Tscan Therapeutics, Inc. · NASDAQ:TCRX
Tscan Therapeutics — Investor Presentation (June 2023)
61 slides from Tscan Therapeutics's investor presentation, June 2023
Slide 1: Unleash Immunity
Unleash Immunity Investor Presentation June 2023 1
Slide 2: Disclaimers and forward-looking statements
Disclaimers and forward-looking statements This presentation and the accompanying discussion contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding the Company’s plans, prog
Slide 3: TScan: A fully integrated, next-generation TCR-T cell company
TScan: A fully integrated, next-generation TCR-T cell company Transformative platform Heme Program to prevent relapse In-house GMP enables rapid Discovery following allogeneic HCT Manufacturing using non- of Targets and TCRs for • First patient dosed; Phase 1 multi-site viral vectors engineered T ce
Slide 4: Amgen partnership builds value in autoimmune disease
Amgen partnership builds value in autoimmune disease • Multi-year collaboration uses TargetScan to identify targets recognized by CD4+ T cells in patients with Crohn’s disease; option to expand collaboration in ulcerative colitis • Amgen developing modalities to create novel therapeutics using ident
Slide 5: TargetScan screening extended to class II HLAs to identify targets of CD4+ T cells
TargetScan screening extended to class II HLAs to identify targets of CD4+ T cells mediating many autoimmune diseases Class I HLAs present antigens to CD8+ T-cells relevant for TScan oncology program and select autoimmune diseases Class II HLAs present antigens to CD4+ effector and regulatory T cell
Slide 6: TScan's oncology programs sequentially build value
TScan’s oncology programs sequentially build value Target heterogeneity • Melanoma >100k • NSCLC • Head & Neck • Ovarian >15k HPV+ solid tumors ~7k Market size Heme malignancy program Number of TCRs TScan Therapeutics, Inc. 6
Slide 7: Platform delivers broad proprietary pipeline
Platform delivers broad proprietary pipeline PROGRAMS (TARGET) HLA Type Indications Discovery Lead Optimization IND-Enabling Phase 1 Phase 2/3 Hematologic Malignancies TSC-100 (HA-1) HLA-A*02:01 AML, MDS, ALL TSC-101 (HA-2) HLA-A*02:01 Solid Tumors HLA-A*02:01 TSC-200 (HPV16) HLA-B*07:02 HLA-C*07:02
Slide 8: Steady value-generating data flow across clinical programs
Steady value-generating data flow across clinical programs Initiate registration trial Heme Program Complete Phase 1 dosing 2-year relapse data MRD, donor chimerism, & relapse data 6- & 12-month Establish recommended relapse data Enroll patients in all 3 2025 arms of trial Phase 2 dose Safety and bi
Slide 9: Clinical Programs: Hematologic Malignancies
Clinical Programs: Hematologic Malignancies 9
Slide 10: 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
Slide 11: Growing unmet transplant need in myeloid leukemias
Growing unmet transplant need in myeloid leukemias Number of Allogeneic HCTs in Key TSC-100 Program Indications ~7,000 patients annually in the U.S. 6.8k undergo allogeneic transplant (HCT) 7000 ALL 6000 5.6k HCT use has been increasing ~6% per year Annual Allo-HCT (U.S.) MDS on average for the past
Slide 12: Most cell therapy trials in AML are in the pre-transplant setting
Most cell therapy trials in AML are in the pre-transplant setting, where success increases our addressable market Pre-Transplant Peri/Post-Transplant Number of clinical programs Transplant Relapse Post-HCT Add-On Prevention Relapse Tx Key: TCR-T TScan eHSC/CAR-T 44 2 5 1 Sel Exp γδT/NK Vaccine Treg
