NASDAQ: WINT

Corporate PresentationJuly 2019

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Forward-looking Statement

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 should refer to the Company Filings for a fuller discussion of the matters presented here.

To the extent that statements in this presentation are not strictly historical, including statements about the Company’s clinical development programs, business strategy, outlook, objectives, plans, intentions, goals, future financial conditions, future collaboration agreements, the success of the Company’s product development activities, 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 including risks relating to the Company’s recent merger with CVieTherapeutics. 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”)

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§ Public, biopharmaceutical / medical device company (OTCQB: WINT)

§ Successful merger and a simultaneous private placement in Q4 2018• Three Late-stage assets in development– Istaroxomine– AeroSurf– Rostafuroxin

• Pre-clinical pipeline of additional platform assets

§ Current market cap of approximately $145MM.

§ Headquarters in Pennsylvania, USA • Operations in Taipei, Taiwan• Research in Milan, Italy

Windtree – Post-Merger Global Company

Windtree Therapeutics Global, Diversified, Late-Stage Development Company

Rostafuroxin+ Pre-Clinical Programs:

SERCA2a(Selective Action) Oral & i.v. for chronic

and acute heart failure

CV-IST2 (Next Generation Dual

Action SERCA2a) Oral & i.v. for chronic and

acute heart failure

EleisonAerosol Oncology collaboration

KL4 Platformfor lung protection and drug delivery

for RDS treatment

for genetically targeted resistant hypertension and renal impairment

+ Pre-Clinical Heart Failure Candidates and Programs:

Cardiovascular Acute Pulmonary

for non-invasive treatment of RDS

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Multiple Planned MilestonesShort to Mid Term Strategy Intended for Value Creation

2019 2020 2021AEROSURF Bridge Study(transition to ph3)

Ista Study*(transition to ph3)

Advance Pre-Clinical Oral HF agents

Advance LS and KL4 platform studies

Nasdaq application

* Next step Ista clinical program still under discussion

Multiple Potential Clinical and Business Development

Activities for News Flow

Data, EOP2 into Ph3

Data, Partner,

EOP2 into Ph3

ü Ista: Complete ph2 in a manner to create strong “phase 3 asset” clin/reg and partnership position while also advancing oral follow-on product candidates through POC with the objective of developing greater platform value

ü AEROSURF: Bridge new device to ph3. Leverage partnerships and non-dilutive funding ü Rosta: Out-license and use the money as non-dilutive funding of other, core programs ü Investment Support: Apply for Nasdaq listing, multiple clinical and BD activities for

potential news flow. Continue to be open to M&A opportunities

Rosta deal processfor out-license

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§ 6 million patients in the U.S. and over 18 million worldwide. The prevalence of HF is on the rise

§ HF is the #1 cause of hospitalizations in the United Stateswith greater than 1 million admissions annually and the top reason for readmissions in patients over 65 years old.

§ Inpatient mortality is 7 percent and 30-day mortality exceeds 10 percent

§ $35B spent on HF annually in the U.S. alone with over half being direct hospital cost for acute treatment.

Heart Failure – A Significant Healthcare Issue

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Heart Failure - Significant Unmet Clinical Need

§ Acute heart failure is a complex condition and patients are often difficult to treat

§ Current treatments have unwanted side-effects• Heart rhythm disturbances• Increased heart rate and myocardial oxygen demand• Decreased blood pressure• Potential damage to the heart muscle (increased troponin)• Worsening renal function• Mortality• Lack of approved treatment or treatment options in certain patients

(such as those with lower blood pressure and diuretic resistant)

§ Treatment is needed to improve cardiac function without causing other adverse clinical outcomes

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§ Novel intravenous agent designed to improve systolic contraction and diastolic relaxation and fill function of the heart

§ Unique, dual luso-inotropic mechanism of effect that impacts bothsystolic and diastolic dysfunction

