Cstone Pharmaceuticals · HKEX:2616
Cstone Pharmaceuticals — Corporate Update (December 2023)
34 slides from Cstone Pharmaceuticals's corporate update, Dec 20, 2023
Slide 1: CStone Business Update
CStone Business Update December 20th, 2023 Stock Code: 2616. HK
Slide 2: Presentation Disclaimer
Presentation Disclaimer • By attending the meeting where this presentation is made, or by reading the presentation materials, you agree to be bound by the following: • The information in this presentation has been prepared by representatives of CStone Pharmaceuticals (the "Company" and, together wit
Slide 3: Agenda
1. ROR1 ADC Updates 2. PD-L1 ex-China Progress Agenda 3. Commercialization Strategy 4. Expected Catalysts 3
Slide 4: 1. ROR1 ADC Updates
1. ROR1 ADC Updates 2. PD-L1 ex-China Progress Agenda 3. Commercialization Strategy 4. Expected Catalysts 4
Slide 5: CS5001 (ROR1 ADC) is a potential FIC/BIC ROR1 ADC globally with Ph1 study ongoing
CS5001 (ROR1 ADC) is a potential FIC/BIC ROR1 ADC globally with Ph1 study ongoing in US, Australia and China 4 key differentiators support best-in-class potential: An ADC target for both hematological malignancies 1 and solid tumors 3 4 • Largely absent in normal blood lymphocytes and adult tissues
Slide 6: Novel prodrug technology minimize systematic toxicity of conventional PBD
Novel prodrug technology minimize systematic toxicity of conventional PBD ▪ PBD prodrug is inactive compared to naked PBD ▪ Prodrug, being in a highly polar form, cannot penetrate and kill normal cells ▪ Prodrug mitigates toxicity risk associated with systemic exposure of conventional PBD payloads ▪
Slide 7: ROR1 is a promising target for the treatment of multiple tumor types
ROR1 is a promising target for the treatment of multiple tumor types Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the receptor tyrosine kinase family Broad expression of ROR1 in both solid tumor and hematological malignancies (e.g., TNBC, lung cancer, ovarian cancer, pan
Slide 8: ROR1 expression in solid tumor has been validated by CStone proprietary mAb
ROR1 expression in solid tumor has been validated by CStone proprietary mAb 300 nsq-NSCLC CRC ROR1 H-Score (M） 200 100 TNBC Pancreatic cancer 0 ad-NSCLC CRC TNBC Pancreas sq-NSCLC SCLC Tumor type Tumor type H-Score≥50 Nsq-NSCLC 70% CRC 60% sq-NSCLC SCLC TNBC 50% Pancreatic cancer 30% Sq-NSCLC 20% SC
Slide 9: CS5001 selectively bound to human ROR1 with high affinity and triggered rapid internalization
CS5001 selectively bound to human ROR1 with high affinity and triggered rapid and high internalization nm CS5001 showed high affinity to human ROR1 Internalization and intracellular trafficking of CS5001-IgG1 Sample ka (1/Ms) kd (1/s) KD (M) CS5001 1.59E+06 2.19E-03 1.38E-09 CS5001 was highly select
Slide 10: CS5001 demonstrated highly potent ROR1-dependent cytotoxicity in solid tumor and hematological cell lines
CS5001 demonstrated highly potent ROR1-dependent cytotoxicity in solid tumor and hematological malignancy cell lines CS5001 killed tumor cells with potency and ROR1- dependency ROR1 negative ROR1 expressing MCF7 JeKo-1 rMFI 0.93 rMFI 15.48 PA-1 CS5001 rMFI 53.58 CS5001 CS5001 120 140 % of surviving
Slide 11: CS5001 demonstrated robust bystander killing effect in co-culturing assays
CS5001 demonstrated robust bystander killing effect in co-culturing assays with ROR1+/- cells ROR1- tumor cells co-cultured with the same cells but transfected with ROR1 CHO-S & CHO-S-ROR1 coculture K562 & K562-ROR1 coculture 120 120 CHO-S-ROR1- monoculture K562-ROR1- monoculture 100 100 CHO-S-ROR1+
