Developing innovative therapies for the treatment of respiratory diseases January Nasdaq: VRNA

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(1)

Developing innovative

therapies for the treatment

of respiratory diseases

January 2021

(2)

Forward-looking statements

This presentation contains “forward‐looking” statements that are based on the beliefs and assumptions and on information curr

ently

available to management of Verona Pharma plc (together with its consolidated subsidiaries, the “Company”). All statements oth

er than

statements of historical fact contained in this presentation are forward-

looking statements. Forward‐looking statements include

information concerning the initiation, timing, progress and results of clinical trials of the Company’s product candidate, th

e timing or

likelihood of regulatory filings and approvals for of its product candidate, and estimates regarding the Company’s expenses,

future

revenues and future capital requirements. In some cases, you can identify forward-

looking statements by terminology such as “may,”

“will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the ne

gative of these

terms or other comparable terminology.

Forward-

looking statements involve known and unknown risks, uncertainties and other factors that may cause the Company’s actual

results, performance or achievements to be materially different from any future results, performance or achievements expressed or

implied by the forward-

looking statements. These risks, uncertainties and other factors include those under “Risk Factors” in th

e

Company’s annual report on Form 20

-

F filed with the Securities and Exchange Commission (the “SEC”) on February 27, 2020, under

“Supplemental Risk Factor Disclosures” in our Report on Form 6

-

K filed with the SEC on April 30, 2020, under “Risk Factors” in o

ur

Registration Statement on Form 6-K filed with the SEC on August 17, 2020, and in its other reports filed with the SEC. Forward-looking

statements represent the Company’s beliefs and assumptions only as of the date of this presentation. Although the Company bel

ieves that

the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee future results, levels of activity,

performance or achievements. Except as required by law, the Company assumes no obligation to publicly update any forward‐look

ing

statements for any reason after the date of this presentation, or to conform any of the forward-looking statements to actual results or to

changes in its expectations.

This presentation also contains estimates, projections and other information concerning the Company’s business and the market

s for the

Company’s product candidate, including data regarding the estimated size of those markets, and the incidence and prevalence o

f certain

medical conditions. Information that is based on estimates, forecasts, projections, market research, or similar methodologies is inherently

subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this

information. Unless otherwise expressly stated, the Company obtained this industry, business, market and other data from reports,

research surveys, clinical trials studies and similar data prepared by market research firms and other third parties, from industry, medical

and general publications, and from government data and similar sources.

(3)

Ensifentrine is a Phase 3, first-in-class candidate for

unmet respiratory needs

Large COPD opportunity

Total US sales of $9.6 billion chronic maintenance COPD therapies

1

1.2M US COPD patients failing despite maximum therapy

2,3

Targeted HCP prescriber base to support US commercialization

4

Unique profile

First novel class of bronchodilator in COPD in over 40 years

5

Results from 16 clinical trials, including two Phase 2b trials

Safety profile similar to placebo in trials involving over 1300 subjects

Pathway to approval

Well-validated demonstrated path to US FDA approval

Well capitalized to support activities

Expert team has developed and commercialized many leading respiratory products

Inhaled PDE3 and PDE4 inhibitor

3

Bronchodilator

and

anti-inflammatory

activity

1Internal calculations by Verona Pharma derived from IQVIA database; MIDAS Quarterly and MIDAS Medical 2019 data; 2Mahler D, et al., Eur Respir J, 2014; 3Vestbo J, et al., The Lancet, 2017; 4IQVIA LAAD Longitudinal Claims Database Analysis Q1:2020; 5Barnes P, et al., Eur Respir J, 2015

(4)

Execution driven leadership team

Decades of respiratory and commercialization experience

4

David Zaccardelli, Pharm D

President & CEO

Mark Hahn, CPA

CFO

Kathy Rickard, MD

CMO

Chris Martin

VP, Commercial

Peter Spargo, PhD

Senior VP, CMC

Claire Poll, LLB

General Counsel

Desiree Luthman, DDS

VP, Regulatory Affairs

Tara Rheault, PhD

VP, R&D and Global Project

Management

Verona’s team has expertise in developing /

(5)

