Corporate Presentation April 2017 NASDAQ: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)

Nasdaq: WINT

Windtreetx.com

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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

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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)

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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%

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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

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+

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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 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 of

adminstration

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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 respiratory distress

until either endogenous surfactant production or

transfer to SRT

Significant nCPAP failure rate leading to delayed surfactant

therapy via IMV and the associated risk of

adminstration

All the benefits of traditional surfactant therapy without the

complications associated with intubation and

mechanical ventilation

Eliminates 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).

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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%

Focus of 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 – Mid-Year’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

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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*

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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 – Mid-Year’17

Comprehensive AEROSURF® Phase 2 Program Ongoing Trials

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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

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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

Aerosol Delivery System 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

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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

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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

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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

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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

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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)

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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

Focus on Execution for Value Creation

Deliver positive phase 2 results

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

Transaction / Strategic Partnership

Initiate RDS phase 3

Initiate 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)

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Financial Overview

• Cash and cash equivalents of $5.6 million as of December 31, 2016

• 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 future payments of 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 mid-2017 with a modest cushion

• $25 million long-term debt: $12.5 million due in February 2018 (subject to potential deferral if specified milestone is achieved) 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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