Bioasis Technologies Inc. · OTC:BIOAF
Bioasis Technologies — Investor Presentation (September 2019)
55 slides from Bioasis Technologies's investor presentation, September 2019
Slide 1: The Blood Brain Barrier Delivery Company
The Blood Brain Barrier Delivery Company Opening the door to large molecule biologic therapies for neurological diseases September 2019 BTI.V (TSX), BIOAF (OTCQB)
Slide 2: Forward Looking Information
Forward Looking Information This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and forward-looking information within the meaning of Canadian securities legislation. This information and these statements, referred to herei
Slide 3: Bioasis Strategy
Bioasis Strategy Delivery of Therapeutics Across the BBB Using Our Proprietary xB3 Platform Technology • Enables delivery of a variety of therapeutics across the BBB, including enzymes, siRNA, antibodies and xB3 TM Platform : other biologics (also small molecules) • Outperforms all other BBB technol
Slide 4: Bioasis Pipeline: Robust and Low-Risk
Bioasis Pipeline: Robust and Low-Risk Opening the door to large molecule biologic therapies for neurological diseases Program Discovery Preclinical POC IND Enabling Ph 1 CNS Oncology xB3-001 (Herceptin ®): HER2+ Breast cancer and brain mets xB3-003 (DOX): Glioma xB3-002 (Avastin ®): Glioblastoma Lys
Slide 5: Criteria for Internal Program Prioritization
Criteria for Internal Program Prioritization Potential to Expand Orphan Indication or Use to a Broad Approved Therapy Rare Disease Patient Population or Patient Subset 5
Slide 6: xB3 Platform Technology
xB3 Platform Technology
Slide 7: The Blood Brain Barrier
The Blood Brain Barrier • The blood-brain barrier (BBB) is a highly selective barrier that separates circulating blood from the brain and extracellular fluid in the CNS. • The BBB functions to prevent the movement of bacteria, large molecules and most small molecules into the brain. • The purpose of
Slide 8: The Bioasis Platform Technology: Active Transport Across the BBB via LRP1
The Bioasis Platform Technology Active Transport Across the BBB via the LRP1 Receptor xB3 Peptide Derived from an iron-binding human protein found at low Blood Vessel concentrations in the blood Capillary Endothelial CNS Extracellular • xB3 has been optimized by Bioasis’ scientists to its key consti
Slide 9: xB3 Platform is Superior to Transferrin
xB3 Platform is Superior to Transferrin Greater CNS Transport Efficiency demonstrated in vivo xB3 platform demonstrates superior volume of distribution in the brain compared to Transferrin as measured by in situ brain perfusion 50 45 Homogenate 40 Capillaries VD (ml/100g/10min) 35 Brain Parenchyma 3
Slide 10: The xB3 Platform Technology Outperforms Competing BBB Technologies
The xB3 Platform Technology Outperforms Competing BBB Technologies xB3 demonstrates superior Bioasis xB3 Features Denali Genentech Roche Armagen Angiochem transcytosis across in vitro BBB Platform model (BBCEC) 1.25 % injected dose in brain 4-6% 1-1.5% 1-1.5% 1-1.5% 1-1.5% ~1.5% Mode of Action LRP1
Slide 11: The xB3 Platform Technology Key Advantages
The xB3 Platform Technology Key Advantages Enables the delivery of Capable of delivering large Does not impact either PK, large molecule and small molecules binding, or activity of therapeutics across the across the BBB payload BBB into the CNS • Antibodies • Improved brain uptake over • siRNA • Her
Slide 12: xB3 Platform Validation
xB3 Platform Validation Brain penetration Pharmacodynamic Preclinical POC biomarkers • Confocal • Target engagement • Brain tumor models microscopy to • Modulation of • Metastasis & demonstrate brain target activity primary tumor uptake of labelled • Downstream models payload biomarker • Pain • Brai