Slide 12: ROR1-dependent anti-tumor activity was demonstrated in solid tumor PDX models
ROR1-dependent anti-tumor activity was demonstrated in solid tumor PDX models DS placebo BR1282 BR9493 BR9465 IsoADC, 0.5 mg/kg x1 4000 CS5001, 0.5 mg/kg x1 2000 DS placebo 2000 DS placebo IsoADC, 0.5 mg/kg, q3w x2 Tumor Volume (mm3) Tumor Volume (mm3) CS5001, 0.5 mg/kg x1 Tumor Volume (mm3) CS5001,
Slide 13: Phase 1 Study Design: CS5001-101
Phase 1 Study Design: CS5001-101 A Phase 1, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of CS5001, an Anti-ROR1 Antibody Drug Conjugate, in Patients with Advanced Solid Tumors and Lymphomas Phase 1a Dose Escalation (BOIN De
Slide 14: CS5001 is a well tolerated and stable ADC with preliminary anti-tumor activities
CS5001 is a well tolerated and stable ADC and has demonstrated preliminary anti- tumor activities A Escalated to Dose Level 8 (DL8) with no DLT events • DLT evaluation completed at prior 7 dose levels, DL8 currently under evaluation • DLT not observed, suggesting the drug being safe and well-tolerat
Slide 15: Human pharmacokinetics profile as expected
Human pharmacokinetics profile as expected CS5001 and Total Antibody Mean Concentration-Time • PK data suggested a dose proportional exposure of CS5001 following i.v. administration • Immunoconjugate exhibited excellent linker stability, with close similarity observed between ADC and total antibody
Slide 16: Background information of three relevant ADCs for safety comparisons
Background information of three relevant ADCs for safety comparisons CS5001 Zilovertamab Vedotin Loncastuximab Tesirine (ROR1/PBD prodrug) (ROR1/MMAE) (CD19/naked PBD) Antibody Fully human ROR1 mAb Humanized ROR1 mAb Humanized CD19 mAb Linker Isoprenoid--glucuronide Mc-vc-PAB cathepsin-cleavable va
Slide 17: Favorable phase 1 safety profile of CS5001 vs. two other relevant ADCs
Favorable phase 1 safety profile of CS5001 vs. two other relevant ADCs Lower frequency of hematologic and nonhematologic AEs observed for CS5001 up to Dose Level 7 Hematologic TEAEs Nonhematologic TEAEs 80% 80% 70% 70% 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% Platelet count Neutrophil c
Slide 18: CS5001 exhibited lower hematologic toxicity across different dose levels
Comparing to other PBD-based ADC, CS5001 exhibited lower hematologic toxicity across different dose levels Hematologic TEAEs by Dose Levels-Loncastuximab Tesirine vs. CS5001 Loncastuximab Tesirine CS5001 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% <=90ug/kg 120ug/kg 150ug/kg 200ug/kg total DL1-4 DL5 DL6
Slide 19: Preliminary efficacy observed in Hodgkin Lymphoma during dose escalation
Preliminary efficacy observed in Hodgkin Lymphoma during dose escalation Two partial responses and one mixed response observed in Hodgkin Lymphoma patients Best Changes in Index Tumor Dimensions • Five Hodgkin Lymphoma patients from DL3, DL5 and DL6 had at least one post-baseline tumor assessment ➢
Slide 20: Patient 0104003: 33-year-old male, Stage IV Hodgkin Lymphoma
Patient 0104003: 33-year-old (y/o) male, Stage IV Hodgkin Lymphoma ✓ The patient’s disease relapsed following two prior lines of chemotherapies, which included ABVD and RCHOP. ✓ After receiving 4 cycles of CS5001 treatment, a partial response was observed per Lugano 2014. Baseline After 4 cycles tre
