Windtree Therapeutics : November ’20 Corporate Presentation

Windtree Therapeutics

Company Overview

November 15, 2020

(NASDAQ: WINT)

Forward-looking Statements

This presentation includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements, among other things, include 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. The forward-looking statements provide our current expectations or forecasts of future events and financial performance and may be identified by the use of forward-looking terminology, including such terms as "believes," "estimates," "anticipates," "expects," "plans," "intends," "may," "will," "should," "could," "targets," "projects," "contemplates," "predicts," "potential" or "continues" or, in each case, their negative, or other variations or comparable terminology, though the absence of these words does not necessarily mean that a statement is not forward-looking. We intend that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. These risks and uncertainties are further described in the Company's periodic filings with the Securities and Exchange

Commission ("SEC"), including the most recent reports on Form 10-K, Form 10-Q and Form 8-K, and any amendments thereto ("Company Filings"). Moreover, we operate in an evolving environment. New risks and uncertainties may

emerge from time to time, and it is not possible for management to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

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.

2

Biopharmaceutical / device company located in Pennsylvania with research operations in Milan and Taipei. NASDAQ: WINT

Multiple clinical assets and a pipeline focused on important acute cardiovascular and acute pulmonary needs and markets

Currently executing several clinical programs which we believe have the potential to be catalysts for growth

Highly experienced management team and company leadership

3

Windtree Therapeutics

Windtree Therapeutics is a clinical-stage biopharmaceutical and medical device company with multiple advanced clinical programs spanning cardiovascular and respiratory disease states

	Lead Products	Pre-	Phase I Phase II Phase III	Next Milestone
FDA Fast Track	Istaroxime					▪ Initiate study start up in 2H 2020 for
Designation	(Acute Heart Failure)		Phase 2b				second phase 2b clinical trial in ~300
							patients targeted to start in mid2021
Potential for						▪ Active study in ~60 patients in early
Istaroxime
Breakthrough	(Cardiogenic Shock)		Phase 2			cardiogenic shock; Data currently
designation							expected Q3 2021
						▪ IND Accepted; Initiate trial Q4 2020;
FDA, EMA	KL4 Surfactant - COVID 19
Orphan Drug for	(COVID 19 Pilot; Possible invasive		Phase 2			anticipate data in late Q1 / early Q2
RDS	Tx for RDS in neonates)						2021
						▪ Bridge study in ~80 patients with
FDA Fast Track	AEROSURF
Designation,	(Non-Invasive Tx for RDS)		Phase 2b			new ADS to be funded and executed
Orphan Drug							by licensee
						▪	Out-licensing opportunity
	Rostafuroxin		Phase 2b
	(Genetically Associated HTN)
						▪	High interest target for partnership
	Oral SERCA2a Activators
	(Chronic HF; including HFpEF)					▪ Chronic and Acute Heart Failure

4

Strategy for Value Creation

Planned Milestones

To be updated once full assessment of potential COVID-19 impact to trial conduct is fully understood

• Four clinical programs focused on significant markets with unmet needs
• Multiple clinical and business milestones which may have the potential to be catalysts

Clinical Milestones

Corporate	Milestones

	2020					2021
Q2		Q3	Q4	Q1		Q2	Q3	Q4
		Early Cardiogenic Shock Study	Data,
		FDA Mtg
							Acute Heart Failure Study
							(transition to Phase 3)
		KL4 Surfactant	COVID-19		Data,
		Lung Injury
				FDA Mtg
			Treatment
							Timing TBD:
	AEROSURF Bridging Study				Data, FDA
							EOP2 into Ph3

Advance Pre-Clinical Oral Heart Failure Agents, LS and KL4 platform studies

NASDAQ up listing

SERCA2a & CV deal process

Rosta deal process

Data, EOP2 into Ph3,

potential partnering

(potential for out-license)	5

Dual Mechanism, SERCA2a Activator for the Treatment of

Acute Heart Failure and Early Cardiogenic Shock

Heart Failure -

A Large Market with Significant Unmet Need

The prevalence of heart failure is high and increasing (as is mortality)

• 6M U.S., 18-20M worldwide patients
• #1 cause of U.S. hospitalization in patients > 65 years old;
• • > 1.3M admissions annually (U.S.) ~1.5M admissions annually (E.U.)
• In-patientmortality up to 7%; 30-day: can exceed 10%
• Most expensive of the Medicare diagnoses; U.S. hospitals spend > $18B annually

Lack of therapeutic advances led the FDA to issue new Heart Failure Guidance in July 2019 for greater development flexibility in acceptable endpoints, specifically acknowledging mortality is not required

