Treating COPD: Late Stage Global Program

including China

May 2019

22

Executive Summary

q Chronic Obstructive Pulmonary Disease (“COPD”) is a major health issue in China that impacts 13.7% ofthe population over the age of 40

q Excessive and abnormal mucus production is the primary cause of death in COPD. As yet, no currenttreatments address this underlying cause

q Chronic Airway Therapeutics (“CAT”) is newly formed through a spinout, with a unique and proprietarydrug program to address this underlying cause of death

q CAT is using unique properties of nadolol to treat respiratory disease, using a patented technique thathas regulatory and commercial precedent

q Phase 1 and 2 US FDA clinical trials have been completed for the oral application and we are in processto proceed to late stage trials in China through dialogue with NMPA (“China FDA”) as well as USA

q Concurrently, we will work on Phase IIB in the US, and progress the development of the inhalerapplication

q We are looking for partners to help fund and deliver the clinical trials

The Need

4

§ Top 3 leading cause of death in China1

§ Direct medical costs US$72-$3,565 per capita (33-118% of avg income)1

§ 12 million hospitalizations each year§ 12 million will die in the next 5 years § 1.2 billion doctor visits each year § Current treatments address peripheral symptoms and do not resolve the root

cause

13.7% of China’s population over the age of 40 has COPD, amounting to 99 million people in China

– Huadong Hospital, Nov 2018

Disease % # China # Hospital # Deaths (next 5 yrs)

Notes

Severe Asthma 0.85% of population

12mm (8mm children, 4mm adults)

8mm p.a.(0-1 p.a. 50%, 1-2 p.a. 25%, 2+ p.a. 25%)

1.5mm(10-15% have 5 year mortality)

• 5% population has asthma • 17% of asthma patients have severe

asthma• 36.7 per 100,000 asthmatics die p.a.

Chronic Bronchitis 5% 50mm 4.2mm 10mm (15%)

1mm cases in US (330mm population, extrapolate to China)

Disease % # China # Doctor Visits Notes

Chronic Cough• Smoking (1/3)• Pollution (1/3)• Post-Pneumonia (1/3)

24% 330mm 1.2 billion visits3-4 times p.a.

3-4 doctor visits p.a.

Source: • Initial management estimates. To be further refined 1. Disease burden of COPD in China a systematic review, International Journal of COPD 2018 Zhu et al• April 2018, The Lancet: COPD is widespread in China with 8.6 percent of its adult population -- almost 100 million people -suffering from the disease, according to a new Tulane University study, based on lung-function

screenings for >50,990 participants - the largest survey of COPD across age groups ever conducted in China

COPD: A major health issue in China with no effective treatment

The Science

6

Severe asthma

Chronic bronchitis

Normal respiratory epithelium

Cystic Fibrosis

Excess mucus“goblet”

cells

Change in the lining of the airway (epithelium) is shared among severe lung diseases

SiteOf Action

Nadolol

Major classes of approved drugs

7

Autopsy slide from 8 year old girl with fatal asthma. Mucus is increased AND abnormal.

Mucus causes death due to asthma, COPD, CF

Mucus plug in bronchus

Smooth muscle: target of bronchodilators

8

Only Nadolol blocks increase and persistence of mucus cells in airway lining (epithelium)

Control VehicleSens/Chall

AlprenololSens/Chall

NadololSens/Chall

Oral Nadolol (Nad) an inverse agonist and biased ligand, but not the antagonist Aprenolol(Alp) is effective in preventing mucus metaplasia

Sens = sensitized

Chall = challenged

9

Control

IL-13

IL-13 + Nadolol 0123456789

10111213141516

*

#

Control IL-13Muc

in v

olum

e d

ensi

ty (

nl/m

m2 )

IL-13 + Nadolol

Nadolol reverses/prevents exogenous IL-13 induced mucus metaplasia

9

10

D. Formoterol enhances, and inhaled nadolol inhibits mucus metaplasia

22

Inhaled nadolol blocks mucus metaplasia (D)

11

Beta agonist or beta blocker

The canonical cAMP-dependent pathway

Beta-arrestinAdenylyl cyclase

Newly discovered pathway ~2000(R. Lefkowitz)

