Bioasis Technologies Inc. · OTC:BIOAF
Bioasis Technologies — Investor Presentation (April 2022)
41 slides from Bioasis Technologies's investor presentation, April 2022
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 April 2022 BTI.V (TSX), BIOAF (OTCQB) www.bioasis.us
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 Overview
Bioasis Overview Delivery of Therapeutics Across the BBB Using Our Proprietary xB3 TM Platform Technology • Enables delivery of a variety of therapeutics across the BBB, including enzymes, siRNA, antibodies and other xB3 TM Platform : biologics and small molecules • Outperforms all other BBB technol
Slide 4: Strategic Approach: Two Pillar Strategy to Maximize Value and Success
Strategic Approach: Two Pillar Strategy to Maximize Value and Success • De-risked programs • Approved drugs, well-established with Pipeline regulatory agencies, physicians and Programs: patients Maximizing Value Well-established • Orphan indications, including CNS cancers and Success of and rare gen
Slide 5: 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 6: 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 7: Delivery of Antibody Targeting Beta-amyloid
Delivery of Antibody Targeting Beta-amyloid xB3-mAb Fusion Protein Demonstrates More Than 17 X Greater Localization to Brain Parenchyma Than mAb Alone Two Hours Post Single IV Administration (10mg/kg) in Wild-type Mice 2.50E-04 Parenchyma Localization *** 2.00E-04 Volume fraction 1.50E-04 1.00E-04 1
Slide 8: The xB3 Platform Technology Outperforms Competing BBB Technologies
The xB3 TM Platform Technology Outperforms Competing BBB Technologies xB3 demonstrates superior Bioasis xB3 transcytosis across in vitro BBB Features Denali Genentech Roche Armagen Angiochem 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% 1 Mode of Action
Slide 9: Disruption of Normal Lysosomal Function Leads to Neuroinflammation and Neurodegeneration
Disruption of Normal Lysosomal Function Leads to Neuroinflammation and Neurodegeneration • Neurodegenerative diseases result in a significant burden of mortality and Lysosomal morbidity worldwide Dysfunction • Disease-modifying therapies are not available for many patients including patients with: x
Slide 10: xB3 can Effectively Deliver Enzymes to Treat Lysosomal Storage Disorders
xB3 can Effectively Deliver Enzymes 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 Bioasis’ xB3 peptide-I2S fusion molecule increased I2S uptake in
Slide 11: xB3-I2S Treatment Facilitated the Reduction of Heparan Sulfate Levels
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 12: GBA1 Gene Mutations: Parkinson's Disease to Neuronopathic Gaucher Disease
GBA1 Gene Mutations: A Continuum of Pathology from Parkinson’s Disease to Neuronopathic Gaucher Disease 0 mutations 1 mild to 1 severe 2 mild to 2 severe • “Sporadic” moderate mutation moderate mutations Parkinson’s mutation • PD-GBA with mutations • Type 2 & 3 Disease more severe Gaucher • PD-GBA w
Slide 13: GRN Gene Mutations: Frontotemporal Dementia to Neuronal Ceroid Lipofusinosis
GRN Gene Mutations: A Continuum Of Pathology From Frontotemporal Dementia to Neuronal Ceroid Lipofusinosis Increasing number of GRN mutations = Increasing loss of Progranulin function = Lysosomal dysfunction = neurodegeneration and inflammation Loss of both GRN No loss of GRN Loss of 1 copy of the a
Slide 14: 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 15: Opportunity Summary
Opportunity Summary • Bioasis' xB3 platform validated through multiple partnerships • Opportunity to collaborate with partners to improve CNS delivery for their assets • Improved safety/efficacy • New IP/Life Cycle Management • Lead asset xB3-001 in neuro-oncology : • Targets HER2+ breast and gastri
Slide 16: The Blood-Brain Barrier Delivery Company
The Blood-Brain Barrier Delivery Company Opening the door to large molecule biologic therapies for neurological diseases BTI.V (TSX), BIOAF (OTCQB) www.bioasis.us
Slide 17: xB3-004 IL-1 Receptor Antagonist for Multiple Sclerosis and Other Autoinflammatory Disorders
xB3-004 IL-1 Receptor Antagonist for Multiple Sclerosis and Other Autoinflammatory Disorders • xB3-004 inhibits brain and peripheral nerve interleukin 1 (IL-1) by blocking IL-1 receptor binding and reducing neuroinflammation • Demonstrated efficacy in an animal models of neuropathic pain and multipl
Slide 18: 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 19: 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 19 Source: Kantar Treatment Architecture
Slide 20: 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 21: 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 1 8 mos median duration of therapy 1L no CNS
Slide 22: 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 1L no Market Potential 1 CNS mets CNS mets $2.2B US/$4.4B WW 4,765 22,100 xB3-001 Potential (@ 30
Slide 23: xB3-Herceptin Retains Peripheral Anti-Tumor Efficacy in the 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 23 Work performed at Biopharmaceutical
Slide 24: xB3-001 Demonstrates Significantly Increased Localization in Brain Parenchyma
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 25: 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 26: 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 27: xB3 Platform Delivers 10-Fold Higher Herceptin to Brain Metastases
xB3 TM 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 Her
Slide 28: xB3 Platform Reduces Both Tumor Number and Size
xB3 TM 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 ns ns Number of Tumors per
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: MedImmune - Bioasis Collaboration
xB3 TM Platform Technology MedImmune - Bioasis Collaboration
Slide 31: xB3 Facilitated Penetration and Localization of IL-1RA Antibodies in Brain Parenchyma
xB3 Facilitated the Penetration and Preferential Localization of IL-1RA 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
Slide 32: xB3 Resulted in Significant Exposure in the Brain 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 33: 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 34: Systemic xB3-IL1RA Fusion: Dose Dependent Effects in Neuropathic Pain Model
Systemic administration of xB3 – 004 (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. Ipsil
Slide 35: 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 36: 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 54 Work performed at National Research Council of Ca
Slide 37: 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 38: Pretreatment with xB3-siRNA Conjugates 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 MTfp-siRNA xB3-siRNA PBS siRNA xB3-siRNA * P ≤ 0.05 (1 way Anova); n=4 ** P ≤ 0.01 (1 wa
Slide 39: 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 40: 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 ADR Mean % change in Significance dosed) survival mean Compounds (Days) survival 120 Intracranial PBS 10 - - Zr-75-1 P
Slide 41: The Blood-Brain Barrier Delivery Company
The Blood-Brain Barrier Delivery Company Opening the door to large molecule biologic therapies for neurological diseases BTI.V (TSX), BIOAF (OTCQB) www.bioasis.us
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