Scorpius Holdings Inc. · OTC:SCPX
Scorpius — Heat Biologics — Investor Presentation (February 2019)
42 slides from Scorpius's investor presentation, Feb 28, 2019
Slide 1: Heat Biologics Corporate Presentation
Heat Biologics Corporate PresentationFebruary 28, 2019
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation includes statements that are, or may be deemed, ‘‘forward-looking statements’’ within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. In some cases, these forward-looking statements can be identified by the use of forward-
Slide 3: Our Mission
Our Mission To improve patient outcomes by developing more effective immunotherapies designed to Turn “COLD” tumors “HOT 3
Slide 4: Heat's Core Focus: Three Legs of Immuno-Oncology Stool
T-cell Activation Co-stimulation Heat’s Core Focus Checkpoint Inhibition Effective Immuno-Oncology TherapyThe three legs of an Immuno-Oncology Stool 4
Slide 5: Combination Therapies: Broad Range of Combination Therapies
Combination TherapiesUnlocking the Body’s Natural Defenses with a Broad Range of Combination Therapies Checkpoint Inhibitors PD1/PDL1CTLA-4Lag-3TIM-3Plus others Combined with Co-Stimulation T-cell Activation Pelican PTX-35Monoclonal AntibodyPelican PTX-45Fusion Protein ImPACT® TherapyCell-based Deli
Slide 6: Product Pipeline
Product Pipeline Combination Therapies Designed to Activate CD8+ T-cells Against Cancer Combination Therapies Indication Comments ImPACT® HS-110 NSCLC ImPACT™ activation technology in combination with nivolumab and pembrolizumab ComPACT® HS-130 Multiple Solid Tumors ComPACT™ activation technology in
Slide 7: ImPACT Off-the-shelf Manufacturing
ImPACT® “Off-the-shelf” ManufacturingDesigned for Robust, Pan-antigen T-cell Activation Frozen, fully-diluted single-dose vialFinal drug product: 10 million cellsEasily scaled manufacturing Low COG, off-the-shelf alternative to autologous therapies 7 Sample Screen Select Scale Collect Cancer Cell Li
Slide 8: Introducing gp96 – Its dual role
Introducing gp96 – Its dual roleThe Immune System’s “Swiss Army Knife”* *Schild, H. & Rammensee, H. Gp-96 – The Immune System’s Swiss Army Knife. Nature Immunology 2, 100-101 (2000) “Molecular Warning System” A natural biological process to deliver proteins (antigens) & gp96 to our immune systemGp96
Slide 9: ImPACT technology severing the leash
ImPACT® technology genetically modifies tumor cells by “severing the leash” that binds the gp96 to the endoplasmic reticulum, and replacing it with a secretory sequence that pumps gp96 out of the cellMimics necrotic cell death by enabling fully-allogeneic “off-the-shelf” living cancer cells to “pump
Slide 10: ImPACT: Immune Pan-antigen Cytotoxic Therapy
ImPACT®: Immune Pan-antigen Cytotoxic Therapy ImPACT Cell Cancer-killing T-cell ImPACT cells secrete antigens designed to specifically activate patient’s killer T-cells T-cells circulate to destroy patient’s tumor Cluster of five 0.1 mL intradermal injections Activated cells EXPRESS chaperoned antig
Slide 11: ImPACT Generates an Adaptive Immune Response
ImPact Generates an Adaptive Immune Response Secretion of gp96-Ig carrying tumor specific proteins represented on the patients tumorActivation of APCs (TLR2/4) and cross- presentation of antigens (CD91)Specific T-cell receptor engagementClonal Expansion of Tumor Antigen Specific T cells. 2 signals D
Slide 12: ImPACT + Opdivo Combination Therapy
ImPACT + Opdivo Combination TherapyPotential to improve clinical responses and survival, without additional toxicity Source: BMS images 12
Slide 13: HS-110 Trial Design
HS-110 Trial DesignA Phase 1b/2 study of HS-110 in combination with multiple treatment regimens for patients with non-small cell lung cancer (The “DURGA” Trial) Primary EndpointsPhase 1b: SafetyPhase 2: Cohort A&B: ORRCohort C&D: PFSSecondary EndpointsOS, PFS, DCR, DOR Exploratory EndpointsCorrelati
Slide 14: CD8+ TIL Infiltration Associated with Clinical Response
Baseline(Cold) Week 10(Hot) CD8+ TIL Infiltration Associated with Clinical Response Patient 1:Partial Response at Week 18 High CD8+ TIL (>10%) Patient 2:Partial Response at Week 9 High CD8+ TIL (>10%) Patient 3:Partial Response at Week 18 Low CD8+ TIL (<10%) High CD8+ TIL (>10%) Combination treatmen
Slide 15: Increased Killing Activity in Tumor Microenvironment
