Carbavance® TANGO-1 phase III trial results

Carbavance®(meropenem-vaborbactam)

TANGO-1phase III trial results

Conference call • 27th June 2016

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Carbavance (meropenem-vaborbactam) phase III trial results

Agenda

Introduction Clive Meanwell, MD, PhDChief Executive Officer

TANGO I results Jeff Loutit, MB, ChBVice President, Chief Medical OfficerInfectious Disease Innovation Group

CommentaryNext steps

Mike Dudley, PharmDSenior Vice President, Research & Development and Co-LeadInfectious Disease Innovation Group

Investment thesisQ&A

Clive Meanwell

Introduction

Clive MeanwellChief Executive Officer

Key strategic objectives for MDCOExecution focus

November 2015 Progress

Deliver on R&D Advancing 4 potential blockbusters

Divest non-core assets Divested 6 in-market products

Raise non-dilutive capital Up to $1.15b via divestitures1

Reduce cash burn Cutting SG&A by $65-80m per year

Optimize capitalstructure

Refinanced/extended maturity for $220m of 2017 convertible notes

1: Includes approximately $438 million in upfront payments and $715 millon in potential future milestone payments

Delivering on R&DAdvancing 4 potential blockbusters

Carbavance®Gram negativeinfections including CRE

PCSK9siLDL lowering

in ASCVD

MDCO-216 arterial plaque regression

ABP-700iv sedation and

anesthesia


Overview

• Carbavance® (meropenem-vaborbactam) met FDA and EMA pre-specified 1o endpoints for non-inferiority

• Achieved statistical superiority over piperacillin-tazobactam using FDA primary endpoint

• Safety and tolerability comparable to control treatment

• TANGO 1 will be central to regulatory submissions

• Plan to submit NDA to FDA in early 2017

• FDA designated Qualified Infectious Disease Product and granted Fast Track status

• Urgent, growing global threat of deadly gram-negative CRE superbugs

Carbavance® (meropenem-vaborbactam) is an investigational agent not approved for commercial use in any market

TANGO-1 results

Jeff Loutit, MBChBVice President, Chief Medical Officer

Infectious Disease Innovation Group


Background

• Complicated UTIs are a major cause of hospitalization

• Anatomic or functional abnormalities, or co-morbidities

• Enterobacteriaceae (E. coli, Klebsiella sp.) common causes

• Treated in inpatient setting with cephalosporins, piperacillin-tazobacatam, fluoroquinolones and carbapenems

• Emerging carbapenemases in Enterobacteriaceae pose a major and increasing threat to therapeutic effectiveness



Rationale

Carbavance: combination designed to treat CRE infections

Meropenem

• Widely used carbapenem

• Standard-of-care for serious G- infections

• High potency and safety

• Broad spectrum coverage

• Resistant to ESBLs

Vaborbactam

• First in a new class of BLIs

• Discovered at MDCO labs

• Potent inhibitory activity optimized against KPC carbapenemase

• Pharmacologically well-matched with meropenem



Objectives

Double-blind, double dummy active controlled trial to assess:

• Efficacy of Carbavance (meropenem-vaborbactam)

• Safety and tolerability



Study design

-1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

Screen Treat for up to 10 days Follow-up

cU

TI o

r A

Pre

qu

irin

g ≥

5 d

ays

IV R

x

End Of IV Treat’(≥15 doses)FDA endpoint

Test of cureEMA endpointDay 15-19

Last follow-upDay 22-26

Meropenen-vaborbactam2g-2g q8h iv 3 hDummy (saline)

≥15 doses transition to oral Rx if clinically indicated and criteria met

Piperacillin-tazobactam4g/0.5g q8h iv 30 minDummy (saline)



Study population

Populations Meropenem-vaborbactam

Piperacillin-tazobactam

Total

N N N

Intention to treat 274 276 550

Modified intention to treat (MITT)/Safety

272 273 545

Microbiologic modified intent to treat (mMITT)

192 182 374

Microbiologic evaluable (ME) 178 169 347



Efficacy: FDA primary endpoint

FDA Primary EndpointmMITT Population

Meropenem-Vaborbactam

Piperacillin-Tazobactam

Overall Success1 at EOIVT 188/192 (98.4%) 171/182 (94.0%)

Difference (95% CI) 4.5% (0.7%, 9.1%)

Overall success: Clinical outcome of Cure or Improvement and microbiologic outcome of eradication (defined as the baseline bacterial pathogen being reduced to < 104 CFU/ml)EOIVT: End of Intravenous TherapymMITT: Microbiologic modified intent to treat population



Efficacy: EMA co-primary endpoints

EMA Primary EndpointCo-Primary

Meropenem-Vaborbactam

Piperacillin-Tazobactam

Microbial Eradication at TOC mMITT Population

128/192 (66.7%) 105/182 (57.7%)

Difference (95% CI) 9.0% (-0.9%, 18.7%)

Microbial Eradication at TOCME Population

118/178 (66.3%) 102/169 (60.4%)

Difference (95% CI) 5.9% (-4.2%, 16.0%)