• Inhibits the sodium-potassium pump and effects on the sodium-calcium exchanger, resulting in more calcium available for contraction Inotropic effect (systole)

• Stimulates SERCA2a activity to enhance calcium reuptake improving the relaxation-contraction cyclelusitropic effect (diastole) – may also serve to enhance safety as

well

Istaroxime – Novel, First in Class Therapy

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Development Highlights

- 6 studies conducted in 280 patients with 3 doses- Positive phase 2b trial results replicated positive phase 2a results

The primary assessments of pulmonary capillary wedge pressure and secondary assessment of stroke volume were significantly improved by all doses. Uniquely, increases in systolic blood pressure (SBP) and GFR also significantly increased in two phase 2 trials

Decrease in heart rate, no effect on troponin, lower O2 consumption and did not impair renal function. Appears less pro-arrhythmic than many current therapies with less clinically significant arrhythmias than placebo.

Safety

Efficacy

Studiedto Date

Istaroxime Phase 2b Study Design and Measures

Following a positive phase 2a study, the company conducted a Phase 2b trial

§ Multicenter, double blind, placebo-controlled, parallel group in 120 patients (24 Italy, 96 China)

§ 3 arms: 0.5 or 1.0 µg/kg/min, or placebo – infused over 24 hours

§ Hospitalized for recurrent AHF (dyspnea at rest/minimal exertion plus need for IV furosemide ≥40 mg); adult population

• Left Ventricle Ejection Fraction (LVEF) ≤ 40%, E/Ea ratio >10• BNP ≥ 350 or NT-pro-BNP ≥1400 pg/mL• SBP 90-125 mmHg

§ Outcome measures• Echo - primary endpoint: Δ E/Ea at 24 hrs• BNP, cTnT, ventricular ectopy• Dyspnea measured by VAS

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§ The primary endpoint, E/Ea, was significantly (p<0.05) improved by both doses of istaroxime in the ITT and PP populations

§ Stroke volume also significantly increased (~5ml) with both doses§ Uniquely, Ista increased SBP and there was also a post infusion improvement in

GFR. • Also, HR decreased lowering myocardial oxygen demand.

§ Perhaps as important as the efficacy assessments, during the istaroxime infusion there were:

• No signals of increased arrhythmias and clinically significant arrythmias were lower with both doses of ista vs. placebo

• No signals of increased troponin (no heart muscle damage)• No adverse impact to renal function was observed

§ The most common adverse events were infusion site reactions and nausea and vomiting similar to the Phase 2a trial

§ These safety assessments confirmed the profile from the Phase 2a trial and suggest that istaroxime may be able to provide the improved cardiac performance needed in AHF patients without the untoward effects seen with current therapies

Istaroxime Phase 2b Study – Results Summary

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Istaroxime Next StepsFocus on rigorous, smart development

1. Windtree is working with top Heart Failure advisors and has had good engagement and guidance from the FDA in planning the direction for the program. It plans to also seek EMA Scientific Advice as well.

2. To transition Ista to a good phase 3 ready position, the company plans produce additional clinical results to include endpoints acceptable to the agencies for phase 3 (and that may ultimately support commercial and payer messaging). Windtree plans to leverage the characteristics of Ista in a target population that may particularly benefit from the unique attributes of the drug, those with lower SBP and / or diuretic resistant patients and dose patients earlier and infuse longer.

3. For business development, Windtree intends to advance to a solid “phase 3 ready asset” clinical, regulatory and partnership position while also advancing oral follow-on assets through proof of concept to solidify the total heart failure platform

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Dual Mechanism SERCA2a Activators

§ SERCA2a activators with Na+/K+

pump inhibitory activities§ As oral and i.v. therapies for AHF

and/or CHF

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Novel Heart Failure Portfolio-Oral and IV SERCA2a Activators for Chronic & Acute Heart Failure

Selective SERCA2a Activators

§ Selective SERCA2a Activators devoid of any Na+/K+ pump inhibitory activities

§ As oral therapies for AHF and/or CHF

• Heart Failure is a therapeutic area of interests for many large pharmaceutical companies and SERCA2a is of particular interest. As such we are in early discussions with multiple companies.

