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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):  May 21, 2018

 

NABRIVA THERAPEUTICS PLC

(Exact name of registrant as specified in its charter)

 

Ireland

 

001-37558

 

Not Applicable

(State or other jurisdiction of
incorporation)

 

(Commission File Number)

 

(I.R.S. Employer Identification
No.)

 

25-28 North Wall Quay,
IFSC, Dublin 1, Ireland

 

Not Applicable

(Address of principal executive offices)

 

(Zip Code)

 

Registrant’s telephone number, including area code: (610) 816-6640

 

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))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company x

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x

 

 

 



 

Item 7.01.  Regulation FD Disclosure.

 

On May 21, 2018, Nabriva Therapeutics plc (the “Company”) announced topline results from its second Phase 3 clinical trial of lefamulin for the treatment of community-acquired bacterial pneumonia, which is also referred to as the LEAP 2 trial.

 

The Company will host a conference call to discuss the topline results of the LEAP 2 trial on Monday, May 21, 2018 at 8:30 AM Eastern Time, and a live webcast of the call will be available through the investor relations section of the Company’s website.

 

The slide presentation to be used by the Company during the call is attached hereto as Exhibit 99.1 and incorporated herein by reference. The information in this Item 7.01, including Exhibit 99.1, 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 8.01.  Other Events.

 

The press release announcing the topline results from the LEAP 2 trial is attached hereto as Exhibit 99.2 and incorporated herein by reference.

 

Item 9.01.                                        Financial Statements and Exhibits.

 

(d)  Exhibits.

 

Exhibit
No.

 

Description

99.1

 

LEAP 2 Presentation dated May 21, 2018.

99.2

 

Press Release dated May 21, 2018.

 

2



 

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.

 

 

NABRIVA THERAPEUTICS PLC

 

 

Date: May 21, 2018

By:

/s/ Colin Broom

 

 

Colin Broom, M.D.

 

 

Chief Executive Officer

 

3


Exhibit 99.1

Lefamulin Evaluation Against Pneumonia (LEAP 2) Phase 3 Topline Results May 21, 2018

 


Safe Harbor and Disclaimer 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, the clinical utility of lefamulin for CABP, our plans for filing of regulatory approvals, 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, our plans to enter into arrangements with external collaborators, the sufficiency of our existing cash resources 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, whether results of our Phase 3 clinical trials of lefamulin are indicative of the clinical utility of lefamulin for CABP, 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 the annual and quarterly reports we file 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. 2

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Nabriva: Addressing the Demand for New Antibiotics Lefamulin, the lead molecule of a new class of antibiotics in clinical development for CABP, demonstrated positive topline results in both the LEAP 1 and LEAP 2 Phase 3 trials, with an NDA filing expected in the fourth quarter of 2018 Pre-commercial activities initiated to optimize adoption at launch and long term potential for a large underserved market* Highly experienced management team in place to build a fully integrated anti-infective company Focused on creating value through innovation and business development 3 * Lefamulin is an investigational drug candidate and has not received regulatory approval for any indication. Information provided in this slide is based on research and development performed to date.

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4 Overview of the Lefamulin Clinical Program Extensive PK/PD Characterization and Preclinical Program with 20 Phase I studies Proof-of-Concept Phase 2 ABSSSI LEAP 1: Efficacy and Safety of IV-to-Oral Lefamulin in Adults with CABP LEAP 2: Efficacy and Safety of Oral Lefamulin in Adults with CABP Pediatric Program and Life Cycle Management

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LEAP 2 TRIAL DESIGN and DEMOGRAPHICS

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LEAP 2 Phase 3 Trial Design Oral Administration 6 Lefamulin Moxifloxacin Informed Consent & Baseline Assessments Randomization Early Clinical Response (ECR) Assessment (96 +/- 24 hrs After 1st Dose) End of Treatment Within 2 Days After Last Dose Late Follow Up 30 +/-3 Days After 1st Dose 5 days lefamulin vs 7 days moxifloxacin Follow Up Study Drug Administration Enrollment: Must Dose Within 24 h IACR at Test of Cure (TOC) 5-10 Days After Last Dose 7 days *10 days if MRSA confirmed as the causative pathogen Placebo