Asthma and COPD

phenotype

Beta-arrestinAdenylyl cyclase

Restored epithelium

NadololLABA

Mechanism of action of Nadolol is unique among drugsNadolol reverses epithelial changes via inhibition of the beta-arrestin pathway in b2 airway receptors

Beta agonist or beta blocker

12

Nadolol is different from other beta-blockers

0

20

40

60

80

100

-0.004 -0.003 -0.002 -0.001

ER

K1/2 activation

Rate of cAMP accumulation

Beta

arr

estin

signa

ling

0.001 0.501 1.001

Carvedilol Alprenolol

Epinephrine

Propranolol

Nadolol

q Beta blockers typically associated with adverse mucus production via the beta arrestin pathway

q Only Nadolol has been found to block the beta arrestin pathway (that changes the normal epithelium)

q Allows cAMP to be open

13

Nadolol is unique in airway healingDrug Class Effect on airway

production of mucusImpact on use of nadolol

Bronchodilators

SABA and LABA Worsen Increased need

SAMA and LAMA None Complementary

Anti-inflammatory None

Corticosteroid None Complementary

Anti-leukotriene None None. Indicated for milder disease

PDE4 (roflumilast) None Complementary

Biologics / Anti –IL4, 5, 13 None Complementary in severe asthma

Mucolytic/ expectorants

Guaifenisin None (expectorant) None. Used but ineffective

(N) Acetyl cysteine None (mucolytic) Complementary

Anti-infectives

Inhaled, oral IV None Complementary

Disease Modifying agents

Pirfenidone None IPF only

Nadolol Reduction Unique MOA

1. Number of active trials per clinicaltrials.org as at Jan 2019

14

Nadolol: Safety data support expanded program

q Background: nadolol has been taken regularly by > 8 million patients worldwide for > 30 years

q Nadolol for respiratory diseases: 2 US INDs

q Asthma: 80 patients in 3 clinical trials (40mg/ day) § No excess of adverse events § No evidence of respiratory intolerance with titration

q COPD/ Smokers: 78 patients (100mg/ day) § No excess of adverse events

q Conclusion: Efficacy, titration and safety data support nadolol progress into global late phase development for COPD

15

Nadolol in Mild Asthma (NIMA)

q NIH (US) sponsored clinical trial in USq 3 centers: Duke U., Baylor College of Medicine, Washington U.

(St Louis)q 66 subjects 1:1 randomizationq Titration to MTD nadolol (50mg/day)q 26 weeks treatment q Primary endpoint: change in airway hyper-responsivenessq Safetyq NOTE: Patients were too mild and did not show epithelial

changes

16

Nadolol in Mild Asthma (NIMA)Adjusted linear predictions of FEV1 by treatment armNadolol did not negatively affect pulmonary function

2.75

2.8

2.85

2.9

2.95

Linea

r Pred

iction

, Fixe

d Port

ion

0 14 30 45 60 75 110 140

Days from Baseline Visit

Placebo Nadolol

17

Oral Nadolol: Phase 2 study of impact on sputum and smoking cessation

11-15wks 2wks

ORAL DOSING WASHOUTINCLUSION ENDPOINTS

N=155

Randomised(IWRS)

Controlled Clinical Trial

Failed to quitand chronic cough

Nadolol Treatment (n=78)3wks titration & 5-8wks maintenance

Placebo Control (n=77)“titration” & maintenance

PrimaryClinical:Decrease in # of cigarettes per dayduring last 28 daysMechanism:Reduction in markers of β-arrestin activation

SafetyChange in FEV1,

exacerbations, adverse events

Trial conducted under our sponsored IND with the the FDA Division of Anesthesia, Analgesia and Addiction Products (DAAAP).Principal Investigator: Mario Castro, MD (Washington University)

18

Effect of Nadolol on MUC5 AC

End of dosing

P<0.05

q Statistically significant impact on the beta arrestin pathway in the respiratory tract of smokers

q Note that after dosing ended, the phenotype regressed toward the mean, arguing for longer term treatment to enhance and maintain benefit

19

Reduction from baseline cigarette useq Clinical endpoint for smoking cessation study shows that 61% of patients on Nadolol reduced cigarettes over

the last 28 days course of the study by ≥ 70% reduction. This compares with 32% for the placebo group

q This is a clinically relevant difference of over 80% between Nadolol and placebo group

q Note participants had history of failing to quit smoking programs at least 5 times

