UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): February 15, 2017
NABRIVA THERAPEUTICS AG
(Exact Name of Registrant as Specified in its Charter)
Republic of Austria |
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001-37558 |
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Not applicable |
(State or Other Jurisdiction |
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(Commission |
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(IRS Employer |
Leberstrasse 20 |
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Not applicable |
(Address of Principal Executive Offices) |
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(Zip Code) |
Registrants telephone number, including area code: +43 (0)1 740 930
Not applicable
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Item 7.01 Regulation FD Disclosure.
On February 8, 2017, Nabriva Therapeutics AG (the Company) issued a press release announcing its upcoming participation in two investor conferences on February 15, 2017 and February 22, 2017. Information about accessing a live webcast and a subsequent replay of the Companys presentation at each of the investor conferences is included in the press release, which is attached hereto as Exhibit 99.1 and is incorporated by reference into this Form 8-K.
The Company also intends to meet with additional investors and analysts over the course of the next several weeks. A copy of the materials to be used at these meetings, which will also be referenced at the Companys presentations at its upcoming investor conferences, is attached hereto as Exhibit 99.2 and is incorporated by reference into this Form 8-K.
The information in this Form 8-K, including Exhibits 99.1 and 99.2, shall not be deemed filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the Exchange Act), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
See Exhibit Index attached hereto.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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NABRIVA THERAPEUTICS AG | |
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Date: February 14, 2017 |
By: |
/s/ Colin Broom |
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Colin Broom |
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Chief Executive Officer |
Exhibit 99.1
Nabriva Therapeutics to Participate in Two Investor Conferences in February
VIENNA, Austria, and KING OF PRUSSIA, Pa., February 8, 2017 Nabriva Therapeutics AG (NASDAQ:NBRV), a clinical stage biopharmaceutical company engaged in the research and development of novel anti-infective agents to treat serious infections, with a focus on the pleuromutilin class of antibiotics, today announced that Colin Broom, M.D., Chief Executive Officer of Nabriva Therapeutics, will provide a company overview and business update at the following conferences in February.
· Leerink Partners 6th Annual Global Healthcare Conference
· Presentation Date: Wednesday, February 15, 2017
· Presentation Time: 11:30am ET
· Location: Lotte New York Palace Hotel, New York, NY
· RBC Capital Markets 2017 Global Healthcare Conference
· Presentation Date: Wednesday, February 22, 2017
· Presentation Time: 11:00am ET
· Location: Lotte New York Palace Hotel, New York, NY
The presentations will be webcast live and may be accessed by visiting the Investors section of the Companys web site under the Events and Presentations tab at http://investors.nabriva.com. A replay of each webcast will be available for 90 days.
About Nabriva Therapeutics AG
Nabriva Therapeutics is a clinical stage biopharmaceutical company engaged in the research and development of novel anti-infectives to treat serious bacterial infections, with a focus on the pleuromutilin class of antibiotics. Nabriva Therapeutics medicinal chemistry expertise has enabled targeted discovery of novel pleuromutilins, including both intravenous and oral formulations of its lead product candidate. Nabriva Therapeutics lead product candidate, lefamulin, is a novel semi-synthetic pleuromutilin antibiotic with the potential to be the first-in-class available for systemic
administration in humans. The company believes that lefamulin is the first antibiotic with a novel mechanism of action to have reached late-stage clinical development in more than a decade. Lefamulin is currently being evaluated in two global, registrational Phase 3 clinical trials in patients with moderate to severe CABP. Nabriva Therapeutics believes lefamulin is well positioned for use as a first-line empiric monotherapy for the treatment of moderate to severe CABP due to its novel mechanism of action, targeted spectrum of activity, resistance profile, achievement of substantial drug concentration in lung tissue and fluid, oral and IV formulations and a favorable tolerability profile. Nabriva Therapeutics intends to further pursue development of lefamulin for additional indications, including the treatment of acute bacterial skin and skin structure infections (ABSSSI), and is developing a formulation of lefamulin appropriate for pediatric use.
