Xenetic Biosciences, Inc. · NASDAQ:XBIO
Xenetic Biosciences — Corporate Update (June 2019)
32 slides from Xenetic Biosciences's corporate update, Jun 18, 2019
Slide 1: Corporate Presentation June 2019
Enhancing lives with transformative therapies www.xeneticbio.com NASDAQ: XBIO Corporate Presentation June 2019 Filed by Xenetic Biosciences, Inc. pursuant to Rule 425 under the Securities Act of 1933, as amended, and deemed filed pursuant to Rule 14a - 6 under the Securities Exchange Act of 1934, as
Slide 2: Forward-Looking Statements
Forward - Looking Statements This presentation contains forward - looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 . All statements contained in this presentation other than statements of historical facts may constitute forward - l
Slide 3: Forward-Looking Statements: Additional Information and Where to Find It
Forward - Looking Statements ADDITIONAL INFORMATION AND WHERE TO FIND IT In connection with the acquisition, the Company has filed and had declared effective with the Securities and Exchange Commission (the “SEC”), a registration statement on Form S - 4 that includes a combined definitive proxy stat
Slide 4: Xenetic Investment Highlights
Xenetic Investment Highlights 4 1: The acquisition of 1) Hesperix , which owned rights to the XCART platform based on the assignment agreement discussed in greater detail in a Form 8 - K filed wit h the SEC on March 4, 2019 as amended, and 2) an exclusive license of the rights to the XCART platform
Slide 5: Experienced Management Team
Experienced Management Team 5 Jeffrey F. Eisenberg Chief Executive Officer & Director Life Sciences executive with over 20 years of successful track record in value creation in both private and public companies; former CEO of Noven Pharmaceuticals and responsible for 2 product launches and led Noven
Slide 6: Board of Directors
Board of Directors 6 Adam Logal Chairman CFO, OPKO Health; Former Director, VBI Vaccines; Nabi Biopharmaceuticals Dmitry Genkin Director Former Head of Pharmavit , one of Russia’s largest pharmaceutical companies; Chairman, PJSC Pharmsynthez James Eric Callaway, Ph.D. Director Seasoned CEO within th
Slide 7: Scientific Advisory Board
Scientific Advisory Board Dr. Matthew Frigault Medical Oncologist in the Hematologic Malignancy Program at the Massachusetts General Hospital Cancer Center, as well as Assistant Director of the Cellular Immunotherapy Program, serves as Instructor at Harvard Medical School. Prof. Dr. Franco Cavalli F
Slide 8: XCART Platform: Expanding the Potential of CAR T Cell Therapy
XCART Platform 1 Expanding the Potential of CAR T Cell Therapy 1: Acquisition, subject to the satisfaction of the closing conditions, is expected to close in the first half of 2019. Please see our Registration Statement on Form S - 4 for more details
Slide 9: CAR T Cell Therapy is Driving New Breakthroughs in the Treatment of Cancer
CAR T Cell Therapy is Driving New Breakthroughs in the Treatment of Cancer 9 New CAR T Treatment Giving Hope To Some Cancer Patients CAR T Cell Therapy Is Here to Stay With Latest Gene Therapy Approval, a New Medical Era Has Officially Arrived 1: BioInformant , Database of CAR T - Cell Therapy Compa
Slide 10: CAR T Value Indicators Suggest Potential Significant Upside
CAR T Value Indicators Suggest Potential Significant Upside 10 1: Lead program in preclinical development at time of acquisition; 2: Lead program in Pivotal trial at time of acquisition; 3 : L ead program BLA under priority review at time of acquisition; 4: As of June 7, 2019 EBV+ PTLD following HCT
Slide 11: XCART Has the Potential to Transform CAR T Therapy
