biOasis Technologies, Inc. (BTI:TSXV & BIOAF:OTCQX) Presentation - May 2014

Corporate NC Presenta-on May 2014

OTCQX:BIOAF & TSX.V:BTI

Delivering Breakthrough Therapeu3cs Across the Blood-‐Brain Barrier

TSX.V: BTI

Important Cau-ons Regarding Forward Looking Statements

Certain statements in this presenta-on contain forward-‐looking statements within the meaning of the Private Securi-es Li-ga-on Reform Act of 1995 or forward-‐looking informa-on under applicable Canadian securi-es legisla-on that may not be based on historical fact, including without limita-on statements containing the words “believe”, “may”, “plan”, “will”, “es-mate”, “con-nue”, “an-cipate”, “intend”, “expect” and similar expressions. Such forward-‐looking statements or informa-on involve known and unknown risks, uncertain-es and other factors that may cause our actual results, events or developments, or industry results, to be materially different from any future results, events or developments express or implied by such forward-‐looking statements or informa-on.

Such factors include, among others, our stage of development, lack of any product revenues, addi-onal capital requirements, risk associated with the comple-on of clinical trials and obtaining regulatory approval to market our products, the ability to protect our intellectual property, dependence on collabora-ve partners and the prospects for nego-a-ng addi-onal corporate collabora-ons or licensing arrangements and their -ming. Specifically, certain risks and uncertain-es that could cause such actual events or results expressed or implied by such forward-‐looking statements and informa-on to differ materially from any future events or results expressed or implied by such statements and informa-on include, but are not limited to, the risks and uncertain-es that: we may not be able to successfully develop and obtain regulatory approval for p97 as a Physician’s Aid to Diagnose Alzheimer’s, or future products in our targeted corporate objec-ves; our future opera-ng results are uncertain and likely to fluctuate; we may not be able to raise addi-onal capital; we may not be successful in establishing addi-onal corporate collabora-ons or licensing arrangements; we may not be able to establish marke-ng and the costs of launching our products may be greater than an-cipated; we have no experience in commercial manufacturing; we may face unknown risks related to intellectual property maPers; we face increased compe--on from pharmaceu-cal and biotechnology companies; and other factors as described in detail in our filings with the Canadian securi-es regulatory authori-es at www.sedar.com.

Given these risks and uncertain-es, you are cau-oned not to place undue reliance on such forward-‐looking statements and informa-on, which are qualified in their en-rety by this cau-onary statement. All forward-‐looking statements and informa-on made herein are based on our current expecta-ons and we undertake no obliga-on to revise or update such forward-‐looking statements and informa-on to reflect subsequent events or circumstances, except as required by law.

TSX.V: BTI

Who We Are…

•  Our patented “Transcend Family” of technologies allows proven and experimental drug therapies to penetrate the blood-‐brain barrier (BBB) and offer poten-al treatments for diseases, such as, but not limited to: •  Brain Cancers •  Neurodegenera-ve Diseases •  Lysosomal Storage Diseases

•  The “Transcend Family” is a Market Leading technology in BBB transport

•  New therapeu-c en--es based on the Transcend Family may offer hope for pa-ents while providing value to industry thru extending the patent life of numerous blockbuster drugs

•  Several drug development programs are currently underway

TSX.V: BTI

The Blood-‐Brain Barrier Challenge

•  The blood-‐brain barrier (BBB) safeguards the 400+ miles of capillaries and blood vessels in the brain which carry 20% of the body’s blood flow

•  While cancers origina-ng in the brain are fewer than in other regions of the body, 10x as many people develop brain tumors from cancers that begin elsewhere in the body (metasta-c)1

•  However, the BBB totally stymies modern cancer therapies that work effec-vely elsewhere in the body by blocking 98% of small molecule drugs and virtually 100% of large molecule drugs1

•  Crea-ng a ‘carrier’ to deliver these proven cancer treatments through the BBB could not only save lives, it could extend the patent life of many of exis-ng drug therapies

1)  Royal Society of Chemistry

The BBB consists of endothelial cells lining the blood vessels in the brain. In sharp contrast to blood vessels, this thin layer of ‘fortress cells’ are bound together so -ghtly, there are no gaps for blood-‐borne materials to leak into the brain.