Sources: American Heart Association; DRG Data	7

Acute Heart Failure -

Significant Healthcare Issue with Significant Unmet Clinical Need

• There has not been meaningful new pharmacologic advancements in acute heart failure for decades
• Current approaches to acutely improve cardiac function are associated with unwanted 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
• Patients with low blood pressure (SBP) and peripheral hypoperfusion are high risk, challenging patients. These patients are also generally resistant to diuretic therapy and often discharged in a sub-optimal state
• • Low SBP in-patient mortality approximately two-fold greater than normal / high SBP1
  • There is a direct relationship between early drop in SBP and worsening renal function in acute heart failure2

1)	ADHERE Registry, n=48,567; JAMA 2006	8
2)	European Journal of Heart Failure; Voors, PRE-RELAX AHF Study; 2011; 13

Istaroxime - Novel First-in-Class Therapy

Novel intravenous agent designed to improve systolic contraction

and diastolic relaxation of the heart.

Dual Mechanism

of Action

1

2

Inhibition of the sodium-

Stimulation of SERCA2a activity enhances

potassium pump and effects on

calcium reuptake resulting in

the sodium-calcium exchanger

improvement of the diastolic relaxation

results in increased contraction

and subsequent contraction cycle

Impact on both

systolic and diastolic

dysfunction

9

Istaroxime AHF Phase 2a & 2b Studies - Summary

Multicenter, double blind, placebo-controlled, parallel group in 240 patients

Phase	n=120	Dosing=	6 hour
ADHF Patients	0.5, 1, 1.5µg/kg/min	Infusion
2a (dyspnea plus need for

IV furosemide ≥ 40mg)

Phase	n=120	Dosing=	24 hour
2b	ADHF Patients	1.0, 1.5µg/kg/min	Infusion

Phase 2 trial results demonstrated improved cardiac function without unwanted side effects of existing therapies

• Primary: PCWP significantly improved
• Stroke Vol & SBP - significant increase
• Heart Rate (HR) - lowered
• Primary: E/e' (echocardiographic assessment of PWCP) was significantly improved by both doses
• Heart rate decreased and stroke volume increased
• Istaroxime maintained / increased systolic blood pressure
• Renal function tended to improve
• No evidence for increased risk of arrythmia or increases in troponin
• Generally well tolerated (nausea and

infusion site discomfort were the most common AEs)

10

Primary Endpoint -

Significant Changes in E/e' Ratio and Stroke Volume

		istaroxime 1.0 µg/kg/min vs. placebo
istaroxime 0.5 µg/kg/min vs. placebo

	2.0						2.0
	1.0						1.0
	0.0						0.0
Ratio	-1.0					Ratio	-1.0
-2.0					-2.0
E/e'				E/e'	E/e'
-4.0				-4.0		*	*
	-3.0						-3.0
	-5.0						-5.0	Infusion period
	-6.0	Infusion period	*			-6.0			* p-values ≤ 0.034
			* p-value = 0.029
	-7.0
						-7.0
		Baseline	6 hours	24 hours	48 hours				Baseline	6 hours	24 hours	48 hours
		Placebo - Cohort 1	Istaroxime 0.5 µg/kg/min				Placebo - Cohort 2	Istaroxime 1.0 µg/kg/min
	8.0							8.0
	7.0		*					7.0
	6.0						6.0
								*
(ml/beat/m2)	5.0							5.0
			Stroke		(ml/beat/m2)
2.0					4.0
	4.0
	3.0							3.0
SVI					Volume		SVI	2.0
1.0					1.0
	0.0							0.0
	-1.0		Infusion period	* p-value = 0.031			-1.0		Infusion period
	-2.0							-2.0			* p-value = 0.009
		Baseline	6 hours	24 hours	48 hours
					Baseline	6 hours	24 hours	48 hours
		Placebo - Cohort 1	Istaroxime 0.5 µg/kg/min
					Placebo - Cohort 2	Istaroxime 1.0 µg/kg/min

Data shown as means and standard errors	11

Systolic Blood Pressure Maintained or Increased During Treatment and Renal Function Tended to Improve

istaroxime 0.5 µg/kg/min vs. placebo

istaroxime 1.0 µg/kg/min vs. placebo

	12
									12
	9											*
SBPinChange(mmHg)									9		**	**
6
		*
						(mmHg)SBPinChange	6
3		Infusion period
	0						SBP		3
	-3								0
	-6								-3
	-9								-6		Infusion period
									-9		* p-value = 0.011, ** p-values ≤ 0.006
											Baseline 3 hours	6 hours 12 hours 24 hours 48 hours 72 hours
			Placebo - Cohort 1	Istaroxime 0.5 µg/Kg/min					Placebo - Cohort 2	Istaroxime 1.0 µg/Kg/min
	20							20
	15							15
	10							10		*
	(mL/min/m2)eGFR						GFR
	5						(mL/min/m2)eGFR	5
		0								0
		-5							-5
			Infusion period					Infusion period
	-10
							-10
	-15							-15
	-20	Placebo - Cohort 1	Istaroxime 0.5 µg/Kg/min					Placebo - Cohort 2	Istaroxime 1.0 µg/Kg/min
							-20			* p-value = 0.044
			Baseline	24 hours	48 hours	72 hours
							Baseline	24 hours	48 hours	72 hours
						Data shown as means and standard errors		12

