Scorpius Holdings Inc. · OTC:SCPX
Scorpius — Heat Biologics — Investor Presentation (June 2019)
48 slides from Scorpius's investor presentation, Jun 24, 2019
Slide 1: Heat Biologics Corporate Presentation
Heat Biologics NASDAQ: HTBX CORPORATE PRESENTATION June 24, 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 fo
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 Therapy The three legs of an Immuno - Oncology Stool 4
Slide 5: Heat's Combination Platforms
Heat’s Combination Platforms Unlocking the Body’s Natural Defenses with a Broad Range of Combination Therapies Checkpoint Inhibitors PD1/PDL1 CTLA - 4 Lag - 3 TIM - 3 Plus others Combined with Co - Stimulation T - cell Activation Pelican PTX - 35 Monoclonal Antibody ImPACT® Therapy Cell - 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 tech
Slide 7: ImPACT Off-the-shelf Manufacturing
ImPACT® “Off - the - shelf” Manufacturing Designed for Robust, Pan - antigen T - cell Activation • Frozen, fully - diluted single - dose vial • Final drug product: 10 million cells • Easily scaled manufacturing Low COG, off - the - shelf alternative to autologous therapies 7
Slide 8: Introducing gp96 – Its Dual Role
Introducing gp96 – Its dual role The 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
Slide 9: ImPACT 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 cell Mimics necrotic cell death by enabling fully - allogeneic “off - the - shelf” living cancer cells
Slide 10: ImPACT: Immune Pan-antigen Cytotoxic Therapy
ImPACT® : I mmune P an - a ntigen C ytotoxic T herapy 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
Slide 11: HS-110 Generates an Adaptive Immune Response
HS - 110 Generates an Adaptive Immune Response 1. Secretion of gp96 - Ig carrying tumor specific proteins represented on the patients tumor 2. Activation of APCs (TLR2/4) and cross - presentation of antigens (CD91) 3. Specific T - cell receptor engagement 4. Clonal Expansion of Tumor Antigen Specifi
Slide 12: HS-110 + Opdivo Combination Therapy
HS - 110 + Opdivo Combination Therapy Potential to improve clinical responses and survival, without additional toxicity Source: BMS images 12
Slide 13: HS-110 Trial Design
HS - 110 Trial Design A 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 Endpoints Phase 1b: Safety Phase 2: Cohort A&B: ORR Cohort C&D: PFS Secondary Endpoints OS, PFS, DCR, DOR Exploratory Endpoi
Slide 14: Cohort A: Patient Characteristics
Cohort A: Patient Characteristics 14 Stage III or IV Advanced NSCLC Patients Cohort A (N = 42) EGFR or ALK positive 9 (22%) Prior lines of Tx 1 2 or more Unavailable 27 (64%) 13 (30%) 2 (5%) PD - L1 < 1% ≥ 1% Unevaluable 16 (38%) 13 (31%) 13 (31%) CD8+ TIL ≤ 10% > 10% Unevaluable 12 (29%) 8 (19%) 22
Slide 15: 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%) Combina
Slide 16: Increased Killing Activity in Patient Tumor Microenvironment
Combination Treatment Substantially Increased Killing Activity in Patient Tumor Microenvironment Substantial increase of CD3+ TILs and CD3+ Granzyme B+ TILs for enhanced tumor killing activity 16
Slide 17: Progression-Free Survival
0 6 12 18 24 30 0 25 50 75 100 Months P r o g r e s s i o n - F r e e S u r v i v a l ( % ) 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
Slide 18: Overall Survival
0 6 12 18 24 30 36 42 0 25 50 75 100 Months S u r v i v a l ( % ) 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
Slide 19: 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%) -100 -75 -50 -25 0 25 50 75 100 C h a n g e f r o m B a s e l i n e ( % ) Change from Baseline (%) Best Target Lesion Response Best Overall Response
Slide 20: Duration of Benefit
Duration of Benefit Cohort A: CPI Naïve pts treated by HS - 110 + Nivolumab at > 2L 20 Responses and disease stabilization are durable and long - lasting 25 50 75 100 0 - 30 - 50 - 75 Change from Baseline (%) 0 3 6 9 12 15 18 21 24 27 Months from the First Dose of HS - 110 - 100 HS - 110 Dosing Comp
Slide 21: Improved Survival in Cold Tumor Patients
