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CHEMGENEX

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Two drug candidates in Phase II clinical trials for cancer. Commercial in confidence ... Ceflatonin Phase II Clinical Trials for MDS & CML ... – PowerPoint PPT presentation

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Title: CHEMGENEX


1
CHEMGENEX Pharmaceuticals
2
ChemGenex Pharmaceuticals
  • The merger of AGT Biosciences and ChemGenex
    creates a new genomics-driven biopharmaceutical
    company with
  • Leading-edge capabilities for drug discovery and
    development
  • Two drug candidates in Phase II clinical trials
    for cancer

3
ChemGenex Pharmaceuticals
  • ChemGenex Pharmaceuticals discovers and develops
    novel therapeutics for prevalent human diseases
  • Broad and deep product portfolio offers
    development opportunities
  • On our own in cancer and other niche markets
  • In partnership with leading pharmaceutical
    companies in diabetes/obesity and CNS diseases

4
ChemGenex Pharmaceuticals Capabilities
  • Melbourne, Australia ? Human genomics center with
    over 44,000 human DNA samples
  • Geelong, Australia ? Animal models and functional
    genomics
  • San Antonio, TX, USA ? Statistical Genomics
  • Menlo Park, CA, USA ? Preclinical drug
    development and clinical trials

5
Vertically integrated to deliverpersonalised
medicine solutions
Discovery
Preclinical
Clinical
Target Discovery
Target Validation
Biomarker Development
Clinical Trial Management
Chemistry
Lead Optimisation
Genomics Technologies
Genetics
Expression Analysis
Functional Genomics
Chemogenomics
Pharmacogenomics
Proteomics Technologies
Protein Biochemistry
Pathway Analysis
Functional Proteomics
Bioinformatics Technologies
Data Mining
IP Management
Chemogenomics
Pharmacogenomics
Clinical Data Management
6
Clinical Trial Pipeline
  • Ceflatonin Phase II Clinical Trials for MDS
    CML
  • Quinamed Phase II Clinical Trials for solid
    tumors

7
Ceflatonin
  • Natural product with established broad clinical
    activity as a single agent in hematological
    malignancies.
  • A potent inhibitor of angiogenesis
  • Orally bioavailable
  • CML Opportunity
  • Currently no approved therapies for CML patients
    who have failed treatment with Gleevec (Novartis)
  • Ceflatonin has demonstrated good clinical
    activity for all stages of CML
  • High probability of approval

8
Ceflatonin Phase II MDS Study
  • Indication Myelodysplastic syndrome (MDS)
  • Center M. D. Anderson Cancer Center
  • Principle Investigator Hagop Kantarjian, M.D.
  • Dosing
  • Induce Remission 2.5mg/m2 daily for 7 days every
    month
  • Maintain Remission 2.5mg/m2/day x 7days/month
    12 courses or until treatment failure or
    unacceptable toxicity
  • Endpoints
  • Response rate, time to progression and survival
  • Patients up to 30

9
Ceflatonin Phase II CML Study
  • Indication Chronic myelogenous leukemia (CML)
    recurrence after Gleevec failure
  • Center M. D. Anderson Cancer Center
  • Principle Investigator Hagop Kantarjian, M.D.
  • Dosing
  • Induce remission 2.5mg/m2 daily for 14 days
    every month
  • Maintain remission 2.5mg/m2 daily x 7 days/mo
    12 courses or until treatment failure or
    unacceptable toxicity
  • Endpoints
  • Response rate, time to progression and survival
  • Patients up to 30
  • Protocol under development

10
Ceflatonin Development Strategy
  • Current and Planned Phase II Studies
  • Chronic myelogenous leukemia (CML)
  • Myelodysplastic syndrome (MDS)
  • Acute myeloid leukemia (AML)
  • Phase III
  • Chronic myelogenous leukemia (CML)
  • Recurrence after Gleevec
  • Ceflatonin vs. best supportive care

11
Ceflatonin U.S. Market Potential
Market (millions)
US Annual Incidence
Indication
  • MDS 15,000 630
  • CML 4,700 396
  • AML 10,000 336

12
Clinical Trial Pipeline
  • Ceflatonin Phase II Clinical Trials for MDS
    CML
  • Quinamed Phase II Clinical Trials for solid
    tumors

13
QuinamedTM
  • Amonafide dihydrochloride
  • Substituted isoquinoline
  • Topoisomerase inhibitor
  • Also affects ADP-ribosylation and EGFR pathway
  • Potential targets include PKC, PLCg and c-Jun
  • Active as a single agent in solid tumors
  • Chemopotentiates widely used agents
  • Platinum compounds
  • Taxanes
  • Others

14
QuinamedTM
  • Multiple NCI studies thru 1990s
  • Metabolized by N-acetyltransferase into active
    form
  • Three patient genotypes
  • Fast acetylators highest toxicity
  • Intermediate acetylators - moderate toxicity
  • Slow acetylators limited toxicity
  • Hypothesis Personalized dosing will improve
    therapeutic indices and optimize response
  • Phase I to determine optimal dose by genotype
  • Phase II to confirm efficacy

