//

//

D12 (AOC): Key 2° EndpointClinical Response at the AOC Visit

D40 (AOC): 1° EndpointSCR to 30 days post EOT

D70: 2° EndpointSCR to 60 days post EOT

D100 (EOS): 2° EndpointSCR to 90 Days Post EOT

Company presentation

20

Phase 3 Clinical Trials Powered to Test for Superiority in SCR


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

Aiming for Dominant Position in Front-Line Treatment


• 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

~$6,000ESTIMATED SAVINGS OF

PER PATIENTIN 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

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


1. Summit estimate based on Flores-Morales, 2015

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


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.

0

20

40

60

80

100

China Greece India Italy Russia Turkey US

E. coli carbapenemK. pneumoniae carbapenem

E. coli cephalosporinK. pneumoniae cephalosporin

Percent of resistant isolatesDDS-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

1.4m cases in US & EU78m worldwide1

N. Gonorrhoeae has consistently developed resistance to known classes of antibiotics

Clinicians are using the last CDCrecommendedtreatment option; no new treatment options available

About Gonorrhea


1. World Health Organization, July 2017 press release

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 oral bioavailability

Potential to replace inappropriate use of ceftriaxone

Discovered and optimized using Discuva Platform


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

Currently in lead optimization studies

Resistance of gonococcal isolates to antibiotics

Afric

a

Amer

icas

E M

ed.

Euro

pe

SE A

sia

W P

ac

Tota

l

Countries (%) reporting resistance/ decreased susceptibility

Ceftriaxone and/or

Cefixime

Countries 9 16 3 27 6 16 77

≥5% 1 0 0 15 4 6 2651 (66%)

<5% 2 6 0 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 0 21 1 2 2947 (81%)

<5% 0 4 0 3 4 7 18

Full susceptibility 0 1 1 2 1 6 11

Ciprofloxacin

Countries 8 16 1 26 6 15 72

>90% 0 1 1 3 4 5 14

70 (97%)≥5% 6 14 0 23 2 7 52

<5% 0 1 0 0 0 3 4

Full susceptibility 2 0 0 0 0 0 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

Planned Upcoming Milestones & Newsflow


202220212020

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

Antibiotic Experience at Summit

David Roblin, MD, President of R&DPrevious antibiotic experience at Pfizer and Bayer

Richard Vickers, PhD, CSODiscovered ridinilazole

Dave Powell, PhD, SVP, ResearchPrevious antibiotic experience at GSK

Nawaz Khan, VP, Anti-infectives DiscoveryDiscovered SMT-571

Clive Mason, Senior Director, Platform DiscoveryDiscovered SMT-571


Brought8 antibiotics

to market

28

Summary Financials


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

Contact Details

[email protected]: @summitplc

136a Eastern AvenueMilton ParkOxfordshire UK

One BroadwayCambridgeMassachusetts US


mailto:[email protected]

Avoidable Economic Burden

31

~$2.7B saving3 US Healthcare System, 2023

COST OF CDI RECURRENCE OVER ONE YEAR

2013 DATARodrigues 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 patient2NumberNeeded toTreat = 6.7


Documents

From New Mechanisms to New Standards of Care...Quinolones. Glycopeptides, Nitroimidazoles, Streptogramins. Trimethoprim. Oxazolidinones. Sulfonamides. Polymyxins, Phenicols. Cephalosporins