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Corporate Presentation May 2017 OTCQB:WINT
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Forward Looking Statement
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.
Public, small cap biopharmaceutical / medical device company
Based in Warrington, PA with approximately 50 employees
Focused in the acute respiratory area with a lead program expected to address a significant need and expand the Respiratory Distress Syndrome (RDS) in premature infants market (currently valued at $400 million)
OTCQB: WINT
Windtreetx.com
3
Windtree Therapeutics
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 replacement within the first hours of life
1
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)
Respiratory Distress Syndrome (RDS)
4
RDS Treatment Pathways
Surfactant Therapy
nCPAP Support until presumptive endogenous surfactant production
Invasive mechanical ventilation (IMV)
• Animal-derived surfactant
• Delivered via intubation, usually in combination with mechanical ventilation
• 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
Timely therapy delivery vs.
Exposure to known significant complications
Avoid exposure to known significant complications
vs. Cannot deliver surfactant and risk failure
Initial treatment options include invasive and non-invasive methods:
TRADE-OFFS
>50% intubation and IMV
+
~40% ~60%
5
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 non-specialist staff
Reduce cost of treating premature infants
1. Pillow & Minocchieri: Neonatology, 2012
“…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.
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AEROSURF® - Aerosolized Surfactant for RDS
Proprietary Synthetic
KL4 Surfactant
Designed to be structurally similar to human
lung surfactant
Liquid KL4 surfactant (intratracheal instillate) for RDS approved by the FDA
Lyophilized (freeze-dried) KL4 surfactant – developed initially for AEROSURF®
Proprietary Innovative Aerosol
Delivery System (ADS)
Designed specifically to aerosolize
and deliver KL4 surfactant
7
+
8
A Closer Look at RDS Treatment Option Trade-Offs
Reversing surfactant deficiency has a profound positive impact on
respiration
Surfactant therapy delivers near-immediate clinical improvement B
ENEF
ITS
RIS
KS
Surfactant Therapy
nCPAP Respiratory Support
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
Avoid exposure to the risks of invasive delivery of surfactant
therapy
Negative impacts of delayed surfactant therapy
Extended RDS until either
endogenous surfactant production or transfer to
invasive SRT
Significant rate of nCPAP failure leading to delayed
surfactant therapy via intubation and mechanical
ventilation
9
Transformative Potential of AEROSURF®
Reversing surfactant deficiency has a profound positive impact on
respiration
Surfactant therapy delivers near-immediate clinical
improvement
BEN
EFIT
S R
ISK
S
Surfactant Replacement Therapy (SRT)
nCPAP Respiratory Support
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
Avoid exposure to the risks of invasive delivery of surfactant
therapy
Negative impacts of delayed surfactant therapy
Extended RDS until either
endogenous surfactant production or transfer to SRT
Significant rate of nCPAP failure leading to delayed
surfactant therapy via intubation and mechanical
ventilation
All the benefits of traditional surfactant therapy without the
complications associated with intubation and
mechanical ventilation
Noninvasive administration eliminates or reduces the need
to delay surfactant therapy
Physiologic benefits of a synthetic formulation
Reduced morbidity
Lower total cost of care
Improved peace of mind
The potential for AEROSURF
Prevalence of RDS Spans Across Gestational Ages / Severity
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).
10
Severity of RDS & Incidence of CPAP Failure Rate
HIGHER
LOWER
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 LOWER Size of Sub-Population
HIGHER
9%
12%
32% 31%
15%
% of RDS Population
<26 weeks GA
26-28 weeks GA
29-32 weeks GA
33-34 weeks GA
35-36 weeks GA
RDS Prevalence (est. 135k in U.S.)
