Scorpius Holdings Inc. · OTC:SCPX
Scorpius — Heat Biologics — Investor Presentation (January 2019)
43 slides from Scorpius's investor presentation, Jan 8, 2019
Slide 1: Heat Biologics Corporate Presentation January 2019
Heat Biologics Corporate PresentationJanuary 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
To activate CD8+ “Killer” T-cells to turn “COLD” tumors “HOT” 3 Our Mission We seek to combine with checkpoint inhibitors and other immunotherapies to dramatically increase their effectiveness 3
Slide 4: 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 5: What are Hot and Cold Tumors?
5 Cold Tumors Tumors that have not been subject to robust CD8+ “Killer” T-cell attackBiopsied tumors contain minimal CD8+ T-cells Hot Tumors Tumors that have been subject to robust CD8+ “Killer” T-cell attack Biopsied tumors are loaded with CD8+ T-cells HOT tumors are associated with clinical respon
Slide 6: Current NSCLC checkpoint inhibitor treatment
Current NSCLC checkpoint inhibitor treatment Checkpoint Inhibitor Monotherapy Heat BiologicsCombination Therapy Cold Tumor Cold Tumor Hot Tumor Hot Tumor Current Responders Target Responders Goal Unmet medical need in 2nd line NSCLC Combination therapies can improve patient outcomes 6 17% - 20% resp
Slide 7: Immuno-Oncology Combination Therapy
7 Immuno-Oncology Combination Therapy The three legs of an Immuno-Oncology Stool T-cell Activation Co-stimulation Checkpoint Inhibition Heat’s Core Focus Heat’s goal is to dramatically increase the number of patients responding to checkpoint inhibitors
Slide 8: Unlocking the Body's Natural Defenses with a Broad Range of Combination Therapies
Unlocking the Body’s Natural Defenses with a Broad Range of Combination Therapies 8 Combination Therapies T-cell Activation Co-Stimulation Pelican PTX-35Monoclonal AntibodyPelican PTX-15Fusion Protein Checkpoint Inhibitors PD1/PDL1CTLA-4Lag-3TIM-3Plus others Combined with ImPACT® TherapyCell-based D
Slide 9: Introducing gp96: The Immune System's Swiss Army Knife
9 Introducing gp96 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” Natural biological process to deliver proteins (antigens) & gp96 adjuvant to our immune systemGp96 “chap
Slide 10: ImPACT Platform: Severing the Leash
Genetically modify tumor cells by “severing the leash” that binds the gp96 to the endoplasmic reticulum of the cell and replacing it with a sequence that pumps gp96 out of the cellEnables living cancer cells to “pump-out” their own surface antigens along with their gp96 chaperoneMimics necrotic cell
Slide 11: ImPACT: Immune Pan-antigen Cytotoxic Therapy
11 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 an
Slide 12: ImPACT + Opdivo Combination Therapy
ImPACT + Opdivo Combination Therapy 12 Source: BMS images Potential to improve clinical responses and survival, without additional toxicity
Slide 13: Product Pipeline
13 Product Pipeline Combination Therapies Designed to Activate CD8+ T-cells Against Cancer T-cell infiltration seen deep inside tumorsPositive safety profile to date Clinical proof of mechanism activating an immune responseActivated T-cell immune response seen at 10 weeks Combination Therapies Indic
Slide 14: Phase 1b/2 DURGA Trial of HS-110 in NSCLC
A Phase 1b/2 study of Viagenpumatucel-L (HS-110) in Combination with Multiple Treatment Regimens in Patients with Non-Small Cell Lung Cancer (the “DURGA” Trial) Objective Evaluate objective response rate of HS-110 and anti-PD-1 immune checkpoint inhibitor and other agents Patient Population NSCLCAde
Slide 15: TIL Infiltration Associated with Clinical Response
Baseline(Cold) Week 10(Hot) TIL Infiltration Associated with Clinical Response 15 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%) “Killer” CD8+ T-cells
Slide 16: Survival Data Are Still Maturing
