Carsgen Therapeutics Holdings Ltd. · HKEX:2171
Carsgen Therapeutics — Investor Presentation (December 2024)
55 slides from Carsgen Therapeutics's investor presentation, December 2024
Slide 1: CARsgen Therapeutics: Making Cancer Curable
CARsgen Therapeutics (HKEX: 02171) December 2024 Making Cancer Curable
Slide 2: Disclaimer
Disclaimer THIS DOCUMENT IS FOR INFORMATIONAL PURPOSES ONLY AND IS NOT INTENDED TO BE, AND SHALL NOT BE CONSTRUED AS, AN OFFER, INDUCEMENT, INVITATION, SOLICITATION, COMMITMENT OR ADVERTISEMENT WITH RESPECT TO THE PURCHASE, SUBSCRIPTION OR SALE OF ANY SECURITY AND NO PART OF IT SHALL FORM THE BASIS
Slide 3: We Develop Innovative and Differentiated Cell Therapies to Make Cancer Curable
We Develop Innovative and Differentiated Cell Therapies to Make Cancer Curable 1 Marketed product: 3 CAR-T Products at IND stage: 4+ Core technology platforms: • zevorcabtagene autoleucel • Satri-cel (Claudin18.2) • CycloCAR®, THANK-uCAR®, (zevor-cel, CT053) • CT011 (GPC3) LADAR®, CARcelerate® • CT0
Slide 4: Global Reach with Integrated R&D and Manufacturing Capabilities
Global Reach with Integrated R&D and Manufacturing Capabilities Complemented with Synergistic Partnership CGMP Facility Beijing Office Headquarter (Xuhui) Shanghai Headquarter, research, clinical development, GMP Durham Beijing commercial and clinical manufacturing facility Shanghai Durham, North Ca
Slide 5: Continuous Innovation and Technology Advancement to Tackle Major Challenges with CAR-T
Continuous Innovation and Technology Advancement to Tackle the Major Challenges with CAR-T therapies Since 2014 Allogeneic Enabling Technologies • THANK-uCAR®, THANK-u Plus platforms CycloCAR® co-expression of IL-7 + CCL21 “One day” culture LADAR® • CT071, developed utilizing the (Precise Targeting)
Slide 6: Focus on Differentiated CAR-T Products and Programs
Focus on Differentiated CAR-T Products and Programs Solid tumors: adjuvant clinical studies Fast manufacturing flatform Allogeneic platforms CT041 (Claudin18.2) CT071 (GPRC5D) CT0590 ✓ For R/R MM and PCL (enrollment ◼ GC (3L+) Confirmatory Phase II trial finished) ✓ The proprietary CARcelerate® plat
Slide 7: CARsgen's Competitive Product Pipeline with Global Rights
CARsgen’s Competitive Product Pipeline with Global Rights Product BLA Target Indication Pre-clinical Phase I Phase II/III2 Candidate1 NDA R/R MM LUMMICAR 1 (China) launched Zevor-cel (CT053)3 BCMA R/R MM LUMMICAR 2 (US, Canada) GC/GEJ ST-01 (China) ST-02 (US, Canada) Autologous GC/PC Satri-cel (CT04
Slide 8: Zevor-cel (CT053): BCMA-Targeted CAR-T for Multiple Myeloma
Zevor-cel (CT053): BCMA-Targeted CAR-T for Multiple Myeloma
Slide 9: Zevor-cel (CT053): Differentiated Fully-human BCMA CAR-T
Zevor-cel (CT053): Differentiated Fully-human BCMA CAR-T Zevor-cel Highlights 38 heavily pretreated R/R MM patients (IIT + China Phase 1)1 ✓ Optimized scFv with enhanced binding affinity • High Disease Burden and stability ✓ Competitive efficacies ✓ Acceptable safety Extramedullary disease High-risk
Slide 10: IIT and LUMMICAR-1 Efficacy and Safety Data
