Tscan Therapeutics, Inc. · NASDAQ:TCRX
Tscan Therapeutics — Investor Presentation (April 2024)
47 slides from Tscan Therapeutics's investor presentation, Apr 16, 2024
Slide 1: TScan Therapeutics April 2024
Exhibit 99.2 TScan Therapeutics April 2024
Slide 2: Disclaimers and forward-looking statements
Disclaimers and forward-looking statements This presentation and the accompanying discussion contain forward-looking TScan’s plans relating to developing and commercializing its TCR-T therapy statements within the meaning of the Private Securities Litigation Reform Act of candidates, if approved, in
Slide 3: How do we aim to cure cancer?
How do we aim to cure cancer? PROBLEM PROVEN SOLUTIONS • Cancer is heterogeneous Treat cancer when it is 1 • Cancer is rapidly evolving at its lowest HEME PROGRAM Tumor Treat with multiple 2 agents simultaneously SOLID TUMOR PROGRAM Blood vessel 3 CONFIDENTIAL
Slide 4: TScan is building on the remarkable success of immunotherapy
TScan is building on the remarkable success of immunotherapy What we have learned from immuno-oncology Our proposed solution is TCR-T cell therapy Genetically reprogramming T cells with Checkpoint therapy (Keytruda®, Yervoy®, Opdivo®) T-cell receptors leverages the body’s natural mechanism for fight
Slide 5: T-cells search for and kill abnormal cells
T-cells search for and kill abnormal cells Normal cell Cancer cell T-cell T-cell TCR Tumor-specific antigen Self antigen HLA HLA Healthy cell Cancer cell Healthy cells display normal self-antigens that do Tumor-specific antigens activate circulating T-cells not activate circulating T-cells to kill c
Slide 6: TScan is targeting the most frequent HLAs to address a broad patient population
TScan is targeting the most frequent HLAs to address a broad patient population Everyone has six ~90% of people in the U.S. are class I HLAs positive for at least one of the top six HLA types Chromosome 6 Tumor cell Mother Father % people positive A A for each HLA type C C B B United HLA type Europe
Slide 7: TScan is a fully integrated, next-generation TCR-T cell therapy company
TScan is a fully integrated, next-generation TCR-T cell therapy company Proprietary discovery platform Rapidly-growing oncology pipeline T-cell receptor (TCR) Clinical-phase programs in heme Rapid discovery of targets and TCRs and solid tumor malignancies In-house GMP manufacturing Broad therapeutic
Slide 8: Platform delivers broad proprietary pipeline
Platform delivers broad proprietary pipeline HLA type Indications Programs (target) Discovery Lead optimization IND-enabling Phase 1 Phase 2/3 TSC-100 AML, HLA-A*02:01 (HA-1) HEMATOLOGIC MDS, MALIGNANCIES TSC-101 ALL HLA-A*02:01 (HA-2) Head & Neck, HPV+ TSC-200 HLA-A*02:01 Cervical, SOLID TUMORS (HP
Slide 9: TScan programs are designed to sequentially build value
TScan programs are designed to sequentially build value • Melanoma • NSCLC >100k • Head & Neck • Ovarian ~15k + HPV solid tumors U.S. market size ~7k Heme malignancy program Time to market 9 CONFIDENTIAL Target heterogeneity
Slide 10: Steady value-generating data flow planned across clinical programs
Steady value-generating data flow planned across clinical programs Heme Program Fully enroll clinical study Launch pivotal study Report updated data Open expansion cohorts at at TANDEM RP2D One-year data on initial Two-year relapse data patients H1 2024 H2 2024 YE 2024 2025 Initiate multiplexed dosi
Slide 11: Heme malignancies: targeting residual disease to prevent relapse
Heme malignancies: targeting residual disease to prevent relapse in patients undergoing allogeneic HCT
Slide 12: Relapse after hematopoietic cell transplant remains an unmet need
Relapse after hematopoietic cell transplant remains an unmet need AML, MDS, some ALL not ~35,000 addressed by CAR-T due cases/year US to shared antigens with normal blood cells Targeting antigens 1 mismatched between ~7,350 Allogeneic hematopoietic undergo transplant patients and donors can cell tra
Slide 13: TSC-100 and TSC-101 are engineered TCR-T cells to prevent relapse
