Top-Line Data Results Omadacycline in Acute Skin and Skin Structure - - PowerPoint PPT Presentation

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Top-Line Data Results Omadacycline in Acute Skin and Skin Structure - - PowerPoint PPT Presentation

ABSSSI-16301 Study Design: Top-Line Data Results Omadacycline in Acute Skin and Skin Structure Infections Study (OASIS-2) A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare the Safety and Efficacy of Oral Omadacycline to


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Omadacycline in Acute Skin and Skin Structure Infections Study (OASIS-2)

A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare the Safety and Efficacy of Oral Omadacycline to Linezolid for Treating Adult Subjects with ABSSSI

17 July 2017

ABSSSI-16301 Study Design: Top-Line Data Results

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Certain statements in this presentation, including responses to questions, contain or may contain “forward-looking statements” within the meaning

  • f the Private Securities Litigation Reform Act of 1995. Examples of such statements include, but are not limited to, statements about our strategy,

future operations, prospects, plans, objectives of management, availability of data from our clinical studies, potential use of our product candidates, including Omadacycline and Sarecycline, the market acceptance of our product candidates, the strength of, and protection offered by, our intellectual property position, the potential clinical risks and efficacy of, and market opportunities for, our product candidates, the timing and stability of our supply chain, the timing of clinical development of, and regulatory approval for, our product candidates, and the nature and timing of our collaboration agreements with respect to our product candidates. The words “anticipate,” “estimate,” “expect,” “potential,” “will,” “project” and similar terms and phrases are used to identify forward-looking statements. These statements are based on current information and belief and are not guarantees of future performance. Our ability to predict results, financial or otherwise, or the actual effect of future plans or strategies, is inherently uncertain and actual results may differ from those predicted depending on a variety of factors. Our operations involve risks and uncertainties, many

  • f which are outside our control, and any one of which, or a combination of which, could materially affect our results of operations or whether the

forward-looking statements ultimately prove to be correct. Except as required by law, we undertake no obligation to publicly update any forward- looking statement, whether as a result of new information, future events or otherwise. Among the risks and uncertainties that could cause actual results to differ materially from those indicated by such forward-looking statements include: delays in clinical trials or unexpected results; the risk that data to date and trends may not be predictive of future results; the failure of collaborators to perform obligations under our collaboration agreements; our failure to obtain regulatory approval for our product candidates; if we obtain regulatory approval for our product candidates, the risk that the terms of such approval may limit how we manufacture and market our product candidates; delays in our supply chain, delays in undertaking or completing clinical trials; our products not gaining the anticipated acceptance in the marketplace or acceptance being delayed; our products not receiving reimbursement from healthcare payors; the effects of competition; our inability to protect our intellectual property and proprietary technology through patents and other means; the need for substantial additional funding to complete the development and commercialization of our product candidates; and the other risks described in the “Risk Factors” section and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2016, and our other filings with the SEC.

Safe Harbor Statement

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Omadacycline in Acute Skin and Skin Structure Infections Study (OASIS-2)

Michael Bigham

CEO and Chairman of the Board

Evan Loh, MD

President, COO, and CMO

ABSSSI-16301 Study Design: Top-Line Data Results

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Acute Bacterial Skin and Skin Structure Infections

Unmet need for antibiotics (especially oral

  • ptions) to treat serious ABSSSI infections

– Hospital admissions up 73% between 1997-2011 – Average hospital stay 5.2 days at approx. $10,000 / stay – Tetracyclines (e.g., oral doxycycline) emerged as important

  • ptions for ABSSSI caused by MRSA, however, use is

limited by resistance

Omadacycline has potential to meet this need

– Potent activity against most common ABSSSI pathogens (including MSSA/MRSA, Group A Strep) – Oral and IV option – Circumvents common tetracycline resistance mechanisms – Important treatment option for patients who can’t receive

  • ther antimicrobial classes (e.g., intolerance or bacterial

resistance leading to poor response) Cellulitis Abscess on the back Suture abscess and cellulitis

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Phase 3 Trial Design for OASIS-2 (ABSI-16301)

Designed to Satisfy FDA and EMA Requirements

[1] 720 mITT Subjects with qualifying infections [2] Early Clinical Response = primary end point for FDA. [3] PTE end point = Co-primary end points confirmed through EMA scientific advice.

d2-3

FDA - Early Clinical Response[2]

d7 to d14

End of Treatment

d1

Oral Omadacycline Oral Linezolid

ABSSSI

735 patients[1]

