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OTCQX: BIOAF
TSX.V: BTI
Corporate &
Technology Summary
A naturally occurring
physiological solution
to the delivery of
therapeutics to brain
biOasis.ca
Q2-2015
Overview: Company & Transcend Platform
biOasis Technologies Inc.
biOasis Technologies, Inc. (OTCQX:BIOF & TSX-V:BTI) is a publically
traded biopharmaceutical company focused on developing and
commercializing proprietary pharmaceutical products for central
nervous system ("CNS") diseases and disorders. Of particular interest
is the creation of therapeutic options for patient management to
address the limitations to bio-distribution presented by the properties of
the blood-brain barrier ("BBB").
TRANSCEND
Patented platform
technology based on the human protein
melanotransferrin (MTf) and peptides
found within (MTfp), for carriers that
deliver therapeutics across the BBB for
the treatment of CNS diseases.
2
Challenge
The Blood Brain Barrier (“BBB”)
A protective barrier that separates the brain from the
circulatory system, which blocks harmful chemicals from
entering the brain tissue
Problem
The BBB prevents medicines (anti-cancer drugs,
enzymes, antibodies, gene silencing siRNA, etc.) from
entering the brain at levels effective for treatment,
blocking about:
• 98% of small molecule drugs
• 100% of large molecule drugs1
Solution
biOasis discovered a naturally occurring biological
process that can transport drugs across the BBB and into
the brain tissue for the treatment of thousands of CNS
diseases and brain disorders
1) Royal Society of Chemistry
Capillary network of tightly woven
endothelial cells lining the blood vessels in
the brain, regulating transport of essential
molecules and maintaining a stable
environment
3
biOasis Presents: The Transcend Program
The Transcend Drug Delivery Platform
Patented carriers that deliver medicines across
the BBB for the treatment of CNS diseases
Transcend offers potential treatments for:
Brain Cancers &
Tumours
Neurodegenerativ
e Diseases like
Alzheimer's
Disease
Stroke and
Traumatic Brain
Injury
Metabolic
Diseases like
Lysosomal
Storage Diseases
Gene
Silencing
Therapy
…siRNA
& mRNA
4
Breakthrough Solution
The Transcend Program
Exploits a natural, biological process to deliver therapeutics into the brain tissue by linking
pre-existing drugs to a human protein and peptide thereof, that freely crosses the BBB
through receptors located on the brain capillary wall in a process called Receptor Mediated
Transcytosis.
MTf (Melanotransferrin)
• Iron-binding human protein found at low concentrations in
the blood
• When linked to existing drugs, MTf can deliver effective
doses of therapeutics into the brain, distributing the
compounds with a wide distribution throughout the brain
tissue
MTfp (MTf peptide)
• biOasis discovered the peptide found within the full-length
protein (MTf) that is responsible for transport of MTf across
the BBB
• MTfp has shown improved brain penetration and greater
commercial potential over the full-length MTf protein
5
Advantage of MTfp

