Carsgen Therapeutics Holdings Ltd. · HKEX:2171
Carsgen Therapeutics — Investor Presentation (January 2025)
49 slides from Carsgen Therapeutics's investor presentation, January 2025
Slide 1: CARsgen Therapeutics (HKEX: 02171)
CARsgen Therapeutics (HKEX: 02171) January 2025 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 and Other Diseases Curable
We Develop Innovative and Differentiated Cell Therapies to Make Cancer and Other Diseases 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®,
Slide 4: Global Reach with Integrated R&D and Manufacturing Capabilities Complemented with Synergistic Partnership
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 the Major Challenges with CAR-T therapies
Continuous Innovation and Technology Advancement to Tackle the Major Challenges with CAR-T therapies Since 2014 Enabling Technologies Allogeneic CAR-T • THANK-uCAR®, THANK-u Plus CycloCAR® platforms co-expression of IL-7 + CCL21 LADAR® (precise targeting) Autologous CAR-T • BCMA CAR-T (zevor-cel) Ly
Slide 6: 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) Autologous GC/PC ST-02 (US, Canada) CAR-T Satri-cel
Slide 7: Autologous CAR-T Against Hematologic Malignancies
Autologous CAR-T Against Hematologic Malignancies
Slide 8: Zevor-cel: Differentiated Fully-human BCMA CAR-T for R/R MM (Approved in China)
Zevor-cel: Differentiated Fully-human BCMA CAR-T for R/R MM (Approved in China) Zevor-cel Highlights China Pivotal Phase II (LUMMICAR-1) 1 N=102 Follow-up, median (range), Month 20.3 (0.4-27) • Optimized scFv ISS stage III, No. (%) 39 (38.2%) • Enhanced binding affinity High risk Cytogenetic, No. (%
Slide 9: Zevor-cel: Outstanding Efficacy and Manageable Safety
Zevor-cel: Outstanding Efficacy and Manageable Safety ISS-based subgroups Higher safety, lower incidence 100 93.7% 93.7% Long-term survival with deep response 89.7% 87.2% of SAE 80 77.8% Response rate (%) 61.5% 60 40 It has been reported that ISS-III and high risk ◆ In IIT, Phase I, and Phase II stu
Slide 10: 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 Man
Slide 11: CT071: Baseline Characteristics
CT071: Baseline Characteristics 0.1 106 cells/kg 0.3 106 cells/kg All Patients Patient Characteristics (n=8) (n=9) (n=17) R-ISS disease stage, No. (%) II 4 (50.0) 8 (88.9) 12 (70.6) III 4 (50.0) 0 4 (23.5) ECOG PS, No. (%) 1 4 (50.0) 5 (55.6) 9 (52.9) 2 1 (12.5) 0 1 (5.9) Extramedullary Disease a, N
Slide 12: CT071: Early and Deep Responses with Promising Safety Profile
CT071: Early and Deep Responses with Promising Safety Profile 0.1 106 cells/kg 0.3 106 cells/kg All Patients (n=8) (n=9) (n=17) ORR, No. (%) 8 (100) 8 (88.9) 16 (94.1) CR/sCR rate, No. (%) 5 (62.5) 4 (44.4) 9 (52.9) VGPR or better rate, No. (%) 5 (62.5) 5 (55.6) 10 (58.8) Time to CR or better, Media
Slide 13: CT071: Rapid and Durable Responses
CT071: Rapid and Durable Responses • 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 with SD demonstrated ongoing tumor shrinkage of a large EMD (125 mm 99 * mm at baseline) with 38.2% de
Slide 14: Autologous CAR-T Against Solid Tumors
Autologous CAR-T Against Solid Tumors
Slide 15: 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 Incidence ~25.6K1 Incidence ~358.7K1 Gastric Resectable ~10.0K • • Resectable ~300.0K Cancer Mortality ~11.0K1 Mortality ~260.4K1 5-year survival rate of advanced GC is 5-20%; For advanced GC (3L+), ORR i
Slide 16: CARsgen Proprietary Claudin18.2 IHC Test
CARsgen Proprietary Claudin18.2 IHC Test Claudin18.2 IHC test kit with high sensitivity Gastric Cancer Pancreatic Cancer Bile Duct Cancer Medium & high positivity rate Medium & high positivity rate Medium & high positivity rate (≥2+, ≥40%) (≥2+, ≥40%) (≥2+, ≥40%) 68% 55% 25% Confidential Copyrights
Slide 17: 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; positive ✓ High stability • Orphan Drug (
Slide 18: 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 19: Breakthrough Efficacy Data of Satri-cel in 3L+ GC/GEJ
Breakthrough Efficacy Data of Satri-cel in 3L+ GC/GEJ mPFS | mOS Presentations at international conferences ORR (month) and publications in top-tier journals 55% CT041 5.8 | 9.0 11% Immunotherapy 1.6 | 5.2 <5% Chemotherapy, <2 | <6 Targeted Therapy 1. Qi C, et. al. Nat Med. 2022 Jun;28(6):1189-1198.
