OTCQX: BIOAF TSX.V: BTI A natural solution to deliver medicine to the brain ! biOasis.ca! QUARTER 1 ! 2015! Forward Looking Statements Certain statements in this presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 or forward-looking information under applicable Canadian securities legislation that may not be based on historical fact, including without limitation statements containing the words “believe”, “may”, “plan”, “will”, “estimate”, “continue”, “anticipate”, “intend”, “expect” and similar expressions. Such forward-looking statements or information involve known and unknown risks, uncertainties 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 information. Such factors include, among others, our stage of development, lack of any product revenues, additional capital requirements, risk associated with the completion of clinical trials and obtaining regulatory approval to market our products, the ability to protect our intellectual property, dependence on collaborative partners and the prospects for negotiating additional corporate collaborations or licensing arrangements and their timing. Specifically, certain risks and uncertainties that could cause such actual events or results expressed or implied by such forward-looking statements and information to diﬀer materially from any future events or results expressed or implied by such statements and information include, but are not limited to, the risks and uncertainties that: products that we develop may not succeed in preclinical or clinical trials, or future products in our targeted corporate objectives; our future operating results are uncertain and likely to fluctuate; we may not be able to raise additional capital; we may not be successful in establishing additional corporate collaborations or licensing arrangements; we may not be able to establish marketing and the costs of launching our products may be greater than anticipated; we have no experience in commercial manufacturing; we may face unknown risks related to intellectual property matters; we face increased competition from pharmaceutical and biotechnology companies; and other factors as described in detail in our filings with the Canadian securities regulatory authorities at www.sedar.com. Given these risks and uncertainties, you are cautioned not to place undue reliance on such forward-looking statements and information, which are qualified in their entirety by this cautionary statement. All forwardlooking statements and information made herein are based on our current expectations and we undertake no obligation to revise or update such forward- looking statements and information to reflect subsequent events or circumstances, except as required by law. 2" Central Nervous System Diseases AFFECT 1 IN 6 PEOPLE ! CNS diseases account for 12% of global deaths1 Incidence of CNS diseases will increase by 12% by 20301 Over 1000 diﬀerent CNS diseases with drugs hindered by BBB2 Total cost of CNS diseases is over $500 billion in USA alone2 CNS disease market is over $81.2 billion US and rising3 ALL TREATMENTS HINDERED BY THE BLOOD BRAIN BARRIER ! 1) (2012). Brain Facts; A Primer on the Brain and Nervous System . Publication, Society for Neuroscience. 2) (2007). Neurological disorders: Public health challenges . Study, UN World Health Organization . 3) bcc Research . (2010, September ). Therapeutic Drugs for Central Nervous System (CNS) Disorders: Technologies and Global Markets, PHM068A. 3" " 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 has 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 Capillary network of tightly woven endothelial cells lining the blood vessels in the brain, regulating transport of essential molecules and maintaining a stable environment 1) Royal Society of Chemistry 4" 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 Neurodegenerative Diseases like Alzheimer's Disease Stroke and Traumatic Brain Injury Metabolic Diseases like Lysosomal Storage Diseases Gene Silencing Therapy for ALS 5" Breakthrough Solution The Transcend Program Exploits a natural, biological process to deliver medicines into the brain tissue by linking preexisting drugs to a human protein 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 medicine into the brain, distributing the medicine with a wide distribution throughout the brain tissue MTfp (MTf peptide) • biOasis has 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 6" 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 ! ! ! MTfp in Action Brain Tissue RMT! Blood Vessels Transports a variety of compounds with no apparent size limitation Extends biOasis patent portfolio for additional ~20 years Pharmaceutical collaborators currently licensing MTfp MTfp Therapeutic RMT -Receptor Mediated Transcytosis 7" Market Opportunities for Transcend Lysosomal ! ! 