Tscan Therapeutics, Inc. · NASDAQ:TCRX
Tscan Therapeutics — Investor Day (December 2024)
51 slides from Tscan Therapeutics's investor day presentation, Dec 10, 2024
Slide 1: KOL Event December 10, 2024
KOL Event December 10, 2024 Exhibit 99.2
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 Tscan Therapeutics, Inc.
Slide 3: Agenda
Agenda Ran Reshef, M.D., M.Sc., Director of Translational Research, Blood and Marrow Transplantation Program, Columbia University Irving Medical Center Results from ALLOHA™ Phase 1 trial study of TSC-100 and TSC-101 in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), a
Slide 4: ALLOHA Phase 1 study authors and affiliations
Monzr M. Al Malki, MD1, Alla Keyzner, MD2, Uday Popat, MD3, Yi-Bin Chen, MD, MS4,Hyung C Suh, MD, PhD5, Tania Jain, MD6, Melhem M. Solh, MD7, Anson Snow, MD8, Saar Gill, MD, PhD9, Lohith Gowda, MD10, Joseph Uberti, MD, PhD11, Erica Buonomo, PhD12, Yun Wang, PhD12, Nancy Nabilsi, PhD12, Timothy White
Slide 5: HCT can cure some patients with AML, ALL or MDS
Allogeneic hematopoietic cell transplantation (HCT) can cure some patients with AML, ALL or MDS Advances in reduced intensity conditioning (RIC-HCT) regimens as well as GvHD prophylaxis with post-transplant cyclophosphamide (PTCy) have expanded patient access to HCT by markedly improving treatment-r
Slide 6: TSC-100 and TSC-101 are adjuvant engineered TCR-T cells
TSC-100 and TSC-101 are adjuvant engineered TCR-T cells designed to eliminate residual recipient cells and prevent relapse following HCT Conditioning therapy PATIENT DONOR Hematopoietic cell transplant Stem cells Prevent relapse Adjuvant TCR T-cell therapy T-cell HA-1 or HA-2 TCR Cancer cell Normal
Slide 7: Multi-arm Phase 1 trial for TSC-100 & TSC-101
Multi-arm Phase 1 trial for TSC-100 & TSC-101 in subjects with AML, ALL, and MDS Transplant + TSC-100 (HA-1 positive) Treatment Arms Transplant + TSC-101 (HA-2 positive) Control Arm Transplant Alone Long term follow-up HCT Pre-transplant screening Endpoint and safety monitoring RIC Day 0 Day +21 Day
Slide 8: Majority of subjects are at high risk for relapse
Majority of subjects in the treatment and control arms are at high risk for relapse As of Nov 20, 2024 data cut TSC-100 TSC-101 Any TSC Control Subjects Enrolled and assigned 14 12 26 13 Subjects Transplanted (efficacy data cohort) 14 12 26 12 Subjects Infused (safety data cohort) 10 12 22 N/A* Medi
Slide 9: Subjects treated at all three dose levels with no DLTs
Subjects treated at all three dose levels with no dose-limiting toxicities Dose Level Planned Day of Infusion Post HCT TSC 100 N=10 TSC 101 N=12 +21 +61 DL1 5×106 TCR-T cells/kg N/A 1 1 DL2 5×106 TCR-T cells/kg 5×106 TCR-T cells/kg 1 2 DL3 5×106 TCR-T cells/kg 20×106 TCR-T cells/kg 8 9 As of Nov 20,
Slide 10: TCR-T cells detected for over one year
TSC-100 and TSC-101 TCR-T cells detected for over one year with increased persistence seen at highest dose level (DL3) TSC persistence over time TSC-101 TSC-100 *AUC of TSC-100/TSC-101 between Day 90-180 (Geometric mean(geometric CV)): DL1: 2.26(47.2%); DL2 and sDL2: 8.15(42.2%); DL3 and sDL3: 34.47
Slide 11: Adverse events of special interest were low grade and manageable
Adverse events of special interest were low grade and manageable Adverse Event of Special Interest* TSC-100 n=10 TSC-101 n=12 Any TSC n=22 Control n=12 Any Acute GvHD** 5 (50%) 6 (50%) 11 (50%) 4 (33%) Grade II - IV 0 (0%) 2 (17%) 2 (9%) 3 (25%) Grade III - IV 0 (0%) 1 (8%) 1 (5%) 2 (17%) Any CRS 4
Slide 12: Grade >3 treatment emergent adverse events consistent with transplantation
Grade >3 treatment emergent adverse events are consistent with transplantation Events in >5% of subjects Any TSC n=22 Control n=12 Anemia 7 (31.8) 2 (16.7) Platelet count decreased 4 (18.2) 3 (25.0) Neutrophil count decreased 3 (13.6) 1 (8.3) Pneumonia 3 (13.6) 1 (8.3) Sepsis 3 (13.6) 0 Decreased ap
