US Respiratory DevelopmentCompounds

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Planned filing Project/Product Mechanism of action Potential indication/disease area Phase

Anti-IgE Ab Nasal polyposis 3

DP2 antagonist Asthma 3

Anti-IL17 Ab Asthma 2

Anti-TSLP antibody fragment

Asthma 1

CFTR potentiator COPD 2

2019

≥ 2021

QAW039

CSJ117

Investigational. Efficacy and safety have not been establishedDP2, D prostanoid type 2 receptor; CFTR, cystic fibrosis transmembrane conductance regulator1. Novartis clinical pipeline. https://www.novartis.com/our-work/research-development/clinical-pipeline. Accessed April 28, 2018.. 2. Novartis 2017 Annual Report. https://www.novartis.com/sites/www.novartis.com/files/novartis-annual-report-2017-en.pdf . Accessed April 25, 2018.3. https://clinicaltrials.gov/ct2/show/NCT03299686?term=cjm&draw=1&rank=1 Accessed April 25, 20184. https://clinicaltrials.gov/ct2/results?cond=&term=csj117&cntry=&state=&city=&dist= Accessed April 25, 2018

2019 Omalizumab

≥ 2021 CJM112

Respiratory Pipeline Overview

Business Use Only

QBW251≥ 2021

Omalizumab(Anti-IgE antibody)

5

• Planned filing in 2019

Polyps-1 and Polyps-2 trials in active enrollment.

• 24-week trials including ~120 patients with a nasal polyp score of≥5 with a unilateral score of ≥ 2 for each nostril.

• Omalizumab administered either every 2 or 4 weeks as a subcutaneous injection.

• Primary objective to determine the efficacy and safety of omalizuamb compared with placebo in adult patients with chronic rhinosinusitits with nasal polyps who have had an inadequate response to standard of care treatments.

Phase III Study Design

1. Clinicaltrials.gov. NCT03280537 https://clinicaltrials.gov/ct2/show/NCT03280537?term=omalizumab&cond=nasal+polyps&rank=1 Accessed October 5, 2017

2. Clinicaltrials.gov. NCT03280550 https://clinicaltrials.gov/ct2/show/NCT03280550?term=omalizumab&cond=nasal+polyps&rank=2 Accessed October 5, 2017

3. Gevaert et al. J Allergy Clin Immunol 131, 110-6, 2013

5 weekRun-in omalizumab Q2W or Q4W

placebo Q2W or Q4W

24 Week Treatment PeriodSafety

Follow up

Open Label

Extension

28 weeks

Xolair: Anti-IgE in nasal polyposis

Investigational. Efficacy and safety have not been established

Fevipiprant – QAW039(Prostaglandin D2 receptor antagonist)

7

DP2 = D prostanoid receptor 2; ILC2 = Type 2 Innate Lymphoid Cells; PGD2 = Prostaglandin D2; Th2 = Type 2 T helper cells

Prostaglandin D2 (PGD2) release

Fevipiprantinhibits binding

of PGD2 to DP2 receptor

Downstream effects inhibited

EosinophilsTh2 cells, ILC2 cells

Mast cell

IL-4, IL-5, IL-13 releaseMigration, activation and mediator release

IgE

PGD2

Stimuli

Fevipiprant

Fevipiprant (QAW039): A prostaglandin D2 receptor antagonist

Townley RG, Agrawal S. Ann Allergy Asthma Immunol. 2012;109:365-374.

Previously reviewed

Investigational. Efficacy and safety have not been established

8

0 6 12 18

0.5

1

2

4

8

16

Time (weeks)

QAW039Placebo

p=0.0077 p=0.0014 p=0.92

Treatment Wash out

Patient population Primary endpoint

Asthma patients receiving ICSACQ ≥1.5 or ≥1 severe exacerbation in prior 12 months*Sputum eosinophils ≥2%

Sputum eosinophils after 12 weeks of treatment

• 3.5-fold reduction in sputum eosinophils vs placebo (p=0.0014)

• Clinically and statistically significant improvement in ACQ vs placebo (-0.56 point difference; p=0.046) – Observed in pre-specified subgroup with

uncontrolled asthma at baseline (ACQ ≥1.5; n=40/61)

Geometric mean ± 95% confidence interval ; last observation carried forward

Fold

redu

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asel

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A2208: Effect on sputum eosinophils

*Severe exacerbation defined as requiring an increase in systemic corticosteroid therapy for ≥3 days

Gonem S et al. Lancet Respir Med. 2016;4:699-707.