7-14d after last treatment day

EMA - Post-Treatment Evaluation[3]

Day 1 Day 2 Day 3 and beyond

0h 12h 24h 36h

Omadacycline

450 mg 450 mg After Day 2: 300mg oral once daily Oral Oral

Linezolid

600mg 600mg 600mg 600mg 600mg oral twice daily Oral Oral Oral Oral

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Demographics, Baseline Characteristics, and Subject Disposition

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Key Study Populations

Balanced Between Treatment Arms

ITT: all subjects who were randomized Safety: subjects who received test article mITT: randomized subjects without a sole Gram-negative causative pathogen at screening micro-mITT: Consists of subjects in mITT with at least one Gram-positive causative bacterial pathogen CE-PTE: mITT subjects who received test article, had a qualifying ABSSSI, an assessment of outcome at PTE, and met other key evaluability criteria

Population Omadacycline n (%) Linezolid n (%) All subjects n (%) ITT 368 367 735 Safety 368 (100.0) 367 (100.0) 735 (100.0) mITT 360 (97.8) 360 (98.1) 720 (98.0) micro-mITT 276 (75.0) 287 (78.2) 563 (76.6) CE-PTE 284 (77.2) 292 (79.6) 576 (78.4)

Source: 14.1.1.2

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Safety Population Demographics

Balanced Between Treatment Arms

Characteristics Omadacycline (n=368) Linezolid (n=367) All Subjects (n=735) Gender n (%) Female 126 (34.2) 147 (40.1) 273 (37.1) Male 242 (65.8) 220 (59.9) 462 (62.9) Age (years) Mean (SD) 42.8 (12.72) 44.5 (13.11) 43.7 (12.94) Median 41.0 46.0 43.0 Min, Max 18, 86 20, 84 18, 86 Categorical Age (years) n (%) 18-45 213 (57.9) 183 (49.9) 396 (53.9) >45-65 141 (38.3) 164 (44.7) 305 (41.5) >65-75 11 (3.0) 12 (3.3) 23 (3.1) >75 3 (0.8) 8 (2.2) 11 (1.5) Weight (kg) n 368 367 735 Mean (SD) 81.62 (18.286) 80.15 (19.778) 80.89 (19.047) Median 79.40 76.20 77.70 Min, Max 41.7, 167.0 44.5, 156.3 41.7, 167.0 BMI (kg/m^2) n 368 367 735 Mean (SD) 27.91 (6.472) 27.93 (6.556) 27.92 (6.510)

Source: 14.1.2.1

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Type of Primary Infection

Balanced Between Treatment Arms

Characteristics Omadacycline (n=360) n (%) Linezolid (n=360) n (%) Type of Primary Infection 360 360 Wound Infection 210 (58.3) 214 (59.4) Cellulitis/erysipelas 86 (23.9) 84 (23.3) Major Abscess 64 (17.8) 62 (17.2)

Source: 14.1.4.1.1

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Subject Disposition – ITT Population (Completed Study Treatment)

High Percentage of Patients Completing Treatment

Parameter/Category Omadacycline (n=368) n (%) Linezolid (n=367) n (%) All Subjects (n=735) n (%) Randomized 368 (100.0) 367 (100.0) 735 (100.0) Completed Study Treatment 328 (89.1) 315 (85.8) 643 (87.5) Prematurely Discontinued from Study Treatment 40 (10.9) 52 (14.2) 92 (12.5) Reason For Premature Discontinuation from Study Treatment Adverse Event 6 (1.6) 4 (1.1) 10 (1.4) Lost to Follow-up 18 (4.9) 25 (6.8) 43 (5.9) Withdrawal by Subject 6 (1.6) 8 (2.2) 14 (1.9) Physician Decision 3 (0.8) 7 (1.9) 10 (1.4) Death Other 7 (1.9) 8 (2.2) 15 (2.0)

Source: 14.1.1.4.1

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Efficacy Results

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Primary Endpoints Achieved for Both FDA and EMA

87.5 84.2 97.9 82.5 80.8 95.5

10 20 30 40 50 60 70 80 90 100

mITT Early Clinical Response mITT PTE - Clinical Success CE-PTE - Clinical Success Clinical Success (%) Omadacycline Linezolid

EMA Co-Primary Endpoints

Delta (95% CI) +5.0 (-0.2, 10.3) Delta (95% CI) +3.3 (-2.2, 9.0) Delta (95% CI) +2.3 (-0.5, 5.8)

FDA Primary Endpoint

Source: 14.2.1.1.1 and 14.2.2.1.1

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Clinical Success at PTE by Gram-Positive Baseline Pathogen