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LEAP 2: Phase 3 Trial Design 7 FDA Primary Endpoint: Early Clinical Response (ECR) ITT Population EMA Primary Endpoint: Investigator Assessment of Clinical Response (IACR) at Test of Cure (mITT and CE-TOC Population) FDA and EMA Primary Endpoints 72-120 hours after first dose of study drug Improvement in > 2 of 4 CABP signs/symptoms No worsening in any CABP signs/symptoms Alive Did not receive non-study antibacterial therapy for the treatment of CABP Non-inferiority margin 10%, >90% power At 5-10 days after the last dose of study drug: Signs/symptoms of CABP have resolved/improved such that no additional antibacterial therapy is administered for the treatment of CABP Non-inferiority margin 10%, >90% power ITT = Intent to Treat, mITT = Modified Intent to Treat, CE-TOC = Clinically Evaluable at Test of Cure

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LEAP 2 Phase 3 Trial Design CABP Symptom Assessment for ECR Symptom Absent (0) Mild (1) Moderate (2) Severe (3) Dyspnea Resolution (to pre-CABP baseline) or absence of dyspnea Dyspnea on exertion (e.g., climbing stairs) Dyspnea with normal/routine activities (e.g., walking) Dyspnea at rest or requiring oxygen therapy Cough Resolution (to pre-CABP baseline) or absence of cough Transient, does not interfere with normal activity Frequent, interferes with normal activity or sleep Constant, interferes with most or all activity or sleep Production of purulent sputum Resolution (to pre-CABP baseline) or absence of sputum production Sputum production rarely causes difficulty or distress Sputum production often causes difficulty or distress Constant difficulty with sputum production Chest pain Resolution or absence of chest pain related to CABP Transient, does not interfere with normal activity Frequent, interferes with normal activity or sleep Constant, interferes with most or all activity or sleep 8

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LEAP 2 Phase 3 Trial Populations and Disposition High Patient Completion and Microbiological Isolate Recovery Rates 9 Category Lefamulin n (%) Moxifloxacin n (%) TOTAL n (%) All Randomized (ITT) 370 368 738 Modified ITT (mITT) 368 (99.5%) 368 (100%) 736 (99.7%) Clinically Evaluable-Test of Cure (CE-TOC) 330 (89.2%) 326 (88.6%) 656 (88.9%) Microbiological ITT (microITT) 205 (55.4%) 186 (50.5%) 391 (53.0%) Completed Study 353 (95.4%) 354 (96.2%) 707 (95.8%) Completed ECR Assessment 356 (96.2%) 362 (98.4%) 718 (97.3%) Completed TOC Assessment 355 (95.9%) 354 (96.2%) 709 (96.1%)

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LEAP 2 Phase 3 Trial ITT Population Balanced Baseline Characteristics Between Treatment Groups 10 Category Lefamulin n (%) Moxifloxacin n (%) TOTAL n (%) Age <65 years 234 (63.2%) 227 (61.7%) 461 (62.5%) 65-74 78 (21.1%) 79 (21.5%) 157 (21.3%) >75 58 (15.7%) 62 (16.8%) 120 (16.3%) Demographics Male 207 (55.9%) 180 (48.9%) 387 (52.4%) BMI (kg/m2) (Mean) 26.54 26.48 26.51 Race (White) 274 (74.1%) 270 (73.4%) 544 (73.7%) Renal Status Severe impairment (CrCl <30 ml/min) 4 (1.1%) 3 (0.8%) 7 (0.9%) Moderate impairment (CrCl 30-<60ml/min) 64 (17.3%) 70 (19.0%) 134 (18.2%) Mild impairment (CrCl 60-<90 ml/min) 112 (30.3%) 117 (31.8%) 229 (31.0%) Normal function (CrCl >90 ml/min) 190 (51.4%) 178 (48.4%) 368 (49.9%)

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LEAP 2 Phase 3 Trial PORT Risk Classification: ITT Population 11 PORT Class Lefamulin n (%) Moxifloxacin n (%) TOTAL n (%) I 1 (0.3%) 2 (0.5%) 3 (0.4%) II 183 (49.5%) 189 (51.4%) 372 (50.4%) III 145 (39.2%) 133 (36.1%) 278 (37.7%) IV 40 (10.8%) 42 (11.4%) 82 (11.1%) V 1 (0.3%) 2 (0.5%) 3 (0.4%)