IIT and LUMMICAR-1 Efficacy and Safety Data China investigator-initiated China Phase I China Phase II trials1 (LUMMICAR-1)2 (LUMMICAR-1) 3 N=24 N=14 N=102 Follow-up, median (range), 17.4 (0.9-38.7) 37.7 (14.8-44.2) 20.3 (0.4-27) Month EMD+ , No. (%) 10 (41.7%) 2 (14.3%) 11 (10.8%) High risk Cytogene
Slide 11: Pipeline Products Against Solid Tumors
Pipeline Products Against Solid Tumors
Slide 12: Addressing Large Population of Claudin18.2 Positive Tumors with Significant Unmet Medical Needs
Addressing Large Population of Claudin18.2 Positive Tumors with Significant Unmet Medical Needs Gastric Incidence ~25.6K1 Incidence ~358.7K1 Cancer Mortality ~11.0K1 Mortality ~260.4K1 5-year survival rate of advanced GC is 5-20%; For advanced GC (3L+), ORR is 4.5%, mPFS < 2months, mOS < 6 months (T
Slide 13: Claudin18.2 Franchise Offers a Comprehensive Multi-modal Solution for Patients
Claudin18.2 Franchise Offers a Comprehensive Multi-modal Solution for Patients Satri-cel (CT041) CT048 First-in-class Claudin 18.2 CAR-T; GC Utilizing CARsgen’s Proprietary CycloCAR® (3L+) confirmatory Phase II trial in China Technology to enhance efficacy in solid tumor; completed enrollment entere
Slide 14: Satri-cel (CT041): Global First-in-Class CAR-T for Claudin18.2-Positive Solid Tumors
Satri-cel (CT041): Global First-in-Class CAR-T for Claudin18.2- Positive Solid Tumors Product Designations Clinical Development Plan • RMAT (FDA) • Optimized scFv1 • GC (3L+) Confirmatory Phase II trial in ✓ High binding affinity China: Enrollment Completed; Plan to ✓ High stability • Orphan Drug (F
Slide 15: Satri-cel: Clinical Data from China and the United States
Satri-cel: Clinical Data from China and the United States China investigator-initiated Phase Ib/II in China Phase 1b in the US trial (NCT03874897)1,2 (NCT04581473)3 (NCT04404595)4 Sample size, No. 51 GC/GEJ* 14 GC/GEJ 7 GC/GEJ 12 PC Median follow-up, Month 32.4* 8.8 8.9 ORR 54.9%* 57.1% 42.9% 16.7%
Slide 16: Breakthrough Efficacy Data of Satri-cel in 3L+ GC/GEJ
Breakthrough Efficacy Data of Satri-cel in 3L+ GC/GEJ Satri-cel, CT041-CG4006 1 18 GC/GEJ patients who had failed at least 2 prior lines of therapies at a dose 2.5×108 CAR-T cells. ORR mPFS* mOS** 61.1% 5.6 mos 9.5 mos DCR DoR rate at 6 months 83.3% 57.1% *PFS and OS above were calculated from CAR-T
Slide 17: Satri-cel: Extension to GC/PC Earlier Line Treatment
Satri-cel: Extension to GC/PC Earlier Line Treatment Great clinical value in earlier line / earlier disease stage and providing better chances of cure for a much broader patient population More Accessible Tumor Better Tolerability • Low disease burden & • Mild CRS aggressiveness 01 04 • Good hematop
Slide 18: Liver Cancer: The Third Leading Cause of Cancer Mortality Worldwide
Liver Cancer: The Third Leading Cause of Cancer Mortality Worldwide 2022 Liver Cancer Epidemiology in the US and China1 Incidence ~43.5K Incidence ~367.7K Mortality ~30.9K Mortality ~316.5K Liver Cancer 5-year survival rate Global2 US3 China4 Liver Cancer, all stages 18% 20% 12% 1. International Age
Slide 19: CT011: First-in-class CAR-T in Hepatocellular Carcinoma with PoC Clinical Results
