Scorpius Holdings Inc. · OTC:SCPX
Scorpius — Heat Biologics — Investor Presentation (November 2019)
43 slides from Scorpius's investor presentation, Nov 29, 2019
Slide 1: Heat Biologics Corporate Presentation November 2019
Heat Biologics NASDAQ: HTBX CORPORATE PRESENTATION NOVEMBER 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: Snapshot of Heat Biologics
Snapshot of Heat Biologics (Nasdaq: HTBX) • Biopharmaceutical company developing a suite of potential first - in - class immunotherapy products • HS - 110, an “off the shelf” cell - based immunotherapy product that has the potential to improve PD(L) - 1 based therapy - Planning for registrational tr
Slide 4: Product Pipeline
Product Pipeline 4 Product MOA (Modality) Indication Preclinical Phase 1 Phase 2 Phase 3 HS - 110 gp96 (Cell Therapy) NSCLC HS - 130 OX40L (Cell Therapy) Multiple Solid Tumor PTX - 35 TNFRSF25 (mAb) Multiple Solid Tumor
Slide 5: Overview
HS - 110 Overview • HS - 110 is a Phase 2 cell - based immunotherapy administered in combination with PD - (L)1 therapies to improve clinical outcomes for NSCLC patients - Allogeneic cells with engineered gp96 to present 70+ different cancer testis antigens - Selectively activate CD8+ “killer” T cel
Slide 6: PD(L)-1 Therapy is Approved for Multiple Cancers
PD(L) - 1 Therapy is Approved for Multiple Cancers 6 Data Source: Globocan 2018. Graph production by Cancer Cases Number Percentage Lung 2 093 876 11.6% Breast 2 088 849 11.6% Colorectum 1 849 518 10.2% Prostate 1 276 106 7.1% Stomach 1 033 701 5.7% Liver 841 080 4.7% Esophagus 572 034 3.2% Other ca
Slide 7: Combination with PD(L)-1 therapy
Combination of HS - 110 and PD(L) - 1 therapy • HS - 110 is designed to overcome mechanisms of immune evasion, thereby having the potential to enable effective treatment with PD(L) - 1 - Target to be effective in patients that generally do not benefit from PD(L) - 1 therapy 7 Cold Tumor HS - 110 + P
Slide 8: Clinical Support for + Nivolumab MOA
Clinical Support for HS - 110 + Nivolumab MOA 8 CD8+ TIL Infiltration Associated with Clinical Response Combination treatment drives “killer” CD8+ T - cells deep into tumors Baseline (Cold) Week 10 (Hot) Patient 1 Partial Response at Week 18 High CD8+ TIL ( > 10%) Patient 2 Partial Response at Week
Slide 9: Clinical Data: Phase 1b/2 Study in NSCLC
HS - 110 Clinical Data A Phase 1b/2 Study of HS - 110 in Combination with Multiple Treatment Regimens in Patients with NSCLC 9 Exploratory Endpoints • Baseline CD8+ TILs (Low defined as ≤ 10% stromal CD8+ TILs) • PD - L1 expression (Negative defined as < 1% on tumor cells) • Peripheral blood tumor m
Slide 10: Trial Result Summary Compared with Published Data
Trial Result Summary Compare with Published Data 10 A comparison with published literature in NSCLC patients treated with nivolumab as a single agent HS - 110 + Nivolumab Δ 93% Non - squamous NSCLC 7% Squamous NSCLC Nivolumab * Checkmate 57 Non - squamous NSCLC Nivolumab ‡ Checkmate 17 Squamous NSCL
Slide 11: PFS by Injection Site Reaction (ISR)
PFS by Injection Site Reaction (ISR) 11 Cohort A: CPI naïve pts treated by HS - 110 + Nivolumab at > 2L Progression free survival (PFS) is significantly better in patients who experienced dermal injection site reaction, thus supporting the HS - 110 mechanism of action As of July 2019 data cut ISR =
Slide 12: OS by Injection Site Reaction (ISR)
OS by Injection Site Reaction (ISR) 12 Cohort A: CPI naïve pts treated by HS - 110 + Nivolumab at > 2L Overall survival (OS) is significantly better in patients who experienced dermal injection site reaction, thus supporting the HS - 110 mechanism of action As of July 2019 data cut ISR = Yes refers
Slide 13: Summary of PFS and OS Compared with Published Data
Summary of PFS and OS Compare with Published Data 13 • Cohort A: Stage III or IV advanced NSCLC patients • A comparison with published literature in NSCLC patients treated with nivolumab as a single agent (Months) HS - 110 + Nivolumab Δ 93% Non - squamous NSCLC and 7% Squamous NSCLC Nivolumab Non -