15
Quinamed Phase I/II Study
  • Solid tumor indications prostate, colon, breast,
    lung
  • Schedule
  • Weekly dosing
  • Two-hour infusion for three weeks, one week of
    rest
  • Start dose 400mg/m2/week, escalate by 100 mg
    increments (3 pts each group)
  • Genotype by acetylation status
  • Phase I to establish MTD by genotype
  • Phase II to evaluate efficacy
  • Principal Investigator Howard Burris, M.D.,
    Director or Drug Development, Sarah Cannon Cancer
    Center

16
Quinamed Genotype Predicts PK
17
Quinamed Phase I/II Study
  • 32 patients enrolled
  • Indications of activity in five different tumor
    types
  • Manageable side effects
  • MTD established by genotype
  • Phase I data to be presented at American Society
    of Clinical Oncology (ASCO) in June 2004

18
Quinamed Development Plan
  • Phase II trials to begin patient enrollment in Q2
    2004
  • Potential Indications include
  • Prostate cancer
  • Breast cancer
  • Ovarian cancer
  • Gastric cancer
  • Colon cancer
  • Approval-directed studies planned for late 2004

19
Quinamed Market Potential
Market (millions)
US Annual Incidence
Indication
Colon 144,000 2160 Breast
220,000 3300 Prostate 140,000
2100
20
Discovery Pipeline
  • Diabetes/Obesity
  • Depression/Anxiety
  • Cancer/Inflammation

21
Discovery Pipeline
Protein Therapeutic Target
100 targets
Antibody Therapeutic Target
Small Molecule Therapeutic Target
Develop and apply disease-relevant cellular assays
Screen for pharmaceutical relevance
Develop targeted therapeutic applications
22
Discovery Pipeline
Example AGT121
Genomics Technologies
  • Gene expressed exclusively in neurons
  • Gene expression increased in hypothalamus of
    obese animals
  • 19 SNPs discovered in human gene
  • 2 SNPs associated with obesity phenotypes
  • siRNA suppression in animals profoundly reduced
    food intake and body weight
  • siRNA suppression in animals increased
    sensitivity to melanocortin receptor antagonist

Proteomics Technologies
  • Interacts with endophilins 1 and 3
  • Proposed role in clathrin-mediated endocytosis
  • Elevated levels in brains of agouti mice
  • Localised in hypothalamic nuclei involved in
    regulation of food intake

Bioinformatics Technologies
  • Extremely proline-rich
  • Contains multiple SH3 and WW domains
  • No IP encumberance

AGT121 is a novel neuronal protein involved in
the regulation of food intake
23
AGT-121
  • Antisense studies in rats
  • n8-9 per group
  • 24 mg/day constant infusion into right lateral
    ventricle

(A) Cumulative food intake. psaline controls pcontrols pcontrols. (B) Cumulative change in body weight.
p0.038 compared to jumbled controls, pcompared to jumbled and saline controls.
24
AGT-121 Mechanism of Action
MC4R
X
Signalling cascade
25
Merck-Santé diabetes/obesity program
Discovery
Bio-informatics Candidate ID
Target ID
Functional Genomics Target Validation
Lead Generation
Pre-clinical Toxicology
Clinical Trials
Drug Production
Diabetes Obesity
  • Merck provides
  • Minimum 3.8 million per annum
  • Chemistry, preclinical and clinical expertise
  • Funding for all clinical development
  • 5 million per target that progresses to phase 2
    clinical trial
  • 5-7 royalty on net sales (markets worth US8
    billion/yr)

26
Depression Anxiety Program
Discovery
Bio-informatics Candidate ID
Target ID
Functional Genomics Target Validation
Lead Generation
Pre-clinical Toxicology
Clinical Trials
Drug Production
Diabetes Obesity
Depression Anxiety
Pharmaceutical Partner
  • With global sales of US16 billion,
    anti-depressants are the highest selling drug
    class
  • AGT Biosciences has a competitive advantage and
    growing IP position
  • Animal model for discovery and testing
  • Nine new genes associated with onset of depression

27
Cancer and Inflammation Targets
Discovery
Bio-informatics Candidate ID
Target ID
Functional Genomics Target Validation
Lead Generation
Pre-clinical Toxicology
Clinical Trials
Drug Production
Diabetes Obesity
Depression Anxiety
Pharmaceutical Partner
Internal Development
Cancer Inflammation
  • 2 novel cancer targets
  • 3 novel inflammation targets

28
Oncology Program
Discovery
Bio-informatics Candidate ID
Target ID
Functional Genomics Target Validation
Lead Generation
Pre-clinical Toxicology
Clinical Trials
Drug Production
Diabetes Obesity
Depression Anxiety
Pharmaceutical Partner
Internal Development
Cancer Inflammation
Oncology Program
  • Quinamed Phase II Clinical Trial
  • Ceflatonin Phase II Clinical Trial

