Tango Therapeutics, Inc. · NASDAQ:TNGX
Tango Therapeutics — Technical Presentation (2021)
7 slides from Tango Therapeutics's technical presentation, 2021
Slide 1: CRISPR screens identify sensitizers to trametinib in KRAS mutant cancer cell lines
CRISPR screens identify sensitizers to trametinib in KRAS mutant cancer cell lines Silvia Fenoglio, Aileen Cristo, James Tepper, Teng Teng, Samuel Meier, Ashley Choi, Hongxiang Zhang, Shan-chuan Zhao, Shangtao Liu, Yi Yu, Leanne Ahronian, Dan Aird, Nikita M. Das, Robert Tjin Tham Sjin, Jannik N. And
Slide 2: The Tango Therapeutics CRISPR platform
The Tango Therapeutics CRISPR platform Expansive target space Single gRNA Diverse screening formats CRISPR(i/a) libraries Non- • 2D synthetic lethality screens redundant Genes with • 3D synthetic lethality screens paralogs Single gene or Mini-pool Isogenic • FACS-based screens target screens Paralog
Slide 3: Trametinib CRISPR screens in NSCLC and PDAC cell lines
Trametinib CRISPR screens in NSCLC and PDAC cell lines gene A549 H1355 H358 KP4 MIA Paca-2 MAPK1 1 16 3 1 1 FGFR1 2 2 2619 167 109 RAF1 3 1 7 3 11 BRAF 4 5 6 2 38 DMSO MAPK7 5 1695 1 453 3081 CRISPR library HS2ST1 SLC35B2 6 7 11 9 341 63 73 15 28 10 RCE1 8 23 740 13 84 MAPK EXTL3 9 35 276 40 17 PTPN
Slide 4: Target validation using minipool screens in an expanded cell line panel
Target validation using minipool screens in an expanded cell line panel GENE Synergy Log2FC CELL LINE HEPARAN SULFATE MAPK7 SYNTHETIC PATHWAY PATHWAY
Slide 5: SHOC2, MAPK7, MAP2K5 are validated sensitizers to MEKi
SHOC2, MAPK7, MAP2K5 are validated sensitizers to MEKi COMPETITION ASSAY NCI H358 NCI H358 Transform X of Tram 11/12 4k norm to low dose A549 DMSO 1 nM 3 nM 10 nM 60 100 % CTG 40 %RFP 20 50 0 A549 7 T A M TR PK W 84 84 C + K K sg M A 7 + + sg PK 7 7 M A PK PK 0 A A sg gM M s sg -5 -4 -3 -2 -1 0 Tram
Slide 6: Conclusions
Conclusions ▪ CRISPR screening identifies gene KO that enhance the response to trametinib ▪ Distinct signaling pathways are uniquely involved in trametinib resistance in different cell lines ▪ MAPK7, SHOC2 and HS2ST1are validated sensitizers to trametinib (Leanne Ahronian, poster P146 for HS2ST1 val
Slide 7: Thank you!
Thank you! • Tango Therapeutics: • Contract research partners: Scientific teams at ChemPartner Contact information • Tango Therapeutics: [email protected]