TSX.V: BTI

How We Address this Opportunity: Our Breakthrough Solu-on -‐ Transcend

•  Transcend is based on Melanotransferrin (aka “MTf” or “p97”), an endogenous protein that is ac-vely transported across the BBB – Transcendpep is a family of pep-des origina-ng from Transcend offering improved brain penetra-on over Transcend -‐ the “Transcend Family”

•  The Transcend Family can uniquely ‘piggy back’ conjugated or fusion drugs and using Receptor Mediated Transcytosis, deliver them into the brain

•  Transcend Family conjugates may have improved PK and biodistribu-on, as well as a bePer side effect profile than the parent drug alone

•  Transcend Family conjugates & fusions may be designed in order to make the combined therapeu3c inac3ve in the blood un3l processed intracellularly by targeted brain cells and released as ac3ve inside the cells

Melanotransferrin (MTf) Protein

Transcend Conjugate

Transcend in Ac-on Receptor Mediated Transcytosis

BBB

TSX.V: BTI

Melanotransferrin (Transcend)

First iden-fied as cell surface marker associated with human skin cancer – p97 Melanoma-‐Associated An-gen

•  Belongs to a group of iron binding proteins transferrin, lactoferrin, ovotransferrin (Rose et al., 1985). Shares 40% sequence iden-ty with human lactoferrin

•  2 forms: GPI anchor and soluble (Food et al., 1994) •  Expressed in an array of normal -ssue, brain capillary endothelial cells, and reac-ve microglia associated with Aβ plaques in brain -ssues from AD pa-ents (Jefferies et al., 1995; Rothenberger et al., 1995)

TSX.V: BTI

Biodistribu-on of the Transcend Vector to the Brain Following IV Administra-on in Mice

This analysis indicated that there could be Species Specific factors in play hMTf = Human Transcend – mMTf = Mouse Transcend

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

0 5 10 15 20 25 30

%ID/g BM

Time

% Injected Dose in the Brain

hMTf mMTf

TSX.V: BTI

Transcend is Rapidly Taken up by the Brain

Drug Brain Kin (ml/s/g)

Reference

Glucose 9.5 x 10-‐3 Smith (2003)

Transcend 6.4 x 10-‐4 Demeule et al. (2002) Morphine 2.0 x 10-‐4 Cisternino et al. (2001)

Apro-nin *1 1.6 x 10-‐4 Demeule et al. (2008)

Insulin Rec An-body *2 1.0 x 10-‐4 Pardridge (1997)

Leu-‐Enkephalin 6.0 x 10-‐5 Zlokovic (1987)

Morphine-‐6-‐Glucuronide 2.4 x 10-‐5 Temsamani et al. (2005)

RAP *3 1.0 x 10-‐5 Pan (2004)

Beta Amyloid 6.5 x 10-‐6 Banks (1991)

DADLE 6.5 x 10-‐6 Chen (2002)

TNF-‐α 4.3 x 10-‐6 Pan (2002)

Transport Efficiency

More

Less

In situ brain uptake – measurement of rate of transport

1.  Angiochem 2.  Armagen Technoologies 3.  Raptor Pharmaceu-cals

TSX.V: BTI

βA mAb-cy5.5 (60x)

Transcend-cy5.5 (20x) Transcend-cy5.5 (60x) §  Transcend CONJUGATED TO CY5.5

§  CAPILLARIES STAINED WITH VESSEL GREEN (FITC-LECTIN)

§  NUCLEI OF BRAIN CELLS STAINED WITH DAPI BLUE

Transcend-cy5.5 is localized in the brain parenchyma in contrast to mAb against β amyloid peptide which do not cross efficiently the BBB and is mostly seen associated to brain capillaries

In Capillaries

In Parenchyma In Parenchyma

Transcend-‐cy5.5 Located in the Brain Parenchyma (2h Post IV Injec-on)

TSX.V: BTI

Transcend-‐Rhodamine Localizes in Brain Neuron Lysosomes (2h Post IV Injec-on)

Transcend is associated with a lysosomal compartment in neurons as shown with co-staining of NeuN and cathepsin B

