Stuart Silverman – CEO & Founder

Major DPI Market Trends and Perspectives

Double digit growth on DPI market

Western European Asthma/COPD marketOral, injectable,inhaled drugs

CAGR 2008–2018: 4%* 2008 sales: $6.9 billion 2018 sales: $9.9 billion

*Source: 2009–2018 forecast = Datamonitor; 2004–08 sales data from MIDAS, IMS Health Western Europe: France, Germany, UK, Spain, Italy

Worldwide DPI Market Global Sales revenue $19 bn to $38 bn by 2015

( GIA report 2010)

Key Drivers for Choice of Inhalation Technology

RiskRisk•Innovation is long to be established •Safe, well-known inhalation solution•Technology mastering/in-house technology

Patient’s need •Acceptability, convenience •Familiarity of patient group with device •Small / High volumes of drug

Differentiation •Ability to get competitive advantage •Patent protection •Bring innovation, choice, diversity

Performance •Technical performance (lung deposition, API protection) •Ability to effectively deliver the dose•Cost effectiveness

In the last six years Dry Powder Inhalers have continued to take sharefrom the MDI market, a trend that we expect to continue for several reasons

including patient preference and environmental impact.

DPI- A growing technology

*

6

CapsulesBlister Reservoir

Weaknesses

•High dose variation•No ability to see remaining doses

Strengths

Accurate dosingPre-metered dose

Humidity protection

•All-in-one system•COGs•Multidose (no handling)

•No ability to see dose is effectively taken•More expensive than capsules

•Control of inhaled dose•Flexibility: •number of doses,•remaining dose, emptied dose,•Potential for combination

•API protection •Multidose inhaler •Easy to handle •All-in-one system

•Handling•Device and capsule are separated

Perceived Strengths and Weaknesses of DPIs Technologies

Trends in capsule-based DPI systems•Improving quantity of inhaled drug •100% protection of active ingredient•No humidity constraint• API improvement for less side-effects• Excipient-free•Ability to combine different APIs

•Reduction of device size •Improving handling

•Easier way of dispensing and removing the capsule •Pre-loaded system with several capsules

•Ability to maintain cost low•Recycling material•Reusable / refill cartridge

•Colored / Imprinted capsule•Same device for different capsule/application• Specific design to protect from copy

Performance User-Friendly

Eco-Friendly Differentiation

Two opposed trends in Inhalation Technology:

ComplexSimple

Product handlingLess manipulation in between 2 dosesElderly patients, cognitive or physical impairmentFits naïve users

Simple devices cheap to developFit developing market, large market size with strong economic pressureBeing able to produce in very large number very quickly (pandemic)

Patient convenience

Device attributes / technologyExtra attributes like counting dose, blocking system to avoid accidental charge of the next dose, cleanliness, monitoring dose intake for compliance

Cost effectiveness

Complex device offering innovation Fits disease with few medications on the market to be able to deliver an innovative product both on API and delivery mechanism

Current and future applications

Current Future

MDIs is the historical device for inhalation

Asthma

COPD

Relatively sophisticated users: Want multi-dose solution, high number of dose, cost-effective solution

Naïve users: one unique dosage to smaller number of dosage, need for simple device, easy to use

DPIs is well positioned for future application

Vaccines

Preferred inhalation device

still to be assessed

Biologics

Naïve users who need convenient mode of administration: alternative to injection, frequent usage, sophisticated by easy to use device

Nasal routes

Central nervous system

Pain relief

Migraines

Macromolecules

Anti-viral

Summary of Capsule-Based Delivery Systems

Summary of Capsule-based Devices

 Spiriva® HandiHaler® (tiotropium bromide inhalation powder) is an inhaled once-a-day maintenance prescription treatment for bronchospasm (airway narrowing) associated with chronic obstructive pulmonary disease (COPD). Inhalation device: Handihaler

Atrovent is used to prevent bronchospasm, or narrowing airways in the lungs, in people with bronchitis, emphysema, or COPD (chronic obstructive pulmonary disease). Inhalation device: Aerohaler Multidose

Summary of Capsule-based DevicesForadil relaxes the muscles in the walls of the airways, allowing them to expand. Taken on a twice-daily basis, it helps to control asthma in people who need regular treatment with short-acting inhalers, including people with nighttime asthma. Regular twice-daily use can also relieve tightening of the airways in people with Chronic Obstructive Pulmonary Disease, including chronic bronchitis and emphysema. Inhalation device: Aerolizer

Inhalation device: Osmohaler:

Summary of Capsule-based Devices This drug relaxes the smooth muscle in the lungs and dilates airways to improve breathing. It is used in the treatment of asthma, chronic bronchitis, and emphysema. VENTOLIN ROTACAPS for Inhalation are indicated for the prevention and relief of bronchospasm in patients 4 years of age and older with reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm in patients 4 years of age and older. The VENTOLIN ROTACAPS for Inhalation formulation is particularly useful in patients who are unable to properly use the pressurized aerosol form of albuterol or who prefer an alternative formulation. 

Inhalation device: Rotahaler and Spinhaler.

Summary of Capsule-based Devices The inhalation capsule Avessa is available as Rheocaps Avessa 100 mcg, Avessa 250 mcg, Avessa 500 mcg, depending on the severity of Asthma. Indian pharmaceutical major Ranbaxy Laboratories Limited has launched Avessa (Formoterol + Fluticasone) inhalation capsules in India for the treatment of asthma. Ranbaxy claims that this unique combination has been launched for the first time in the world combining the fastest acting Long Acting Beta 2 Agonist Formoterol and the most potent inhaled corticosteroid Fluticasone. The product is to be used only with the Rheohaler - the world's first capsule-based multi-dose dry powder inhaler, Ranbaxy.Inhalation device: FlowCaps® - Rheohaler (developed by Hovione)

Inhalation device: FlowCaps® - Rheohaler (developed by Hovione)

Continuous improvement in DPI systems

The key challenge for inhalation drug delivery systems is a consistent and high lung deposition

The first DPI systems had ~5 % lung deposition which has been increased by 4 – 5 times meanwhile

This has been achieved by optimization ofthe formulationthe inhalation devicethe inhalation capsule

Labiris & Dolovich 2003