• Survival benefit observed in patients with low CD8+ TIL at baseline , as compared to high CD8+ TIL at baseline, HR = 0.39 (95% CI: 0.06 – 2.31) • Median overall survival not reached for both groups • The above benefit is contrary to what is expected based on current literature Gibney et al. Lancet
Slide 22: Benefit Independent of PD-L1 Status
Cohort A: CPI Naïve pts treated by HS - 110 + Nivolumab at > 2L PD - L1 (<1%), N = 16 PD - L1 ( > 1%), N = 13 PD - L1 NE, N = 13 22 0 6 12 18 24 30 36 42 0 25 50 75 100 Months S u r v i v a l ( % ) PD-L1 (<1%), n = 16 PD-L1 (1%), n = 13 PD-L1 NE, n = 13 0 6 12 18 24 30 36 42 25 50 75 Overall Surviv
Slide 23: OS by Injection Site Reaction
23 Cohort A: CPI Naïve pts treated by HS - 110 + Nivolumab at > 2L OS by Injection Site Reaction (ISR) Survival is significantly better in patients who experienced dermal injection site reaction, thus supporting the HS - 110 mechanism of action 0 6 12 18 24 30 36 42 0 25 50 75 100 Months S u r v i v
Slide 24: Survival Benefit with Increased Immune Activity
0 12 24 36 Low High OS (months) H S - 1 1 0 G e n e r a t e d E L I S P O T s 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
Slide 25: Cohort B: Patient Characteristics
Cohort B: Patient Characteristics 25 As of last data cut - off in January, 2019 • Stage III or IV advanced NSCLC patients • Patients were heavily pretreated (80% with 2 + lines of prior therapy) Cohort B (N = 20) PD - L1 < 1% ≥ 1% Unevaluable 7 (35%) 8 (40%) 5 (25%) CD8+ TIL ≤ 10% > 10% Unevaluable
Slide 26: Objective Response Rate Cohort B
Objective Response Rate Cohort B: CPI progressors treated by HS - 110 + Nivolumab at > 2L As of last data cut - off in April, 2019 4 2 6 2 3 1 1 4 2 2 1 2 4 2 4 4 2 1 RECIST 1.1 ORR = 15% (95% CI: 3.2% - 37.9%) Per investigator assessment: PR = 4 (20%) SD = 7 (35%) DCR = 11 (55%) • Stabilization of
Slide 27: PFS by Injection Site Reaction
PFS by Injection Site Reaction (ISR) Cohort B: CPI progressors treated by HS - 110 + Nivolumab at > 2L As of last data cut - off in April, 2019 Progression - Free Survival (%) As of last data cut - off in April, 2019 ISR = Yes (N = 12) ISR = No (N = 8) mPFS: NR vs. 1.8 months HR = 0.17 (95% CI, 0.03
Slide 28: OS by Injection Site Reaction
OS by Injection Site Reaction (ISR) Cohort B: CPI progressors treated by HS - 110 + Nivolumab at > 2L Progression - Free Survival (%) As of last data cut - off in April, 2019 ISR = Yes (N = 12) ISR = No (N = 8) mOS : NR vs. 5 months HR = 0.13 (95% CI, 0.02 - 0.71) p = 0.002 O S is significantly bett
Slide 29: Duration of Clinical Benefit
Duration of Clinical Benefit Cohort B: CPI progressors treated by HS - 110 + Nivolumab at > 2L Median Progression - Free Survival (PFS) 2.7 months 5 out of 20 patients have not progressed on therapy As of last data cut - off in A pril , 2019 On study Disease Progression Alive Deceased 0 1 2 3 4 5 6
Slide 30: Safety Profile to Date
Safety Profile to Date 1,000+ Doses - No Serious Adverse Reactions • Over 1,000 doses administered to 12 0 + patients • Only one patient ended treatment due to a non - serious adverse reaction* • No systemic use of steroids required to treat reactions • No treatment - related serious adverse reactio
Slide 31: Summary of HS-110 Phase 2 Interim Data
Summary of HS - 110 Phase 2 Interim Data • HS - 110 in combination with nivolumab appears safe and well tolerated • Preliminary results demonstrate the ability of HS - 110 plus nivolumab to induce CD8+ T - cell tumor infiltration in previously “cold” tumors • The occurrence of dermal injection site
Slide 32: Heat Biologics Acquires Pelican Therapeutics
» Heat acquired 80% controlling interest in Pelican in May 2017 » Pre - 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 program » PTX
Slide 33: TNFRSF25 as a Novel I/O Combination Target
TNFRSF25 as a Novel I/O Combination Target • TNFRSF25 is the most recently discovered T cell costimulator, and is a rapidly emerging target • Pelican is the only company that has publicly announced developing TNFRSF25 agonist antibodies for I/O Mahoney K. et al . Nat Rev Drug Discov . 2015 “Although
Slide 34: TNFRSF25: Why So Complicated?