Slide 20: 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 21: 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 22: 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 in hepatocellular carcinomas (HCC), Product and is associated with poor disease prognosis ✓ an autologous GPC3 CAR-T product CARsgen’s GPC3 IHC test kit Clin
Slide 23: CAR-T in Combination with Small Molecules Against HCC
CAR-T in Combination with Small Molecules Against HCC: First publication in Molecular Therapy 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 C
Slide 24: CAR-T in Combination with Local Therapy Against HCC
CAR-T in Combination with Local Therapy Against HCC: Cover Story in Cancer Communications, Highlighting Two Cases of Disease-free Survival over 7 Years Liver resection of Multiple Metastasis; tumor free survival primary HCC GKRS and 2* MWA GKRS (> 5 years) Dec 2014 July - Oct 2015 July 2016 Nov 2021
Slide 25: Allogeneic CAR-T Platforms and Pipeline Products
Allogeneic CAR-T Platforms and Pipeline Products
Slide 26: 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 27: 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 28: 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 29: 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 30: CT0590 Exhibits Enhanced in Vivo Antitumor Activity in Mice in the 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 29
Slide 31: 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 32: CT0590 IIT: Baseline Characteristics and Outcomes
CT0590 IIT: Baseline Characteristics and Outcomes % Baseline Peak CAR High risk # of Refractorine Patient ISS NKG2A Best overall DOR TTR copy number cytogenetics prior ss to PI/ (Diagnosis) stage expression NK response (mo) (mo) (copies/µg Y/N lines IMiD* cells gDNA) PT 1 (MM) BLQ Y I 2 1 23 SD NA N
Slide 33: CT0590: Manageable Safety Profile
CT0590: Manageable Safety Profile n (%) SAEs 1（20.0） • Two patients experienced CRS 4（80.0） Treatment related TEAEs ✓ One patient each at Grade 1 and Grade 2; no ≥ Grade 3 CRS; SAE 0 ✓ Time to onset was 8-10 days post- 2（40.0） infusion; CRS ✓ Duration was 3-4 days. ICANS 0 • No cases of ICANS or GvH
Slide 34: 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 35: A Case of CT0590 to Treat R/R MM
A Case of CT0590 to Treat R/R MM 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 subjec
Slide 36: A Case of CT0590 to Treat R/R pPCL
A Case of CT0590 to Treat R/R pPCL 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 tr
Slide 37: 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 38: 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 39: 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 40: 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 41: CD19/20X Allogeneic CAR-T Exhibits Robust Anti-lymphoma Activity in the Presence of 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 42: The Sustained and Enhanced Expansion of KJ-C2320 in the 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 41
Slide 43: KJ-C2320 Exhibits Enhanced Antitumor Activity in Mice in the 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 42
Slide 44: 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 45: 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 46: 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 47: 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 48: 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 49: Making Cancer Curable
Making Cancer Curable oS cARSGEN
CARsgen Therapeutics — Investor Presentation (January 2025) on 6ix