Slide 13: Independent validation of the xB3 platform
Independent validation of the xB3 platform Antibodies and Cytokines – IL-1RA preclinical POC in neuropathic pain-Medimmune collaboration Enzymes – Preclinical POC in Hunters Syndrome – University of Padova siRNA – Preclinical POC in ischemic induced stroke mouse model – National Research Council of
Slide 14: Lead Program: xB3-001 for HER2+ Breast Cancer and Brain Metastases
The Blood Brain Barrier Company Lead Program : xB3-001 (xB3 - Trastuzumab) for the Treatment of HER2+ Breast Cancer and Brain Metastases
Slide 15: Breast Cancer Brain Metastases: Unmet Clinical Need
Breast Cancer Brain Metastases: Unmet Clinical Need • Brain metastases are among the most common form of brain cancer in adults, with an estimated 200,000 patients newly diagnosed each year in the United States. • Breast cancer is the second most common cause of brain metastases and is associated wi
Slide 16: xB3-001 is Designed to Improve upon the Efficacy of Herceptin
xB3-001 is Designed to Improve upon the Efficacy of Herceptin, Improving upon CNS Disease Control and Potentially Development of CNS Metastases xB3-001 in HER2+ mBC xB3-001 Product Attribute Utilizes the most widely used HER2-targeting agent, trastuzumab xB3-001 could launch as HER2-targeted thera
Slide 17: The Majority of HER2+ mBC Patients Receive Herceptin in all Lines of Therapy
The Majority of HER2+ mBC Patients Receive Herceptin in all Lines of Therapy Market Share for HER2-Targeting Agents by Line of Therapy 1L 2L 3L+ 5% 5% 7% 13% 15% 31% 38% 32% 51% 49% 40% 13% ~85% receive ~55% receive ~55% receive Herceptin Herceptin Herceptin 17 Source: Kantar Treatment Architecture
Slide 18: Datamonitor Expects Continued Growth of the US HER2+ Breast Cancer Market
Datamonitor Expects Continued Growth of the US HER2+ Breast Cancer Market, Reaching >$6B by 2025 US HER2+ Breast Cancer Market Datamonitor Forecast $8,000 $7,000 $6,000 $5,000 $4,000 $3,000 $2,000 $1,000 $0 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 Herceptin Herceptin biosim Margetuximab Per
Slide 19: xB3-001 Revenue Potential for 2L+ Patients with CNS Metastases
xB3-001 Revenue Potential for 2L+ Patients with CNS Metastases is ~US$440M Worldwide Market Potential – xB3-001 CNS Metastases Treatment CNS Metastases Treatment HER2+ mBC Patients Late Line Improved CNS disease control in 3L+ patients ~4,765 candidates 1 Late line 1 8 mos median duration of therapy
Slide 20: Market Potential – xB3-001 CNS Metastases Prevention
Market Potential – xB3-001 CNS Metastases Prevention HER2+ mBC Patients CNS Metastases Prevention 2L+ Patients without CNS Metastases ~24,000 candidates 2 3 8-10 mos median duration of therapy Late line 1 1L no CNS mets Market Potential CNS $2.2B US/$4.4B WW 4,765 mets xB3-001 Potential (@ 30% share
Slide 21: xB3-001 (xB3-Trastuzumab) Summary
xB3-001 (xB3 - Trastuzumab) Summary Indication TREATMENT OF HER2+ BREAST CANCER AND BRAIN METASTASES Preclinical Evidence • Confocal microscopy demonstration of enhanced brain uptake in normal murine brain • Autoradiographic demonstration of co-localization with brain metastases, higher calculated b
Slide 22: xB3-Herceptin Retains Peripheral Anti-Tumor Efficacy in BT474 Xenograft Model
xB3-Herceptin Retains Peripheral Anti-Tumor Efficacy in the BT474 Xenograft Model xB3 can be added to a therapeutic through chemical conjugation or fusion xB3-NH IgG BT2111 = xB3-001 (xB3-Herceptin) Ip injection 2x/wk for 5 weeks; 10mg/kg molar equivalent; n=10 22 Work performed at Biopharmaceutical
Slide 23: xB3-001 Increased Localization in Brain Parenchyma Compared to Herceptin