2014 Drug Market Estimates Storage Disease ! Billion USD ~$2 Neurodegenerative Disease" ~$20 Billion USD Disorders Stroke & Traumatic Brain Injury Billion USD ~$81.2 Billion USD ~$32.3USD Central Nervous System Psychiatry Billion Clinical need met but improved BBB penetration could increase eﬃcacy Pain & Migraine " ~$33.7USD Billion ~$7.5 Infection ~$138Billion USD A carrier to cross the BBB would establish a foothold within these major markets 8" Brain Cancer Drugs 2013 drug sales for cancers that frequently metastasize in the brain1 Herceptin® (trastuzumab) $6.6Billion USD 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 1) Company Reported Data $1.9Billion USD $92Million USD $7.5Billion USD Improved cancer treatments have led to an increase in brain tumours, creating a need for anti-cancer drugs that target the brain The Transcend Program has been shown to reduce brain tumour volume by 84% when anti-cancer drugs are linked to MTf Anti-cancer drugs linked to MTf penetrate the blood tumour barrier 10 times more efficiently 9" Business Opportunities Patent Cliff Estimated ~$250 billion in lost revenue from patent expirations from 2012-20151 " Oﬀers potential patent extensions to the pharmaceutical industry through New Chemical Entity designation for many preexisting, patent-expiring drugs 1) 2) 3) Market Growth Unmet Medical Need CNS Drug Market is the second largest pharmaceutical segment behind oncology3 Over 1000 CNS diseases and brain disorders with treatments hindered by drug delivery across the BBB2 " Aid in the development of new therapies and revitalize dormant candidates that are proven eﬃcacious but do not cross the BBB drug market by Expand the CNS " opening up an industry that has been heavily stagnated by ineﬀective drug delivery to the brain DeRuiter, J., & Holston, P. L. (2012, June 20). Drug Patent Expirations and the “Patent Cliff”. U.S. Pharm. 2012;37(6)(Generic suppl):12-20. (2007). Neurological disorders: Public health challenges . Study, UN World Health Organization . http://www.un.org/apps/news/story.asp?newsid=21689&cr=neurological#.U7iNnBa4klI (2012). Brain Facts; A Primer on the Brain and Nervous System . Publication, Society for Neuroscience. 10" Management Board of Directors Rob Hutchison, Chair & CEO Former: CEO & Chief Scientist at eCharge Corporation (One of the world’s first internet banking system) Chris Fibiger, PhD Former: Head of Neuroscience, Amgen; VP Neuroscience, Eli Lily & CSO, Biovail Laboratories Greg Gubitz, LLB Former: VP, Biovail Corporation & COO, MDS Capital Terry Pearson, PhD Professor: Biochemistry & Microbiology, UVIC Ron Erickson Current: Chair & CEO, Visulant Technologies Michael Hutchison, QC, LLB Current: Partner, Smith Hutchison Law Corporation Team Judi Dalling, LLB, CFO Seasoned public company CFO and corporate lawyer Wilfred Jeﬀeries, PhD, Founding Scientist Discovered MTf’s ability to cross the BBB Professor: Microbiology & Immunology, UBC Reinhard Gabathuler, PhD, Chief Scientist Former: VP Brain Research, Biomarin & CSO, Angiochem Inc. Mei Mei Tian, PhD, Scientist UBC, Microbiology and Immunology (MTf expert) Laura Ho, MSc, Scientist UBC, Microbiology and Immunology Tiﬀany Tolmie, Corporate Communications Honours, Wilfrid Laurier University Corporate Strategy Obtain independent, 3rd party validation of MTf & MTfp • National Research Council • BC Cancer Research Centre • Texas Tech University Health Sciences Center • Southern Research Institute • University of Alabama Expand & protect intellectual property portfolio • Over 30 patents granted for blood-brain barrier drug delivery and neurodegenerative diseases • Strong pending patent portfolio • Over 20 year patent protection on MTfp Advance internal development programs at UBC • Successful delivery of over 12 therapeutic compounds and over 6 imaging agents to the brain (enzymes, antibodies, small molecule drugs & biological agents) • Potential to achieve major, near-term milestones Collaborate with reputable pharmaceutical companies & institutions • Many “shots on goal” leading to commercial transactions with numerous licensees • Collaborations with large pharmaceutical partners " 12" Strategic Collaborations The Transcend Program MTfp MedImmune Brains for Brain Foundation (AstraZeneca: AZN) Licensing Agreement Research Agreement AbbVie UCB Pharmaceuticals MTf (Abbott Labs: ABT ) Research Agreement (UCB) Research Agreement Ongoing discussions with large pharmaceutical companies on licensing and research agreements. 