Marker Therapeutics, Inc. · NASDAQ:MRKR
Marker Therapeutics — Technical Presentation (June 2020)
40 slides from Marker Therapeutics's technical presentation, Jun 1, 2020
Slide 1: Phase 1 Trial in Pancreatic Adenocarcinoma (TACTOPS)
Phase 1 Trial in Pancreatic Adenocarcinoma (TACTOPS) JUNE 1, 2020
Slide 2: Forward Looking Statements
FORWARD LOOKING STATEMENTS This presentation includes forward-looking statements. All statements contained in this presentation other than statements of historical facts, including statements regarding future results of operations and financial position of Marker Therapeutics, Inc. (“Marker,” “we,”
Slide 3: Pancreatic Cancer Overview
Pancreatic Cancer Overview Pancreatic cancer is the seventh leading cause of global cancer deaths and the third leading cause of cancer death in the U.S. • In 2017, there were an estimated 78,969 people living with pancreatic cancer in the U.S. • Estimated new cases in 2020: 57,600 • Estimated death
Slide 4: Expected PFS in Phase 1 Pancreatic Study at Baylor College of Medicine
Expected PFS in Phase 1 Pancreatic Study at Baylor College of Medicine (BCM) We commissioned an outside statistician to analyze the expected PFS for patients consistent with the eligibility of BCM Ph1 TACTOPS study by removing patients who progressed during the first 3 months of chemotherapy alone m
Slide 5: MultiTAA-Specific T Cell Therapy in First-Line Setting
MultiTAA-Specific T Cell Therapy in First-Line Setting 5 Demonstrates benefit on top of standard-of-care chemotherapy in patients with advanced and metastatic pancreatic cancer ASCO 2020 Presentation ✓ MultiTAA-specific T cells was well tolerated when administered to patients with advanced pancreati
Slide 6: Brandon G. Smaglo, M.D., FACP
Brandon G. Smaglo, M.D., FACP Associate Professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 6 TACTOPS study conducted by Baylor College of Medicine
Slide 7: A Phase I Trial Targeting Advanced or Metastatic Pancreatic Cancer (TACTOPS)
A Phase I Trial Targeting Advanced or Metastatic Pancreatic Cancer using a Combination of Standard Chemotherapy and Adoptively Transferred Nonengineered, Multiantigen Specific T Cells in the First-Line Setting (TACTOPS) Brandon G Smaglo, MD, FACP 7
Slide 8: Pancreatic Cancer Mortality
Pancreatic Cancer Mortality American Cancer Society Fact & Figures 2018 Trends in Age-adjusted Cancer Death Rates, Females, US, 1930-2015 Trends in Age-adjusted Cancer Death Rates, Males, US, 1930-2015 Colon & rectum Uterus† Stomach Breast Lung & bronchus Rate per 100,000 male population 100 80 60 4
Slide 9: ACCORD-11: FOLFIRINOX
ACCORD-11:FOLFIRINOX • First line option for metastatic disease • Toxic • Not all patients can tolerate • Cannot continue indefinitely • mOS 11.1 months • mPFS 6.4 months Conroy T, et al. N Engl J Med 364:1817; 2011. 9
Slide 10: MPACT: gemcitabine/nab-paclitaxel
MPACT:gemcitabine/nabpaclitaxel • First line option for metastatic disease • Thought of as less toxic • mOS 8.5 months • mPFS 5.5 months Von Hoff DD, et al. N Engl J Med 369:1691;2013. 10
Slide 11: Pancreatic Cancer: Treatment
Pancreatic Cancer: Treatment • Combination chemotherapy (FFX or G/A) – Non-chemotherapy options very limited • Side effects – Cumulative: fatigue, neuropathy, cytopenias – Repetitive: nausea, vomiting, diarrhea – Distressing: alopecia, cold-hypersensitivity • T cell therapy options attractive for ex