Heart Rate Decreased and No Increases in Cardiac Troponins

Istaroxime 0.5 µg/kg/min vs. placebo

Istaroxime 1.0 µg/kg/min vs. placebo

(bpm)	9
6
3
Rate	0
-3
Heart
-6		*
-9	Infusion period
in	-12		* p-value = 0.014
Change	-15
		Placebo - Cohort 1	Istaroxime 0.5 µg/Kg/min

		9
		6	Infusion period
		3		*
Heart		0
	-3
RateRate		-9
		-6
Heartin	(bpm)	-12		**	** **	* p-value = 0.011,
-15	**	** p-values ≤ 0.005
Change		Placebo - Cohort 2		Istaroxime 1.0 µg/Kg/min

Cardiac TnT

cTnT - 0 to 24 hours

cTnT - 24 to 72 hours

50									50
45									45
40									40
35									35
30									30
25									25
20									20
0	3	6	9	12	15	18	21	24	24	36	48	60	72

Favorable Profile Observed with 24-hour Holter Monitoring

	Clinically significant arrhythmias				Clinically significant arrhythmias
12.0%
10.5%			10.5%			10.5%			25.0%
10.0%																				20.0%			20.0%			20.0%
8.0%																			20.0%
																																12.5%
																		15.0%
6.0%																						10.0%					10.0%
																		10.0%
4.0%
			2.4%					2.4%			2.4%
2.0%																				5.0%
0.0%																				0.0%
		Baseline	Day 1 (Infusion)		Day 2			Baseline	Day 1 (Infusion)		Day 2
		Placebo - Cohort 1				Istaroxime 0.5 µg/Kg/min				Placebo - Cohort 2				Istaroxime 1.0 µg/Kg/min

				Ventricular Tachycardia					Ventricular Tachycardia
			47.4%			47.4%
50.0%	43.9%	46.3%	42.1%			80.0%
													60.0%60.0%	60.0%
40.0%													31.7%	60.0%
													50.0%									50.0%
30.0%
																	40.0%
20.0%																40.0%
10.0%																20.0%
0.0%
Baseline		Day 1		Day 2	0.0%
								(Infusion)								Baseline	Day 1 (Infusion)		Day 2
		Placebo - Cohort 1		Istaroxime 0.5 µg/Kg/min			Placebo - Cohort 2			Istaroxime 1.0 µg/Kg/min

PVCs (n°/24 hours) shown as median, ventricular tachycardia and clinically significant arrhythmias shown as percentage of patients

14

Istaroxime - Acute Heart Failure

Next Steps

Objective: Create a strong phase 3 and partnership position

Execute an additional study designed to complete Phase 2 and inform Phase 3

• 300 patients, 75 centers globally (estimates)

Leverage characteristics in a target population whose needs match the unique attributes of istaroxime: patients with low blood pressure and/or diuretic resistance

Increase infusion time to >24 hours

Obtain data on measures that can be primary endpoints for phase 3

Planned study start up in 2H 2020 to be able to

enroll in mid-2021 with resourcing

15

Early Cardiogenic Shock Treatment

Istaroxime Potential Opportunity for Accelerated Approval Pathway

Cardiogenic shock is a severe presentation of heart failure characterized by very low blood

pressure and hypoperfusion accompanied by high PCWP and decreased urine output

Challenges

FDA Regulatory Commentary

with Break-Through Therapy

Designation Potential

No satisfactory pharmacological intervention

to reverse the conditions

High associated mortality and morbidity

Sponsors are potentially not required to show a benefit other than an increase in blood pressure to support approval of drugs to treat hypotension in the setting of shock1. (Precedent:

NDA for Giapreza® (IV Angiotensin II), approved in 2017 for increasing

MAP in distributive shock)2

Precedent lead us to believe there may be opportunities

for an accelerated regulatory pathway and review

1. Kosaraju A, Hai O. Cardiogenic Shock. [Updated 2019 Jan 25]. In: https://www.ncbi.nlm.nih.gov/books/NBK482255/

CSRC Think Tank - July 24, 2019	16
2) Senatore et al., Am J Cardiovasc Drugs, February 2019, Volume 19, Issue 1, pp 11-20(https://doi.org/10.1007/s40256-018-0297-9)

Istaroxime SBP Change from Baseline to 6 or 24 Hours from the Phase 2a and 2b Dose Groups

SBP Mean Change ± SE (mmHg)