Lysosome in neuron localization

Transcend Vessels Cathepsin B NeuN

TSX.V: BTI

Our Transcend Planorm Offers Mul-ple Development Opportuni-es

We have conjugated therapeu-c compounds that include an-bodies, enzymes, other biologics and small molecules to the Transcend Family that target:

a)  Specific brain cells (e.g., neurons, astrocytes and tumors)

b)  Certain intracellular compartments (e.g., lysosomes, endosomes, cytoplasm and nuclei)

c)  Delivery into the brain of exis3ng therapeu-c drugs currently not approved for central nervous system (CNS) indica-ons

d)  Delivery into the brain of promising new agents in development

…. and offer patent term extension of exis-ng drugs through crea-on of NCEs, combining the Transcend Family with generic agents or those about to lose exclusivity

TSX.V: BTI

Chronic Neurodegenera-ve Disorders •  Many biologics in development, require delivery

•  Disease modifica-on need is unmet by current drugs

•  Direct costs of trea-ng Alzheimer’s will total an es-mated $203 billion in the US in 2013

Stroke & Trauma-c Brain Injury •  BBB disrupted in first few hours but is intact in the recovery phase

•  Clinical need is unmet by current drugs

•  History of failure of neuro-‐protec-ve drugs in clinical trials

•  The direct costs of medical care and therapy in the US are es-mated at $28 billion per year.

Lysosomal Storage Diseases (LSD) with CNS Involvement •  Niche indica-ons, but lucra-ve •  Relevant drugs do not cross BBB •  Clinical need unmet by current drugs

•  Elaprase treatment for MPSII costs ~375,000 per year

•  Annual US sales in 2012 were $498 million

Infec-on (Bacterial, Viral, Fungal) •  In most cases clinical need is well met by current drugs

•  BePer BBB penetra-on could make make a significant difference in certain infec-ons

Psychiatry •  Most drugs cross the BBB and the clinical need is generally well met

•  Injec-ons are problema-c for most chronic indica-ons

Oncology •  Clinical need is unmet by current drugs

•  Many drugs do not cross the BBB •  Large market opportunity •  Market for biological therapies for cancer is expected to reach $53.7 billion in 2014.

Pain & Migraine •  Latest genera-on drugs have limited BBB penetra-on

• In 2012 the total cost for pain in the United States ranged from $560 to $635 billion

Mul-ple Opportuni-es for Transcend Across a Range of Therapeu-c Areas

TSX.V: BTI

Current & Future Brain Opportuni-es -‐ Diseases to be Treated

Crossing the BBB Would be the Most Effec-ve Method to Treat These Condi-ons; Poten-al Annual Market Value, Greater than $50B

•  Brain cancers

10,000 new cases diagnosed with glioblastomas annually in US

>200,000 new cases diagnosed with brain metastasis annually in US

•  Chemotherapeu-cs and small drugs •  MAbs against HER, EGFR, VEGF, etc… •  siRNA

•  Neurodegenera-ve diseases (AD, PD, MS, ALS, HD,…)

4M cases of AD in 2003 in US, exponen-al growth with 14M of AD by 2025

•  Neurotrophic Factors •  Small Drugs •  siRNAs •  Monoclonal an-bodies against an--‐No Go an-bodies

(MS), an- Ab pep-des and an- BACE-‐1 (AD) •  Pep-des

•  Obesity •  Neurotrophic Factors •  Pep-des

•  Rare Gene-c Diseases (MPSI, II, III) •  Lysosomal enzymes such as IDU, IDS or sulphamidases

•  Infec-ous Diseases (AIDS, meningi-s, encephili-s…) •  An-bio-cs •  An--‐HIV

•  Psychiatric Diseases •  Small drugs

•  Pain Therapy •  Small drugs •  Pep-des

13

TSX.V: BTI

Market Opportunity for Brain Cancer Treatment

•  Brain metastases occur in 20%-‐40% of pa-ents with systemic cancer, 30%-‐40% present with a single metastasis 1-‐2

•  Adjuvant value for Oncology (Metasta-c Breast Cancer) – Current market for Transcend is greater than $6 billion