Slide 13: TCR-T infusion is associated with fewer relapses
TCR-T infusion is associated with fewer relapses Probability of relapse 0.40 0.20 0.30 0.00 0 90 135 180 270 360 450 540 585 Days post HCT 12 26 11 23 9 17 9 15 5 12 4 10 4 8 1 4 1 3 Number at risk Cumulative number of events 0 0 0 0 1 0 1 1 3 2 4 2 4 2 Control arm Treatment arm Control arm Treatmen
Slide 14: Event-free survival favors the treatment arm
Event-free survival (EFS) favors the treatment arm 1.00 0.75 0.25 0.50 0.00 0 60 120 180 240 300 360 420 480 Days post HCT EFS probability 12 26 11 23 7 17 3 12 2 10 2 8 2 8 0 7 0 4 Number at risk Cumulative number of events 0 0 1 1 4 2 6 4 7 4 7 4 7 4 7 5 7 6 Control arm Treatment arm Control arm T
Slide 15: Complete donor chimerism achieved after initial TSC infusion
Complete donor chimerism achieved in all patients after initial TSC infusion 101 DL1 100 DL1 101 DL2s‡ 100 DL2 101 DL2 100 DL3 101 DL3s‡ 100 DL3 101 DL3 100 DL3 101 DL3 101 DL3 101 DL3 100 DL3 100 DL3 101 DL3 100 DL3 101 DL3 100 DL3 100 DL3 100 n/a 100 n/a C 1 C 2 C 3 C 4 C 5 C 6 C 7 C 8 C 9 C 10 C
Slide 16: Unusual circumstances for both subjects who relapsed
Unusual circumstances for both subjects who relapsed post TCR-T cell infusions TSC-101 Dose Level 3 65 y/o male with AML Did not respond to induction chemotherapy (4% blasts) Taken to transplant after reinduction chemotherapy without achieving CR 1 Died Day 129 post transplant with suspected relapse
Slide 17: Subject outcomes by arm and dose level
Pre-HCT MRD Control-1 Control-2 Control-3 Control-7 Control-8 Control-5 Control-4 Control-6 Control-9 Control-10 Control-11 Control-12 Arm ‡Dose did not meet target dose criteria in supplemental cohorts MRD-positive MRD-negative MRD pending TSC-100/TSC-101 infusion Clinical intervention for concern
Slide 18: Summary
Summary Infusions with TSC-100 and TSC-101 were well-tolerated with no DLTs and adverse events consistent with HCT TSC-100 and TSC-101 TCR-T cells have been detected >1 year post infusion and have a clear dose-persistence relationship 2 of 26 (8%) treatment-arm subjects relapsed as compared to 4 of
Slide 19: Pivotal trial design and heme development strategy
Pivotal trial design and heme development strategy
Slide 20: Collaborative RMAT meeting with FDA provided clear feedback
Highly collaborative RMAT meeting with FDA provided clear feedback on a path to registration Proposed patient population is acceptable: AML, MDS, and ALL undergoing allo-HCT with haploidentical or MMUD donors Analytical comparability is sufficient to support a commercial-ready process Proposed poten
Slide 21: TSC-101 captures ~98% of HLA-A*02:01-positive patients
% eligible donors % eligible patients TSC-101 captures ~98% of HLA-A*02:01-positive patients, obviating the need for TSC-100 or a companion diagnostic TSC-101 (~33%) Almost all subjects infused to date [19/22 (86.3%)] qualified for treatment with TSC-101 Sources: Wang, AACR 2022; Spierings, PLoS Gen
Slide 22: Pivotal study designed for full approval using external control arm
Pivotal study designed for full approval using an external control arm Subjects: AML, MDS, ALL undergoing transplant with reduced intensity conditioning (RIC) Donors: Haploidentical and mismatched unrelated donors Enrollment: TSC-101 vs matched controls (1:3) Companion Diagnostic: Not needed Endpoin
Slide 23: Target RFS hazard ratio of 0.60 supported by Phase 1 data
Target RFS hazard ratio of 0.60 is well supported by data from the ALLOHA Phase 1 study 1.00 0.75 0.25 0.50 0.00 Days post HCT RFS probability Number at risk Cumulative number of events Control arm Treatment arm Control arm Treatment arm Event defined as relapse, or death CoxPH Ratio = 0.2, CI = (0.
