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 September 2018 Forward-Looking Statements Statements in this presentation, other than statements of historical fact, constitute forward-looking statements within the meaning of
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 discovery and development platform, strategies, future performance, expectations, assumptions, financial condition, liquidity and capital resources. These forward-looking statements may be preceded by, followed by or
- therwise 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.
September 2018 Company presentation 2
Creating a Different Antibiotic Company
September 2018 Company presentation
New bacterial targets New drugs against those targets
NEW SCIENCE
The right drug for the right bug Real unmet needs Innovative development plans Stewardship
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
September 2018 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
- No new mechanisms
- Incremental benefits
- Niche market positioning with low
commercial return
- Resistance becoming clinical issue
Lipopeptides
4
New Mechanisms Deliver Strong Commercial Returns
2011 Linezolid - Peak sales = $1.4 billion
- Novel mechanism agent
- Label and launch clearly focused on treatment of
MRSA – the unmet need
- Clinical superiority over vancomycin demonstrated
for MRSA nosocomial pneumonia and skin infections
- Additional tangible benefits over SoC vancomycin
demonstrated
- IV/oral switch & community use
- Reduced length of stay
- Possible mortality benefits
September 2018 Company presentation
1968
First reported MRSA case in US
1959
Methicillin introduced to treat penicillin resistant S. aureus
1980
Healthcare associated MRSA outbreaks
1989-1991
Community acquired MRSA
- utbreaks
2000
Linezolid approved
5
Stewardship: Alignment with Summit’s Strategy
Need for stewardship driven by a lack of innovation against a background of antimicrobial resistance
- Stewardship an integrated multidisciplinary approach to
- ptimize clinical outcome
Stewardship is not purely about reservation
- f agents. Reservation alone:
- Promotes inappropriate empiric therapy and resistance
development to standard of care
September 2018 Company presentation
CDC Definition …provide every patient with the right antibiotics, at the right time, at the right dose, and for the right duration - to reduce adverse events associated with antibiotics and improve patient
- utcome…
6
Stewardship and Commercial Success Aligned
Stewardship ultimately about upfront use of the correct drug
- Improves clinical outcomes and reduces healthcare costs
- Novel mechanism agents address specific indications and
unmet needs
Summit’s approach aligns with stewardship and could result in commercial success
- Development program designed to meet needs of
patients, providers and payors
- Promotes market uptake of agents into front-line settings
- Acceptable pricing achieved through clear and
demonstrable package of benefits
August 2018 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
7
Executing Across Drug Development Pathway
September 2018 Company presentation
Discovered several programs
- f distinct new mechanism
antibiotics to date Discuva Platform allows for expansion of pipeline covering serious pathogenic threats
DISCOVER
Expect to initiate Phase 3 clinical trials in C. difficile infection (CDI) Q1 2019 Expect to initiate Phase 1 clinical trial in gonorrhea H2 2019
DEVELOP
Seeking to maximize pipeline value Expect to file for FDA approval for ridinilazole in 2022, if Phase 3 results are positive Potential global peak sales ~$700M for ridinilazole
COMMERCIALIZE
8
Our New Mechanism Antibiotic Pipeline
September 2018 Company presentation
CDI (ridinilazole) Gonorrhoea (SMT-571) Gonorrhea (Target #2) Roche Collaboration1 ESKAPE Program Phase 1 Phase 2 Phase 3 Discovery Preclinical Funding source
BARDA Discuva Platform
9 (1) 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 September 2018
Discuva Platform: Enabling Optimized Candidate Selection
September 2018 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
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
September 2018 Company presentation
Library of mutant engineered bacteria Next-generation sequencing Genome map of mutation insertions
12
Discuva Platform: Elucidate Mechanism of Action and Optimize Against Resistance
August 2018 Company presentation
- drug of interest
Next-generation sequencing
13
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
Proprietary Libraries Enable Potential Pipeline Expansion
September 2018 Company presentation *Current Summit preclinical program
Gram positive Gram negative
14
- 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
Ridinilazole
Our Phase 3-ready precision antibiotic in development for front-line treatment of C. difficile infection September 2018
About C. difficile Infection (CDI)
September 2018 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 prevent recurrence in around a third
- f cases
Failure likely connected to microbiome impact of standard
- f care
16
Ridinilazole: Potent, Oral & Narrow Spectrum
September 2018 Company presentation
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
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 recurrent CDI Expect to file NDA in 2022, if Phase 3 results are positive Potential ~$700M global peak sales Patents through 2029, exclusivity expected through 2034 in US, Europe and Japan
NEW OPPORTUNITY
17
Ridinilazole Highly Preserving of Microbiome of CDI Patients Compared to Vancomycin
Cladograms Showing Changes in Relative Abundancy of Microbiome Following 10 Days Dosing
September 2018 Company presentation
RIDINILAZOLE VANCOMYCIN Increased relative abundancy
Source: CoDIFy Phase 2 clinical trial
Reduced relative abundancy
18
Ridinilazole: Statistical Superiority Over Vancomycin in Phase 2 CoDIFy Trial in SCR
September 2018 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 19
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
September 2018 Company presentation 20
Plan to Deliver Clinical and Economic Evidence at Launch
Primary endpoint:
SCR to 30 days post EOT 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
September 2018 Company presentation
Group Design Group N Agent Regimen 1 340 Ridinilazole 200mg BID 10 days 2 340 Vancomycin 125mg QID 10 days
21
Potential Opportunity for Broad Use Across CDI Disease Spectrum
September 2018 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
22
Why Can Ridinilazole Succeed Where FDX Failed?
