ABN 75 082 811 630 Human therapeutic products for chronic - - PowerPoint PPT Presentation

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ABN 75 082 811 630 Human therapeutic products for chronic - - PowerPoint PPT Presentation

ABN 75 082 811 630 Human therapeutic products for chronic respiratory and autoimmune diseases August 2004 Investor Presentation Disclaimer This presentation contains forward-looking statements within the meaning of the safe harbor


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ABN 75 082 811 630 Human therapeutic products for chronic respiratory and autoimmune diseases August 2004

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This presentation contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and beliefs and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. The forward-looking statements contained in this presentation include statements about future financial and operating results, and risks and uncertainties that could affect Pharmaxis’ product and products under development. These statements are not guarantees of future performance, involve certain risks, uncertainties and assumptions that are difficult to predict, and are based upon assumptions as to future events that may not prove accurate. Therefore, actual outcomes and results may differ materially from what is expressed herein. In any forward- looking statement in which Pharmaxis expresses an expectation or belief as to future results, such expectation

  • r belief is expressed in good faith and believed to have a reasonable basis, but there can be no assurance that

the statement or expectation or belief will result or be achieved or accomplished. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: risks associated with preclinical, clinical and sales and marketing developments in the biopharmaceutical industry in general and in particular including, without limitation, the potential failure to meet Aridol revenue goals, the potential failure of Bronchitol to prove safe and effective for treatment of COPD and/or Cystic Fibrosis, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling Aridol, Bronchitol and Pharmaxis’ other products under development; and other economic, business, competitive, and/or regulatory factors affecting Pharmaxis’ business generally, including those set forth in Pharmaxis’ filings with the ASIC, including its Annual Report for its most recent fiscal year and its most recent Quarterly Report, especially in the “Factors Affecting Our Operating Results” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections, and its Current Reports. Pharmaxis is under no

  • bligation to (and expressly disclaims any such obligation to) update or alter its forward-looking statements

whether as a result of new information, future events, or otherwise.

Investor Presentation Disclaimer

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Investment Highlights

Emerging specialty biotech company with two products in late stage development

Aridol - Phase III for asthma diagnosis complete, data 9/04 Bronchitol - expected to report phase II efficacy data in COPD & CF by end 2004

Targeting large, underserved markets

Aridol filling a need for diagnosis and management of asthma Bronchitol offers treatment for CF & COPD lung diseases

All product marketing rights have been retained Strong intellectual property – granted in US/Pending in Europe Multiple near-term value driving milestones Experienced management

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Product Pipeline

  • -------Clinical Trials----------

research preclinical phase I phase II phase III registration market

Respiratory diseases

Aridol – airway function Bronchitol - bronchiectasis Bronchitol - cystic fibrosis Bronchitol - chronic bronchitis*

Autoimmune diseases

PXS25 - multiple sclerosis PXS2030 – multiple sclerosis PXS2076 – rheumatoid arthritis Mid 2005 Early 2008 Late 2007 Late 2008 * CB trial pending outcome of bronchiectasis trial

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Strategy

Build a fully integrated specialty pharmaceutical company spanning research, development and commercialization Focus on attractive product development and commercialization opportunities Undertake product development and commercialization Focus on respiratory and autoimmune markets Expand R&D pipeline through research and licensing

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Respiratory market opportunity

1 Dollar figure based on current 400,000 bronchial challenge tests at $250 charge / test

Moderate 75,000 75,000 $294 M Cystic Fibrosis Bronchitol Low 15 M 30 M $399 M COPD (bronchiectasis and chronic bronchitis) Bronchitol High 31 M 52 M $100 M Diagnostic/Theranostic Aridol Projected penetration Potential Market Patients diagnosed Current Market (US$) Target Application Product

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Aridol

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Aridol

New product for the diagnosis and management of Asthma and COPD Indirect airway provocation for accurately measuring level of ongoing inflammation

Current standard for diagnosis in Australia Proposed replacement for direct provocation with methacholine in the US

Quick and easy to use – ideal for PCP

  • utpatient clinic setting

Phase III completed in July 2004, results in September Supported by international opinion leaders in respiratory medicine