Slide 21: Patient 0104002: 34 y/o female, Stage IV Hodgkin Lymphoma
Patient 0104002: 34 y/o female, Stage IV Hodgkin Lymphoma ✓ The patient had a refractory disease following five prior lines of therapies, which included ABVD, GVD, Sintilimab+Decitabine, ICE+Sintilimab, and IBI-322. ✓ Following 4 cycles of CS5001 treatment, a partial response was observed per Lugano
Slide 22: Preliminary efficacy observed in Pancreatic Adenocarcinoma during dose escalation
Preliminary efficacy observed in Pancreatic Adenocarcinoma during dose escalation One partial response observed in pancreatic adenocarcinoma • 52 y/o Jordanian female with advanced pancreas Changes in Tumor Size and Tumor Marker Level from Baseline adenocarcinoma treated at Scientia Clinical Researc
Slide 23: Patient 0201010: 52 y/o female with advanced pancreatic adenocarcinoma
Patient 0201010: 52 y/o female with advanced pancreatic adenocarcinoma Screening After 9 weeks of CS5001 treatment After 18 weeks of CS5001 treatment 37 mm 28 mm (SD -24%) 24 mm (PR -35%) ✓ 52 y/o female with advanced pancreatic adenocarcinoma ✓ Baseline MRI: target lesion pancreatic surgical bed so
Slide 24: Summary
Summary CS5001, a novel ROR1–directed PBD-ADC, appears well tolerated and safe in the first-in- 1 human phase 1 study • No DLT was observed and MTD was not reached • Lower toxicities were observed comparing to other relevant ADCs CS5001 demonstrated preliminary antitumor activities in both solid tum
Slide 25: 2. PD-L1 ex-China Progress
1. ROR1 ADC Updates 2. PD-L1 ex-China Progress Agenda 3. Commercialization Strategy 4. Expected Catalysts 26
Slide 26: Sugemalimab – Ex-China Progress
Sugemalimab – Ex-China Progress EU/UK MAA regulatory review proceeding as expected; positive feedback from FDA type B consultation EMA MAA: 2023 • D120 LoQ received in Jun. with all the questions addressed Transition from EQRx completed and response submitted in Oct. Aug 8 • D180 LoOI received from
Slide 27: 3. Commercialization Strategy
1. ROR1 ADC Updates 2. PD-L1 ex-China Progress Agenda 3. Commercialization Strategy 4. Expected Catalysts 28
Slide 28: Commercialization Strategy
Commercialization Strategy Leverage the strength of partners in commercialization to maximize the value of commercial / late-stage pipeline Nov. 1st, 2023 Nov. 8th, 2023 Partner with: Partner with: Strategic partnership and Exclusive commercial exclusive licensing promotion right Nofazinlimab Pralse
Slide 29: Internally-developed multiple pipeline assets for future growth
Internally-developed multiple pipeline assets for future growth Tri-specific antibody CS2009 ✓ Potential FIC next-generation IO backbone to replace current PD-(L)1 based SOC (PD-1 x VEGF x another IO target) ✓ Target 3 critical immune-suppressive pathways in the tumor microenvironment Expect IND in
Slide 30: 4. Expected Catalysts
1. ROR1 ADC Updates 2. PD-L1 ex-China Progress Agenda 3. Commercialization Strategy 4. Expected Catalysts 31
Slide 31: Expected Catalysts for the Next 12 Months
Expected Catalysts for the Next 12 Months Assets Catalysts Date Sugemalimab (PD-L1) Marketed Regulatory decision for 1L stage IV NSCLC in EU and ex-China partnership exploration 1H 2024 Regulatory decision for 1L stage IV NSCLC in UK 2H 2024 NDA approval for 1L GC/GEJ in mainland China Q1 2024 Lorla
Slide 32: Thanks
Thanks 33
Slide 33: Q&A
Q&A 34
Slide 34: END
END 35
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