Slide 1: StemVax, LLC
STEMVAX, LLC Dwain Morris-Irvin, PhD, MPH Founder, Chief Scientific Officer StemVax Therapeutics Los Angeles, California, A NovAccess Global Company (XSNX)
Slide 2: Overview
Overview • Investment Highlights • Program Overview • Technology • Phase I Trial (Intro) • Investor Opportunity • Summary XSNX
Slide 3: Investment Highlights
Investment Highlights Clinical and Pre-Clinical stage biopharmaceutical company developing next-generation immunotherapy products to treat Brain Cancer. • Personalized Immunotherapy • Dendritic cell-based approach to promote anti-tumor immunity • Enhanced dendritic cell maturation and functionality
Slide 4: Program Overview
Program Overview Immunotherapy in Development: TLR-AD1 • Preclinical development demonstrated efficacy over leading dendritic cell immunotherapy approach currently in Phase II clinical trials (“ICT”) • Can be combined with various antigens, including cancer stem cell antigens • Preparing IND to be f
Slide 5: Program Overview
Program Overview StemVax, LLC Company Development: • Seeking initial funding through NIH SBIR and Investors • Business Plan development • Executive Board Development • Scientific Advisory Board XSNX
Slide 6: Targeting Tumor
Targeting Tumor Progenitor cell Differentiated cell Normal Stem cell Cancers originate in tissue progenitor or stem cells through dysregulation of the self-renewal process Various antigens produce varying level of immunogenicity Various antigens produce varying level of immunogenicity Cancer Stem/pr
Slide 7: Glioblastoma Multiforme (GBM)
Glioblastoma Multiforme (GBM) o More than 18,000 brain tumors are diagnosed each year in the United States. o GBM is the most common primary brain tumor in adults. o Five-year survival rates are less than 5% for GBM. XSNX
Slide 8: Glioblastoma Multiforme (GBM)
Glioblastoma Multiforme (GBM) § Standard of Care: Surgical resection followed by radiation and temozolamide chemotherapy remains the most effective treatment. § 15-month median survival. § Additional GBM therapies needed - Immunotherapy? § Vaccination with cytokine-transfected tumor cells § Adoptive
Slide 9: Dendritic Cell Vaccine (1st Generation)
Dendritic Cell Vaccine (1st Generation) o Improves survival in responders (Phase I and II) o Not a cure o Needs improvement-survival rates, outcomes XSNX
Slide 10: Brain Tumor Vaccine
Brain Tumor Vaccine Isolate tumor cells Tumor Isolate blood Tumor cell Blood Tumor Tumor cell cell Tumor cell Antigen Presenting Cells (Dendritic cells) XSNX
Slide 11: Brain Tumor Vaccine
Brain Tumor Vaccine Inject GBM vaccine GBM tumor lysate activated DCs Tumor Anti-tumor immune response Tumor Tumor 2. Tumor 1. Glioma cell lysate Freeze-thaw method XSNX
Slide 12: 1st Generation Vaccine-Bulk Tumor Lysate
1st Generation Vaccine-Bulk Tumor Lysate TTS (time from surgical resection immediately preceding vaccination to time of death) (Wheeler et al, 2008, Cancer Research) XSNX
Slide 13: How do we improve DC vaccine?