TSC-100 and TSC-101 are engineered TCR-T cells designed to eliminate residual recipient cells and prevent relapse following HCT POST-TRANSPLANT PATIENT PATIENT HA-1 or HA-2 positive Cancer Residual HA-1 or HA-2 cell cancer Residual negative Conditioning cancer therapy HA-1 or HA-2 positive CURE Resi
Slide 14: Multi-arm Phase trial has reached highest dose level
Multi-arm Phase 1 trial for TSC-100 & TSC-101 has reached highest dose level AML, MDS, ALL undergoing haploidentical transplant with reduced intensity conditioning Control Arm Treatment Arms Dose Day Level (HLA-A*02:01 negative) (HLA-A*02:01 positive: 42%) 21 61 6 5×10 /kg 1 Transplant Transplant Tr
Slide 15: Risk factors well-balanced between control-arm and treatment-arm patients
Risk factors well-balanced between control-arm and treatment-arm patients Control Arm TSC-100 TSC-101 TSC-101 TSC-101 Control Control Control Control Control Control Control Control TSC-100 TSC-100 TSC-100 TSC-100 TSC-101 TSC-101 Patient ID DL2- DL3- 1 2 3 4 5 6 7 8 DL1 DL2 DL3 DL3 DL1 DL2 supp supp
Slide 16: Donor chimerism serves as an early surrogate of efficacy
Donor chimerism serves as an early surrogate of efficacy Post-transplant Patient Complete donor chimerism Mixed donor chimerism 1,2 1,2 (low risk of relapse ) (high risk of relapse ) Malignant, patient-derived blood cell Nonmalignant, patient-derived blood cell Normal, donor- Normal, donor- derived
Slide 17: All patients on the treatment arm remain relapse-free
All 8 patients on the treatment arm remain relapse-free with no detectable cancer Treatment-arm patients Control-arm patients Day TSC-100 TSC-100 TSC-100 TSC-100 TSC-101 TSC-101 TSC-101 TSC-101 Control Control Control Control Control Control Control Control post 1 2 3 4 5 6 7 8 DL 1 DL 2 DL 3 DL 3 D
Slide 18: No relapses and complete chimerism in treatment arms
No relapses and complete chimerism in cancer lineage in treatment arms Two relapses, two deaths and mixed chimerism in cancer lineage in control arm Control arm Treatment arms Donor chimerism in control arm: C R D3+ ecipi an en d t CD3 chime 3+r su ism bsets Donor chimerism in treatment arms: Recipi
Slide 19: Early data from ACROBAT trial show low risk of relapse
Early data from ACROBAT trial* show low risk of relapse in patients not showing increasing mixed chimerism 1 Chimerism by ultra-sensitive NGS assay • Early data from the ACROBAT trial suggest a 1 relapse out of favorable prognosis for patients that rapidly 50 patients achieve and maintain complete c
Slide 20: Minimal residual disease serves as a supportive surrogate of efficacy
Minimal residual disease serves as a supportive surrogate of efficacy Post-transplant patient Minimal Residual Disease (MRD) Nonmalignant, patient-derived Next-generation sequencing blood cell • Deep sequencing of leukemia- associated genes (centrally) • Sensitivity 0.05-0.1% Malignant, MRD+ patient
Slide 21: All treated patients to date achieved MRD negativity
* All treated patients to date achieved MRD negativity Dose Pre-HCT 6 months 12 months level MRD Rx Disease TSC-100/TSC-101 dose Control-1 MDS # MRD-positive MDS Control-2 RELAPSE MRD-negative MDS Control-3 RELAPSE X AML Control-4 Clinical intervention # AML Control-5 Death X AML Control-6 Ongoing f
Slide 22: Very different outcomes observed for two patients with TP53-mutated MDS
Very different outcomes observed for two patients with TP53-mutated MDS Pre-HCT MRD 6 months 12 months Disease RELAPSE Death X Control-3 Del5q, Mono7, mTP53 MDS FPI (TSC-101) Del5q, mTP53 MDS HCT Feb 16, 2023 0 100 200 300 400 Time (days post-transplant) TSC-101 dose MRD-positive Complete chimerism
Slide 23: TSC-100 & TSC-101 persisted in peripheral circulation for over 12 months
TSC-100 & TSC-101 persisted in peripheral circulation for over 12 months • TSC-100 and TSC-101 TCR-T cells detected in all patients at all time points to date • Repeat dosing resulted in increased levels of circulating TCR-T cells Single dose cohorts Repeat dose cohorts Persistence of engineered T c
Slide 24: Serious adverse events were similar between treatment and control arms
