Tscan Therapeutics, Inc. · NASDAQ:TCRX

Tscan Therapeutics — Investor Presentation (May 2022)

39 slides from Tscan Therapeutics's investor presentation, May 2022

  1. Slide 1: Unleash Immunity: Corporate Presentation

    Unleash Immunity Corporate Presentation May 2022 TScan Therapeutics, Inc. 1

  2. Slide 2: Disclaimers and forward-looking statements

    Disclaimers and forward-looking statements This presentation and the accompanying oral presentation contain forward-looking statements. All statements other than statements of historical fact contained in this presentation, including statements regarding possible or assumed future results of operati

  3. Slide 3: TScan highlights

    TScan highlights Transformative Platform to Discover the Natural Targets of T cells Platform Enables Enhanced Multiplexed TCR-T cell Therapy Two INDs Filed in 2021; Additional INDs Planned for 2022 Strategic Target Discovery Partnership with Novartis Cash Position of $140.8 MM as of 3/31/2022 Funds

  4. Slide 4: TScan solves three key challenges of TCR-T for solid tumors

    TScan is differentiated from the competition by solving the three key challenges of TCR-T for solid tumors 1 TCR-T has shown high response rates, but limited durability Multiplex Multiplexed targets and HLAs TCR-T TGFb TScan solution: Enhance TCR-T cells with CD8a/b and TGFb trap trap TCR-T cells re

  5. Slide 5: Platform delivers broad proprietary pipeline

    Platform delivers broad proprietary pipeline Lead IND- Target Indications Discovery Optimization Enabling Phase 1 Phase 2/3 PROPRIETARY PROGRAMS Liquid Tumor Program TSC-100 HA-1 AML, MDS, TSC-101 HA-2 ALL Solid Tumor Program TSC-200 HPV16 TSC-201 Target-201 Head & Neck, TSC-202 Target-202 Cervical,

  6. Slide 6: Broad pipeline drives multiple value-creating milestones

    Broad pipeline drives multiple value-creating milestones TScan Anticipated Milestone Timeline 2021 2022 2023 Q4 - 2021 H1 - 2022 H2 - 2022 2023 Pre-clinical data on Pre-clinical data on 2 IND filings for solid Solid tumor program liquid tumor program solid tumor program tumor program clinical data Q

  7. Slide 7: TScan Platform

    TScan Platform TScan Therapeutics, Inc. 7

  8. Slide 8: Platform enables discovery and manufacturing of enhanced TCR-T candidates

    Platform enables discovery and manufacturing of enhanced TCR-T candidates ImmunoBank SafetyScan SafetyScan Screen Screen TargetScan TargetScan ReceptorScan RECEPTORSCAN Discover the natural Discover highly active target of any TCR TCRs for any target Cell (2019) 178, 1016-28 Engineer and manufacture

  9. Slide 9: Clinically active TCRs identified from expanded T cells of responders

    Clinically active TCRs are identified from expanded T cells of Head & Neck cancer patients that respond to immunotherapy Focus on patients that have exceptional T cell sequencing data for a patient with responses to immunotherapy a complete immunotherapy response 10% Ipilimumab Expanded T CELL CLONE

  10. Slide 10: Multiplexed screen identified MAGE-A1 as a target in Head & Neck patient

    Multiplexed screen identified MAGE-A1 as a target in a Head & Neck cancer patient responding to immunotherapy • Patient 32 had 60% reduction in primary tumor size following anti-PD1 and anti-CTLA4 therapy POSITIVE CONTROL NOVEL TARGET MAGE-A1 TCR Target HLA HN-P32-39 MAGEA1 C*07:02 HN-P32-41 TScan T

  11. Slide 11: TCR-204-C7 shows strong in vitro activity

    TScan’s TCR-204-C7 shows strong in vitro activity MAGEA1+ 359 TPM MAGEA1+ 191 TPM MAGEA1+ 128 TPM MAGEA1+ 25 TPM MAGEA1- 0TPM A101D HS936T A2058 H1437 C7-HEK293T TCR-204-C7 TScan Therapeutics, Inc. 11

  12. Slide 12: ReceptorScan identifies ultrahigh affinity, naturally occurring TCRs

    ReceptorScan identifies ultrahigh affinity, naturally occurring TCRs with low risk of off-target effects Key Problem TScan Solution Most naturally-occurring TCRs ReceptorScan is a high-throughput platform CHALLENGE to self antigens have low affinity that identifies the best TCR for a desired and/or

  13. Slide 13: ReceptorScan platform identifies natural high-affinity TCRs

    ReceptorScan platform identifies natural high-affinity TCRs for identified targets and desired HLA restrictions 1 Expansion of target- 2 Isolation and single-cell 3 Gene synthesis and specific CD8+ T cells sequencing of CD8+ T cells cloning of TCR libraries PBMCs from Vb Cb Vα Cα healthy donors (4-1

