Promising Therapies Inspired by Urgent Unmet Patient Needs - Insmed
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Promising Therapies Inspired by Urgent Unmet Patient Needs
Forward Looking Statement
This presentation contains forward-looking statements that involve for ARIKAYCE; development of unexpected safety or efficacy obligations under such agreements; the cost and potential
substantial risks and uncertainties. "Forward-looking statements," as concerns related to ARIKAYCE or brensocatib; inaccuracies in the reputational damage resulting from litigation to which the
that term is defined in the Private Securities Litigation Reform Act of Company's estimates of the size of the potential markets for Company is or may become a party, including product liability
1995, are statements that are not historical facts and involve a ARIKAYCE or brensocatib or in data the Company has used to claims; the Company's limited experience operating internationally;
number of risks and uncertainties. Words herein such as "may," "will," identify physicians; expected rates of patient uptake, duration of changes in laws and regulations applicable to the Company's
"should," "could," "would," "expects," "plans," "anticipates," "believes," expected treatment, or expected patient adherence or business, including any pricing reform, and failure to comply with
"estimates," "projects," "predicts," "intends," "potential," "continues," discontinuation rates; the Company's inability to create an effective such laws and regulations; inability to repay the Company's existing
and similar expressions (as well as other words or expressions direct sales and marketing infrastructure or to partner with third indebtedness and uncertainties with respect to the Company's
referencing future events, conditions or circumstances) may identify parties that offer such an infrastructure for distribution of ARIKAYCE; ability to access future capital; and delays in the execution of plans
forward-looking statements. failure to obtain regulatory approval to expand ARIKAYCE's to build out an additional FDA-approved third-party manufacturing
indication to a broader patient population; failure to successfully facility and unexpected expenses associated with those plans.
The forward-looking statements in this presentation are based conduct future clinical trials for ARIKAYCE, brensocatib and the
upon the Company's current expectations and beliefs, and involve Company's other product candidates, including due to the The Company may not actually achieve the results, plans, intentions
known and unknown risks, uncertainties and other factors, which Company's limited experience in conducting preclinical or expectations indicated by the Company's forward-looking
may cause the Company's actual results, performance and development activities and clinical trials necessary for regulatory statements because, by their nature, forward-looking statements
achievements and the timing of certain events to differ materially approval and the Company's inability to enroll or retain sufficient involve risks and uncertainties because they relate to events and
from the results, performance, achievements or timing discussed, patients to conduct and complete the trials or generate data depend on circumstances that may or may not occur in the future.
projected, anticipated or indicated in any forward-looking necessary for regulatory approval; risks that the Company's clinical For additional information about the risks and uncertainties that
statements. Such risks, uncertainties and other factors include, studies will be delayed or that serious side effects will be identified may affect the Company's business, please see the factors discussed
among others, the following: the risk that brensocatib does not during drug development; failure to obtain, or delays in obtaining, in Item 1A, "Risk Factors," in the Company's Annual Report on Form
prove effective or safe for patients in the STOP-COVID19 study; regulatory approvals for ARIKAYCE outside the U.S. or for the 10-K for the year ended December 31, 2019, our Quarterly Report on
business or economic disruptions due to catastrophes or other Company's product candidates in the U.S., Europe, Japan or other Form 10-Q for the quarter ended March 31, 2020 and any
events, including natural disasters or public health crises; impact of markets, including the United Kingdom as a result of its recent exit subsequent Company filings with the SEC.
the novel coronavirus (COVID-19) pandemic and efforts to reduce its from the European Union; failure of third parties on which the
spread on our business, employees, including key personnel, The Company cautions readers not to place undue reliance on any
Company is dependent to manufacture sufficient quantities of such forward-looking statements, which speak only as of the date of
patients, partners and suppliers; failure to successfully ARIKAYCE or the Company's product candidates for commercial or
commercialize or maintain U.S. approval for ARIKAYCE®, the this presentation. The Company disclaims any obligation, except as
clinical needs, to conduct the Company's clinical trials, or to comply specifically required by law and the rules of the SEC, to publicly
Company's only approved product; uncertainties in the degree of with laws and regulations that impact the Company's business or
market acceptance of ARIKAYCE by physicians, patients, third-party update or revise any such statements to reflect any change in
agreements with the Company; the Company's inability to attract expectations or in events, conditions or circumstances on which any
payors and others in the healthcare community; the Company's and retain key personnel or to effectively manage the Company's
inability to obtain full approval of ARIKAYCE from the FDA, such statements may be based, or that may affect the likelihood
growth; the Company's inability to adapt to its highly competitive that actual results will differ from those set forth in the forward-
including the risk that the Company will not timely and successfully and changing environment; the Company's inability to adequately
complete the study to validate a PRO tool and complete the looking statements.
