Current Report Filing (8-k)
24 Mars 2015 - 1:02PM
Edgar (US Regulatory)
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): March 24, 2015
INSMED INCORPORATED
(Exact name of registrant as specified in its charter)
Virginia |
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0-30739 |
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54-1972729 |
(State or other jurisdiction of incorporation) |
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(Commission File Number) |
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(I.R.S. Employer Identification No.) |
10 Finderne Avenue, Building 10 Bridgewater, NJ |
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08807 |
(Address of principal executive offices) |
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(Zip Code) |
Registrants telephone number, including area code: (908) 997-9900
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 March 24, 2015, Insmed Incorporated (the Company) will host a live webcast of the senior management presentations at its Analyst and Investor Day. The Company has made available on its website (www.insmed.com) a slide presentation dated March 24, 2015 that is intended to accompany the live webcast. The slide presentation is attached hereto as Exhibit 99.1 and is incorporated herein by reference.
The information in this Current Report on Form 8-K shall not be deemed filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the Exchange Act), or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. |
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Description |
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99.1 |
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Insmed Incorporated Analyst and Investor Day Presentation, dated March 24, 2015 |
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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.
Dated: March 24, 2015 |
INSMED INCORPORATED |
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By: |
/s/ Christine Pellizzari |
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Name: |
Christine Pellizzari |
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Title: |
General Counsel and Corporate Secretary |
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Exhibit
99.1
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Insmed
Copyright 2015 © All Rights Reserved. Analyst and Investor Day March 24, 2015
NASDAQ: INSM
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2 Agenda I. Introduction
and Overview Will Lewis II.NTM Lung Disease & Clinical Trials Dr.
Gina Eagle III. Regulatory Peggy Berry IV. Research and Development INS1009
Dr. Walter Perkins and Dr. Gene Sullivan I. Global Commercial Plan &
Corporate Development Wes Kaupinen, Dr. Olaf Bartsch, Drayton Wise and
Kevin McDermott II. Tech Ops, Cash and Tax Planning Andy Drechsler III. Q&A
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3 Safe Harbor
Statement ARIKAYCE is a trademark of Insmed Incorporated in the United States
and various other countries. eFlow® Electronic Nebulizer (eFlow®) is a
registered trademark of PARI Pharma GmbH. TOBI (Tobramycin Inhalation
Solution) is a registered trademark of Novartis. Cayston (aztreonam for
inhalation solution) is a registered trademark of Gilead Sciences. All other
trademarks and registered trademarks are the property of their respective
owners. Persons shown throughout this presentation are models used for
illustrative purposes and are not patients. This presentation contains
forward-looking statements. Words, and variations of words, such as
"intend," "expect," "will,"
"anticipate," "believe," "continue,"
"propose" and similar expressions are intended to identify
forward-looking statements. Investors are cautioned that such statements in
this presentation, including statements relating to the status, results and
timing of clinical trials and clinical data, the anticipated benefits of Insmed's
products, the anticipated timing of regulatory submissions, and the ability
to obtain required regulatory approvals, bring products to market and
successfully commercialize products constitute forward-looking statements
that involve risks and uncertainties that could cause actual results to
differ materially from those in the forward-looking statements. Such risks
and uncertainties include, without limitation, failure or delay of European,
Canadian, U.S. Food and Drug Administration and other regulatory reviews and
approvals, competitive developments affecting Insmeds product candidates,
delays in product development or clinical trials or other studies, patent
disputes and other intellectual property developments relating to Insmeds
product candidates, unexpected regulatory actions, delays or requests, the
failure of clinical trials or other studies or results of clinical trials or
other studies that do not meet expectations, the fact that subsequent
analyses of clinical trial or study data may lead to different (including
less favorable) interpretations of trial or study results or may identify
important implications of a trial or study that are not reflected in the
statements contained in this presentation, and the fact that trial or study
results or subsequent analyses may be subject to differing interpretations by
regulatory agencies, the inability by Insmed to successfully develop its
product candidates or receive necessary regulatory approvals, the inability
by Insmed to make product candidates commercially successful, changes in
anticipated expenses, changes in Insmeds financing requirements or ability
to raise additional capital, and other risks and challenges detailed in our
filings with the U.S. Securities and Exchange Commission, including, without
limitation, our Annual Report on Form 10-K for the year ended December 31,
2014. Investors are cautioned not to place undue reliance on any
forward-looking statements that speak only as of the date of this
presentation. Insmed undertakes no obligation to update these forward-looking
statements to reflect events or circumstances or changes in its expectations.
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4 Insmed Company
Vision We are building a self-sustaining biopharmaceutical company focused on
patient needs at the intersection of orphan and pulmonary disease
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5 Insmeds
Orphan Product Portfolio ARIKAYCE liposomal amikacin for inhalation INS1009
inhaled treprostinil-prodrug NTM PAH Additional Programs in Orphan Diseases
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6 2015 The
Year of the Deliverables I. Enroll the 212 NTM Global Phase 3 Trial II. Pursue
European Approval of ARIKAYCE NTM & CF III. Continue Manufacturing
Build-out and Redundancy Planning IV. Submit IND for INS1009 and Enroll Phase
1 Trial V. Corporate Development
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7 Team
Introduction Introduction & OverviewWill Lewis NTM Disease & Clinical
TrialsDr. Gina Eagle Regulatory Peggy Berry R&D, INS1009 & IP Dr.