  14. Slide 14: Most dramatic TCR-T results in solid tumors targeted HPV E7

    The most dramatic TCR-T results to date in solid tumors were achieved by targeting E7 of HPV Before treatment 7 months Nagarsheth NB, …, Hinrichs CS (2021) Nature Medicine, 27, 419-425. “Patient 5 had metastatic anal SCC with more than 90 metastatic tumors that involved the thorax, retroperitoneum,

  15. Slide 15: TCR-200-A2 shows comparable activity to Kite-439

    TScan’s TCR-200-A2 shows comparable activity to Kite-439 HLA-A*02:01+ HPV16+ HLA-A*02:01+ HPV16+ HLA-A*02:01+ HPV16+ HLA-A*02:01- HPV16+ HLA-A*02:01+ HPV16- CaSki SCC152 SCC090 SiHa NCI-H1792 TCR-200-A2 Kite-439 * Calculated with one way ANOVA, Dunnett’s multiple comparisons test TScan Therapeutics,

  16. Slide 16: TSC-200-A2 shows superior effector function to comparator NCI TCR

    TScan’s TSC-200-A2 shows superior effector function to comparator NCI TCR CaSki (HLA-A*02:01+ HPV16+) Cytotoxicity Cytokine production T cell proliferation Interferon-g IL-2 CD8+ T cells Granzyme B TNF-a CD4+ T cells * Calculated with one way ANOVA, Dunnett’s multiple comparisons test TScan Therapeu

  17. Slide 17: TSC-200-A2 shows activity in mouse model of HPV-positive cancer

    TSC-200-A2 shows promising activity in a mouse model of HPV-positive cancer Vehicle Non transduced T cells TSC-200-A2 (20e6 TCR-positive cells) T cell dosing day TScan Therapeutics, Inc. 17

  18. Slide 18: Vision to build a diverse ImmunoBank of TCRs

    Vision is to build a diverse ImmunoBank of TCRs to provide customized, off- the-shelf, multiplexed TCR-T HLA Type HLAs Targets Profile Tumor Customized Cancer Patient TCR Therapy Healthy Patient ImmunoBank of therapeutic TCRs Multiplexed TCR-T may overcome both tumor heterogeneity and resistance due

  19. Slide 19: T-Fish enables directed target discovery of patient-derived T cells

    T-Fish enables directed target discovery of patient-derived T cells that recognize a particular target of interest Pool of T cells from a cancer patient AIM+ AIM+ MACS FACS Target-reactive + T cell for new HLA type HEK cells expressing HLAs and target of Targets include oncogenic interest viruses, C

  20. Slide 20: T-Fish can identify T cells present at 1 part in 10,000

    T-Fish can identify T cells present at 1 part in 10,000 • Proof-of-concept conducted with T cells that recognize Nectin1 • Nectin1-reactive T cells (6-192) spiked in at varying percentages ~530-fold enrichment Efficient recovery of cells initially Cells initially present at 0.01% present at 0.01% ~5

  21. Slide 21: EpitopeScan enables rapid identification of precise epitope

    EpitopeScan enables rapid identification of the precise epitope of target- reactive T cells Targets of interest (e.g., oncogenic viruses, C/TAs, etc.) N C Fully mapped Target-reactive novel epitope T cell for new HLA High-density tiling at single amino acid resolution Current EpitopeScan library til

  22. Slide 22: Discovery technologies used to generate ImmunoBank

    TargetScan, ReceptorScan, EpitopeScan, T-Fish, & SafetyScan used to generate ImmunoBank of de-risked antigens/TCRs Suite of TScan ImmunoBank Discovery Technologies of Therapeutic Antigens/TCRs TargetScan Targets ReceptorScan T-Fish EpitopeScan SafetyScan HLAs TScan Therapeutics, Inc. 22

  23. Slide 23: T-Integrate technology overcomes lentiviral constraints

    T-Integrate technology overcomes lentiviral constraints - enables TCR-T multiplexing and T cell enhancements T-Integrate: Genetic Cargo Delivery System Advantages of T-Integrate non-viral delivery over Transposon: lentivirus: Contains TCR & cell enhancements • Greater cargo size enables delivery of

  24. Slide 24: Clinical Programs: Liquid Tumor Program

    Clinical Programs: Liquid Tumor Program TScan Therapeutics, Inc. 24

  25. Slide 25: TCR-T uniquely addresses myeloid leukemias

    TCR-T uniquely addresses myeloid leukemias Non-B Cell Malignancies ~40,000 cases/year Not addressable by CAR-T therapy Transplant is considered curative for many AML and is expected to remain standard of care ~40% of patients relapse post-transplant with MDS few treatment options (~90% mortality wit

  26. Slide 26: Growing unmet transplant need in myeloid leukemias

    Growing unmet transplant need in myeloid leukemias Number of Allogeneic HCTs in Key TSC-100 Currently ~7,000 patients annually in the Program Indications U.S. undergo allogeneic transplant ALL Transplant use has been increasing ~7% MDS per year for the past 20 years AML Market anticipated to grow as

  27. Slide 27: Eliminate residual cancer by targeting blood-specific antigens

    Eliminate residual cancer by targeting blood-specific antigens PATIENT HA-1 positive Cancer HA-1 Residual cell negative Conditioning cancer HA-1 therapy X CURE positive Immune cell DONOR HA-1 TCR Stem Hematopoietic cell cells Stem T cell HA-1 cell transplant negative T cell TCR T-cell therapy TScan