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Market Opportunity

Significant addressable market, 31 M patients Estimated 400,000 bronchial provocation tests used in 2003 in major pharmaceutical markets Methacholine provocation test is currently reimbursed in the U.S. ($150 - $300 per test)

Addressable Market (000 pts)

440 3,052 5,966 17,299 1,308 3,660

Lung testing Asthma diagnosis Asthma management, Specialists Asthma management, GP COPD diagnosis COPD management

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Phase II Clinical Trial Design: Asthma

Progressive Protocol: 0, 5, 10, 20, 40, 80, 160, 160, 160 mg Diagnostic Measurement: FEV1 1 minute post dose Positive Diagnosis: Fall in FEV1 >14.9% Time taken: 10 minutes (Mean positive test with PD15) Numbers: > 750 pts Clinical Sites: Worldwide 20 minutes (negative test with PD15) Recovery: Spontaneous recovery to baseline FEV1 in 30 minutes (or Bronchodilator)

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Aridol Aridol

TM TM

1 10 100

% Fall FEV1

(measurement of lung function)

5 10 15 20 25 Severe ≤ 35mg Moderate ≤ 155mg Mild > 155mg Normal

Cumulative dose of Aridol (mg)

635

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Effect on response to Aridol challenge of 8 weeks Rx with Budesonide

100 40

Cumulative dose of Mannitol (mg)

0.1 1 10 100 1000

% Predicted FEV1

20 40 60 80

Cumulative Dose of Mannitol (mg)

0.1 1 10 100

% Fall FEV1

5 10 15 20 25 30 35 0.1 Before Budesonide With Budesonide

n=18

Phase II Trial Results

Measuring the effectiveness of inhaled steroid therapy

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Phase III Clinical Trial Design

Progressive Protocol: 0, 5, 10, 20, 40, 80, 160, 160, 160 mg Diagnostic Measurements: FEV1 1 minute post dose Positive Response: Fall in FEV1 >14.9% or >9.9% Number: 600 pts Clinical Sites: 12 Time taken: 10 minutes (Mean positive test with PD10) 20 minutes (negative test with PD10) Recovery: Spontaneous recovery to baseline FEV1 in 30 minutes (or Bronchodilator) Results Expected: September 2004

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Next steps in clinical development

Aridol as an asthma diagnostic

Results Nov 04 IST in 50 patients vs methacholine for clinical diagnosis in asthma Sept 04 Phase III clinical trial results Aridol vs hypertonic saline and physician diagnosis in 600 patients

Aridol as an asthma management tool

Results Nov 05 IST in 300 patients with 12 month follow up using Aridol to guide steroid dosage Endpoint is number of exacerbations with Aridol vs standard British Thoracic guidelines

Aridol as a COPD management tool

Results Jun 05 Investigator sponsored 100 patient study to determine sensitivity / specificity of Aridol test in identifying COPD patients who will respond to steroids (smokers) Investigator sponsored 40 patient study to determine sensitivity of Aridol in identifying steroid responsive COPD patients (ex-smokers)

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Bronchitol

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Product Detail

Inhaled mannitol for CF & COPD

Phase IIb for COPD Phase IIa for CF Patents granted in the U.S. and Australia, pending in Europe and Japan

Uniform, respirable osmotically active sugar

Delivers compound into deep, smaller airways Simple dry-powder delivery without need for nebulizer

Therapeutic benefits

Reduce exacerbations Reduce hospitalizations Extend life expectancy

impaired mucus clearance infection increased mucus production inflammation

X

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Detailed Mechanism of Action

Airway Surface Airway Surface Liquid Liquid

Lung defense (normal)

Mucus Mucus Submucosal glands Submucosal glands Cilia Cilia

Goblet Cell Ciliated Cell

Airway Surface Airway Surface Liquid Liquid

Lung defense (normal)

Mucus Mucus Submucosal glands Submucosal glands Cilia Cilia

Goblet Cell Ciliated Cell

Lung defense (normal)