Highly Effective Across Key Pathogens

Omadacycline (n=276) Linezolid (n=287) Baseline Pathogen n1 Clinical Success n (%) n1 Clinical Success n (%) Staphylococcus aureus 220 182 (82.7) 233 186 (79.8) MRSA 104 89 (85.6) 107 85 (79.4) MSSA 120 97 (80.8) 130 103 (79.2) Staphylococcus lugdunensis 5 4 (80.0) Streptococcus pyogenes 29 20 (69.0) 16 9 (56.3) Streptococcus anginosus group 57 49 (86.0) 45 33 (73.3) Streptococcus anginosus 27 24 (88.9) 20 16 (80.0) Streptococcus intermedius 23 18 (78.3) 24 16 (66.7) Streptococcus constellatus 9 8 (88.9) 7 5 (71.4) Enterococcus faecalis 8 8 (100.0) 12 9 (75.0) VRE 2 2 (100.0) VSE 7 7 (100.0) 10 7 (70.0)

Source: 14.2.2.6.1

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Safety Results

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Overview of Adverse Events – Safety Population

1TEAE is defined as an AE occurring after first dose of active test article

Parameter Omadacycline (n=368) n (%) Linezolid (n=367) n (%) Subjects with at Least One, n (%) Adverse Events (AE) 201 (54.6) 140 (38.1) Treatment Emergent Adverse Event (TEAE)1 197 (53.5) 137 (37.3) Drug-Related TEAE 139 (37.8) 52 (14.2) Severe TEAE 6 (1.6) 7 (1.9) Serious TEAE 5 (1.4) 5 (1.4) Drug-Related Serious TEAE 1 (0.3) Serious TEAE leading to Death 1 (0.3) TEAE leading to premature discontinuation of test article 6 (1.6) 3 (0.8) TEAE leading to premature discontinuation of study 3 (0.8) 1 (0.3) Serious TEAEs leading to premature discontinuation of test article 3 (0.8) 2 (0.5) Subjects who died, n (%) 1 (0.3)

Source: 14.3.1.1

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Most Frequent TEAEs (> 3%) – Safety Population

1Nausea:

Omadacycline = 75% mild and 25% moderate. Linezolid = 78.1% mild and 21.9% moderate. One patient on omadacycline arm discontinued due to nausea and vomiting .

Preferred Term (PT) Omadacycline (n=368) n (%) Linezolid (n=367) n (%) Subjects with at Least One TEAE 197 (53.5) 137 (37.3) Nausea1 111 (30.2) 28 (7.6) Vomiting 62 (16.8) 11 (3.0) Wound Infection 22 (6.0) 17 (4.6) ALT Increased 19 (5.2) 11 (3.0) AST Increased 17 (4.6) 12 (3.3) Diarrhea 15 (4.1) 10 (2.7) Headache 13 (3.5) 8 (2.2) Cellulitis 12 (3.3) 9 (2.5)

Source: 14.3.1.1.2.1

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Liver Chemistry - Safety Population

Low Incidence of Elevated LFTs – No Hy’s Law Cases Observed1

Lab Parameter Visit Elevation Omadacycline (n=368) n (%) Linezolid (n=367) n (%) ALT (U/L) Normal at Baseline, n 257 292 Worst post-baseline time point, n 251 286 >3 x ULN 3 (1.2) 13 (4.5) >5 x ULN 2 (0.8) 2 (0.7) >10 x ULN 2 (0.8) 2 (0.7) AST (U/L) Normal at Baseline, n 279 285 Worst post-baseline time point, n 272 280 >3 x ULN 5 (1.8) 10 (3.6) >5 x ULN 3 (1.1) 3 (1.1) >10 x ULN 2 (0.7) 1 (0.4) BILI (umol/L) Normal at Baseline, n 291 296 Worst post-baseline time point, n 284 287 >1.5 x ULN 4 (1.4) 1 (0.3) >2 x ULN 3 (1.1)

1One omadacycline patient with acute hepatitis B infection unrelated to test article experienced elevated AST, ALT, and BILI on treatment

Source: 14.3.3.2.4

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Notable Cardiovascular Increases at Any Post Baseline Time Point

