Download You Title Goes Here - Windtree Therapeutics

Corporate Presentation
January 2017
NASDAQ:WINT
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To the extent that statements in this presentation are not strictly historical, including
statements about the Company’s business strategy, outlook, objectives, plans, intentions,
goals, future financial conditions, future collaboration agreements, the success of the
Company’s product development, or otherwise as to future events, such statements are
forward-looking, and are made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995. The forward-looking statements contained in this
presentation are subject to certain risks and uncertainties that could cause actual results
to differ materially from the statements made. These risks are further described in the
Company's periodic filings with the Securities and Exchange Commission (SEC), including
the most recent reports on Forms 10-K, 8-K and 10-Q, and any amendments thereto
(“Company Filings”).
Under no circumstances shall this presentation be construed as an offer to sell or as a
solicitation of an offer to buy any of the Company’s securities. In addition, the
information presented in this deck is qualified in its entirety by the Company Filings. The
reader is encouraged to refer to the Company Filings for a fuller discussion of the matters
presented here.
2
Windtree Therapeutics
 Public, small cap biopharmaceutical / medical device company
 Based in Warrington, PA with approximately 50 employees
 Technology and development focused in the acute respiratory area
with a lead program based in Respiratory Distress Syndrome (RDS)
in premature infants
 Nasdaq: WINT
 Windtreetx.com
3
Highly Experienced Management Team
Craig Fraser
CEO
Steve Simonson, MD
Chief Development Officer
John Tattory
CFO
Mary Templeton
General Counsel
Kathy Cole
Human Resources
George Cox
Manufacturing & Supply
Ron Dundore
Regulatory and Quality
Larry Weinstein
Medical Device
4
Respiratory Distress Syndrome (RDS)
Primary characteristic is surfactant deficiency in underdeveloped lungs of
premature infants (born with a lack of natural lung surfactant required for open
airways and proper gas exchange – O2 in and CO2 out)
American Academy of Pediatrics guidelines recommend providing surfactant
1
replacement within the first hours of life
Neonatologists believe the highest unmet need in RDS is the ability to deliver
surfactant non-invasively to patients2
1. AAP guidelines, 2013
2. WINDTREE primary market research (2014)
5
RDS Treatment Pathways
Initial treatment options include
invasive and non-invasive methods:
~40%
Surfactant
Therapy
• Animal-derived surfactant
• Delivered via intubation,
usually in combination with
mechanical ventilation
~60%
+
nCPAP Support until presumptive
endogenous surfactant production
Invasive mechanical
ventilation (IMV)
• Requires sustained
intubation
• Supports breathing until
patient can be weaned
• Non-invasive nasal delivery of
continuous positive airway pressure
• Supports breathing until the infant can
be weaned
TRADE-OFFS
Timely therapy delivery
vs.
Exposure to known significant
complications
Avoid exposure to known significant
complications
vs.
Cannot deliver surfactant and risk failure
>50% intubation and IMV
6
Clinicians seeking a non-invasive way to deliver surfactant
What is wanted1:
 Avoid the risks and complications
associated with delivery of surfactant
replacement therapy via intubation
and mechanical ventilation
 Possibility of repeat doses
 Avoid clinical instability associated
with administration of liquid
surfactant bolus administration
 Enable administration by nonspecialist staff
 Reduce cost of treating premature
infants
“…optimization of less invasive method
of surfactant administration will be
one of the most important subjects for
research in the field of surfactant
therapy of RDS in coming years”.
Kribs A. How best to administer surfactant to VLBW infants.
Arch Dis Child Fetal Neonatal Ed 2011;doi:10.1136.