Nabriva Therapeutics owns exclusive, worldwide rights to lefamulin, which is protected by composition of matter patents issued in the United States, Europe and Japan.
Forward Looking Statements
Any statements in this press release about future expectations, plans and prospects for Nabriva, including but not limited to statements about the development of Nabrivas product candidates, such as plans for the design, conduct and timelines of Phase 3 clinical trials of lefamulin for CABP, the clinical utility of lefamulin for CABP and Nabrivas plans for filing of regulatory approvals and efforts to bring lefamulin to market, the development of lefamulin for additional indications, the development of additional formulations of lefamulin, plans to pursue research and development of other product candidates, and other statements containing the words anticipate, believe, estimate, expect, intend, may, plan, predict, project, target, potential, likely, will, would, could, should, continue, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from clinical trials, whether results of early clinical trials or trials in different disease indications will be indicative of the results of ongoing or future trials, uncertainties associated with regulatory review of clinical trials and applications for marketing approvals, the availability or commercial potential of product candidates including lefamulin for use
as a first-line empiric monotherapy for the treatment of moderate to severe CABP, the sufficiency of cash resources and need for additional financing and such other important factors as are set forth under the caption Risk Factors in Nabrivas annual report on Form 20-F and its prospectus supplement dated November 29, 2016 filed with the United States Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Nabrivas views as of the date of this release. Nabriva anticipates that subsequent events and developments will cause its views to change. However, while Nabriva may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Nabrivas views as of any date subsequent to the date of this release.
CONTACT:
INVESTOR RELATIONS
Will Sargent
Nabriva Therapeutics AG
William.Sargent@nabriva.com
610-813-6406
MEDIA
Katie Engleman
Pure Communications, Inc.
Katie@purecommunicationsinc.com
910-509-3977
Exhibit 99.2
February 2017 Developing Novel Anti-Infectives
This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements about our future expectations, plans and prospects, including but not limited to statements about the development of our product candidates, such as plans for the design, conduct and timelines of Phase 3 clinical trials of lefamulin for CABP, the clinical utility of lefamulin for CABP and our plans for filing of regulatory approvals and efforts to bring lefamulin to market, the development of lefamulin for additional indications, the development of additional formulations of lefamulin, plans to pursue research and development of other product candidates, and other statements containing the words anticipate, believe, estimate, expect, intend, may, plan, predict, project, target, potential, will, would, could, should, continue, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from clinical trials, whether results of early clinical trials or trials in different disease indications will be indicative of the results of ongoing or future trials, uncertainties associated with regulatory review of clinical trials and applications for marketing approvals, the availability or commercial potential of product candidates, the sufficiency of cash resources, whether research programs will result in product candidates that are advanced into future clinical trials, and need for additional financing and such other important factors as are set forth under the caption "Risk Factors" in our Annual Report on Form 20-F as filed with the United States Securities and Exchange Commission. In addition, the forward-looking statements included in this presentation represent our views as of the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this presentation. Safe Harbor and Disclaimer