Walter Perkins Dr. Gene Sullivan Tech Ops, Cash and Tax Planning Andy
Drechsler Global Commercial Plan& Corporate Development Wes Kaupinen
Drayton Wise Dr. Olaf Bartsch
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8 NTM Lung
Disease & Clinical Trials Dr. Gina Eagle
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9 ARIKAYCE
liposomal amikacin for inhalation INS1009 inhaled treprostinil-prodrug NTM
PAH Additional Programs in Orphan Diseases ARIKAYCETM NTM and CF
Indications
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10
Nontuberculous Mycobacteria (NTM) Lung Infections Rx No Approved Treatmentin
US and EU Progressive Lung Disease and Increased Mortality in High Risk
Patient Groups Common in: Source: Company website; Clarity Pharma Research;
American Journal of Respiratory and Critical Care Medicine; American Lung
Association; UCSF Medical Center.; Medscape Education; NTM Info and Research;
Prevots (2010) 10 COPD, bronchiectasis, asthma and CF
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11Source:
Company website; Clarity Pharma Research; American Journal of Respiratory and
Critical Care Medicine; AmericanLung Association; UCSF Medical Center.;
Medscape Education; NTM Info and Research; Prevots (2010); (a) Adjemian et al
2012; (b) Yutaki, January 2015 Journal of Infection and chemotherapy); (c)
Marras 2007 ; (d) Ringhausen 2013, Panagiotou 2014 ; (e) Thomson 2010 11
Nontuberculous Mycobacteria (NTM) Lung Infections © INSCALE GmbH, 05.05.2010
http://www.presentationload.com/US a 55-70K © INSCALE GmbH, 05.05.2010
http://www.presentationload.com/Diagnosed Patients Treatment Resistant Populations
(estimate) EU d Japan b Australia e Canada c 30K 20K within EU5 30K 5-10K
5-10K 10-20K 5-10K 5-10K 1-2K 1-2K +13% +6% +9% +9% +11% Annual Prevalence
Increase
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12 Patient
Journey Is Long and Difficult for Most Only a few are diagnosed correctly
from the outset Symptom Presentation Seek out Physician Mis-diagnosis
Treatment initiation Symptom persistence Physician Referral/Change Diagnosis
correction Treatment initiation Living with NTM (NTM Management) Primary Care
Doctor Pulmonary Doctor Infectious Disease Dr. COPD Flu Bronchitis Asthma
Misdiagnosis Phase Tuberculosis Lung Cancer
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13 NTM Lung
Disease Risk Factors and Mortality
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14 To date
>150 identified NTM species .MAC (Mycobacterium avium Complex) is the most
common .Ubiquitous organisms: found in soil and water .Animal to human and
human to human transmission not widely documented .Asymptomatic infections
and symptomatic disease is possible with many NTM species Nontuberculous
Mycobacterium (NTM) Overview
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15
Nontuberculous Mycobacterial Pulmonary Pathogens } M. Avium Complex (MAC)
Common M. avium M. intracellulare M. kansasii M. abscessus M. chelonae
Infrequent M. xenopi (zin oh pee) M. szulgai (sull guy) M. malmoense (mal
moh en suh) M. fortuitum Rare M. celatum (sell ah tum) M. scrofulaceum M.
simiae M. terrae M. immunogenum Never (almost) M. gordonae
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16 Risk Factors
in MAC Lung Disease 5-year-all-cause overall mortality (Ito et al*): 25.6%
.untreated chronic MAC patients: 33.3% .treated MAC patients: 22.2% p = 0.30
Adjusting for clinical, microbiological and radiological confounders,
independent factors for 5-year mortality were a high Charlson comorbidity
index and presence of cavitary lesions Conclusion: Patients with cavitary
lesions require immediate treatment for sputum culture conversion and to
improve their chances of survival *Ito et al INT J TUBERC LUNG DIS
16(3):408414; A study of 78 patients with definite MAC disease (including
treated and untreated chronic MAC patients) Hazard Ratio (HR) Comparisons
High Charlson Comorbidity Index Presence of Cavitary Lesions Definite MAC HR
1.76 HR 1.82 Untreated chronic MAC HR 3.08 HR 3.91
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17 Risk Factors
in MAC Lung Disease Literature on Risk Factors in MAC Lung Disease Advanced
Stage at Diagnosis Cavitary Lung Low BMI Macrolide- Resistance at Diagnosis
Ito et al INT J TUBERC LUNG DIS 16(3):408414 . Masao Okumura et al, Inter
Med 47: 1465-1472, 2008 DOI: 10.2169/internalmedicine.47.1114 . . Kim et al
INT J TUBERC LUNG DIS 18(6):730736 . .* Kitada INT J TUBERC LUNG DIS
16(5):660664 . . . *21.0 kg/m2 and more than four lung segments involved had
a 240-fold increased risk of deterioration (P , 0.001)
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18 High Risk
Factor: Cavitary Lung
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19 NTM Lung
Disease Advantages of LAI
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20 Liposomal
Amikacin for Inhalation (LAI) .Amikacin is an aminoglycoside antibiotic with
in vitro evidence of activity against NTM .Novel liposomal formulation for
inhalation via nebuliser .High lung Cmax, AUC, and t½ improved AUC:MIC ratio
.Liposomes have a neutral charge and can be taken up by lung macrophages allowing
intracellular delivery of drug into infected cells that harbor nontuberculous
mycobacteria (NTM) while maintaining normal macrophage function .Low serum
Cmax and low bioavailability (<12%) .Decreased potential for systemic
toxicity such as renal and ototoxicity
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21 NTM Lung
Disease Recap of Study 112
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22 Study 112:
Study Design Randomized 90 Subjects (1:1): Stratified: CF vs non-CF MAC vs M.
abscessus Primary Endpoint: Efficacy Change on Semi-Quantitative Scale for
mycobacterial culture at Day 84 Screening perioda,b,cDay 42to Day 2 12
Weeks Once-Daily Dosing Background therapyd+ LAI* once daily by eFlow® Day 1
Background therapyd + placebo once daily by eFlow Day 1 Day 85 Day 168 12
Weeks Once-Daily Dosing, Open-Label 28-Day follow-up No inhaled antibiotics
LAI once daily by eFlow a2007 American Thoracic Society/Infectious Diseases
Society of America (ATS/IDSA) criteria with evidence of nodular
bronchiectasis and/or fibrocavitary disease by chest computed tomography
scan. bAt least 2 documented positive cultures in the prior 2 years, of which
at least 1 was obtained in the 6 months prior to screening. cReceiving
ATS/IDSA guideline-based treatment for at least 6 months prior to screening
with persistently positive cultures. dContinuing on ATS/IDSA guideline-based
therapy. R 4 Weeks CF=cystic fibrosis; LAI=liposomal amikacin for inhalation;
MAC=Mycobacterium avium complex.