September 2018 Company presentation
Target benefit Ridinilazole Fidaxomicin
Clearly superior patient
- utcomes vs generic Rx
(optimal label)
- Phase 3 superiority trials planned
with SCR as primary endpoint
- Already showed statistical
superiority vs vancomycin on SCR in Phase 2
- Phase 3 non-inferiority trials - cure
as primary endpoint
- Superior SCR vs vancomycin but
secondary/exploratory endpoint and not shown for NAP1 strain
Health economic benefits associated with Rx
- Phase 3 to include key HEOR
metrics – length of stay, 30-day readmissions
- Lack of support at launch
Meets preferences / needs of patients and payors
- Higher awareness of recurrence +
microbiome
- Guidelines, quality frameworks
- Lack of context for key features
and benefits
- Fewer relevant incentives
2020s 2011
23
Potential Path to Regulatory Approvals for Ridinilazole
September 2018 Company presentation 24
Planned Milestones
H2 2021
Phase 3 clinical trials top-line data
2022
File NDA with the FDA
Q1 2019
Phase 3 clinical trials initiation
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
September 2018 Company presentation 25
- 1. World Health Organization, July 2017 press release
Gonorrhea: Opportunity to Develop New Standards of Care
September 2018 Company presentation
Two novel targets from Discuva Platform New series against both targets 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
26
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
- Bactericidal with a 5 Log reduction in CFU/mL after 4-8 hours
September 2018 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
27
Potential Path to Proof of Concept for SMT-571
September 2018 Company presentation 28
Planned Milestones
H2 2019
Phase 1 clinical trial initiation
H2 2020
Phase 1 clinical trial top-line data; Phase 2 clinical trial initiation
Sept 2018
Nominated SMT-571 as lead candidate
H2 2021
Phase 2 clinical trial top-line data
Able to Capitalize, but not Depend on Push and Pull Incentives
September 2018 Company presentation
Ridinilazole
BARDA award worth up to $62M for Phase 3 clinical trials and regulatory development Wellcome Trust provided ~$10M for development through Phase 2
Gonorrhea
SMT-571 granted up to $4.5M by CARB-X for development potentially through end
- f Phase 1
PUSH INCENTIVES Ridinilazole
QIDP and Fast Track designations as provided through the US GAIN Act – includes eligibility for five year market exclusivity
Future opportunities
US Congress continues to propose bills to incentivize antibiotic innovation (REVAMP Act, DISARM Act, 21st Century Cures Act) G20 has committed to enhance pull incentives at 2017 meeting
PULL INCENTIVES
29
CDI
Planned Upcoming Milestones
September 2018 Company presentation
2022 2021 2019 2018 2020
Gonorrhea
Q1 2019
Phase 3 initiation
H2 2021
Phase 3 top-line data
2022
File NDA for FDA approval
Sept 2018
Nominated SMT-571 as lead candidate
H2 2019
Phase 1 initiation
H2 2020
Phase 1 top-line data Phase 2 initiation
H2 2021
Phase 2 top-line data
30
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
September 2018 Company presentation
Brought 8 antibiotics to market
31
Summary Financials
September 2018 Company presentation
Key Items Amount
Nasdaq Share Price (Sept. 24, 2018): $2.21 Issued Share Capital O/S(1): 16.4M Current Market Cap (Sept. 24, 2018): ~$36M Cash Balance (Jul. 31, 2018)(2): $22.5M Debt (Jul. 31, 2018): $0
SYMBOL: SMMT SYMBOL: SUMM
(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 $1.3125 to £1.00 32
Contact Details
investors@summitplc.com Twitter: @summitplc 136a Eastern Avenue Milton Park Oxfordshire UK One Broadway Cambridge Massachusetts US
September 2018 Company presentation 33