Istaroxime has the potential to improve blood pressure

and organ perfusion in patients with AHF

20.0

18.0

16.0

14.0

12.0

10.0

8.0

6.0

4.0

2.0

0.0

2a Study	2b Study	2a Study	2b Study	2a Study
0.5 µg/kg/min	1.0 µg/kg/min	1.5 µg/kg/min

Study/Dose

Mean SBP at Baseline ~112 mmHg	6 Hours 24 Hours

17

Istaroxime -

Early Cardiogenic Shock in Severe AHF Study

Goal:

• Improve SBP with acceptable safety profile
• • Increased systolic and diastolic cardiac function without increasing heart rate, risk for arrythmias or myocardial oxygen demand
• Support a breakthrough therapy regulatory application

Ongoing early cardiogenic shock study:

(while we are preparing for the larger phase 2b acute heart failure study):

~60 patients in early cardiogenic shock (SBP 75-90mmHg) with AHF in the EU and US 1.5µg/kg/min target dose for 24 hours

• Primary endpoint is SBP AUC at 6 hours
• Other measures include: arrythmias, SBP AUC at 24 hours, echo measures, etc.

Started Q3-2020 with data expected in Q3 2021

18

Pre-Clinical Programs

Novel Oral SERCA2a Activators for HF + Acute Pulmonary Platform

The Company also has early exploratory research programs to identify potential product candidates including:

Cardiovascular

Selective SERCA2a	Dual Mechanism Compounds
Activators	for Heart Failure
▪ Oral & i.v. therapies for chronic heart failure	▪ Oral & i.v. therapies for CHF, AHF
(CHF) and AHF
▪ Attractive approach for heart failure with
preserved ejection fraction (HFpEF)

These next generation agents and platform are part of a complete chronic and acute portfolio for licensing / partnership and the market

Acute Pulmonary

KL4 Platform

for lung protection and drug delivery

19

COVID-19

Lung Injury Treatment

Synthetic KL4 Surfactant for the Treatment of Lung Injury in COVID-19 Patients

COVID-19 and ARDS Have A Significant Negative Impact On Surfactant Related Lung Function

Uses angiosten-

converting enzyme 2 (ACE2) for entry into host cells

ACE2 is a surface molecule on alveolar Type 2 cells of lungs, the source of surfactant in the lung

Damaged Type 2 cells	Increased likelihood of
results in impaired	mechanical ventilation
surfactant production

• COVID-19infection can cause serious lung injury resulting in acute respiratory distress syndrome (ARDS) - a condition with high mortality and no approved drug therapies and where surfactant abnormalities are an important factor.
• Recent publications suggest that lung fibrosis and severe interstitial changes occur in COVID-19 patients who developed ARDS1, 2, 3.
• • These changes resemble those seen in premature infants who are initially ventilated due to RDS and later develop bronchopulmonary dysplasia (BPD).
  • These observations support the rationale for use of exogenous surfactant in the treatment of ARDS

caused by COVID-19.

1)	Bernheim, A., X. Mei, et al. (2020). "Chest CT Findings in Coronavirus Disease-19(COVID-19): Relationship to Duration of Infection." Radiology: 200463.
2)	Hosseiny, M., S. Kooraki, et al. (2020). "Radiology Perspective of Coronavirus Disease 2019 (COVID-19): Lessons From Severe Acute Respiratory
Syndrome and Middle East Respiratory Syndrome." American Journal of Roentgenology: 1-5.	21
3) Song, F., N. Shi, et al. (0). "Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia10.1148/radiol.2020200274." Radiology0(0): 200274

KL4 Surfactant Significantly Reduced Mortality in a Pre-ClinicalH5N1 Study - With and Without Anti-Viral Agent

• Ferrets Infected with highly pathogenic avian (H5N1) influenza
• Results in significant viral and inflammation related lung damage that

is substantially ameliorated by KL4 surfactant treatment

KL4 = aerosolize KL4 surfactant, WFI = aerosolized water (control), AVD = aerosolized KL4 surfactant + antiviral

22

Surfactant Administration In Severe COVID-19 Lung Injury May Have Potential to Provide Significant Benefits

• We believe our synthetic KL4 surfactant may have the potential to mitigate surfactant deficiency and resist the widespread surfactant destruction that can occur as a result of COVID-19
• Synthetic KL4 surfactant removes any immunological concerns and has manufacturing scalability versus animal- derived surfactants

Pre-clinical and clinical evidence shows surfactant replacement therapy has the potential to:

Improve

• Lung function
• Gas exchange and oxygenation
• Lung compliance

Decrease

• Inflammation in the lung
• Which may decrease lung damage, facilitate recovery and decrease mechanical ventilation

References in appendix

23

Lucinactant (KL4 Surfactant) For The Treatment of COVID-19

Initial phase 2 study is to demonstrate changes in physiological parameters in COVID-19 associated lung injury and ARDS