Ensifentrine: Differentiated profile as dual

bronchodilator and anti-inflammatory

Ensifentrine impacts 3 key mechanisms in respiratory disease

5

Airway Smooth Muscle

1-4

Inflammatory Cells

5,6

Epithelial Cells

7,8

Epithelial cells

PDE3, PDE4

Neutrophils

PDE4

Macrophages

PDE3, PDE4

Lymphocytes

PDE3, PDE4

Eosinophils

PDE4

Fibroblasts

PDE4

PDE3, PDE4

Bronchial relaxation

PDE3, PDE4

CFTR activation

anti-inflammatory effects

bronchodilation

mucociliary clearance

cAMP

Ciliary function

cAMP

Cell proliferation

cAMP

survival & activity

1Calzetta L, et al., J Pharmacol Exp Ther 2013; 2Calzetta L, et al., Pulm Pharmacol Ther 2015; 3Matera MG, et al., Am J Respir Crit Care Med 2013; 4Venkatasamy R, et al., Br J

Pharmacol 2016; 5Boswell-Smith V, et al., J Pharmacol Exp Ther 2006; 6Franciosi LG, et al., Lancet Respir Med 2013; 7Schmidt D, et al., Br J Pharmacol 2000; 8Turner MJ, et al.,

(6)

Ensifentrine improves lung function and symptoms

in moderate to severe COPD patients

Summary of Phase 2b data:

Lung function:

Statistically significant and clinically meaningful improvements

with optimal efficacy observed consistently with the 3 mg dose

Symptoms:

Statistically significant and clinically meaningful improvements in

symptoms and Quality of Life measures

Twice-daily:

Statistically significant and clinically meaningful improvements in

average FEV

1

over 12 hours

Summary of Phase 1 and 2a data:

Anti-inflammatory:

Significant reduction in all inflammatory cell types in

sputum in LPS challenged healthy subjects (COPD-like inflammation)

Lung function and volumes:

Improved when added to background dual/triple

therapy

Improvements shown with or without background therapy

6

Well tolerated

in 16 clinical

trials in over

1300 subjects

(7)

0

20

40

60

80

100

120

140

160

180

200

0.75 mg

1.5 mg

3 mg

6 mg

mL

0

20

40

60

80

100

120

140

tio + 0.375 mg tio + 0.75 mg

tio + 1.5 mg

tio + 3 mg

mL

*

**

***

Ensifentrine: Efficacy demonstrated in two large Phase 2b trials

Improvements in lung function seen at Phase 3 trial dose

7

Study 203:

Ensifentrine Monotherapy

1

Study 205:

Ensifentrine + Tiotropium

2

1RPL554-CO-203, Singh D, et al., Respiratory Research 2020;

2RPL554-CO-205 Full Phase 2b Analysis Set, data on file; tiotropium (Spiriva®)

Lung function

Peak Change FEV

1

(mL) at day 28

N=403

*

Peak Change from Day 1 in Baseline in FEV1(mL) on Day 28, Week 4, Primary endpoint met; placebo corrected

***

***

***

***

***p ≤ 0.001

Lung function

Peak Change FEV

1

(mL) at week 4

N=413

*

(8)

12-Hour spirometry profile at week 4 supports twice daily dosing

Ensifentrine: Spirometry across Phase 2b program

8

Study 205:

Ensifentrine + Tiotropium

2

Study 203:

Ensifentrine Monotherapy

1

Study 203:

Ensifentrine Monotherapy

1

+200 mL (p<0.001) peak FEV

1

vs placebo

+119 mL (p<0.001) average FEV

1

over 12 hours

vs placebo

3 mg ensifentrine

tio + placebo

+124 mL (p<0.001) peak FEV

1

vs tio + placebo

+87 mL (p=0.011) average FEV

1

over 12 hours

vs tio + placebo

tio + 3 mg ensifentrine

placebo

FE V1 m ean ch an ge f ro m b ase line, m L FE V1 m ean ch an ge f ro m b ase line, m L

1RPL554-CO-203, Singh D, et al., Respiratory Research 2020;

(9)

-3

-2.5

-2

-1.5

-1

-0.5

0

0.75 mg

1.5 mg

3 mg

6 mg

week 1

week 2

week 3

week 4

Ensifentrine: Symptom improvement in two large Phase 2b trials

Improvements seen at Phase 3 trial dose

9 1RPL554-CO-203, Singh D, et al., Respiratory Research 2020;