>95%
85-95%
65-75%
40-50%
5-10%
AEROSURF® Clinical Development Program
Phase 2a Prospective
Observational Study Phase 2a Phase 2b
Gestational Age (wks)
29 – 34 26 – 34 26 - 28 28– 32
Dose Groups
15 min; 30 min; 45 min, 60 min and 90 min
( 25, 50, 75, 100 & 150 TPL mg/kg)
8 active, 8 control / group Primarily single dose
N/A
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
# of patients
80 2,000+ 48-64 Up to 240
Objective(s)
Safety and tolerability
Physiological data suggesting delivery of KL4
surfactant to the lungs
Therapeutic Index
Performance of Aerosol Delivery System
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
Safety and tolerability
Physiological assessment
Provide evidence of efficacy on an acceptable endpoint
Identify dose regimens for
phase 3 study
Provide est. of effect size
# of sites 12 (US) 28 (US, EU, Canada) Up to 20 (US) 50+ (US, EU, Canada, LATAM)
Timeline / Milestones
Completed Oct 2015 Completed Sept 2016 Target top line data for first three dose groups – Q2’17
Target top line data – July ’17
Comprehensive AEROSURF® Phase 2 Program Completed Trials – Initial Clinical Experience
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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
12
Phase 2a Study (29 to 34 wks GA) 45 and 60 Minute Dose Groups - nCPAP Failure through 72 hours
Time to nCPAP Failure
* One intubated patient excluded due to being inappropriately enrolled
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%
(45 & 60 min)
53%
27%
0%
20%
40%
60%
80%
100%
nCPAP Only 75 & 100 mg/kg
Pe
rce
nt
Sub
ject
s Fa
iled
Treatment Group
21/40
(45 & 60 min)
4/15*
13
49% relative
reduction
AEROSURF® Phase 2a Study (29 to 34 wks GA) 45 and 60 Minute Dose Groups - nCPAP Failure through 72 hours
• 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
45 and 60 minute Dose Groups
0% 0%
27%* 27%* 27%*
15%
18%
25%
30%
53%
0%
10%
20%
30%
40%
50%
60%
3 hrs 6 hrs 12 hrs 24 hrs 72 hrs
Cu
mu
lati
ve %
Intu
bat
ed
Active
nCPAP
14 * One intubated patient excluded due to being inappropriately enrolled
Potential to repeat dose
Phase 2a Prospective
Observational Study Phase 2a Phase 2b
Gestational Age (wks)
29 – 34 26 – 34 26 - 28 28– 32
Dose Groups
15 min; 30 min; 45 min, 60 min and 90 min
( 25, 50, 75, 100 & 150 TPL mg/kg)
8 active, 8 control / group Primarily single dose
N/A
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 three doses
# of patients
80 2,000+ 48-64 Up to 240
Objective(s)
Safety and tolerability
Physiological data suggesting delivery of KL4
surfactant to the lungs
Therapeutic Index
Performance of Aerosol Delivery System
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
Safety and tolerability
Physiological assessment
Provide evidence of efficacy on an acceptable endpoint
Identify dose regimens for
phase 3 study
Provide est. of effect size
# of sites 12 (US) 28 (US, EU, Canada) Up to 20 (US) 50 (US, EU, Canada, LATAM)
Timeline / Milestones
Completed Oct 2015 Completed Sept 2016 Top line data for first 3 dose groups – Q2’17
Top line data – July ’17
Comprehensive AEROSURF® Phase 2 Program Ongoing Trials
15
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
16
Aerosolizing surfactant has been a daunting task
Encouraging clinical results suggest ADS is delivering KL4 surfactant to the lungs - but could we obtain direct evidence?
Aerosol Delivery System (ADS)
ADS allows for a very well controlled and consistent KL4 surfactant delivery system:
Controlled and reproducible experience
A solid platform for potential life-cycle advancements
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• 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
Lung Deposition Study in Non-Human Primates
18
Plan
ar 1
Planar 1
SPECT
Planar 2 Planar 1 SPECT Planar 2
Scintigraphy images indicating wide spread distribution throughout entire lung
• Use of non-human primates (cynomolgus macaques)
– Nose, throat, & lung anatomy comparable to infants
– Respiratory function similar to preterm infants
• In vitro studies validated 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
• Measured total & regional pulmonary deposition by a series of gamma images with SPECT data used to determine regional lung deposition using a quantitative model
Lung Deposition Study – Quantitative Analysis of Distribution
19
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
Model divides the lung into 10 equal volume shells Total Deposition Across 10 Equal Shells
48% 52%
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 life-threatening 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
20
Fast Track Designation and Regulatory Interactions
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
Conventional bioequivalence studies and not relevant as Surfactants are Non-Receptor Based
21
22
Potential Drivers of Opportunity in RDS
#1 stated unmet need in RDS
“Non-invasive surfactant delivery” = 54% top, unaided response (3x higher than next response)
20-30% reduction in
CPAP failure is meaningful
Results in >40% reported, expected
patient share
Price (but Total
Cost)
Potential for positive Health
Economics related to non-invasive approach, cost avoidance, etc.