• Our HF product assets share a common, novel SERCA2a platform and form a heart failure portfolio. This mechanism and platform is to be leveraged as complete portfolio opportunity for licensing / partnership

NASDAQ: WINT

AEROSURFUpdate

®

Respiratory Distress Syndrome (RDS) Current 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 (nCPAP)• Supports breathing until the infant can be

weaned

Timely therapy deliveryvs.

Exposure to known significant complications

Initial treatment options include invasive and non-invasive methods:

Avoid exposure to known significant complications

vs. Cannot deliver surfactant and risk failure

TRADE-OFFS

nCPAP failure

>50% are intubated and ventilated

+

~40% ~60%

Source: Windtree and third-party market research16

Premature infants experience RDS due to underdeveloped lungs lacking endogenous surfactant. Surfactant helps keep lungs open between breaths and proper gas exchange

Clinicians Seeking a Noninvasive Way to Deliver Surfactant

What is wanted1:

üAvoid the risks, complications and clinical instability associated with delivery of surfactant therapy via intubation and mechanical ventilation

üPossibility of repeat doses

üEnable administration by non-specialist staff

üReduce costs of treatment

üBetter long term outcomes

1. Pillow & Minocchieri: Neonatology, 2012

Kribs A. How best to administer surfactant to VLBW infants. Arch Dis Child Fetal Neonatal Ed 2011;doi:10.1136.

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“…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”.

Windtree Technology Platform - AEROSURF®Potential to Provide Both Non-Invasive and Invasive Solutions to Treat RDS

Proprietary Synthetic KL4 Surfactant

Structurally similar to human lung surfactant

Liquid KL4 surfactant (intratracheal instillate) for RDS approved by the FDA

Lyophilized (freeze-dried) KL4 surfactant –currently being developed for AEROSURF®

Proprietary Innovative Aerosol Delivery System (ADS)

Utilizing pressure and heated capillary has demonstrated ability to break through the

barrier to effectively aerosolize KL4

surfactant

Controlled, effective and reproducible performance validated in bench comparative studies and in the lung deposition study

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+

• KL4 has been shown to reduce surface tension to keep the infants lungs inflated better than nCPAP alone, thus resulting in decreased nCPAP failures and need for invasive intubation

• KL4 also has anti-inflammatory and other potentially positive effects on the lungs of premature infants

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Significant Program Evolution and Applied Learnings

Through Ph2b (3 studies in ~380 patients)

• Innovative non-invasive administration of surfactant that avoids the complications and helps make the SOC (nCPAP) fail less often

• Phase 2a & 2b provided promising data that the drug worked with positive / targeted results when dosed as intended

• Prototype device produced treatment interruptions -- we needed to evolve device development

Program Evolution Since 2b

• Successful development of new, improved design ph3+ ADS device. Ready to bridge to ph3

• In addition to failing nCPAP less often with AEROSURF, Ph2 long term outcomes and analysis (in all ITT) suggest AEROSURF exposure in first 24 hours may have the potential to change clinical outcomes and may have durable benefit to the preterm infants pulmonary health

Recent Advancements and Finding’s

AEROSURF® Latest Data -Decreased BPD Incidence and Severity

Definition

AEROSURF (≥75 mg/kg)

(N=88)

Control(N=95) p-value

O2 at 36 Weeks Incidence 7 (8.0%) 16 (16.8%) 0.07NIH definition Mild 3 (3.5%) 4 (4.2%)

Moderate 3 (3.4%) 4 (4.2%)

Severe 1 (1.1%) 8 (8.4%)

High Dose Patients (n=183): Rate and Severity for Doses ≥75 mg/kg or Control

26-28 Weeks PMA 28-32 Weeks PMA

DefinitionAEROSURF

(N=24)Control(N=24)

