Kymera Therapeutics, Inc. · NASDAQ:KYMR

Kymera Therapeutics — Technical Presentation (December 2020)

9 slides from Kymera Therapeutics's technical presentation, December 2020

  1. Slide 1: KTX-120, A Novel IRAKIMiD Degrader of IRAK4 and IMiD Substrates

    KTX-120, A Novel IRAKIMiD Degrader of IRAK4 and IMiD Substrates, Shows Preferential Activity and Induces Regressions in MYD88-Mutant DLBCL Cell and Patient Derived Xenograft Models D u n c a n H . W a l k e r, M i c h e l e M a y o , C h r i s t i n e K l a u s , D a p e n g C h e n , S a m y a b r

  2. Slide 2: Disclosures

    Disclosures Duncan H. Walker, Michele Mayo, Christine Klaus, Dapeng Chen, Samyabrata Bhaduri, Kirti Sharma, Scott Rusin, Alice McDonald, Jared Gollob, Nello Mainolfi, Matthew Weiss: Kymera Therapeutics Employment and Equity Ownership. ©2020 KYMERA THERAPEUTICS, INC. PAGE 2 CONFIDENTIAL

  3. Slide 3: IRAK4 Degradation and IMiDs have Complementary Activity

    IRAK4 Degradation and IMiDs have Complementary Activity IMiD Degrader IRAKIMiD Degrader CRBN IMiD CRBN IMiD IRAK4 IL-1R (E3 Ligase) Binder (E3 Ligase) Binder LINKER Binder B Cell Receptor IFNAR1/2 Degradation of IMiD Substrate s Degradation of IMiD Substrates and IRAK4 IRAK4 Degraders inhibit NFkB a

  4. Slide 4: KTX-120: Potent Degrader of Substrates

    KTX-120: Potent Degrader of IRAK4 and IMiD Substrates Deep Proteomics show degradation of IRAK4 and IMiD substrates in PBMC and OCI-Ly10 • Activation of Type 1 IFN signaling in OCI-Ly10 MYD88MT DLBCL PBMC OCI-Ly10 DC90 24hr IC90 16hr Degradation time course shows hierarchical substrate degradation •

  5. Slide 5: KTX-120 Shows Strong In Vitro Activity in MYD88MT DLBCL Superior to Potent IMiD

    KTX-120 Shows Strong In Vitro Activity in MYD88MT DLBCL that is Superior to Potent IMiD Cell line Co Mutations KTX-120 (CTG IC50, nM) OCI-LY10 CD79B, TNFAIP3 7 MYD88 Mut TNFAIP3, IRF4, SU-DHL2 14 BCL6 KTX-120 shows potent and preferential TMD8 CD79B, IRF4 29 activity in MYD88MT DLBCL lines regardles

  6. Slide 6: KTX-120 Degrades Substrates and Induces Regressions in MYD88MT DLBCL CDx Models

    KTX-120 Degrades IRAK4 and IMiD Substrates and Induces Regressions in MYD88MT DLBCL CDx Models KTX-120 IV PK/PD in OCI-Ly10 10000 1.50 IRAK4/Ikaros (% of control) 1.25 1000 [KTX-120] (ng/g) 1.00 KTX-120 shows strong activity, including regressions, in multiple MYD88-MT tumor 100 0.75 0.50 xenograft

  7. Slide 7: KTX-120 Shows Regressions in MYD88MT Patient-Derived Xenograft Models

    KTX-120 Shows Regressions in MYD88MT Patient-Derived Xenograft Models KTX-120 PDX LY14019CD79mut/MYD88L265Pmut Model MYD88 CD79B TNFAIP3 Other (%TGI) 2000 LY14019 L265P MT MT 100 Tumor Volume (mm3) LY2264 L265P MT IRF4 100 1500 LY2298 L265P MT BCL2/BCL6 90 median 1000 LY12699 L265P MT 87 LY2345 WT M

  8. Slide 8: KT-413 (KTX-120) is a Development Candidate IRAKIMiD Degrader

    KT-413 (KTX-120) is a Development Candidate IRAKIMiD Degrader • Potent, equipotent degrader of IRAK4 and IMiD substrates • Potent, preferential activity in MYD88MT DLBCL cell lines • Rapid onset of cell death - commitment to death within 48-72h • Superior cell activity compared to the IMiD CC-220 in

  9. Slide 9: Thank You

    THANK YOU December 2020

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