• Up to 20 patients from 4-5 US sites
• • led by investigators at Brigham & Women's and Duke Medical Center
• Dosing through the endotracheal tube, target 80 mg TPL/kg. Repeat dosing

based on improvement in oxygenation

• Outcome measures include:
• • Physiologic response: Oxygenation Index (OI)
  • Lung compliance on the ventilator
  • Clinical parameters (time on MV, days in ICU, mortality)

Q4 2020 start; expected recruitment in approximately 3 - 6 months of time

(depending on COVID-19 rates)

If study outcomes are favorable, plan can be to initiate 2 expanded trials:

1. Expanded study in ventilated patients to establish outcomes
2. Aerosolized delivery to avoid mechanical ventilation (similar to our respiratory distress syndrome studies)

24

Evidence of KL4 Surfactant Potential Utility in COVID-19 - Demonstrated Utility Across Various Respiratory Distress

We have been evaluating the applicability of KL4 surfactant for multiple etiologies of

lung injury as well as pandemic influenza long before the COVID-19 pandemic

Demonstrated Utility of KL4

	Extensive Studies in	▪ 13 studies for intratracheal administration including RDS, BPD, acute
	Acute Lung	hypoxemic respiratory failure and adults with ARDS
	Conditions:	▪ 2,148 patients enrolled | 1,028 treated
		▪ Aerosolized KL4 surfactant studied in 366 subjects enrolled, 223 subjects
		treated
	SARS and Subsequent	▪ ~$10M of NIH support for clinical and non-clinical programs including lung
	Support for Acute	protection studies involving viral infections with H1N1 and RDS
	Lung Injury Studies	▪ CEO testified before congressional committee regarding KL4 for the treatment
		of SARS
	American Thoracic	▪ KL4 surfactant has to the potential to be employed to protect the lung and
	Society	reduce mortality in patients exposed to highly pathogenic influenza as well as
	Presentation	against pandemic strains

In May 2018 data from a preclinical animal model of a highly

pathogenic H5N1 viralpneumonia was presented showing aerosolized KL4 surfactant reduced lung damage and improved overall survival

25

AEROSURF®

Synthetic KL4 Surfactant with Proprietary Aerosol Delivery System for the Treatment of RDS

Respiratory Distress Syndrome (RDS)

Current Treatment Pathways

• Premature infants experience respiratory distress syndrome ("RDS") due to lungs lacking endogenous surfactant. Surfactant helps keep lungs open between breaths and gas exchange
• Physicians must choose between invasive surfactant delivery with known, significant complications or non-invasive nasal continuous positive airway pressure (nCPAP) alone (that often fails without surfactant)

			AEROSURF			Current Treatment
			Non-Invasive Synthetic Surfactant	Invasive Surfactant (~40%)		nCPAP Only (~60%)
	▪		Proprietary Synthetic KL4 surfactant1:
Surfactant		- Structurally similar to human lung	▪	Animal derived	▪	None
			surfactant
Method of	▪		Proprietary aerosol delivery system (ADS)	▪	Intubation usually in	▪	Nasal prongs
		combination with
Delivery			with nCPAP
			mechanical ventilation
	▪ Timely surfactant therapy delivered non-
			invasively to avoid potential complications	▪	Timely therapy, but	▪	Avoid exposure to
The	▪		Improves respiratory parameters		exposure to known		significant complications
AEROSURF	▪		Potential for decreased nCPAP failures and		significant complications	▪	Foregoing surfactant
Difference			decreased need for invasive intubation and		associated with invasive		treatment results in
			decreased rates of bronchopulmonary		intubation		notable nCPAP failure rate
			dysplasia (BPD)				and intubations

1. Liquid KL4surfactant for RDS approved by the FDA. Lyophilized KL4 currently being developed for AEROSURF

27

AEROSURF® - Potential to Impact the Clinical Course of RDS

Building Evidence From Nearly 400 Patients Studied

Long-Term

Outcomes

Reduced Rates and

Severity of BPD

Noninvasive RDS

treatment

Study results across each

of these important

parameters show evidence of a potential impact on the clinical course of RDS and respiratory health of preterm infants

Less Intubation

and Respiratory

Support Required

Improved

Respiratory

Parameters

Decreased Rate of

nCPAP Failures

28

AEROSURF® Program Evolution and Strategy

Mitigating Risks and Strengthening Our Approach

Program Evolution

✓ Transitioned to the newly-developed ADS

• • Demonstrated efficacy in
    reducing nCPAP failure, need for
    intubation and BPD with a
    generally positive safety profile
• Completed three phase 2a

and 2b trials

Program Strategy

1 Execute a small (n=~80 - 90) Bridging Study to transition to EOP2 / Phase 3:

• Demonstrate the new ADS works and supplement phase 2 data
• Optimize dosing with more drug and shorter repeat intervals

