From New Mechanisms to New Standards of Care. Corporate Presentation October 2018

Transcription

1 From New Mechanisms to New Standards of Care Corporate Presentation

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 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 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. 2

3 Creating a Different Antibiotic Company NEW SCIENCE NEW PHILOSOPHY NEW OPPORTUNITY New bacterial targets New drugs against them The right drug for the right bug Real unmet needs Innovative development plans Beat standard of care Economic and clinical data to support premium price 3

4 Past Commercial Success Associated with Innovation Macrolides Glycopeptides, Nitroimidazoles, Streptogramins Pleuromutilins Cephalosporins Polymyxins, Phenicols Nitrofurans Tetracyclines Aminoglycosides, Bacitracin Sulfonamides Penicillin Cycloserine, Novobiocin Rifamycins Trimethoprim Quinolones Fosfomycin Mupirocin Carbapenems Oxazolidinones Monobactams Lipopeptides 1920s 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s 1920s-1980s Multiple novel mechanisms & classes Multiple examples of significant commercial success Ciprofloxacin; azithromycin; ceftriaxone Resistance not clinical issue YEAR ANTIBIOTIC CLASS DISCOVERED Since 1990 No new mechanisms; only incremental benefits Niche market positioning with low commercial return Resistance is a clinical issue 4 Adapted from ReAct Group 2015

5 Only Two Late Stage Antibiotics are Novel 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 Approved (US) Tetracycline Iclaprim Motif Bio Pre-Reg 2,4 diaminopyrimidine Cefiderocol Shionogi 3 Cephalosporin Cefilavancin Theravance 3 Glycopeptide beta lactam Imipenem & relebactam Merck 3 Carbapenem/BLI Lefamulin Nabriva 3 Pleuromutilin Cefepime & tazobactam Wockhardt 3 Cephalosporin/BLI Murepavadin Polyphor 3 Novel; P. aeruginosa specific Ridinilazole Summit 3-ready Novel; C. difficile specific 5

6 Stewardship and Commercial Success Aligned Stewardship ultimately about upfront use of the correct drug Novel mechanism agents address specific indications and unmet needs Their use improves clinical outcomes and reduces healthcare costs Vancomycin for CDI and ceftriaxone for gonorrhoea used front-line do not equate to stewardship Summit s approach aligns with stewardship and could result in commercial success Development programs designed to meet needs of patients, providers and payors Data from these programs promote market uptake of agents into front-line settings Acceptable pricing achieved through clear and demonstrable package of benefits Ridinilazole for CDI and SMT-571 for gonorrhoea used front-line do equate to stewardship 6

7 Our New Mechanism Antibiotic Pipeline Phase 1 Phase 2 Phase 3 Discovery Preclinical Funding source CDI (ridinilazole) 1 BARDA Gonorrhoea (SMT-571) 1 Roche Collaboration 2 Gonorrhea (Target #2) 1 ESKAPE Program 1 Discuva Platform 7 (1) We own worldwide rights to ridinilazole, outside of certain Latin American countries and Caribbean islands, and own worldwide rights to our gonorrhea and ESKAPE programs (2) Roche holds worldwide development and commercialization rights to these compounds and Summit is entitled to specified development, commercialization and sales milestone payments from Roche.

8 New Science Discovering new mechanism antibiotics with our Discuva Platform

9 Discuva Platform: Enabling Optimized Candidate Selection From discovery through candidate selection, our Discuva Platform delivers optimized antibiotics with: New mechanisms of action Low propensities for resistance Targeted spectrums of activity We advance those new mechanism candidates where a major commercial opportunity exists and we can show significant advantages over the current standard of care 9

10 Proprietary Libraries Cover Major Unmet Needs, Enable Potential Pipeline Expansion K. pneumoniae CDC Urgent / WHO Critical Threats P. aeruginosa E. coli N. gonorrhoeae* E. faecalis CDC Serious Threats / Other ESKAPE Pathogens E. faecium A. baumannii S. aureus Gram negative Gram positive S. pneumoniae 10 *Current Summit preclinical program

11 Discuva Platform: Rapid Screening to Identify New Bacterial Targets Through the process of creating hundreds of thousands of mutant bacteria of a single species, genes essential for the survival of that species can be identified as those which have no insertions Library of mutant engineered bacteria Next-generation sequencing Genome map of mutation insertions 11

12 Discuva Platform: Elucidate Mechanism of Action and Optimize Against Resistance Our libraries of mutant bacteria allow us to have exquisite control over gene expression in a given species These mutants have increased, decreased or disrupted gene expression levels In the presence of an antibiotic, the mutant libraries can help us to rapidly elucidate mechanisms of action and optimize against potential resistance mechanisms -drug of interest +drug of interest +gene manipulation Next-generation sequencing Which genes are involved in MOA? Are there any resistance liabilities? 12

13 Ridinilazole Our Phase 3-ready precision antibiotic in development for front-line treatment of C. difficile infection

14 About C. difficile Infection (CDI) >1.0m cases per year in US and EU 1, 29,000 deaths per year in the US 2 Initial treatment fails to cure or sustain cures in around a third of cases Failure likely connected to microbiome impact of standard of care Decision Resources, New England Journal of Medicine, 2015

15 Ridinilazole: Potent, Oral & Narrow Spectrum NEW SCIENCE NEW PHILOSOPHY NEW OPPORTUNITY Phase 2 clinical trial demonstrated superiority over standard of care Highly selective antibiotic preserved microbiome Activity restricted to gut Well-tolerated in Phase 1 and 2 clinical trials Replace front-line broad spectrum generics Differentiated label Provide clinical and economic evidence at launch Front-line treatment for CDI and reduction of rcdi Expect to file NDA in 2022, if Phase 3 results positive Potential ~$700M global peak sales Exclusivity expected through 2034 in US, Europe and Japan 15