1. Pillow & Minocchieri: Neonatology, 2012
7
AEROSURF® - Aerosolized Surfactant for RDS
Proprietary Synthetic
KL4 Surfactant
Designed to be structurally similar to human
lung surfactant
+
Proprietary Innovative Aerosol
Delivery System (ADS)
Designed specifically to aerosolize
and deliver KL4 surfactant
Liquid KL4 surfactant (intratracheal instillate) for
RDS approved by the FDA
Lyophilized (freeze-dried) KL4 surfactant –
developed initially for AEROSURF®
8
A Closer Look at RDS Treatment Option Trade-Offs
RISKS
BENEFITS
Surfactant
Therapy
Reversing surfactant deficiency has
a profound positive impact on
respiration
Surfactant therapy delivers nearimmediate clinical improvement
BPD
Infection, ventilator-induced
pneumonia
Bradycardia, hypertension, and
hypoxemia
Peri-dosing events associated with
bolus administration
Airway trauma
Lung injury
Pain, discomfort
Long-term impacts including vocal
cord damage, asthma, lung damage
nCPAP Supportive
Avoid exposure to the risks of
invasive delivery of surfactant
therapy
Negative impacts of delayed
surfactant therapy
Extended respiratory distress
until either endogenous
surfactant production or
transfer to invasive SRT
Significant nCPAP failure rate
leading to delayed surfactant
therapy via IMV and the
associated risk with that
therapy
9
Transformative Potential of AEROSURF®
RISKS
BENEFITS
Surfactant Replacement
Therapy (SRT)
Reversing surfactant deficiency has
a profound positive impact on
respiration
Surfactant therapy delivers
near-immediate clinical
improvement
BPD
Infection, ventilator-induced
pneumonia
Bradycardia, hypertension, and
hypoxemia
Peri-dosing events associated with
bolus administration
Airway trauma
Lung injury
Pain, discomfort
Long-term impacts including vocal
cord damage, asthma, lung damage
nCPAP Supportive
Avoid exposure to the risks of
invasive delivery of surfactant
therapy
The potential for
AEROSURF
All the benefits of
traditional surfactant
therapy without the
complications associated
with intubation and
mechanical ventilation
Negative impacts of delayed
surfactant therapy
Eliminates the need to
delay surfactant therapy
Extended respiratory distress
until either endogenous
surfactant production or
transfer to SRT
Physiologic benefits of a
synthetic formulation
Significant nCPAP failure rate
leading to delayed surfactant
therapy via IMV and the
associated risk with that
therapy
Reduced morbidity
Lower total cost of care
Improved peace of mind
10
Potential Drivers of Opportunity in RDS
#1
30%
Price
stated unmet
need in RDS
reduction in
CPAP failure is
meaningful
(but Total
Results in >40%
reported,
expected
patient share 1
Potential for
positive Health
Economics related
to non-invasive
approach, cost
avoidance, etc.2
“Non-invasive
surfactant delivery”
= 54% top, unaided
response (3x higher
1
than next response)
Market
Expansion
Cost)
Potential to bring
surfactant therapy
to new, lower
skilled / certified
hospitals and
geographies due to
non-invasive , less
specialized delivery 3
1) N=278 Neonatalogists, US & EU; Quant Research, November 2014
2) Defined Health Payer Research; Quant Research 2014
3) Windtree research and estimates
11
Prevalence of RDS Spans Across Gestational Ages / Severity
% of RDS Population
RDS Prevalance
<26 weeks GA
>95%
15% 9%
12%
31%
HIGHER
LOWER
32%
26-28 weeks GA
85-95%
29-32 weeks GA
65-75%
33-34 weeks GA
40-50%
35-36 weeks GA
5-10%
Size of Sub-Population
HIGHER
GA 26-28 wks
GA 29-32 wks
GA 33-34 wks
30% nCPAP 1st line
55% nCPAP 1st line
70% nCPAP 1st line
HIGHER
Severity of RDS & Incidence of CPAP Failure Rate
LOWER
Source: WINDTREE primary market research (2014); IMS MIDAS data (2012); CDC National Vital Statistics, 2014, Healthcare Costs and
Utilization Project (HCUP), 2013; Agency for Healthcare Research and Quality (AHRQ), 2012; Births by birth weight (CDC Website).