Slide 13: Current US addressable market for heme program of 3,000+ patients could more than double
Current US addressable market for heme program of 3,000+ patients could more than double with additional HLAs and changes in transplant practice Ability to achieve remission is expected to improve with the ~6 K advent of novel therapies & (~17%) TSC100/101 is expected to ~7 K increase rate of HCT in
Slide 14: Eliminate residual cancer by targeting blood-specific antigens present in the patient but not the donor
Eliminate residual cancer by targeting blood-specific antigens present in the patient but not the donor PATIENT HA-1 positive Cancer HA-1 Residual cell negative Conditioning Residual cancer HA-1 therapy cancer X CURE positive Normal Normal blood cell blood cell DONOR HA-1 TCR Stem Hematopoietic cell
Slide 15: TSC-100 and TSC-101 address 40% of patients undergoing allogeneic HCT
TSC-100 and TSC-101 address 40% of patients undergoing allogeneic HCT TSC-100 TSC-101 (HA-1 TCR-T) (HA-2 TCR-T) HA-1- or HA-2-positive 1400 40% of allo-HCT survival % Cancer cell survival Survival 700 HA-1 Targetcell 200 Cancer HA-2 100 %% 0 0 50 100 Time Time (Hours) (hours) Time (hours) TScan Ther
Slide 16: Hematologic malignancy program multi-arm Phase 1 clinical trial open for enrollment
Hematologic malignancy program multi-arm Phase 1 clinical trial open for enrollment Inclusion Criteria: Reduced Intensity Conditioning; Haploidentical donor transplant Treatment Arms Control Arm Patient HLA-A*02:01 positive Patient HLA-A*02:01 negative (~42% US pop) (~58% US pop) Patient HA-1 positi
Slide 17: Key biomarkers measure residual leukemia or residual patient-derived blood cells
Key biomarkers measure residual leukemia or residual patient-derived blood cells as surrogates of efficacy Minimal Residual Disease (MRD) POST-TRANSPLANT PATIENT Mixed donor cell chimerism Residual Conventional Leukemia Conventional • MRD by flow cytometry (HA-1-positive) • STR assay • Sensitivity ~
Slide 18: AML, MDS, and ALL transplant patients eligible for TScan trial
AML, MDS, and ALL transplant patients eligible for TScan trial Hematopoietic Cancer Induction Consolidation Donor Pre-transplant Cell TSC-10X TSC-10X diagnosis chemo chemo leukapheresis conditioning Transplant Dose 1 Dose 2 remission remission ~21 days 40 days Hematopoietic cell transplant TScan the
Slide 19: Clinical Programs: Solid Tumor Program
Clinical Programs: Solid Tumor Program 19
Slide 20: TScan platform was deployed to understand, exploit, and enhance how T cells recognize and fight cancer
TScan platform was deployed to understand, exploit, and enhance how T cells recognize and fight cancer THE CHALLENGE NATURE’S SOLUTION Cancer cells T cells CD8+ CD4+ Heterogeneous target expression Diverse repertoire of CD4+ and CD8+ T cells HLA loss What do T cells naturally recognize and how can w
Slide 21: T cells are Nature's most effective way to kill cancer cells
T cells are Nature’s most effective way to kill cancer cells Everyone has six ~90% of people in the U.S. class I HLA alleles are positive for at least one of the top 6 class I HLAs Tumor cell Chromosome 6 Mother Father % people positive A*01:01 A*02:01 for each HLA type C*08:01 C*15:01 HLA class I B
Slide 22: TScan is building an ImmunoBank of TCRs to enable enhanced, multiplexed TCR-T cell therapy
