Thor Borgford, PhD

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Novel and Targeted Prodrugs

• Thor Borgford, PhD
• President CEO
• 8081 Lougheed Highway
• Burnaby, B.C., V5A 1W9
• www.twinstrand.com

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Investment Opportunity

• Commencing Phase I with Anti-Cancer Lead
• Robust Product Platform with
• A wide range of potential disease applications
• Rapid and cost-effective pipeline development
• Unique Mechanism of Action
• Strong IP Position with Broad Claims
• Portfolio of issued patents
• Compelling Preclinical Data

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Targeted Prodrugs
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Ribosome Inactivating Proteins

• Ricin, Abrin and Viscumin
• Exquisite cell killers
• Phase I human trials of the natural ricin and
  viscumin have demonstrated tumour responses
• Unique mechanisms of action

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Ribosome Inactivators Engineered into Prodrugs

• NEW IP CREATED

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Mechanism of Action Catalytic
QuickTime Movie
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Proteases with well established roles in Disease

• Cancer-related
• Matrix Metalloproteinases
• Prostate Specific Antigen
• Cathepsins
• Plasminogen Activators

• Virus-related
• Hepatitis C Protease
• HIV Protease
• HTLV Protease

• Parasite-related
• Malarial Protease

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Development of TST10088 (MMP Lead)
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Lead Prodrug TST10088

• Activation by MT1MMP, MMP2 and MMP9
• MMPs prevalent in all solid tumours
• Highly correlated with poor prognosis
• Small Cell Lung Ovarian Cancer
• SCLC 99,000 new cases annually and 63,000 deaths
  (7 Major)
• Ovarian 54,000 diagnoses annually and 36,000
  deaths (7 Major)
• Current Drug Revenue for the 2 Markets 1.4B
  and projected to reach 2.2B in 2012

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MMPs in Solid Tumor Progression
Tumor Vascularization
Primary Tumor
Metastasis
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Competitive Advantages

• Extraordinary synergy with conventional drugs
• Efficacy against drug resistant tumors
• Improved side-effect profile as compared to
  conventional therapies
• Twinstrand Prodrugs will not cause genetic damage
  or bone marrow suppression

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Drug Synergy Murine Lymphoma Model (P388)
Doxorubicin
TST10088
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Drug Synergy Human Prostate Model (LnCap)
Paclitaxel
TST10088
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Immune Response (Rodent)
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Drug Product

• Sterile single-dose solution
• 1 mg/mL in PBS
• For intravenous infusion
• GMP Manufacture by Eurogentec

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TST10088 Clinical Plan Phase I Commenced May 2005
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Proposed Indications

• Treatment of patients with advanced solid tumours
  
• Where MMPs are present
• Combination therapy with conventional
  chemotherapeutic agents
• Reflecting the synergy seen in preclinical
  models

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Phase I Dosing (Safety Trial)

• Intravenous (IV) infusion
• 26 32 Patients
• One cycle 3 injections
• Days 1, 8 and 15 of a 28-day period
• Anticipate 2 2.5 treatment cycles
• Anticipated Completion Q1 2006

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Phase I Sites

• Canadian Site
• Princess Margaret Hospital (Toronto)
• PI - Dr. Lillian Siu
• US Site
• University of Colorado Cancer Center (Denver)
• PI Dr. Lia Gore

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TST10088 Clinical Plan Phase II Commencing H2
2006
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TST10088 Phase II Plan

• Small Cell Lung and Ovarian Carcinoma
• Randomized
• Two arms
• 80-100 Patients
• Efficacy and safety in combination with
  conventional cytotoxics
• Seek NCI collaboration to broaden program (not
  critical path) in liver cancer (hepatocellular
  carcinoma)

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Pipeline Products
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Pipeline Products

• PSA Prodrug
• Activation by Prostate-Specific Antigen
• Ricin-based Prodrug
• In vivo studies with lead candidates underway
• Abrin Prodrug
• Activating Protease MMP or PSA
• Family member with greater potency
• higher production yields relative to ricin

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Proprietary Position

• Major patent families filed in US, EU Japan
• Retroviral Disease (HIV/HTLV)
• Cancer, viral diseases, fungal and parasitic
  infections (e.g., malaria)
• Second and third generations of molecules
• 5 key patents issued in US
• 10 patents pending

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Management
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Senior Management

• Dr. Thor Borgford, PhD
• - President CEO
• Dr. Larry Gontovnick, PhD
• - VP, Development
• Dr. Curtis Braun, PhD
• - VP, Operations
• Ms. Marjorie Co, Bsc, LLB, MBA
• - Business Development Officer
• Ms. Evelyn Lomba, CPA, CGA
• - Controller

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Board of Directors

• Dr. Robert Fildes
• - Former President of Biogen
• - Former President CEO - Cetus Corporation
• Dr. Julia Levy
• - Former President and CEO - QLT Inc.
• Ms. Jeanne Bertonis
• - Chief Business Officer, Angiotech
  Pharmaceuticals
• Mr. Pat Brady
• - VP, Investments - GrowthWorks Capital
• Ms. Brenda Irwin
• Director, Venture Capital - Business Development
  Bank
• Dr. Hakan Telenuis
• VP, Investments MDS Capital Corporation
• Dr. Thor Borgford

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Key Advisors

• Professor K.R. Harrap CBE, DSc.
• Former Director - Cancer Therapeutics (CRC - UK)
• Preclinical/Clinical Programs Advisor, SAB Chair
• Dr. Malcolm Moore, MD, PhD,
• Princess Margaret Hospital
• Medical Advisor
• Dr. Robert Royds, M.B., B.S., MRCP.
• Theradex Inc., Princeton, NJ
• Clinical Focus Group
• Dr. Bruce Silver, MD PhD, FACP
• PRA International, Reston, VA
• Clinical Focus Group
• Ms. Deborah Ramsdell, MSc,
• Compliance Management, Boston, MA
• Regulatory Advisor, US Agent

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Corporate Strategy
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Corporate Strategy

• Develop TST-10088 independently through Phase
  I/II
• Seek partnership for later stage clinical
  development
• Rapid cost effective pipeline expansion
• Leverage non-dilutive funding
• Ricin Countermeasure Technology
• Maintain virtual organization structure

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Financing
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DEVELOPMENT PROCESS
TWINSTRAND
DISCOVERY, ANIMAL EFFICACY
GMP MANUFACT., RELEASE, STABILITY
PRECLINICAL TOXICOLOGY, BIOANALYTICAL
PHASE I
PHASE II/III
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Product Pipeline2005 - 2008
Ricin Counter- measure

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Conclusion

• Commencing Phase I with Lead Anticancer Product
• Unique MOA that works well with other drugs
• Cost-effective product development
• Product Platform with Multiple Potential
  Applications
• Supported by a strong IP position