xB3- 001 Demonstrates Significantly Increased Localization in Brain Parenchyma Compared to Herceptin® Confocal Images Two Hours Post IV Administration (10mg/kg) in mouse brain xB3-Herceptin Herceptin Red: Brain capillaries Red: Brain capillaries Blue: Brain Nuclei Blue: Nuclei Green: xB3-Herceptin i
Slide 24: HER2+ Human Breast Cancer Brain Metastasis Mouse Model
HER2+ Human Breast Cancer Brain Metastasis Mouse Model 5 weeks post breast cancer cell administration Autoradiography 2h Intracardiac injection Following establishment of brain metastases single IV injection of 125I labeled test articles (10 mg/kg molar equivalent; n=3) Quantification of brain radio
Slide 25: xB3-001 in Human HER2+ Brain Metastasis Mouse Model
xB3-001 in Human HER2+ Brain Metastasis Mouse Model Target Engagement and Biological Effects Metastases localization 5 weeks Post Inoculation Concentrations of xB3 -001 within Brain Regions at 2hrs post dose 72.9ng/g 48.4ng/g 109.2ng/g 66.8ng/g 131.7ng/g 142.6ng/g 110.2ng/g 25.1ng/g Brain tissue dis
Slide 26: xB3 Platform Delivers 10-Fold Higher Herceptin to Brain Metastases
xB3 Platform Delivers 10-Fold Higher Herceptin® to Brain Metastases Normal Brain Tissue Brain Tumor 1.2E-05 1.2E-05 Unidirectional drug uptake rate (mL/s/g) Unidirectional drug uptake rate (mL/s/g) 1.0E-05 1.0E-05 8.0E-06 8.0E-06 6.0E-06 6.0E-06 4.0E-06 4.0E-06 2.0E-06 2.0E-06 0.0E+00 0.0E+00 Hercep
Slide 27: xB3 Platform Reduces Both Tumor Number and Size
xB3 Platform Delivers Herceptin® (Trastuzumab, TZM) to Brain Metastases and Reduces Both Tumor Number and Size xB3-001: Significant Tumor Reduction Tumor size based on pooled data from all individual values in group Group ns Tumor size (mm2) 120 # of tumor Mean ± STDEV Number of Tumors per animal (2
Slide 28: xB3-001 (TZM) HER2+ Breast Cancer Brain Metastasis
xB3-001 (TZM) HER2+ Breast Cancer Brain Metastasis 2018 2019 2020 2021 2022 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Manufacture Toxicology Material FDA Pre-IND Feedback Bioanalytical and Toxicology Development and Manufacture GMP Material Submit IND Ph 1b/2 Study in Patients Key
Slide 29: xB3-001 Path to Market
xB3 – 001 Path to Market • If clinically active, xB3-001 has the potential to be a candidate for accelerated approval: • Addresses a serious or life-threatening condition. • Must demonstrate an effect on an intermediate clinical endpoint or surrogate endpoint, for example tumor shrinkage, in a way t
Slide 30: A Strong Patent Portfolio Underpins Bioasis' Platform and Products
A Strong Patent Portfolio Underpins Bioasis’ Platform and Products Patent portfolio covers Bioasis’ platform technologies (their uses and indications) • Comprises over 120 patents and pending applications (10+ patent families) covering xB3, p97, fusion proteins of p97 or xB3 with antibodies, includi
Slide 31: MedImmune - Bioasis Collaboration
xB3 Platform Technology MedImmune - Bioasis Collaboration
Slide 32: MedImmune Collaboration: Independent Validation of Bioasis Technology
MedImmune Collaboration: Independent Validation of Bioasis Technology Why • MedImmune was evaluating blood-brain barrier platforms using test antibodies for brain delivery • They evaluated eight blood-brain companies and selected Bioasis • The selection was based on speed of delivery, superiority to
Slide 33: xB3 Facilitated Penetration and Localization of Antibodies in Brain Parenchyma
xB3 Facilitated the Penetration and Preferential Localization of Antibodies in the Brain Parenchyma Confocal Images Two Hours Post Single IV Administration (10mg/kg) in Wild-type Mice 5.0E-03 Capillaries Parenchyma Total 4.0E-03 Mean ± SE Volume Fraction 3.0E-03 2.0E-03 1.0E-03 0.0E+00 hIgG 1 xB3-hI