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23 Study 112 :
Patient Profiles 0 5 10 15 20 25 30 35 40 6 - 12 Months >12 - 24 Months
>24 Months Patients (n) Length of Time on NTM Treatment Regimen Prior to
Baseline Lesion Type N(%) Cavitary 6 (6.70%) Nodularand Cavitary 63 (70.0%)
Nodular 21 (23.3%) Lung Lesion Type on HRCTscan at Baseline
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24 Study 112:
Recap of Main Results . Reduction in mycobacterium burden (numerically
superior, not statistically significant) .Achievement of a negative sputum
culture in 11 out of 44 patients at Day 84 (statistically significant)
.Safety: more frequent respiratory events; consistent similar inhaled
antibiotics 25.0%25.0% 6.7% 6.7% 0% 5% 10% 15% 20% 25% ARIKAYCE + Standard of
Care Placebo + Standard of Care Percent of patients whose sputum culture
tested negative for NTM at Day 84 (mITT population.) (11/44)(11/44) (3/45)
(3/45)
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25 Study 112:
Patients with at least 1 negative sputum culture for NTM Treatment Arm CF
Status NTM Oragnism Length of NTM Prior to Baseline (Months) Baseline Day 28
Day 56 Day 84 Day 112 Day 140 Day 16828 24>24>24>24 Broth Broth
>24 >12 - 24 Early Term Resp 12 - 24>12 - 24>12 - 24>12 -
24>12 - 24 Broth Broth Broth 6 - 126 - 12 Broth 6 - 126 - 12 Broth M.
abscessus >12 - 24MAC >12 - 24 Early Term">246 -
12>24>24>24>12 - 24>12 - 24>12 - 24>12 - 24 Broth 6 - 12
Early Term FEV1 - 12 Broth>24>24 PBON on-CF Patient MACM. abscessus
LAIN on-CFMACCFM. abscessus
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26 Study 112:
Patients with Sputum Culture Conversion* Treatment Arm CF Status NTM Oragnism
Length of NTM Prior to Baseline (Months) Baseline Day 28 Day 56 Day 84 Day
112 Day 140 Day 16828 24>24>24>24 Broth Broth>24>12 - 24>12
- 24>12 - 24>12 - 24 Broth Broth Broth 6 - 126 - 12 Broth 6 - 12
Broth>24>24>12 - 24 Broth 6 - 12 Broth M.abscessus >24
LAINon-CFMACPBO Non-CF Patient MAC *ATS definition of conversion = 3
consecutive monthly negative sputum cultures
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27 Study 112: 6
Minute Walk Test -60 -50 -40 -30 -20 -10 0 10 20 30 40 0 28 56 84 112 Least
Squares Mean (SE) Study Day Change From Baseline in 6MWT Distance Missing
Values Excluded (mITT Population) Arikayce Placebo P= .009
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28 Study 112:
Safety Recap 0% 10% 20% 30% 40% 50% Chest discomfort Wheezing Pyrexia Fatigue
Nausea Haemoptysis Oropharyngeal pain Cough Dysphonia Infective exacerbation
of bronchiectasis LAI (n=44) Placebo (n=45) LAI, liposomal amikacin for
inhalation. Treatment-Emergent Adverse Events with >10% occurrence Through
End of Open-label Phase (Safety Population)
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29 NTM Lung
Disease Study 212
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30 Study
212-Global Sites North America . United States (34) . Canada (5) Europe . UK (15) . Germany (13) . Italy (12) . Spain (7) . France (6) Europe . Poland (4) . Austria (2) . Netherlands (1) Asia-Pac . Australia (17) . Japan (8) . New Zealand (3) Goal is to have 80+ sites active in the 1H 2015
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31 Study 212:
Study Design Overview Primary Endpoint at 6 Months for Accelerated Approval .
Percentage of patients that achieve culture conversion . Secondary:
Six-minute walk test Screening Period 8 Months Daily Dosing ARIKAYCE once
daily + Background Therapy Background Therapy Converters Continue Treatment
for 12 Months Post Conversion 3 Month Off Treatment Follow-Up Non-converters
Enter 312 Follow-on Study ARIKAYCE + Background Therapy for 12 Months R Key
Inclusion Criteria .Age > 18 years < 85 years .DX of pulmonary NTM lung
disease with MAC .Failed prior treatment . Multi-drug regimen for at least 6
months; last dose within the prior 12 months ARIKAYCE once daily + Background
Therapy ~200 patients ~100 patients Background Therapy 3 Month Off Treatment
Follow-Up Key Facts: INS-212 Trial . Randomized ~300 patients (2:1) . Non-CF
MAC Only . Stratifications: (1) Smokers vs. non-smokers; (2) Background
Therapy last 6 months
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32 Study 212:
Sputum Sampling Primary Endpoint: . 3 sputum samples will be collected for
each monthly visit (Baseline to Month 6) . Patients will interrupt LAI
administration on day -2 until they visit the clinic . Sputum processing will
be . Performed per standard lab procedures . Globally aligned No LAI 24 Hours
No LAI 48 Hours No LAI 72 Hours Re-Start LAI Dosing Last LAI Sputum #1 Sputum
#2 Sputum #3
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33 Central
Micro Labs Globally Region Central Micro Lab Microbiology Director USA/Canada
University of Texas at Tyler Health Northeast (USA) Richard J. Wallace
Jr.M.D. Europe Radboud University Medical Center (Netherlands) Jakko van
Ingen, MD, PhD Australia/Asia Queensland Mycobacterium Reference Laboratory
(Australia) Dr. Chris Coulter, Director
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34 Methodology
Across Global Central Micro Labs Methodology/Supplies TylerNorth America
Radbound Europe QMRL Australia/Asia Control strain ATC700898 ATC700898
ATCC700898 Liquid medium VersaTrek BD MGIT BDMGIT Solid medium Agar 7H11 Agar
7H11 Agar 7H11 Mac Growth (ID) Gen-Probe Gen-Probe Hain CM Line Probe MIC
Testing (MAC Susceptibility) MIC Panel; (Thermofisher) MIC Panel;
(Thermofisher) MIC Panel; (Thermofisher) MAC Mutation Sequencing Yes Yes Yes Growth
Conditions 35 oC 36oC-37oC 36-37 C Standards CLSI CLSI CLSI
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35 Study 212
Sample Size Calculation . Primary Endpoint Proportion of subjects achieving
culture conversion by Month 6 . Assumptions Month 6 culture conversion rate:
20% for LAI+MDR; 5% for MDR Chi-square test at a 2-sided significance level
of 0.05 A 2:1 randomization ratio to either LAI+MDR or MDR At least 90% power
. Sample Size A total of 261 subjects: 174 for LAI+MDR; 87 for MDR
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36 Study 212
Sample Size Calculation . Secondary Endpoint Change from baseline to Month 6
in 6MWT distance . Assumptions A common standard deviation (SD) of 100 A
between-treatment difference of 50 meters in mean change two group t-test at
a 2-sided significance level of 0.05 A 2:1 randomization ratio to either
LAI+MDR or MDR At least 90% power . Sample Size A total of 192 subjects: 128
for LAI+MDR; 64 for MDR
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37 Study 212
Statistical Methods .Stratification Randomization stratified by: Smoking
Status (current smoker or not) and Prior Multi-drug Regimen (on treatment or
off treatment for at least 3 months) .Primary Analysis Population Modified
Intent-to-treat population: all randomized subjects who received at least 1
dose of either LAI plus a multi-drug regimen or a multi drug regimen
.Hypothesis Primary Endpoint H0: Culture conversion is independent of
treatment H1: Culture conversion is associated with treatment .Analysis of
Primary Endpoint Cochran-Mantel-Haenszel test adjusting for the 2
stratification variables at a 2-sided significance level of 0.05
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38 Study 212
Statistical Methods .Hypothesis Secondary Endpoint H0: No between-treatment
difference in mean change from baseline to Month 6 in 6MWT distanceH1: There
is a between-treatment difference in mean change .Analysis of Secondary Endpoint
Mixed-effects Model for Repeated Measures (MMRM) over Months 4 and 6; The
MMRM model includes treatment, month, the treatment-by-month interaction,
smoking status, and prior multi-drug regimen (on treatment or off treatment
for at least 3 months) as fixed factors, the baseline (Day 1) 6MWT distance
as a covariate, as well as the baseline 6MWT distance-by-month interaction.
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39 Cystic
Fibrosis Program TR02-110 Update
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40 Cystic
Fibrosis Program Update LAI for the Management of Pain Patients with Cystic
Fibrosis Anecdotal Trial Experience 8 patients have requested compassionate
use of LAI to follow TR02-110 . Very positive feedback from PIs in general
regarding slowing of disease progression (even reversal in some cases) and
the patient experience -25 -20 -15 -10 -5 0 5 10 15 20 25 0 28 56 84 112
140 168 196 224 252 280 308 336 364 Relative Mean Change from Baseline (L)
Study Day LAI 590 mg QD LAI-Naïve 590 mgQD TR02-110 Mean Relative Change from
Baseline in FEV1(L) Missing Values Excluded mITT Population (Interim Data Cut
-149 Complete Day 337 [1 Year])
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41 Cystic
Fibrosis Program Update Reasons for Patient Discontinuation in TR02-110 0 2 4
6 8 10 12 14 16 18 Death Adverse Event Withdrawl of Concent Lost to Follow-Up
PermatureTermination of Study Other Prior LAI arm in TR02-108 Prior TOBI arm
in TR02-108 Reason for Early Discontinuation Number of Patients 1 3 0 15 8 16
1 0 0 1 10 12
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42 Regulatory
Peggy Berry peggy-berry-headshot.jpg
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43 Regulatory
Overview ARIKAYCE .European update .US update .Rest of World activities
INS1009 .US update .Rest of World activities
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44 EMA
Regulatory Timeline Clock Stop Clock Stop Pre-submission Assessment of new
marketing authorisation application Decision-making phase Day 1 (Feb 2015)
Day 120 List of Questions Day 121 Day 180 List of Outstanding issues or
opinion Day 181 Day 210 Opinion Day 277: EC Decision European Marketing
Application (for NTM Lung Infections and Pseudomonas Aeruginosa CF patients)
Submitted late 2014; Validated February 2015 Expect feedback at Day 120; late
June 2015 (preparing responses to potential questions) Assuming standard
response time Day 180 (final issues) will be mid-Q4 Day 210 (opinion) will be
late Q4 Day 277 (final decision) will be mid-Q1 2016
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45 D:INSMED2012IR
DeckArtworkNew LogoLogo Master v1a Small .pngARIKAYCE US Update Reached
agreement on protocol INS-212 Anticipate beginning rolling NDA submission in
mid-2016 with final at end of 2016 for possible SubPart H approval .Permits
an approval based upon culture conversation & 6-minute walk test (6MWT)
distance at the 6 month timepoint .Requires a commitment to submit additional
clinical data when available; discussions with the FDA will occur to
determine requirements for full approval to be granted .completion of the 212
study through 16+ months of treatment for patients who have converted
.completion of the 312 safety study through 12 additional months of treatment
for those patients who have not converted .possible additional requirements
depending on the data from the studies
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46 SubPart H
Approval .If agreed requirements are metand the data on the final endpoints
are achieved, the FDA could issue a full approval of the drug with updated
labeling that incorporates information from the study results .If agreed
requirements are not met or if the clinical data do not succeedon the final
endpoints, the FDA may modify the product labeling to include the new data
and to specify any limitations of use of the drug based upon the results
achieved or they may convene an advisory committee meeting to discuss the
data and recommended changes to the product labeling. In rare circumstances,
they may also rescind the approval of the drug.