Previously reviewed

Investigational. Efficacy and safety have not been established

9

Effect of Fevipiprant on Lung Function in Moderate-to-Severe Asthma

12-week, multicenter, randomized, double-blind, placebo-controlled studies to assess the efficacy and safety of QAW039 when added to standard-of-care asthma therapy in patients with uncontrolled asthma

https://clinicaltrials.gov/ct2/show/NCT03215758?term=QAW039&recrs=ab&rank=1https://clinicaltrials.gov/ct2/show/NCT03226392?term=QAW039&recrs=ab&rank=2https://clinicaltrials.gov/ct2/show/NCT03052517?term=QAW039&recrs=ab&rank=4https://clinicaltrials.gov/ct2/show/NCT02563067?term=QAW039&recrs=ab&rank=5https://clinicaltrials.gov/ct2/show/NCT02555683?term=QAW039&recrs=ab&rank=6

Effect of Fevipiprant on Exacerbations in Severe Asthma

52-week, multicenter, randomized, double-blind, placebo-controlled studies to assess the efficacy and safety of QAW039 when added to standard-of-care asthma therapy in patients with uncontrolled asthma

Long-term Safety of Fevipiprant in Moderate-to-Severe Asthma

A 2-treatment period (52-week, 104-week), randomized, placebo-controlled, multicenter parallel-group study to assess the safety of QAW039 when added to existing GINA steps 3, 4, and 5 asthma therapy in patients with uncontrolled asthma

Ongoing Phase 3 studies

Investigational. Efficacy and safety have not been established

CJM112(Anti-IL17A antibody)

CJM112: Anti-IL17A in T2-low Asthma

• Studied in uncontrolled moderate-to- severe asthma with low IgE and low serum eosinophils (T2-low) • Not eligible for biologics developed for T2-high (allergic/eosinophilic) asthma

• Phase 2 randomized, subject/investigator blinded, placebo-controlled multi-dose study

• Primary endpoint: Change in FEV1, Day 92

• Secondary endpoints include Asthma Control Questionnaire (ACQ) and AEs, Day 92

• Patients (N=110)– 18-75 yrs with moderate-to-severe asthma

– FEV1 40-90% predicted

– Symptomatic (ACQ ≥1.5)

– IgE <150 IU/mL and serum eosinophils <300/microliter

• Status: Ongoing, estimated study completion Sept 20191. Clinicaltrials.gov. NCT03299686

Investigational. Efficacy and safety have not been established

CSJ117(Inhaled anti-TSLP antibody fragment)

CSJ117: Inhaled Once Daily Anti-TSLP in Asthma

• Studied in mild stable atopic asthma• Phase 1 randomized, subject/investigator blinded, placebo-controlled multi-dose

study

• Primary endpoint:– AEs, SAEs, 12 wks

– Late asthmatic response based on AUC for time adjusted percent decrease in FEV1 after allergen inhalation challenge, 12 wks

– Late asthmatic response as measured by the maximum percentage decrease in FEV1 after allergen inhalation challenge, 12 wks

• Secondary endpoints include early asthmatic response based on the above mentioned measures and PK, 12 wks

• Patients (N=55)– 18-60 yrs with mild stable atopic asthma

– Must exhibit an early and late asthmatic response to a common inhaled allergen during the screening allergen inhalation challenge

• Status: Ongoing, estimated study completion July 2019

TSLP = Thymic stromal lymphopoetinClinicaltrials.gov. NCT03138811

Investigational. Efficacy and safety have not been established

QBW251(CFTR Potentiator)

QBW251: CFTR Potentiator in Bronchitic COPD

• Studied in GOLD II-III COPD with chronic bronchitis

• Phase 2 randomized, double blind, placebo-controlled study

• Primary endpoint: Change in lung clearance index (LCI), Day 29

• Secondary endpoints include change in FEV1 and other spirometric measures and PK, Day 29

• Patients (N=92)– 18-75 yrs– GOLD stage II-III COPD with chronic bronchitis, severe emphysema excluded– Current smoker or ex-smoker with ≥10 pack-year smoking history

• Status: Completed

CFTR = Cystic fibrosis transmembrane conductance regulator protein; COPD = Chronic obstructive pulmonary disease; GOLD = The Global Initiative for Chronic Obstructive Lung Disease .Clinicaltrials.gov. NCT02449018

Investigational. Efficacy and safety have not been established