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LEAP 2 TRIAL EFFICACY RESULTS

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LEAP 2 Trial Efficacy Results 13 Lefamulin Met FDA Primary Endpoint 336 / 370 334 / 368 High Response Rates on Both Arms Delta (95% CI) 0.1 (-4.4, 4.5) 336 / 370 334 / 368

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LEAP 2 Trial Efficacy Results Lefamulin Met EMA Co-Primary Endpoints 14 Delta (95% CI) -3.9 (-8.2, 0.5) Delta (95% CI) -1.6 (-6.3, 3.1) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% IACR mITT IACR CE - TOC 87.5% 89.7% 89.1% 93.6% Percent Responders EMA Primary Endpoints: IACR in mITT and CE at TOC Lefamulin Moxifloxacin

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ECR by PORT Risk Classification: ITT Population Lefamulin Demonstrated High Response Rates Across All Severities of CABP 15 PORT Class Lefamulin Moxifloxacin Treatment Difference (95% CI) I 1/1 (100%) 2/2 (100%) - II 168/183 (91.8%) 176/189 (93.1%) -1.3 (-7.2, 4.6) III 132/145 (91.0%) 120/133 (90.2%) 0.8 (-6.8, 8.4) IV 34/40 (85.0%) 36/42 (85.7%) -0.7 (-18.5, 17.0) V 1/1 (100%) 0/2 - Consistently High Responses Seen by Age, Gender and Renal Status

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Lefamulin Demonstrated High Response Rate Against All of the Most Common Causes of CABP 16 Lefamulin Moxifloxacin Microbiological ITT (microITT) N = 205 N = 186 Baseline Pathogen ECR (%) ECR (%) Gram Positive S. pneumoniae 110/123 89.4% 115/126 91.3% Penicillin Susceptible 19/25 76.0% 36/38 94.7% Penicillin Resistant 5/5 100% 4/4 100% Multi-Drug Resistant 8/8 100% 10/12 83.3% Macrolide-Resistant 8/9 88.9% 9/11 81.8% S. aureus 13/13 100% 6/6 100% MRSA 2/2 100% 1/1 100% ECR by Baseline Pathogen – Typical Pathogens [micro ITT]

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Lefamulin Demonstrated High Response Rate Against All of the Most Common Causes of CABP 17 ECR by Baseline Pathogen – Typical Pathogens [micro ITT] continued Lefamulin Moxifloxacin Baseline Pathogen ECR (%) ECR (%) Gram Negative H. influenzae 50/56 89.3% 44/48 91.7% M. catarrhalis 18/21 85.7% 11/11 100% Atypicals M. pneumoniae 20/20 100% 14/14 100% L. pneumophila 13/16 81.3% 16/17 94.1% C. pneumoniae 15/16 93.8% 12/12 100%

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LEAP 2 TRIAL SAFETY and TOLERABILITY DATA

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Overview of Adverse Events (mITT) Low Rates of Discontinuation Observed 19 Patients with at Least One Lefamulin (n=368) Moxifloxacin (n=368) Treatment Emergent AE (TEAE) 120 (32.6%) 92 (25.0%) AE Leading to Discontinuation of Study Drug 11 (3.0%) 8 (2.2%) AE Leading to Withdrawal from Study 5 (1.4%) 5 (1.4%) Serious AE (SAE) 17 (4.6%) 18 (4.9%) Treatment Related SAE - 1 (0.3%) Deaths within 30 days 3 (0.8%) 3 (0.8%)

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20 TEAE Lefamulin (n=368) Moxifloxacin (n=368) Diarrhea/ Loose Stools 45 (12.2%) 4 (1.1%) Nausea 19 (5.2%) 7 (1.9%) Vomiting 12 (3.3%) 3 (0.8%) Hypertension 5 (1.4%) 5 (1.4%) Respiratory Tract Infection Viral 5 (1.4%) 1 (0.3%) Gastritis 4 (1.1%) 2 (0.5%) Pneumonia 4 (1.1%) 1 (0.3%) Chronic Obstructive Pulmonary Disease 4 (1.1%) - Headache 4 (1.1%) 6 (1.6%) Urinary Tract Infection 3 (0.8%) 6 (1.6%) ALT Increased 3 (0.8%) 4 (1.1%) AST Increased 2 (0.5%) 4 (1.1%) Anemia - 4 (1.1%) Insomnia - 4 (1.1%) TEAEs > 1% in either arm: Safety Population (mITT)