Combination Treatment Substantially Increased Killing Activity in Patient Tumor Microenvironment RECIST 1.1 Stable Disease for 19+ months Pathology analysis performed by Yale School of Medicine CD3+ TILsCD3+ Ki67 TILsPD-1+ Cells CD3+ Granzyme B + TILsPD-L1+ Tumor CellsCD4+ Foxp3+ Cells (Tregs)CD4+ T
Slide 16: Progression-Free Survival (PFS)
Progression-Free Survival (PFS) Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L * Borghaei et al. 2015 Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of Medicine Median PFS2.6 months(95% CI: 1.8 - 8 months) Months 0 6 12 18 24 30 25 50
Slide 17: Overall Survival (OS)
Overall Survival (%) Overall Survival (OS) Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L Median OS of nivolumab alone 12.2 months*(95% CI: 9.7 – 15.0 months) *Borghaei et al. 2015 NEJM Median OS Not Reached (95% CI: 8.1 months - NR)60% of patients still alive with median follow-up time
Slide 18: Best Target Lesion Response
Best Target Lesion Response PR 9 (21%) SD 12 (29%) Not evaluable 4 (10%) DCR 21 (50%) RECIST 1.1 Objective Response Rate = 21.4% (95% CI: 10.3 - 36.8%) Change from Baseline (%) Best Target Lesion Response Best Overall Response Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L Nivolumab alo
Slide 19: Duration of Benefit
Duration of Benefit Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L 19 Responses and disease stabilization are durable and long-lasting 25 50 75 100 0 -30 -50 -75 -100 Change from Baseline (%) 0 3 6 9 12 15 18 21 24 27 Months from the First Dose of HS-110
Slide 20: Improved Survival in Cold Tumor Patients
Improved Survival in “Cold” Tumor PatientsOverall Survival (OS) by Baseline CD8+ TIL Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L *TIL NE = Tumor infiltrating lymphocyte not evaluable Low CD8+ TIL(< 10%) High CD8+ TIL (> 10%) Median OS NR NR HR 0.39(95% CI: 0.06 – 2.31) CD8+ TIL (<10%
Slide 21: Benefit Independent of PD-L1 Status
Benefit Independent of PD-L1 StatusOverall Survival (OS) by Baseline PD-L1 Status Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L Negative PD-L1(< 1%) Positive PD-L1(> 1%) Median OS NR NR HR 0.85(95% CI: 0.26 – 2.79) PD-L1 (<1%), N = 16PD-L1 (>1%), N = 13PD-L1 NE, N = 13 0 6 12 18 24 30
Slide 22: OS by Injection Site Reaction
OS by Injection Site Reaction (ISR) Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L Overall Survival (%) Typical Injection Site Reaction Injection Site Reaction Yes (n = 24)No (n=18) mOS: NR vs. 7.2 monthsHR: 0.15 (95% CI: 0.05-0.45)p = 0.0001 Survival is significantly better in patients
Slide 23: Survival Benefit with Increased Immune Activity
Median OS (months) 17.3 23.5 Survival Benefit with Increased Immune Activity Cohort A:CPI Naïve pts treated by HS-110 + Nivolumab at >2L OS (Months) 0 12 24 36 High Low HS-110 Generated ELISPOTs High = Patients with absolute ELISPOT increases above the group medianLow = Patients with absolute ELISPO
Slide 24: Objective Response Rate Cohort B
Objective Response Rate Cohort B:CPI progressors treated by HS-110 + Nivolumab at >2L RECIST 1.1 ORR = 15% (95% CI, 3.2 - 37.9%) PR* 4 (20%) SD 7 (35%) Not evaluable 2 (10%) DCR 11 (55%) Best Target Lesion Response with # of Prior Lines of Therapy 25 50 100 75 0 -25 -50 -75 Change from Baseline (%)
Slide 25: Duration of Clinical Benefit Cohort B
Duration of Clinical Benefit Cohort B:CPI progressors treated by HS-110 + Nivolumab at >2L Median Progression-Free Survival (PFS)2.7 months(95% CI: 1.8 - 4.0 months) 4 out of 20 patients have not progressed on therapy 25
Slide 26: Safety Profile to Date
Safety Profile to Date1,000+ Doses - No Serious Adverse Reactions Over 1,000 doses administered to ~200 patients Only one patient ended treatment due to a non-serious adverse reaction* No systemic use of steroids required to treat reactionsNo treatment-related serious adverse reactions Favorable Saf
Slide 27: Summary of HS-110 Phase 2 Interim Data
Summary of HS-110 Phase 2 Interim Data HS-110 in combination with nivolumab is well tolerated Preliminary results demonstrate the ability of HS-110 plus nivolumab to induce CD8+ T-cell tumor infiltration in previously “cold” tumorsIn Cohort A, the occurrence of injection site reactions and increased
Slide 28: Heat Biologics Acquires Pelican Therapeutics
Heat acquired 80% controlling interest in Pelican in May 2017Pre-clinical synergy with Heat’s ImPACT® and checkpoint therapy$15.2M grant award from the Cancer Prevention Research Institute of Texas (CPRIT) propels PTX-35 through a 70-patient, first-in-human clinical programPTX-35 is a potential bes
