From New Mechanisms to New Standards of Care
Corporate Presentation January 2020
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
Corporate Presentation January 2020
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
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
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
1920s-1980s
success
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
incremental benefits
low commercial return
Lipopeptides
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Bedaquiline
January 2020 Company presentation 4
Targeted to infection/pathogen to work in harmony with the microbiome
Economic outcomes data gathered in clinical trials Superiority clinical trials
Enterobacteriaceae >1 million cases per year in US
per year in US and Europe Gonorrhea ~1.4 million cases per year in US and Europe
January 2020 Company presentation
CDI (Ridinilazole)1 Gonorrhea (Target #1) Enterobacteriaceae (DDS-04 Series)
Phase 1 Phase 2 Phase 3 Discovery Preclinical Threat Status
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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
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
Failure likely connected to impact on microbiome of standard of care
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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
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
November 6-7, 2019
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
November 6-7, 2019
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Cholesterol Taurocholate Glycocholate Cholate Deoxycholate Liver Gut microbiota-mediated bile salts transformation Glycine Taurine Bile salt hydrolase 7-Dehydroxylase Taurocholate Glycocholate
Gut
Vegetative cell growth
Conjugated bile salts Primary bile salts Secondary bile salts
and Winston and Theriot, Anaerobe, 2016
November 6-7, 2019
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Cholesterol Taurocholate Glycocholate Cholate Deoxycholate Liver Glycine Taurine Taurocholate Glycocholate
Gut
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
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
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
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
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
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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
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Source: X. Qian et al., ID Week 2019
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
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
November 6-7, 2019
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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
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
January 2020
Primary Endpoint
Important Secondary Endpoint
Secondary & Exploratory Endpoints
Health Economic Outcomes Endpoints
Global Studies
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
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
January 2020 Company presentation 22
Goal of Phase 3 clinical trials is to show clear benefits of ridinilazole
ESTIMATED SAVINGS OF PER PATIENT IN THE US1
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
January 2020 Company presentation 23
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
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
1.4m cases in US & EU 78m worldwide1
has consistently developed resistance to known classes
Clinicians are using the last CDC recommended treatment option; no new treatment
January 2020 Company presentation 25
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
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
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
January 2020 Company presentation
2022 2021 2020
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Phase 3 recruitment
topline Phase 3 data for ridinilazole
Phase 3 results, expect to file NDA for FDA approval of ridinilazole
Phase 3 sites active
enrollment complete in Phase 3 trials
progress
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
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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
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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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COST OF CDI RECURRENCE OVER ONE YEAR 2013 DATA Rodrigues et al.
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
Number Needed to Treat = 6.7
January 2020 Company presentation