Slide 14: Clinical Data: Phase 1b/2 Study in NSCLC
HS - 110 Clinical Data A Phase 1b/2 Study of HS - 110 in Combination with Multiple Treatment Regimens in Patients with NSCLC 14 Exploratory Endpoints • Baseline CD8+ TILs (Low defined as ≤ 10% stromal CD8+ TILs) • PD - L1 expression (Negative defined as < 1% on tumor cells) • Peripheral blood tumor
Slide 15: Response and Disease Control Comparison with Published Data
Response and Disease Control Comparison with Published Data 15 Cohort B: CPI progressors treated by HS - 110 + Nivolumab at > 2L -100 -75 -50 -25 0 25 50 75 100 % C h a n g e i n t u m o r b u r d e n * f r o m b a s e l i n e Tumor shrinkage observed in 38% of patients *Waterfall plot of evaluable
Slide 16: PFS by Injection Site Reaction (ISR)
PFS by Injection Site Reaction (ISR) 16 As of July 2019 data cut Cohort B: CPI progressors treated by HS - 110 + Nivolumab at > 2L 0 3 6 9 12 0 25 50 75 100 P r o g r e s s i o n F r e e S u r v i v a l ( % ) ISR = Yes ISR = No ISR Median PFS, 95% CI (mos) Yes (n=39) 3.7 (1.9, 5.8) No (n=17) 1.8 (1.
Slide 17: OS by Injection Site Reaction (ISR)
OS by Injection Site Reaction (ISR) 17 As of July 2019 data cut Cohort B: CPI progressors treated by HS - 110 + Nivolumab at > 2L Months 0 3 6 9 12 0 25 50 75 100 O v e r a l l S u r v i v a l ( % ) ISR = No ISR = Yes ISR Median OS, 95% CI (mos) Yes (n=39) 12.0 (9.4, Not Reached) No (n=17) 5.0 (3.0,
Slide 18: Summary of PFS and OS Compared with Published Data
Summary of PFS and OS Compared with Published Data 18 • Unresectable or metastatic NSCLC patients, heavily pretreated(63% with ≥ 2 lines of prior therapy) • A comparison with published literature in NSCLC patients after PD - (L)1 progression (Months) HS - 110 + Nivolumab at ≥ 2nd line after CPI fail
Slide 19: Favorable Safety Profile to Date
Favorable Safety Profile to Date • Over 1,000 doses administered to 150+ patients • Only one patient ended treatment due to an HS - 110 related non - serious adverse reaction * • No treatment - related serious adverse reactions • No increase in immune - related adverse events compared to single - ag
Slide 20: Product Pipeline
Product Pipeline 20 Product MOA (Modality) Indication Preclinical Phase 1 Phase 2 Phase 3 HS - 110 gp96 (Cell Therapy) NSCLC HS - 130 OX40L (Cell Therapy) Multiple Solid Tumor PTX - 35 TNFRSF25 (mAb) Multiple Solid Tumor
Slide 21: HS-130 Overview
HS - 130 Overview • HS - 130 is the first allogeneic, off - the - shelf, cell therapy approach utilizing OX40 - mediated co - stimulation to enhance activation of dormant immune signal - Leverage HS - 110 clinical experience and manufacturing know - how - Addition of OX40L fusion protein to extend a
Slide 22: Product Pipeline
Product Pipeline 22 Product MOA (Modality) Indication Preclinical Phase 1 Phase 2 Phase 3 HS - 110 gp96 (Cell Therapy) NSCLC HS - 130 OX40L (Cell Therapy) Multiple Solid Tumor PTX - 35 TNFRSF25 (mAb) Multiple Solid Tumor
Slide 23: PTX-35 Overview
PTX - 35 Overview • Potential first - in - class T cell co - stimulator targeting TNFRSF25, with preferential specificity to generate “memory” CD8+ T cells - FDA clearance of PTX - 35 IND expected in Q2, 2020 • Broad market potential - Efficacy demonstrated in multiple preclinical in vivo colon, lun
Slide 24: Appendix
Heat Biologics NASDAQ: HTBX APPENDIX 24
Slide 25: MOA and Preclinical Data
HS - 110 MOA AND PRECLINICAL DATA 25
Slide 26: PD(L)-1 Therapy is Approved for Multiple Cancers
PD(L) - 1 Therapy is Approved for Multiple Cancers Lung cancer 733.3 Gastric cancer 679.1 Esophageal cancer 477.9 Liver cancer 466.1 Colorectal cancer 376.3 Pancreas cancer 90.1 Lymphoma 88.2 Bladder cancer 80.5 Leukemia 75.3 Prostate cancer 60.3 Others 1164.5 Lung cancer Gastric cancer Esophageal c
Slide 27: 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 28: Introducing gp96 – Its dual role