Higher commercial value over MTf

More efficient delivery across the
BBB

Lower cost of production

Greater consistency in manufacturing

Improved quality control

Simpler to link to medicines

Transports a variety of compounds
with no apparent size limitation


Extends biOasis patent portfolio for
additional ~20 years
Pharmaceutical collaborators
currently licensing MTfp
MTfp in Action
Brain Tissue
RMT
Blood Vessels
MTfp
Therapeutic
RMT -Receptor
Mediated
Transcytosis
6
Market Opportunities for Transcend
2014 Drug Market Estimates
Lysosomal
Storage
Disease
Billion
USD
~$2
Psychiatry
~$32.
Neurodegenerative
Disease
3
Central Nervous
~$20
Billion
USD
Stroke &
Traumatic
Brain Injury
Billion
USD
System
Disorders
Pain &
~$81.2
Migraine
Billio
n
USD
~$33.7USD
Billion
~$7.5
A carrier to cross the BBB would
establish a foothold within these major
markets
Billion
USD
Clinical
need met
but
improved
BBB
penetration
could
increase
efficacy
Infection
~$138Billion
USD
7
Brain Cancer Drugs
2013 drug sales for cancers that frequently metastasize in the
brain1
Herceptin® (trastuzumab)
$6.6
HER2+ Breast Cancer
~40% Metastasize
Rituxan® (Rituximab)
Blood cancers: lymphoma, leukemia
~24% Metastasize
Erbitux® (Cetuximab)
Lung. colon cancer, etc.
~35% Metastasize
Taxol® (Paclitaxel)
Lung, ovarian, etc.
~35% Metastasize
Improved cancer
treatments have
Billion
USD
led to an
increase in brain
tumours,
creating a need
Billion
USD
for anti-cancer
drugs that target
the brain
Anti-cancer
The Transcend
drugs linked to
Program has
MTf penetrate
been shown to
the blood
reduce brain
tumour barrier
tumour volume by
10 times more
efficiently
84% when anticancer drugs are
linked to MTf
$1.9Billion
USD
$92Million
USD
$7.5
1) Company Reported Data
8
Opportunities with biOasis Technology
biOasis provides a number of opportunities
through its Transcend platform:
1. In-Licensing of biOasis BBB Drug Platform Technology
 For: Approved Therapeutics
 For: Research Therapeutics
2. Strategic Research Alliances
3. Lifecycle Management – Off Patent Therapeutics, “creating new
IP on old drugs”
9
Development Program: MTf + Trastuzumab
(Herceptin®)
• Trastuzumab (Herceptin®)1 is a humanized
monoclonal antibody used to treat HER2+
breast cancer with annual global sales ~$6.6
billion2
MTf + Trastuzumab (Herceptin®)
Confocal Images Two Hours Post IV Administration
Brain Capillaries
• Herceptin® increases survival rate but ~40%
of patients eventually develop breast cancer
metastasis in the brain3
Cell Nuclei
• Trastuzumab (Herceptin®) does not cross
the BBB on its own
• biOasis aims to, not only prevent and treat
HER2+ breast cancer that metastasizes in
the brain, but also for Transcend to become
the ‘Standard of Care’ for HER2+ breast
cancer
MTf + Trastuzumab (Herceptin®)
Confocal Image Performed by iCapture at
St. Paul’s Hospital Vancouver Canada
1) Herceptin® is a registered trademark of Roche/Genentech
2) Company Reported Data – 2013
3) Britta Weigelt, Johannes L. Peterse & Laura J. van't Veer. (2005, August). Breast cancer metastasis: markers and models. Nature Reviews
Cancer 5 , 591-602.
10
Transcend + Trastuzumab (Herceptin®)
Texas Tech University - Breast Cancer Model
Number of Tumours
Highlights
•
•
•
•
•
Reduced the number of HER2+ breast
cancer tumours in the brain by 68%
Total tumor volume reduced by 84% in
only 14 days, after 4 treatments
Penetrated the Blood-Tumour Barrier
10 times better than Herceptin®
alone
Increased cancer killing effect of
Herceptin® in tumours throughout the
body when linked with MTf
Offers the potential to be used in
conjunction with HER2+ cancer
therapy as a treatment and
preventative measure BEFORE the
cancer metastasizes to the brain
90
80
70
60
50