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47
ARIKAYCERest of World Update Australia .Orphan drug designation achieved in
February 2015 for CF and refractory NTM Canada .Held pre-submission meetings
with regulatory agencies Japan .Reached agreement on clinical study
requirements for phase 3 study and PK
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48 INS1009 US
& RoW update .Reached general agreement on development program .Agreed
that 505(b)(2) is possible pending review of the data confirming that
INS1009 is a prodrug of treprostinil (FDA data review to occur 2Q 2015)
.Anticipated Benefits of 505(b)(2) .No carcinogenicity study .Only one phase 3
study required .No drug-drug interaction studies required .Orphan drug
application in preparation .Seeking advice from EU regulators to ensure that
the development program will satisfy their requirements
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49 Research and
Development INS1009 Dr. Walter Perkins Dr. Gene Sullivan
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50 Pulmonary
Arterial Hypertension (PAH): Our Next Target Indication ARIKAYCE liposomal
amikacin for inhalation INS1009 inhaled treprostinil-prodrug NTM PAH
Additional Programs in Orphan Diseases
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51 Pulmonary
Arterial Hypertension (PAH) Orphan Disease Progressive Disease Leading to
Heart Failure .No curative treatments .15% one-year mortality .100,000*
patients afflicted globally .25,000 treated patients in the U.S.1,2,3
.Treatment is progressive combo therapy, including: .Calcium channel
blockers; Endothelin receptor antagonists (ERAs); PDE-5 inhibitors; and
Prostacyclins .Prostacyclins are perceived to be the most effective class but
are limited by toxicity/tolerability issues .4 to 9x daily inhalations,
continuous infusion, or modest efficacy at tolerable doses Source: Company
estimates. 1) Yang X, Mardekian J, Sanders KN, Mychaskiw MA, Thomas J.
Prevalence of pulmonary arterial hypertension in patients with connectivet
issue diseases: a systematic review of the literature. Clinical Rheumatology
2013 Oct;32(10):1519-31. 2) Peacock AJ, Murphy NF, McMurray JJV, et al. An
epidemiological study of pulmonary arterial hypertension. Eur Respir J
2007;30:1049 3) Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin
V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C,
Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Simonneau. Pulmonary
arterial hypertension in France: results from a national registry. ; Am J
Respir Crit Care Med. 2006;173(9):1023. 4) McLaughlin VV, Archer SL, Badesch
DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension:
a report of the American College of Cardiology Foundation Task Force on
Expert Consensus Documents and the American Heart Association: developed in
collaboration with the American College of Chest Physicians, American
Thoracic Society, Inc., and the Pulmonary Hypertension Association.
Circulation 2009; 28:119:2250-94
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52 Current
Marketed Prostanoids for Pulmonary Arterial Hypertension Drug Dosing Pros
Cons Flolan, Veletri (epoprostinil) Intravenous via continuous infusion
Continuous drug level .Intravenous central line infection .Requires
infusion pump Ventavis (iloprost) Inhaled with 6-9x daily dosing Less
invasive than infusion .Swings in peak/trough plasma levels .Lack of drug
overnight .Inconvenient 6-9x/day dosing Remodulin (treprostinil) Subcutaneous
/ Intravenous via continuous infusion Continuous drug level .Subcutaneous --
site pain .Intravenous central line infection .Requires infusion pump
Tyvaso (treprostinil) Inhaled with 4x daily dosing Less invasive than
infusion .Swings in peak/trough plasma levels .Lack of drug overnight
.Inconvenient 4x daily dosing Orinetram (treprostinil) Oral with BID/TID
dosing Convenient dosage form .Swings in peak/trough plasma levels .Lack of
drug overnight
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53 INS1009:
Treprostinil-Prodrug Formulated in a Nanoparticle ~100 nm in diameter C16TR
.Hexadecyl-treprostinil (C16TR) Prodrug .Nanoparticles in aqueous suspension
.Administered by state-of-the-art nebulizer .Patent applications filed 24
hour Coverage via Convenient Once-Daily Dosing without Large Peak/Trough
Swings in Plasma Levels
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54 A single 6
µg/kg dose administered by inhalation to ventilated rats *Estimation based on
correlation of treprostinil plasma levels with changes in mean pulmonary
arterial pressure (mPAP) from multiple experiments in rats From ERS 2014
Poster 2367. 0.01 0.10 1.00 10.00 0 1 2 3 4 5 6 7 Treprostinil Plasma Level
(ng/mL) Time (hr) Treprostinil INS1009 Therapeutic threshold* INS1009
.Sustained Release .Cmax reduced significantly INS1009 Provides Sustained
Release of Treprostinil
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55 INS1009
Extends Vasodilation Period Significantly Rat Acute Hypoxia Model of PAH 40.0
50.0 60.0 70.0 80.0 90.0 100.0 110.0 -5 0 0.5 1 1.5 2 2.5 3 5 10 20 30 40 50
60 70 80 90 100 110 120 130 140 150 160 170 180 Time (min) mPAP (as % initial
hypoxic value) Buffer Control Treprostinil INS1009 Mean Pulmonary Arterial
Pressure (mPAP) as a % of hypoxic baseline value. mPAP is elevated in rats in
response to hypoxia (10% oxygen). Single dose of INS1009 or treprostinil
(both at 6 µg/kg treprostinil). Rats are anesthetized and ventilated. The
initial time scale is expanded and the dotted line denotes the change in the
time scale. Ns= 8-10
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56 INS1009
Provides Sustained Release of Treprostinil over 24 Hours 0.01 0.1 1 10 0 5 10
15 20 25 Time (h) Stays above threshold of 0.1ng/mL for full vasodilatory
effect* Dose of 6 µg/kg Treprostinil Plasma Level (ng/mL) With nose-only
inhalation plasma levels are higher than those in ventilated rats due to
additional deposition/absorption in nasal passages *Estimation based on
correlation of treprostinil plasma levels with changes in mean pulmonary
arterial pressure (mPAP) from multiple experiments in rats Rats dosed by
Nose-Only Inhalation
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57 Tre 5 µg/kg
Tre 16 µg/kg INS1009 7 µg/kg INS1009 22 µg/kg INS1009 46 µg/kg INS1009 95
µg/kg 0 6 12 18 24 30 36 42 48 0.01 0.1 1 10 Active Lung Dose in Ventilated
Dogs (Single Inhalation) Treprostinil Plasma Level (ng/mL) Inhaled INS1009
Provides Sustained Release of Treprostinil in Dogs
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58 INS1009
Better Tolerated in Dogs than Inhaled Treprostinil Compound Lung Dose (µg/kg)
Observed Side Effects Treprostinil 5 0 of 3 dogs 16 4 of 5 dogs INS1009 7 0
of 3 dogs 22 0 of 5 dogs 46 0 of 3 dogs 95 1 of 3 dogs Observed side effects
after drug delivery: . Treprostinil -- cough, rapid shallow breathing, pale
gums and emesis . INS1009 1 dog at highest dose exhibited rapid shallow
breathing, pale gums, and emesis
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59 INS1009 for
PAH: Path to Market Pursuing 505(b)(2) FDA NDA Approval . Can be faster to
market* . Lower risk by leveraging prior drug approval . Lower costs due to
fewer studies FDA IND . IND: expect to file in 2H 2015 Clinical . Phase 1 Study:
Expect to Start by Year-end 2015 . Phase 2 Study: Expect to Start in 2016 .
