Marker Therapeutics, Inc. · NASDAQ:MRKR

Marker Therapeutics — Technical Presentation (February 2019)

26 slides from Marker Therapeutics's technical presentation, Feb 25, 2019

  1. Slide 1: Administering AML-directed DLIs to patients with AML or MDS Post-Allogeneic HSCT Relapse

    Administering AML - directed DLIs to patients with AML or MDS Post - Allogeneic HSCT Relapse Premal Lulla, Swati Naik, Ifigeneia Tzannou, Shivani Mukhi, Manik Kuvalekar, Catherine Robertson, Carlos A Ramos, George Carrum, Rammurti Kamble, Jasleen Randhawa, Adrian P Gee, Bambi Grilley Malcolm K Brenn

  2. Slide 2: Acute Myeloid Leukemia

    Acute Myeloid Leukemia 16% Koreth J et al, DeAngelo DJ JAMA 2009 20% Cured 80% Adverse risk/relapsed AML ~26,000/yr Allo - HSCT potentially curative Adverse risks >CR2 Complex cytogenetics Monosomy 7 MDS  AML t - AML MLL - r FLT3/DNMT3A etc

  3. Slide 3: Outcomes of AML patients post-alloHSCT

    BMT - CTN 0901. Scott et al J Clin Oncol. 2017 Outcomes of AML patients post - alloHSCT 1 - year survival after relapse: 23% 18 month Relapse rate post - HSCT MAC - SCT 14% RIC - SCT 48% Bejanyan et al BBMT 2015

  4. Slide 4: Adoptive T cell transfer

    Infusion SCT recipient Cell expansion Tumor - specific T cells Antigen specificity Blood draw Donor lymphocytes Adoptive T cell transfer SCT donor

  5. Slide 5: MultiTAA-T cells for AML/MDS

    MultiTAA - T cells for AML/MDS TAA Freq. WT1 72 - 90% PRAME 40 - 60% Survivin 90 - 100% NY - ESO1 0 - 36%

  6. Slide 6: 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

  7. Slide 7: MultiTAA Manufacture

    MultiTAA Manufacture DC Overlapping pepmixes PBMCs MultiTAA T cells

  8. Slide 8: Profile of MultiTAA-T cells

    CD3+ CD4+ CD8+ RO+/ 62L+/ CCR7 - Profile of MultiTAA - T cells % Positive cells Phenotype % Specific lysis n=24 0% 5% 10% 15% 20% 25% 30% 0% 20% 40% 60% 80% 100% RO+/ 62L+/ CCR7+ RO+/ 62L - / CCR7 - Alloreactive potential

  9. Slide 9: MultiTAA T cell specificity

    PRAME WT1 NYESO1 Survivin 0.1 1 10 100 1000 MultiTAA T cell specificity SFC/2x10 5

  10. Slide 10: MultiTAA T cell specificity and line clones

    PRAME WT1 NYESO1 Survivin 0.1 1 10 100 1000 MultiTAA T cell specificity SFC/2x10 5 Line clones 1 10 100 1000 10000 100000 # of clones mean = 5382 clones (1697 – 16227) n=12

  11. Slide 11: Phase I trial - ADSPAM AML/MDS

    Any patient with AML/MDS post allo - HSCT Phase I trial - ADSPAM AML/MDS patients  30 days post allo - HSCT AML/MDS patients  30 days post allo - HSCT GROUP B – Active disease GROUP A - Adjuvant DL1 5x10 6 cells/m 2 DL2 1x10 7 cells/m 2 DL3 2x10 7 cells/m 2 Dose Escalation Donor - derived multiTAA

  12. Slide 12: Clinical trial: Current status

    Clinical trial: Current status 27 patients (24 AML and 3 MDS) Patients Enrolled: 20 patients (0.5 - 2x10 7 cells/m 2 ) Patients Treated: Grade II or lesser Grade III 3 (all grade I elevation in LFTs 1 grade III LFT elevation (resolved with 0.5 mg/kg prednisone)

  13. Slide 13: Patient characteristics, Group A

    ID Age/ G Disease Prior Treatments 1* 57/F FLT3 - ITD CIA  Sorafenib  CIAx2  RIC - SCT 2 18/F FLT3 - ITD Bortezomib / Dauno EC  sorafenib  MAC - SCT 5 55/F MLL - r 7+3  HiDAC  MAC - SCT 6 70/F AML CR3 7+3  HiDAC  CIA  RIC - SCT - Relapse  7+3 7 53/F DNMT3a 7+3  HiDAC  MAC - SCT 10 65/M

