L-DOS47L-DOS47A phase I/II lung cancer candidate

that uses tumour alkalization as a

therapeutic approach

Safe Harbor Statement

This presentation contains certain forward-looking statements and information

(collectively, “forward-looking statements”), regarding the development of our

new drug candidate, L-DOS47, and include statements regarding our planned

Phase I/II programs and submission of a European study for regulatory approval.

Certain material assumptions have been made in making these forward-looking

statements, including successful and timely completion of pre-regulatory

submission activities; receipt, on a timely basis of all regulatory approvals and

appropriate financing; and sufficient patient enrolment. These forward-looking

This presentation contains certain forward-looking statements and information

(collectively, “forward-looking statements”), regarding the development of our

new drug candidate, L-DOS47, and include statements regarding our planned

Phase I/II programs and submission of a European study for regulatory approval.

Certain material assumptions have been made in making these forward-looking

statements, including successful and timely completion of pre-regulatory

submission activities; receipt, on a timely basis of all regulatory approvals and

appropriate financing; and sufficient patient enrolment. These forward-lookingappropriate financing; and sufficient patient enrolment. These forward-looking

statements are subject to risks and uncertainties that may cause actual events or

results to differ materially from such statements, including without limitation, our

need for further financing, which may not be available; the delay or denial of

regulatory approvals needed; that future events, including patient enrolment,

may not proceed or be completed as planned or within expected timelines; and

that the planned studies may not be completed or achieve expected results.

appropriate financing; and sufficient patient enrolment. These forward-looking

statements are subject to risks and uncertainties that may cause actual events or

results to differ materially from such statements, including without limitation, our

need for further financing, which may not be available; the delay or denial of

regulatory approvals needed; that future events, including patient enrolment,

may not proceed or be completed as planned or within expected timelines; and

that the planned studies may not be completed or achieve expected results.

Tumour Microenvironment

Robert A. Gatenby and Robert J. Gillies

Nature Reviews Cancer 4:891 2004

License:2601421317277

Acidic and Hypoxic Environment

Robert A. Gatenby and Robert J. Gillies

Nature Reviews Cancer 4:891 2004

License:2601421317277

Acidosis and Hypoxia

�Increase radio-resistance

�Resistance to chemotherapeutics

�Increase metastases

�Increase migration and invasion

DOS47 – Proposed MOA

�Reverse Tumour Acidity

�Apply Natural Metabolic Toxin

�Induce Chemo-optimized Environment

Urea 2NH4+ + OH- + HCO3

-

3H2O

Urease

Effects of pH on cell survival

60

80

100

% S

urvi

val

7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.50

20

40A549MB231

pH

% S

urvi

val

2h @ 37oC

pH and Ammonium

NH4+ + OH-H2O + NH3

Ammonia Ammonium

75

100

125pH 7.4

pH 8.4

pH 9.0

pH 9.6

% S

urvi

val

A549

0 10 20 30 40 50 60 70

0

25

50

75 pH 9.6

pH 10.0

[NH4Cl] mM

% S

urvi

val

DOS47- Cell Proliferation Inhibition

40

60

80

100

8.6

8.8

9.0

pH

% C

ell P

rolif

erat

ion

Inhi

bitio

n

0 50 100 150 200

0

20

40

% Inhibition

pH

8.0

8.2

8.4

% C

ell P

rolif

erat

ion

Inhi

bitio

n

[Urea] mM

DOS47 Activity Inhibition

60

80

100

% S

urvi

val

Acetohydroxamic acid (AHA)

0 1 2 3 4 5 6 7 8 9 10 11 12 13

0

20

40No Urea

5 mM Urea

25 mM Urea

25 mM Urea (no DOS47)

[AHA] mM

% S

urvi

val

acid (AHA)

DOS47 MCF7 and A549 Xenograft

MCF-7

A549

Journal of Experimental Therapeutics and Oncology

(volume 5, number 2, pp. 93-99) – DOS47

A Lung Cancer Specific Antibody

Llama single domain antibody fragment “L”

Cell Surface Specific

A549 cell A549 tumour slide

Antigen Identification

(kDa)

10377

50

1 2 3 1 2 3

1 = total protein

2 = soluble protein

3 = hydrophobic protein

50

34

29

21 +ES1 -ES1

2nd Ab = rabbit anti-VT1B

3rd Ab = goat anti-rabbit AP

Antigen Identification by MS

carcinoembryonic antigen related cell adhesion molecule 6

(CEACAM6), 344 aa, MW = 37,159. Peptides shown in red.

MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQLHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDGPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQAHNSATGLNRTTVTMITVSGSAPVLSAVATVGITIGVLARVALI

L-DOS47

Antibody “L”

urease

L-DOS47 Tight Binding to CEACAM6

L-DOS47 Imaging

Tumour specific localization

Full Body ScanA549 tumour (8 x 7 mm)

L-DOS47-Cy5.5

Filtered ScanL-DOS47-Cy5.5

Cy5.5 emission max @710nm

L-DOS47 Imaging

80

100

120

No

rma

lize

d F

luo

resc

en

ce I

nte

nsi

ty

12hrs

24hrs

48hrs

72 hrs

0

20

40

60

Time post injection (hours)

No

rma

lize

d F

luo

resc

en

ce I

nte

nsi

ty

72 hrs

L-DOS47 A549 Xenograft

200

250

300

350VehicleCisplatinL-DOS47 (35U/kg)L-DOS47 (20U/kg)

%C

hang

e in

Tum

our

Volu

me

0 5 10 15 20

0

50

100

150

200 L-DOS47 (20U/kg)L-DOS47 (10U/kg)

Days

%C

hang

e in

Tum

our

Volu

me

Human Cancer Tissue Screening

Positive Negative NegativeKidney carcinoma 12/12 12/12Parathyroid adenoma 1/1 n/a

Plaenta, umbilical cord, allantois 1/1Myofibroblastic tumor 1/1 n/a

Prostate carcinoma 4/4 4/4Thyroid carcinoma 2/2 2/2

7/57 weak8/57 v. weak

Neuroendocrine tumors 9/9 n/a

Brain, heart muscle, testis, spleen 30/30n/a

Samples

Pancreas adenocarcinoma 42/57

Age-matched Normal Tissue

Tumour Tissue

n/a

25/25

Brain, heart muscle, testis, spleen 30/30Testis - teratoma and seminoma 3/3 3/3Parotis tumor 1/1 1/1Cervix squamous carcinoma 2/2 n/a

Thymoma 2/2 n/a

Colon adenocarcinoma 14/24 weak 10/24- lymph node metastasis 3/3

Breast adenocarcinoma 13/13- lymph node metastasis 2/2

Leiomoma - lung metastasis 1/1 n/a

Ovary carcinoma 4/4 n/a

Bladder carcinoma 42/42- lymph node metastasis 1/1 strong- squamous carcinoma metastasis 2/2

Lung - small cell carcinoma 1/1- adenocarcinoma 5/5 strong

Stomach adenocarcinoma 3/3 3/3Liver carcinoma 4/4 4/4Soft tissue tumors 3/3 n/a

Melanoma 48/48- metastasis 18/18

18/18

36/36

24/24

13/13

5/5

Weakly Basic Drug

Mitoxantrone pKa 8.13 Doxorubcin pKa 8.34

Vinblastine pKa 7.4

Vincristine

Vinorelbine

Effect of pH on Drug’s Efficacy

A549 cells

doxorubicin (100 µM), mitoxantrone (75 µM), and vinblastine (150 µM)

Effect of L-DOS47 and Vinorelbine on A549

Vi

% V

iabl

e C

ance

r C

ell

Vinorelbine only

Vinorelbine + L-DOS47

Vinorelbine (µM)

% V

iabl

e C

ance

r C

ell

L-DOS47 Phase I/II Program

� Helix plans to conduct a comprehensive Phase I/II program

� Two parallel, open-label studies are under consideration:

� U.S. Phase I safety study in refractory solid tumours

� European, multi-arm, Phase I/II safety/efficacy study in patients with

Stage III/IV NSCLCStage III/IV NSCLC

� L-DOS47 monotherapy

� L-DOS47 adjunct chemotherapy/radiation therapy regimens

� US Phase I study has been approved by the FDA

� European study to be submitted and subject to regulatory approval

Summary

�A different approach to cancer therapy� Targeting tumour microenvironment

�Specific for lung adenocarcinoma� Unique antibody � Unique antibody � Specific binding to lung cancer tissue

�Clinical program underway� US Phase I recently approved� European Phase I/II planned

Acknowledgement

�Helix BioPharma Corp

�Wah Wong, Carl De Luca, Baomin Tian, Kim Gaspar, Iain Wilson, Sharon Molund, Terri Hinkley, Jill Chapman, Axel Wellmann, John Docherty and Don SegalSegal

�National Research Council of Canada

�Institute of Biological Sciences

�Roger MacKenzie, Jianbing Zhang

�Institute for Bio-diagnostics

�Elda Hegmann, Mike Sowa

THANK YOU

Helix BioPharma Corp