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Treatment Emergent Adverse Events of Interest 21 TEAEs in 17.9% and 7.6% of patients receiving lefamulin and moxifloxacin, respectively Diarrhea/ Loose Stools was observed in 12.2% and 1.1% of patients receiving lefamulin and moxifloxacin, respectively 1 case of C. difficile infection was reported in the lefamulin treatment arm TEAEs in 1.1% and 0.5% of patients receiving lefamulin and moxifloxacin, respectively Low incidence of liver enzyme elevation in both treatment groups consistent with CABP patient population Gastrointestinal System Organ Class (SOC) Hepatobiliary SOC Cardiac Disorders SOC TEAEs in 2.2% and 2.4% of patients receiving lefamulin and moxifloxacin, respectively Changes in QT interval of potential clinical concern were uncommon and of similar frequency between treatment groups

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Gastrointestinal System Organ Class Adverse Events 22 Diarrhea/Loose Stools Diarrhea/loose stools were generally of short duration (approximately 2 days) and none led to discontinuation of lefamulin. Nausea Vomiting Nausea/vomiting generally mild and of limited duration. No patients discontinued due to nausea and two discontinued due to vomiting Most cases were mild and did not lead to discontinuation 71% 29% 0% Lefamulin (n=45/368) Mild Moderate Severe 84% 16% 0% Lefamulin (n=19/368) Mild Moderate Severe 75% 25% 0% Lefamulin (n=12/368) Mild Moderate Severe

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Treatment Emergent Adverse Events of Interest 23 TEAEs in 17.9% and 7.6% of patients receiving lefamulin and moxifloxacin, respectively Diarrhea/ Loose Stools was observed in 12.2% and 1.1% of patients receiving lefamulin and moxifloxacin, respectively 1 case of C. difficile infection was reported in the lefamulin treatment arm TEAEs in 1.1% and 0.5% of patients receiving lefamulin and moxifloxacin, respectively Low incidence of liver enzyme elevation in both treatment groups consistent with CABP patient population Gastrointestinal System Organ Class (SOC) Hepatobiliary SOC Cardiac Disorders SOC TEAEs in 2.2% and 2.4% of patients receiving lefamulin and moxifloxacin, respectively Changes in QT interval of potential clinical concern were uncommon and of similar frequency between treatment groups

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Maximum Post Baseline Liver Enzymes: Safety Population Low Incidence of Hepatic Enzyme Elevations 24 Lab Parameter Lefamulin Moxifloxacin Any Post Baseline ALT >3xULN 15/355 (4.2%) 17/361 (4.7%) >5xULN 7/355 (2.0%) 3/361 (0.8%) >10xULN 1/355 (0.3%) 0/361 Any Post Baseline AST >3xULN 12/355 (3.4%) 8/361 (2.2%) >5xULN 6/355 (1.7%) 5/361 (1.4%) >10xULN 1/355 (0.3%) 0/361 Any Post Baseline Total Bilirubin >1.5xULN 3/355 (0.8%) 3/361 (0.8%) >2xULN 2/355 (0.6%) 0/361 Any Post Baseline ALP >2xULN 14/357 (3.9%) 6/362 (1.7%) No subject met laboratory criteria for Hy’s Law

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Treatment Emergent Adverse Events of Interest 25 TEAEs in 17.9% and 7.6% of patients receiving lefamulin and moxifloxacin, respectively Diarrhea/ Loose Stools was observed in 12.2% and 1.1% of patients receiving lefamulin and moxifloxacin, respectively 1 case of C. difficile infection was reported in the lefamulin treatment arm TEAEs in 1.1% and 0.5% of patients receiving lefamulin and moxifloxacin, respectively Low incidence of liver enzyme elevation in both treatment groups consistent with CABP patient population Gastrointestinal System Organ Class (SOC) Hepatobiliary SOC Cardiac Disorders SOC TEAEs in 2.2% and 2.4% of patients receiving lefamulin and moxifloxacin, respectively Changes in QT interval of potential clinical concern were uncommon and of similar frequency between treatment groups