12
Initial Clinical Experience
AEROSURF® Phase 2a Study in 29 to 34 week gestational age (GA)
Phase 2a
Gestational Age (wks)
Phase 2a Expansion
29 – 34
15 min; 30 min; 45 min
( 25, 50, 75 TPL mg/kg)
(8 active, 8 control per group)
60 min; 90 min
(100 and 150 TPL mg/kg)
(8 active, 8 control per group)
Single dose
Primarily single dose
48
32
Safety and tolerability
Physiological data suggesting delivery of
KL4 surfactant to the lungs
Safety and tolerability of higher doses
and determine therapeutic index
(safety window)
Performance of Aerosol Delivery System
Continue physiological assessment
# of sites
Initiated with 3; increased to 8 (US)
12 (US)
Timeline / Milestones
Completed May 2015; key objectives
achieved
Completed Oct 2015
Dose Groups
# of patients
Objective(s)
13
AEROSURF® Phase 2a Study (29 to 34 wks GA)
Safety and Tolerability - Summary
The safety and tolerability profile of AEROSURF was generally comparable to the
control group
The Aerosol Delivery System delivered KL4 surfactant to the infants in a way that
was well tolerated
The adverse events and serious adverse events (SAE) seen were expected for
this patient population and generally comparable between AEROSURF® and
control groups
• Most common adverse events were jaundice, constipation, apnea and anemia
• Most common SAE’s were air leaks (including pneumothorax,
pneumomediastinum and pulmonary interstitial emphysema)
There was no pattern of increased adverse events or serious adverse events
with increasing doses of AEROSURF
14
AEROSURF® Phase 2a Study (29 to 34 wk GA)
nCPAP Failure by Treatment Group through 72 hours
100%
% Subjects Failed Through 72 Hrs
90%
70%
60%
50%
Focus for dose
selection going
forward
6/8
80%
5/8
21/40
75%
63%
53%
40%
30%
3/8
3/8
38%
38%
20%
1/7*
14%
10%
0%
nCPAP Only
25 mg/kg
(15 min)
50 mg/kg
75 mg/kg
100 mg/kg
(30 min)
(45 min)
(60 min)
Treatment Group
150 mg/kg
(90 min)
AEROSURF® treatment, primarily in single doses of 45 minutes and greater,
appears to be associated with lower rates of nCPAP failure.
* One intubated patient excluded due to being inappropriately enrolled
15
Phase 2a Study (29 to 34 wks GA)
45 and 60 Minute Dose Groups - nCPAP Failure through 72 hours
Time to nCPAP Failure
Percent Subjects Failed
100%
49%
relative
reduction
80%
60%
40%
21/40
53%
4/15*
27%
20%
0%
nCPAP Only
75 & 100 mg/kg
(45 & 60 min)
Treatment Group
(45 & 60 min)
At 72 hours post-dosing, 27% of AEROSURF® patients in the combined 45 and 60 minute dose groups
required intubation compared to 53% in the control group; a relative reduction in nCPAP failure of 49%
* One intubated patient excluded due to being inappropriately enrolled
16
AEROSURF® Phase 2a Study (29 to 34 wks GA)
45 and 60 Minute Dose Groups - nCPAP Failure through 72 hours
45 and 60 minute Dose Groups
Cumulative % Intubated
60%
50%
40%
Active
nCPAP
53%
Potential to repeat dose
27% 30%
27%
30%
27%
25%
18%
20%
15%
10%
0%
0%
3 hrs
0%
6 hrs
12 hrs
24 hrs
72 hrs
• Aerosolized KL4 surfactant produces physiological changes that are expected with surfactant
replacement therapy
• No AEROSURF patients in the 45 and 60 minute dose groups required intubation at 3 or 6 hours
post-dosing compared to 18% (7/40) of control patients
• AEROSURF 45 and 60 minute doses may be reducing the rates of intubation and also prolonging
the time to intubation – repeat dosing may be important to extend this effect until the patient’s
endogenous surfactant production is adequate
* One intubated patient excluded due to being inappropriately enrolled 17
Comprehensive AEROSURF® Phase 2 Program
Ongoing Trials
Phase 2a
Gestational
Age (wks)
Dose
Groups
Phase 2a Expansion
29 – 34
15 min; 30 min; 45 min
( 25, 50, 75 TPL mg/kg)
(8 active, 8 control per group)
Single dose
# of
patients
60 min; 90 min
(100 and 150 TPL mg/kg)
(8 active, 8 control per