2RPL554-CO-205 Full Phase 2b Analysis Set, data on file; tiotropium (Spiriva®)

Study 203:

Ensifentrine Monotherapy

1

Study 205:

Ensifentrine + Tiotropium

2

Placebo corrected

1Minimal clinically important difference (-4 units)

*

p ≤ 0.05

Symptom & QOL relief

Total Score SGRQ-C: COPD by Week

-5

-4

-3

-2

-1

0

tio + 0.375

mg

tio + 0.75 mg tio + 1.5 mg

tio + 3 mg

week 2

week 4

N=413

Progressive Quality of

Life Improvement

MCID

1

*

*

MCID

(1)

Symptom relief

Total Score E-RS: COPD by Week

Placebo corrected

(1) Minimal clinically important difference

Continuous, progressive

symptom improvement

N=403

*

******

**

**

**

***

*

**

*****

*

*

******

***p ≤ 0.001 **p ≤ 0.01 *p ≤ 0.05

*

(10)

Safety profile similar to placebo

Ensifentrine well tolerated at all doses in trials involving over 1,300 patients

Adverse events generally balanced between ensifentrine and

placebo

Gastrointestinal profile similar to placebo

Cardiovascular profile similar to placebo

No consistent or dose related changes in adverse events, blood

pressure, heart rate or QT in independent cardiologist review

16 clinical trials

980 COPD patients on

nebulized ensifentrine

across 6 studies

Safety Database:

10

(11)

End-of-Phase 2 outcome

FDA supports planned Phase 3 program

11

End-of-Phase 2 briefing package included data from 16 clinical

trials and supportive non-clinical and product development data

Non-clinical, clinical pharmacology and CMC alignment

Clarity on key Phase 3 features: dose, primary and secondary

endpoints, patient population and design

Alignment on long-term safety database and assessments

Phase 3 trials

(12)

Nebulized ensifentrine Phase 3 program enrolling

Two pivotal efficacy and safety studies: ENHANCE-1 and ENHANCE-2

12

Ensifentrine

3mg BID N=500

Placebo BID N=300

E

nsifentrine as a

N

ovel in

HA

led

N

ebulized

C

OPD th

E

rapy in moderate to severe COPD

ENHANCE-1

N=800

ENHANCE-2

N=800

Ensifentrine

3mg BID N=500

Placebo BID N=300

Long-term safety

N=100

Long-term safety

N=300

Primary Endpoint

FEV

1

(AUC over 12 hours)

at week 12

Secondary Endpoints

Symptoms (E-RS: COPD)

Quality of Life (SGRQ)

Other FEV1 (Trough, peak)

Other Endpoints

Exacerbations in pooled

analysis

24 Weeks

48 Weeks

Patient population:

LAMA or LABA background allowed (Target: 50% of trial population)

30-70% predicted FEV1

Symptomatic (mMRC ≥ 2)

Additional information:

Long-term safety established in ENHANCE-1

(13)

Ensifentrine

“Pipeline in a product”

13

Pre-Clinical

Phase 1

Phase 2

Phase 3

COPD

Maintenance (Home)

Asthma

Cystic Fibrosis

Nebulized

Inhaled

Nebulizer

DPI

MDI

COPD

Maintenance (Home)

1

Severe Asthma

Cystic Fibrosis

Asthma

Cystic Fibrosis

1

DPI formulation met primary & secondary endpoints in single and multidose Phase 2

(14)

0

50

100

150

200

250

300

350

400

100 mcg

300 mcg

1000 mcg

3000 mcg

6000 mcg

0

50

100

150

200

250

300

350

400

150 mcg

500 mcg

1500 mcg

3000 mcg

Placebo

mL

DPI Formulation Primary endpoint

Peak FEV

1

on Day 7

DPI and MDI formulations of ensifentrine improved lung function

Clinically meaningful, statistically significant bronchodilation

14

N=32-34

***p

≤ 0.001

***

***

***

***

**

*

***

N=40

***p

≤ 0.001

** p

≤ 0.01

* P ≤ 0.05

DPI Ensifentrine

MDI Ensifentrine

* Placebo corrected

RPL554-DP-201 Rheault T, et al., ERS 2019; RPL554-MD-201 Ph 2 study, data on file

