Kymera Therapeutics, Inc. · NASDAQ:KYMR

Kymera Therapeutics — Technical Presentation (April 2021)

11 slides from Kymera Therapeutics's technical presentation, April 2021

  1. Slide 1: Mechanisms Underlying Synergistic Activity of KT-413, a Targeted Degrader of IRAK4 and IMiD Substrates

    Mechanisms Underlying Synergistic Activity of KT-413, a Targeted Degrader of IRAK4 and IMiD Substrates in Hematopoietic Cancers Christine Klaus, Scott Rusin, Samya Bhaduri, Dirk Walther, Kirti Sharma, Michele Mayo, Alice McDonald, Matthew Weiss, Duncan Walker, Rahul Karnik Poster # LB118

  2. Slide 2: Forward-Looking Statements

    Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA) and other federal securities laws. These statements include information about our current and future prospects and our operations and fi

  3. Slide 3: Financial Disclosures

    Financial Disclosures Christine Klaus, Scott Rusin, Samya Bhaduri, Dirk Walther, Kirti Sharma, Michele Mayo, Alice McDonald, Matthew Weiss, Duncan Walker, Rahul Karnik Kymera Therapeutics Employment and Equity Ownership. © 2 0 2 1 K YM E R A T H E R A P E U T I C S , I N C . PAGE 3

  4. Slide 4: KT-413 Targets Redundant Pro-survival Pathways in MYD88 MT DLBCL

    KT-413 Targets Redundant Pro-survival Pathways in MYD88MT DLBCL • Alternative pathway activation of NF-kB and downregulation of cell death signals is common in MYD88MT lymphoma via activating mutations in CD79B and CARD11, TNFAIP3 loss, or IRF4 upregulation • Inhibiting multiple pathways of NF-kB ac

  5. Slide 5: KT-413 Selectively Degrades IRAK4 and IMiD Substrates

    KT-413 Selectively Degrades IRAK4 and IMiD Substrates KT-413 41 nM CC220 at 41 nM KTX-545 at 5 nM Peripheral blood mononuclear IMiD Substrates IRAK4 cells (PBMCs) were treated 3 with KT-413 for 16 hours and subsequent -log10(p-value) quantitative 2 proteomic analysis was IRAK4 performed IRAK4 Ikaros

  6. Slide 6: KT-413 is Active in MYD88MT Lymphoma and Shows Greater Activity than IRAK4-Selective Agents or IMiDs

    KT-413 is Active in MYD88MT Lymphoma and Shows Greater Activity than either IRAK4-Selective Agents or IMiDs Alone OCI-Ly10 SUDHL2 Compound OCI-Ly10 SUDHL2 CGI max CGI max IC50 (nM) IC50 (nM) (%) (%) Fraction of DMSO Fraction of DMSO KT-413 28 99.3 35 99.9 CC-220 62 83.2 128 79 KTX-545 -- 5 1960 94 l

  7. Slide 7: KT-413 is More Efficacious than IMiDs In Vivo

    KT-413 is More Efficacious than IMiDs In Vivo • We have previously demonstrated that KT-413 is highly active with intermittent (QW, Q2W) dosing • In the OCI-Ly10 MYD88MT xenograft model, KT-413 dosed at 9mg/kg on D1,2 every 3 weeks induced strong regressions • The IMiDs pomalidomide or CC220 (dosed

  8. Slide 8: KT-413 Uniquely Inhibits Both IRAK4 and IMiD Dependent Pathways

    KT-413 Uniquely Inhibits Both IRAK4 and IMiD Dependent Pathways Demonstrating the Dual-Targeting Activity of IRAKIMiDs KT-413 Inhibits MYD88-dependent A NF-kB Transcription B DMSO CC-220 KT-413 KTX-545 60nM 60nM 10nM 16h 48h 16h 48h 16h 48h 16h 48h 2h 8h 2h 8h 2h 8h 2h 8h IRF4 IRF7 Actin A. KT-413 a

  9. Slide 9: KT-413 Preferentially Downregulates NF-kB, Cell Cycle and Upregulates Apoptosis Pathways

    KT-413 Preferentially Downregulates NF-kB, Cell Cycle and Upregulates Apoptosis Pathways Compared to IMiDs or IRAK4-Selective Degradation Preferential downregulation of NF-kB and cell cycle pathways and upregulation of IFN signaling and apoptosis signals are consistent with greater and more potent K

  10. Slide 10: KT-413 Activates CDKN2A and BNIP3L, while CC220 Does Not

    KT-413 Activates CDKN2A and BNIP3L, while CC220 Does Not • Analysis of upstream pathways regulated by KT-413 (by Ingenuity IPA upstream regulator analysis) identified both pro-apoptotic and cell cycle regulation as exclusively activated by KT-413 as compared to CC220; these pathways are not observed

  11. Slide 11: Conclusions

    Conclusions • KT-413 is a potent, selective degrader of both IRAK4 and IMiD substrates in DLBCL cells • KT-413 is more potent with greater cell kill in MYD88MT cell lines compared to IMiDs or IRAK4 degradation or inhibition • KT-413 shows superior in vivo activity in MYD88MT lymphoma compared to IMi

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