Expert team advancing pleuromutilins, a new class of antibiotics, for systemic use in humans Lefamulin in two international, pivotal Phase 3 trials for moderate-to-severe CABP with top-line data expected by end of 3Q17 and around year end 2017 Investing in pre-commercial activities to maximize commercial potential Cash resources expected to fund operations at least into 2Q18 2017- A Transformational Year for Nabriva Building a Fully Integrated Anti-Infectives Company
US legislation continues to drive discovery of novel antibiotics GAIN Act (Generating Antibiotic Incentives Now) ADAPT Act (Antibiotic Development to Advance Patient Treatment) DISARM Act (Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms)- part of 21st Century Cures Act CDC Antibiotic Resistance Threats in US, 2013 FDA CABP clinical trial guidance issued 2014 IDSA/SHEA 2016 Stewardship guidelines IDSA/ATS 2016 HAP/VAP Treatment Guidelines Recent FDA Advisory Committees for Fluoroquinolones and Solithromycin Update to 2007 IDSA/ATS CABP Treatment Guidelines in progress We believe that a need exists for novel antibiotics for infectious diseases, including CABP Scientific, Regulatory and Government Agencies Focused on Infectious Diseases
In 2010, direct hospitalization costs of CAP were estimated at over $17 billiona H Pneumonia is responsible for ~140,000 hospital readmissions per year, estimated to cost more than $10B in hospital expendituresb In 2013, in the US, ~150 people died every day due to CABPd Commercial payor average cost of ~$28K (median ~$12K) for hospitalized CABP patients over 50c Burden of Pneumonia is Increasing due to Significant Morbidity and Mortality R Sources: aFile TM Jr, Marrie TJ. Burden of community-acquired pneumonia in North American adults. Postgrad Med. 2010;122:13041 bDe Alba Pneumonia Readmissions: Risk Factors and Implications TheOchsner Journal 14:649654, 2014 cSato CAP Episode Costs by Age and Risk in Commercially Insured U.S. Adults Aged >50 Years Frontiers in Microbiology 2016;7:974 Appl Health Econ Health Policy (2013) 11:251258 dHealthcare Costs and Utilization Project 2013
Bacterial Resistance Complicates the Choice of Appropriate Empiric Therapy Macrolide resistance is increasing globally for both S. pneumoniaea,b and M. pneumoniaec Sources: aMorrissey, I. ECCMID 2014. Abstract P1584 bKim, SH AAC, 2012, 56: 1418-1426 cPereyre C. Mycoplasma pneumoniae: susceptibility and resistance to antibiotics Future Microbiology, April 2011 ,Vol. 6, No. 4, Pages 423-431 US Susceptibility Rates Have Decreased across Many Antibiotics for S. pneumoniae, the Most Common Cause of CABP
Achieve the best clinical outcome, while lessening or mitigating adverse events and limiting selective pressures Effective January 1, 2017, Joint Commission & CMS require that all hospitals have Antibiotic Stewardship Committees (ASC) Decrease excessive costs due to suboptimal antibiotic use Realize a fiduciary responsibility across the continuum of care IDSA/SHEA Antibiotic Stewardship guidelines for antibiotic use updated in 2016: Reduce the use of high-risk antibiotics associated with a high risk of C. Diff infections Increase use of oral antibiotics as a strategy to improve outcomes or decrease costs Reduce antibiotic therapy to the shortest effective duration Antibiotic Stewardship Should Increasingly Drive Antibiotic Choices ASC Goalsa Sources: a Policy Statement on Antimicrobial Stewardship by SHEA, IDSA, and Pediatric Infectious Diseases Society (PIDS)nfect Control Hosp Epidemiol 2012;33(4):322-327