2 Leveraging the partnership with

Lee's to execute in Asia (the largest market) and fund the above study in a non-dilutive manner

• We believe this allows Windtree to do more investment across adult applications (i.e. Lung Injury) and with acute cardiovascular programs)

3 Continue business development for potential additional partnerships and licensing ex-Asia

29

Summary

Financial Summary & Capitalization as of Sept. 30, 2020

• Cash & Equivalents of ~$22.4 million
• Bank Debt: ~$2.4M credit facility due in March 2022

Securities	Common Equivalents
Common Stock	16,921,482
Options (WAEP $15.76)	1,906,878
Warrants (WAEP $16.40)	7,896,150
Fully Diluted Equivalents	26,724,510

31

Strategy for Value Generation

Strong Clinical Execution to Deliver Milestones: Execute well our several important, late-stageclinical programs for news flow and achievement of milestones that may be catalysts for growth

Transactions:

• Secure focused BD transactions for deal revenue and non-dilutive financial support of clinical development.
• Progress the heart failure platform to an attractive and valuable position for global partnership (while retaining US co-promotion rights)

Optimization: Leverage our highly experienced team in execution and in portfolio optimization efforts that may bring in new, well suited development opportunities / transactions

32

Windtree Therapeutics

"Striving to deliver Hope for a Lifetime!"

Appendix

Cardiac Output, Blood Pressure and Renal Function are Critical Factors in Managing AHF Patients and Their Outcomes

In-Hospital Mortality Rates by Admission

Systolic Blood Pressure Deciles (n = 48,567)

Gheorghiade, M. et al. JAMA 2006;296:2217-2226.

35

Istaroxime Phase 2a (HORIZON-HF) Study

• Multicenter, double blind, placebo-controlled, doses 6-hour infusion of istaroxime 0.5, 1.0, 1.5 ug/kg/min, conducted in the EU
• Hospitalized with AHF, with criteria including:
• • LVEF ≤ 35%
  • SBP 90-150 mmHg
• N=120 (30/group)
• Significant improvement in PCWP, SBP, heart rate was lower. Istaroxime was generally well tolerated with no unexpected adverse events

Primary Endpoint:

PCWP Significant Improvements

Dose-dependent Increase in SBP

36

Istaroxime Phase 2b Adverse Events

	Pooled placebo	istaroxime 0.5	istaroxime 1.0
Event	mg/Kg/min	mg/Kg/min
(n=39)
	(n=41)	(n=40)
All adverse events	23	(59.0%)	31 (75.6%)	33 (82.5%)
Adverse events leading to	1	(2.6%)	-	4 (10.0%)
discontinuation
Serious adverse events	2	(5.1%)	2 (4.9%)	6 (15.0%)
Cardiac death		-	-	1 (2.5%)
Cardiogenic shock		-	-	1 (2.5%)*
Cardiac failure	1 (2.6%)	2 (4.9%)	3 (7.5%)
Renal embolism		-	-	1 (2.5%)
Transient ischemic attack	1 (2.6%)	-	-
Hyperventilation	1	(2.6%)	-	-
Hypotension	1	(2.6%)	-	-
Adverse Drug Reactions†	10	(25.6%)	23 (56.1%)	25 (62.5%)
Cardiovascular††	9 (23.1%)	4 (9.8%)	7 (17.5%)
Gastrointestinal‡	2 (5.1%)	4 (9.8%)	14 (35.0%)
Infusion site pain/inflammation		-	20 (48.8%)	13 (32.5%)

Note: data shown as n° patients (%) - patients can have more than one event during the 30-day follow up period

• Same patient who then died, and 1 additional death occurred at Day 31 (cardiac death) outside the 30 day window
  † Adverse Drug Reactions are AEs related to study drug
  ††Most common - arrhythmia, atrial fibrillation, cardiac failure, ventricular tachycardia
  ‡ Most common - abdominal pain, nausea, vomiting, diarrhoea

37

References Supporting Utilization of KL4 Surfactant for the Treatment of Lung Injury