AEROSURF(N=142)

Control (n=71)

O2 at 36 Weeks 0 (0%) 6 (25%) 14 (10%) 10 (14%)

p-value 0.02 0.37

Incidence for ALL Patients (n = 261)

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Bronchopulmonary Dysplasia (BPD), a chronic lung disease of the newborn who have required intubation, mechanical ventilation and oxygen therapy. BPD is associated with ongoing pulmonary disease, neurodevelopmental impairment and increased healthcare utilization contributing to substantial patient morbidity and healthcare costs. Despite its importance, effective prevention and treatment strategies for BPD have been elusive and there is no approved treatment.

Noninvasive RDS treatment

Improved Respiratory Parameters

Decreased Rate of nCPAP Failures

Less Intubation and Respiratory

Support Required

Reduced Rates and Severity of BPD

Long Term: reduced hospitalizations in

first year of life

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AEROSURF® Building Evidence Potential to Impact on the Clinical Course of RDS

Study results across each of these important

parameters show evidence of the potential to impact the clinical course of RDS and respiratory health of

preterm infants

Evolution of Aerosolized Delivery System (ADS) from Phase 2 Prototype to the Phase 3 / Commercial Device

• 2012 – 2017• Developed,

designed and assembled by Battelle Memorial Institute (Battelle)• Used in prior

phase 2 clinical experience

Current ADS is our Phase 3 and

forward device

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§ Same aerosol delivery technology to provide comparable key aerosol characteristics of emitted dose and particle size of the phase 2 device for bridging of device and data

§ Enhanced design with 4x larger filters (that must meet new standards for flow) to avoid treatment interruptions.

• Tested this improvement in over 90 high dose runs § Faster start-up and change-over. Built in step by step

instructions with detailed images§ Transferring manufacturing and technology to Mack

Medical

Phase 2 Prototype

§ nCPAP alone as control versus adding AEROSURF® treatment in blinded study

§ GA range: 26-32 weeks. N=70 planned (35 per group) in a design similar to Phase 2b

§ ~20-25 select sites, planned Timing: ~3 quarters study duration, plan is to start in 2H of 2019

§ Key Measures:• CPAP failure (primary endpoint)• ADS Device performance

• Safety and tolerability

AEROSURF® Bridge Study Objectives and Design

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§ Dose: Initial 100 min dose for all infants; with up to 3 repeat doses of 50 min (determined by infant FiO2); minimum 20 minute assessment between doses

• Ph2b was 50 min. high dose, 2 repeats possible with a 2 hour interval between doses

§ FiO2 > 25% to qualify, >21% for repeat dosing to allow infants to receive more treatments

§ Bridge Study not powered for significance, however we would like to show magnitude of effect >20%

Transition to and set up a strong Phase 3Execute a Bridge Study to transition the new, Phase 3 and forward platform ADS device in order to meet the following objectives:üDemonstrate consistent, phase 3 ready performance with the new ADSüGenerate additional supportive data with more intensive dosing

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Potential Drivers of AEROSURF® Opportunity

#1stated unmet need in RDS

“Noninvasive surfactant delivery” = 54% top, unaided response (3x higher than next response)

20-30%reduction in

nCPAP failure is meaningfulResults in >40%

reported, expected

patient share

Price(but Total

Hospital Cost)

Potential for positive health

economics related to noninvasive approach, cost avoidance, etc.