Total patients measured• Nadolol 62• Placebo 65

19%

29%

61%

77%

84%

94% 94% 94% 94%

11%15%

32%

58%

66%

78%

91%95% 97%

0%

20%

40%

60%

80%

100%

>90% >80% >70% >60% >50% >40% >30% >20% >10%

% P

atie

nts

Reduction of Cigarettes Smoked in Excess of %

Smoking Reduction in Cigarettes (% Patients) Last 28 Days of Phase 2 Study

Nadolol Placebo

20

Summary of 155 Patient Phase II USA Clinical Trial

Phase II trial in smoking cessation (reported Q3 2015) shows:q MUC5AC levels were reduced by 82% in nadolol treated patients, compared to 54% in

placebo subjectsERK1 levels were reduced by 47% for nadolol, compared with 27% for placebo

q Trial subjects treated with nadolol were more likely to achieve abstinence at the conclusion of dosing (12/62, 19.3%), compared to those administered placebo (7/59, 11%)

q More patients treated with nadolol achieved a >70% reduction in cigarettes smoked, compared with placebo treated patients (38/62, 61% on INV102 and 21/59, 36% on placebo)

q No material safety issues or adverse effects measured

21

Lead program: Oral nadolol for COPD is under review in China

q Science is fully validated: Nobel Prize in Chemistry 2012q Drug is well known and off patent: IP based on titration doses and

method of useq Chemistry and manufacturing: completedq Toxicology and pharmacokinetics: completedq Clinical target: validated Phase II studies under US IND showed safety and

efficacy in decreasing abnormal mucus in patients who attempted to quit smoking

q Conclusion CAT has made a strong case for oral nadolol progressing directly into late Phase development in China for COPD

22

Medical, regulatory and commercial precedent

Precedent: Chronic Heart Failure (CHF)

CAT target: Chronic Obstructive Pulmonary Disease (COPD)

CONTRAINDICATEDWarning against use of beta blockers in CHF for > 25 years. Carvedilol annual sales (1998) $40m

STANDARD OF CAREAfter careful titration, beta blocker Carvedilol reduced mortality in all classes of CHFFirst in class: Carvedilol peak annual sales $1.5 BILLION (2010)

FROM TO

CONTRAINDICATEDWarning against use of beta blockers in COPD for > 25 years. Nadolol current sales: $ nominal (generic)

STANDARD OF CAREAfter careful titration, beta blocker nadolol targeted to reduce airflow obstruction due to damaged airways. Target: First in class

FROM TO

NOTE: Nadolol effect on airways cells is unique among β blockers

Program for China

24

Plan for Oral Nadolol Approval in ChinaGoal: Enable first registration in China in < 3 years

Package submitted to NMPA and CDE in December 2018

Proposal: Accelerated pathway to Phase III Pivotal clinical trial

Protocol: Efficacy and Safety of Oral β-adrenoceptor Inverse Agonist and Biased Ligand, Nadolol in Patients with COPD

§ Primary Endpoint: Improved Lung Function§ Secondary Endpoints:

1. Airway healing (histology)2. Mechanistic studies (β arrestin pathway down regulation)3. Reduction in exacerbations and reductions of admissions after

exacerbations 4. Reduction in CT evidence of bronchiectasis

25

Oral nadolol

Asthma

COPD China

Inhaled zafirlukast

Research Formulation development and clinical feasibility

Phase 1 Phase 2

NIH funded

Beta arrestin Results from Phase II clinical trial

COPD (bronchitis)

Asthma (mod-severe

Cystic Fibrosis

Inhaled nadolol

……

……

..

……

……

..

……

……

..

Next milestone

EOP2 Meeting ChinaPhase 3 planning

Safety confirmed: plan study in moderate to severely asthmatic patients

Pre-IND status achieved 1Q15

Toxicology and clinical supplies remanufacture

Toxicology studies commenced

Mild to moderate Asthma DPI feasibility demonstrated Manufacture

EOP2

……

……

..

Toxicology

……

……

..

Phase 3

……

……

..