group)
Primarily single dose
Phase 2a
Phase 2b
26 - 28
28– 32
30 min; 45 min; 60 min; 90
min (if needed)
(50, 75, 100 and 150 TPL
mg/kg)
(8 active, 8 control per
group)
Up to two doses
25 min; 50 min; Control
(40 and 80 TPL mg/kg)
Up to 3 doses
48-64
Up to 240
Safety and tolerability
Provide evidence of efficacy
on an acceptable endpoint
Physiological assessment
Identify dose regimens for
phase 3 study
48
32
Safety and tolerability
Physiological data suggesting
delivery of KL4 surfactant to
the lungs
Safety and tolerability of
higher doses and determine
therapeutic index (safety
window)
Performance of Aerosol
Delivery System
Continue physiological
assessment
# of sites
Initiated with 3; increased to
8 (US)
12 (US)
Up to 20 (US)
50+ (US, EU, Canada, LATAM)
Timeline /
Milestones
Completed May 2015; key
objectives achieved
Completed Oct 2015
Target top line data for first
three dose groups – Q1’17
Target top line data –
Mid-Year’17
Objective(s)
Provide est. of effect size
18
Prospective Observational Study
Study Overview
Findings
 Prospective observational study
of approximately 2,000
premature infants (U.S.,
Canada, E.U.) to collect data on
the treatment and outcomes in
the gestational ages we are
studying
 Approximately 75% of the 26-28 week
GA infants required intubation.
 Gain further understanding of
nCPAP use, intubations, oxygen
requirements and other
treatments that impact nCPAP
success/failure and the need
for intubation to better inform
our development and forecasts
 A lower proportion of the 29-34 week
GA infants require intubation, however,
the number of babies in this GA group is
much larger than the number of babies
in the younger GA group and actually
account for more intubations
 Infants whose oxygen requirement is
lower than used in our trial (including
“room air” / no oxygen requirement)
had a higher rate of nCPAP failure and
need for intubation than expected
19
Implications for the AEROSURF® Program
What we have learned  There is a greater clinical need and potential market opportunity in the
larger population of 29-34 week gestational age infants than many
previously considered
 The total addressable market opportunity for AEROSURF may extend to
neonates with a lower severity level of RDS at presentation and may begin
earlier in the treatment pathway (i.e. Delivery Room) for RDS treatment
optimization
 These and other observations help inform our current and future trial
design related to oxygen requirements, mix of gestational age groups, etc.
20
Encouraging clinical results suggest ADS is delivering KL4 surfactant
to the lungs but can we obtain direct evidence?
Can we demonstrate and quantify that aerosolized KL4
surfactant is actually getting into the lung?
Factors to consider:
• Pulmonary drug delivery through inhalation is challenging
• Characteristics of surfactants
• Device needed that can deliver a constant and acceptable
output rate and particle size
21
Pulmonary Drug Delivery Through Inhalation
Pulmonary drug delivery through inhalation can be very advantageous but
comes with significant challenges:
• Creating the appropriate particle size and aerosol concentration
• Producing consistent drug output from the aerosol device
• Delivering the drug through the patient’s anatomy and other breathing
apparatus
• Delivering the drug in different breathing characteristics
22
Aerosolizing surfactant has been a daunting task
 Currently available liquid surfactants are generally effective for treating RDS
but are administered via invasive intubation, which increases the risk of
serious complications – thus the pursuit for a noninvasive approach
 Surfactant characteristics make it a particularly challenging substance to
aerosolize due to:
• High viscosity; tendency to foam and bubble
