Kymera Therapeutics, Inc. · NASDAQ:KYMR

Kymera Therapeutics — Society for Investigative Dermatology 2021 Annual Meeting

14 slides from Kymera Therapeutics's conference presentation, May 2021

  1. Slide 1: Multiple Mediators of Inflammation Correlate with IRAK4 Expression in HS Skin

    Multiple Mediators of Inflammation Correlate with IRAK4 Expression in the Skin of Hidradenitis Suppurativa Patients and are Blocked by the IRAK4 Degrader KT-474 in TLR-activated Monocytes Afsaneh Alavi, Veronica Campbell, Alice McDonald, Stephanie Skouras, Jeffrey Davis, Anthony Slavin, Rahul Karnik

  2. Slide 2: Forward-looking Statements

    Forward-looking Statements This presentation and statements made orally during this presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA) and other federal securities laws. These statements include beliefs and conclusions r

  3. Slide 3: Financial Disclosures

    Financial Disclosures Afsaneh Alavi Dr. Alavi has been investigator and received honoraria from AbbVie, Arcutis, BMS, Boehringer-Ingelheim, Bausch, Celgene , Dermira, Dermovant, DSBiopharma, Eli Lilly, EMD Serono, Galderma, Glenmark, GSK, Incyte, Ilkos, Janssen, LEO Pharma, Kyowa Kirin, Kymera, Merc

  4. Slide 4: Central Role of IRAK4 in TLR/IL-1R Pathway Activation

    Central Role of IRAK4 in TLR/IL-1R Pathway Activation Development of Kymera IRAK4 degrader KT-474 IL-1/IL-18/IL-33/IL-36 • IRAK4 is a key component of the myddosome complex mediating signaling through TLRs and IL-1Rs TLRs IL-1Rs • Both the scaffolding and kinase functions of IRAK4 are involved in th

  5. Slide 5: Non-interventional Study of IRAK4 and Inflammatory Biomarkers in HS and AD Patients

    Non-interventional Study of IRAK4 and Inflammatory Biomarkers in HS and AD Patients Design Baseline Demographics & Biomarkers Single center (York Dermatology Clinic and Research Center, Ontario, Study • FPI: 28May2020 Number of Sites Canada) Duration • HS and AD accrual completed: 24Mar2021 PI: Dr.

  6. Slide 6: Methods for Measuring IRAK4 Protein and Pro-Inflammatory Gene Transcripts

    Methods for Measuring IRAK4 Protein and Pro-Inflammatory Gene Transcripts in HS Skin Biopsies and Healthy Subject Skin/Monocytes NI Study Methods Control Methods HS Skin Biopsies (N=30) Healthy Subject Skin Biopsies (N=10) Lesion (L), Peri-lesion (PL), Non-lesion (NL) IRAK4 IRAK4 Immunofluorescence

  7. Slide 7: IRAK4 Protein Expression is Elevated in HS Skin Compared to Skin from Healthy Subjects

    IRAK4 Protein Expression is Elevated in HS Skin Compared to Skin from Healthy Subjects Immunofluorescence (IF) Mass Spectrometry (MS) • Concordance between IF and MS for HS patients • HS patients: Lesion > Peri-lesion > Non-lesion • IF shows significant difference between HS Non-lesion skin and Immu

  8. Slide 8: IRAK4 is Upregulated in Dermis and Epidermis of HS Patients

    IRAK4 is Upregulated in Dermis and Epidermis of HS Patients Relative to Skin of Healthy Subjects Dermal Immune Cells Epidermal Keratinocytes • IF shows increased number of IRAK4+ immune cells in dermis with HS Lesion/Peri-lesion > HS Non- lesion > Healthy subjects • Epidermal IRAK4 positivity simila

  9. Slide 9: IRAK4 is Upregulated in Dermis and Epidermis of HS Patients

    IRAK4 is Upregulated in Dermis and Epidermis of HS Patients Relative to Skin of Healthy Subjects Dermal Immune Cells Lesion Peri-lesion Non-lesion Healthy subject Histology H&E Epidermal Keratinocytes IF Stain Nuclear IRAK4 Morphology • IF shows increased number of IRAK4+ Mask immune cells in dermis

  10. Slide 10: Transcriptional Profiling Shows Clear Differences Between HS Skin Biopsy Sites

    genes relative to Peri- PAGE 10 Lesion samples show Transcriptional Profiling Shows Clear Differences Between HS Skin many upregulated and Non-lesion p-value < 0.0001, fold change >= 4 samples Biopsy Sites, But Not Across Disease Severity Differentiated by Disease Severity Non-lesion Peri-lesion Mod

  11. Slide 11: Transcripts for Multiple Mediators of Inflammation are Upregulated in HS Skin Lesions

    Transcripts for Multiple Mediators of Inflammation are Upregulated in HS Skin Lesions Non-lesion Peri-lesion Healthy Lesion CCL2 CCL20 CSF3 CXCL1 Chemokines CXCL2 CXCL6 CXCL8 CXCL11 CXCL13 Cellular GZMB Cytotoxicity PRF1 IFNG IL10 IL1B Cytokines & IL32 Cytokine Signaling IL36G IL6 IRF7 SOCS3 TNF IL2

  12. Slide 12: Multiple Proinflammatory Transcripts Correlate with IRAK4 Protein Levels in HS Skin Lesions

    Multiple Proinflammatory Transcripts Correlate with IRAK4 Protein Levels in HS Skin Lesions IRAK4 Lesion Correlation vs. Non-lesion IF MS CCL2 &&/ &6) &;&/ Chemokines CXCL2 CXCL6 CXCL8 &;&/ &;&/ Spearman correlation ,)1* ,/ ,/% Cytokines & ,/ Cytokine Signaling ,/* ü IL6 IRF7 ü 62&6 TNF ,/5$ Cytokin

  13. Slide 13: IRAK4 Degrader KT-474 Inhibits TLR-Mediated Induction of Proinflammatory Transcripts

    IRAK4 Degrader KT-474 Inhibits TLR-Mediated Induction of HS- Overexpressed Proinflammatory Transcripts in Healthy Monocytes * *Lack of KT-474 effect on MYD88 consistent with MYD88 being upstream of IRAK4 ©2021 KYMERA THERAPEUTICS, INC. PAGE 13

  14. Slide 14: Conclusions

    Conclusions • IRAK4 is overexpressed in HS skin relative to healthy subjects due to increase in number of IRAK4+ dermal immune cells and epidermal keratinocytes • Higher expression in active HS skin Lesions compared to Peri-lesion and/or Non-lesion skin associated with increase in infiltrating IRAK4

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