TScan is building an ImmunoBank of TCRs to enable enhanced, multiplexed TCR-T cell therapy HLA Type HLAs Targets Profile Tumor Customized Cancer Patient Multiplexed Healthy Individual TCR-T Therapy ImmunoBank of therapeutic TCRs • Engineer T cells with potent, anti-cancer TCRs • Enhance T cells to o
Slide 23: Platform enables discovery and manufacturing of a broad range of enhanced TCR-T candidates
Platform enables discovery and manufacturing of a broad range of enhanced TCR-T cell therapy 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, 10
Slide 24: In-house non-viral manufacturing delivers customized, enhanced TCR-T cells to patients
In-house non-viral manufacturing delivers customized, enhanced TCR-T cells to patients Leukapheresis Transport to Isolate T cells TScan Infuse patient with Transport Engineer T cells ImmunoBank engineered T cells to Hospital Transposon/transposase system enables lower COGs, faster development times,
Slide 25: TScan solution is to develop enhanced, multiplexed TCR-T
TScan solution is to develop enhanced, multiplexed TCR-T TScan’s solution for increasing duration of response Prevent Prospectively Increase Enhance relapse select patients response rates persistence 1 Multiplexed TCR-T 2 Target and HLA LOH 3 CD8a/b 4 DN-TGFbRII ImmunoBank TScan Therapeutics, Inc. 2
Slide 26: Target or HLA loss leads to TCR-T resistance in solid tumors
Target or HLA loss leads to TCR-T resistance in solid tumors Prevent 1 relapse Tumor cell HLA lost HLA Target lost CD8 Target TCR T cell TScan Therapeutics, Inc. 26
Slide 27: If the target is missing or lost, the patient is likely to experience a partial response followed by relapse
If the target is missing or lost, the patient is likely to experience a partial response followed by a rapid relapse SOLID TUMOR Tumor exhibiting target heterogeneity MAGE PRAME PRAME Partial MAGE response Relapse TScan Therapeutics, Inc. 27
Slide 28: Cancer cells often lose half their HLA genes, becoming resistant to singleplexed TCR-T therapy
Cancer cells often lose half their HLA genes, becoming resistant to singleplexed TCR-T therapy Normal cells Cancer cells Chromosome 6 Chromosome 6 Mother Father Mother Father A*01:01 A*02:01 A*01:01 A*02:01Resistant to C*08:01 C*15:01 C*08:01 B*27:01TCR-T for HLA-A*02:01 B*07:02 B*27:01 B*07:02 C*15
Slide 29: HLA loss of heterozygosity (LOH) is a prevalent and overlooked mechanism of resistance
HLA loss of heterozygosity (LOH) is a prevalent and overlooked mechanism of resistance to immunotherapy • 15-30% of solid tumors exhibit clonal HLA loss • These patients CANNOT respond to singleplexed TCR-T Non-small cell lung cancer Melanoma Head & neck cancer Percentage of patients 60 57% 57% 58%
Slide 30: Multiplexed TCR-T is designed to prevent relapse due to either target or HLA loss
Multiplexed TCR-T is designed to prevent relapse due to either target or HLA loss Prevent SOLID TUMOR 1 relapse Target 1 Target 2 HLA 1 HLA 2 First Gen TCR-T Multiplexed TCR-T for Target 1 for Target 1 + Target 2 Partial response Potential for a complete response Targeting Relapse long-term remissio
Slide 31: Patients will be prospectively selected and TCRs assigned based on target expression and HLA loss
Patients will be prospectively selected and TCRs assigned based on target expression and HLA loss Prospectively 2 select patients Tumor TCR-T selection Germline Target testing HLA LOH HLA testing HLA loss detected HLA loss Target HLAs on IHC / ISH intact haplotype HLA in ImmunoBank No HLA loss Neoge