Slide 34: xB3 Resulted in Significant Brain Exposure Without Negative Impact on Plasma PK
xB3 Resulted in Significant Exposure in the Brain Without Negative Impact on Plasma PK xB3 peptide-Ab Fusion show improved Plasma PK xB3-Ab Fusion significantly increased Brain compared to xB3 full length-Ab fusion Exposure over Ab alone 10000 6 hIgG1 20 mg/kg xB3 peptide –hIgG1 fusion 20 mg/kg 5 xB
Slide 35: Efficacy Model: Neuropathic Pain Mouse Model
Efficacy Model: Neuropathic Pain Mouse Model • Neuropathic pain model (Seltzer et al, 1990) Sciatic nerve of one limb partially ligated Results in mechanical hyperalgesia • Neuropathic pain centrally mediated Drug must reach CNS to relieve pain • Analgesic drug will reduce pain if it reaches t
Slide 36: Systemic xB3-IL1RA Fusion: Dose Dependent PD Effects in Neuropathic Pain Model
Systemic administration of xB3 –IL1RA Fusion: Dose Dependent PD Effects in Neuropathic Pain Model Effect of xB3-hIgG1-IL1RA on Reversal of PNL Induced Mechanical Hyperalgesia – Ipsi/Contra Ratio 120 Sham + PBS 10ml/kg s.c. +++ +++ +++ +++ * ** ** ** 100 Op = xB³-hlgG1-ILRa 100mg/kg s.c. Ipsilateral/
Slide 37: Neurodegeneration: Parkinson's Disease
Neurodegeneration: Parkinson’s Disease The Need for Improved Delivery of Therapeutics to the CNS Continues to Increase 37
Slide 38: xB3-007: Glucocerebrosidase Untreated Neuropathic Gaucher's Disease Type II
xB3-007: Glucocerebrosidase Untreated Neuropathic Gaucher’s Disease Type II • Gaucher’s disease (GD) results in the deficiency in an enzyme, causing a portion of old cells to be stored in areas such as the liver, spleen, lungs, lymph system, and bones instead of being expelled from the body. It is c
Slide 39: xB3 Effectively Delivers Enzymes to the Brain to Treat Lysosomal Storage Disorders
xB3 is able to Effectively Deliver Enzymes to the Brain to Treat Lysosomal Storage Disorders Hunter Syndrome (MPS II) • Lysosomal Storage disease, MPS II is caused by an iduronate 2-sulfatase (I2S) enzyme deficiency • Currently CNS effects are untreatable enzyme Capillary Nucleus Bioasis’ xB3 peptid
Slide 40: xB3-I2S Treatment Reduced Heparan Sulfate Levels and Storage Cell Vacuoles
xB3-I2S Treatment Facilitated the Reduction of Heparan Sulfate Levels, Reduced Number of Storage Cell Vacuoles & Reduction in Number of Lysosome Vesicles in the Brain • Significant reduction in brain heparan sulfate accumulation, cell vacuolation and lysosome vesicles in a Hunter Syndrome mouse mode
Slide 41: Recent Achievements
Recent Achievements • January 2019: Bioasis Announces Agreement With Leading Pharmaceutical Company for Pre-Clinical Research Using the xB3 Platform Technology o $500,000 upfront, up to $3M in R&D costs • October 2018: Bioasis Announces xB3 ™ Platform Technology Licensing Agreement with Prothena o $
Slide 42: Strategic Approach: Two Pillar Strategy to Maximize Value and Success
Strategic Approach: Two Pillar Strategy to Maximize Value and Success • De-risked programs Pipeline • Approved drugs, well-established with Programs: regulatory agencies, physicians and Well-established patients medicines, fast path • Orphan indications, including CNS cancers to BLA/NDA and rare gen
Slide 43: Appendix
Appendix
Slide 44: Delivery of siRNA-based treatment to brain in an induced ischemic stroke
Delivery of siRNA-based treatment to brain in an induced ischemic stroke Why • Utility of siRNA therapeutic approaches for CNS diseases has been limited by their distribution in vivo • Preferentially localize to the kidney and liver, unable to cross the BBB Aim • Delivery of siRNA to brain to knock
Slide 45: Conjugation to xB3 Facilitated Transport of siRNA Across the BBB