Significant US Adult CABP Opportunity in Hospital-Initiated Therapy ~4.2MM Oral Antibiotic Prescriptions for Hospital-Initiated Adult Outpatient CABP TreatmentB A Decision Resources Group/AMR, Age 18+ for 12 months ended December 2015 B Source Health Solutions (12 months ending September 2016), Age 18+ Nabriva Commercial Strategy Plans to Focus on Driving Early Adoption In Hospital-Initiated Patients Prioritized Hospital Formulary Acceptance Targeted Hospital Field Force ~5.3MM Orders written (avg. 4.4 days) of Inpatient IV TherapyA ~1.4MM Orders written (avg. 3.3 days) of Inpatient Oral TherapyA ~6 out of 10 Adult Outpatient Oral Prescriptions result from Hospital-Initiated CABP Treatment
Lefamulin A site P site PTC of the 23S rRNA of the large ribosomal subunit Pleuromutilins Represent a New Class of Antibiotics for Systemic Human Use Lefamulin: Novel mechanism of action with 4 distinctive binding sites in highly conserved core of the ribosomal peptidyl transferase center (PTC) Targeted anti-bacterial spectrum against respiratory pathogens (Gram-positive, Gram-negative and atypical bacteria) Minimal effect on off-target GI flora such as B. fragilis, E. coli and E. faecalis Low propensity for development of bacterial resistance and lack of cross-resistance with other antibiotic classes, based on in vitro studies lefamulin
5-7 days IV/PO Monotherapy for Most* Patients Novel Mechanism of Action CABP Targeted Spectrum of Activity Stewardship Guidelines recommend use of targeted antibiotics, not broad spectrum, and shortest effective treatment duration Resistance to many current antibiotics is rising and increases the need for antibiotics with novel mechanisms of action LEFAMULIN *10 days in clinical trials for confirmed MRSA CABP patients External Factors Likely to Influence Future Antibiotic Treatment Choices for CABP
Non-ICU Inpatient B-lactam (IV or IM) + Macrolide (IV or PO) Respiratory Quinolone (IV or PO) B-lactam (IV or IM) + Doxycycline (IV or PO) ICU Inpatient B-lactam (IV) + Macrolide (IV) B-lactam (IV) + respiratory Quinolone (IV) B-lactam (IV) + Aminoglycoside (IV) + respiratory Quinolone (IV) Mandell L. et al Clin Infect Dis. 2007; 44 (Supplement 2) :S27-S72; modified to show Community Acquired MRSA occurring in hospital, not just in ICU Outpatient If healthy, no antimicrobial use in 3 months and no Risk Factors for Drug-Resistant S. pneumoniae (DRSP) Macrolide (PO) Doxycycline (PO) Co-morbidities or Risk Factors for DRSP B-lactam (PO) + Macrolide (PO) Respiratory Quinolone (PO) At Risk for CA-MRSA Add oxazolidinone (IV) or glycopeptide (IV) Lefamulin May Be Used in Multiple CABP Treatment Settings CABP Treatment Guidelines Recommend Empiric Broad Spectrum or Combination ABx
Lefamulin: First in Class Systemic Pleuromutilin In Development for Targeted Empiric CABP Monotherapy Targeted spectrum of activity covering key CABP pathogens Gram-positive, Gram-negative, atypicals, including multi-drug resistant (MDR) strains Substantial penetration into lung fluids and macrophages Confirmed in animal models and Phase 1 studies Convenience of IV and oral formulations allowing for option to switch Enabling step down therapy and efficient patient management X-ray showing pneumonia
Lefamulin Spectrum of in vitro Activity Well Suited for CABP Extensively investigated against most prevalent pathogens Not affected by increasing antibiotic resistance observed in CABP pathogens: Cephalosporin/ fluoroquinolone/ macrolide/ penicillin resistance in S. pneumoniae Macrolide-resistant Mycoplasma spp. Note: S. pneumoniae resistant to macrolides or to levofloxacin showed 100% susceptibility to lefamulin (SENTRY 2015-16 surveillance with S. pneumoniae isolates collected world-wide) * Data from SENTRY 2015-16 world-wide surveillance program ** Waites KB et al. ASM-Microbe Meeting, June 19, 2016; Abstract#3972 Organism n MIC90 [mg/L] Organism n MIC90 [mg/L] S. pneumoniae* 2886 0.12 L. pneumophila 30 0.5 M. catarrhalis* 779 0.06 C. pneumoniae 50 0.04 H. influenzae* 1108 1 M. pneumoniae** 50 0.002 S. aureus (including HA-MRSA, CA-MRSA and MSSA) 3077 0.12