1. Hoffmann, M., H. Kleine-Weber, et al. (2020). "The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells 10.1101/2020.01.31.929042." bioRxiv: 2020.01.31.929042.
2. Bernheim, A., X. Mei, et al. (2020). "Chest CT Findings in Coronavirus Disease-19(COVID-19): Relationship to Duration of Infection." Radiology: 200463.
3. Hosseiny, M., S. Kooraki, et al. (2020). "Radiology Perspective of Coronavirus Disease 2019 (COVID-19): Lessons From Severe Acute Respiratory Syndrome and Middle East
   Respiratory Syndrome." American Journal of Roentgenology: 1-5.
4. Song, F., N. Shi, et al. (0). "Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia10.1148/radiol.2020200274." Radiology0(0): 200274
5. Gregory TJ, Steinberg KP, Spragg R, Gadek JE, Hyers TM, Longmore WJ, et al. Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1997;155:1309-1315.
6. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European consensus conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149:818-824.
7. Nicholas TE, Doyle IR, Bersten AD. Surfactant replacement therapy in ARDS. White knight or noise in the system? Thorax. 1997;52:195-197.
8. Brandstetter RD, Sharma KC, DellaBadia M, Cabreros LJ, Kabinoff GS. Adult respiratory distress syndrome: A disorder in need of improved outcome. Heart & Lung. 1997;26:3-14.
9. Wiedemann HP, Tai DY. Adult respiratory distress syndrome (ARDS): Current management, future directions. Cleve Clin J Med. 1997;64:365-372.
10. Fulkerson WJ, MacIntyre N, Stamler J, Crapo JD. Pathogenesis and treatment of the adult respiratory distress syndrome. Arch Intern Med. 1996;156:29-38.
11. Schuster DP, Kollef MH. Acute respiratory distress syndrome. Disease A Month. 1996;42:267-326.
12. Schuster DP, Kollef MH. The acute respiratory distress syndrome. New Engl J Med. 1995;332:27-37.
13. Sachdeva RC, Guntupalli KK. Acute respiratory distress syndrome. Crit Care Clin. 1997;13:503-521.
14. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2:319-323.
15. Petty TL, Reiss OK, Paul GW, et al., Characteristics of pulmonary surfactant in adult respiratory distress syndrome associated with trauma and shock. Am Rev Respir Dis. 1977;115:531-536.
16. Petty TL, Silvers, Paul GW, Stanford RE. Abnormalities on lung properties and surfactant function in adult respiratory distress syndrome. Chest. 1979;75:571-574.
17. Hallman M, Spragg RG, Harrell JH, Moser KM, Gluck L. Evidence of lung surfactant abnormality in respiratory failure: Study of bronchoalveolar lavage phospholipids, surface activity, phospholipase activity, and plasma myoinositol. J Clin Invest. 1982;70:673-683.
18. Pison U, Seeger W, Buchhorn R, Joka T, Brand M, Obertacke U, et al. Surfactant abnormalities in patients with respiratory failure after multiple trauma. Am Rev Respir Dis. 1989;140:1033-1039.
19. Pison U, Overtacke U, Brand M, Seeger W, Joka T, Bruch J, et al. Altered pulmonary surfactant in uncomplicated and septicemia-complicated courses of acute respiratory failure. J Trauma. 1990;30:19-26.
20. Gregory TJ, Longmore WJ, Moxley MA, Whitsett JA, Reed CR, Fowler AI, et al. Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest. 1991;88:1976-1981.
21. Greene KE, Wright JR, Steinburg KP, et al., Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med. 1999;160:1843-1850