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Maximum Post Dose QTcF Changes from Baseline (mITT) 26 Parameter Lefamulin (n=368) Moxifloxacin (n=368) Any Post Baseline Increase >30 msec 56 (15.4%) 68 (18.5%) Any Post Baseline Increase > 60 msec 4 (1.1%) 7 (1.9%) Any Post Baseline Value > 500 msec 1 (0.3%) 2 (0.5%) Any Post Baseline Increase > 60 and a Value > 500msec - 1 (0.3%) Changes of potential clinical significance were uncommon

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LEAP Phase 3 Clinical Trials Achieved All Primary Endpoints

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LEAP Phase 3 Clinical Trials Achieved All Primary Endpoints 28 For both the IV-to-Oral and Oral Trials of Lefamulin Compared to Moxifloxacin for CABP FDA Primary Endpoint: ECR LEAP 1 LEAP 2 Delta (95% CI) 0.1 (-4.4, 4.5) Delta (95% CI) -2.9 (-8.5, 2.8)

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LEAP Phase 3 Clinical Trials Achieved All Primary Endpoints 29 For both the IV-to-Oral and Oral Trials of Lefamulin Compared to Moxifloxacin for CABP EMA Primary Endpoints: IACR in mITT and CE at TOC LEAP 1 LEAP 2 Delta (95% CI) -3.9 (-8.2, 0.5) Delta (95% CI) -2.6 (-8.9, 3.9) Delta (95% CI) --1.6 (-6.3, 3.1) Delta (95% CI) -2.5 (-8.4, 3.4) LEAP 1 LEAP 2

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30 % of Patients Discontinuing Study Drug Low Rate of Premature Discontinuations of Study Drug Across Phase 3 Program LEAP 1 IV to Oral LEAP 2 Oral Only

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Lefamulin: A Promising Potential Treatment Option for CABP Lefamulin met all primary FDA and EMA endpoints in both LEAP 1 and LEAP 2 trials 31 Complete Spectrum of Coverage of Main CABP Pathogens Monotherapy shown to provide the appropriate coverage with a low risk of C. difficile infection Generally Well Tolerated Profile Low rates of discontinuations due to adverse events New Class New Mechanism of Action Overcomes existing mechanism of resistance in vitro and low propensity for development of bacterial resistance Convenient for Patients in Hospital, Transition of Care and the Community Flexible IV and Oral formulations and short course of monotherapy Excellent PK-PD Profile No loading dose; no dose adjustment expected for renal or hepatic insufficiency; mild food interaction potential

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Acknowledgments 32 We are grateful for the participation and contributions of the following in the LEAP Program: Anita Das, Ph. D. Gary Moore, M.Sc. The Nabriva Therapeutics team Patients and families Clinical investigators and their staff Collaborating research organizations

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May 2018 Topline data from LEAP 2 Phase 3 trial for CABP Recent and Anticipated Lefamulin Milestones 33 Sept 2017 Topline data from LEAP 1 Phase 3 trial for CABP Mid 2018 Pediatric Study Initiation Q4 2018 Regulatory filing in US (priority review request to FDA) for CABP

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34 Gram Negative or MRSA Products Broad Spectrum Products CABP Focus with MRSA Coverage 34 CABP: Underserved by Anti-Infective Portfolios of Other Companies A Potentially Significant Opportunity for Lefamulin

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Nabriva: Addressing the Demand for New Antibiotics Lefamulin, the lead molecule of a new class of antibiotics in clinical development for CABP, demonstrated positive topline results in both the LEAP 1 and LEAP 2 Phase 3 trials, with an NDA filing expected in the fourth quarter of 2018 Pre-commercial activities initiated to optimize adoption at launch and long term potential for a large underserved market* Highly experienced management team in place to build a fully integrated anti-infective company Focused on creating value through innovation and business development 35 * Lefamulin is an investigational drug candidate and has not received regulatory approval for any indication. Information provided in this slide is based on research and development performed to date.

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Questions?