•  13,000 people die from cancerous brain tumors annually in the U.S.3

•  Global brain tumor treatment therapies market forecasted to grow 11% annually over the next five years to $2.1 billion by 20174

•  Small molecule therapeu-cs can be designed to be inac-ve in blood, but retain their full ac-vity once released in the intracellular compartment of brain tumor cells

1)  Cairncross JG, Kim JH, Posner JB. Radia-on therapy for brain metastases. Ann Neurol 1980; 7: 529–41. 2)  Lohr F, Pirzkall A, Hof H, Fleckenstein K, Debus J. Adjuvant treatment of brain metastases. Semin Surg Oncol 2001; 20: 50–56. 3)  The New York Times 4)  GlobalData “Brain Tumor – Pipeline Assessment and Market Forecasts to 2017” released Jan. 17, 2011.

$0.9B

$2.1B

2009 2010 2011 2012 2013F 2014F 2015F 2016F 2017F

($ Billions) Global Brain Tumor Therapies Market

Applica-ons of Transcend & Transcendpep

Ac?ve Program: Delivery of Enzymes to Treat LSD’s

Delivery of mAbs: Alzheimer’s Delivery of Small Drugs – Cancer Ac?ve Program: Cancer Trastuzumab

Delivery of siRNA

TSX.V: BTI

Ac-ve Development Program: Lysosomal Storage Diseases

•  Lysosomal Storage Diseases (LSDs) comprise a large group of rare inherited metabolic disorders arising from an enzyme deficiency

•  Approximately 50 LSDs have been described including Tay Sachs Disease, Fabry Disease, Gaucher’s Disease, Hunter syndrome and mucopolysaccharidosis (MPS)

•  The disorders affects children many of whom suffer and die within several years of birth

Lysosomal Storage Disease (LSD)

TSX.V: BTI

Enzyme Replacement Therapy (ERT)

•  There are no cures for LSDs. •  Most effec-ve therapeu-c strategy is enzyme replacement therapy (ERT) in which intravenous delivery of the deficient enzyme is used in an aPempt to ameliorate symptoms in pa-ents with certain LSDs.

•  Costs of ERT are extremely high, ranging $90,000 to $720,000 per pa-ent annually.

•  Because of the blood-‐brain barrier, current ERT is unable to restore enzyme func-on in the brain and therefore does not address the neurological symptoms associated with LSDs.

TSX.V: BTI

Hurler Syndrome -‐ MPS I Lysosomal Storage Disease

•  Rare inherited gene-c disorder •  MPS I is caused by a deficiency of α-‐L-‐iduronidase (IDU)

•  IDU deficiency results in accumula-on of GAGs in the lysosome resul-ng in cell death

•  ERT can treat the peripheral effects of the disease but the BBB prevents CNS treatment resul-ng in progressive mental retarda-on

TSX.V: BTI

Dose-‐Dependent Increase in Brain Enzyme Ac-vity

•  Dose-‐Dependent Increase in Brain Enzyme Ac-vity in MPS I Knockout Mice With Transcend-‐IDU Administered IV

•  Conjuga-on to Transcend restores IDU brain enzyme ac-vity towards wild type levels in a dose-‐dependent fashion

0

0.2

0.4

0.6

0.8

1

1.2

IDU) Transcend-‐IDU

Total IDU

ac-vity

Capillaries Parenchyma

MPS I Ac-vity

TSX.V: BTI

1 Unit = 23.9 µm

Non-‐Conjugated Lysosomal EnzymeAF647 in Brain Sec-ons

1 Unit = 23.9 µm

Blue: Nuclei Green: Capillaries Red: Lysosomal EnzymeAF647

TSX.V: BTI

MTf-‐dpIDSAF647

1 Unit = 23.9 µm

Transcend-‐Lysosomal EnzymeAF647 Conjugate in Brain Sec-ons

Blue: Nuclei Cyan: Capillaries Pink: Transcend-‐EnzymeAF647 Conjugate

1 Unit = 23.9 µm

LAMP-‐1 staining and lipofuscin fluorescence indicates that the Transcend-‐Enzyme conjugates are localized with the lysosomal compartment