13" MTf: Rate of Uptake in Brain Compound Kin (x10-6; mL-1/s-1/g-1) Glucose 9500 Reference Smith (2003) Melanotransferrin (MTf) 640 biOasis’ Transcend Program is the only drug delivery platform that utilizes a natural process to deliver drugs into the brain1 Morphine 200 Cisternino et al. (2001) Aprotinin 160 Angiochem in Stage 2 Clinical Trials2 Insulin Rec Antibody 100 ArmaGen licensing to Shire (2014)3 Leu-Enkephalin 60 Zlokovic (1987) Morphine-6-Glucuronide 24 Temsamani et al. (2005) RAP 10 Raptor Therapeutics – Licensing Issues4 Beta Amyloid 6.5 Banks (1991) DADLE 6.5 Chen (2002) TNF-α 4.3 Pan (2002) 1) 2) 3) 4) More Transport Efficiency ! Competitors Compounds that freely cross the BBB compared to MTf Less Demeule et al. (2002) Demeule et al. (2008) Pardridge (1997) Pan (2004) 14" Development Program: " biOasis’ MTf + Anti-Aβ antibody Alzheimer’s Disease Results biOasis’ MTf + anti-Aβ antibody conjugate increases transport into brain tissue by ~5-fold Anti-Aβ antibodies have undergone clinical trials for Quantitative Image Analysis by Laser treatment of Alzheimer’s disease Opportunity Scanning Confocal Microscopy 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) 15" Development Program:" biOasis’ 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" 1" Problem • MPS I is caused by an IDU enzyme deficiency • Currently CNS effects untreatable Results • biOasis’ MTf + IDU (lysosomal enzyme) conjugate increased IDU brain enzyme activity ~ 4-fold, showing delivery to the brain tissue Opportunity • Offers the promise of an efficient enzyme replacement therapy Total IDU activity Hurler Syndrome (MPS I) Parenchyma Capillaries 0.8" 0.6" 0.4" 0.2" 0" IDU MTf - IDU 16" Development Program:" biOasis’ MTf + 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 Native Enzyme ~20-fold, showing delivery to the brain tissue does not enter the brain tissue eﬃcaciously Opportunity • Brains for Brain Foundation are in studies with MTfp + IDS, which offers the opportunity to fast-track to human trials • Offers promise of an efficient enzyme replacement therapy MTf + IDS Enzyme enters the brain tissue 17" Development Program: " biOasis’ 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 brain 0.00" MTf + DOXO DOXO 18" MTf Reduces Doxorubicin Uptake in the Heart • Doxorubicin’s most serious adverse effect is life-threatening heart damage Results • biOasis’ MTf + Doxorubicin vs. Doxorubicin on its own showed a significant DECREASE in uptake in the heart Opportunity • Could be used to treat brain cancers and decrease heart-uptake side effect, offering increased usage of Doxorubicin for brain cancer treatment % INJECTED DOSE (gram brain tissue/gram body mass)*100 Problem 20.0" 15.0" 10.0" 5.0" 0.0" MTf + DOXO DOXO 19" Development Program: " biOasis’ 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. 20" MTf + Trastuzumab (Herceptin®) " Texas Tech University - Breast Cancer Model 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 Number of Tumours 90" 80" 70" 60" 50" 40" 30" 20" 10" 0" 68% Reduction MTf TZM MTf-TZM Saline Control ! TZM = Trastuzumab (Herceptin®) 21" Development Program: " 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 22" Pipeline Brain Transport Quantity in the Brain Localization in Brain (Cellular) Eﬃcacy Models Brain Cancer Herceptin: Breast Cancer Lysosomal Storage Disease Hunters Syndrome: MPS II Model Sandhoff Disease: Hex B Model siRNA Stroke Model A ALS Model B 23" Market Profile " TSX.V:BTI; OTCQX:BIOAF Shares Issued & Outstanding 44,034,257 Fully Diluted 52,073,734 Options 6,095,000 Warrants 1,944,477 Market Cap Directors, officers & employees IP Warrants ~$52.8m @ $1.20 Share Price (Feb. 2, 2015) Cash Position ~$2,095,329 Ownership Insiders & Affiliates ~35% Institutional ~10% Data source: S&P Capital IQ 24" Summary Market Profile Large Market Opportunities Good cash position Clean share structure Exit strategy in place High internal ownership Transcend Program Enhanced technology “The first natural Greater commercial carrier to effectively potential transport therapeutic " drugs into the brain.” Ability to extend patent life Commercialize new therapeutics and/or revitalize dormant candidates Contribute to the growth in CNS drug market " Intellectual ! Property & Collaborations Strong patent protection Patent portfolio of >30 patents Large pharmaceutical collaborations Positive results; successful demonstration Management Major success in: Drug commercialization Biotechnology & venture capital startups Academia Treatment Potential " Awarded TSX.V Top 50® in 2013 Leader in providing shareholder value Discovery of MTfp " Metabolic diseases Neurodegenerative diseases Brain Cancer 25"
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