Slide 24: Market opportunity
Market opportunity ‘TSCAN
Slide 25: Positive data should accelerate changes in clinical practice
Haploidentical and mismatched unrelated donors (MMUDs) Reduced intensity conditioning (RIC) Positive data should accelerate changes in clinical practice and increase the total addressable market Myeloablative conditioning (MAC) Matched unrelated donors (MUDs) Matched related donors (MRDs) 28%* Other
Slide 26: Positive data should accelerate changes in clinical practice
Haploidentical and mismatched unrelated donors (MMUDs) Reduced intensity conditioning (RIC) Positive data should accelerate changes in clinical practice and increase the total addressable market Myeloablative conditioning (MAC) Matched unrelated donors (MUDs) Matched related donors (MRDs) 28%* Other
Slide 27: Positive data should accelerate changes in clinical practice
Haploidentical and mismatched unrelated donors (MMUDs) Reduced intensity conditioning (RIC) Positive data should accelerate changes in clinical practice and increase the total addressable market Myeloablative conditioning (MAC) Matched unrelated donors (MUDs) Matched related donors (MRDs) 28%* Other
Slide 28: Increased use of RIC with haplo/MMUD donors expands addressable market
Addressable patients Increased use of reduced intensity conditioning with haploidentical/MMUD donors has the potential to expand the addressable market dramatically Sources: CIBMTR 2022 and 2023; Wang, AACR 2022; NMDP analysis; ClearView analysis assumes maximum practice change in each case MUD to H
Slide 29: Expansion to Europe could more than double addressable patients
Addressable patients Expansion to Europe offers the opportunity to more than double the addressable patient population Sources: Passweg, Bone Marrow Transplantation 2024 (EBMT Survey Results 2022); Allelefrequencies.net; NMDP analysis; ClearView analysis assumes maximum practice change in each case
Slide 30: New cell therapy approvals benchmark potential TSC-101 pricing
New cell therapy approvals benchmark potential TSC-101 pricing approach CAR-T/Transplant Products Recent TIL and TCR-T Approvals One-time Curative Therapies Strong clinical efficacy across multiple lines of therapy Existing reimbursement pathway ~$300-500 K ~$500-750 K $1+ M Strong clinical efficacy
Slide 31: Expansion opportunities
Expansion opportunities ‘TSCAN
Slide 32: Addressable market can be expanded with additional TCR-Ts
% eligible donors % eligible patients The addressable market can be expanded with the introduction of additional TCR-Ts that target other HLA types TSC-101 (33.6%) TSC-102 targets a hematopoietic antigen on HLA-A*03:01 10.4% 7.2% TSC-102 (17.6%)
Slide 33: TCRs for additional HLA types will target CD45 epitopes
AML ALL -2 0 2 4 6 8 10 log2(TPM+0.001) Source: TCGA CD45 is a lineage-specific antigen with expression in all hematopoietic cells, including HSCs CD45 is a large protein with many well-known epitopes for high frequency HLAs Antigen-negative donors can be selected by mismatching on HLA (using haploi
Slide 34: Lead TCR for TSC-102 selectively kills A*03:01+/CD45+ cancer cell lines
Lead TCR for TSC-102 selectively kills A*03:01+/CD45+ cancer cell lines Burkitt’s lymphoma Myeloid leukemia B cell lymphoma TCR-T cells effectively kill heme-derived cancer cell lines TSC-102 Non-engineered T cells
Slide 35: Eight TCR-T candidates in clinical development
Eight TCR-T candidates in clinical development, with new TCR-Ts advancing HLA type Indications Programs (target) TSC-100 (HA-1) HLA-A*02:01 HLA-A*02:01 HLA-A*02:01 HLA-C*07:02 HLA-B*07:02 HLA-A*02:01 HLA-A*24:02 HLA-A*02:01 HLA-C*07:02 HLA-A*01:01 HLA-A*03:01 HLA-B*07:02 HLA-A*02:01 HLA-B*07:02 HLA-
Slide 36: Heme expansion could reach over 10,000 patients in U.S. and Europe
Addressable patients Expansion opportunities for the heme program provide a way to reach over 10,000 patients in the U.S. and Europe Source: SEER, CIBMTR, EBMT, ClearView analysis TSC-101 (assumes change in practice) Addition of three TCRs for other HLA types Addition of frail and R/R patients Addit