TSX.V: BTI

Rela-ve Increase of Lysosomal Enzyme in Brain

0

5

10

15

20

25

Enzyme Alone Transcend-‐Enzyme

Parenchyma

Fold In

crease over e

nzym

e

TSX.V: BTI

Enzyme Replacement Therapy for Lysosomal Storage Diseases in the CNS

§  40% to 60% of the Transcend-‐Lysosomal Enzymes conjugates (determined from AF647) in the brain was located in the parenchyma with the remainder in the capillaries

§  Conjuga-on of the Enzymes to Transcend resulted in a 8 to 10 fold increase in the volume frac-on of the Enzymes in the brain parenchyma

§  The consequence of the Transcend-‐Enzyme conjuga-ons and M6P dephosphoryla-on was addi-ve and highly significant

§  Greater than 40% of lipofuscin (lysosomes) was associated with the Enzymes when administered as a conjugate of Transcend

§  Less than 18% of lipofuscin was associated with the Enzymes when not conjugated to Transcend

§  Confirms that Enzymes conjugated to Transcend co-‐localizes within the lysosome within the brain parenchyma

Summary

TSX.V: BTI

Enzyme Replacement Therapy for Lysosomal Storage Diseases in the CNS

•  biOasis’s Transcend vector can deliver lysosomal enzymes from the blood, across the blood-‐brain barrier and into brain -ssue

•  Conjuga-on to Transcend restores IDU brain enzyme ac-vity in IDU-‐deficient mice towards wild type levels in a dose-‐dependent fashion

•  Conjuga-on with Transcend results in a marked transport of lysosomal enzymes from the blood into CNS lysosomes

•  Transcend offers the promise of an enzyme replacement therapy to ameliorate CNS pathology associated with Lysosomal Storage Diseases

Lysosomal Membrane Proteins

Summary con’t…

TSX.V: BTI

Development Program: Alzheimer's Disease Delivery of An--‐Amyloid Beta An-body

Conjuga-on of An--‐Aβ-‐pep-de an-body to Transcend increases transport into brain parenchyma by ~5-‐fold This increase of transport may result in a therapeu-c concentra-on in brain

0.000#

0.001#

0.002#

0.003#

0.004#

0.005#

0.006#

0.007#

Transcend3an43AB#mAb# an43Ab#mab#

Volume'Frac,o

n''' Parenchyma#

Image Analysis by Laser Scanning Confocal Microscopy

TSX.V: BTI

Delivery of Doxorubicin for Treatment of Primary & Metasta-c Brain Cancers

•  Doxorubicin is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and sov -ssue sarcomas

•  Doxorubicin is available in a liposome-‐encapsulated form as Doxil, which used primarily for the treatment of ovarian cancer or AIDS-‐related Kaposi's sarcoma

•  Doxorubicin could be be highly effec-ve for trea-ng brain tumors if it could be delivered into the brain

•  Doxorubicin is excluded from the brain because it is recognized by the mdr-‐1 protein at the BBB

•  Also, its most serious adverse effect is life-‐threatening heart damage

Doxorubicin (Adriamycin®)

TSX.V: BTI

Transcend-‐ADR Conjugate Enhances Doxorubicin Transport into the Brain •  Covalent Linkage •  Stable in Plasma — Half-‐life of 8 hours

•  Bioconjugates inac-ve in blood but Doxo retains full ac-vity once released in the intracellular compartment of brain tumor cells

•  Significant INCREASE in brain uptake with the Transcend Vector vs. Doxo on its own

0.00

1.00

2.00

3.00

Transcend-‐Doxo Doxo

% INJECTED DOSE (G TISSUE/G BODY MASS)*100%

Transcend Significantly Enhances Doxorubicin Transport into the Brain

TSX.V: BTI

Transcend Significantly Reduces Doxorubicin Transport into the Heart

With Doxo’s most serious adverse effect being life-‐threatening heart damage, Transcend vs Doxo on its own showed a significant DECREASE in uptake to the heart

0.0

5.0

10.0

15.0

20.0

Transcend-‐Doxo Doxo

% IN

JECT

ED DOSE

(gram brain -ssue

/gram bod

y mass)*100

TSX.V: BTI

Transcend-‐DOXO Conjugate Achieves Therapeu-c Levels in the Brain Increase survival of treated nude mice implanted IC with ZR-‐75-‐1 mammary tumor cells.

