From New Mechanisms to New Standards of Care Corporate Presentation - - PowerPoint PPT Presentation
From New Mechanisms to New Standards of Care Corporate Presentation - - PowerPoint PPT Presentation
From New Mechanisms to New Standards of Care Corporate Presentation Forward-Looking Statements Statements in this presentation, other than statements of historical fact, constitute forward-looking statements within the meaning of the safe
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 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
- f clinical trial designs or the execution of clinical trials and the timing, cost and design of future clinical trials and research activities, the timing
- f 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.
March 2019 Company presentation 2
Creating a Different Antibiotic Company
March 2019 Company presentation
New bacterial targets New drugs against them NEW SCIENCE The right drug for the right bug Real unmet needs Innovative development plans NEW PHILOSOPHY Beat standard of care Economic and clinical data to support premium price NEW OPPORTUNITY
3
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
March 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
- Few new mechanisms; only
incremental benefits
- Niche market positioning with
low commercial return
- Resistance is a clinical issue
Lipopeptides
4
Bedaquiline
Only Two Late Stage Antibiotics are Novel
March 2019 Company presentation 5
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 Murepavadin Polyphor 3 Novel; P. aeruginosa specific Ridinilazole Summit 3 Novel; C. difficile specific
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
Summit’s approach aligns with stewardship and could result in commercial success
- Development programs designed to meet needs
- f 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
March 2019 Company presentation
Vancomycin for CDI and ceftriaxone for gonorrhoea used front-line do not equate to stewardship Ridinilazole for CDI and SMT-571 for gonorrhoea used front-line do equate to stewardship
6
Our New Mechanism Antibiotic Pipeline
March 2019 Company presentation
CDI (ridinilazole)1 Gonorrhea (SMT-571)1 Gonorrhea (Target #2)1 Roche Collaboration2 ESKAPE Program1
Phase 1 Phase 2 Phase 3 Discovery Preclinical Funding source
BARDA 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.
New Science
Discovering new mechanism antibiotics with our Discuva Platform
Discuva Platform: Enabling Optimized Candidate Selection
March 2019 Company presentation
From discovery through candidate selection,
- ur Discuva Platform delivers optimized antibiotics with:
New mechanisms
- f action
Low propensities for resistance Targeted spectrums of activity
9
We advance those new mechanism candidates where a major commercial opportunity exists and we can show significant advantages over the current standard of care
Proprietary Libraries Cover Major Unmet Needs, Enable Potential Pipeline Expansion
March 2019 Company presentation 10
Gram positive Gram negative
- P. aeruginosa
- E. coli
- N. gonorrhoeae
- K. pneumoniae
- A. baumannii
CDC Urgent / WHO Critical Threats
- S. aureus
- E. faecium
- E. faecalis
CDC Serious Threats / Other ESKAPE Pathogens
- S. pneumoniae
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
March 2019 Company presentation
Library of mutant engineered bacteria Next-generation sequencing Genome map of mutation insertions
11
Discuva Platform: Elucidate Mechanism of Action and Optimize Against Resistance
March 2019 Company presentation
- drug of interest
Next-generation sequencing
12
Which genes are involved in MOA? Are there any resistance liabilities?