• The need to avoid clogging or obstruction in the delivery system
• The need to deliver an adequate dose in the right particle size in a reasonable
amount of time
 Many have tried but there has been little success in aerosolizing surfactants
and there are no commercially available devices
 Given the characteristics of RDS and of premature infants, as well as the
heightened need for efficacy and safety in this fragile patient population, the
performance standard is high
23
Aerosol Delivery System
Summary
Aerosol Delivery System allows for a very well controlled and consistent
KL4 surfactant delivery system:
• High output
• Pre- and post-aerosolization characteristics of KL4 surfactant
are comparable
• Consistent output rate and particle size from device to
device
• Consistent output rate and particle size throughout the
dosing period
Controlled and reproducible experience
A solid platform for potential life-cycle advancements
24
Lung Deposition Study in Non-Human Primates
• Use of non-human primates (cynomolgus macaques)
– Nose, throat, & lung anatomy comparable to infants
– Respiratory function similar to preterm infants
– Lightly anesthetized, spontaneously breathing via nasal cannula
• In vitro studies performed to validate that admixed technetium-99m (99mTc)
travels with the aerosolized KL4 surfactant in a measurable and consistent
manner
• Radiolabeled KL4 surfactant aerosolized using Aerosol Delivery System (ADS),
delivered via nasal cannula in 3-10 min exposures inhaled from a nCPAP circuit
(3 L/min aerosol flow & 3 L/min CPAP flow) by 3 cynomolgus macaques
• Measured total & regional pulmonary deposition by a series of gamma images
with SPECT data used to determine regional lung deposition using a quantitative model
25
Lung Deposition Study - Distribution Information
nCPAP: NHP-3 Gamma Images
Planar
1
Planar
Planar 1
SPECT
SPECT
Planar
Planar22
1
Scintigraphy provided qualitative images indicating
wide spread distribution throughout entire lung
26
Lung Deposition Study – Quantitative Analysis of Distribution
Model divides the lung into 10 equal volume shells
Total Deposition Across 10 Equal Shells
52%
48%
Drug deposition observed across all areas of the lung after 3 to 10 min
of inhalation demonstrating generally uniform distribution of drug
between the inner half and the outer half of the lungs
27
Lung Deposition Study
Summary
• Aerosolized KL4 surfactant, delivered using the Aerosol Delivery System (ADS)
via nCPAP, is deposited within a few minutes throughout the lungs of NHPs
• The aerosol is observed to be homogeneously deposited in all regions of the
lungs
• These results are complemented by the clinical evidence seen in our phase
2a clinical trial in premature infants 29 to 34 weeks gestational age
• This study, along with other testing and
studies, should serve as a validation of
our ADS ability to effectively aerosolize
and deliver KL4 surfactant
28
Windtree as a Platform Company
KL4 surfactant + innovative Aerosol Delivery System (ADS) technology create a platform strategy that could enable
potential prevention / protection, treatment, and delivery of therapeutics in an array of diseases
RDS
Phase 2b
Program Focus
ALI - Radiation
Preclinical development
Prevention of acute &
chronic changes (fibrotic)
Mitigate lung injury,
prevent vent. / ECMO
Potential Application
Metastatic Breast & Lung
Rad.Onc; Biodefense
SARS, H1N1, MERS,
Viral pneumo (peds), etc.
ALI - Viral
Preclinical
ALI - Chemical
Preclinical
Mitigate lung injury, prevent
vent. / ECMO
Defense, industrial
Drug Delivery
Preclinical
Better delivery of drugs to
lungs / higher concentration
Antivirals, Antibiotics,
chemo agents, anti-fibrotic…
Planned Assessment & Prioritization in Q4’16
Cystic
Fibrosis
ECMO
Liberation
Acute
Asthma
Severe
Pneumonia
Post Surgical
Adhesion
COPD
+ Others?
