Scorpius Holdings Inc. · OTC:SCPX
Scorpius — Heat Biologics — Investor Day (February 2018)
42 slides from Scorpius's investor day presentation, Feb 28, 2018
Slide 1: Heat Biologics Analyst and Investor Day
1 Heat Biologics Analyst and Investor DayFebruary 28, 2018
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: Roger B. Cohen, Professor of Medicine, University of Pennsylvania
Roger B. Cohen Professor of MedicineUniversity of PennsylvaniaAssociate Director Clinical Research Abramson Cancer CenterChief Clinical Research Officer Abramson Cancer CenterCo-Director, Head and Neck Cancer Research Center
Slide 4: Therapy for Advanced Lung Cancer
Therapy for Advanced Lung Cancer There have been some modest gains since 1980 Immunotherapy Are we doing better with immunotherapy? Targeted Therapies
Slide 5: Cancer-Immunity Cycle
Cancer-Immunity Cycle Chen DS, Mellman I. Immunity. 2013;39:1-10. Release of cancer cell antigens(cancer cell death) 1 Cancer antigen presentation(dendritic cells/APCs) 2 Priming and activation(APCs & T cells) 3 Trafficking of T cells to tumors (CTLs) 4 Infiltration of T cells into tumors(CTLs, endo
Slide 6: Immune Checkpoints
Immune Checkpoints Immune checkpoints are normal ‘brakes’ on the activity of the immune system; checkpoint proteins turn off activated T cells when they are no longer neededImmune checkpoints have been ‘hijacked’ by the cancer to evade the immune systemCheckpoint Inhibitors remove the checkpoint and
Slide 7: 1st Line NSCLC Treatment Landscape
1st Line NSCLC Treatment Landscape Incurable NSCLC (adenocarcinoma) without activating EGFR, ALK, etc. mutations:If PD-L1 is ≥ 50%, consider Keytruda as monotherapyIf PD-L1 <50%, consider Keytruda in combination with chemotherapyPlatinum doublet chemotherapyIncurable NSCLC (squamous cell):If PD-L1 i
Slide 8: 2nd Line NSCLC Treatment Landscape
2nd Line NSCLC Treatment Landscape Adenocarcinoma: chemotherapy (taxanes) or checkpoint inhibitor if not given previouslySquamous Cell: chemotherapy (taxanes) or checkpoint inhibitor (Keytruda, Opdivo, Tecentriq) if not given previouslyWhat if the patient already received a checkpoint inhibitor and
Slide 9: The Big Challenge: Most NSCLC patients don't respond to checkpoint inhibition
The Big Challenge:Most patients with NSCLC don’t respond to checkpoint inhibition
Slide 10: Even ideal patients don't all respond to checkpoint inhibitors
Even the “ideal” pts (PD-L1 ≥ 50%) don’t all respond to checkpoint inhibitors Reck M et al. N Engl J Med 2016;375:1823-1833
Slide 11: Considerable Unmet Need in All Lines of Therapy
Considerable Unmet Need in All Lines of Therapy In the PDL-1 intermediate (1-50%) patients the response rate is lower: ~20-25% In the PDL-1 negative (<1%) patients the response rates are < 10%And patients who do respond are not curedThey eventually get worse and die from NSCLCReasons for failure of
Slide 12: Immunotherapy Combinations
Immunotherapy Combinations Improving response rates and response duration will require IO combinations Existing combinations, such as Opdivo-Yervoy are significantly more toxic than Opdivo monotherapyImmune-related toxicities include pneumonitis, colitis, rashes, hepatitis, nephritis, encephalitis a
Slide 13: Cancer Immunity Cycle (continued)
Cancer Immunity Cycle (continued) Infiltration of T cells into tumorsLFA1/1CAM1SelectinsVEGFEndothelin B receptor 5 Trafficking ofT cells to tumors 4 CX3CL1CXCL9CXCL10CCL5 Recognition of cancer cells by T cellsT cell receptorReduced pMHC on cancer cells 6 Killing of cancer cells IFN-γT cell granule
Slide 14: What might a therapeutic vaccine like HS-110 do?