+drug of interest +gene manipulation
- 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
- ptimize against potential resistance mechanisms
Ridinilazole
Our Phase 3 precision antibiotic in development for front-line treatment of C. difficile infection
About C. difficile Infection (CDI)
March 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
- f cases
Failure likely connected to microbiome impact of standard
- f care
14
Ridinilazole: Potent, Oral & Narrow Spectrum
March 2019 Company presentation
Phase 2 clinical trial demonstrated superiority
- ver standard of care
Highly selective antibiotic preserved microbiome Activity restricted to gut Well-tolerated in Phase 1 and 2 clinical trials
NEW SCIENCE
Replace front-line broad spectrum generics Differentiated label Provide clinical and economic evidence at launch
NEW PHILOSOPHY
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
NEW OPPORTUNITY
15
Ridinilazole Highly Preserving of Microbiome of CDI Patients Compared to Vancomycin
Cladograms Showing Changes in Relative Abundancy of Microbiome Following 10 Days Dosing
March 2019 Company presentation
RIDINILAZOLE VANCOMYCIN Increased relative abundancy
Source: Thorpe et al., PLOS ONE, 2018
Reduced relative abundancy
16
Ridinilazole: Statistical Superiority Over Vancomycin in Phase 2 CoDIFy Trial in SCR
March 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)
Source: Vickers et al, Lancet ID, 2017 17
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
First patient dosed in February 2019
March 2019 Company presentation
Group Design Group N Agent Regimen 1 340 Ridinilazole 200mg BID for 10 days 2 340 Vancomycin 125mg QID for 10 days
18
Potential Path to Regulatory Approvals for Ridinilazole
March 2019 Company presentation 19
Planned Milestones
H2 2021
Phase 3 clinical trials top-line data
2022
File NDA with the FDA
- Feb. 2019
Phase 3 clinical trials initiated
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
March 2019 Company presentation 20
Potential Opportunity for Broad Use Across CDI Disease Spectrum
March 2019 Company presentation
Initial Episode
~75%
Recurrent Disease
~ 25%
Initial + mild-moderate
~50%
Initial + severe
~ 25%
Initial mild-moderate
Hospital
~ 25%
Initial mild-moderate
Community
~ 25%
Patient Segment Current Treatments Opportunity >1M cases (US & EU)
RDZ
RDZ
RDZ
RDZ
Metronidazole, Vancomycin Vancomycin Fidaxomicin, Bezlotoxumab, FMT Vancomycin
21
1.4m cases in US & EU 78m worldwide1
- N. Gonorrhoeae
has consistently developed resistance to known classes
- f antibiotics
We are using the last CDC recommended treatment option; no new treatment
- ptions available
About Gonorrhea
March 2019 Company presentation 22
- 1. World Health Organization, July 2017 press release
Gonorrhea: Opportunity to Develop New Standards of Care
March 2019 Company presentation
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
NEW SCIENCE
Be adopted onto WHO guidelines Develop compounds which are oral, single dose, narrow spectrum, target three sites of infection
NEW PHILOSOPHY
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
NEW OPPORTUNITY
23
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
March 2019 Company presentation
Strain MIC (μg/mL) FA1090 0.08 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 0.09
24
Potential Path to Proof of Concept for SMT-571
March 2019 Company presentation 25
Planned Milestones
H2 2020
Phase 1 clinical trial top-line data; Phase 2 clinical trial initiation
H2 2022
Phase 2 clinical trial top-line data
H2 2019
Phase 1 clinical trial initiation
Planned Upcoming Milestones
March 2019 Company presentation
2022 2021 2019 2020
Feb, 2019
Phase 3 initiated
H2 2021
Phase 3 top-line data
2022
File NDA for FDA approval
H2 2019
Phase 1 initiation
H2 2020
Phase 1 top-line data Phase 2 initiation
H2 2021
Phase 2 top-line data
26
CDI Ridinilazole Gonorrhea SMT-571
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 Clive Mason, Senior Director, Platform Discovery Discovered SMT-571 Frank Armstrong, MD, Chairman Previous antibiotic experience at Astrazeneca and Bayer
March 2019 Company presentation
Brought 8 antibiotics to market
27
Summary Financials
March 2019 Company presentation
Key Items Amount
Nasdaq Share Price (Mar 15, 2019): $2.03 Issued Share Capital O/S(1): 32.1M Market Cap (Mar 15, 2019): $65M Cash Balance (Oct 31, 2018)(2): $16.7M Pro-Forma Cash Balance (Oct. 31, 2018)(3): $41.3M Debt (Oct. 31, 2018): $0
SYMBOL: SMMT SYMBOL: SUMM
(1) Based on total Ordinary Shares outstanding; Ordinary Shares outstanding as of Dec. 17, 2018, were 160.4 million; one ADS is equivalent to five Ordinary Shares (2) Assumes an exchange rate of $1. 2779 to £1.00 (3) Pro forma figure includes net proceeds of approximately $24.6 million relating to Summit’s private placement on Jan 10, 2019 28
Contact Details
investors@summitplc.com Twitter: @summitplc 136a Eastern Avenue Milton Park Oxfordshire UK One Broadway Cambridge Massachusetts US
March 2019 Company presentation 29