Alx Oncology Holdings Inc. · NASDAQ:ALXO
Alx Oncology — Technical Presentation (2017)
11 slides from Alx Oncology's technical presentation, 2017
Slide 1: ALX148 is a High Affinity SIRPα Fusion Protein that Blocks CD47
ALX148 is a High Affinity SIRPα Fusion Protein that Blocks CD47, Enhances the Activity of Anti-Cancer Antibodies and Checkpoint Inhibitors, and Has a Favorable Safety Profile in Preclinical Models Steven E Kauder, Tracy C Kuo, Amy Chen, Ons Harrabi, Sony S Rocha, Laura Doyle, Sangeetha Bollini, Bora
Slide 2: The CD47-SIRPα Interaction Regulates Myeloid Cell Function
The CD47-SIRPα Interaction Regulates Myeloid Cell Function • CD47 – Broadly expressed cell Myeloid Cell surface protein Phagocytosis – Overexpressed on tumor cells Tumor Cell SIRPα CD47 Inflammation • SIRPα Activation – Receptor for CD47 on myeloid cells – Inhibitory signaling upon CD47 binding • CD
Slide 3: Unique Design of ALX148 is Responsible for Improved Safety
Unique Design of ALX148 is Responsible for Improved Safety ALX148 • Engineered SIRPα domain binds CD47 High Affinity SIRPα Domain with picomolar affinity S-S S-S • Blocks CD47-SIRPα interaction • Binds CD47 from humans, non-human primates, and mice Inactive Fc Domain • Fc domain does not bind Fcγ re
Slide 4: Enhances Activity of Targeted Antitumor Antibodies
ALX148 Enhances Activity of Targeted Antitumor Antibodies Phagocytosis of Daudi Inhibition of Z138 Xenograft Tumor Cells in vitro Tumorigenesis 2000 15 Tumor Volume, mm3 + SEM Phagocytosis, percent 1500 10 **** 1000 5 500 0 0 -2 -1 0 1 2 3 14 16 18 20 22 24 26 28 30 32 34 ALX protein, nM (log10) Day
Slide 5: Enhances Efficacy of Checkpoint Inhibitors in Multiple Syngeneic Models
ALX148 Enhances Efficacy of Checkpoint Inhibitors in Multiple Syngeneic Models Combination With Combination With αPD-1 in CT26 Model αPD-L1 in MC38 Model 800 Tumor volume, mm3 ± SEM 600 400 **** ** 200 0 5 10 15 20 Days post implantation PBS anti-PD-L1 ALX148 ALX148 + anti-PD-L1 BALB/c mice C57BL/6
Slide 6: Activates Splenic Dendritic Cells in Tumor-Bearing Mice
ALX148 Activates Splenic Dendritic Cells in Tumor-Bearing Mice CD8+ Dendritic Cells CD86 Expression CCR7 Expression Spleen CCR7 CD8+ DC of CD45 0.5 500 650 ** ** * ** ** * ** * Percent of CD45+ (MFI) (MFI) Geo Mean (MFI) 0.4 600 450 550 Mean 0.3 Mean 400 500 Geometric 0.2 450 350 Geo 0.1 400 0.0 300
Slide 7: ALX148 and Anti-PD-L1 Cooperatively Increase CD8+ T Cell Function in the Tumor
ALX148 and Anti-PD-L1 Cooperatively Increase CD8+ T Cell Function in the Tumor Infiltrating CD8+ T Cells IFNγ+ CD8+ T Cells Granzyme B+ CD8+ T Cells **** ** **** **** 0.8 * **** Percent of CD45+ Percent of CD45+ Percent of CD45+ **** **** 0.6 0.4 0.2 0.0 PBS ALX148 αPD-L1 ALX148 PBS ALX148 αPD-L1 AL
Slide 8: Reduces Immunosuppressive Populations in the Tumor Microenvironment
ALX148 Reduces Immunosuppressive Populations in the Tumor Microenvironment Tumor-Associated Myeloid-Derived Macrophages Suppressor Cells * ** 15 * * Percent of CD45+ ** * ratio M1/M2 Ratio 10 M1/M2 5 0 PBS ALX148 αPD-L1 ALX148 PBS ALX148 αPD-L1 ALX148 + + αPD-1 αPD-L1 BALB/c mice C57BL/6 mice CT26 t
Slide 9: Has a Favorable Safety Profile in Nonhuman Primates
ALX148 Has a Favorable Safety Profile in Nonhuman Primates • Four week repeat dose toxicity study • No ALX148 mechanism-related toxicity or adverse events up to 100 mg/kg • Separate PK/PD study: PK profile similar to CD47 antibody; Sustained CD47 target occupancy 12, 10 13, 1 Pharmacokinetics CD47 O
Slide 10: Summary
Summary ALX148 Inhibits the CD47-SIRPα Checkpoint ALX148 activates DCs, enhancing T cell priming ALX148 decreases suppressive cells ALX148 enhances macrophage ALX148 increases phagocytosis cytotoxic T cell function After Chen and Mellman, 2013 • ALX148 enhances the efficacy of antitumor and checkpoi
Slide 11: Summary
Summary ALX148 Inhibits the CD47-SIRPα Checkpoint ALX148 activates DCs, enhancing T cell priming ALX148 decreases suppressive cells ALX148 enhances macrophage ALX148 increases phagocytosis cytotoxic T cell function After Chen and Mellman, 2013 • ALX148 is currently being investigated in a Phase 1 cl
ALX Oncology Holdings — Technical Presentation (2017) on 6ix