40
30
20
10
0
68%
Reduction
MTf
TZM
MTf-TZM
Saline
Control
TZM = Trastuzumab (Herceptin®)
11
Transcend + iduronate-2-sulfatase (“IDS”)
Hunters Syndrome (MPS II)
• Lysosomal Storage disease, MPS II is caused by
an IDS enzyme deficiency
• Currently CNS effects untreatable
Results
• biOasis’ MTf + IDS (lysosomal enzyme)
conjugate increased IDS brain enzyme activity
~20-fold, showing delivery to the brain tissue
Native Enzyme
does not enter the brain tissue efficaciously
Opportunity
• Brains for Brain Foundation are in studies with
MTfp + IDS, which offers the opportunity to fasttrack to human trials
• Offers promise of an efficient enzyme
replacement therapy
MTf + IDS Enzyme enters the brain tissue
12
Development Program: MTf + α-L-iduronidase
(“IDU”)
Lysosomal Storage Diseases
IDU Brain Enzymatic Activity
Rare inherited metabolic diseases caused by an
enzyme deficiency primarily affecting children
1.2
Hurler Syndrome (MPS I)
Results
• biOasis’ MTf + IDU (lysosomal enzyme)
conjugate increased IDU brain enzyme activity
~ 4-fold, showing delivery to the brain tissue
Total IDU activity
Problem
• MPS I is caused by an IDU enzyme deficiency
• Currently CNS effects untreatable
1
Parenchyma
Capillaries
0.8
0.6
0.4
0.2
Opportunity
• Offers the promise of an efficient enzyme
replacement therapy
0
IDU
MTf - IDU
13
Development Program: MTf + Doxorubicin
• Doxorubicin is currently used as a cancer
treatment for breast, lung, ovarian, thyroid,
and stomach cancers; multiple myeloma,
leukemia, Hodgkin's lymphoma, etc.
Problem
• These cancers metastasize in the brain but
MTf Significantly Enhances
Doxorubicin Transport into the Brain
% INJECTED DOSE
(G TISSUE/G BODY MASS)*100%
3.00
Doxorubicin does not efficiently penetrate the
BBB
Results
2.00
Conjugate retains
full activity once
released in the
brain
• Significant INCREASE in brain uptake with
the MTf + Doxorubicin conjugate vs.
Doxorubicin alone
1.00
Opportunity
• MTf + Doxorubicin conjugate could be used to
treat brain cancers that metastasize in the
0.00
MTf + DOXO
DOXO
14
MTf - Doxorubicin Achieves
Therapeutic Levels in the Brain
MTf delivered a therapeutic dose of Doxorubicin in the Brain
Increase survival of treated nude mice implanted
IC with ZR-75-1 mammary tumor cells
Injection Schedule
Increase survival of treated nude mice implanted IC with
C6 glioma cells
Southern Research Institute – Alabama
15
Transcend + Anti-Aβ antibody
Alzheimer’s Disease
Anti-Aβ antibodies have
undergone clinical trials for
treatment of Alzheimer’s disease
Results
biOasis’ MTf + anti-Aβ antibody conjugate increases
transport into brain tissue by ~5-fold
Quantitative Image Analysis by Laser
Scanning Confocal Microscopy
Opportunity
Using antibodies directed at Aβ
are potential therapeutics for
reducing amyloid plaques in the
brain, which are indicative of
Alzheimer's disease
MTf + Anti-Aβ
Anti-Aβ
National Research Council of Canada (NRC)
16
MTfp PK & Transport Data – Work Performed By
MedImmune
MTfp
• > 20 amino acid sequence
peptides, found within MTf that
was discovered after many
years of research
• MTfp has been conjugated to
fluorescently labeled:
• mAbs
• Enzymes
• siRNA
… all showing greater transport
than full length MTf protein alone
17
MTfp Facilitates Significant Amounts of Brain
Exposure with a Peak at 24h Post Single Dose
Ab 20 mg/kg
Ab-NH-MTf pep 20 mg/kg (fusion)
Ab-ADC-MTf pep 20 mg/kg (conjugate)
Ab-MTf40 mg/kg (fusion)
MTfp transported the
selected antibody at a rate
that equated to a %
injected dose/g brain of
3.8-4.8% - over 14.58
days
Re-plotted to focus on 1st 72h
18
MTf – PK Conclusions
Plasma exposure for full length MTf (P97) significantly lower than
for MTf peptides or IgG Isotype control
