Sutro Biopharma, Inc. · NASDAQ:STRO
Sutro Biopharma — ASH Annual Meeting 2016
18 slides from Sutro Biopharma's conference presentation, Dec 4, 2016
Slide 1: Targeting CD74 with Novel Antibody Drug Conjugates (ADCs) for B-Cell Non-Hodgkin's Lymphoma
Targeting CD74 with Novel Antibody Drug Conjugates (ADCs) for the Treatment of B-Cell Non-Hodgkin’s Lymphoma Arturo Molina, MD, MS Sutro Biopharma ASH Annual Meeting December 4, 2016
Slide 2: Co-Authors & Disclosures
Co-Authors & Disclosures Sutro Xiaofan Li, Cristina Abrahams, Millicent Embry, Biopharma Abigail Yu, James Zawada, Heather Stephenson, Maureen Bruhns, Stuart Bussell, Alexander Steiner, Adam Galan, Toni Kline, Alice Yam, Ryan Stafford, Heidi Hoffmann, Shannon Matheny, Venita DeAlmeida, Nicki Vasquez
Slide 3: CD74 Expression in B-cell Lymphoma and Myeloma
CD74 Expression in B-cell Lymphoma and Myeloma • CD74 is a transmembrane glycoprotein involved in MHC protein formation and transport • Observed in ~90% of B-cell malignancies evaluated • Minimally expressed in normal tissue Immunohistology of patient biopsy specimens No. positive / % Target Diagnos
Slide 4: Antibody Drug Conjugates: Components and Mechanism of Action
Antibody Drug Conjugates: Components and Mechanism of Action Antibody Antibody: Specifically targets the drug to the tumor cell, usually internalized upon binding to target Conjugation site: Random (lysine) or site-specific Linker: Cleavable or non-cleavable, stable in plasma Drug: Cytotoxic with di
Slide 5: Sutro's CD74-Targeting ADCs: Cell-Free Aglycosylated Antibody Synthesis With Site-Specific Conjugation
Sutro’s CD74-Targeting ADCs: Cell-Free Aglycosylated Antibody Synthesis With Site-Specific Conjugation
Slide 6: STRO-001 and SP7676: Combining Optimized Antibody, Conjugation Sites, Linker and Warhead
STRO-001 and SP7676: Combining Optimized Antibody, Conjugation Sites, Linker and Warhead Antibody: Aglycosylated, high affinity and specificity Warhead: Non-cleavable maytansinoid linker-warhead. DAR of 2. Major catabolite has limited permeability Optimized Conjugation Sites: Specific sites that con
Slide 7: Cytotoxicity of STRO-001 in ABC-DLBCL Cell Lines
Cytotoxicity of STRO-001 in ABC-DLBCL Cell Lines STRO-001 Cell Line IC50 Span (nM) (%) OCI-Ly3 0.46 96 U2932 1.3 80 RI-1 3.3 77 SU-DHL-2 >100 N/A
Slide 8: Efficacy of STRO-001 in GCB-DLBCL Cell Lines
Efficacy of STRO-001 in GCB-DLBCL Cell Lines STRO-001 Cell Line IC50 Span (nM) (%) SU-DHL-4 0.24 97 WSU- 0.17 97 DLCL-2 SU-DHL-6 0.56 96 OCI-Ly19 1.3 38 NUDUL-1 0.3 98 WSU-NHL 0.69 96 Pfeiffer 0.54 88 HT 0.34 68 OCI-Ly1 0.69 96
Slide 9: Efficacy of STRO-001 in Mantle Cell Lymphoma Cell Lines
Efficacy of STRO-001 in Mantle Cell Lymphoma Cell Lines STRO-001 Cell Line IC50 Span (nM) (%) Mino 0.5 97 JVM-2 1.2 60 Rec-1 15 53 JeKo-1 0.4 97
Slide 10: Cytotoxicity of STRO-001 in Other B-cell Malignant Cell Lines
Cytotoxicity of STRO-001 in Other B-cell Malignant Cell Lines - Follicular, Hodgkin’s, ALL, CLL STRO-001 Cell Line IC50 Span (%) (nM) WSU- 0.5 92 FSCCL RPMI-6666 1 85 SUP-B15 3 65 JVM-13 1.5 65
Slide 11: SP7676 is Active in WSU-DLCL2 Double Hit GCB-DLBCL Xenograft Model
SP7676 is Active in WSU-DLCL2 “Double Hit” GCB-DLBCL Xenograft Model Vehicle SP7219 SP7676 (10mg/kg Q7Dx3)x2 SP7676 (10mg/kg Q3Dx5)x2 2000 1500 Tumor Volume (mm3) 1000 500 0 -500 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 Days Post Inoculation
Slide 12: SP7676 Exhibits Potent Anti-tumor Activity in ABC-DLBCL OCI-LY10 Xenograft Model
SP7676 Exhibits Potent Anti-tumor Activity in the ABC-DLBCL OCI-LY10 Xenograft Model 2000 1500 Tumor Volume (mm3) Vehicle 1000 SP7219 CHOP SP7676 (10mg/kg Q3Dx5) SP7676 (10mg/kg Q7Dx3) 500 SP7676 (3mg/kg Q3Dx5) SP7676 (1mg/kg Q3Dx5) 0 20 40 60 Days Post Tumor Inoculation
Slide 13: STRO-001 and SP7676 are Equally Efficacious in the SU-DHL-6 Tumor Model
STRO-001 and SP7676 are Equally Efficacious in the SU-DHL-6 (GCB) Tumor Model
Slide 14: STRO-001 Inhibits Tumor Growth in Dose-Dependent Manner in SU-DHL-6 Xenografts
STRO-001 Inhibits Tumor Growth in Dose- Dependent Manner in SU-DHL-6 Xenografts
Slide 15: STRO-001 and SP7676 Ablate Myeloma Cells in Bone Marrow in ARP-1 Model
STRO-001 and SP7676 Ablate Myeloma Cells in Bone Marrow in ARP-1 Disseminated Myeloma Model - Poster #4465 Monday, Dec 5, 6pm-8pm CD138+ Non-inoculated Control (NIC) Vehicle STRO-001 SP7676
Slide 16: STRO-001 Inhibits Tumor Growth in ARP-1 Disseminated Myeloma Model
STRO-001 Inhibits Tumor Growth in ARP-1 Disseminated Myeloma Model - Poster #4465 Monday, Dec 5 6pm-8pm STRO-001 (3 mg/kg, q1wx4) inhibits visceral tumor growth Tumor-Bearing Animals Healthy animals Vehicle STRO-001 NIC Ovary: Kidney:
Slide 17: STRO-001 Induces Dose-Responsive Ablation Of B-cells in Cynomolgous Monkeys
STRO-001 Induces Dose-Responsive Ablation Of B-cells in Cynomolgous Monkeys Control (0 mg/kg) 1 mg/kg 3 mg/kg 10 mg/kg 30 mg/kg 2 doses total, given Days 1 and Day 15; Day 15 samples pre-dose
Slide 18: Conclusions
Conclusions • Sutro Biopharma’s cell-free antibody synthesis and site-specific conjugation technologies were used to generate optimized CD74- targeting ADCs • STRO-001 exhibits potent cell killing across multiple lymphoma cell lines • STRO-001 and SP7676, exhibit potent anti-tumor activity in lympho