14 What might a therapeutic vaccine like HS-110 do?Generate CD8+ cells (TILs) that penetrate tumors and make them “hot” CD8+ (TIL+) patients may respond to anti-PD-(L)1 CD8- (TIL-) patients may not respond to anti-PD-(L)1 Teng et al., 2015 Can ResGettinger et al., 2015 JCO Hypothesis Combining Thera
Slide 15: Biopsies from the DURGA Trial: TIL Infiltration and Clinical Response
Baseline Week 10 Biopsies from the DURGA Trial: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%)
Slide 16: Previous lung cancer vaccines were not designed to elicit robust CD8+ response
Previous lung cancer vaccines were not designed to elicit a robust CD8+ T-cell response
Slide 17: Introducing gp96 - The Immune System's Swiss Army Knife
17 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) A Natural “Molecular Warning System” Gp96 “chaperones” newly-created proteins to the cell membrane where they are released and em
Slide 18: Heat's gp96 ImPACT Therapy: 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 the gp96 chaperoneThis process mimics ne
Slide 19: Heat Biologics ImPACT Mechanism of Action
19 Heat Biologics ImPACT Mechanism of ActionJeff Hutchins PhDChief Scientific OfficerFebruary 28, 2018
Slide 20: ImPACT/ComPACT Manufacturing
20 ImPACT/ComPACT Manufacturing
Slide 21: ImPACT: Immune Pan-antigen Cytotoxic Therapy
21 ImPACT: Immune Pan-antigen Cytotoxic Therapy
Slide 22: Successful Immuno-oncology: A Legged Stool
Successful Immuno-oncology: A 3 Legged Stool 22
Slide 23: ImPACT Generates an Adaptive Immune Response
ImPact Generates an Adaptive Immune Response Secretion of gp96-Ig carrying tumor specific proteins represented on the patients tumor.Activation of APCs (TLR2/4) and cross- presentation of antigens (CD91).Specific T-cell receptor engagement.Clonal Expansion of Tumor Antigen Specific T cells. 23
Slide 24: Clinical Proof of Mechanism in NSCLC
Clinical Proof of Mechanism in NCSLC 24 Increased levels of CD8+ T cells deep into the tumorTumors with no previous immune activation made highly activeAssociation with radiographic clinical response Histopathological evidence that HS-110 is turning COLD tumors HOT
Slide 25: ImPACT + Opdivo Combination Therapy
25 ImPACT + Opdivo Combination Therapy The potential to improve clinical responses and survival, without additional toxicity
Slide 26: Strong support for our clinical approaches
Strong support for our clinical approaches Pre-clinical Data of T-cell Expansion 26 Source: Fromm et al. Society for Immunotherapy of Cancer Annual Meeting, 2016 CD8+ T-cell Expansion Higher T-cell responses observed in mice treated with ImPACT aloneImPACT boosted CD8+ T-cells to even higher levels
Slide 27: Heat Biologics DURGA Interim Data Review
27 Heat Biologics DURGA Interim Data ReviewGeorge Peoples MD FACSChief Medical OfficerFebruary 28, 2018
Slide 28: HS-110-102 DURGA Trial
HS-110-102 DURGA Trial Objective Evaluate objective response rate of HS-110 with a PD-1 checkpoint inhibitor (nivolumab) Design Single arm multicenter trial of up to 120 patientsCohort analysis based on histology, prior checkpoint inhibitor therapy, TIL levels and PD-L1 expression Endpoints Objectiv
Slide 29: DURGA Schema
DURGA Schema X = CT Scan = Biopsy (or recent archival tissue at baseline) KEY: Nivolumab: HS-110: Biopsies: CT Scans: Timepoint:
Slide 30: Pre-Specified Patient Populations Analyzed
Pre-Specified Patient Populations Analyzed ITT (n=35)The Intent-to-Treat Population includes all patients enrolled into the study PP (n=26)The Per Protocol Population includes patients who have received at least 6 doses of HS-110 and a pre/post treatment tumor assessment 3 patients died before compl
Slide 31: ImPACT (HS-110) Safety Profile to Date
ImPACT (HS-110) Safety Profile to Date
Slide 32: Primary Efficacy Analysis Population
Primary Efficacy Analysis Population Objective Response Rate (RECIST 1.1) Disease Control Rate (RECIST 1.1) ITT (n=35) 17% 40% PP (n=26) 23% 50% ORR: Objective Response Rate is defined as the % of patients who have reached Partial Response (PR) per RECIST 1.1 which requires a 30% reduction in the su
Slide 33: Best Target Lesion Response
Best Target Lesion Response Change from Baseline (%) All evaluable ITT patients with a baseline and on-treatment scan (n=27) ORR (26%) and disease control (67%)
Slide 34: Durable Target Lesion Response
Durable Target Lesion Response Change from Baseline (%) All enrolled patients (ITT) with a baseline and on-treatment scan Days From First Dose All evaluable ITT patients with a baseline and on-treatment scan (n=27) Overall responses are durable and long lasting (> 6 months)
Slide 35: ITT Overall Survival: Encouraging and Still Maturing
ITT Overall Survival: Encouraging and Still Maturing ITT survival curve has not yet reached medianm(OS) of nivolumab alone = 12.2 months mOS nivolumab12.2 months* *N Engl J Med 2015; 373: 1627-1639
Slide 36: PP Overall Survival: Encouraging and Still Maturing
PP Overall Survival: Encouraging and Still Maturing PP survival curve has not yet reached medianm(OS) of nivolumab alone = 12.2 months mOS nivolumab12.2 months* *N Engl J Med 2015; 373: 1627-1639
Slide 37: Target Lesion Response Based on Initial TIL Status
Target Lesion Response Based on Initial TIL Status Change from Baseline (%) Evaluable ITT Population Change from Baseline (%) High TIL Low TIL HS-110 shows effect in low TIL “cold tumor” patients who typically do not respond well to PD-1 inhibitors4 of 9 achieved a partial clinical response
Slide 38: Durable Target Lesion Responses Based on Initial TIL Status
Durable Target Lesion Responses Based on Initial TIL Status Low TIL High TIL Change from Baseline (%) Tumor Type at Baseline Evaluable ITT Population Days from First Dose Durable responses (> 6 months) observed in difficult-to-treat low TIL “cold” patients
Slide 39: Target Lesion Response Based on Initial PD-L1 Status
Target Lesion Response Based on Initial PD-L1 Status Change from Baseline (%) Evaluable ITT Population Change from Baseline (%) >1% PD-L1 Tumor Type at Baseline <1% PD-L1 Tumor Type at Baseline High PD-L1 Low PD-L1 HS-110 shows effect in low PD-L1 patients, who typically do not respond to checkpoint
Slide 40: Durable Target Lesion Responses Based on Initial PD-L1 Status
Durable Target Lesion Responses Based on Initial PD-L1 Status Change from Baseline (%) 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 Durable responses observed in difficult-to-treat low PD
Slide 41: ELISPOT Activity and Survival
ELISPOT Activity and Survival 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
Slide 42: Summary of Interim Data
Summary of Interim Data Tumor shrinkage and disease control demonstrated in a majority of evaluable patientsOverall responses are durable and long lastingWhile survival data is still maturing, the median overall survival has not yet been reachedHS-110 shows durable responses in difficult-to-treat lo