Slide 12: Adoptive T cell transfer
Patient Adoptive T cell transfer Infusion Tumor-specific T cells Antigen Specificity Blood draw PBMCs 12
Slide 13: T cell therapy for pancreatic cancer
T cell therapy for pancreatic cancer T cell 13
Slide 14: Challenge: Tumor heterogeneity
Challenge: Tumor heterogeneity 14
Slide 15: Immune Escape
Immune Escape 15
Slide 16: Our approach
• Simultaneously target multiple TAAs • Target multiple epitopes (CD4 and CD8) within each antigen • T cells with native T cell receptor specificity (non-engineered) Our approach 16
Slide 17: MultiTAA T cell therapy for PDAC
MultiTAA T cells MultiTAA T cell therapy for PDAC MAGEA4 PRAME Survivin NYESO1 SSX2 17
Slide 18: TAA Expression in PDAC
TAA Expression in PDAC TAA Expression in PDAC Survivin >75%1-2 SSX family 3-30%3-5 MAGE-A family 20-86%3, 5-8 PRAME >30%9 NY-ESO-1 2-10%3,5 1 Koido et al, Clin Dev Immunol. 2011, 2 Dodson et al, Immunotherapy 2011, 3 Kubuschok et al, In.t J. Cancer 2004, 4 Abate- Daga et al, PLoS One. 2014, 5 Schmit
Slide 19: MultiTAA-T Cell Generation
MultiTAA-T Cell Generation Activation DC Overlapping pepmixes PBMCs MultiTAA T cells Expansion 19
Slide 20: Profile of MultiTAA-T cells: Phenotype and Safety
-10% 0% 10% 20% 30% 40% 50% Profile of MultiTAA-T cells Phenotype Safety % specific lysis 0 20 40 60 80 100 CD3 CD4 CD8 CD3- CD16+ CD56+ CD3- HLADR+ CD83+ TCM TEM % expression n=54 E:T 20:1 20
Slide 21: MultiTAA T cell specificity
0 50 100 150 200 250 Targeted antigens control Survivin NY-ESO-1 MAGE-A4 SSX2 PRAME no pepmix MultiTAA T cell specificity SFC/2x105 Specificity n=54 21
Slide 22: Clinical Trial: TACTOPS
Clinical Trial: TACTOPS • 6 Infusions, fixed cell dose (1x107/m2) - no lymphodepletion • Receive 3months chemotherapy • Procurement performed and T cells generated • If cancer controlled after 3 months, start receiving monthly T cell infusions along with ongoing chemotherapy 22
Slide 23: Clinical Trial: TACTOPS
Clinical Trial: TACTOPS • Primary endpoints – safety, feasibility • Exploratory – efficacy • 13 patients infused • Sufficient cells generated for all 6 infusions for 12 patients • 2 doses generated for the remaining patient 23
Slide 24: Radiographic CR: pt#7
6 months post multiTAA T cells 14.4mm 13.0mm 0 50 100 150 200 Baseline Peak post Survivin NYESO1 MAGEA4 SSX2 Prame 0 100 200 300 400 500 Baseline Peak post WT1 AFP MART1 MC1 MA3 MA2B MA1 SFC/2x105 SFC/2x105 Targeted antigens Non-targeted antigens Radiographic CR : pt#7 Prior to multiTAA T cells 24
Slide 25: Clinical response: pt#1
0 50 100 150 Baseline Peak post Survivin NYESO1 MAGEA4 SSX2 Prame 0 50 100 150 Baseline Peak post WT1 AFP MART1 MC1 MA3 MA2B MA1 Clinical response : pt#1 40.4mm 27.4mm 26.7mm >30% reduction of index lesion Targeted antigens Non-targeted antigens SFC/2x105 SFC/2x105 2 months post multiTAA T cells Pri
Slide 26: Clinical response: pt#3
Clinical response : pt#3 0 30 60 90 120 Baseline Peak post Survivin NYESO1 MAGEA4 SSX2 Prame 0 100 200 300 400 500 Baseline Peak post WT1 AFP MART1 MC1 MA3 MA2B MA1 SFC/2x105 SFC/2x105 23mm 32.0mm 30.2mm 47.3mm >40% reduction of index lesion 6 months post multiTAA T cells Non-targeted antigens Targe
Slide 27: Clinical response: pt#12
Clinical response : pt#12 0 20 40 60 Baseline Peak Post Survivin NYESO1 MAGEA4 SSX2 Prame 0 20 40 60 Baseline Peak Post WT1 AFP MART1 MC1 MA3 MA2B MA1 SFC/2x105 SFC/2x105 Non-targeted antigens Targeted antigens 10mm x 10mm Prior to multiTAA T cells 6 months post multiTAA T cells 27