Conjugation to xB3 Facilitated the Transport of siRNA Across the BBB into Brain Parenchyma of Wild Type Mice Confocal Images One Hour Post Single IV Administration (10mg/kg) in Wild-type Mice siRNA / xB3-siRNA Capillary PBS siRNA xB3-siRNA Nucleus 45 Work performed at National Research Council of Ca
Slide 46: Stroke Induction Via Middle Cerebral Artery Occlusion
Stroke Induction Via Middle Cerebral Artery Occlusion Model: • Middle cerebral artery occlusion via filament • Duration of occlusion: 60 min • Animal sacrificed 24 hrs post reperfusion • Dose: 30 mg/kg • Administration: i.v. prior to stroke induction Analysis> • Cerebral infarction – via 2,3,5-triph
Slide 47: Pretreatment with xB3-siRNA Reduced Infarct Volume and Improved Neurological Deficit
Pretreatment with xB3-siRNA Conjugates Significantly Reduced the Infarct Volume and Improved Neurological Deficit 60 * 3 * ** 50 Neurological Score Infarct Volume (% loss) 40 2 30 20 1 10 0 0 PBS PBS siRNA siRNA xB3-siRNA MTfp-siRNA PBS siRNA xB3-siRNA * P ≤ 0.05 (1 way Anova); n=4 ** P ≤ 0.01 (1 wa
Slide 48: xB3-siRNA Pretreatment Reduced NOX4 Expression
xB3-siRNA Pretreatment Reduced NOX4 Expression Compared to siRNA or PBS in Stroke Induced Brain at mRNA Level 2.0 Relative expression of NOX4 compare to PBS-sham Left brain (stroke induced) Right brain (control) 1.5 (fold) 1.0 0.5 PBS-sham PBS-sham PBS-stroke PBS-stroke siRNA-stroke siRNA-stroke xBM
Slide 49: Small Molecule: Doxorubicin Conjugate Increases Survival in Intracranial Tumor Models
Small Molecule: Doxorubicin Conjugate Achieves Significant Increase in Survival in Intracranial Tumor Mouse Models A Unique Carrier For Delivery Of Therapeutic Model Compound (Total Mean % change Significance ADR dosed) survival in mean Compounds (Days) survival 120 Intracranial PBS 10 - - Zr-75-1 P
Slide 50: Neuro-oncology Applications Beyond xB3-001
Neuro-oncology Applications Beyond xB3-001 xB3-002 for the Treatment of Glioblastoma
Slide 51: xB3-002 Program for the Treatment of Glioblastoma
xB3-002 Program for the Treatment of Glioblastoma: One of the Most Aggressive Cancers Originating from the Brain • Approximately 80% of all diagnosed primary malignant brain tumors are malignant gliomas (GBM). • The deadliest form of brain cancer due to the high infiltration of the tumor with surrou
Slide 52: Avastin and Glioblastoma
Avastin and Glioblastoma Antiangiogenic compounds such as bevacizumab (Avastin, BEV) has been shown to prolong progression-free survival in glioblastoma, with no overall survival benefit. Due to a higher expression of LRP1 on glioblastoma, xB3- bevacizumab (xB3-002) therapy may provide advantages ov
Slide 53: Our Management Team
Our Management Team Deborah Rathjen, Christine Antalik Caroline Dircks, Mei Mei Tian, Ph.D., MAICD, FTSE Ph.D. Ph.D. Chief Executive Chief Financial Chief Operating VP, Head of Officer & Executive Officer Officer External Research Chair 25+ years of Former BMS head 15 years of experience in of speci
Slide 54: Our Board of Directors
Our Board of Directors Deborah Rathjen, Ph.D., Mario Saltarelli, M.D., Ph.D. Nancy Stagliano, Ph.D. John E. Curran, CPA David M. Wurzer, CPA MAICD, FTSE Director Director Director Lead Director Executive Chair Previous Chief Executive Former Partner, Deloitte Executive Vice President Former Executiv
Slide 55: Our Scientific Advisory Board
Our Scientific Advisory Board Prof. John H. Krystal, M.D. Jeffery L. Cummings, M.D. Mario Saltarelli, M.D., Ph.D. Chair Member Member Yale University School of Medicine Cleveland Clinic, Center for Neurodegeneration and Former Chief Medical Officer, Syntimmune Yale-New Haven Hospital Translational N
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