Phase 3 Study: TBD following completion of Phase 2 INS1009 (graphical
representation) * Camargo Pharmaceutical Services
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60 Phase 1 A
single ascending dose (SAD) study in healthy volunteers for tolerability and
pharmacokinetics Phase 2 A single 12-week dose exploration study in PAH
patients INS1009 for PAH: Clinical Plans through Phase 2
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61 Insmeds
Orphan Product Portfolio ARIKAYCE liposomal amikacin for inhalation INS1009
inhaled treprostinil-prodrug NTM PAH Additional Programs in Orphan Diseases
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62 Global
Commercial Plan & Corporate Development Wes Kaupinen Drayton Wise Dr.
Olaf Bartsch Drayton
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63 ARIKAYCE:
Near-term Commercial Launches 2016 2017 2018 30K Diagnosed Patients Treatment
Resistant Populations (estimate) 30K 5-10K 5-10K 55-70K 10-20K Estimated
Approval Timing PARTNERSHIP DISCUSSIONS UNDERWAY LAUNCH ALONE;EXPERIENCED EU
LEADERSHIP IN PLACE LAUNCH ALONE; BUILDING AN EXPERIENCED U.S. TEAM EU US
Japan
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64 Europe Dr.
Olaf Bartsch
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65 Targeted EU
Build-out to Pursue NTM and CF Indications Medical Science Liaison Focus
Phase I Initial Hires In Place . Germany . France Phase II . UK . Italy .
Sweden . Netherlands
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66 Diagnosed
NTM Prevalence in EU 5 . Includes both newly diagnosed patients and those
with active ongoing disease diagnosed in a previous year . Treatment of NTM
often extends well into the second year . Of the ~30k diagnosed NTM patients
. ~20k are in EU5 . Germany has the largest population with >5k Source:
Clarity Pharma Chart Audit. UK (4,103) France (3,857) Germany (5,373) Italy
(3,714) Spain (2,764)
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67 The Unmet
Need - NTM NTM infections mostly occur in patient with underlying pulmonary
diseases like COPD, bronchiectasis and asthma and CF. .No on-label treatment
available in Europe .Cocktail of 3-4 antibiotics used off-label with
significant side effects .KOL quote in Europe: Make sure you get this
product approved for any indication; we are in real need for a safe treatment
option for these patients
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68 EU CF
PATIENTS 35K Fatal genetic disease Life expectancyof 38-40 years CF Patients
with Pseudomonas Lung Infections Adults CF patients with chronic Pseudomonas
aeruginosa infection1 80% Increase inresistance to TOBI® 1Adapted from Cystic
Fibrosis Foundation, Patient Registry Annual Data Reports, 2012.2Since 1999
per FDA advisory panel US-FDA-AIDAC for TOBI-Podhaler-September 2012. 3 Liou
et al, Journal of Cystic Fibrosis 9 (2010) 250-256. 85% 2 Annual declinein
lung function 1% to 3% 3
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69 The Need
CF / Pseudomonas aeruginosa .Several inhaled antibiotics already available
with acceptable treatment results .Market very competitive with downward
pressure on prices .ARIKAYCE adds another treatment option for those patients
intolerant or resistant to existing therapies Product Treatment Status
ArikayceTM Inhaled, liposomal formulation of amikacin Phase 3 trial completed
in Europe and Canada TOBI® (Novartis) Inhaled tobramycin Marketed Combined
total sales of $281MM in 2014 TOBI Podhaler® (Novartis) Inhaled tobramycin
powder Cayston® (Gilead Sciences) Inhaled aztreonam Marketedin Europe and US
Colimycin and Colobreathe (Actavis) Inhaled colistimethate sodium Marketed in
Europe Bramitob® (ChiesiGroup) Inhaled tobramycin Marketed in Europe BETHKIS®
(Chiesi USA) Inhaled tobramycin Marketed in the US Aeroquin® (Actavis)
Inhaled levofloxacin Phase 3
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70 The
Addressable Market CF /Pseudomonas: slow market penetration foreseen .80% of
the adult CF patients have chronic Pseudomonas infections .The current gold
standard is Tobramycin .ARIKAYCE has some advantages in QoL (once daily) and
is just another option for HCP´s All NTM: Major unmet need .33% refractory
patients represent the primary ARIKAYCE market .The phase 2 data included
patients with MAC and M abscessus
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71 Key
Considerations for Insmed Europe .Launch strategy taking into account market
sizes & market access possibilities, i.e. start in the 2 major countries
(Germany & France), explore the UK and Italy and be opportunistic