Mucus Mucus Submucosal glands Submucosal glands Cilia Cilia

Goblet Cell Ciliated Cell

Lung Lung defense defense (compromised) (compromised)

Ciliated Cell Goblet Cell

Mucus Mucus

Airway Surface Airway Surface Liquid (thin/viscous) Liquid (thin/viscous)

Submucosal glands Submucosal glands Cilia Cilia

Lung Lung defense defense (compromised) (compromised)

Ciliated Cell Goblet Cell

Mucus Mucus

Airway Surface Airway Surface Liquid (thin/viscous) Liquid (thin/viscous)

Submucosal glands Submucosal glands Cilia Cilia

Lung Lung defense defense (after (after Bronchitol Bronchitol) )

Mucus Mucus Airway Surface Airway Surface Liquid Liquid Submucosal glands Submucosal glands Cilia Cilia

H2O H2O H2O H2O H2O Goblet Cell Ciliated Cell

Lung Lung defense defense (after (after Bronchitol Bronchitol) )

Mucus Mucus Airway Surface Airway Surface Liquid Liquid Submucosal glands Submucosal glands Cilia Cilia

H2O H2O H2O H2O H2O Goblet Cell Ciliated Cell

Restores Airway Surface Liquid

Non-absorbable sugar creates osmotic gradient No risk of post-receptor effects limiting chronic utility

Changes rheologic properties

Correction of mucus rheology increases action of ciliary elevator

Increases ciliary beat frequency

Decreased infection and chronic inflammation Increased pulmonary function

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Chronic bronchitis Chronic bronchitis

without Mannitol without Mannitol

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Chronic bronchitis Chronic bronchitis

with Mannitol (400mg) with Mannitol (400mg)

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Bronchitol

Status in COPD

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Chronic Obstructive Pulmonary Disease

Epidemiology

COPD represents emphysema, chronic bronchitis and bronchiectasis 4th leading cause of death in US – estimated 12 M affected, 1.4 M diagnosed Direct cost to US healthcare estimated at $18 billion per year

Disease progression

Airway hyper-reactivity / obstruction (overlaps asthma) Chronic infections Irreversible lung tissue damage Hypoxemia, pulmonary hypertension, right heart failure

Current Management

Bronchodilators Mucoactive agents Oral corticosteroids (1 in 5 respond to steroids) Prevention / Treatment of infections Supplemental oxygen

Source: National Heart, Lung, and Blood Institute. Morbidity and Mortality: 2002

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Proof-of-Concept Data - Bronchiectasis

Right Peripheral Region of Lung Right Peripheral Region of Lung

  • 10

10 20 30 40

120min 120min 24hr 24hr without without Bronchitol Bronchitol with with Bronchitol Bronchitol p<0.001 p<0.001 p<0.003 p<0.003 Mean % Clearance Mean % Clearance

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Proof Proof-

  • of
  • f-
  • Concept Data

Concept Data -

  • Bronchiectasis

Bronchiectasis

40 50 60 70 80 90 100 110

20 40 60 80 100 120 Mean Retention (%) Mean Retention (%)

Time since mid Time since mid-

  • inhalation of

inhalation of radioaerosol radioaerosol (min) (min)

Baseline Baseline Control (cough) Control (cough) Mannitol Mannitol Initial Initial Baseline Baseline

Intervention Intervention

Post Intervention Post Intervention

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Phase Phase IIb IIb Clinical Trial Design Clinical Trial Design

Study Population: Patients with known bronchiectasis Study Protocol: Blinded, multicenter, cross-over trial Dosage: 400 mg twice daily for 14 days Numbers 60 pts Clinical Sites: 4 Primary Endpoint: QOL (St. George questionnaire) Additional Endpoints: FEV1, sputum microbiology, rheology and 24hr sputum volume Results Expected: September 2004

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Bronchitol

Status in CF

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Cystic Fibrosis Cystic Fibrosis

Epidemiology Epidemiology

Genetic disease - affects or 1000 new infants per year in the U.S. 30,000 children and adults affected in the US Median survival now early-thirties Disease progression Abnormal pulmonary mucus secretions Early infections with S. aureus, or H. influenza Chronic infections with Pseudomonas aeruginosa and Burkholderia Lung tissue damage (bronchiectasis), hypoxia, death