protect its intellectual property rights or prevent disclosure of its
confirmatory post-marketing study required for full approval of trade secrets and other proprietary information and costs associated
ARIKAYCE; inability of the Company, PARI or the Company's other with litigation or other proceedings related to such matters;
third party manufacturers to comply with regulatory requirements restrictions or other obligations imposed on the Company by its
related to ARIKAYCE or the Lamira® Nebulizer System; the agreements related to ARIKAYCE or the Company's product
Company's inability to obtain adequate reimbursement from candidates, including its license agreements with PARI and
government or third-party payors for ARIKAYCE or acceptable prices AstraZeneca AB, and failure of the Company to comply with its
2
Our Mission
To transform the lives
of patients with serious
and rare diseases
3Our Vision
To be a globally-recognized
leading biotech company that
empowers great people to
deliver, with a profound sense
of urgency and compassion, life-
altering therapies to small
patient populations
experiencing big health
problems
4Robust Development Cycle Capabilities with Clear
Commercialization Path
Pipeline Highlight: Populations with
Urgent Unmet Patient Needs
Drug Discovery
Research
ARIKAYCE®
Management of the Global
Treprostinil Palmitil Clinical Development
Regulatory Pathway Commercialization
RV94
Business Development
(Licensing and Acquisition)
Brensocatib
An advanced research and development Successfully brought a first-in-disease
pipeline has potential to address the therapy independently from concept
unmet needs of patients with serious to market and has expertise in every
and rare diseases. stage of the development cycle.
5Growing Pipeline
PRECLINICAL PHASE 1 PHASE 2 PHASE 3 APPROVED
ARIKAYCE® (Amikacin Liposome Inhalation Suspension) *
Refractory NTM: M. avium complex (MAC)
ARIKAYCE® (Amikacin Liposome Inhalation Suspension)
Label Expansion
Front line, maintenance, other non-MAC NTM species, e.g., M. Abscessus
Brensocatib: DPP1 Inhibitor
Bronchiectasis
Brensocatib: DPP1 Inhibitor
COVID-19 (IIR)
Treprostinil Palmitil: Inhaled Prostanoid
Pulmonary arterial hypertension (PAH)
RV94
Gram-positive infections
Internal R&D
Various indications
Corporate Development
* As a condition of accelerated approval, Insmed is collaborating with the FDA on the design of an additional clinical study to support full approval. The study design is currently under discussion with FDA and is proposed to
be a randomized, double-blind, placebo-controlled clinical trial to assess and describe the clinical benefit of ARIKAYCE in patients with NTM lung disease caused by MAC.
6Brensocatib
7Inhibiting Inflammatory Response
Cathepsin G
Proteinase 3
(CatG)
Neutrophil Elastase (Pr3)
(NE)
N-terminal dipeptide removed
Brensocatib Inactive Neutrophil Serine
Proteases (NSPs)
Novel once-a-day pill,
Inactive Neutrophil
Serine Proteases (NSPs) reversible inhibitor of
DPP1 dipeptidyl peptidase Brensocatib
DPP1 Inhibitor
DPP1
Neutrophil Elastase
(NE)
Activated (NSPs)
1 (DPP1)
Cathepsin G
Proteinase 3 (CatG)
(Pr3)
DPP1 is an enzyme Neutrophils are the By inhibiting the
most common type of Positive Phase 2 Data in
that catalyzes the activation of NSPs,
white blood cell and bronchiectasis underscores potential
activation of NSPs brensocatib may offer
play an essential role in of brensocatib
in neutrophils when applicability in a
they are formed in pathogen destruction range of neutrophil-
and inflammatory Strong rationale for further
the bone marrow. mediated diseases.