 

Exhibit 99.2

 

 

Nabriva Therapeutics Announces Positive Topline Results from Pivotal Phase 3 Clinical Trial of Oral Lefamulin for the Treatment of Community-Acquired Bacterial Pneumonia

 

- Lefamulin met all FDA and EMA primary endpoints
 and was shown to be generally well tolerated -

 

- Company plans to file a New Drug Application with the U.S. Food and Drug Administration
 in the fourth quarter of 2018 -

 

- Conference call and webcast today at 8:30 a.m. EDT to review topline data -

 

DUBLIN, Ireland and KING OF PRUSSIA, Pa., May 21, 2018 — Nabriva Therapeutics plc (NASDAQ: NBRV) today announced positive topline results from its Lefamulin Evaluation Against Pneumonia (LEAP 2) clinical trial, the second of two global, pivotal Phase 3 clinical trials of lefamulin.  LEAP 2 evaluated the safety and efficacy of 5 days of oral lefamulin compared to 7 days of oral moxifloxacin in adult patients with moderate community-acquired bacterial pneumonia (CABP). In September 2017, the company announced positive results from its first Phase 3 clinical trial, in which intravenous (IV) to oral lefamulin was found to be non-inferior to IV to oral moxifloxacin with or without linezolid.

 

In LEAP 2, lefamulin met the U.S. Food and Drug Administration (FDA) primary endpoint of non-inferiority (NI, 10.0% margin) compared to moxifloxacin for early clinical response (ECR) assessed 72 to 120 hours following initiation of therapy in the intent to treat (ITT) patient population. ECR was 90.8% for the 5-day treatment course of lefamulin and 90.8% for the 7-day treatment course of moxifloxacin (treatment difference 0.1 [95% confidence interval (CI) -4.4, 4.5]).

 

“Today marks an exciting advance in the treatment of CABP as we are one step closer to potentially making a much-needed new class of antibiotics available to patients and health care providers,” said Dr. Jennifer Schranz, chief medical officer of Nabriva Therapeutics. “Lefamulin has the potential to be the first-in-class pleuromutilin antibiotic available for IV or oral administration, and results from LEAP 2 provide additional evidence of its efficacy and tolerability in the treatment of adult patients with CABP. We believe lefamulin is well-suited for the empiric treatment of CABP given its short-course regimen, novel mechanism of action, targeted spectrum of activity against the most common and problematic CABP pathogens, and its safety and tolerability profile. I speak for the entire Nabriva team in acknowledging the participation of the patients, their families, investigators, and research organizations who contributed to the successful completion of this clinical trial.”

 

Lefamulin also met the European Medicines Agency (EMA) primary endpoint for non-inferiority (NI, 10.0% margin) compared to moxifloxacin based on an investigator assessment of clinical response (IACR) 5 to 10 days following the completion of study drug dosing in the modified intent to treat (mITT) and clinically evaluable at test of cure (CE-TOC) patient populations.  IACR rates for the mITT population were 87.5% for lefamulin and 89.1% for moxifloxacin (treatment difference -1.6 [95% CI -6.3, 3.1]) and for the CE-TOC population were 89.7% for lefamulin and 93.6% for moxifloxacin (treatment difference -3.9 [95% CI -8.2, 0.5]).

 



 

“Coupled with our successful LEAP 1 trial, the positive results from LEAP 2 suggest lefamulin could be an excellent empiric treatment option for patients with CABP and help address the problem of antibiotic resistance.  With these LEAP 2 results, we believe there is a significant opportunity for oral lefamulin as a 5-day treatment option for CABP in the community,” said Dr. Colin Broom, chief executive officer of Nabriva Therapeutics. “We are especially pleased with the high response rates for lefamulin in LEAP 1 and LEAP 2 and plan to file a New Drug Application with the FDA in the fourth quarter of 2018.  With these LEAP 2 results, we have achieved another important and rewarding milestone. My sincere appreciation goes to our highly dedicated Nabriva team who have worked diligently for over a decade to develop this novel antibiotic for patients in need.”