Lefamulin Data Supporting Progression to Phase 3 CABP Trials Program discussed with both FDA and EU regulatory authorities Trials follow current EMA and draft FDA guidance CABP Animal Studies PK/PD and Microbiology Phase 2 ABSSSI Proof of Concept Phase 1 IV and oral data in over 400 patients and healthy subjects
Lefamulin Clinical Development Plan Supports Differentiation in CABP Phase 3 CABP registration program initiated in the fall of 2015 Lefamulin Evaluation of Adults with Pneumonia (LEAP 1) trial (IV to oral) in moderate-to-severe CABP (Pneumonia Outcomes Research Team (PORT) III, IV and V) Site selection planned to enrich for MDR pathogens, including MRSA February 2017- confirmation of ~550 patients sample size Second trial (LEAP 2 oral) in moderate CABP (PORT II, III and IV) initiated April 2016 Continuing to activate sites around the globe Anticipate having ~160 sites enrolling patients LEAP 1 sample size recommendation Hepatic / Renal Impairment Additional Phase 1 studies LEAP 2: CABP Oral CP3, global, ~740 pts. LEAP 1: CABP IV to Oral CP3, global, ~550 pts. 2016 2018 2017 Q1 Q4 Q4 Q2 Q3 Q4 Non-Clinical Activities Blue = Clinical Programs Q3 Q2 Q1 Q3 Q2 Q1 NDA/MAA submission target in 2018
LEAP Phase 3 Trial Designs Cover Multiple Treatment Settings for CABP LEAP 1 (IV to Oral) Trial ~550 adult patients with PORT Risk Class >III (moderate to severe) 1:1 randomization: lefamulin vs. moxifloxacin ± linezolid Rx for 7 days (10 days for MRSA) PORT Risk Class III vs. IV and V >25% of patients will have a PORT risk class of IV or V Special Protocol Assessment with FDA LEAP 2 (Oral) Trial ~740 adult patients with PORT Risk Class II-IV (moderate) 1:1 randomization: lefamulin vs. moxifloxacin 5 days lefamulin / 7 days moxifloxacin PORT Risk Class II vs. III and IV >50% of patients will have a PORT risk class of III or IV Double-blind, randomized, active comparator >100 multinational centers Stratification according to: Geographic region (US vs. ex-US) Prior short-acting antibiotic therapy for CABP vs. none PORT Class
Lefamulin Fluoro-quinolones Macrolides Cephalo-sporins PCN/ BLI Tetra-cyclines Oxazo-lidinones First-in class Targeted Spectrum Activity vs. MRSA Activity vs. atypicals Activity vs. H. influenzae IV to oral switch Low Propensity for Resistance Development Empiric monotherapy Note: Nabriva management perspectives on product profiles (based on publicly available information). Lefamulin Has a Differentiated Profile in CABP Compared with Approved Classes
Financial Highlights $73.9MM Cash, cash equivalents and investments as of September 30, 2016 ~$21MM Net proceeds from Dec 2016 financing to be used for general corporate purposes, including working capital and pre-commercial activities 2,719,025 Common shares as of Dec 19, 2016 (includes 2,186,718 common shares represented by 21,867,180 ADSs, with each ADS representing 1/10 of a common share) Cash resources expected to fund operations at least into 2Q18
Anticipated Lefamulin Milestones February 2017 Blinded, interim analysis to confirm LEAP 1 sample size Around Year End 2017 Top-line data from LEAP 2 Phase 3 trial for CABP 2018 Regulatory filings in US and EU (priority review request to FDA) for CABP End of 3Q 2017 Top-line data from LEAP 1 Phase 3 trial for CABP
Advancing Pleuromutilin Development Pipeline Program Indications Discovery Pre-clinical Phase 1 Phase 2 Phase 3 Comments Lefamulin (IV/oral) CABP* LEAP 1 and LEAP 2 top-line data expected by end of 3Q17 and around year end 2017 ABSSSI Phase 2 complete Lefamulin (IV/oral) Pediatric Indications Preclinical work and formulation development ongoing Lefamulin (IV/oral) STIs, HABP/VABP, Osteomyelitis, Prosthetic Joint Infections Potential indications BC-7013 (Topical) uSSSI Phase 1 complete *We have not completed any clinical trials of lefamulin specifically for patients with CABP.