Increase survival of treated nude mice implanted IC with C6 glioma cells

Injec-on Schedule •  Study Performed at the Southern Research Ins-tute – Alabama •  Showed the Transcend Vector delivered a therapeu-c dose of Doxo in the Brain

TSX.V: BTI

Ac-ve Development Program Hercep-n® (trastuzumab)

•  This humanized monoclonal an-body interferes with the HER2/neu receptor (regulates cell growth, survival, migra-on and differen-a-on)

•  Greater than 30% of breast cancers overexpress HER2 (HER2+) causing breast cells to reproduce uncontrollably

•  One-‐year course of Hercep-n treatment costs ~$70,000 and annual global sales are ~$6 billion

•  Hercep-n increases pa-ent survival in late-‐stage metasta-c breast cancer, but ~30% develop breast cancer metastasis in the brain

•  Hercep-n does not cross the blood-‐brain barrier

Hercep-n® is a registered trademark of Roche/Genentech

Hercep-n: How it works

TSX.V: BTI

Hercep-n-‐Transcend (research code BT2111) to Treat Brain Metastases of Breast Cancer

•  Preclinical studies are being conducted with Transcend conjugated to Hercep-n using heterobifunc-onal protein crosslinkers followed by purifica-on of heterodimer enriched frac-on

•  In vivo ac-vity of the conjugate was assessed in a number of HER2+ breast cancer cell lines

•  For in vivo an ex vivo studies involving microscopic visualiza-on and measurement of distribu-on of the conjugated molecule in the brain, prior to conjuga-on, Hercep-n is labeled with a fluorescent dye or with radioac-ve iodine

Hercep-n-‐TranscendBT2111

TSX.V: BTI

Hercep-n & Hercep-n-‐TranscendBT2111 Halt Tumor Growth BT474 HER2/neu Over-‐Expressing Tumor Xenogra{ Model •  40 six to eight week old female athymic nude mice inoculated subcutaneously with 1x107 BT474 cells

•  Mice dosed subcutaneously with estradiol twice a month

•  Tumor size was determined using the formula length (mm) x width (mm) x depth (mm) x 0.52

•  Treatment with test ar-cles began when tumors reached a size of 50 to 100 mm3

•  Test ar-cles were administered via intraperitoneal injec-on twice weekly for 40 days (5 weeks) and tumor size measured

BT2111 & Hercep-n® Halt Growth of BT474 HER2/neu Over-‐Expressing Tumors

25

50

75

100

125

150

175

200

225

Day 0 Day 10 Day 20 Day 30 Day 40 Day 50

Tumor Size (m

m3)

PBS

Hercep-n

BT2111

BT2111 – Benign Toxicity Profile •  Female athymic nude mice were treated with BT2111 (18.5 mg/kg, IP, biweekly for five weeks)

•  No test-‐ar-cle related effects on body weight •  No test-‐ar-cle related clinical signs of toxicity •  No test ar-cle-‐related histopathology findings (selected organs)

TSX.V: BTI

Hercep-n-‐TranscendBT2111 Localiza-on in Brain

Brain Capillaries

Nuclei

BT2111: Hercep-n®-‐Transcend

Confocal Image Performed by iCapture at St. Paul’s Hospital Vancouver Canada

Confocal Images Two Hours Post IV Administra-on

Data at 2 Hours Post IV Administra-on

0.0E+00

5.0E-‐04

1.0E-‐03

1.5E-‐03

MTf-‐Hercep-n 2h Hercep-n 2h Vo

lume Frac-o

n

Fluorescence Localized to Brain Parenchyma

Work performed at Na-onal Research Council of Canada – Research Facility

Hercep-n-‐TranscendBT2111 Localizes in Brain Parenchyma

TSX.V: BTI

Frozen Brain Sec-on Analyzed Using Immunofluorescent Staining & Autoradiography

Hercep-n-‐TranscendBT2111 Distribu-on in Brain and Breast Cancer Tumors

Mouse Model of Breast Cancer Metastasis to Brain

•  Images to the right show quan-fica-on of Hercep-n-‐TranscendBT2111 taken up in brain parenchyma and in metastasis