MDI Formulation Day 1 endpoint

*

Peak FEV

1

(15)

Rationale for ensifentrine in COVID-19

Ensifentrine impacts 3 key mechanisms in respiratory disease

Bronchodilation

Anti-inflammatory

CFTR channel

Mechanism

Rationale

Reduce symptoms of dyspnea

and improve the patient’s

oxygen levels

Expected Effect

Used extensively in COVID-19

patients to alleviate respiratory

symptoms

Elevated inflammatory cells and

markers such as TNFα and IL

-6

have been shown to be

associated with COVID-19

severity in patients

CFTR dysfunction is associated

with pneumonia

Prevent further clinical

deterioration resulting from

unchecked inflammatory

response and reduced

oxygenation

Prevent secondary infections

related to mucus

hypersecretion

(16)

16

Ensifentrine: Treatment of hospitalized patients with COVID-19

Enrollment complete, top-line results in 2Q 21

To evaluate treatment with ensifentrine on key outcomes in patients hospitalized with COVID-19

Facilitation of recovery from the viral infection, clinical status improvement, supplemental

oxygen use and reduction of progression to mechanical ventilation

Pilot Study

Objectives

Randomized, double-blind, single-center at University of Alabama, Birmingham

2 mg dose or placebo; delivered twice daily added-on to standard of care

N=45 patients hospitalized with COVID-19 not on mechanical ventilator

Primary endpoint: Proportion of patients who recover from COVID-19 and are not hospitalized

on day 29

Pilot Study

Details

Treatment Arm 2 (N=15):

Blinded placebo pMDI BID + SoC

Treatment Arm 1 (N=30):

Blinded ensifentrine (2 mg) pMDI BID + SoC

R

Day 60

Follow up

Screening /

Hospitalization:

0-4 days

Study Treatment:

(17)

Anticipated milestones as ensifentrine advances

17

FDA:

End-of-Phase 2

meeting

Nebulized

ensifentrine as

maintenance

treatment for COPD

DPI/MDI Inhaler

ensifentrine as

maintenance

treatment for COPD

Start

Phase 3

NDA

filing

Phase 2 MDI

results

Single dose

Phase 2 MDI results

Multiple doses

Q2 2020

Q3 2020

Q4 2020

2021

2022

2023

Conduct

Phase 3

Safety

extension

Phase 3

FDA

review

PDUFA

date

Phase 3

data

MDI Inhaler

Ensifentrine as a

treatment for

COVID-19

(18)

COPD: a global problem

>384 million patients suffering worldwide and the 3

rd

leading cause of death

1

18

Prevalence of COPD in United States:

~25M patients

2

Prevalence of COPD in EU:

~70m patients

4

Prevalence of COPD in China:

~100m patients

3

1Quaderi SA., J Glob Health, Apr 2018; 2https://www.cdc.gov/copd/index.html, 3Wang et. al, The Lancet, April 2018 4NCD Alliance estimates,

(19)

COPD places a tremendous burden on US

medical system & patients

19

~740k Hospitalizations

1

~1.9m Emergency

room visits

1

~$50b in costs

(Direct/Indirect)

2

COPD patients have limited activity

70%

53%

51%

COPD patients feel socially limited

COPD patients limited at work

US Medical System

Patients

1https://hcupnet.ahrq.gov/accessed September 2020, 2CDC International Journal Of Chronic Obstructive Pulmonary Disease, 2020 Iheanancho et. Al. 3.https://www.healthline.com/health/copd/facts-statistics-infographic, accessed September 2020

(20)

COPD is a progressive disease with no cure

Current treatments are aimed at improving lung function, QOL, and exacerbations

20

LABA + ICS

Or

LABA + LAMA + ICS

Initial diagnosis:

Present w/ decreased lung function &

symptoms

LAMA

or

LABA

LAMA + LABA

De-escalation of ICS is

recommended if risk

outweighs benefits

Chr

onic

P

rogr

es

siv

e

Di

se

as

e

Persistent

symptoms /

Activity

limitations

Frequent

Exacerbations

Long acting beta2 agonist (LABA), Long acting anti-muscarinic antagonist (LAMA), Inhaled corticosteroids (ICS), short-acting muscarinic antagonists (SAMA), Short acting beta agonists (SABA)