29
Product and Target Pipeline
Animal Validation
Preclinical
Phase I
Phase II
Phase III
Project Modality Lead Indication Quinamed S
mall Molecule Oncology Ceflatonin Small
Molecule Oncology CGX-6001B Small
Molecule Oncology CGX-2101 Small Molecule
Oncology CGX-273 Small Molecule
Oncology AGT101 Small Molecule
Metabolism - Obesity AGT102 Protein
Metabolism - Diabetes AGT203 Protein
Metabolism - Diabetes AGT121 Small Molecule
Metabolism - Obesity AGT706 Small Molecule
Metabolism - Diabetes AGT114 Small Molecule
Metabolism - Diabetes AGT708 Small Molecule
Metabolism - Diabetes AGT701 Protein
Metabolism - Diabetes AGT711 Small Molecule
Metabolism - Diabetes AGT301 Small Molecule
CNS - Depression AGT302 Small Molecule
CNS - Depression AGT303 Small Molecule CNS
- Depression AGT304 Small Molecule CNS -
Depression AGT305 Small Molecule CNS -
Depression AGT901 Antibody
Inflammation AGT902 Antibody
Inflammation AGT903 Small Molecule
Inflammation
Oncology Program (ChemGenex)
Metabolism Program (Merck)
CNS Program (AGT)
Inflammation Program (AGT)
30
Milestones 2004
  • Present Quinamed Phase I study results at the
    American Society of Clinical oncology (ASCO)
    Meeting in June
  • Initiate Phase IIb trials on Quinamed
  • Complete Phase II MDS trial on Ceflatonin
  • Present Ceflatonin Phase II MDS results at a
    major medical meeting
  • Preclinical development of diabetes/obesity
    targets with Merck
  • Establish pharmaceutical partner for
    depression/anxiety program

31
ChemGenex Pharmaceuticals
  • Creation of a new biopharmaceutical company
  • Compelling synergies and strategic reasons for a
    merger between ChemGenex and AGT Biosciences
  • Integration of ChemGenexs clinical development
    strength and regulatory expertise with AGTs
    discovery capabilities and infrastructure
  • Combination of ChemGenexs chemistry capabilities
    with AGTs target discovery/target validation
    capabilities
  • Enhancement of AGTs current cancer targets via
    ChemGenexs oncology expertise (creation of a
    focused cancer target validation program)
  • Establish an experienced management team with
    broad biotech experience
  • Access to extremely experienced US-based advisors
    of ChemGenex
  • Creation of a powerful product-focused
    biotechnology company with late stage clinical
    trials in progress

32
Proposed Transaction Structure
  • AGT will issue to the shareholders of ChemGenex
    28 million shares at A0.50 representing A14
    million (49 of its share capital)
  • Post-transaction AGT will have 85 million shares
    outstanding
  • ChemGenex shareholders will collectively own 28
    million shares of AGT representing 32.9
    ownership of the combined entity

33
Post Merger Strategy
  • Initial financing of A5 million
  • Funded by 12 month commercial credit facility
  • Upgrading of Level 1 to Level 2 ADR NASDAQ
    listing of combined entity

34
Management
  • CEO and Managing Director Greg Collier
  • President of US Operations Dennis Brown
  • Business Development Harry Pedersen

  • James Campbell
  • Finance Administration Tina Herbert
  • Senior Scientific Directors Paul Zimmet

  • John Blangero

  • Ken Walder

  • Shawnya Michaels

35
ChemGenex Pharmaceuticals
  • Our strategy is to apply our unique suite of
    target and drug discovery and compound
    development technologies to realise the potential
    of genomics across pharmaceutical research and
    development from target discovery and validation
    through drug discovery, lead optimisation and
    clinical trials

36
Safe Harbor Statement
  • Certain statements made herein that use
    the words estimate, project, intend,
    expect, believe, and similar expressions are
    intended to identify forward-looking statements
    within the meaning of the US Private Securities
    Litigation Reform Act of 1995. These
    forward-looking statements involve known and
    unknown risks and uncertainties which could cause
    the actual results, performance or achievements
    of the company to be materially different from
    those which may be expressed or implied by such
    statements, including, among others, risks or
    uncertainties associated with the development of
    the companys technology, the ability to
    successfully market products in the clinical
    pipeline, the ability to advance promising
    therapeutics through clinical trials, the ability
    to establish our fully integrated technologies,
    the ability to enter into additional
    collaborations and strategic alliances and expand
    current collaborations and obtain milestone
    payments, the suitability of internally
    discovered genes for drug development , the
    ability of the company to meet its financial
    requirements, the ability of the company to
    protect its proprietary technology, potential
    limitations on the companys technology, the
    market for the companys products, government
    regulation in Australia and the United States,
    changes in tax and other laws, changes in
    competition and the loss of key personnel. These
    statements are based on our managements current
    expectations and are subject to a number of
    uncertainties that could change the results
    described in the forward looking statements.
    Investors should be aware that there are no
    assurances that results will not differ from
    those projected.
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