Safety Population: Balanced Between Treatment Arms

Clinically Notable Criteria Omadacycline (n=368) n (%) Linezolid (n=367) n (%) Subjects with Pulse Rate value at any Post-Baseline visit 368 367 Pulse Rate >= 120 bpm 7 (1.9) 11 (3.0) Subjects with Pulse Rate and change from baseline at any Post-Baseline visit 367 367 Pulse Rate >= 120 bpm and Increase of >= 15 bpm 6 (1.6) 9 (2.5) Number of subjects with baseline and post-baseline QTcF 317 310 Subjects with Baseline QTcF <= 450 and any Post-Baseline QTcF > 450 msec 4 (1.3) 9 (2.9) Subjects with Baseline QTcF <= 500 and any Post-Baseline QTcF > 500 msec Blood Pressure value at any Post-Baseline visit 368 367 Systolic Blood Pressure >= 180 mmHg 6 (1.6) 3 (0.8) Diastolic Blood Pressure >= 105 mmHg 22 (6.0) 10 (2.7) Blood Pressure and change from baseline at any Post-Baseline visit 367 367 Systolic Blood Pressure >= 180 mmHg and Increase of >= 20 mmHg 5 (1.4) 2 (0.5) Diastolic Blood Pressure >= 105 mmHg and Increase of >= 15 mmHg 17 (4.6) 9 (2.5)

Source: 14.3.4.2.1 and 14.3.5.2

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Establishing the Safety and Efficacy of Once-Daily Omadacycline in ABSSSI and CABP

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OASIS-1 (ABSSSI) OASIS-2 (ABSSSI) OPTIC (CABP) Pooled Phase 2-3 Adverse Event Omadacycline (n=323) Omadacycline (n=368) Omadacycline (n=382) Omadacycline (n=1252) Nausea 12.4 % 30.2 % 2.4% 15.3 % Vomiting 5.3 % 16.8 % 2.6 % 8.0 % Headache 3.1 % 3.5 % 2.1 % 4.3 % ALT increased 2.8 % 5.2 % 3.7 % 3.7 % AST increased 2.5 % 4.6 % 2.1 % 3.0 % Diarrhea1 2.2 % 4.1 % 1.0 % 2.6 %

Omadacycline is Generally Safe and Well Tolerated

Most Frequent Adverse Events Across Skin Infections and CABP Studies

1 No cases of C. diff were reported across any study

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OASIS-2

ABSSSI

OPTIC

CABP

All Other1

OASIS-1

ABSSSI

Adverse Event

Premature Discontinuation from Study Treatment

Low Discontinuation Rates Across All Pivotal Phase 3 Studies

1.8 2.1 8.2 9.6 10.0 11.7

5 10 15

Omadacycline Linezolid Discontinuation, % 1.6 1.1 9.3 13.1 10.9 14.2 Omadacycline Linezolid 4.4 7.2 4.4 3.6 8.8 10.8 Omadacycline Moxifloxacin

1 All Other: Lost to Follow-up, Withdrawal by Subject, Physician Decision, Death, Other

All Other1 Adverse Event

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81.1 82.7

10 20 30 40 50 60 70 80 90 100

OPTIC Omadacycline Moxifloxacin

Omadacycline Efficacious in ABSSSI and CABP

Robust & Consistent Efficacy (Early Clinical Response - FDA Primary Endpoint) ABSSSI CABP

87.5 82.5 OASIS-2 84.8 85.5

10 20 30 40 50 60 70 80 90 100

OASIS-1 % %

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86.1 84.2 83.6 80.8

10 20 30 40 50 60 70 80 90 100 OASIS-1 OASIS-2

96.3 97.9 93.5 95.5

OASIS-1 OASIS-2

88.4 92.5 85.2 90.5

10 20 30 40 50 60 70 80 90 100 OPTIC OPTIC

ABSSSI CABP

Omadacycline Efficacious in ABSSSI and CABP

Robust & Consistent Efficacy (PTE - EMA Primary Endpoint)

mITT CE ITT CE % %

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Clinical Development Program Required for Submission is Complete

– OASIS-1 and OPTIC meet our 1+1 SPA agreement supporting approval of CABP and ABSSSI – OASIS-2 provides support for oral only dosing at time of initial approval

Robust and Consistent Efficacy Observed for Omadacycline Across All Three Studies

– Omadacycline met ALL primary and secondary FDA and EMA endpoints in each study

Omadacycline Was Generally Safe and Well Tolerated

– Low discontinuation rate for patients on omadacycline and comparators – Changes in Liver chemistries similar for omadacycline and comparators; no Hy’s Law cases in any study

Positive Benefit Risk for Omadacycline in Support of NDA submission Pre-NDA FDA Discussions Planned for Later This Summer NDA Submission on Track, as Early as 1Q2018

Conclusions