T Cell APC TL1a TNFRSF25 CD8 Expand activated CD8+ CD8 Expand but delay activation of existing Treg Treg Treg Inhibits Tconv to iTreg conversion CD4 iTreg X One molecule – three types of T - cells TNFRSF25: Why So Complicated? TNFRSF25’s evolutionary origin Potentially a mechanism that preserves nee
Slide 35: TNFRSF25 Primarily Expressed on CD8+ and CD4+ T-Cells
TNFRSF25 is Primarily Expressed on CD8+ and CD4+ T - Cells compared 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) 35
Slide 36: TNFRSF25 Preferentially Expressed on CD8+ T-cells
TNFRSF25 is preferentially expressed on CD8+ T - cells compared to other T - cell co - stimulators • Co - stimulation occurs only in the context of TCR recognition of antigen • Drives the development of antigen - specific CD8+ T - cells (mimics TL1A, the specific ligand of TNFRSF25) Compared to agon
Slide 37: Development of Agonist Antibody PTX-35
Development of Agonist Antibody: PTX - 35 • The lead mAb, PTX - 35, was affinity - matured and selected based on functional activation of TNFRSF25 across species. • The functional cross - reactivity of PTX - 35 was further validated by demonstrating that PTX - 35 binds a unique epitope conserved in
Slide 38: 2019 Corporate Milestones
2019 Corporate Milestones 38 Q1 Q2 Q3 Q4 Phase 2 interim data readout Complete Phase 2 enrollment Phase 2 interim data readout HS - 110 File IND Initial data readout PTX - 35 File IND Initial data readout HS - 130
Slide 39: Corporate Highlights
Corporate 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
Slide 40: Appendix
Appendix 40
Slide 41: Management and Advisors
Management and Advisors Management Scientific Advisors Robert Levy, Ph.D. University of Miami Roger Cohen, MD University of Pennsylvania Robert Negrin , MD Stanford University Llew Keltner, MD, Ph.D. Epistat Anthony Tolcher , MD Next Oncology Gary Acton, MD Advisor Board of Directors Jeff Wolf Found
Slide 42: Preclinical Data of CD8+ T cell Activation
C o n t r o l V a c c i n e O X 4 0 T N F R S F 2 5 4 - 1 B B G I T R P D - L 1 P D - 1 C T L A - 4 L A G - 3 V a c c i n e + O X 4 0 V a c c i n e + T N F R S F 2 5 V a c c i n e + 4 - 1 B B V a c c i n e + G I T R V a c c i n e + P D - L 1 V a c c i n e + P D - 1 V a c c i n e + C T L A - 4 V a c
Slide 43: ComPACT Platform Technology
ComPACT™ Platform Technology gp96 - Ig OX40L - Fc The first potential dual - acting immunotherapy designed to deliver T - cell activation and co - stimulation in a single product – combination therapy without additive costs 43
Slide 44: 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 reductio
Slide 45: TNFRSF25 - An Emerging Target for T-cell Co-stimulation
TNFRSF25 - An Emerging Target for T - cell Co - stimulation Target Companies Co - stimulator Combinations 4 - 1BB Pfizer, ISA Pharma, Gilead, Bristol Myers, Inhibrx , Immatics , Pieris, NCI Phase 1/2 Combinations: Chemotherapy, epigenetic modulator, CD20 mAb , HPV vaccine, CART, PD - L1, BTK, Hercep
Slide 46: Preferential CD8+ T-cell Induction with TNFRSF25 in Mice
Preferential CD8+ T - cell Induction with TNFRSF25 in Mice Pre - 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 trea
Slide 47: TNFRSF25 Agonist + ImPACT Significantly Increases Survival
TNFRSF25 Agonist + ImPACT Significantly Increases Survival 0 10 20 30 40 0 25 50 75 100 Control OX40 3T3-ova-gp96 3T3-ova-gp96 + OX40 Mantel-Cox p=0.0019 Days Post Tumor Inoculation % S u r v i v a l OX40 GITR 4 - 1BB TNFRSF25 Schreiber T. et al. SITC 2014 Control 4 - 1BB ImPACT ImPACT + 4 - 1BB Con
Slide 48: TNFRSF25 Causes No Intra-tumoral T-reg Proliferation
George Fromm et al 2014 Heat Biologics Internal Data TNFRSF25 Causes No Intra - tumoral T - reg Proliferation in a Lung Tumor Model 48