Slide 37: Next steps and milestones
Next steps and milestones Launch pivotal study Two-year relapse data from Phase 1 trial Open expansion cohorts at proposed RP2D H1 2025 H2 2025 2025 Continue to enroll ALLOHA Phase 1 study using commercial manufacturing process at TScan Transfer commercial process to external CDMO Reach final agreem
Slide 38: Q&A
Q&A
Slide 39: Solid tumor program update
Solid tumor program update ‘TSCAN
Slide 40: Multiplex TCR-T therapy addresses heterogeneity of solid tumors
Multiplex TCR-T therapy is designed to address the heterogeneity of solid tumors Many immune-rich cancers exhibit target heterogeneity MAGE-A4 PRAME Non-small cell lung cancer TCR-Ts against multiple targets may be required to improve efficacy and durability PRAME MAGE-A4 Relapse Targeting long-term
Slide 41: Building and expanding the ImmunoBank of TCRs
TScan is building and expanding the ImmunoBank of TCRs to enable enhanced, multiplex TCR-T cell therapy Customized TCR-T therapy Cancer cells with different HLA types and targets T cells Cancer patient Profile tumor HLA Type ImmunoBank of therapeutic TCRs HLAs Targets Determine target and HLA expres
Slide 42: Dose escalation scheme provides rapid path to multiplex TCR-T
Dose escalation scheme provides a rapid path to multiplex TCR-T in Phase 1 TSC-204-A0201 (MAGE-A1) TSC-204-C0702 (MAGE-A1) DL3 DL4 DL1 DL2 TSC-200-A0201 (HPV16) TSC-203-A0201 (PRAME) TSC-201-B0702 (MAGE-C2) TSC-204-A0101 (MAGE-A1) 2B 0.5B 2B 0.5B 2B 0.5B 2B 0.5B 2B 0.5B 2B T-Plex 28 days Any two TCR
Slide 43: Progressing multiple TCRs through early dose levels
Enroll study efficiently Progressing multiple TCRs through early dose levels sets us up to investigate multiplexed therapy in 2025 Manufacture successfully Manufacture successfully Progress through dose escalation to T-Plex Early signs of anti-tumor activity
Slide 44: Strategy for 2025
Strategy for 2025 ‘TSCAN
Slide 45: Program will focus on immune-rich cancers with high unmet need
Program will focus on immune-rich cancers with high unmet need Initial patients have included all comers Anal, Head & Neck, Melanoma, NSCLC, Ovarian, Sarcoma, Thyroid We have now reached dose levels that enable T-Plex T-Plex and DL3 singleplex are expected to be the first efficacious dose levels Goa
Slide 46: T-Plex enrollment will focus on four key indications
T-Plex enrollment will focus on four key indications with high unmet need NSCLC Sarcoma Head & Neck Anal PRAME + MAGE-A1/C2/A4 HPV16 + PRAME HPV16 + MAGE-A1/C2/A4 High unmet need Evidence of T cell infiltration Clinical signal in early TCR-T trials Significant addressable patient population in secon
Slide 47: Strategically building the ImmunoBank for multiplex TCR-T
TScan is strategically building the ImmunoBank to enable multiplex TCR-T therapy in immune-rich solid tumors In PLEXI-T study HLAs Targets ImmunoBank TSC-200 TSC-203 TSC-202 TSC-204 A*02:01 A*01:01 A*03:01 B*07:02 C*07:02 TSC-201 A*24:02 HPV16 MAGE-A4 MAGE-C2 PRAME MAGE-A1 Recently filed IND
Slide 48: T-Plex eligibility expected to increase with MAGE-A4
T-Plex eligibility expected to increase substantially with addition of MAGE-A4 T-Plex eligibility increases as ImmunoBank grows Eligible patients include patients who are positive for at least two TCR-Ts in the ImmunoBank *Current number of TCR-Ts in ImmunoBank # Addition of MAGE-A4 A*02:01 to Immun
Slide 49: Eight TCR-T candidates in clinical development
Eight TCR-T candidates in clinical development, with new TCR-Ts advancing HLA type Indications Programs (target) TSC-100 (HA-1) HLA-A*02:01 HLA-A*02:01 HLA-A*02:01 HLA-C*07:02 HLA-B*07:02 HLA-A*02:01 HLA-A*24:02 HLA-A*02:01 HLA-C*07:02 HLA-A*01:01 HLA-A*03:01 HLA-B*07:02 HLA-A*02:01 HLA-B*07:02 HLA-
Slide 50: Summary
Summary Q1 2025 H1 2025 YE 2025 Dose first multiplex patient Safety and response data for multiplex therapy Eight patients dosed with singleplex TCR-T Two TCRs advanced through DL2 and now eligible for T-Plex (HPV16 A*02:01 and PRAME A*02:01) First T-Plex product successfully manufactured Early evid
Slide 51: Q&A
Q&A