•  Demonstra-ng poten-al therapeu-c concentra-on

•  Histopathology analysis of -ssue samples showed no Toxicity in Brain and other organs within the body

Time Point 2hr Post IV Injec-on

72.9ng/g

48.4ng/g

109.2ng/g

66.8ng/g

131.7ng/g

142.6ng/g

110.2ng/g

25.1ng/g

Preferen-al uptake of radio labeled BT2111 into tumors compared with BDT

Calculated concentra-ons of BT2111 within brain regions

Breast cancer metastasis distributed throughout the brain

Brain -ssue distal to tumors (BDT)

TSX.V: BTI

Hercep-n-‐TranscendBT2111 and Hercep-n Uptake into Brain & Brain Metastasis of Breast Cancer

0.E+00

2.E-‐06

4.E-‐06

6.E-‐06

8.E-‐06

1.E-‐05

1.E-‐05

Trastuzumab BT2111

Kin (m

L/s/g)

BDT Tumor

Not only was the uptake in brain of Hercep-n-‐TranscendBT2111 significantly higher than Hercep-n alone, but the uptake into the tumors where drama-cally higher

TSX.V: BTI

Brain Metastasis of HER2+ Breast Cancer

0

10

20

30

40

50

60

70

80

90

100

MTf Trastuzumab BT2111 Saline Control

By Number of Tumors

0.0

0.5

1.0

1.5

2.0

2.5

MTf Trastuzumab BT2111 Saline Control

By Mean Tumor Volume

n=20 in each group

TSX.V: BTI

Hercep-n-‐TranscendBT2111 Brain Uptake & Efficacy Summary

•  Hercep-n-‐TranscendBT2111 Uptake into Breast Cancer Metastasis in the Brain •  Hercep-n-‐TranscendBT2111 distributes to brain and brain metastases with a significant uptake into the tumors demonstra-ng blood tumor barrier penetra-on

•  Hercep-n-‐TranscendBT2111 in vivo Efficacy in Breast Cancer Models •  Mouse xenograv Model

•  Hercep-n-‐TranscendBT2111 completely prevents breast HER2+ cancer tumor growth

•  Mouse model of brain metastasis of breast cancer •  Hercep-n-‐TranscendBT2111 reduced the number of HER2+ breast cancer tumors in brain by 68%. The tumors that remained aver treatment were 57% smaller than those in the Hercep-n treated animals

TSX.V: BTI

Transcendpep-‐mAbAF647

Transcendpep are a number of small, under 20 amino acid sequence pep-des, found within Transcend (MTf) which we discovered aver many years of research

We have conjugated Transcendpep to a number of fluorescently labeled mAbs, enzyme and siRNA all showing equal to or greater transport than the full length MTf-‐Transcend protein itself

This confocal image prepared by the Na-onal Research Counsel of Canada, clearly shows the mAb (red) has been transported across the BBB and localizing around the neurons (blue)

TSX.V: BTI


-‐1.0E-‐03

1.0E-‐17

1.0E-‐03

2.0E-‐03

3.0E-‐03

4.0E-‐03

5.0E-‐03

mAb MTfpep MTfpep-‐mAb

Volume Frac-o

n

Capillaries Parenchyma Total

Mean ± SE

Brain Capillary Parenchyma And total Alexa 647

TSX.V: BTI


• mAb-‐AF647 does not cross effec-vely the BBB as determined by its low distribu-on in the brain parenchyma

•  Transcendpep (MTf pep-des) tagged with AF647 (MTfpep-‐AF647) efficiently crosses the BBB and distributes into the brain parenchyma

•  Conjuga-on of the MTfpep to mAbs-‐AF647 increases the an-body transport across the BBB to the brain parenchyma (by ~5 fold) as efficiently as the en-re MTf-‐Transcend protein itself

TSX.V: BTI

siRNAAF680 Will Not Cross the BBB

Lectin-Texas Red

AF680 Composite

TSX.V: BTI

Transcendpep is Able to Deliver siRNAAF680 Across the BBB

Lectin-Texas Red

AF680 Composite

TSX.V: BTI

Summary – Na3onal Research Counsel of Canada •  siRNAAF680: Perinuclear AF680 signal was not detected in the brain

parenchyma of any mice (n=7). No AF680 signal was observed in the vasculature.