CT011: First-in-class CAR-T in Hepatocellular Carcinoma with PoC Clinical Results GPC3: high expression and specificity CT011 • Overexpression of GPC3 has been observed in ~75% of Product hepatocellular carcinomas (HCC), and is associated with ✓ an autologous GPC3 CAR-T product poor disease prognosi
Slide 20: First Publication on CAR-T in Combination with Small Molecules
First publication on CAR-T in Combination with Small Molecules As of Dec 2021 (last follow-up at publication) • CR status has been over 24 months and continues (Photo taken in Jun 2023) 1. Wu X, Mol Ther. 2019 Aug 7;27(8):1483-1494 Confidential Copyrights reserved by CARsgen 19
Slide 21: Cover Story in Cancer Communications Highlighting Two Additional HCC Cases
Cover Story in Cancer Communications Highlighting Two Additional Cases of HCC patients with Disease-free Survival over 7 Years Confidential Copyrights reserved by CARsgen 20
Slide 22: Case Report: Disease-free over 7 Years
Case Report: Disease-free over 7 Years • Diagnosis: • 54-year-old male with Ib-stage HCC • Multifocal lesions in the liver, IVCTT, and retroperitoneal lymphatic metastasis; Liver resection of Multiple Metastasis; tumor free survival primary HCC GKRS and 2* MWA GKRS (> 5 years) • Prior treatment: Pre
Slide 23: CT071: Differentiated GPRC5D CAR-T Based on CARcelerate Platform
CT071: Differentiated GPRC5D CAR-T Based on CARcelerate® Platform
Slide 24: CT071: Differentiated GPRC5D CAR-T with CARcelerate Platform
CT071：Differentiated GPRC5D CAR-T with CARcelerate® Platform Product Clinical Development Status • Fully-human scFV generated by CARsgen • For relapsed R/R Multiple Myeloma or R/R Primary Plasma Cell Leukemia • Proprietary CARcelerate® platform • China investigator-initiated trial for R/R MM and ✓ M
Slide 25: CARcelerate Increases Expansion and Persistence of CAR-T Cells in NPG Mice
CARcelerate® Increases Expansion and Persistence of CAR-T Cells in NPG Mice Bearing Human MM Orthotopic Xenografts T cell number in NPG mice (with human M.M orthotopic xenografts) D7 D14 D21 150 38000 800 Number of human T cells/uL Number of human T cells/uL CD8+ Number of human T cells/uL CD8 + CD4
Slide 26: CT071: Demographics and Baseline Characteristics
CT071：Demographics and Baseline Characteristics 0.1 106 0.3 106 0.1 106 0.3 106 All Patients All Patients Patient Characteristics cells/kg cells/kg Patient Characteristics cells/kg cells/kg (n=17) (n=17) (n=8) (n=9) (n=8) (n=9) Age, median (range), High-risk cytogenetics, n (%) 6 (75.0) 6 (66.7) 12
Slide 27: CT071: Promising Safety Profile
CT071: Promising Safety Profile 0.3 106 0.1 106 cells/kg All Patients Adverse Event (AE), n (%) cells/kg (n=8) (n=17) (n=9) Treatment-emergent AE 8 (100) 9 (100) 17 (100) Treatment-related AE 8 (100) 9 (100) 17 (100) • As of June 21, 2024, the median follow-up time was 6.2 months (range, 1.0 to 11.2
Slide 28: CT071: Early and Deep Responses
CT071: Early and Deep Responses 0.1×106 0.3×106 All Patients cells/kg cells/kg (n=17) (n=8) (n=9) Best Overall Response, n(%) sCR 5 (62.5) 4 (44.4) 9 (52.9) CR 0 0 0 • The ORR achieved 94.1%, with a sCR of VGPR 0 1 (11.1) 1 (5.9) 52.9%. PR 3 (37.5) 3 (33.3) 6 (35.3) • The median time to VGPR or bett