XCART Has the Potential to Transform CAR T Therapy 11 • XCART constructs can target patient - specific tumor neoantigens • Established proof - of - mechanism in B - cell lymphomas • Potential to address various target and tumor types • Compatible with current up - and down - stream CAR T manufacturi
Slide 12: XCART Platform Described in Science Advances
XCART Platform Described in Science Advances 12
Slide 13: Market Opportunity – Non-Hodgkin Lymphoma Therapeutics
Market Opportunity – Non - Hodgkin Lymphoma Therapeutics Estimated 2018 US Incidence of NHL: 75,000 1 13 1: https://seer.cancer.gov/; 2: Crump, M et al . Outcomes in refractory diffuse large B - cell lymphoma: results from the international SCHOLAR - 1 study. Blood 2017 Aug 3; 3: Market Reports Worl
Slide 14: XCART Shown to be Effective in B-Cell Lymphoma
XCART Shown to be Effective in B - Cell Lymphoma 14 XCART: Rationale for BCR Targeting Engineered to target a patient - and tumor - specific neoantigen B - cell Receptor (BCR) on an Individual Patient’s Lymphoma Cells BCR Signaling Pathway • Central regulator of B - cell function • Promising antican
Slide 15: XCART Clinical Workflow
Clinical CAR T Production 14 - 21 days XCART: 6 Month Process Manufacturing & Release Testing CAR Library Screen Characterize & Filter Candidates Verification of CAR Construct for Clinical Use Patient Treatment Patient Biopsy XCART Clinical Workflow 15
Slide 16: Unmet Need in Follicular Lymphoma (FL)
Addressable with 6 - month XCART process Unmet Need in Follicular Lymphoma (FL) 16 1: Casulo C. et al , J. Clin. Oncology , 2015 33:2516 - 2522 2: Montoto et al. J Clin Oncol. 2007 Jun 10;25(17):2426 - 33. Epub 2007 May 7 Time from Risk - Defining Event (months) Survival Probability (%) FL Treatment
Slide 17: Unmet Need in Diffuse Large B-Cell Lymphoma (DLBCL)
Unmet Need in Diffuse Large B - Cell Lymphoma (DLBCL) 17 12 Months 48 Months 24 Months 36 Months 0 Month (50%) Xplant Ineligible (50%) Relapse (20%) (80%) Diagnosis DLBCL 70% 2 nd Line Ablation/ BMT Relapse/ Refractory 50% 50% DLBCL Treatment Timeline 30% Primary Refractory XCART Opportunity 1: From
Slide 18: Selection of Functional CAR Constructs Specific to an Individual's Tumor BCR
Selection of Functional CAR Constructs Specific to an Individual’s Tumor BCR 18 XCART Proof of Mechanism: Workflow Selection of Functional CAR Constructs Specific to an Individual’s Tumor BCR • Lymph node biopsy sample is isolated from a patient with follicular lymphoma • Collected tumor cells used
Slide 19: Cyclopeptide-CAR T Cells Selectively Kill Raji Cell Lines Expressing Target BCRs
Cyclopeptide - CAR T Cells Selectively Kill Raji Cell Lines Expressing Target BCRs • Human CD8+ T cells were transduced with Lentiviral vectors coding for one of pepFL1 - CAR, pepFL2 - CAR, pepFL3 - CAR or CD19 - CAR constructs 19 XCART Proof - of - Mechanism: Patient Specificity Raji Cells (Raji -
Slide 20: Induction of CTL in Ex Vivo Biopsy Material
Induction of CTL in Ex Vivo Biopsy Material 20 XCART Proof - of - Mechanism: Patient Specificity pepFL1 - CAR T cells specifically lysed cells from pt - FL1 Myc - CAR T and Mock CAR T control cells: No lytic activity pepFL2 - CAR T cells specifically lysed cells from pt - FL2 pepFL3 - CAR T showed n
Slide 21: pepFL1-CAR T in In Vivo Tumor Model of Raji-FL1 Cell Line
pepFL1 - CAR T in In Vivo Tumor Model of Raji - FL1 Cell Line 21 XCART Proof - of - Mechanism: Efficacy and Selectivity NOD SCID (CB17 - Prkdc scid / NcrCrl ) mice were engrafted subcutaneously with 5x10 6 Raji - FL1 cells (Raji cells expressing the malignant BCR of Patient pt - FL1) pepFL1 - CAR T