mediation. development in neutrophil-driven
inflammatory conditions
8Novel Treatment with
Significant Growth Opportunity
Robust, Positive Clinical Data Broad Potential in Additional Indications
Bronchiectasis Diseases affected by
neutrophil-driven inflammation
US EU5 † Inflammatory
340-520K diagnosed 350-500K diagnosed GPA(1) Lupus(1) Bowel COPD
patients* patients** Disease(1)
Asia-pacific region Alpha-1 Rheumatoid Cystic
Antitrypsin Arthritis Fibrosis Asthma
~1M-5M diagnosed patients
NOTE: studies indicate lack of consensus on prevalence rates◊
We have the expertise and vision to take full advantage of the potential offered by brensocatib in bronchiectasis
and other potential indications, including leveraging partnerships where and when appropriate.
*Weycker, et al. Prevalence and incidence of NCFBE among US adults in 2013. Chronic Respiratory Disease. 2017; **Estimates suggest broadly similar per capita
prevalence in EU5 as in US; ◊Asia-Pacific rates 3X to ~10X higher than those in the US; Zhou, YM et al. The prevalence and risk factors of BE in (1) Preclinical Data Available 9
residents aged 40 years old and above in seven cities in China. 2013 † EU5 comprised of France, Germany, Italy, Spain and the United Kingdom• WILLOW STUDY •
Data Demonstrates
Potential for First-in-Class AstraZeneca Exercises
Bronchiectasis Treatment First Option in License
Agreement Validating
Randomized, double-blind, Phase 2 study; tested 10
mg, 25 mg and placebo Potential For COPD And
CT scan-confirmed NCFBE; ≥2 pulmonary Asthma
exacerbations in past 12 months
Risk of exacerbation over six months reduced by 42%
June 2020: FDA Grants
for 10 mg group, 38% for 25 mg group
Breakthrough Therapy
Primary and secondary endpoints met with statistical
significance Designation
Data demonstrate positive correlation between
neutrophil elastase reduction and risk of
exacerbation in 10mg group
Plan to initiate Phase 3 program second half of 2020.
10Treatment Potential for Severe
COVID-19 Infections
Could brensocatib be used to treat COVID-19?
Currently under investigation in
multi-site UK investigator-initiated research
(IIR) study
Double-blind, prospective, Up to 300 patents,
placebo-controlled, randomized trial 10 sites
Led by University of Dundee’s Sample size
Professor James Chalmers, MBChB, reassessment
Ph.D. Q3 2020
Prioritized by UK’s National Full results expected
Institute for Health Research end of 2020/early 2021
11ARIKAYCE
12ARIKAYCE a
Blueprint for
Future Success
2019 $136M net sales
Q1 2020 $36.9M
Engaged HCP & patient population
ARIKAYCE was one of the Top 10 most *Excluding
successful rare disease launches* oncology
Positive reimbursement trends
We plan to repeat history
with our growing pipeline.
13First-in-Disease
Therapy for MAC
Lung Disease
ARIKAYCE
Novel, inhaled, once-
MAC lung disease is a rare, daily formulation of
progressive, and chronic liposomal amikacin
condition that can cause severe, taken with a
permanent damage to the lungs nebulizer
Pulmovance™ liposomal technology delivers drug
Symptoms often worsen over time, directly to the lungs
including chronic cough, dyspnea,
fatigue, fever, weight loss, and chest pain Prolongs release of amikacin in the lungs while limiting
systemic exposure
Caused by bacteria in the environment Complementary portfolio
and is more likely to affect those with a Meaningful overlap in patient populations, with over
history of lung conditions, like
60% of bronchiectasis patients also having an NTM
bronchiectasis or COPD
infection
14ARIKAYCE Treats Refractory
MAC Lung Disease
US: 100K patients
Potential Progression Toward
Use as Front-line and/or
Maintenance Therapy
12-17 K ARIKAYCE approved in the United
refractory States for refractory Mycobacterium
avium complex (MAC) lung disease
Label Expansion in Progress
Approved Treatment in MAC Lung Disease
First and only therapy approved in the United States as Action
part of a combination antibacterial drug regimen for Front-line Phase 3 initiated by year-end
adult patients with limited or no alternative treatment
options Opportunity
Successful data and subsequent
Received both breakthrough therapy & orphan drug regulatory approval could result in a 5-fold
designations increase in the addressable market
15Clear Vision for Global Market
Japan
EU Market 125-145K NTM Patients
14K diagnosed patients 15K-18K refractory
MAC patients
1,400 total refractory MAC
patients
16Well Positioned to Support a Successful Global
Launch in Bronchiectasis
Uniquely positioned to commercialize brensocatib
given the synergies that exist between
bronchiectasis and NTM lung disease
Proven US launch Geographic and Experience with
capabilities with target HCP overlap patient finding
ARIKAYCE with current US and activation
Sales structure
EU/Japan teams Advocacy and
mobilized for patient support
launch success
17Treprostinil Palmitil
18Addressing Significant Unmet Need for Effective,
Tolerable Therapy
for Pulmonary Arterial Hypertension (PAH)
PAH is a progressive,
serious and rare disease
Treprostinil Palmitil
causing high blood pressure Potential for sustained release
in pulmonary arteries
above therapeutic index
with significant Treprostinil Palmitil Reduces downstream disease
symptom burden Dry powder inhaled effects and disease
formula designed for advancement
sustained effect with
disease progression can Potential for vascular
1/day dose
lead to heart failure remodeling
Potential for a better tolerated
today’s treatment tolerance is low, therapy
with no positive downstream effect.