•  siRNAAF680-‐Transcendpep: Perinuclear AF680 signal was detected in the brain parenchyma of all mice (n=7). Very low AF680 signal was observed in the vasculature.

Transcendpep is able to deliver siRNA across the BBB in brain parenchyma

cell’s intracellular compartment

Transcendpep-‐siRNAAF680

TSX.V: BTI

Transcend has A}racted a Number of Development Programs

•  Several drug development programs are underway with leading drug companies •  Neurodegenera-ve Diseases (Alzheimer’s) •  Metabolic Diseases (Lysosomal Storage Diseases) •  Oncology (Metasta-c Breast Cancer)

•  Four strategic collabora-ons are underway or have been completed with world-‐leading pharmaceu-cal companies inves-gated the use of the Transcend Family with their target therapeu-c compounds

TSX.V: BTI

Business Strategy

Our overall business strategy can be summarized as follows: • Obtain independent 3rd party valida-on of the Transcend Family

•  Expand and protect our Intellectual Property por~olio •  Advance development of our Brain Oncology & LDS programs thru preclinical studies and move to the clinic

•  Collaborate through research licenses with reputable Pharmaceu-cal companies that are interested in the poten-al of u-lizing the Transcend Family as a pla~orm to deliver their targeted therapeu-cs across the BBB

TSX.V: BTI

Key Takeaways

•  The Transcend Family is a unique brain drug delivery pla~orm with large market opportuni-es

•  An array of biologic and small molecule therapeu-cs can be linked and delivered into the brain with the Transcend Family

•  Transcend Family Conjugates are rapidly transported from the circula-on into brain parenchyma – no apparent limita-on in size or class of therapeu-c agent

•  Proof of principle demonstrated: •  Delivery of an-bodies against Aβ pep-de for the treatment of

Alzheimer’s disease •  Delivery of lysosomal enzymes into brain as poten-al therapies for

Lysosomal Storage Disorders •  Delivery of monoclonal an-bodies into the brain for treatment of

brain cancers

The Transcend Family may address major unmet medical needs in the area of central nervous system diseases &

disorders

BBB

TSX.V: BTI

Publica-ons Samples

PLoS One: A Unique Carrier for Delivery of Therapeu-c Compounds beyond the Blood-‐Brain Barrier

Journal of Neurochemistry: hPp://onlinelibrary.wiley.com/doi/10.1046/j.1471-‐4159.2002.01201.x/abstract

Nature Gene Therapy: Direc-ng adenovirus across the blood–brain barrier via melanotransferrin (P97) transcytosis pathway in an in vitro model

hPp://www.nature.com/gt/journal/v14/n6/abs/3302888a.html

PubMed Iden-fica-on of a Novel Route of Iron Transcytosis across the Mammalian Blood–Brain Barrier

hPp://www.ncbi.nlm.nih.gov/pubmed/14745458

Journal of Neurochemistry, 924–933 High transcytosis of melanotransferrin (P97) across the blood–brain barrier

hPp://www.ncbi.nlm.nih.gov/pubmed/12421365

TSX.V: BTI

Team

Rob Hutchison Founder

Chairman & CEO

Christian Fibiger, PhD Former CSO, Biovail Laboratories

Former head Neuroscience Amgen & Eli Lilly

Wilf Jefferies, PhD Founding Scientist

Ron Erickson Visualant Inc

Chairman & CEO

Reinhard Gabathuler, PhD Chief Scientist

Terry Pearson, PhD Professor University of Victoria

Mei Mei Tian Sr. Scientist

Michael Hutchison, LLB QC Sr. Partner Smith Hutchison

Greg Gubitz, LLB Former Head of Corporate

Development & General Counsel for Biovail Corporation

Board of Directors

TSX.V: BTI

biOasis Technologies Inc. Suite 125-‐10551 Shellbridge Way Richmond BC V6X 2W9 Canada Rob Hutchison [email protected] 1.778.383.3280 ext 101 Dr. Reinhard Gabathuler Chief Scien-st [email protected]

Contact Us