  28. Slide 28: TSC-100 has superior activity relative to comparator HA-1 TCR

    TSC-100 has superior activity relative to comparator HA-1 TCR Cytotoxicity Cytokine Production T Cell Proliferation Interferon-g CD8+ T cells **** ** ** HA-1-positive % Target Cell Survival IFN-g (pg/mL) 25% of allo-HCT HA-1 Hours % Target Cell Survival (90 hours) Granzyme B CD4+ T cells * *** ** **

  29. Slide 29: TSC-101 is highly active and comparable to TSC-100

    TSC-101 is highly active and comparable to TSC-100 Cytotoxicity Cytokine Production T cell Proliferation Interferon-g IL-2 CD8+ T cells HA-1- or HA-2-positive 40% of allo-HCT HA-1 Granzyme B TNF-a CD4+ T cells HA-2 TScan Therapeutics, Inc. 29

  30. Slide 30: TSC-100 SafetyScan screen shows no material off-targets

    TSC-100 SafetyScan screen shows no material off-targets Off-target SafetyScan Data 400 Fold enrichment HA-1 300 on-target hits 200 Positive control 100 0 0 100K 200K 300K 400K 500K 600K • SafetyScan revealed no significant off-targets for the TSC-100 TCR • TSC-100 demonstrated no cross-reactivity or

  31. Slide 31: Liquid tumor program on track for multi-arm Phase 1 trial

    Liquid tumor program on track for multi-arm Phase 1 trial Treatment arms RIC Haploidentical donor transplant + TSC TCR-T Patient A*02:01 positive (~42% US pop) Control arm RIC Haploidentical donor transplant alone Patient HA-1 positive Patient HA-1 negative, (~60%) HA-2 positive Patient A*02:01 nega

  32. Slide 32: Clinical Programs: Solid Tumor Program

    Clinical Programs: Solid Tumor Program TScan Therapeutics, Inc. 32

  33. Slide 33: Multiplexing overcomes the problem of tumor heterogeneity

    Multiplexing overcomes the problem of tumor heterogeneity SOLID TUMOR Target 2 Target 1 First Gen TCR-T for Target 1 Multiplexed TCR-T for Target 1 + Target 2 Partial response Potential for a complete response Targeting Relapse long-term remission or cure TScan Therapeutics, Inc. 33

  34. Slide 34: Multiplexing addresses resistance and expands market

    Multiplexing addresses resistance and expands market HLAs A Multiplexing across targets Targets C A addresses the problem of tumor heterogeneity B Multiplexing across HLAs prevents resistance due to HLA B loss / mutation Multiplexing across both is the C ultimate solution, but requires a well-popula

  35. Slide 35: Building pipeline to enable multiplexed therapy in solid tumors

    We are building our pipeline to enable multiplexed therapy in solid tumors HLAs Frequency of HLA positivity in the U.S. C*07:02 B*07:02 A*02:01 A*01:01 A*24:02 A*03:01 HLA Allele Population Targets percentage HPV16 INDs HLA-A*01:01 23% HLA-A*02:01 42% Target 201 H2, 2022 HLA-A*03:01 21% Target 202 H

  36. Slide 36: Programs address major unmet needs in 'hot' solid tumors

    Programs address major unmet needs in ‘hot’ solid tumors Head & Neck Melanoma 66 K Incident Patients in U.S. 100 K Incident Patients in U.S. 100% 90% 100% 95% 90% 75% % Patients % Patients 75% 75% 45% 50% 50% 50% 25% 25% 50% XXX 25% 25% 0% 0% 0% HPV16 TSC-201 TSC-202 PRAME MAGE-A1 HPV16 TSC-201 TSC-

  37. Slide 37: HPV TCR shows superior activity vs. comparator TCR

    HPV TCR shows superior activity vs. comparator TCR Cytotoxicity Cytokines T cell proliferation CD8+ T cells Interferon-g TSC-200 * • HPV is an oncogenic virus found in many solid tumors • A Phase I trial at the NCI showed an ORR of 50% with a single HPV TCR CD4+ T cells IL-2 • TScan will develop TSC

  38. Slide 38: MAGE-A1 TCR discovered from patient responding to ICI

    MAGE-A1 TCR discovered from patient responding to ICI Rx TSC-204 Cytotoxicity • Discovered from a patient with Head & Neck Cancer cells alone cancer who responded to immunotherapy • MAGE-A1 is a cancer testis antigen Nonengineered T cells expressed in many solid tumors • TSC-204 recognizes a novel a

  39. Slide 39: TScan highlights

    TScan highlights Transformative Platform to Discover the Natural Targets of T cells Platform Enables Enhanced Multiplexed TCR-T cell Therapy Two INDs Filed in 2021; Additional INDs Planned for 2022 Strategic Target Discovery Partnership with Novartis Cash Position of $140.8 MM as of 3/31/2022 Funds

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