16 Ridinilazole Highly Preserving of Microbiome of CDI Patients Compared to Vancomycin Cladograms Showing Changes in Relative Abundancy of Microbiome Following 10 Days Dosing RIDINILAZOLE VANCOMYCIN Reduced relative abundancy Increased relative abundancy 16 Source: Thorpe et al., PLOS ONE, 2018

17 Ridinilazole: Statistical Superiority Over Vancomycin in Phase 2 CoDIFy Trial in SCR Cure at End of Treatment Sustained Clinical Response (SCR) Ridinilazole 77.8% 100 Vancomycin 69.7% Δ % 50 Ridinilazole Recurrence 30 Days Post Treatment 14.3% % Vancomycin 34.8% Vancomycin (90% CI ) Ridinilazole 17 Source: Vickers et al, Lancet ID, 2017

18 Phase 3: Plan to Deliver Clinical and Economic Evidence at Launch Two randomized, double-blind clinical trials Primary endpoint: SCR to 30 days post end of treatment Test for superiority (>95% power) Secondary and exploratory endpoints: Clinical cure at EOT Test for non-inferiority (90% power) 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 Group Design Group N Agent Regimen Ridinilazole 200mg BID for 10 days Vancomycin 125mg QID for 10 days 18

19 Potential Path to Regulatory Approvals for Ridinilazole Planned Milestones Q Phase 3 clinical trials initiation H Phase 3 clinical trials top-line data 2022 File NDA with the FDA 19

20 Ridinilazole: Commercialization Strategy Delivering clinical and economic evidence, at launch, to position ridinilazole as front-line agent. Done by achieving the following goals: Differentiated label 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: Treatment of CDI and reducing the recurrence of CDI Demonstrating economic benefits of reduced recurrence Justifies premium price for ridinilazole over current standard of care Capitalizing on a favorable environment Quality metrics requiring healthcare facilities to minimize readmissions Increasing awareness of the importance of the microbiome Stewardship: CDI specific therapy replacing inappropriate vancomycin use 20

21 Potential Opportunity for Broad Use Across CDI Disease Spectrum >1M cases (US & EU) Initial Episode ~75% Recurrent Disease ~ 25% Initial + mild-moderate ~50% Initial + severe ~ 25% Patient Segment Initial mild-moderate Community ~ 25% Initial mild-moderate Hospital ~ 25% Current Treatments Metronidazole, Vancomycin Vancomycin Vancomycin Fidaxomicin, Bezlotoxumab, FMT Opportunity RDZ RDZ RDZ RDZ 21

22 About Gonorrhea 1.4m cases in US & EU 78m worldwide 1 N. Gonorrhoeae has consistently developed resistance to known classes of antibiotics We are using the last CDC recommended treatment option; no new treatment options available World Health Organization, July 2017 press release

23 Gonorrhea: Opportunity to Develop New Standards of Care NEW SCIENCE NEW PHILOSOPHY NEW OPPORTUNITY Two novel targets from Discuva Platform New series against each Potent against clinical isolates, including multi-drug resistant strains SMT-571 has shown in vivo preclinical activity and oral bioavailability Be adopted onto WHO guidelines Develop compounds which are oral, single dose, narrow spectrum, target three sites of infection Resistance to recommended treatment growing, no approved antibiotics available to replace it Become new standard of care in treatment of gonorrhea 1.4m cases in US & EU, 78m worldwide 23

24 SMT-571: Potent New Mechanism Gonorrhea Antibiotic in IND-Enabling Studies Target: cell division Potent in vitro activity across gonorrhea clinical isolates and WHO reference panel, including multi-drug resistant strains Strain MIC (μg/ml) FA WHO-M 0.09 WHO-L 0.09 WHO-N 0.09 WHO-O 0.09 WHO-G 0.09 WHO-F 0.09 WHO-K 0.09 WHO-P 0.09 WHO-X

25 Potential Path to Proof of Concept for SMT-571 Planned Milestones Sept 2018 Nominated SMT-571 as lead candidate H Phase 1 clinical trial initiation H Phase 1 clinical trial top-line data; Phase 2 clinical trial initiation H Phase 2 clinical trial top-line data 25

26 Planned Upcoming Milestones CDI Ridinilazole Q Phase 3 initiation H Phase 3 top-line data 2022 File NDA for FDA approval Gonorrhea SMT-571 Sept 2018 Nominated SMT-571 as lead candidate H Phase 1 initiation H Phase 1 top-line data Phase 2 initiation H Phase 2 top-line data 26

27 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 Brought 8 antibiotics to market Clive Mason, Senior Director, Platform Discovery Discovered SMT-571 Frank Armstrong, MD, Chairman Previous antibiotic experience at Astrazeneca and Bayer 27

28 Summary Financials Key Items Amount Nasdaq Share Price (Oct. 22, 2018): $2.01 Issued Share Capital O/S (1) : 16.4M SYMBOL: SMMT Current Market Cap (Oct. 22, 2018): $33M Cash Balance (Jul. 31, 2018) (2) : $22.5M Debt (Jul. 31, 2018): $0 SYMBOL: SUMM 28 (1) Based on total Ordinary Shares outstanding; Ordinary Shares outstanding as of Sept. 5, 2018, were 82.1 million; one ADS is equivalent to five Ordinary Shares (2) Assumes an exchange rate of $ to 1.00

29 Contact Details 136a Eastern Avenue Milton Park Oxfordshire UK One Broadway Cambridge Massachusetts US 29