Market Expansion

Potential to bring surfactant therapy

to new, lower skilled and less capable

hospitals and geographies due to noninvasive , less

specialized delivery

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1. N=278 Neonatalogists, US & EU; WINDTRprimary market research (2014)2. WINDTREE primary market research (2014)3. Windtree research and estimates

2BPD: “A trend of >20% reduction in

BPD = 70+% in expected patient

share”

$1.2B+AEROSURF®

Potential(see appendix)

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Hypertension Market –A Unique, Genetically Targeted Approach

• Hypertension is a very large market with high unmet need. • Over 1/3 of the adult population in the U.S. has hypertension and the majority of

treated patients (50-85% globally) do not reach target for control. Well known that ethnicity can impact response to different classes of agents

§ Uncontrolled/resistant hypertension has been associated with certain genetic subsets of the population

• Adducin polymorphisms and endogenous ouabain can trigger hypertension by enhancing renal tubular sodium reabsorption and increasing vascular tone

§ Rostafuroxin is designed to be a potent and selective antagonist of ouabain and of the mutant adducin molecule and the functional effects

• It may offer the possibility to reduce blood pressure in a genetically identified subset of patients representing approximately 28% of hypertensives and reduce the risk of CV events beyond the level expected reduction of blood pressure because the molecular mechanism blocked is also involved in organ damage.

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Rostafuroxin Reduced Blood Pressure in Caucasians with Select Mutation in Both Phase 2a and Phase 2b Trials

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-25

-20

-15

-10

-5

0

rostafuroxin daily dose mg (µmol)

50 mg 0,5 mg 0,05 mg 0,006 mg(1,34) (0,134) (0,0134)

Losartan

Chan

ge in

BP,

mm

Hg

Phase IIb trial in EU (Caucasians) w/ Mutation

• In an earlier Phase 2a trial, rostafuroxin reduced blood pressure in a European population with select genetic profile

• For Phase 2b, CVie conducted a two part study with the first part, n=160, conducted in Italy in Caucasian patients.

• Rostafuxin was generally safe and well tolerated• Efficacy results for the Phase 2b in Europe demonstrated positive response:

Differential Response to Rostafuroxin in the PEARL 2b Study

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0

20

40

60

80

%

% responders

The potential reasons for the limited response in Chinese patients is under review and may include:

• Drug metabolism • Oral bioavailability• Drug Interaction with traditional Chinese medicines

While the BP reduction in Caucasians was notable in two trials, blood pressure response in Chinese patients was significantly less pronounced at the same doses:

CaucasianChinese

1. Complete pharmaceutical development work for final formulation

2. Continue ongoing work to explain the ethnic differences seen in the Phase 2b trial

3. Seek to develop Rostafuroxin into an asset that is attractive for partnering and conduct business development - including with companies that have previously expressed and interest.

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Rostafuroxin Next Steps

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Financial UpdateAs of March 31, 2019

§ Cash and marketable securities of $15.5 million as of March 31, 2019

• Supports development activities, operations and debt service through October 2019

§ Assumed $8.0 million of debt from CVie

• $4.5 million in a bank credit facility currently due in March 2020 (under discussions)

• $3.5 million due to Lee’s Pharmaceuticals; ($3.0M remains)

• Fully diluted outstanding shares of 46.4 million and 72.0 million available for future issuance.

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Multiple Planned MilestonesShort to Mid Term Strategy Intended for Value Creation

2019 2020 2021AEROSURF Bridge Study(transition to ph3)

Ista Study*(transition to ph3)

Advance Pre-Clinical Oral HF agents

Advance LS and KL4 platform studies

Nasdaq application

* Next step Ista clinical program still under discussion

Multiple Potential Clinical and Business Development

Activities for News Flow

Data, EOP2 into Ph3

Data, Partner,

EOP2 into Ph3

ü Ista: Complete ph2 in a manner to create strong “phase 3 asset” clin/reg and partnership position while also advancing oral follow-on product candidates through POC with the objective of developing greater platform value

ü AEROSURF: Bridge new device to ph3. Leverage partnerships and non-dilutive funding ü Rosta: Out-license and use the money as non-dilutive funding of other, core programs ü Investment Support: Apply for Nasdaq listing, multiple clinical and BD activities for

potential news flow. Continue to be open to M&A opportunities

Rosta deal processfor out-license

Windtree Therapeutics

“Striving to deliver Hope for a Lifetime!”