Slide 32: Engineered helper T cells provide support for cytotoxic T cells
Engineered helper T cells provide support for cytotoxic T cells and directly contribute to cytotoxicity Increase 3 Tumor cell response rate CD8 a/b Cytotoxicity Cytotoxicity TCR CD8a/b TCR CD8a/b CD4 Cytotoxic Helper T cell T cell IL-2 Increases TCR-T response rates up to 4-fold in clinic Cytokine H
Slide 33: TGFb is a key immune suppressor in the hostile tumor microenvironment
TGFb is a key immune suppressor in the hostile tumor microenvironment TGFb Enhance 4 persistence TGFβ TGFβ TGFβ DN-TGFbRII TGFBRII TGFBRII TGFBRI TGFBRI DN-TGFbRII Tumor microenvironment Cytotoxic T cell Cytotoxic T cell Suppressive Suppressive signaling signaling Cytokine production T cell prolifer
Slide 34: Adding DN-TGFbRII to TCR-T cells enables proliferation in the presence of TGFb
Adding DN-TGFbRII to TCR-T cells enables proliferation in the presence of TGFb Cytokine production Proliferation Without With Without With DN-TGFβRII DN-TGFβRII DN-TGFβRII DN-TGFβRII 5000 15,000 + TGFb 4000 IFN-g (pg/mL) + TGFb Cell count 10,000 3000 + TGFb 2000 5000 1000 + TGFb 0 0 T-cells: TSC-204
Slide 35: DN-TGFbRII enhances duration of activity in vivo
DN-TGFbRII enhances duration of activity in vivo 800 Tumor volume (mm3) Vehicle 600 Untransfected T cells 400 TSC-204-A0201 (no DN-TGFβRII) 200 TSC-204-A0201 (+ DN-TGFβRII) 0 0 10 20 30 40 50 Days post implant TScan Therapeutics, Inc. 35
Slide 36: Building the ImmunoBank
Building the ImmunoBank SCAN
Slide 37: ImmunoBank is being built with targets that exhibit high prevalence in immune-rich cancers
ImmunoBank is being built with targets that exhibit high prevalence in immune-rich cancers Head & Neck Melanoma 65 K Incident Patients in U.S. 106 K Incident Patients in U.S. 100% 90% 100% 95% 90% 75% % Patients % Patients 75% 75% 45% 50% 50% 50% 50% 50% XXX 40% 25% 25% 25% 25% 0% 0% 0% HPV16 201 20
Slide 38: Prioritized indications provide significant market opportunity
Prioritized indications provide significant market opportunity Incidence NSCLC Melanoma Head and Neck Ovarian Cervical (2021) ~200 K ~106 K ~65 K ~25 K ~15 K Systemic Tx ~145 K ~30 K ~30 K ~20 K ~5 K ~85% ~15% ~60% ~40% ~65% ~35% ~70% ~30% Plat Chemo +/- Bev Chemo ICI +/- ICI or ICI or ICI +/- Chemo
Slide 39: Program initiated with three INDs filed in 2022
Program initiated with three INDs filed in 2022 HLAs B*07:02 C*07:02 A*02:01 A*01:01 A*03:01 A*24:02 INDs HPV16 TSC-200 Q4 2022 TPlex Primary IND Target-201 TSC-201 Q4 2022 2 INDs Targets Target-202 TSC-202 PRAME TSC-203 MAGE-A1 TSC-204 Target-205 TSC-205 ImmunoBank TScan Therapeutics, Inc. 39
Slide 40: TSC-204-C0702 recognizes a novel target on MAGE-A1 discovered using TargetScan
TSC-204-C0702 recognizes a novel target on MAGE-A1 discovered from a patient using TargetScan Discovered from a patient with head & neck cancer responding to immunotherapy HS936T U266B1 MAGE-A1+ melanoma MAGE-A1+ mouse model 250 2000 Target Cell Survival (%) Tumor volume (mm3) Non-engineered Vehicle
Slide 41: HLA coverage of MAGE-A1 extended to A*02:01 by discovering TSC-204-A0201 using ReceptorScan
HLA coverage of MAGE-A1 was extended to A*02:01 by discovering TSC-204-A0201 using ReceptorScan Discovered from a healthy donor using ReceptorScan NCI H1702 U266B1 MAGE-A1+ melanoma MAGE-A1+ mouse model 250 2000 Target Cell Survival (%) Tumor volume (mm3) Non-engineered Vehicle 200 T cells 1500 150