19Insmed Differentiated with Robust
Pipeline and Proven Development
Capabilities
With ARIKAYCE, Brensocatib and Treprostinil Palmitil, we
have developed three value drivers, plus:
Clinical Drug Business
Development Discovery Development
Research
Management of Global
the Regulatory Commercialization
Pathway
Strong expertise and potential across
the development cycle. Many
companies succeed at part of this
equation. We do it all, well.
20Manufacturing
Brensocatib ARIKAYCE Treprostinil Palmitil
API API API
Spain, Canada, Taiwan,
300kg capacity 200L capacity 50g capacity
Drug Product Drug Product Drug Product
Canada, UK, US,
2mm capacity 450L capacity 10,000 capsules
capacity
21Protected with Significant, Global IP
Brensocatib Treprostinil
US, Europe, Japan, China
Palmitil
In-licensed compound patent
exclusivity until 2035
ARIKAYCE US 4 patents
issued to 2034
US multiple issued
Non-CF Bronchiectasis patents to 2035 Japan, EU, Australia,
Treatment Methods patent 12-year regulatory China counterpart
application filed, projected to exclusivity patents issued to
expire in 2037 2034
EU patent to 2035
Oral formulation and ANCA 10-year regulatory
vasculitis patent applications
filed, projected to expire in
exclusivity
2039 Japan patent exclusivity
PTE could extend patent term to 2035 approval to
*No regulatory
of select US patents by 3-5 date in EU and Japan
years for first approved
indication. 22Significant Development Momentum in 2020/21
2020 2021
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
Initiate P3 program
Brensocatib:
Major journal publication of WILLOW
DPP1 Inhibitor
STOP-COVID19 Patient Size
STOP-COVID19 Data
Reassessment
Initiate P3 program in Frontline
ARIKAYCE®
(Amikacin Liposome Launch in Japan
Inhalation Suspension)
Launch in EU
Secure IND
Treprostinil Palmitil:
Initiate first in human trial
Inhaled Prostanoid
Initiate P2a trial
23Strong
Financial
Standing
$428.9M Cash and Cash
Equivalents
as of 3/30/20
+
$259.4M
Capital Raise
Completed
in May 2020
101M Common Shares
Outstanding
post financing
*Excludes stock options unvested RSUs and shares
underlying outstanding convertible notes
24We are committed to bringing forth technologies
and medicines in therapeutic areas with the Investor Relations
greatest potential to make a difference in patients’ investor.relations@insmed.com
646-351-0954
lives.