Lefamulin in two international, pivotal Phase 3 trials for moderate-to-severe CABP with top-line data expected by end of 3Q17 and around year end 2017 Investing in pre-commercial activities to maximize commercial potential Cash resources expected to fund operations at least into 2Q18 Key Takeaways for Transformational Year Expert team advancing pleuromutilins, a new class of antibiotic, for systemic use in humans
February 2017 Developing Novel Anti-Infectives
Market Research Indicates Lefamulin Patient Opportunity from Across Generic CABP Regimens IV In-Patient Market Share 2015 Source: AMR data CEPHALOSPORIN 30% FLUOROQUINOLONE 23% MACROLIDE 17% PENICILLIN - COMBO 10% GLYCOPEPTIDE 10% AMINOGLYCOSIDE 2% TETRACYCLINE 2% CARBAPENEM 2% LINCOSAMIDE 1% MONOBACTAM 1% NITROIMIDAZOLE 1% CARBAPENEM - COMBO 1% OXAZOLIDINONE 1% PENICILLIN 0% ANTIFOLATE 0% POLYMYXIN 0% LIPOPEPTIDE 0%
Resistance and Safety Issues Could Slow Future Macrolide and Fluoroquinolone Use Source: AMR data Oral In-Patient Market Share 2015 MACROLIDE 44% FLUOROQUINOLONE 34% CEPHALOSPORIN 9% PENICILLIN - COMBO 4% TETRACYCLINE 4% ANTIFOLATE 1% OXAZOLIDINONE 1% PENICILLIN 1% LINCOSAMIDE 1% NITROIMIDAZOLE 1% RNA POLYMERASE 0%
Resistance is Growing Among Common Adult CABP Outpatient Oral Prescriptions Based on data provided by Source Health Solutions (12 months ending September 2016), Age 18+ CEFPODOXIME , 1% MINOCYCLINE , 1% MOXIFLOXACIN , 1% CLARITHROMYCIN , 1% PENICILLIN V , 1% Other , 2% CEFDINIR , 3% METRONIDAZOLE , 3% CEFUROXIME , 3% CLINDAMYCIN , 3% CEPHALEXIN , 6% CIPROFLOXACIN , 7% DOXYCYCLINE , 7% AMOXICILLIN , 8% TRIMETHOPRIM - SULFONAMIDE COMBINATION , 8% AMOXICILLIN/CLAVULANATE , 9% LEVOFLOXACIN , 19% AZITHROMYCIN , 19% Hosptial Adult Oral Outpatient Market Share
LEAP 1 and 2: Powering and Primary Objectives FDA Endpoint: Early Clinical Response (ECR) 72-120 hours after first dose of study drug Intent to Treat (ITT) Population LEAP 1 non-inferiority margin 12.5%, >90% power LEAP 2 non-inferiority margin 10%, 90% power EMA endpoint: Investigator Assessment of Clinical Response (IACR) at Test of Cure 5-10 days after the last dose of study drug Modified-ITT (mITT) and Clinically Evaluable Populations LEAP 1 non-inferiority margin 10%, 80% power LEAP 2 non-inferiority margin 10%, >90% power
Lefamulin Pre-clinical Data Supports Advancing to Phase 3 for CABP 24h AUC/MIC was identified as the PK/PD index most relevant for efficacy Time-dependent killing and modest in vitro and in vivo post antibiotic effects Substantial lung penetration, as demonstrated by epithelial lining fluid and macrophage concentrations, in animal and human studies Lefamulin was efficacious in murine lung and thigh infection models predictive of efficacy in ABSSSI and bacterial respiratory tract infections Greater efficacy against S. aureus and S. pneumoniae in murine lung infection models compared to thigh infection models Overall PK/PD target attainment was >96% based on relevant PK/PD targets for both S. pneumoniae and S. aureus and robust worldwide surveillance data Results of PK/PD target attainment analyses support the lefamulin dosing regimen of 150 mg q12h IV and 600 mg q12h oral for CABP
Lefamulin Therapeutic Effect Observed in Phase 2 Trial of ABSSSI Lefamulin achieved clinical response rates comparable to vancomycin Lefamulin was well tolerated Most commonly reported adverse events included headache, nausea and infusion site pain or redness Lefamulin 100 mg Lefamulin 150 mg Vancomycin 1 g N = 70 N = 71 N = 66 ITT population at Test of Cure (TOC) 85.7 83.1 81.8 CE population (N=50, 51, 51) at TOC 90.0 88.9 92.2 No increase in area of erythema plus absence of fever (%) 48-72h (ITT pop.) 85.7 83.1 80.3 20% reduction in area of erythema (%) at 48-72h (ITT pop.) 74.3 70.4 71.2 Treatment Group % response rate Lefamulin 100 mg or 150 mg IV q12h vs. vancomycin in 207 patients with ABSSSI