Slide 42: Process enables facile manufacturing for multiplexed TCR-T
Process enables facile manufacturing for multiplexed TCR-T Patient apheresis product Common for PBMCs all TCRs Transposase mRNA Transposase mRNA + + TCR #1 transposon TCR #2 transposon Unique to each TCR Engineered Engineered TCR-T cells #1 TCR-T cells #2 Administer sequentially to patient TScan The
Slide 43: Dose escalation scheme provides a rapid path to testing multiplexed TCR-T in Phase 1
Dose escalation scheme provides a rapid path to testing and expanding multiplexed TCR-T in Phase 1 TSC-204-A0201 TSC-204-C0702 TSC-200-A0201 TSC-203-A0201 (MAGE-A1) (MAGE-A1) (HPV16) (PRAME) 0.5E9 0.5E9 0.5E9 0.5E9 DL1 Singleplexed 2E9 2E9 2E9 2E9 DL2 2E9 + 2E9 2E9 + 2E9 DL3 28 days T-Plex 5E9 + 5E9
Slide 44: Screening protocol pre-identifies patients for treatment
Screening protocol pre-identifies patients for treatment Patient journey Cancer 1st line 2nd line Leuka- Lympho- T-Plex T-Plex Diagnosis regimen regimen pheresis depletion dose 1 dose 2 progression progression 28 days Screening protocol Treatment protocol • Pre-screens patients for trial • Vein-to-v
Slide 45: Multiplexed TCR-T is enabled by a growing ImmunoBank
Multiplexed TCR-T is enabled by a growing ImmunoBank HLAs B*07:02 C*07:02 A*02:01 A*01:01 A*03:01 A*24:02 INDs Q4 2022 TPlex Primary IND HPV16 TSC-200 Q4 2022 2 INDs H1 2023 2 INDs Target-201 TSC-201 H2 2023 2 INDs Targets Target-202 TSC-202 Discovery 4+ INDs, 2024 PRAME TSC-203 INDs for 6 TCRs by M
Slide 46: Most impressive TCR-T results in solid tumors achieved by targeting E7 of HPV16
To date, the most impressive TCR-T results in solid tumors were achieved by targeting E7 of HPV16 Nagarsheth NB, …, Hinrichs CS (2021) Nature Medicine, 27, 419-425. TScan Therapeutics, Inc. 46
Slide 47: TScan's TCR-200-A02 shows comparable activity to NCI TCR
TScan’s TCR-200-A02 shows comparable activity to NCI TCR In vitro In vivo CaSki SCC152 SCC090 800 600 300 E:T 5:1 10:1 Target Cell Survival (%) Target Cell Survival (%) Target Cell Survival (%) 400 10:1 300 200 200 150 100 TCR-200-A2 100 NCI 0 0 0 0 50 100 0 60 120 0 70 140 Time (Hours) Time (Hours)
Slide 48: Patient eligibility is high for singleplexed dose levels
Patient eligibility is high for singleplexed dose levels, even in the early stages of building the ImmunoBank HPV16+ cancers Other solid tumors 100 100 Head & Neck-single Eligible patients (%) Eligible patients (%) 80 HPV+ tumors 80 Melanoma -single NSCLC-single 60 60 Head & Neck-multi 40 40 Melanom
Slide 49: TScan platform technologies can be deployed across many therapeutic areas
TScan platform technologies can be deployed for target and TCR discovery across many therapeutic areas INFECTIOUS AUTOIMMUNE ONCOLOGY DISEASE DISEASE Shared T cell antigen ID for Shared T cell antigen ID for a Novel antigen and clinic- vaccine development or TCR- tolerizing product modality ready TC
Slide 50: TScan's platforms can be leveraged for novel autoimmune disease target discovery
TScan’s platforms can be leveraged for novel autoimmune disease target discovery for T-cell mediated diseases Example T cell-mediated autoimmune diseases: • Ankylosing Spondylitis • Rheumatoid Arthritis INFECTIOUS DISEASE • Atopic Dermatitis • Scleroderma • Birdshot Uveitis • Sjogren’s Syndrome ONCO
Slide 51: TScan highlights