elsewhere (e.g. NL, Sweden) .European launch provides learning opportunity
for US launch: pricing, optimal positioning, patients onboarding and
compliance with treatment .Insmed enters Europe with a longer term focus: to
broaden its organizational possibilities and enhance the outreach also for
future products
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72 EU Launch
Preparation .Focused build-out of presence in 2015 / 2016 .Direct country
organizations (Germany & France) .4 markets under evaluation for direct
approach (UK, Italy, Sweden, NL) .All other EU markets initially mapped
through 3rd party consultants .Supply & distribution through 3rd party
logistics provider .Medical Education .Disease Awareness (focus on NTM)
.Definition and Communication of the unmet need (NTM & CF) .KOL
Management .Top 5 KOL´s per EU market .Market Access preparation .Focus on
tier 1 countries (Germany, France) .Explore tier 2 markets (UK, Italy, NL,
Sweden)
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73 Example NTM
lung Disease in Germany DX Patterns in DE are similar to other EU markets
.Roughly 20% deemed severe .DE system of referrals drives initial DX at
Internal or General Medicine (38%) followed by Pulmonologist (34%) while TX
Patterns in DE are not. .Majority of patients seen in academic medical
centers or solo private practice (vs UK) .Only 5% of IV treatments involve
amikacin IV vs. 34% amikacin IV in UK .Very high use of beta agonists (34%)
.DE patients are 3 times more likely to visit the ER than in UK Country or
Region Est. Number of NTM Lung Disease Patients Mild Moderate Severe France
3,857 945 2,175 737 Germany 5,373 1,171 3,116 1,086 Italy 3,714 722 2,464 528
Spain 2,764 672 1,531 561 United Kingdom 4,103 845 2,437 821 EU5 19,811 4,355
11,723 3,733 Japan 31,745 21,332 9,873 540 EU5 + Japan 51,556 25,687 21,596
4,273 Number of times patient visited ER for NTM Lung Disease Patients in
past year (mean)
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74 Example
Germany Launch possible shortly after approval Pre launch strategy focused
on: .Medical education .Disease Awareness (NTM) .Definition of the unmet need
.(NTM & CF) .KOL Management .Advisory boards .PR .Market Access
preparation .G-BA consultation process .AMNOG Dossier development
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75 German
Disease Awareness Campaign NTM Lung Disease .German Pulmonologist
Introductory Mailing .DA website www.ntmfakten.de .German Advisory boards
.German Ad Campaign .Medical Education Campaign
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76 NTM Lung
Disease Awareness Launch February March April Digital Print Disease Awareness
Microsite Launch Insmed Introduction Letter Mailer Newsletter (Third party
vendor) Banner Ads Doc Check Email (Third party vendor) Web Key Banner Ads*
DGP Booth NTMinfo Literature Web Key Journal Ad Mailing of Disease Awareness
Poster Journal Ad** *Banner Ads consist of flash banners and static banners
on: doc check, esanum, doc check site seeing. **Journal ads displayed across
10 publication. The same creative will run from March-June. Disease Awareness
Launch Phase 1: Germany Letter
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77 US
Commercial Planning Drayton Wise Drayton Wise
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78 Key Elements
of the U.S. ARIKAYCE Launch Planning Our Approach 1. Targeted Disease State
Awareness, including our key learnings from EU experience 2. SALES + MEDICAL
+ MARKETING field-oriented and working as one 3. Augmenting therapy with
services that maximize patient experience and convenience 4. Voice of the
Patient MUST and WILL be represented in everything we do 5. Recruiting
talented and experienced people to join this mission
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79 Hallmark of
a Successful Orphan Disease Approach: Begins Early with Highly Targeted
Disease State Awareness Campaign
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80 U.S.
ARIKAYCE Launch Planning: Targeted Sales and Medical Presence Focused on
Pulmonologists Field-based pulmonary sales specialists Pulmonologists
represent over 80% of NTM patients Field Medical Science Liaisons To Convey
NTM Medical Story Maximizing convenience: .1. Patient services hub .2.
Specialty pharmacy 30 3,000 MSLs Patient Centricity
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81 ARIKAYCE:
Pricing and Reimbursement in NTMBuilding the Value for Money Story US burden
of illness study with major US payor confirms NTM is a costly disease: .