  14. Slide 14: Outcomes – ARM A

    ID Disease Wk 4 Marrow (% blasts) Relapse? Status at last f/up 1* FLT3 - ITD 0 No, but bone relapse Treated on ARM B (9 mo’s post - infusion) 2 FLT3 - ITD 0 No Alive in CR (2.5 years) 5 MLL - r 0 No, CNS relapse, Local Rx alone Alive in CR (2 years) 6 AML CR3 0 No, CNS relapse Local Rx alone Alive i

  15. Slide 15: Patients infused – ARM B

    ID Ag e/G Disease Prior Treatments 3 70/M IDH1 mut 7+3  decitabine  IDH inhib  cutis relapse  CIA  RIC - SCT  Relapse 4 16/M MDS  AML Double cord SCT  AML Relapse  C  haplo - SCTx2  Relapse 1* 57/F FLT3 - ITD CIA  Sorafenib  CIAx2  RIC - SCT  mTAA - T cells  steroids  Relapse 8 55/M

  16. Slide 16: Outcomes – ARM B

    Outcomes – ARM B ID Disease Day 0 Week 4 Response Status at last f/up 3 IDH1 mut Skin relapse Stable skin lesion NR PD (3 months)  HiDAC chemo 4 MDS  AML 30% blasts 30% NR PD (4 weeks)  Hospice (4 mo ) 1* FLT3 - ITD 4 bone lesions All resolved CR Relapse (13 mo )  7+3 chemo 8 Induc . failure 50%

  17. Slide 17: Outcomes – ARM B

    ID Disease Day 0 Week 4 Response Status at last f/up 3 IDH1 mut Skin relapse Stable skin lesion NR PD (3 mo )  HiDAC chemo 4 MDS  AML 30% blasts 30% NR PD (4 wks )  Hospice 1* FLT3 - ITD 4 bone lesions All resolved CR CR (13 mo )  Relapse  7+3 chemo 8 Induc . failure 50% blasts 15% PR PR (4 mo

  18. Slide 18: Tracking infused clones in vivo

    Tracking infused clones in vivo Rationale: • Infused lymphocytes are not gene modified • Leukemia specific T cell clones enriched in infused line Approach: • TCR Deep sequencing of donor - T cell product • Track expansion of line - derived clones in vivo

  19. Slide 19: In vivo expansion of line clones

    In vivo expansion of line clones 0.5 1 1.5 2 By week 4 Overall Fold change (from baseline) 382 line - exclusive clones 0% 20% 40% 60% Marrow n=4 Week 4 n=12 Productive Frequency 0.5% line - exclusive clones

  20. Slide 20: Responders vs Non-responders

    0% 20% 40% 60% Preinfusion By week 4 By disease response Relapse/progress No relapse/progression Responders vs Non - responders 0 40 80 120 Pre Wk4 Responders Non - responders IFN γ ELISPOT %Repertoire n=3 n=4 n=9 n=7 SFC/5x10 5

  21. Slide 21: Clinical course – Pt#1

    Relapse Lesions - 4 FLT3mut AML received T cells as adjuvant (120 days post HSCT) Clinical course – Pt#1 SFC/5x10 5 0 2 4 6 8 10 12 14 16 pre inf 1 Week 8 Mo5 Prame NYESO1 Survivin WT1 6.1% 7% 1.8% Prednisone

  22. Slide 22: Tumor antigen expression – Pt#1

    Tumor – antigen expression WT1 H+E Clinical course – Pt#1

  23. Slide 23: Clinical course – Pt#1

    Post - T cell (Mo.11) Clinical course – Pt#1 0 5 10 15 20 Post decitabine Post - decitabine (Mo.10) 0 80 160 240 CR NYESO - 1 PRAME WT1 Survivin 0 80 160 240 Marrow • CASSSGQAYEQYF • CASSQVFPNTGELFF 1.45% 2.47% 3.07%

  24. Slide 24: Clinical course – Pt#8

    Clinical course – Pt#8 TAA expression % cells Intensity PRAME 50 - 75% 2+ Survivin <10% 2+ NYESO1 <10% 1+ WT1 <10% 1+ ANC SFC/5x10 5 Blasts%

  25. Slide 25: Summary

    Summary course - SM • Leukemia - directed donor T cell infusions are safe • Mediate anti - tumor effects • In vivo expansion superior in responders • Antigen spreading studies ongoing • Investigation of immune escape mechanisms

  26. Slide 26: Administering AML-directed DLIs to patients with AML or MDS Post-Allogeneic HSCT Relapse

    Administering AML - directed DLIs to patients with AML or MDS Post - Allogeneic HSCT Relapse Premal Lulla, Swati Naik, Ifigeneia Tzannou, Shivani Mukhi, Manik Kuvalekar, Catherine Robertson, Carlos A Ramos, George Carrum, Rammurti Kamble, Jasleen Randhawa, Adrian P Gee, Bambi Grilley Malcolm K Brenn

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