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 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. 2 Company presentation January 2020

Past Commercial Success Associated with Innovation Macrolides Glycopeptides, Nitroimidazoles, Streptogramins Cycloserine, Novobiocin Rifamycins Pleuromutilins Trimethoprim Cephalosporins Quinolones Polymyxins, Phenicols Fosfomycin Nitrofurans Mupirocin Tetracyclines Carbapenems Aminoglycosides, Bacitracin Oxazolidinones Monobactams Sulfonamides Bedaquiline Lipopeptides Penicillin 1990s 2000s 2010s 1920s 1930s 1940s 1950s 1960s 1970s 1980s YEAR ANTIBIOTIC CLASS DISCOVERED 1920s-1980s Since 1990 • Multiple novel mechanisms & classes • Few new mechanisms; only • Multiple examples of significant commercial incremental benefits success • Niche market positioning with • Ciprofloxacin; azithromycin; ceftriaxone low commercial return • Resistance not clinical issue • Resistance is a clinical issue 3 Company presentation January 2020 Adapted from ReAct Group 2015

The Summit Opportunity LARGE INDICATIONS WITH MEASURABLE UNMET NEEDS Gonorrhea ~1.4 million cases per C. difficile infection ~1 million cases Enterobacteriaceae >1 million per year in US and Europe cases per year in US year in US and Europe 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 Superiority clinical trials gathered in clinical trials 4 Company presentation January 2020

Our New Mechanism Antibiotic Pipeline Phase 3 Preclinical Phase 1 Phase 2 Threat Status Discovery Urgent CDI (Ridinilazole) 1 (CDC) Urgent / High Enterobacteriaceae (DDS-04 Series) (CDC / WHO) Urgent / High Gonorrhea (Target #1) (CDC / WHO) Urgent / High ESKAPE (CDC / WHO) Program Gonorrhea Urgent / High (Target #2) (CDC / WHO) Discuva Platform A portfolio created with assistance: BARDA, CARB-X, Innovate UK & Wellcome Trust 5 1. We own worldwide rights to ridinilazole, outside of certain Latin American countries and Caribbean islands. Company presentation January 2020

About C. difficile Infection (CDI) >1.0m cases Initial treatment Failure likely per year in US fails to cure or connected to and EU 1 , 29,000 sustain cures in impact on deaths per year around a third microbiome of in the US 2 of cases standard of care 6 1. Decision Resources, 2015 Company presentation 2. New England Journal of Medicine, 2015 January 2020

Importance of the Microbiome in CDI BROAD-SPECTRUM NO ANTIBIOTIC NO ANTIBIOTIC NO ANTIBIOTIC ANTIBIOTIC Normal Normal microbiome microbiome CDI RISK Microbiome disrupted Low CDI risk Low CDI risk Patients being treated for CDI 7 Company presentation Adapted from Rupnik et al., Nat. Rev. 2009 January 2020

Increasing Risk of CDI Recurrence Associated with Broad-Spectrum Treatments Increasing Risk of Recurrence Recurrent CDI associated with increased microbiome damage Mainstay therapies are broad-spectrum 1st antibiotics that drive microbiome damage Risk: ~25% Infection 2nd Risk: ~45% Infection Each additional episode of CDI associated with increased morbidity and 3rd mortality and increased healthcare cost Risk: ~65% Infection 0 20 40 60 80 Risk of Disease Recurrence (%) 8 Company presentation Source: Kelly, Clinical Microbiology & Infection , 2012 January 2020

Current CDI Treatments Damage the Gut Microbiome ANTIBIOTIC MIC 90 µg/mL Bacteria Vancomycin Metronidazole Fidaxomicin Bifidobacterium spp. 1 128 0.125 ≤0.03 Eggerthella lenta 4 0.5 Various Gram positive rods 4 2 128 Finegoldia magna 0.5 1 2 ≤0.03 Peptostreptococcus anaerobius 0.5 1 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 C. diff Foundation MIC 90 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

Microbiome Plays an Important Role in Bile Salt Metabolism (the Metabolome) to Protect Against C. difficile Infection Liver Gut Gut microbiota-mediated bile salts transformation Cholesterol Conjugated bile Primary bile Secondary bile salts salts salts Bile salt hydrolase 7-Dehydroxylase Taurocholate Taurocholate Deoxycholate Cholate Glycocholate Glycocholate Glycine Taurine - + + + C. diff spore germination Vegetative cell growth 10 C. diff Foundation Adapted from Ridlon et al., Gut Microbes 2016 November 6-7, 2019 and Winston and Theriot, Anaerobe, 2016

Microbiome Damage Results in Imbalance of Bile Salts that Favor C. difficile Growth Liver Gut Cholesterol Conjugated bile Primary bile Secondary bile salts salts salts Bile salt hydrolase Taurocholate Taurocholate Cholate Deoxycholate Glycocholate Glycocholate Glycine Taurine - + + + C. diff spore germination Vegetative cell growth 11 C. diff Foundation Adapted from Ridlon et al., Gut Microbes 2016 November 6-7, 2019 and Winston and Theriot, Anaerobe, 2016