Introducing gp96 – Its dual role The Immune System’s “Swiss Army Knife”* “Molecular Warning System” • A natural biological process to deliver proteins (antigens) & gp96 to our immune system • Gp96 “chaperones” newly - created proteins to the cell membrane where they are released and embedded • Gp96
Slide 29: Heat's T Cell Activation Platform - ImPACT
Heat’s T Cell Activation Platform - ImPACT ® “Severing the Leash” Heat Biologics ImPACT® technology reprograms cancer cells to continuously secrete their own antigens • ImPACT® technology genetically modifies tumor cells by “severing the leash” that binds the gp96 to the endoplasmic reticulum, and r
Slide 30: Mechanism of Action
HS - 110 Mechanism of Action 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 Specific T cells. 2 signa
Slide 31: Mechanism of Action
HS - 110 Mechanism of Action • HS - 110 is derived from a lung adenocarcinoma cell line transfected with gp 96 - Ig, where the gp 96 KDEL ER retention sequence is replaced by IgG 1 Fc • gp 96 - Ig acts as a chaperone protein for tumor associated antigens and is recognized by CD 91 on APCs ; resultin
Slide 32: Cell-secreted gp96 activates dendritic cells and CD8+ T cells
Heat’s unique cell - secreted gp96 firstly activates dendritic cells via TLR signaling and subsequently CD8+ T cells via antigen cross presentation ImPACT Cell Cancer - killing T - cell ImPACT cells secrete antigens designed to specifically activate patient’s killer T - cells T - cells circulate to
Slide 33: 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 33
Slide 34: Key Data Summary
Key Data Summary • Response rate by RECIST 1.1 - Objective response rate (ORR) was 13% - Disease control rate (DCR) was 59% • Median overall survival (OS) was estimated at 11.8 months with 70% of patients still alive • Median progression free survival ( mPFS ) was 3.2 months • Patients who experienc
Slide 35: PTX-35 Preclinical Data
Heat Biologics PTX-35 PRECLINICAL DATA
Slide 36: TNFRSF25 An Emerging Target for T-cell Co-stimulation
TNFRSF25 An Emerging Target for T - cell Co - stimulation • TNFRSF25 is a potential best - in - class T cell co - stimulator due to its preferential specificity to ‘memory’ CD8+ T cells • Pelican is the only company with a disclosed program targeting TNFRSF25 Target Companies Co - stimulator Combina
Slide 37: TNFRSF25 as a Novel I/O Combination Target
TNFRSF25 as a Novel I/O Combination Target • TNFRSF25 is one of the most recently discovered T cell costimulator , and is a rapidly emerging target • Pelican is the only company developing TNFRSF25 agonist antibodies for I/O Mahoney K. et al . Nat Rev Drug Discov . 2015 “Although TNFRSF25 is chromos
Slide 38: TNFRSF25: Why So Complicated?
TNFRSF25: Why So Complicated? TNFRSF25’s evolutionary origin Potentially a mechanism that preserves needed tissue and friendly bacteria during an immune response Example: gut invasion occurs in the context of friendly microbiome bacteria. How does the body protect what is needed while weeding out in
Slide 39: TNFRSF25 is preferentially expressed on CD8+ and CD4+ T-cells
TNFRSF25 is preferentially expressed on CD8+ and CD4+ T - cells 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) 39
Slide 40: PTX-35 Preclinical Data Highlights
PTX - 35 Preclinical Data highlights CD8+ T - cell Specificity 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
Slide 41: 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 42: TNFRSF25 agonist + ImPACT Significantly Increases Survival in Mice
TNFRSF25 agonist + ImPACT Significantly Increases Survival in Mice Established (nine - day) B16 - F10 melanoma mouse model GITR 4 - 1BB TNFRSF25 Control 4 - 1BB ImPACT ImPACT + 4 - 1BB Control GITR ImPACT ImPACT + GITR Control TNFRSF25 ImPACT ImPACT + TNFRSF25 Schreiber T. et al. SITC 2014 42
Slide 43: Heat Biologics
Heat Biologics NASDAQ: HTBX CORPORATE PRESENTATION NOVEMBER 2019 44
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