Slide 29: CT071: 100% MRD Negative in CR/sCR Patients
CT071：100% MRD Negative in CR/sCR Patients • Seven patients achieved CR or better at week 4. # • All 4 patients with previous exposure to BCMA or BCMA/CD19 CAR T # responded (2 sCR and 2 PR). • One patient (PT06) with SD demonstrated ongoing tumor shrinkage of a large EMD (125 * mm 99 mm at baseline
Slide 30: CT071: PT06 - the Only Patient with SD to Date
CT071: PT06 - the Only Patient with SD to Date; Ongoing Shrinkage of the Large EMD Baseline • A 46-year-old male with 5 prior lines. Baseline Week 12 EMD 125mm x 99mm • R-ISS: II, DS: III-A. EMD 119mm x 84mm • EMD (125mm x 99mm at baseline) • GPRC5D (FCM): 13.7% • Type：IgA-λ • Peripheral blood plasm
Slide 31: Allogeneic CAR-T
Allogeneic CAR-T oS cARSGEN
Slide 32: Existing Efficacy Gap between Allogeneic CAR-T and Autologous CAR-T
Existing Efficacy Gap between Allogeneic CAR-T and Autologous CAR-T Allogeneic BCMA CAR-T Autologous BCMA CAR-T Treatment and outcomes ALLO-715 P-BCMA-ALLO12 cilta-cel 3.2 x108 cells, N=241 All Arm**: 0.25-6 x106 cells/kg, Arm C**:2 x106 cells/kg 0.5-1 x106 cells/kg, N=973 N=72 N=23 23 (including 2
Slide 33: Relatively Limited Expansion of Allogeneic CAR-T in Patients
Relatively Limited Expansion of Allogeneic CAR-T in Patients • In allogeneic CAR-T, donor T cells will be recognized and rapidly eliminated by the host immune system (HvGR), which impacts CAR-T cell survival and results in limited expansion. • Compared to autologous CAR-T, in vivo persistence of all
Slide 34: THANK-uCAR or THANK-u Plus: Innovative Allogeneic CAR-T Platform
THANK-uCAR® or THANK-u Plus: Innovative Allogeneic CAR-T Platform Aimed to Address Immune Rejection Target and Hinder the Attack of NK cells on HvGR is the major challenge faced by Allogeneic CAR-T Universal CAR-T cells (THANK-uCAR®) • B2M knockout to overcome HvGR from host T cells, but NK cells at
Slide 35: Enhanced in Vivo Antitumor Activity of NKG2A-Knocked-Out Allogeneic CAR-T Cells
Enhanced in Vivo Antitumor Activity of NKG2A-Knocked-Out Allogeneic CAR-T Cells in the Absence of NK Cells NKG2A/BCMA triple knock-out allogeneic CAR-T: NKG2A/BCMA triple knock-out: improved efficacy enhanced in vivo persistence NKG2A/BCMA triple knock-out allogeneic CAR-T: BCMA triple knock-out: im
Slide 36: CT0590 Exhibits Enhanced in Vivo Antitumor Activity in Mice in Presence of NK Cells
CT0590 Exhibits Enhanced in Vivo Antitumor Activity in Mice in the Presence of NK Cells BCMA TdKO BCMA TdKO BCMA-NKG2A BCMA-NKG2A BCMA-NKG2A UTD TdKO+NK BCMA TdKO +NK(1:1) +NK(1:2) TtKO TtKO +NK(1:1) TtKO +NK(1:2) x Death x Death x Death x Death Confidential Copyrights reserved by CARsgen 35
Slide 37: CT0590 IIT: Study Design
CT0590 IIT: Study Design An open-label, single-arm, phase 1, first-in-human trial in China (NCT05066022). Key eligibility Primary endpoint • 18-75 years • Relapsed/Refractory multiple myeloma (RRMM) ≥ 3 prior regimens including at • Safety and tolerability least one proteasome inhibitor (PI) and on