(21)

Nebulized ensifentrine in COPD:

Significant US market opportunity

21

64%

54%

46%

42%

0%

20%

40%

60%

80%

100%

Non-Responders to

Dual / Triple Therapies

1,2,3,4

3m

6m

1.2m

Patients on COPD

treatment in US

5,6

Patients on

dual/triple therapy

7

Symptomatic

patients despite

maximum

therapy

1,2,3,4

Avg. Annual WAC Price of existing nebulized COPD drugs

8

$12,000

1Verona I US MCOPD Integrated Conjoint Survey, 2Mahler et al., 3 Vestbo et al. , 4Ferguson et al. Lancet Respir Med 2018, 5Make B, et al., International Journal of COPD, 2012; 6ALA, Trends in COPD, 2013; 7IQVIA Patient claims analysis Q4 2019; 5Mahler D, et al., Eur Respir J, 2014; 6Vestbo J, et al., The Lancet, 2017; 8Price Rx, Accessed March 2020

(22)

Ensifentrine: Significant US commercial opportunity

Phase 3 data expected to create broad HCP adoption with sufficient payer access

22

34%

0%

10%

20%

30%

40%

50%

% of Patients

How often HCPs

will prescribe ensifentrine

(n=114)

of lives will be

covered, with

remainder through

Medical Exception

>85%

Payer Research:

35 payers covering

>200m lives

Benefits of ensifentrine

(Payers & HCPS)

1

Novel MOA

2

Symptom, QOL, &

FEV

1

data

3

Safety profile

Verona I US MCOPD Integrated Conjoint Survey

%

of

p

atie

n

ts

Where will HCPs

prescribe ensifentrine

(n=114)

(23)

US is an attractive commercial entry point

Significant US market opportunity

23

Current nebulized products have a average

annual WAC of ~$12,000

4

~1.2m patients continue to have symptoms on

dual/triple therapies

1,2,3

50% of nebulizer claims are reimbursed through

Medicare Part B

5

Significant Unmet Need

Favorable Payer Coverage

Targeted Commercial Footprint

Premium Pricing Achievable

Pulmonologists will drive majority of ensifentrine

use. ~100 FTEs needed to support

commercialization efforts

6

1Ferguson et al. Lancet Respir Med 2018; 2Mahler D, et al., Eur Respir J, 2014; 3Vestbo J, et al., The Lancet, 2017; 4Price Rx, Accessed March 2020; 5IQVIA LAAD Claims

(24)

Ensifentrine in ROW

Strategic partnerships to maximize ensifentrine’s commercial value

24

United States:

~$10b in Sales

1

EU:

~$2.7b in Sales

1

China / Asia:

~$1b in Sales

(expected to double by 2030)

1

Verona Strategy:

Commercialize

Verona Strategy:

Out-license

Verona Strategy:

Out-license

(25)

Ensifentrine patent estate

Global rights through 2030s

25

Invention

Granted/Pending Application

Estimated Patent Expiry

Composition of matter

Granted US, Europe, Asia, other

March 2020

Suspension formulations

Granted US, Europe, Asia, other

2035

Polymorph

Granted US, Europe, Asia, other

2031

MDI formulation

Granted UK, Pending US, Europe, China, other

2039

DPI formulation

Pending

2040

COVID-19

Pending

2041

Manufacturing process

Granted Europe, US, Pending China, other

2037

Salt forms

Granted US; Pending Europe, China, other

2036

Treatment of cystic fibrosis

Granted Europe; Pending US, other

2035

Combinations with beta-agonists

Granted US, Europe, pending Canada

2034

Combinations with anti-muscarinics

Granted US, Europe, China, pending other

2034

(26)

Blue chip shareholder base with long-term focus

26

Cash and

equivalents

(as of December 31, 2020)

$188.0M

Operating expenses

(9 months ended September 30,

2020)

$46.2M

Market cap (Nasdaq: VRNA)

(as of December 31, 2020)

$405.4M

Shares outstanding

(as of December 31, 2020)

57.9M ADSs

Financial highlights

(27)

Thank you

Figure

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References

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