Lefamulin Related Tolerability Profile Observed in Phase 2 Trial of ABSSSI
Lefamulin Clinical Database Supported Advancing to Phase 3 for CABP Studied by IV and oral route in more than 400 patients and healthy subjects Generally well tolerated by IV and oral routes Transient, Cmax related QTc effect comparable to, or less than, that of moxifloxacin Rapid oral absorption (600mg oral q12h similar AUC to 150mg IV q12h) Achieves substantial concentrations in a variety of target tissues High penetration into human lung epithelial lining fluid and macrophages Elimination half-life of 9 to 12 hours Primarily excreted unchanged through the non-renal route Low level of metabolism and low potential for drug-drug interactions Progression to Phase 3 CABP discussed with both FDA and EU regulatory authorities and follows current EMA and draft FDA guidance Amended SPA agreed with FDA on first Phase 3 (IV to oral) CABP trial
LEAP 1 and 2: Treatment Scenarios LEAP 1 All patients: IV therapy for a minimum of three days before switching to oral therapy Patients will receive 7 days of lefamulin vs. 7 days moxifloxacin Patients receive 10 days if: MRSA pneumonia confirmed Both moxifloxacin and linezolid started at baseline (vs. lefamulin + placebo) If MRSA identified: moxifloxacin discontinued, linezolid continued LEAP 2 All patients will receive 5 days of lefamulin vs. 7 days moxifloxacin
Nabriva Has a Strong and Broad Patent Portfolio Nabriva currently has 19 worldwide pleuromutilin patent families active on file Most of the global pleuromutilin IP landscape is covered (including U.S., Europe, Japan) Lefamulin IP protected at least until 2028 by several layers Composition of matter granted in U.S., EP and Japan until 2028 Process patents ensure protection until 2031 Patent extension by up to 5 years in major jurisdictions BC-7013 IP protection until 2027 Composition of matter granted inter alia in U.S., EP and Japan
Lefamulin Manufacturing On Track for NDA Submission in 2018 Nabriva CMC/Manufacturing Team- extensive experience with new product approvals in the US and Europe Nabriva Quality Assurance Team- extensive experience with regulatory agency requirements in the US and Europe Drug Substance (API) Well known contract manufacturer in Europe with good regulatory inspection history API is very stable- expect 4-year retest date Plan to hold sufficient API inventory to reduce business interruption risk Plan to approve second API supplier to further reduce business interruption risk Drug Product (DP) Well known contract manufacturers in Europe with good regulatory inspection histories IV Product- expect 36-month shelf life with refrigerated storage Oral Product- expect 36-month shelf life with room temperature storage Plan to approve second IV and oral DP suppliers to reduce business interruption risk
MRSA Pneumonia Increases Patient Risk Low confirmed prevalence Difficult to distinguish clinically from other pathogens Outcomes worse than with other causative pathogens: MRSA pneumonia associated with more severe clinical outcomes than those with pneumococcal CAP1 intensive care unit admission (86.7% vs 34.8%) in-patient mortality (13.3% vs 4.4%) Empiric coverage: Some research suggests empiric therapy of severe CAP during periods of high influenza activity should include coverage for MRSA, including among those without recognized risk factors for MRSA2 Recent study in US1: although very low confirmed prevalence of S. aureus and MRSA, nearly 1/3 CABP inpatients received anti-MRSA antibiotics 1Self et al Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes Clinical Infectious Diseases Advance Access published June 2, 2016 2Hageman et al Severe community-acquired pneumonia due to Staphylococcus aureus, 200304 influenza season. Emerg Infect Dis. Vol. 12, No. 6, June 2006
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