Chronic
Sinusitis
Lung
Transplant
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Fast Track Designation and Regulatory Interactions
 The company held a Type C meeting with the FDA in April 2016 to obtain FDA
input on several aspects of our clinical development program
• In our assessment, the discussion reaffirmed our current and planned direction for
the AEROSURF® clinical development program
 In September 2016, the FDA granted Windtree a Fast Track designation for our
AEROSURF RDS program
• The Fast Track program was created by the FDA to facilitate the development and
expedite the review of new drugs that are intended to treat serious or lifethreatening conditions that demonstrate the potential to address an unmet medical
need
• This designation underscores the significant need to
reduce the use of invasive intubation and mechanical
ventilation, which are currently required to
administer life-saving surfactant therapy to
premature infants with RDS
30
Platform Exclusivities
Broad Multi-Faceted Exclusivity Portfolio
Regulatory Exclusivities
• Orphan Drug Designation in RDS for the U.S. and EU
Patents
 Lyophilized KL4 Surfactant Portfolio - to 2033
 Aerosol Delivery System Portfolio - through 2031+
Trade Secrets/Know-How
 Methods of Manufacture
 Non-USP Analytical Processes
Potential Challenges to Generic Entry
 Bioequivalence Complexities – Surfactants are Non-Receptor Based
31
Significant RDS Global Revenue Opportunity
8 to 10 Million LBW Children
Born Every Year Globally
Developed World – 250k to 350k RDS Patients
• Only 50% to 60% of RDS patients currently treated
with surfactant therapy
• Current market: invasive, undifferentiated,
animal-derived products
• Opportunity to expand treatment population and
increase the pharmacoeconomic value of surfactant
therapy
Developing World – 1.0 million+ RDS Patients
• Current surfactant market as large as the developed
world – fewer than 50% treated with surfactant
therapy
• Opportunity for growth as access to neonatal care
continues to increase world-wide
Regions
Estimated 2014
Annual Revenue
Invasive surfactant
therapy only†
US
$70 - $75 million
EU
$60 - $70 million
LATAM
$50 - $100 million
China
$50 - $100 million
GLOBAL
$250 - $345 million
Revenue Potential of
AEROSURF‡
$600 million to $1.0B+
† Current global revenue based on ~$900 to $1000 per treatment
‡
Windtree primary market research (2014)
In addition to expanding the number of patients treated, value of
AEROSURF® therapy potentially significantly higher than current
treatments – potentially reduces the largest cost-drivers for treating
premature infants with RDS: in the U.S. the average cost to treat low birth
weight (LBW) infants with RDS on MV is over $50,000; cost to treat patient
with chronic lung disease is over $100,000
CDC National Vital Statistics; UNICEF data; Windtree market research;
IMS MIDAS data; private companies with access to government purchasing
records for Latin America, China and Middle East
32
Financial Update as of September 30, 2016
• Cash and cash equivalents of $12.4 million as of September 30, 2016
– The Company anticipates that existing cash (before any additional
financings) is sufficient to fund operations through February 2017;
the Company is pursuing potential strategic and other transactions to
secure needed additional capital to ensure adequate financial
resources through phase 2b data with a modest cushion
• $25 million long-term debt with Deerfield: $12.5 million due in each
February 2018 (subject to potential deferral if specified milestone is
achieved) and in February 2019
33
Windtree’s Organizational Core Focus - 2017
Deliver Positive
Phase 2b Results
Value
Creation
Position for
Phase 3
Readiness
Successful
Transaction /
Major
Partnership
34
Focus on Execution for Value Creation
Initiate priority
life cycle studies
Initiate RDS phase 3
Milestone
End of phase 2 FDA
& EMA meetings
Phase 2b results
in 28-32 wk GA
Phase 2a
Lung Deposition
Study
(completed)
Phase 2a results
in 29-34wk GA
(Completed)
2016
in 26-28wk GA
2018
Transaction /
Strategic Partnership
Deliver positive phase 2 results
2017
Position Company as attractive, “phase 3 ready”
• Device: phase 3 / “go to market” validated and efficient
• Regulatory strategy and clarity
• Manufacturing efficiency and scale
• Commercial / access needs reflected in development
• Vetted and valued life cycle and platform opportunities
• Any potential risk or concerns mitigated
Strategic
Path
35
High Value-Creating Potential
 Well characterized asset and target application in RDS
 Potentially transformative therapy for the important, acute neonatology
market that has a clear unmet medical need and is growing
 Building data base of potential in safety, clinical effect and benefit
 Opportunity to build a positive health economic position as well as expand
use globally
 Broad IP with the potential to build a pipeline of aerosolized surfactant
therapies to address a variety of respiratory diseases
 Experienced management team focused on rigorous clinical execution and
effective cash management
 Significant near-term milestones
36
Windtree Therapeutics
“Striving to deliver Hope for a Lifetime!”
37