Slide 38: CT0590 IIT: Baseline Characteristics and Outcomes
CT0590 IIT: Baseline Characteristics and Outcomes High risk % Bone % Peak CAR Time to Refract- cytogenetic # of marrow Baseline Best TTR copy peak CAR Patient Dose ISS oriness DOR s prior smear NKG2A overall (mo number copy (Diagnosis) (cells) stage to PI/ (mo) Y/N lines plasma cell expressio respon
Slide 39: CT0590: Manageable Safety Profile
CT0590: Manageable Safety Profile n (%) SAEs 1（20.0） • Two patients experienced CRS ✓ One patient each at Grade 1 and Treatment related TEAEs 4（80.0） Grade 2; no ≥ Grade 3 CRS; ✓ Time to onset was 8-10 days post- SAE 0 infusion; 2（40.0） ✓ Duration was 3-4 days. CRS • No cases of ICANS or GvHD were I
Slide 40: CT0590: Deep and Durable Responses
CT0590: Deep and Durable Responses Median F/U 16.6m (Range: 5.1, 24.2) * • 3 subjects achieved confirmed responses including 2 subjects with stringent complete response (sCR) and 1 subject with partial response (PR). Patient 1 achieved PR but it could not be confirmed due to COVID-19. • CAR copies c
Slide 41: CT0590 IIT Case 1 Baseline Characteristics
CT0590 IIT Case 1 Baseline Characteristics • A 71-year-old male diagnosed with MM, • Double-refractory, with 94.5% plasma cells in bone marrow. • 2 prior lines of therapies, including 3 regimens. • Received 3×108 CT0590 CAR-T cells infusion. 482749 Safety • 1 Grade CRS • Only 1 subject had Grade 3 t
Slide 42: CT0590 IIT Case 2 Baseline Characteristics
CT0590 IIT Case 2 Baseline Characteristics 280863 • A 52-year-old male diagnosed with pPCL • Double-refractory • 3 prior lines, including 3 regimens (ASCT, etc.) • Received an infusion of 3×108 CT0590 CAR-T cells. Safety • 1 Grade CRS • Grade 1 infection (pneumonia), unrelated to treatment. Best Dur
Slide 43: Baseline NKG2A Expression on NK Cells May Be Predictive of CT0590 Responses
Baseline NKG2A expression on NK cells may be predictive of CT0590 responses % Baseline Patient Dose NKG2A Best overall (Diagnosis) (cells) expression response • 4 patients had baseline NKG2A data available. NK cells • Both patients who attained sCR, Patient 2 and PT 1 (MM) 50 106 Patient 5, had rela
Slide 44: THANK-u Plus: Enhanced and Sustained Allogeneic CAR-T Expansion
THANK-u Plus: Enhanced and Sustained Allogeneic CAR-T Expansion Across Different NKG2A Expression Levels NKG2A expression: High Medium Low • THANK-uCAR CT0590 exhibits a decrease in expansion within 72 hours in NK cells with relatively low NKG2A expression, while the expansion of CT059X, produced us
Slide 45: THANK-u Plus Demonstrates Enhanced Anti-Tumor Efficacy in vivo
THANK-u Plus Demonstrates Enhanced Anti-Tumor Efficacy in vivo uUTD uCT053 uCT053+NK CT0590 CT0590+NK CT059 X CT059 X+NK Week 1 Week 2 Week 3 Week 4 Week 5 Death CT059 X demonstrates significantly greater efficacy than allogeneic CT053 and CT0590, in the presence or absence of NK cells. Note: uUTD r
Slide 46: Proprietary Allogeneic CD19/CD20 CAR-T Demonstrates Potential Best-in-class Efficacy in Lymphoma Models