Serious adverse events were similar between treatment and control arms Control-arm Highest Serious Adverse Event Post-transplant Day TSC Relatedness Patient Grade* Control 3 Cytokine release syndrome 2 +2 Not Applicable Control 4 Neck pain 3 +53 Not Applicable Control 2 Acute graft versus host disea
Slide 25: Serious adverse events were similar between treatment and control arms
Serious adverse events were similar between treatment and control arms Treatment-arm Highest Serious Adverse Event Post-transplant Day TSC Relatedness Patient Grade* TSC-100-DL3 Sepsis, respiratory failure 4 +9 Not applicable (pre-TSC) TSC-100-DL2 Pyrexia 1 +136 Not related # TSC-100-DL3 Pericardial
Slide 26: Adverse events of special interest similar between treatment and control arms
Adverse events of special interest similar between treatment and control arms All cytokine release syndrome (CRS) events occurred before TSC-100/ TSC-101 treatment Arm-Dose Level Grade* Adverse Event HCT Day of Onset Duration TSC relatedness TSC-100-DL2 Grade 1 CRS +3 2 days Not applicable (pre-TSC)
Slide 27: Significant increase in enrollment of heme trial post-TANDEM
Significant increase in enrollment of heme trial post-TANDEM SUN MON TUE WED THU FRI SAT 25 26 27 28 29 1 2 3 4 5 6 7 8 9 Feb/Mar 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 SUN MON TUE WED THU FRI SAT 1 2 3 4 5 6 7 8 9 10 11 12 13 April/May 14 15 16 17 18 19 20 21 22 23 24 25
Slide 28: Current program addresses sizable patient population
Current program addresses sizable patient population, with several global and lifecycle management opportunities 20,000 Expansion opportunities in oncology and other 15,000 malignancies Current clinical program 10,000 New TCRs/HLAs Expansion to 5,000 Europe Change in practice 0 - Increased adoption
Slide 29: Solid Tumors: Developing multiplex TCR-T to overcome tumor heterogeneity
Solid Tumors: Developing multiplex TCR-T to overcome tumor heterogeneity
Slide 30: TScan is learning from nature to understand how T cells fight cancer
TScan is learning from nature 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 Diverse repertoire expression of CD4+ and CD8+ T cells HLA loss What do T cells Hostile TME (e.g., TGFβ) natu
Slide 31: TScan is building an ImmunoBank of TCRs
TScan is building an ImmunoBank of TCRs to enable enhanced, multiplex TCR-T cell therapy Cancer patient ImmunoBank of therapeutic TCRs Customized TCR-T therapy HLAs T cells HLA Type Profile tumor Cancer cells with different HLA types and targets • Determine target and HLA expression in patient tumor
Slide 32: Target heterogeneity in solid tumors limits singleplex therapies
Target heterogeneity in solid tumors limits the efficacy of singleplex therapies Melanoma Melanoma MAGE-C2 MAGE-A4 MAGE-C2 PRAME • Treatment with a TCR-T against one target does not address the full tumor • TCR-T therapy against multiple targets may be required improve efficacy and durability 32 CON
Slide 33: Multiplex TCR-T may address heterogeneity in solid tumors
Multiplex TCR-T may address the problem of heterogeneity in solid tumors Multiplex TCR-T is designed to overcome Non-engineered T-cells TSC-203-A0201 (PRAME) target heterogeneity and HLA loss Target 1 Target 2 HLA 1 HLA 2 Singleplex Multiplex TCR-T TCR-T for Target 1 for Target 1 + Target 2 TSC-204-
Slide 34: TScan’s enhancements address the hostile tumor microenvironment
TScan’s enhancements address the hostile tumor microenvironment Enhanced TCR-T to combat the hostile tumor CD8α/β enhances cytokine production in vitro microenvironment 5000 4000 Tumor cell With CD8α/β 3000 2000 Cytotoxicity Cytotoxicity Without CD8 1000 0 Target peptide TCR CD8α/β CD8α/β TCR CD4 DN
Slide 35: Programs address targets frequently co-expressed in prevalent solid tumors
Programs address targets frequently co-expressed in prevalent solid tumors Head & Neck Melanoma 66 K Incident Patients in U.S. 100 K Incident Patients in U.S. 100 90 100 90 80 80 50 50 50 60 60 45 40 40 40 25 25 20 20 0 0 0 HPV16 MAGE-C2 MAGE-A4 PRAME MAGE-A1 HPV16 MAGE-C2 MAGE-A4 PRAME MAGE-A1 Cerv
Slide 36: TScan is rapidly filling the ImmunoBank
