From New Mechanisms to New Standards of Care
Corporate Presentation August 2019
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
Corporate Presentation August 2019
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.
August 2019 Company presentation 2
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
changes fail to combat emerging drug resistance
inferiority trials don’t show clear patient benefit
priced treatments over cheap generics
distinctive features and benefits
health
establish compelling use case
through economic data
August 2019 Company presentation 4
Translating novel science into differentiated products delivered to the patient
DISCOVER
DEVELOP
improved outcomes
COMMERCIALIZE
PATIENT UNMET NEED
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
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
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
Failure likely connected to impact on microbiome of standard of care
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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
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
August 2019 Company presentation 8
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
ESTIMATED SAVINGS OF PER PATIENT IN THE US1
PHYSICIAN PAYOR
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%
Estimated cost savings per US patient with first incidence treated, if recurrence rate was reduced by absolute 15%2
August 2019 Company presentation 9
US PATIENTS TREATED ANNUALLY FOR 1st CDI INCIDENCE
APPROXIMATELY
HAVE A RECURRENCE. RISK RISES TO 45% FOR SECOND, 65% FOR THIRD
COST OF RECURRENCE IN US HOSPITALS1
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
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
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
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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
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
the microbiome
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
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
Demonstrating economic benefits
Quality metrics requiring healthcare facilities to minimize readmissions Increasing awareness of the importance
Stewardship: CDI specific therapy replacing inappropriate vancomycin use
Capitalizing on favorable environment
Discovering new mechanism antibiotics with our Discuva Platform
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
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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Gram positive Gram negative
CDC Urgent / WHO Critical Threats
CDC Serious Threats / Other ESKAPE Pathogens
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
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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
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
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
August 2019 Company presentation 21
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
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
August 2019 Company presentation
2022 2021 2019 2020
23
trial for ridinilazole
topline Phase 3 data for ridinilazole
Phase 3 results, expect to file NDA for FDA approval of ridinilazole
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
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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
Contact Details
investors@summitplc.com Twitter: @summitplc 136a Eastern Avenue Milton Park Oxfordshire UK One Broadway Cambridge Massachusetts US
August 2019 Company presentation 26
1920s-1980s
success
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
incremental benefits
low commercial return
Lipopeptides
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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