 

“Pneumonia is the leading cause of infection-related deaths and the second leading cause of total hospitalizations in the United States,” said Andrew Shorr, MD, MPH, MBA, Section Head, Pulmonary and Critical Care Medicine at MedStar Washington Hospital Center in Washington, DC and Professor of Medicine, at Georgetown University Washington, DC. “As bacterial resistance continues to increase, there is an urgent need for new, safe, and effective IV and oral treatment options for CABP.  The positive topline results from LEAP 1 and LEAP 2 indicate that lefamulin could provide health care providers with a new potential option in the treatment of CABP across the spectrum of care, ranging from the hospital to the community.”

 

Additional Clinical Trial Information

 

LEAP 2 was a global, randomized, double-blind, double-dummy trial that compared the efficacy and safety of 600 mg of oral lefamulin twice a day for 5 days versus 400 mg of oral moxifloxacin once daily for 7 days in 738 patients (370 in the lefamulin arm and 368 in the moxifloxacin arm).  The lefamulin arm enrolled 183 (49.5%), 145 (39.2%) and 40 (10.8%) patients with a Pneumonia Outcomes Research Team (PORT) class of 2, 3 and 4, respectively.  The moxifloxacin arm enrolled 189 (51.4%), 133 (36.1%) and 42 (11.4%) patients with a PORT class of 2, 3 and 4, respectively.  Almost all patients completed the study (95.8%) through late follow-up, which occurred 30 days after administration of the first dose of study medication.

 

In this trial, lefamulin was generally well tolerated.  The rate of treatment-emergent adverse events (TEAEs) was 32.6% in the lefamulin arm and 25.0% in the moxifloxacin arm.  Serious treatment emergent adverse events occurred in 4.6% of lefamulin-treated patients and 4.9% of moxifloxacin-treated patients. One related serious adverse event occurred in a moxifloxacin-treated patient (0.3%).  Death within 30 days occurred in three patients in each treatment arm (0.8%).

 

A low percentage of patients discontinued study drug in the lefamulin arm (6.8%) and in the moxifloxacin arm (7.6%).  TEAEs leading to discontinuation of study drug were uncommon and were observed in 3.0% of patients in the lefamulin arm and 2.2% of patients in the moxifloxacin arm.

 

Adverse events reported in greater than 1.0% of patients receiving study drug (lefamulin versus moxifloxacin) were diarrhea/loose stools (12.2% versus 1.1%), nausea (5.2% versus 1.9%), vomiting (3.3% versus 0.8%), hypertension (1.4% for both), respiratory tract infection viral (1.4% vs. 0.3%), headache (1.1% vs. 1.6%), gastritis (1.1% vs. 0.5%), pneumonia (1.1% vs.  0.3%), COPD (1.1% vs. 0%), urinary tract infection (0.8% vs. 1.6%), increased ALT (0.8% vs. 1.1%), increased AST (0.5% vs. 1.1%), anemia (0% vs. 1.1%), and insomnia (0% vs. 1.1%).  All cases of diarrhea/loose stools in the lefamulin arm were mild (71.1%) or moderate (28.9%) and were generally of short duration (approximately 2 days).  No cases were severe, and none led to discontinuation of study drug.  One patient who had a positive clinical response to lefamulin was later diagnosed with a C. difficile infection during an extended hospital stay.

 



 

In addition, hepatobiliary TEAEs occurred in 1.1% and 0.5% of subjects receiving lefamulin and moxifloxacin, respectively.  There was a low incidence of liver enzyme elevation in both treatment groups consistent with the CABP patient population.  Cardiac TEAEs were reported in 2.2% and 2.4% of patients receiving lefamulin and moxifloxacin, respectively.  Changes in QT interval of potential clinical concern were rare and of similar frequency between treatment groups.

 

Further analysis of the LEAP 2 trial results including analysis of additional patient population groups in the trial and secondary and exploratory endpoints related to these population groups is ongoing and additional results will be presented at upcoming scientific congresses.

 

Conference Call and Webcast

 

The Company will host a conference call and webcast at 8:30 a.m. EDT today. The live webcast can be accessed under “Events and Presentations” in the Investors section of Nabriva Therapeutics’ website at www.nabriva.com and will be accessible for 90 days. The conference call can also be accessed by dialing 1-866-811-8671 (U.S./Canada) or 1-409-981-0874 (international) and providing the passcode 7969239.