Current Management Current Management

Pulmozyme - a mucolytic agent TOBI - inhaled Tobramycin Other antibiotics - oral Bronchodilators Inhaled and oral corticosteroids

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Proof-of-Concept Data - CF

Mannitol Mannitol

20 20 40 40 60 60 80 80 100 100 120 120 140 140

% RETENTION % RETENTION

70 70 80 80 90 90 100 100

post post-

  • intervention

intervention Matched cough Matched cough Intervention Intervention

n =15 patients with CF

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Phase IIa Clinical Trial Design

Study Population: Evaluating children and adults with cystic fibrosis in the hospital setting Study Protocol: Randomized, double blinded, multicenter, placebo controlled, crossover study number: 60 pts Clinical Sites: 4 Dosage: 420 mg twice per day for 14 days Primary Endpoints: FEV1 Additional Endpoints: QOL (St. George questionnaire), lung function and safety Results Expected: November 2004

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Next steps in clinical development

Phase IIb Trial

Study Population: Evaluating children and adults with cystic fibrosis in the hospital setting Study Protocol: Head-to-head, parallel trial versus Pulmozyme in 30 patients Dosage: 400 mg twice per day for 3 months Primary Endpoints: QOL (St. George questionnaire), and FEV1 Additional Endpoints: Safety, sputum microbiology, and rheology Results Expected: November 2005

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Preclinical Pipeline

Product Detail

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Autoimmune Disease

PXS25

Orally available compound effective in MS and RA models IGF-2 receptor antagonist Inhibits diapedesis, immune cell trafficking Human studies Q2 2005 Pro-drug under development with excellent PK profile

PXS2030

Orally available compound targeting symptoms of MS Peripheral cannabinoid receptor agonist Inhibitor of T cell migration & B cell proliferation

PXS2076

Effective in RA models Believed to act through intracellular kinase pathways Inhibits TNF release from immune cells BA of >80%

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Summary

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Upcoming Milestones Upcoming Milestones

Aug 04 Aridol investigator sponsored trials commence

Management of asthma with steroids – UK general practice Management of COPD with steroids – Sydney

Sep 04 Bronchitol in COPD, Phase IIb trial results Sept 04 Aridol Phase III clinical trial results - asthma Oct 04 Aridol in COPD with steroids – Switzerland Oct 04 Submit IND - Aridol study in USA Oct 04 Aridol v methacholine in asymptomatic pts – Denmark Nov 04 Bronchitol in CF - Phase IIa trial results Nov 04 Aridol registration in Aus/EU Early 05 Commence US Aridol study Mid 05 Aridol launch Aus/EU Mid 05 Phase I study with PXS25 pro-drug Nov 05 Bronchitol in CF vs pulmozyme, Phase IIb trial results Late 06 Bronchitol in COPD, Phase III results Early 07 Bronchitol in CF, Phase III results

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Finances

Year to 30 June 03 Year to 30 June 03 Year to 30 June 04 Year to 30 June 04 Income Statement Income Statement US$ US$’ ’000 000 US$ US$’ ’000 000 Revenues Grants 571 789 Interest 166 768 Other 25 34 762 1,591 Expenditures Research and Development (1,047) (4,317) Administration (574) (1,557) Net loss before and after tax (858) (4,284) Depreciation & amortisation 150 350 EBITDA (875) (4,702) Balance Sheet Balance Sheet Cash & equivalents 4,931 17,416 Total assets 7,009 19,518 Long term debt

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Management

Alan Robertson BSc, PhD Chief Executive Wellcome/Faulding/amrad Brett Charlton MBBS, PhD Medical Director Baxter/Stanford/ANU William Cowden BSc, PhD Chief Scientist Progen/Peptech/ANU David McGarvey BA, CA Finance PWC/Memtec/US Filter John Crapper BAS, MBA Operations Syntex/Memtec/US Filter Gary Phillips BPharm, MBA Commercial Novartis 28 employees, 24 in R&D, 4 in G&A