Slide 22: XCART Development Program Driving Towards IND Filing
XCART Development Program Driving Towards IND Filing 22 2019 2020 2021 Screening Method Development Validation of End - to - End XCART Clinical Process Clinical Qualification Method Development Nonclinical Animal Studies CMC Process Development Development Approach Program Planning • TPP • Clinical
Slide 23: XCART is Differentiated from CD19 CAR T Therapies
XCART is Differentiated from CD19 CAR T Therapies 23 Tissue Specificity Off - Tumor Toxicity Tumor Antigen Escape • Recognizes only patient - and tumor - specific neoantigens • Decreased antigen burden implies lower risk of CRS and Neurotoxicity • No expectation of B - cell aplasia • Targets an anti
Slide 24: PolyXen PSA Technology Platform Enables Next Generation Biologic Drugs
PolyXen ™ PSA Technology Platform Enables Next Generation Biologic Drugs
Slide 25: PolyXen: Next Generation Delivery Platform for Biologics
PolyXen : Next Generation Delivery Platform for Biologics 25 Polysialylation employs the biological polymer polysialic acid (PSA) to modulate the pharmacokinetic and pharmacodynamic profiles of protein drugs Seeking to build a pipeline of partnerships utilizing PolyXen Key Features • Retention of na
Slide 26: Summary
Summary 26 1: Acquisition, subject to the satisfaction of the closing conditions, is expected to close in the first half of 2019. Please se e our Registration Statement on Form S - 4 for more details • Innovative XCART platform 1 addressing high - value oncology market • PolyXen platform: next gener
Slide 27: Supplemental Information
Enhancing lives with transformative therapies www.xeneticbio.com NASDAQ: XBIO Supplemental Information
Slide 28: Identification of Individualized BCR-Targeting CAR T Constructs
Identification of Individualized BCR - Targeting CAR T Constructs 28 Selection of cyclopeptide - CARs specific to a targeted BCR: 7aa cyclopeptide library hinge CD28 MT/ cyt OX - 40 cyt CD3 zetta cyt Lymphoma BCR VH/VL IgG1 hinge PDGFR TM Activation FACS anti - CD69 Library of immortal Jurkat human
Slide 29: Selection and Isolation of Individualized Cyclopeptide-CAR Fusion Constructs
• Patient - specific BCRs were cloned from malignant sections of lymph node biopsies in 3 Follicular Lymphoma (FL) patients • Several rounds of selection resulted in discovery of three patient - specific, cyclopeptide - containing CAR constructs Selection and Isolation of Individualized Cyclopeptide
Slide 30: Staining by pepFL1 Peptide Against pt-FL1 and pt-FL4 Ex-Vivo Samples
Staining by pepFL1 Peptide Against pt - FL1 and pt - FL4 Ex - Vivo Samples 30 X - CART Proof - of - Mechanism: Patient and Target Specificity BCR - Specific Peptides Selectively Stain Parental Cells from Corresponding Patient’s Biopsy Material • More than 60% of cells in the biopsy sample are B - ce
Slide 31: pepFL1-CAR T in In Vivo Metastasis Model
pepFL1 - CAR T in In Vivo Metastasis Model 31 Raji - FL1 cells (green) on Day 35 after tumor implantation in mice treated by CD19 - CAR T, FL1 - CAR T and Myc - CAR T CD19 - CAR T and FL1 - CAR T Prevent Development of Metastasis • Bioluminescent imaging of organ - specific metastasis Raji - FL1 cel
Slide 32: pepFL1-CAR T Cells in Mouse Tumor Models of pt-FL1 Cells
pepFL1 - CAR T Cells in Mouse Tumor Models of pt - FL1 Cells 32 X - CART Proof - of - Mechanism: In Vivo PK CAR T staining by human CD8 - specific antibodies Black arrows indicate CD19 - CAR T, pepFL1 - CAR T or Myc - CAR T infiltration into the tumor pepFL1 - CAR T and CD19 - CAR T cells are presen