Tempus Ai, Inc. · NASDAQ:TEM

Tempus Ai — Technical Presentation (December 2021)

14 slides from Tempus Ai's technical presentation, Dec 7, 2021

  1. Slide 1: Loss of ASXL1 tumor suppressor promotes resistance to CDK4/6 inhibitors in ER+ breast cancer

    December 7-10, 2021 Loss of ASXL1 tumor suppressor promotes resistance to CDK4/6 inhibitors in ER+ breast cancer Dhivya R. Sudhan1, Sumanta Chatterjee1, Jiwoong Kim2, Yunguan Wang2, Vishal Kandagatla1, Dan Ye1, Chang-Ching Lin1, Jorge Gomez Tejeda Zanudo3, Esha Jain3, Arnaldo Marin1, Alberto Servett

  2. Slide 2: Disclosure statement

    San Antonio Breast Cancer Symposium®, December 7 -10, 2021 Disclosure statement • AstraZeneca employee since October 2021 • All data were generated during my tenure at the Simmons Comprehensive Cancer Center, in the laboratory of Dr. Carlos Arteaga This presentation is the intellectual property of D

  3. Slide 3: Novel approaches to unravel the CDK4/6 inhibitor resistance landscape

    San Antonio Breast Cancer Symposium®, December 7 -10, 2021 Novel approaches to unravel the CDK4/6 inhibitor resistance landscape Genomic profiling of MBCs progressing on CDK4/6i has identified several resistance- associated somatic alterations, albeit at low frequencies – • RB1 mutations (6/127; 4.7

  4. Slide 4: Accelerated mutagenesis screen to discover novel resistance mutations

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 Accelerated mutagenesis screen to discover a spectrum of novel mutations causally associated with resistance to CDK4/6 blockade Impaired DNA repair accelerates the rate of nucleotide substitution leading to rapid accumulation of new mutations

  5. Slide 5: Accelerated mutagenesis screen: number of mutations accumulated

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 Accelerated mutagenesis screen to discover a spectrum of novel mutations causally associated with resistance to CDK4/6 blockade 200 T47D Parental T47D MSH2-/- lines 150 # of mutations 100 50 0 se e ift se *cross-resistant to fulvestrant e n a

  6. Slide 6: Top hits are associated with clinical resistance to CDK4/6 inhibitors

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 Top hits are associated with clinical resistance to CDK4/6 inhibitors DFCI CCPM / MBC Project Hugo Symbol Protein Change Drug Resistance Category ASXL1 p.RGGE65fs Palbociclib Acquired ASXL1 p.E484K Palbociclib Intrinsic ASXL1 p.E824Q Palbocic

  7. Slide 7: Additional Sex Combs Like Transcriptional Regulator 1 (ASXL1)

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 Additional Sex Combs Like Transcriptional Regulator 1 (ASXL1) Heterozygous truncating mutations in the ASXL1 gene is a common event in myeloid malignancies ASXL1 inactivation induces epigenetic and transcriptional reprogramming through global

  8. Slide 8: ASXL1 deficient ER+ breast cancer cells are resistant to CDK4/6 inhibition

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 ASXL1 deficient ER+ breast cancer cells are resistant to CDK4/6 inhibition 150 150 cell number (% of control) cell number (% of control) shControl shControl shASXL1#1 shASXL1#1 100 shASXL1#2 100 shASXL1#2 50 50 0 0 -4 -2 0 2 -4 -2 0 2 log[pal

  9. Slide 9: ASXL1 deficiency leads to robust induction of E2F target genes

    Normalized enrichment score G E2 2M F (NES) 0 2 4 -4 -2 W M ch ta N yc e r g T c e - M targ kp ts o H cat itoti ets int ed en c _ g in sp V1 Sp eho sig ind er g s na le m ig lin at n g og ali en ng es m U E is TO V Hy M R re po T C s xi 1 po a si n g I n Ap na se TN fl o lin F am C Gl pto g C s ma

  10. Slide 10: Loss of function ASXL1 mutations are acquired in CDK4/6 inhibitor resistant ER+ MBCs

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 Loss of function ASXL1 mutations are acquired in CDK4/6 inhibitor resistant ER+ MBCs ASXL1 loss gene signature queried in clinical datasets CCPM RNAseq dataset MBC Project RNAseq dataset Pre Post-progression This presentation is the intellect

  11. Slide 11: ASXL1 deficiency leads to robust induction of cell cycle genes

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 ASXL1 deficiency leads to robust induction of cell cycle genes Palbociclib (P); Ribociclib (R); Abemaciclib (A) shCTRL shASXL1#1 shASXL1#2 Palbociclib - + - + - + NT CDK2#1 CDK2#2 100 CDK6 #1 CDK6 #2 CCNE1#1 cyclin E1#1 cyclin E1#2 CCNE1#2 50

  12. Slide 12: ASXL1 deficient cells are sensitive to CDK1/CCNA2 targeting

    San Antonio Breast Cancer Symposium®, December 7-10, 2021 ASXL1 deficient cells are sensitive to CDK1/CCNA2 targeting 100 Cell cycle distribution (%) G1 S G2 50 RO3306 (CDK1 inhibitor) 0 - Palbo K03861 RO 3306 shCTRL 100 G1 Cell cycle distribution (%) S G2 50 0 - Palbo K03861 RO 3306 shASXL1#1 CDK2

  13. Slide 13: Summary

    San Antonio Breast Cancer Symposium®, December 7 -10, 2021 Summary Accelerated mutagenesis screening platform discovered a spectrum of novel mutations associated with resistance to CDK4/6 blockade ASXL1 deficiency leads to robust induction of several cell cycle genes thus bypassing G1 arrest induced

  14. Slide 14: Acknowledgements

    San Antonio Breast Cancer Symposium®, December 8 -11, 2020 Acknowledgements Arteaga Laboratory Dana Farber Cancer Institute Carlos Arteaga, MD (Mentor) Nikhil Wagle, MD Sumanta Chatterjee, PhD Jorge Gomez Tejeda Zanudo, PhD Ariella Hanker, PhD Esha Jain, PhD Vishal Kandagatla, MS Dan Ye, MD TEMPUS A

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