Powered by Purpose.Appendix
26Willow Study Efficacy
Summary
Top-Line Data: WILLOW Study Achieves Primary Endpoint
Study Schema Risk of having an exacerbation over
the course of six months reduced by
NCFBE confirmed by CT scan up to 40% with Brensocatib
With documented history of ≥2 pulmonary
exacerbations in prior 12 months
Randomized 1:1:1 Screening up to 6 weeks
Double Blind for sputum evaluation and Time to First
Brensocatib 10 Brensocatib
256 Patients periodontal evaluation Exacerbation
mg 25 mg
vs. Placebo
Brensocatib Brensocatib p-value ^ 0.027 0.044
Placebo
10 mg once daily 25 mg once daily
Hazard Ratio 0.58 0.62
p-value ^ 0.029 0.046
Primary Efficacy: Time to first pulmonary exacerbation
Secondary Efficacy:
Rate of pulmonary exacerbations*
Change in the Respiratory Symptoms Domain Score Brensocatib Brensocatib
of the Quality of Life Safety Placebo 10 mg 25 mg
Bronchiectasis questionnaire
Brensocatib was generally well-tolerated in Rates of (AEs) leading to discontinuation 10.6% 7.4% 6.7%
Change in post-bronchodilator FEV1
the WILLOW study
Change in concentration of active neutrophil elastase Rates of adverse events of special interest (AESIs)
in sputum Most common adverse events (AEs) in
patients treated with Brensocatib were Periodontal disease 2.4% 7.4% 10.1%
Safety: Tolerability (e.g., AEs and AEs of special
cough, headache, sputum increase, dyspnea,
interest – infection, skin, and periodontal conditions)
fatigue, and upper respiratory tract infection Hyperkeratosis 0% 3.7% 1.1%
*Company plans to advance development of Brensocatib with trial results
of a minimum of 20% reduction in rate of pulmonary exacerbations
Infections that were considered AESIs 18.8% 16.0% 16.9%
between placebo and active study arms and an acceptable safety profile 27• TOP-LINE DATA •
WILLOW Study Achieves Key
Secondary Endpoint
Frequency of Brensocatib 10 mg Brensocatib 25 mg
Pulmonary Exacerbations (N=82) (N=87)
Reduction vs. Placebo 36% 25%
p-value 0.041 0.167
FDA Guidance
Frequency of pulmonary exacerbation
should be the primary endpoint in Phase 3
28WILLOW Safety Data
Brensocatib was generally Brensocatib Brensocatib
well-tolerated in the Placebo 10 mg 25 mg
WILLOW study
Rates of (AEs) leading to discontinuation 10.6% 7.4% 6.7%
Rates of adverse events of special interest (AESIs)
Most common adverse events
(AEs) in patients treated with Skina 11.8% 14.8% 23.6%
brensocatib were cough,
Dental 3.5% 16.0% 10.1%
headache, sputum increase,
dyspnea, infective exacerbation Infection 17.6% 13.6% 16.9%
of bronchiectasis, diarrhea,
fatigue, and upper respiratory Change in periodontal pocket depth ≥ 2 mmb 13.0% 16.9% 19.2%
tract infection
Change in periodontal pocket depth ≥ 2 mm
11.6% 11.3% 12.3%
and ≥ 5 mm absolute depthb
a Includes hyperkeratosis:
• Placebo (n = 1), brensocatib 10 mg (n = 3), brensocatib 25 mg (n = 1)
• Resolved or improved at the end of the study
• No interruption of study drug
b Changein 3 or more areas, assessed at 3 dental visits. Includes patients with both a baseline and week 24 dental evaluation (placebo, n = 69; brensocatib 10 mg, n = 71;
brensocatib 25 mg, n = 73) 29WILLOW: Hazard Ratio Pulmonary Exacerbation by
Subgroup
30WILLOW: Frequency of Pulmonary Exacerbations by
Subgroup
31Proposed Registration Study for Frontline Indication
Screening
Key Endpoints
Month 13 Endpoints to include
ARIKAYCE + AZI* + ETH*
•Microbiological endpoints
Adults with Blinded •PROs
new MAC Registration R Months 1-12 Off Treatment** •Function endpoints
lung infection PMR Trial
Placebo + AZI + ETH
Culture Negativity Endpoint
Month 15
ARIKAYCE +
AZI* + ETH*
Parallel psychometric
Adults with Psychometric validation study to generate
new MAC Validation R Months 1- 6 Off Treatment** data in the new population
lung infection Study Month 7 prior to enrollment
Placebo + AZI completion of registration
+ ETH study
Key Endpoints
Not for promotional use 32
*Azithromycin (AZI), Ethambutol (ETH)
**Patients will be enrolled into separate OLE/Natural History Study 32You can also read