TScan highlights Transformative Platform Enables Rapid Discovery of TCRs for Engineered T Cell Therapy - Recent collaboration highlights applicability outside oncology Solid Tumor Program to Deliver Enhanced Multiplexed TCR-T - First three INDs cleared in January 2023; four more planned by EOY Hemat
Slide 52: TScan Platform
TScan Platform SCAN
Slide 53: TargetScan enables ID of the natural targets of any T cell receptor
TScan’s proprietary platform – TargetScan – enables ID of the natural targets of any T cell receptor (TCR) for TCR-T T cells expressing Genome-wide library TCR of interest of target cells Peptide-MHC Protein fragment TargetScan Proteasome can be Cells are co-cultured Protein fragments are processed
Slide 54: Adaptable target library enables discovery of diverse TCR targets using TargetScan
Adaptable target library enables discovery of diverse TCR targets using TargetScan Example TScan Oncology Library – Version 3.0 Wild-type “Dark Matter” Normal Human Proteins (e.g., ncORFs, splicing variants) Cancer- Cancer/ Testis Human Antigens specific Proteins Shared Neoantigens Targets Common SN
Slide 55: TargetScan identifies the targets of Class I TCRs
TargetScan identifies the targets of Class I TCRs Genome-wide screen of a Class I TCR known to recognize MAGE-A3 700 TargetScan correctly MAGE-A3 600 identifies the targets of TCRs FOLD-ENRICHMENT 500 400 300 TargetScan also identifies potential 200 off-targets of TCRs 100 MAGE-A6 PLD5 FAT2 0 0 100,
Slide 56: SafetyScan identifies clinically relevant off-targets
SafetyScan identifies clinically relevant off-targets Genome-wide screen of affinity-enhanced MAGE-A3 TCR FAT2 140 120 FOLD-ENRICHMENT Titin: Off-target 100 responsible for cardiotoxicity PLD5 80 MAGE-A3 ALCAM 60 MAGEB18 STRBP SNX29 40 ZNF536 Titin XM_001717344 ZNF516 Titin 20 GNRHR MAGE-A6 PHAK2 AG
Slide 57: TargetScan screening extended to class II HLAs to identify targets of CD4+ T cells
TargetScan screening extended to class II HLAs to identify targets of CD4+ T cells mediating many autoimmune diseases Class I HLAs present antigens to CD8+ T-cells relevant for TScan oncology program and select autoimmune diseases Class II HLAs present antigens to CD4+ effector and regulatory T cell
Slide 58: 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
Slide 59: TargetScan, ReceptorScan & SafetyScan used to generate ImmunoBank of de-risked antigens/TCRs
TargetScan, ReceptorScan & SafetyScan used to generate ImmunoBank of de-risked antigens/TCRs Suite of TScan ImmunoBank Discovery Technologies of Therapeutic TCRs TargetScan Targets ReceptorScan SafetyScan HLAs TScan Therapeutics, Inc. 59 59
Slide 60: T-Integrate manufacturing platform overcomes lentiviral size constraints
T-Integrate manufacturing platform overcomes lentiviral size constraints - enables production of enhanced TCR-T cells T-Integrate: Genetic Cargo Delivery System Advantages of T-Integrate non- viral delivery over lentivirus: Transposon: Contains TCR & cell enhancements • Greater cargo size enables de
Slide 61: FDA feedback provides clear path to building ImmunoBank
FDA feedback provides clear path to building ImmunoBank and developing multiplexed TCR-T Primary IND T-Plex • Clinical information • Multiplexing • X-Ref secondary INDs CLEARED Subsequent TCRs added as secondary INDs TSC-204-A0201 TSC-204-C0702 TSC-200-A0201 TSC-203-A0201 Secondary • CMC • CMC • CMC
TScan Therapeutics — Investor Presentation (June 2023) on 6ix