Market Expansion
Potential to bring surfactant therapy
to new, lower skilled / less certified hospitals and
geographies due to non-invasive , less
specialized delivery
1 1
1) N=278 Neonatalogists, US & EU; Deerfield Quant Research, November 2014
2) Defined Health Payer Research; Also, Deerfield Research 2014
3) Windtree research and estimates
3
2
Significant RDS Global Revenue Opportunity
• Only 50% to 60% of RDS patients currently treated with surfactant therapy
• Opportunity to expand treatment population due to easier, non-invasive approach enables delivery in less specialized centers
• Positive pharmacoeconomic value supports higher price
8 to 10 Million Low Birth Weight Children Born Every
Year Globally
Regions
Estimated 2016 Annual Revenue
Invasive surfactant therapy only†
US $90 million
EU/ME $85 million
LATAM $90 million
China / Asia
$110 million
GLOBAL $375 million
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$800MM -
$1B
Aerosurf
Potential
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
Funding by NIH • NIH has funded over $9 million for AEROSURF and other KL4 surfactant related
projects, including $5 million for AEROSURF phase 2a and 2b studies in neonatal RDS
What’s known about KL4 Surfactant: • Maintains alveolar patency, improves gas exchange, similar to essential
human surfactant protein SP-B
• Lung protective effects via reduced acute lung inflammation and potential to impact chronic fibrosis
• Immunomodulatory properties
• Anti-inflammatory activity
• Anti-bacterial/anti-viral properties
• Potential for mucus clearance
• Non-immunogenic
• Resistant to inhibition and/or inactivation by plasma proteins/oxidants
• Can be effectively aerosolized (AEROSURF)
24
KL4 Surfactant Platform
Modulation of the inflammatory process, antimicrobial properties and non-immunogenicity. Wolfson, M.R., Wu,, Hubert, Gregory, Mazela, & Shaffer, T.H. 2012
Attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS. Pediatr Res, 72(4), 375
Bactericidal properties of the novel, peptide-containing surfactant - Surfaxin®. Black C, Leon C, Pluim J., Pediatric Academic Societies, Honolulu, HI, May, 2008. E-PAS2008:633756.11; and Clayton RG, Cochrane CG, Gregory TJ
Does not induce an immune response in a standardized preclinical model. Pediatric Academic Societies, Honolulu, HI, May, 2008. E-PAS2008:633756.12
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RDS
ALI - Radiation
ALI - Viral
ALI - Chemical
Phase 2b
Preclinical development
Preclinical
Preclinical
Prevention of acute & chronic changes (fibrotic)
Metastatic Breast & Lung Rad.Onc; Biodefense
SARS, H1N1, MERS, Viral pneumo (peds), etc.
Defense, industrial
Cystic Fibrosis
ECMO Liberation
Post Surgical Adhesion
Planned Assessment & Prioritization in Q2/Q3’17
Acute Asthma
Chronic Sinusitis
Severe Pneumonia
COPD Lung Transplant
Drug Delivery
Preclinical Antivirals, Antibiotics, chemo agents, anti-fibrotic…
+ Others?
Mitigate lung injury, prevent vent. / ECMO
Mitigate lung injury, prevent vent. / ECMO
Better delivery of drugs to lungs / higher concentration
Program Focus Potential Application
Leverage our innovative technology to advance acute pulmonary disease care and outcomes
Value to Windtree Development Plan Characteristics
Lyophilized dosage form of our KL4 surfactant drug product that was previously approved by the FDA as a liquid dosage form
Currently used in AEROSURF® development program
Improvements and benefits include fully synthetic (vs. animal derived), stability expected at 3 years+, cold chain but no need for warming
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Lyophilized Lucinactant A Second Asset Expands the Opportunity
Lucinactant LS
Strengthen RDS position as a provider for all surfactant needs and compete in 100% of market and clinical pathways (non-invasive and invasive)
May enhance WINT’s RDS offering with a second product based on the same drug being studied in AEROSURF and previously approved as SURFAXIN®
LS for bolus application gives Windtree a platform for
non-aerosolized applications
Execute Phase 3 in RDS
(liquid bolus application) in 2H 2018
– Obtain regulatory advice on trial design and approval requirements in 1H 2018
Potential to develop for other future indications where aerosolized KL4 is not indicated (i.e., where patient is intubated for their condition, etc.)
Focus on Execution for Value Creation
Deliver positive phase 2 results
Company “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 • Life cycle and platform opportunities prioritized and valued • Risk mitigation strategy – to address potential risks / concerns
Transaction / Strategic Partnership
Initiate Aerosurf ® RDS phase 3
Initiate LS & priority life cycle studies
2016
2017
2018
Phase 2a in 26-28 wk GA
Lung Deposition Study
(completed)
Phase 2b results in 28-32 wk GA
End of phase 2 FDA & EMA meetings
Milestone
Strategic Path
Phase 2a results in 29-34 wk GA
(Completed)
27
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Current Financial Overview
• Cash and cash equivalents of $8.0 million as of March 31, 2017
• Completed a $10.5 million private placement of convertible preferred stock units in February 2017 (including $1.6 million in non-cash consideration in the form of a reduction in development services expenses)
• During the first quarter of 2017, we completed registered offerings under our ATM Program resulting in net proceeds to us of approximately $1.0
• The Company anticipates that currently existing cash (before any additional financings) is expected to be sufficient to fund its operations through AEROSURF® phase 2b data release in July 2017
• $25 million long-term debt: $12.5 million due in February 2018 and in February 2019
Kathy Cole Human Resources
John Tattory CFO
Steve Simonson, MD Chief Development Officer
Craig Fraser CEO
Mary Templeton General Counsel
George Cox Manufacturing & Supply
Ron Dundore Regulatory and Quality
Larry Weinstein Medical Device
Highly Experienced Management Team
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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
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High Value-Creating Potential
Windtree Therapeutics
“Striving to deliver Hope for a Lifetime!”
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