Monthly medical + pharmacy expenditures = $5,000 less per month for those
diagnosed and treated with existing therapies vs. those diagnosed and
untreated/non-compliant . It pays to aggressively treat NTM: . The economic
impact of treatment is seen immediately in the claims data (reduction in
hospitalizations and ER visits) Treated NTM patients live long enough to
recoup investment in therapy
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82 Corporate
Development Wes Kaupinen
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83 Corporate
Development Focus: Build on our Commitment to NTM Patients 2015 Corporate
Goal: Acquire at least one external asset Key Corporate Development Criteria:
#1: Product/Product Candidate Serves an Orphan / Pulmonary Orphan Patient
Population #2: Therapeutic Indication is NTM-Like
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84 Differential
Criteria Based on Development Stage Commercial Development . World-Class
Patient Management in Rare Disease(s): .Enables leverage of successful orphan
commercial infrastructure . Affordably Priced: .Naturally limits pursuit of
some therapeutic areas . Minimal Upfront Payment: .Consideration structured
to reward success . Asset Currently Under the Radar: .Proprietary sourced
transactions vs. competitive bidding processes
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85 There is a
Broad Spectrum of Pulmonary Orphan Diseases; Many of These Patient
Populations are Severely Underserved Auto-Immune Diseases Anti-basement
membrane syndrome Pulmonary alveolar proteinosis Lung-Limited
idiopathicdisorders Idiopathiceosinophilic pneumonias Tracheobronchopathiaosteochondroplastica
Tracheobronchomegaly (Mounier-Kuhn syndrome) Idiopathic bronchiolitis
Vasculitides Granulomatosis with polyangiitis(Wegeners) Churg-Strauss
syndrome Behçets disease Takayusus arteritis Microscopic polyangiitis
Goodpasturesyndrome Polyarteritis nodusa Interstitial Lung Disease Idiopathic
nonspecificinterstitial pneumonias Idiopathic pulmonary fibrosis (IPF)
Respiratory bronchiolitis interstitial lungdisease (RBILD)
Desquamativeinterstitial pneumonia (DIP) Cryptogenic organizing pneumonia
Acute interstitialpneumonia (AIP) PulmonaryVascular Disease PulmonaryArterial
Hypertension (PAH) Pulmonary veno-occlusivedisease (PVOD) Chronic
thromboembolicpulmonary hypertension (CTEPH) PH-associated with
myeloproliferative diseases Pulmonary capillary hemangiomatosis Hereditary
hemorrhagictelangiectasia Infectious Diseases Psuedomonasinfections
associated with CF MRSAlung infections associated with CF
Non-tuberculousmycobacterium lung infections Fibrosing mediastinitis
Inheritedforms of emphysema Alpha-1 antitrypsindeficiency Elastin mutations
Salla disease Phakomatosis Lymphangioleiomyomatosis Birt-Hogg-Dubésyndrome
Neurofibromatosis type I Channelopathies Pulmonary alveolarmicrolithiasis
Cystic Fibrosis CiliaryDisorders KartagenerSyndrome Primaryciliary dyskinesia
Disorders of Respiratory Drive CentralAlveolar hypoventilation Narcolepsy
Connective Tissue Matrix Disorders Marfan syndrome Ehler-Danlossyndrome
Genetic Surfactant Disorders ABCA3 SP-A-relatedlung disease SP-B-relatedlung
disease SP-C-relatedlung disease Trafficking and Lysosomal Storage Disorders
Hermansky-Pudlak syndrome Gaucher disease NeimanPick C Congenital Cystic
adenomatoidmalformation Pulmonary sequestration Neuroendocrine cell
hyperplasia Neuromuscular disease Amyotrophiclateral sclerosis Myasthenia
gravis Dermatomyositis,polymositis Other Sarcoidosis Throracic endometriosis
Langerhans cell histiocysosis Idiopathic pulmonary hemosiderosis Sickle Cell
anemia Bronchiolitis obliterans Hypersensitivity pneumonitis
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86 Insmed Vision:
Leading Sustainable Pulmonary Orphan Company CF Today NTM PAH
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87 Insmed
Vision: Leading Sustainable Pulmonary Orphan Company CF Today Future Vision
NTM PAH CF NTM PAH AATD LAM SARC NCFB PAP
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88 Tech Ops,
Cash and Tax Planning Andy Drechsler
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p
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89
Manufacturing and Supply ChainProducing Product at Scale for Clinical and
Commercial Supply .Multi-sourced supply chain .Building out commercial scale
manufacturing capabilities .Global distribution
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90
Manufacturing and Global Supply Chain ARIKAYCE Formulation and Filling of
ARIKAYCE .Current: 50kg Althea (US) .Future: 50kg Althea (US) & 200kg
Therapure (CAN) Testing .Covance (UK) Labelling and Packaging .For Clinical
.Xerimis (US) and Biotec (UK) .For Commercial .Almac (US) and Almac (UK) Device
.PARI (GER) Neues BildLOGO_eFLOW-Techn_PRI
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91
Manufacturing and Global Supply Chain ARIKAYCE #1 - Cholesterol (France) #1
- DPPC (Germany) Device (Germany) Testing Sites (UK) Almac US Xerimis US
Clinical Sites ARIKAYCE Manufacture (US & Canada) #2 - Cholesterol
(India) #2 - Amikacin (China) #1 - Amikacin (Italy) #2 - DPPC (Japan) Biotec
UK Almac UK Goal: Dual sources throughout the supply chain Patients
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92
Manufacturing and Global Supply Chain ARIKAYCE Althea: .Current Clinical and
Commercial launch site .50kg scale ~ 5,000 vials of ARIKAYCE per batch
Therapure: .Future Commercial production site - On-line 2H 2015 .200kg scale
~ 20,000 vials of ARIKAYCE per batch
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93
Manufacturing and Supply Chain INS1009 Formulation and Filling .Toxicology
studies .Axcellerate (NJ) 1 liter batch size .Phase 1 Clinical studies
.AMRI (MA) 1 liter batch size Testing .PPD (WI) Labelling and Packaging
.For Clinical .Xerimis (PA) Z:PresentationsNanoparticle
CartoonsManufacturing Cartoon.jpgApril May June July Aug Sep Oct Axcellerate
AMRI
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94 Cash Needs
from Operations .Cash Balance at 12/31/14 = $159.2M .Timing/pace of 2015
spending dependent on: .212 trial enrollment .Manufacturing scale up
.Manufacturing pace/schedule .European infrastructure build .Debt $25M:
interest only, due 1/1/16 .Potentially able to modify 35 40 46 48 56 58 01 02
03 04 05 06 01H 14 2H 14 1H 15 2H 15Cash Burn from Operations($ in millions)
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95 Tax Planning
.Commenced long term tax planning efforts in 2014 .Anticipate that Ireland
will be our IP and tax hub for EU .New entities: Ireland, Germany, France
& Netherlands .Long term plans for manufacturing and distribution
.Current: Althea (San Diego, California, US) .2015: Addition of Therapure
(Toronto, Canada) .Future: Addition of Ireland .Location of intellectual
property and manufacturing operations should provide tax rates below current
US statutory rates
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96 Key
Takeaways Mission .Building a patient-focused and sustainable
biopharmaceutical company focused on orphan, pulmonary indications ARIKAYCE
.Significant global NTM market opportunity .Phase 3 global study in NTM
underway .MAA submitted/validated in EU for NTM and CF INS1009 .IND to be
filed 2H 2015 .Phase 1 enrollment by end of 2015 .Potential 505(b)(2) path to
approval 96
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97 Insmed
Copyright 2015 © All Rights Reserved. Thank You Building aPatient-Focused and
Sustainable Biopharmaceutical Company Focused on Orphan, Pulmonary
Indications www.insmed.com
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