 

About LEAP 2 Study Design

 

LEAP 2 was a multi-center, randomized, controlled, double-blind, global study designed to evaluate the efficacy and safety of oral lefamulin compared to oral moxifloxacin, a fluoroquinolone antibiotic, in 738 adults with moderate CABP. Lefamulin was dosed orally at 600 mg every 12 hours for 5 days. Moxifloxacin was dosed according to the approved labeling, 400 mg orally once daily for 7 days. All patients to be enrolled in this trial were to have a Pneumonia Outcomes Research Team (PORT) risk class severity of 2, 3, or 4 on a scale of 1 to 5, which corresponds to moderate clinical disease. Randomization was 1:1 and was stratified by PORT risk class, geographic region, and exposure to prior antibiotics. No more than 25% of patients were allowed to have received a single dose of a short acting oral or IV antibacterial for the treatment of CABP and patients who received more than a single dose within 72 hours before randomization were excluded from participating.

 

For LEAP 2, the primary efficacy endpoint for the FDA was the proportion of patients in the ITT population achieving ECR.  ECR success is achieved for patients who were alive, had improvement in at least two of the four cardinal symptoms of CABP as outlined in the current FDA guidance, had no worsening in any of the four cardinal symptoms of CABP and had not received a concomitant antibiotic for the treatment of CABP up through 120 hours after the first dose of study drug. The four cardinal symptoms of CABP, as outlined in the current FDA guidance, are difficulty breathing, cough, production of purulent sputum and chest pain. The primary efficacy endpoint for the EMA was the clinical response rate at the test of cure visit for lefamulin in both the CE and mITT populations compared to moxifloxacin. Clinical response to treatment was based on the investigator’s assessment that the patient had complete resolution or significant improvement of all local and systemic signs and symptoms of infection such that no additional antibiotic treatment was administered for the treatment of the current episode of CABP.

 

About CABP

 

Based on Nabriva Therapeutics’ combined analysis of the U.S. Centers for Disease Control and Prevention’s 2007 National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey and 2013 data from the Healthcare Cost and Utilization Project, Nabriva Therapeutics estimates that more than 5 million adults are treated annually for CABP in the United States. Additionally, based on 2013 data from the Healthcare Cost and Utilization Project, Nabriva Therapeutics estimates that approximately 3 million of these adult CABP patients are diagnosed in an in-patient hospital and/or emergency department setting, where most are then treated with in-patient IV and oral antibiotics or out-patient oral antibiotics prescribed for use following hospital discharge or release.

 



 

About Nabriva Therapeutics plc

 

Nabriva Therapeutics is a biopharmaceutical company engaged in the research and development of new medicines 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. 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 CABP in more than a decade. Based on results from its two global, Phase 3 clinical trials, 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  favorable tolerability profile, with the results of its two global, pivotal trials showing a rate of treatment-emergent adverse events comparable to a fluoroquinolone antibiotic for CABP. Nabriva Therapeutics is evaluating the continued development of lefamulin for additional indications and is developing a formulation of lefamulin appropriate for pediatric use.

 

Forward-Looking Statements

 

Any statements in this press release about future expectations, plans and prospects for Nabriva Therapeutics, including but not limited to statements about the development of Nabriva Therapeutics’ product candidates, the clinical utility of lefamulin for CABP Nabriva Therapeutics’ plans for filing of regulatory approvals, 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, Nabriva Therapeutics’ plans to enter into arrangements with external collaborators, the sufficiency of Nabriva Therapeutics’ existing cash resources 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, whether results of Nabriva Therapeutics’ Phase 3 clinical trials of lefamulin are indicative of the clinical utility of lefamulin for CABP, 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 Nabriva Therapeutics’ annual and quarterly reports on file with the U.S. Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Nabriva Therapeutics’ views as of the date of this release. Nabriva Therapeutics anticipates that subsequent events and developments will cause its views to change. However, while Nabriva Therapeutics 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 Nabriva Therapeutics’ views as of any date subsequent to the date of this release.

 

CONTACTS:

 

FOR INVESTORS
Dave Garrett

 



 

Nabriva Therapeutics plc
david.garrett@nabriva.com
610-816-6657

 

FOR MEDIA
Benjamin Navon
W2O Group
bnavon@w2ogroup.com
617-337-4166