Survival Data Are Still MaturingMedian Overall Survival Not Yet Reached 16 ITT survival curve has not yet reached medianMedian OS of nivolumab alone = 12.2 months mOS nivolumab12.2 months* *N Engl J Med 2015; 373: 1627-1639
Slide 17: Change in tumor size from Baseline
17 Change in tumor size from Baseline (%) All evaluable ITT patients with a baseline and on-treatment scan (n=27) All enrolled patients (ITT) with a baseline and on-treatment scan Best Target Lesion Response
Slide 18: Overall Target Lesion Responses are Durable and Long Lasting
Overall Target Lesion Responses are Durable and Long Lasting Change from Baseline (%) All enrolled patients (ITT) with a baseline and on-treatment scan Days From First Dose 18
Slide 19: Target Lesion Response Based on Initial CD8+ TIL Status
Target Lesion Response Based on Initial CD8+ TIL Status 19 Change from Baseline (%*) CD8+ TIL Evaluable ITT Population Change from Baseline (%*) High CD8+ TIL at Baseline Low CD8+ TIL at Baseline 50% 20% 25% 20% 60% 30% 50% 5% 5% 5% 5% 5% 5% 10% 0% 1% * % of CD8+ T-cells in tumor tissue at baseline
Slide 20: Durable Target Lesion Responses Based on Initial CD8+ TIL Status
Durable Target Lesion Responses Based on Initial CD8+ TIL Status 20 Low CD8+ TIL High CD8+ TIL Change from Baseline (%) Tumor Type at Baseline CD8+ TIL Evaluable ITT Population Days from First Dose Durable target lesion responses (> 6 months) observed in difficult-to-treat low TIL “cold” patients
Slide 21: Encouraging Overall Survival Based on CD8+ TIL Status
Encouraging Overall Survival Based on CD8+ TIL Status 21 HS-110 Treated Patients Days Known to Be Alive Low CD8+ TIL High CD8+ TIL Tumor Type at Baseline Ϯ Reported Death TIL Evaluable ITT Population Ϯ Ϯ PD PD PD PD PD PD PD PD PD PD SD SD SD SD SD PR PR PR PR PD * Ongoing Response CR of Non Target
Slide 22: Target Lesion Response Based on Initial PD-L1 Status
Target Lesion Response Based on Initial PD-L1 Status 22 Change from Baseline (%) PD-L1 Evaluable ITT Population Change from Baseline (%) >1% PD-L1 Tumor Type at Baseline <1% PD-L1 Tumor Type at Baseline Positive PD-L1 Negative PD-L1 5% 50% 10% 1% 20% 50% 5% 60% 15% Encouraging Data in Low PD-L1 Pati
Slide 23: Durable Target Lesion Responses Based on Initial PD-L1 Status
Durable Target Lesion Responses Based on Initial PD-L1 Status 23 Change from Baseline (%) PD-L1 Evaluable ITT Population Days from First Dose Change from Baseline (%) Days from First Dose >1% PD-L1 Tumor Type at Baseline <1% PD-L1 Tumor Type at Baseline Positive PD-L1 Negative PD-L1 Durable Target L
Slide 24: HS-110 Shows Favorable Safety Profile to Date
24 HS-110 Shows Favorable Safety Profile to Date ~1,000 HS-110 Doses – No Serious Adverse Reactions Only one patient ended treatment due to a non-serious adverse reaction*No systemic use of steroids required to treat reactionsNo serious adverse reactions beyond those seen with standard of careNo add
Slide 25: Summary of Phase 2 Interim Data
Summary of Phase 2 Interim Data Tumor shrinkage and disease control demonstrated in a majority of evaluable patientsOverall responses are durable and long lastingMedian overall survival has not yet been reachedHS-110 shows effect in difficult-to-treat low TIL and low PD-L1 patients who typically do
Slide 26: Heat Biologics Acquires Pelican Therapeutics
26 Heat Biologics Acquires Pelican Therapeutics Unlocking the Body’s Natural Defenses with a Broad Range of Combination Therapies 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
Slide 27: Highlights from Pelican Pre-clinical Studies
27 Highlights from Pelican Pre-clinical Studies 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
Slide 28: Milestones