38

Surfactant in ARDS References

1. Gregory TJ, Steinberg KP, Spragg R, Gadek JE, Hyers TM, Longmore WJ, et al. Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1997;155:1309-1315.
2. Wiedemann H, Baughman R, de Boisblanc E, et al., A multi centered trail in human sepsis-induced ARDS of aerosolized synthetic surfactant (Exosurf). Am J Respir Crit Care Med. 1992; 145:A184.
3. Weg JG, Balk RA, Tharratt RS, et al., Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrone. JAMA 1994;272:1433-1438.
4. Anzueto A, Baughman RP, Guntapalli KK, et al., Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. New Engl J Med. 1996;334:1417-1421.
5. Spragg RG, Gilliard N, Richman P, et al., Acute effects of a single dose of porcine surfactant on patients with the acute respiratory distress syndrome. Chest 1994;105:195-202.
6. Walmrath D, Gunther A, Ardeschir H, et al., Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis. Am J Respir Crit Care Med 1996;154:57-62.
7. Walmrath D, Grimminger F, Papert D, et al., Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics. Eur Respir J. 2002;19:805-810.
8. Wilson DF, Zaritsky A, Bauman LA, et al., Instillation of calf lung surfactant extract (calfactant) is beneficial in pediatric acute hypoxemic respiratory failure. Crit Care Med 1999;27:188-195.
9. Willson DF, Zaritsky A, Bauman LA, Dockery K, James RL, Conrad D, Craft H, Novotny WE, Egan EA, Dalton H. Instillation of calf lung surfactant extract (calfactant) is beneficial in pediatric acute hypoxemic respiratory failure. Members of the Mid-Atlantic Pediatric Critical Care Network. Crit Care Med. 1999;27(1):188-95.
10. Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, Jacobs BR, Jefferson LS, Conaway MR, Egan EA; Pediatric Acute Lung Injury and Sepsis Investigators. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA. 2005;293(4):470-6.
11. Willson DF, Thomas NJ, Tamburro R, Truemper E, Truwit J, Conaway M, Traul C, Egan EE; Pediatric Acute Lung and Sepsis Investigators Network. Pediatric calfactant in acute respiratory distress syndrome trial. Pediatr Crit Care Med. 2013;14(7):657-65.
12. Willson DF, Truwit JD, Conaway MR, Traul CS, Egan EE. The Adult Calfactant in Acute Respiratory Distress Syndrome Trial. Chest. 2015;148(2):356-364.
13. Walmrath D, De Vaal JB, Bruining HA, et al. Treatment of ARDS with a recombinant SP-C(rSP-C) based synthetic surfactant. Am J Respir Crit Care Med 2000;161:A379.
14. Spragg RG, Lewis JF, Wurst W, Häfner D, Baughman RP, Wewers MD, Marsh JJ. Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant. Am J Respir Crit Care Med. 2003;167(11):1562-6.
15. Spragg RG, Lewis JF, Walmrath HD, Johannigman J, Bellingan G, Laterre PF, Witte MC, Richards GA, Rippin G, Rathgeb F, Häfner D, Taut FJ, Seeger W. Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome. N Engl J Med. 2004;351(9):884-92.
16. Taut FJ, Rippin G, Schenk P, Findlay G, Wurst W, Häfner D, Lewis JF, Seeger W, Günther A, Spragg RG. A Search for subgroups of patients with ARDS who may benefit from surfactant replacement therapy: a pooled analysis of five studies with recombinant surfactant protein-C surfactant (Venticute). Chest. 2008;134(4):724-32.
17. Spragg RG, Taut FJ, Lewis JF, Schenk P, Ruppert C, Dean N, Krell K, Karabinis A, Günther A. Recombinant surfactant protein C-based surfactant for patients with severe direct lung injury. Am J Respir Crit Care Med. 2011;183(8):1055-61.
18. Wiswell TE, Smith RM, Katz LB, et al., Bronchopulmonary segmental lavage with Surfaxin (KL4-surfactant) for acute respiratory distress syndrome. Am J Respir Crit Care Med 1999;160:1188-1195.

39

Respiratory Distress Syndrome (RDS)

Current Treatment Pathways

Premature infants experience RDS due to underdeveloped lungs lacking endogenous surfactant.

Surfactant helps keep lungs open between breaths and proper gas exchange

Initial treatment options include

~40%

invasive and noninvasive methods:

~60%

Surfactant

+

Invasive mechanical

nCPAP support until endogenous

therapy

ventilation (IMV)

surfactant production

vs.

• Animal-derived surfactant

• Noninvasive nasal delivery of continuous

• Delivered via intubation, usually in

positive airway pressure (nCPAP)

combination with mechanical ventilation

• Supports breathing

TRADE-OFFS

Timely therapy delivery

Avoid exposure to significant complications

vs.

vs.

Exposure to known significant

Foregoing surfactant treatment results in

complications

notable nCPAP failure rate

Ultimately, more than 50% of RDS infants are intubated and ventilated

Source: Windtree and third-party market research	40

Windtree Technology Platform - AEROSURF®

Proprietary Synthetic	+	Proprietary Innovative Aerosol
KL4 Surfactant	Delivery System (ADS)
Structurally similar to human lung surfactant		Utilizing pressure and heated
Liquid KL4 surfactant (intratracheal instillate)		capillary has demonstrated
	ability to aerosolize KL4 surfactant
for RDS approved by the FDA
Lyophilized KL4 surfactant currently being		Controlled, effective and
developed for AEROSURF
	reproducible performance
		validated in studies

• KL4 surfactant has been shown to improve lung function in premature infants, resulting in decreased nCPAP failures and need for invasive intubation
• KL4 surfactant also has anti-inflammatory and other potentially positive attributes

41

Transformative Potential of AEROSURF®

BENEFITS

RISKS

Surfactant

Therapy

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

Respiratory Support

Avoids exposure to the risks

of invasive delivery of

surfactant therapy

Negative impacts of delayed

surfactant replacement

therapy (SRT)

Prolonged RDS until either

endogenous surfactant production or transfer to invasive surfactant therapy

Significant rate of nCPAP failure leading to delayed surfactant therapy via intubation and mechanical ventilation

The potential for

AEROSURF

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

Synthetic formulation

Reduced morbidity

Lower total cost of care

42

Business Development Focus

Short- term

Mid-term

(Data & EOP2)

Long-term

(Strategy)

We are actively engaged in discussions with multiple

companies with a proactive focus as follows:

Cardiovascular Partner - China

Pure SERCA2a Pharma Partner - Global

AEROSURF® / KL4 Licensing ex-Asia

Heart Failure Portfolio Partner - Global

Rosta Out-License - Global

Portfolio Optimization and Expansion

Retained US Co-Promo Rights

43