Microbial eradication: defined as the baseline bacterial pathogen being reduced to < 103 CFU/mlTOC-Test of CuremMITT-microbiologic modified intent to treat populationME-microbiologic evaluable population



Safety: Adverse events

System organ class preferred term

Meropenem-vaborbactam

Piperacillin-tazobactam

Total

N = 272 N = 273 N = 545

n (%) n (%) n (%)

Treatment emergent adverse events (TEAEs)

106 (39.0) 97 (35.5) 203 (37.2)

Drug-related TEAEs 41 (15.1) 35 (12.8) 76 (13.9)

Discontinuation of study drug due to an AE

7 (2.6) 14 (5.1) 21 (3.9)

Serious AE 11 (4.0) 12 (4.4) 23 (4.2)

Death 2 (0.7) 2 (0.7) 4 (0.7)



Summary

In a double-blind, double dummy active controlled trial versus piperacillin-tazobactam in cUTI, Carbavance:

• Met FDA pre-specified non-inferiority margin and met criteria for superiority for efficacy

• Met EMA pre-specified non-inferiority margin for efficacy

• Demonstrated comparable safety and tolerability

• Results were consistent across clinical and microbiological endpoints, in different study populations and in subgroups


Commentary

Mike Dudley, PharmDSenior Vice President, Research & Development and Co-Lead

Infectious Disease Innovation Group

Commentary on Carbavance programPlanned NDA/MAA phase III package

TANGO 1 TANGO 2

Patients Complicated UTI and acute pyelonephritis(cUTI/AP)

cUTI/AP, HABP/VABP, cIAI and/or bacteremia known/suspected CRE

Design Randomized 1:1Double blind

Randomized 2:1Open label

Comparator Piperacillin-tazobactam

Best available therapy

Total patients 550 Up to 150

Study sites 60 60

BARDA contract Yes Yes


Commentary on Carbavance programOngoing BARDA support

Progressive partnership and contract

Efficient program - 6 years from discovery to end of TANGO-1

BARDA contract total commitment to date ~$55.8 million (total $91.8 million if all options exercised)

Cost-sharing arrangement includes non-clinical, clinical, manufacturing, and associated regulatory activities


Commentary on Carbavance programCRE a growing and urgent threat

CDC threat category “Urgent”

Extensive IV antibiotic use in hospital1

Rise of resistance2,4

High disease burden and mortality (20-50%)3,4,5

Limited treatment options

1. Arlington Medical Resource (AMR) Audit; Decision Resources Pharmacor; HCUP National Inpatient Sample (NIS) Database2. Sievert et al. Infect Cont Hosp Epidem. 2013; 34(1):1-14; Eurofins-TSN / CDDEP3. Spellberg and Rex. Nat Rev Drug Discov. 2013; Dec; 12(12): 963; EviMed Analysis of Premier Database4. Vital Signs: Carbapenem-Resistant Enterobacteriaceae. MMWR 2013;62:165-70.5. Alexander E et al. ICAAC 2015


Commentary on Carbavance programEvolving resistance demands innovation

Successive generations of beta lactam antibiotics ± BLIs

Most recent challenge of carbapenemases (KPC)

1970sTEM-1

TEM-2

2010KPCs

2015Ceph+ BLI

20171

Carbapenem+ BLI

1980s -ESBLs

1: Estimate


Commentary on Carbavance programEvolving resistance demands innovation

Antibiotic resistance in Klebsiella pneumoniae in the U.S.

0%

5%

10%

15%

20%

1999 2003 2007 2011

% r

esi

sta

nc

e

.

Aminoglycosides

Carbapenems

Cephalosporins

Fluoroquinolones


Commentary on Carbavance programMarket demand for new products strong

Company Product Year Sales

Johnson & Johnson Levaquin® 2008 $1.64B

Pfizer/Wyeth Zosyn® 2008 $1.26B

AstraZeneca Merrem® 2008 $897M

Merck Primaxin® 2007 $763M

Merck Invanz® 2015 $569M

Source: Company SEC filings


Commentary on Carbavance programNext steps

Complete manufacturing development in 2016

Continue to enroll TANGO-2

Compile NDA for submission in early 2017

QIDP

Fast track review

EMA submission 2017



Summary

• Carbavance® met FDA and EMA pre-specified primary endpoints in patients with cUTI

• Statistical superiority over piperacillin-tazobactam using FDA primary endpoint

• Safety and tolerability comparable to control treatment

• TANGO 1 will support regulatory submissions

• Plan to submit NDA to FDA in early 2017

• FDA designated Qualified Infectious Disease Product and granted Fast Track status

• Urgent, growing global threat of deadly gram-negative CRE


Investment thesis

Clive MeanwellChief Executive Officer

Investment thesisPotential for attractive growth in antimicrobial medicine

Platform of antibiotic and beta-lactamase inhibitors targeting serious drug-resistance threats

Proven product discovery, development, regulatory capabilities

Effective partnership with BARDA

Established relationships with leading investigators

Productive interactions with regulators

Commercial set-up in US Orbactiv® and Minocin IV®

Potential partnerships ex-US


Questions& Answers

Carbavance® TANGO-1 phase III trial results

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