28 NSCLC Phase 2 interim data readout File IND for HS-130 ComPACT trial File IND for PTX-35 Phase 1 trial Complete Phase 2 NSCLC enrollment NSCLC Milestones Pelican and ComPACT Milestones Interim PTX-35 data readout Interim ComPACT data readout NSCLC Phase 2 interim data readout Corporate Milestones
Slide 29: Corporate Highlights
29 Market Cap$34.4M1 Cash & Equiv.$27.7M2,3 NasdaqHTBX Shares Outstanding32.5M Share Price$1.061 Grant Funds$15.2M Corporate Highlights Closing price as January 2, 2018Includes November 2018 financingDoes not include grant funding due to Heat or its subsidiaries
Slide 30: Investment Highlights
Investment Highlights Potential Best in Class Oncology Treatment Off-the-shelf Therapies Clinical Data with Checkpoint Inhibitors Diverse Technology Platforms Strong Balance Sheet 30
Slide 31: Turning COLD Tumors HOT
Cold Tumors Hot Tumors Turning COLD Tumors HOT 31
Slide 32: Appendix
Appendix 32
Slide 33: 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. 33 2 signal
Slide 34: ImPACT Manufacturing
34 ImPACT® Manufacturing Robust, Multi-antigen T-cell Activation Frozen, fully-diluted single-dose vialFinal drug product: 1 million or 10 million cellsEasily scaled manufacturing Low COG, off-the-shelf alternative to autologous therapies
Slide 35: Cost-Effective Therapy
Cost-Effective Therapy 35 Source: “The Million-Dollar Cancer Treatment: Who Will Pay?, WSJ, 4/28/18 Them – Autologous Approach Us – Allogeneic Approach Scalable manufacturing Nothing extracted Ready-to-use / off-the-shelf Intradermal injection Lower cost of production than autologous cell therapies
Slide 36: ELISPOT Activity and Survival
ELISPOT Activity and Survival 36 High = ELISPOT activity above the median of patients tested Low = ELISPOT activity below the median of patients tested A trend of survival benefit is observed higher ELISPOT activity of immune response 203 337 ELISPOT Evaluable ITT Population
Slide 37: Strong supporting pre-clinical data
Strong supporting pre-clinical data 37 Pre-clinical Data Source: Fromm et al. Society for Immunotherapy of Cancer Annual Meeting, 2016 CD8+ T-cell Activation Higher T-cell responses observed in mice treated with ImPACT aloneImPACT® boosted CD+ T-cells to even higher levels when combined with co-stim
Slide 38: ComPACT Platform Technology
38 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
Slide 39: ComPACT Outperforms OX40 Monoclonal Antibodies in Pre-clinical Models
39 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
Slide 40: PTX-35 Comparative Pre-clinical Anti-tumor Activity
40 PTX-35 Comparative Pre-clinical Anti-tumor Activity Schreiber T. et al. SITC 2014 Activity of agonists TNFRSF25, 4-1BB, OX40 and GITR during nine-day B16-F10 melanoma model TNFRSF25 agonists leads to increased survival compared to other co-stimulatory antibodies 4-1BB and GITR agonists have a mod
Slide 41: Preferential CD8+ T-cell Induction with TNFRSF25
41 Preferential CD8+ T-cell Induction with TNFRSF25 Pre-clinical studies with murine agonist antibody shows preferential CD8+ T-cell Induction; differentiation from other T-cell co-stimulators The frequency of antigen-specific memory CD4+ or memory CD8+ T-cells following treatment of mice with ImPAC
Slide 42: Many companies are pursuing co-stimulators with less specificity for CD8+ memory activation
Many companies are pursuing co-stimulators with less specificity for CD8+ “memory” activation 42 Emerging Target in T-cell Co-stimulation Only Pelican is targeting TNFRSF25, an emerging target in immuno-oncology Target Agonist to Target Clinical Stage Company Comments 4-1BB PF-05082566 (utomilumab)B
Slide 43: Expression of T-cell Co-stimulators
43 Expression of T-cell Co-stimulators TNFRSF25 is preferentially expressed on CD8+ 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)
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