COPD USA Beta arrestin Results from Phase II clinical trial Phase IIB bridging study

US

3 year stability with patented

formulation and device

3M

Pipeline

26

MildAsthma

Moderate Asthma

SevereAsthma

COPD(Chronic Bronchitis Dominant)

Smoker’sCough

Cystic Fibrosis

ZafirlukastMonotherapy + combinations

Global market size: $34B $2.4B $1.2B

ExerciseInducedAsthma

NadololMonotherapy + combinations

Spectrum of airway disease and opportunities

27

James P. KempMitchell GlassThian Chew

Chairmanq Managing Partner, Polar Ventures

q Executive Director, Goldman Sachs proprietary investing (New York, Hong Kong), public and private across capital structure

q Strategic Services Group, Morgan Stanley (New York) consultant on post-merger integration program

q Director, KPMG Consulting (Singapore, Sydney): Business transformation, operational turnaround programs

q Senior Manager, KPMG (Taipei, Melbourne): Audit and assurance, IT risk management

q Adjunct Professor, Hong Kong University of Science & Technology MBA Program

q Chartered Accountant, MBA/MA Wharton School (Palmer Scholar)

CEO and Managing Directorq 30 year veteran of Pharma (AZ, GSK) and

Biotech (AGIX)

q 7 years of research, teaching and patient care at the University of Pennsylvania

q Board certified pulmonary and critical care specialist

q 5 FDA approved drugs

q Managed more than 40 drug developments including “first in class”

q Led development of beta blocker carvedilol (Coreg®)

q Led development phases I - III of oral zafirlukast (Accolate®)

q Former Chief Scientific Officer at the University City Science Center (Philadelphia, PA) where he advised 54 client companies on strategy for developing and commercializing devices, diagnostics, and therapeutics

q In 2013, founded Accolade LLC to exploit non-oral formulations of Zafirlukast

Chief Medical Officerq Clinical Professor of Pediatrics, Division

of Allergy and Immunology, University of California

q Founder: Allergy & Asthma Medical Group and Research Center San Diego

q Fellow and former president, American Academy of Allergy, Asthma and Immunology

q Task Force on Establishing Guidelines for Evaluation of Non-bronchodilator, Anti-Asthmatic Drugs, FDA

q (Former) editorial board members of multiple publications including Respiratory Medicine Today and Journal of Asthma

q Consultant of Food and Drug Administration National Institutes of Health, State of California

q Consultant/Research Support experience for multiple pharmaceutical companies.

Our Team

28

Melanie FarrisVinod VijayakumarMichael P. Silvon

CMC / Toxicologyq Principal Consultant, supporting

startups, growing established businesses and University engagement, PalantekLLC

q Division Vice President, Global Biopharmaceutical Services, Preclinical Services, Charles River Laboratories

q Vice President, Corporate Planning & Development, Bioanalytical Systems, INC.

q Vice President, Sales & Marketing, Hi-Port, INC.

q Regional Business Manager, ICI Americas/Zeneca

q Business Manager & Manager, Commercial Development, Stauffer Chemical Company

q Postdoctoral Fellowships in Organometallic Chemistry, Fellow, Alexander von Humboldt Foundation, Tech. University of Munich. Organometallic Chemistry, Pennsylvania State University.

Regulatoryq 12+ years of pharmaceutical, biotechnology

and medical device products.

q 6+ years of pharmaceutical Regulatory Leadership experience, responsible for 4 IND, 7 pre-IND and 1 EOPII fillings.

q Principal, Pharmaceutical Product Development Consulting, Broom Street Associates

q Director of Regulatory Affairs and LLC Member, Accolade Pharma LLC

q Director of Regulatory Affairs, Invion, Inc.

q Director of Clinical & Regulatory Affairs and Co-Founder, Third Eye Diagnostics (3ED), Inc.

q Director of Technology Assessment, Agumen, K.K.

q Authored 15+ peer-reviewed publications, including in Clinical Biomechanics

q Adjunct Associate Professor of Engineering, Widener University

q Adjunct Assistant Professor of Engineering, Drexel University

CFOq Project manager of complex business

activities, including restructure, IPO, M&A and shareholder action

q Experienced in governance, board operations, communications, financial and compliance reporting, policy development for ASX Listed companies

q Successful applications for large sum of R&D tax rebates

q Previous roles include with HRH The Prince of Wales’s Office, Global Asset Management, Imperial Cancer Research Fund, and The Prince’s Foundation

q FGIA FCIS MAICD, B Communication (Public Relations), Graduate Diploma in Applied Corporate Governance.

