From New Mechanisms to New Standards of Care Corporate Presentation - - PowerPoint PPT Presentation

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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


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SLIDE 1

From New Mechanisms to New Standards of Care

Corporate Presentation September 2018

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SLIDE 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 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

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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

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SLIDE 4

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

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SLIDE 5

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

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SLIDE 6

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…

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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

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SLIDE 8

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

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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.

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New Science

Discovering new mechanism antibiotics with our Discuva Platform September 2018

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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

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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

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Discuva Platform: Elucidate Mechanism of Action and Optimize Against Resistance

August 2018 Company presentation

  • drug of interest

Next-generation sequencing

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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
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SLIDE 14

Proprietary Libraries Enable Potential Pipeline Expansion

September 2018 Company presentation *Current Summit preclinical program

Gram positive Gram negative

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  • 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
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SLIDE 15

Ridinilazole

Our Phase 3-ready precision antibiotic in development for front-line treatment of C. difficile infection September 2018

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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

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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

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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

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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

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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

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SLIDE 21

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

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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

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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

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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

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SLIDE 25

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
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SLIDE 26

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

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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

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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

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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

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SLIDE 30

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

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SLIDE 31

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

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SLIDE 32

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

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SLIDE 33

Contact Details

investors@summitplc.com Twitter: @summitplc 136a Eastern Avenue Milton Park Oxfordshire UK One Broadway Cambridge Massachusetts US

September 2018 Company presentation 33