 due to shorter half-life peripherally
Brain exposure for full length MTf (P97) initially significant but short
lived – peak exposure at 2H time point
MTf peptides possess significant amounts of brain exposure, with
peak exposure at 24H post dose
Brain : plasma ratio peaks at one week following single i.v. dose
for all MTf constructs
19
Transcend (MTfp) + siRNA
Small Interfering RNA (siRNA)
• Silences target gene expression by knocking down disease
causing genes associated with human diseases
(i.e. cancers, neurodegenerative and metabolic diseases, etc.)
Problem
• Gene targeting within the brain is currently unachievable
because siRNA does not cross the BBB
NO siRNA detected in Brain
Results
• MTfp + siRNA conjugate delivered into the brain tissue
• Demonstrated 40% to 50% decrease in target gene vs. siRNA
alone
Opportunity
• A potential cornerstone technology for the development of new
therapeutics suppressing disease-linked genes in the brain
• siRNA is a rapidly emerging field of medicine
National Research Council
MTf + siRNA detected in Brain
20
MTfp Facilitated the Increased Transport of siRNA
Across the BBB into Brain Parenchyma
6.0E-04
Capillary
Volume Fraction
5.0E-04
Parenchyma
Mean ± SE
4.0E-04
3.0E-04
2.0E-04
1.0E-04
0.0E+00
siRNA alone
MTfp-siRNA
21
Part 2: Stroke Model via Middle Cerebral Artery
Occlusion (MCAO)
Rationale:
• Majority of strokes (88%) result from blockage of blood vessels in
the brain (ischemic stroke)
• Since most ischemic strokes (~80%) occur in the region of middle
cerebral artery (MCA), many animal stroke models developed to
date have focused on this artery.
• The most commonly used MCAO involves the insertion of a
surgical filament into the external carotid artery.
Transcend (MTfp) + siRNA in MCAO Stroke Model
MTfp delivered a therapeutic level of a siRNA targeting Nox4
in this MCAO model in two clear readouts -
2) Significant improvement in Neurological Scores
1) Significant reduction of area
of infarct
4
MTfp-SiRNA-stroke
Neurological Score
PBS-stroke
0.5h post MCAO
24h post MCAO
siRNA-stroke
MTfp-siRNA-stroke
3
2
1
0
PBS-stroke
National Research Council
23
Compounds Delivered - Pipeline
Objectives Achieved
Brain
Transport
Quantity in
the Brain
Localization in
Brain
(Cellular)
Efficacy
Models
Brain Cancer
Doxorubicin: Gliomas
~77% increase in survival time
Paclitaxel: Tumours
Herceptin: Breast Cancer
84% overall tumour reduction
Cetuximab: Lung Cancer
Lysosomal Storage Disease
Hurlers Syndrome : MPS l Model
~4 Fold Increase
Hunters Syndrome: MPS II Model
~20 Fold Increase
Sandhoff Disease: Hex B Model
siRNA
Stroke Model
ALS Model
24
Summary
Market Profile
Large Market
Opportunities
Good cash position
Clean share structure
Exit strategy in place
High internal
ownership
Ability to extend patent life
Commercialize new therapeutics
and/or revitalize dormant
candidates
Contribute to the growth
in CNS drug market
Management
Major success in:
Drug commercialization
Biotechnology & venture
capital startups
Academia
Awarded TSX.V
Top 50® in 2013
Leader in providing shareholder value
Transcend
Program
Discovery
of MTfp
Enhanced technology
“The first natural
Greater commercial
carrier to effectively
potential
transport therapeutic
drugs into the brain.”
Intellectual
Property
& Collaborations
Strong patent protection
Patent portfolio of >30 patents
Large pharmaceutical
collaborations
Positive results;
successful demonstration
Treatment
Potential
Metabolic diseases
Neurodegenerative
diseases
Brain Cancer
25
Thank you for your time!
biOasis Business Development
Team:
Cathy Miner
[email protected]
416 -569-5105
David Young
[email protected]
David Murayama
[email protected]
Michael Pettigrew
[email protected]
www.bioasis.ca