How do we improve DC vaccine? • Toll-like receptor (TLR) adjuvants XSNX
Slide 14: 2nd Generation Vaccine - Common Antigens (ICT-107)
2nd Generation Vaccine - 6 Common Antigens (ICT-107) ICT-107 - Targets Cancer Stem Cells Lead Indication in GBM • PII data not encouraging and why we overcome the issues with ICT-107 • Why we are better and will succeed? Antigen Treats gp100 melanoma, brain MAGE-1 melanoma, brain, ovarian IL-13Ra2 b
Slide 15: Phase I Trial Results for ICT-107
Phase I Trial Results for ICT-107 Significant increase in median Progression Free Survival (PFS) • 16.9 months for ICT-107 • 6.9 months for historical SOC* Significant increase in 3-year PFS • 38% for ICT-107 • 6% for historical SOC* Significant increase in median Overall Survival (OS) • 38.4 months
Slide 16: 3rd Generation Vaccine-TLR-AD-1
3rd Generation Vaccine-TLR-AD-1 • Antigen specific or antigens derived from bulk lysate combined with Toll-like receptor (TLR) adjuvants • Pre-clinical mouse model data show significant improvements in survival and dendritic cell activation and function XSNX
Slide 17: Dendritic Cell Assay
Dendritic Cell Assay 1.-Current Glioma Antigens-Specificity (e.g. bulk lysate, ICT-107) 2.- Current Toll-like receptor (TLR) Adjuvants-Activate TLR2, TLR4, TLR9 XSNX
Slide 18: TLR Signaling Pathway
TLR Signaling Pathway • Each TLR family member has its specific signaling pathway. • TLR signaling is a common pathway to induce inflammatory cytokines. XSNX
Slide 19: Pre-Clinical Kaplan-Mier Survival Analysis (Controls)
Pre-Clinical Kaplan-Mier Survival Analysis of Vaccinated Glioma Bearing Mice (Controls) Median Survival No Vaccine: 30 days Vaccine: 60 days XSNX
Slide 20: Pre-Clinical Kaplan-Mier Survival Analysis (Vaccine vs. TLR adjuvants)
Pre-Clinical Kaplan-Mier Survival Analysis of Vaccinated Glioma Bearing Mice (Vaccine vs. TLR adjuvants) * Median Survival Median Survival Vaccine: 60 days Vaccine: 60 days Vaccine + Pam3Cys: <90 days Vaccine + LPS: 60 days * * Median Survival Median Survival Vaccine: 60 days Vaccine: 60 days Vaccin
Slide 21: DC Activation Molecules
DC Activation Molecules • Co-stimulatory: • CD80 (B7-1) • CD86 (B7-2) • CD40 • MHC II (Major histocompatability complex for antigen presentation to T cells) • Pro-inflammatory cytokines (IL-12, TNF-α, IL-6) XSNX
Slide 22: Co-Signaling Molecules
Co-Signaling Molecules B7-H1 PD-1 Inhibition CD80/86 CTLA-4 MHC TCR APC T-cell CD3 CD80/86 CD28 Activation CD40 CD40L XSNX
Slide 23: Glioma Lysate Activates vs. Normal Brain Control
Glioma Lysate Activates vs. Normal Brain Control (Flow Cyotmetry Assay) * MFI XSNX
Slide 24: Glioma Lysate Activates DC Through TLRs TLR2
Glioma Lysate Activates DC Through TLRs TLR2 (Flow Cytometry Assay) * * XSNX
Slide 25: Glioma Lysate Activates DC Through TLRs TLR4
Glioma Lysate Activates DC Through TLRs TLR4 (Flow Cytometry Assay) * * * * * * * XSNX
Slide 26: DC Cytokine Expression (IL-12)
DC Cytokine Expression (IL-12) After Glioma Lysate and TLR Ligands (ELISA Based Assay) * * * * XSNX
Slide 27: DC Cytokine Expression (TNF-α)
DC Cytokine Expression (TNF-α) After Glioma Lysate and TLR Ligands (ELISA Based Assay) * * * XSNX
Slide 28: PBMDC Cytokine Expression (IL-6)
PBMDC Cytokine Expression (IL-6) After Glioma Lysate and TLR Ligands (ELISA Based Assay) * * XSNX
Slide 29: Summary
Summary • Glioma lysate activation of DCs is at least partially regulated through TLR signaling and is MyD88 dependent. • TLR2 signaling in DCs may be one the predominant receptors for glioma lysate signaling. • Glioma lysate and TLR ligands may work together to maximize an anti-tumor immune respons
Slide 30: Highlights
Highlights • Can be combined with any antigen specific technology • Proven mechanism of dendritic cell maturation and function • Essential for patient-based (personalized) immunotherapy XSNX
Slide 31: Phase I Trial with TLR-AD1
Phase I Trial with TLR-AD1 Nonrandomized, single-center study • Cedars-Sinai Medical Center, Department of Neurosurgery • Twenty GBM patients, newly diagnosed • Patients will receive Standard of Care (surgery and chemo-radiation) followed by three vaccinations of TLR-AD1 every 2 weeks XSNX
Slide 32: Milestones Over Next 18 Months
Milestones Over Next 18 Months • File for IND for Orphan Drug Designation; Initiate Phase I or II Clinical Trial • Apply for NIH SBIR grant • Complete Seed/Series A rounds for a total investment of 5 million XSNX
Slide 33: Current Management Team
Current Management Team • Dwain Morris-Irvin, PhD, MPH Founder, Chief Scientific Officer • Christopher Wheeler, PhD President • Peter Weinstein, PhD, JD Legal Council • XSNX Biotech Advisory Board XSNX