Our Team (continued)

29

Yuanlin Song, MD

Principal Investigatorq Chair, Department of Pulmonary and

Critical Care Medicine, ZhongshanHospital of Fudan University, Shanghai

q Associate Director, Shanghai Respiratory Research Institute

q Associate Director, Shanghai Respiratory Research Institute

q Postdoctoral: cystic fibrosis/CFTR, UCSF

q Medical Science Award by Chinese Medical Association

q Steering Committee member, Chinese Respiratory Society, Youth Committee

q Led 14 studies as PI; >140 publications

q 2018-present Editor, Am J Physiol. Lung.

q 2018-2021, National Natural Science Foundation, Role: PI, Title: KGF-2 in lung derived stem cell proliferation

q 2015-2019: PI, Ministry of Science and Technology, 973 project

q Shanghai Medical University, M.D , Medicine, M.S., Pulmonary Medicine

Our Team (China - continued)Jiayuan Sun, MD

Principal Investigatorq Chief Physician, Department of

Pulmonary Medicine, Director, Department of Respiratory Endoscopy and Interventional Pulmonology, Shanghai Chest Hospital, Shanghai Jiao Tong University

q Principal Investigator on 16 funded grants

q Shanghai Medical Science & Technology Award

q Visiting professor of thoracic Hospital Affiliated to University of Heidelberg, Germany

q Deputy Head of the Youth Committee of the Chinese Thoracic Society

q Deputy Head of Minimally Invasive Interventional Respiratory Branch of the China Medicine Education Association

q Member of International Association for the Study of Lung Cancer

q Member of American Thoracic Societyq Heilongjiang University of Chinese

Medicine, Clinical Medicine Bachelorq Heilongjiang University of Chinese

Medicine, Internal Medicine (cardiology) Master

Changhui Wang, MD

Principal Investigatorq Director, Institute of Environmental and

Respiratory Diseases, Tongji University; Director, Department of Internal Medicine Diagnostics; Professor, Director, Chief Physician, Department of Pulmonary Medicine, Shanghai 10th People’s Hospital affiliated to TongjiUniversity

q 7 funded scientific researches and 12 clinical research projects

q Shanghai Medical Science and Technology Award, ERS Silver Sponsorship, APSR Travel Award

q Member of standing committee, Endoscopic Diagnosis and Treatment Technology of National Health Planning Commission(China)

q BOR, World Congress of Bronchologyand Interventional Pulmonary

q Doctor Degree, Master Degree, Bachelor Degree in Internal Medicine/Clinical Medicine, Second Military Medical University

q Postdoctoral training, Molecular Biology, University of Pennsylvania

Mitchell Glass, MD

CEO and Managing Director mitchell.glass@chronic-airway-therapeutics.com

www.chronic-airway-therapeutics.com

Disclaimer: The information in this presentation does not constitute personal investment advice. The presentation is not intended to be comprehensive or provide all information required by investors to make an informed decision on any investment in Chronic Airway Therapeutics Limited (Company). In preparing this presentation, the Company did not take into account the investment objectives, financial situation and particular needs of any particular investor. Further advice should be obtained from a professional investment adviser before taking any action on any information dealt with in the presentation. Those acting upon any information without advice do so entirely at their own risk. Whilst this presentation is based on information from sources which are considered reliable, no representation or warranty, express or implied, is made or given by or on behalf of the Company, any of its directors, or any other person about the

accuracy, completeness or fairness of the information or opinions contained in this presentation. No responsibility or liability is accepted by any of them for that information or those opinions or for any errors, omissions, misstatements (negligent or otherwise) or for any communication written or otherwise, contained or referred to in this presentation. Accordingly, neither the Company nor any of its directors, officers, employees, advisers, associated persons or subsidiaries

are liable for any direct, indirect or consequential loss or damage suffered by any person as a result of relying upon any statement in this presentation or any document supplied with this presentation, or by any future communications in connection with those documents and all of those losses and damages are expressly disclaimed. Any opinions expressed reflect the Company’s position at the date of this presentation and are subject to change.