TScan is rapidly filling the ImmunoBank to enable multiplexed TCR-T therapy in solid tumors TCRs covering multiple antigen HLAs and HLA alleles may enable 50-75% of patients to receive multiplex therapy INDs HPV16 TSC-200 Cleared MAGE-C2 TSC-201 Planned 2024 INDs MAGE-A4 TSC-202 Discovery Currently
Slide 37: Dose escalation scheme provides a rapid path to multiplex TCR-T
Dose escalation scheme provides a rapid path to multiplex TCR-T in Phase 1 TSC-204-A0201 TSC-204-C0702 TSC-200-A0201 TSC-203-A0201 TSC-201-B0702 TSC-204-A0101 (MAGE-A1) (HPV16) (PRAME) (MAGE-C2) (MAGE-A1) (MAGE-A1) 0.5B 0.5B 0.5B 0.5B 0.5B 0.5B DL1 2B 2B 2B 2B 2B 2B DL2 Option for singleplex (HPV16)
Slide 38: Prospectively selecting for target and HLA expression
Prospectively selecting for target and HLA expression maximizes chance of success Tumor TCR-T selection Germline Target testing HLA LOH HLA loss detected HLA testing Target HLAs on HLA loss intact haplotype IHC / ISH HLA in ImmunoBank No HLA loss Neogenomics Target HLAs on opposite haplotypes Tempus
Slide 39: Screening protocol pre-identifies patients for treatment
Screening protocol pre-identifies patients for treatment Patient journey Leukapheresis T-Plex D2 T-Plex D1 Current Lympho- Progression 28 days Follow-up therapy depletion Screening protocol: Treatment protocol: • Pre-screens patients for trial eligibility • Rapid enrollment during standard-of-care t
Slide 40: Investigators are highly motivated and have screened many patients
Investigators are highly motivated and have screened over 250 patients to date Enrollment status 1000 251 222 165 127 97 100 71 Targeting 43 20 sites 28 20 20 16 15 15 14 14 14 13 12 11 10 10 9 9 8 10 4 3 2 2 1 1 1 1 Jun Jul Aug Sept Oct Nov Dec Jan Feb Mar Apr Q2 2023 2024 # of sites open in screen
Slide 41: Broad array of tumor types with ~70% matching to an HLA in the ImmunoBank
Broad array of tumor types with ~70% matching to an HLA in the ImmunoBank ~70% of patients have at least one HLA TUMOR TYPES match to the ImmunoBank Cutaneous melanoma 68, 31% 88, 43% NSCLC 36, 17% HNSCC 151, 69% 28, 14% Ovarian Other 15, 7% 18, 9% Cervical 5 Acral 2 Endometrial 2 Uveal melanoma Ana
Slide 42: High percentage of patients have a TCR match for singleplex therapy
High percentage of patients have a TCR match for singleplex therapy and many would be eligible for T-Plex ~60% of patients with all testing completed ~30% of patients with TCR-T have at least one TCR in ImmunoBank would qualify for T-Plex 50 44 3, 11% 40 5, 19% 27 30 20 19, 70% 10 0 All testing comp
Slide 43: Patients identified across all cohorts and into DL2 and DL3
Patients identified across all cohorts and into DL2 and DL3 in some cohorts Dose Level MAGE-A1 A*02:01 MAGE-A1 C*07:02 HPV-16 A*02:01 PRAME A*02:01 MAGE-A1 A*0101 MAGE-C2 B*0702 DL1 • Melanoma (Yale) • Melanoma • Head & Neck • Melanoma (Orlando) • Head & Neck • Melanoma • Apheresis 4/30 (Alleghany)
Slide 44: Enrollment proceeding rapidly across heme and solid tumor programs
Enrollment proceeding rapidly across heme and solid tumor programs SUN MON TUE WED THU FRI SAT 25 26 27 28 29 1 2 3 4 5 6 7 8 9 Feb/Mar 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 SUN MON TUE WED THU FRI SAT 1 2 3 4 5 6 7 8 9 10 11 12 13 April/May 14 15 16 17 18 19 20 21 22 23
Slide 45: Patient eligibility expected to increase rapidly as ImmunoBank grows
Patient eligibility expected to increase rapidly as ImmunoBank grows HPV16+ cancers Other solid tumors 100 100 Head & Neck-single 80 80 Melanoma -single NSCLC-single 60 60 Head & Neck-multi 40 40 Melanoma-multi NSCLC-multi HPV+ tumors 20 20 0 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 Number of TCRs Number of TC
Slide 46: TScan highlights
TScan highlights Q4 2023: Transformative platform Hematologic malignancies Solid tumor program to $192.0 M enables rapid discovery program to prevent deliver enhanced of TCRs and targets for relapse with HCT multiplex TCR-T Net cash, cash engineered T cell therapy Eight patients treated to INDs clea
Slide 47: THANK YOU
THANK YOU
TScan Therapeutics — Investor Presentation (April 2024) on 6ix