Sutro Biopharma, Inc. · NASDAQ:STRO
Sutro Biopharma — ASH Annual Meeting 2017
16 slides from Sutro Biopharma's conference presentation, Dec 11, 2017
Slide 1: High Frequency of CD74 Expression in B-cell NHL and Targeting with STRO-001
High Frequency of CD74 Expression in B-cell Non-Hodgkin’s Lymphoma (NHL) and Targeting with STRO-001, a Novel Anti-CD74 Antibody Drug Conjugate (ADC) with Potent In Vitro Cytotoxicity and In Vivo Anti-Tumor Activity Arturo Molina, MD, MS Sutro Biopharma ASH Annual Meeting December 11, 2017
Slide 2: Co-Authors & Disclosures
Co-Authors & Disclosures Sutro Abigail Yu, Cristina Abrahams, Millicent Embry, Xiaofan Biopharma Li, Robert Henningsen, Venita DeAlmeida, Shannon Matheny, Toni Kline, Alice Yam, Ryan Stafford, Trevor Hallam, Mark Lupher and Arturo Molina are employees of Sutro Biopharma Stanford Shuchun Zhao, Yasodh
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: Combining Optimized Antibody, Conjugation Sites, Linker and Warhead
STRO-001: 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 confer the hig
Slide 7: Anti-CD74 Antibody SP7219 Binds to Both Human and Cyno CD74 Extracellular Domain
Anti-CD74 Antibody SP7219 Binds to Both Human and Cyno CD74 Extracellular Domain with High Affinity Biochemical Characterization of SP2719 Antibody Kd Biacore; recombinant human CD74 ECD 1.74 nM Biacore; recombinant cynomolgus monkey CD74 ECD 2.70 nM Biacore; recombinant mouse CD74 ECD No Binding FA
Slide 8: Frequent CD74 Expression in Multiple B-cell NHL Subtypes by IHC
Frequent CD74 Expression in Multiple B-cell NHL Subtypes by IHC CD74 positive % B cell lymphoma – total samples 404/423 96 Follicular lymphoma 148/151 98 Grade 1 and 2 90/91 99 Grade 3 A and B 58/60 97 Diffuse large B-cell lymphoma 135/140 96 Extranodal marginal zone lymphoma 22/24 92 Splenic margin
Slide 9: Frequent CD74 Expression in Multiple B-cell NHL Subtypes by IHC
Frequent CD74 Expression in Multiple B-cell NHL Subtypes by IHC DLBCL Follicular Mantle Cell NHL Lymphoma x400 x400 x400
Slide 10: STRO-001 Exhibits Potent In vitro Cytotoxicity Across Multiple Cell lines
STRO-001 Exhibits Potent In vitro Cytotoxicity Across Multiple Cell lines STRO-001 Cell Killing Disease Cell Line CD74 Receptor Copy# EC50 (nM) Span (%) OCI-Ly3 77,435 0.54 95 Activated B-cell-like U2932 10,649 2 79 Diffuse Large B-Cell Lymphoma (ABC-DLBCL) RI-1 <4,131 3.7 72 SU-DHL-2 <4,131 NC NC W
Slide 11: Effect of STRO-001 Treatment on U2932 ABC-DLBCL Xenograft Tumor Growth
Effect of STRO-001 Treatment on U2932 ABC-DLBCL Xenograft Tumor Growth
Slide 12: Effect of STRO-001 Treatment on Jeko-1 Mantle Cell Lymphoma Xenograft Tumor Growth
Effect of STRO-001 Treatment on Jeko-1 Mantle Cell Lymphoma Xenograft Tumor Growth
Slide 13: Effect of STRO-001 on Survival in Disseminated Mino Xenograft Model
Effect of STRO-001 Treatment on Survival in the Disseminated Mino Mantle Cell Lymphoma Xenograft Model
Slide 14: STRO-001 Demonstrates Potent Anti-tumor Activity in Disseminated MM.1S-luc Model
STRO-001 Demonstrates Potent Anti-tumor Activity in Disseminated MM.1S-luc Model D7 D14 D21 D28 Vehicle photons/second photons/second 1 mg/kg STRO-001 14 Similar response with 3 and 10 mg/kg STRO-001 • Single dose of 1, 3, and 10 mg/kg STRO-001 results in significant reduction of tumor burden on day
Slide 15: Conclusions (1)
Conclusions (1) • Sutro’s cell-free antibody synthesis and site-specific conjugation technologies were used to generate STRO-001, an optimized CD74-targeting ADC with a DAR of 2 • CD74 is detected in 404/423 (96%) of B-cell NHL specimens in this large IHC study • STRO-001 exhibits potent in vitro cy
Slide 16: Conclusions (2)
Conclusions (2) • STRO-001 exhibits potent in vivo anti-tumor activity in NHL and myeloma xenograft models • STRO-001 produces dose-dependent B cell depletion in the cynomolgus monkey, consistent with the intended pharmacodynamic effect • STRO-001-BCM1, a phase 1 study of STRO-001 in B-cell NHL and