Slide 29: TNFRSF25 Preferentially Expressed on CD8+ T-cells
TNFRSF25 is preferentially expressed on CD8+ T-cells compared to other T-cell co-stimulatorsCo-stimulation occurs only in the context of TCR recognition of antigenDrives the development of antigen-specific CD8+ T-cells (mimics TL1A, the specific ligand of TNFRSF25)Compared to agonists OX40, GITR, 4-
Slide 30: Corporate Milestones
Corporate Milestones ImPACT NSCLC Phase 2 interim data readout File IND for HS-130 ComPACT trial File IND for PTX-35 Phase 1 trial ImPACT NSCLC Complete Phase 2 enrollment ImPACT NSCLC Milestones Pelican and ComPACT Milestones Interim PTX-35 data readout Interim ComPACT data readout ImPACT NSCLC Pha
Slide 31: Corporate Highlights
Corporate Highlights NasdaqHTBX Shares Outstanding32.5M Cash & Equiv.$27.7M Capitalization Table(as of 12/31/2018) Shares Common shares outstanding 32.5 M Warrants 9.0 M Outstanding stock options 3.1 M Unvested restricted stock 1.6 M Fully Diluted Shares Outstanding 46.2 M Founded in2008 Grant Award
Slide 32: Investment Highlights
Investment Highlights Potential Best in Class Oncology Treatment - T-cell activating platform (TCAP) produces allogeneic, off-the-shelf therapies designed to activate the immune system to turn immunologically “cold” tumors “hot”Combination Effect - Our therapies are designed to be administered with
Slide 33: Appendix
Appendix 33
Slide 34: Cohort A & B: Patient Characteristics
Cohort A & B: Patient Characteristics Cohort A (N = 42) Cohort B (N = 20) EGFR or ALK positive 9 (22%) 2 (10%) Prior lines 12 or more Unavailable 27 (64%)13 (30%)2 (5%) 3 (15%)16 (80%)1 (5%) PD-L1 < 1%≥ 1%Unevaluable 16 (38%)13 (31%)13 (31%) 7 (35%)8 (40%)5 (25%) CD8+ TIL ≤ 10%> 10%Unevaluable 12 (2
Slide 35: Preclinical Data of CD8+ T cell Activation
Preclinical Data of CD8+ T cell ActivationImPACT® alone and in combination with co-stimulator agonists: OX40, TNFRSF25, PD-1 Source: Fromm et al. Society for Immunotherapy of Cancer Annual Meeting, 2016 Higher T-cell responses observed in mice treated with ImPACT aloneImPACT® boosted CD8+ T-cells to
Slide 36: ComPACT Platform Technology
ComPACT™ Platform Technology gp96-Ig OX40L-Fc The first potential dual-acting immunotherapy designed to deliver T-cell activation andco-stimulation in a single product – combination therapy without additive costs 36
Slide 37: ComPACT Outperforms OX40 Monoclonal Antibodies
ComPACT™ Outperforms OX40 Monoclonal Antibodies in Pre-clinical Models ComPACT generates ~50% complete tumor rejection compared to ~16% with OX40 agonist antibody combinations Superior primary and memory T-cell response in mouse model Translates into increased overall survival and tumor reduction in
Slide 38: TNFRSF25 - An Emerging Target for T-cell Co-stimulation
TNFRSF25 - An Emerging Target for T-cell Co-stimulation 38 Target Companies Co-stimulator Combinations 4-1BB Pfizer, ISA Pharma, Gilead, Bristol Myers, Inhibrx, Immatics, Pieris, NCI Phase 1/2Combinations: Chemotherapy, epigenetic modulator, CD20 mAb, HPV vaccine, CART, PD-L1, BTK, Herceptin, modifi
Slide 39: TNFRSF25 agonist + ImPACT Increases Survival in Mice
TNFRSF25 agonist + ImPACT Significantly Increases Survival in Mice OX40 GITR 4-1BB TNFRSF25 Schreiber T. et al. SITC 2014 Control4-1BBImPACTImPACT + 4-1BB ControlOX40ImPACTImPACT + OX40 ControlGITRImPACTImPACT + GITR ControlTNFRSF25ImPACTImPACT + TNFRSF25 39 Nine-day B16-F10 melanoma model
Slide 40: Preferential CD8+ T-cell Induction with TNFRSF25
Preferential CD8+ T-cell Induction with TNFRSF25 in MicePre-clinical studies with murine agonist antibody shows TNFRSF25 preferentially ‘boosts’ CD8+ T-cells, whereas OX40 is preferential to CD4+ T-cells The frequency of antigen-specific memory CD4+ or memory CD8+ T-cells following treatment of mice
Slide 41: TNFRSF25 Preferentially Expressed on CD8+ T-cells
TNFRSF25 is preferentially expressed on CD8+ T-cellscompared to other T-cell co-stimulators Genomics Institute of the Novartis Research Foundation Su et al. PNAS 2004:101(16);6062-7 (red = high expression) 41
Slide 42: Management and Advisors
Management and Advisors Jeff WolfFounder & CEO Ann RosarVP of Finance Janice McCourtVP of Business Devt. Lori McDermottVP of Clinical Dev. Gary VinsonVP of Manufacturing Jeff Hutchins, Ph.D.CSO/COO George Peoples, MDChief Medical Advisor Management Scientific Advisors Robert Levy, Ph.D.University of
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