Proprietary Allogeneic CD19/CD20 CAR-T Demonstrates Potential Best-in-class Efficacy in Lymphoma Models D17 D54 D61 D71 D76 D83 D97 D111 D125 D131 uUTD uCD19 uCD20 uCD19/20 (Benchmark) uCD19/20 (Carsgen) CARsgen's allogeneic CD19/CD20 dual-target CAR-T demonstrates superior efficacy in a B-cell lymp
Slide 47: CD19/20X Allogeneic CAR-T Exhibits Robust Anti-lymphoma Activity with NK Cells
CD19/20X Allogeneic CAR-T Exhibits Robust Anti-lymphoma Activity in the Presence of NK Cells uUTD+NK uCD19/20 uCD19/20+NK CD19/20X CD19/20X +NK Week 1 Week 2 Week 3 Week 4 Death Week 5 Death In the presence of NK cells, CD19/20X allogeneic CAR-T (THANK-u Plus platform) demonstrates much better anti-
Slide 48: Sustained and Enhanced Expansion of KJ-C2320 in Presence of NK Cells
The Sustained and Enhanced Expansion of KJ-C2320 in the Presence of NK Cells from Different Donor Sources Confidential Copyrights reserved by CARsgen 47
Slide 49: KJ-C2320 Exhibits Enhanced Antitumor Activity in Mice in Presence of NK Cells
KJ-C2320 Exhibits Enhanced Antitumor Activity in Mice in the Presence of NK Cells uUTD uCD38 uCD38+NK KJ-C2320 KJ-C2320+NK Week 1 Week 2 Week 3 Week 4 Death Confidential Copyrights reserved by CARsgen 48
Slide 50: Summary of CT0590 and CARsgen's Allogeneic CAR-T Platform
Summary of CT0590 and CARsgen’s Allogeneic CAR-T Platform ➢ CT0590 displayed a manageable safety profile which embodies the safety of the THANK-uCAR platform. ➢ CT0590 had an expansion level comparable to autologous CAR-T in two patients with complete response. ➢ The duration of complete res
Slide 51: Multiple Value Inflection Milestones in the Near Future
Multiple Value Inflection Milestones in the Near Future • With the market price of zevor-cel set at 1.15 million RMB, we expect that the terminal market sales corresponding to our orders will reach 100 million RMB in 2024. • CT041: to submit NDA application to the NMPA in the H1 of 2025. • New produ
Slide 52: CycloCAR: Enhanced Anti-tumor Effect and Potentially Lymphodepletion Free
CycloCAR®: Enhanced Anti-tumor Effect and Potentially Lymphodepletion Free CycloCAR® (CYtokine (IL7) and Chemokine (CCL21) LOaded CAR) enables the CAR-T cells to co-express IL7 and CCL21 Advantages of CycloCAR® (7×21) technology: • Increased accumulation of T cells and Dendritic cells in tumor tissu
Slide 53: LADAR: A Powerful Technology for Precise Targeting
LADAR®: A Powerful Technology for Precise Targeting LADAR®: Local Action Driven by Artificial Receptor LADAR® is an artificial receptor that only induces the therapeutic protein expression in the presence of the LADAR ligand, leading to local antitumor activity, thereby: • Significantly reducing the
Slide 54: Experienced Senior Management Team in China & US
Experienced Senior Management Team in China & US Zonghai Li, MD, PhD Huamao Wang, PhD Raffaele Baffa, MD, PhD Co-founder, Chairman of Co-founder and Chief Medical Officer the Board, CEO, CSO COO Sylvie Peltier, PharmD, MHL Andy (Peng) Zang, PhD Senior Vice President Hua Jiang, MD, PhD Vice President
Slide 55: Making Cancer Curable
Making Cancer Curable oS cARSGEN
CARsgen Therapeutics — Investor Presentation (December 2024) on 6ix