Slide 28: Aggregate Tumor Measurements
Aggregate Tumor Measurements 0 1 2 3 4 5 6 7 8 Tumor Size (cm) Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Patient 11 Patient 12 Patient 13 3 mths ChemoTx Post #3 infusion Post #6 infusion 3 mths Post T cells 6 mths Post T cells Baseline Start
Slide 29: Radiographic CR: pt#7
Radiographic CR : pt#7 0 0.5 1 1.5 2 2.5 Tumor Size (cm) Start T-cells 1 Year Therapy 3 mths ChemoTx Baseline 29
Slide 30: Radiographic CR: pt#7
Radiographic CR : pt#7 0 0.5 1 1.5 2 2.5 Tumor Size (cm) Start T cells 1 Year Therapy 3 mths ChemoTx Post #3 infusion Post #6 infusion 3 mths Post T cells 6 mths Post T cells Baseline 30
Slide 31: Radiographic CR: pt#7
Radiographic CR : pt#7 0 0.5 1 1.5 2 2.5 Tumor Size (cm) Start T cells 1 Year Therapy 3 mths ChemoTx Post #3 infusion Post #6 infusion 3 mths Post T cells 6 mths Post T cells Baseline 31
Slide 32: Enhanced Responses
Enhanced Responses 0 1 2 3 4 5 6 7 Tumor Size (cm) Patient 1 Patient 3 Patient 12 3 mths ChemoTx Post #3 infusion Post #6 infusion 3 mths Post T cells 6 mths Post T cells Baseline Start T cells 1 Year Therapy 32
Slide 33: Arresting Progression
Arresting Progression 0 2 4 6 8 Tumor Size (cm) Patient 8 Patient 10 3 mths ChemoTx Post #3 infusion Post #6 infusion 3 mths Post T cells 6 mths Post T cells Baseline Start T cells 1 Year Therapy 33
Slide 34: Summary: Gemcitabine + Nab-paclitaxel Patients
0 3 6 9 12 15 18 21 Pt 8 Pt 6 Pt 5 Pt 1 gemcitabine + nabpaclitaxel MultiTAA T cells + Chemo Summary Chemotx Chemotx + T cells On-going chemotx Died Remain on study Progressed Patient Best RECIST response on T cell therapy 1 Partial Response 5 Progressive Disease 6 Stable Disease 8 Stable Disease Mo
Slide 35: Summary: FOLFIRINOX Patients
0 3 6 9 12 15 18 21 Pt 13 Pt 12 Pt 11 Pt 10 Pt 9 Pt 7 Pt 4 Pt 3 Pt 2 FOLFIRINOX MultiTAA T cells + Chemo Summary Months Chemotx Chemotx + T cells On-going chemotx Died Remain on study Progressed Patient Best RECIST response on T cell therapy 2 Mixed response 3 Partial Response 4 Stable Disease 7 Rad
Slide 36: CA 19-9 trends
CA 19-9 trends 0 10000 20000 30000 40000 50000 60000 70000 80000 90000 0 3 6 9 CA 19-9 (U/mL) Months pt 2 0 50 100 150 200 250 300 350 0 3 6 9 12 15 CA 19-9 (U/mL) Months pt 1 pt 3 pt 6 pt 7 pt 11 pt 12 0 500 1000 1500 2000 2500 3000 3500 4000 0 3 6 9 12 15 CA 19-9 (U/mL) Months pt 4 pt 5 pt 8 pt 9
Slide 37: Treatment Summary
Treatment Summary • No additional side effect when adding t-cell therapy • Durable cancer control with 9/13 patients exceeding historical control of overall survival • Measurable tumor responses in 4 patients 37
Slide 38: Conclusions
•Feasible to manufacture multiTAA T cells •Well tolerated •Encouraging cancer treatment results •In vivo expansion of tumor-specific T cells observed •Antigen spreading Conclusions 38
Slide 39: Future
•Encouraging effects seen with chemotherapy •Explore first line therapy in advanced cancer with earlier t-cell initiation •Refine which antigens to target Future 39
Slide 40: Acknowledgements
TRL Lab PIs Ann Leen Helen Heslop Cliona Rooney Malcolm Brenner Juan Vera QA/QC Laboratory Adrian Gee Sara Richman Natasha Lapteva Debbie Lyon April Durett Suzanne Poole Zhuyong Mei Crystal Silva-Lentz GMP Laboratory Huimin Zhang Birju Mehta Clinical Team Brandon Smaglo Yvonne Sada Benjamin Musher P
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