#1KYMERA 5 KYMERA EST. 2016 Kymera 2021 R&D Day December 16, 2021 KYMERA R&D DAY - December 16th, 2021#2Forward-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 financial results, which are based on currently available information. All statements other than statements of historical facts contained in this presentation, including express or implied statements regarding our strategy, future financial condition, future operations, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. 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KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 2#3Kymera 2021 R&D Day Nello Mainolfi, Ph.D., Founder, President and CEO, Kymera KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#4KYMERA Proteome Editing is the New Frontier of Medicine Genome Essentially static Alterations are responsible for some diseases Editing is irreversible ©2021 KYMERA THERAPEUTICS, INC. C Encodes KYMERA R&D DAY - December 16th, 2021 Proteome Changes based on internal (genetic) and external (epigenetic) events Alterations are responsible for all diseases Editing is reversible PAGE 4#5E3 1 Proteome Editing with Targeted Protein Degradation A Nobel Prize (2004) Inspired Technology KYMERA Disease-causing Target Protein Degrader E2 Peptides from Degraded Protein Ubiquitin 3 Ubiquitin Proteasome System (UPS) Proteasome 2 ©2021 KYMERA THERAPEUTICS, INC. Targeted Small Molecule Protein Degraders Ubiquitin Chain KYMERA R&D DAY - December 16th, 2021 ● Expanded Opportunities Small molecule binds to E3 and target protein to effect its degradation Small Molecule only needs to "weakly" bind to protein: Not inhibit its function Highly potent/catalytic: Small amount of drug needed Highly specific Genetic-like knock-down effects Advantage of small molecule development: Route of administration, manufacturing Agnostic to protein type and disease PAGE 5#6Expanding Druggable Proteome with Targeted Protein Degradation All therapeutic modalities to date only drug up to 20% of proteome KYMERA ©2021 KYMERA THERAPEUTICS, INC. Undrugged Opportunity Drugged C Traditional Small Molecule Antibody KYMERA R&D DAY - December 16th, 2021 #DOD Antisense N TIT Cell/Gene Therapy RNAi Kymera is expanding the drugged proteome with Targeted Protein Degradation (TPD) PAGE 6#7Exponential Clinical Pipeline Growth of Degraders C Existing Modalities TTTTTTT Therapeutic Modality Small molecule inhibitor Antibody Drugs FDA Approved >2000 >100 ~10 ~5 ~4 ~3 ASO Cell Therapy Gene Therapy RNAi Gene editing KYMERA ©2021 KYMERA THERAPEUTICS, INC. Targeted Protein Degradation Drugs FDA Approved 4 ● ● Degraders 2010 Drugs in Clinical Development >15 2020 Elucidation of MOA of thalidomide circa 2010 has profoundly accelerated TPD Clinical programs with protein degraders have grown exponentially in the past 12 months KYMERA R&D DAY - December 16th, 2021 This growth will continue in foreseeable future 2030 PAGE 7#8Bruce Nello Jacobs, CFA, MBA Mainolfi, PhD CFO KYMERA Founder, President and CEO ©2021 KYMERA THERAPEUTICS, INC. Today's Speakers Jared Gollob, MD CMO Naimish Patel, MD SVP, Head of Global Development, Immunology and Inflammation SANOFI Ashwin Gollerkeri, MD SVP, Head of Development KYMERA R&D DAY - December 16th, 2021 Juliet Williams, PhD SVP, Head of Biology Chris De Savi, PhD VP, Head of Drug Discovery PAGE 8#9Introduction to Kymera Clinical Stage Pipeline IRAK4 Degrader KT-474 Ph1 HV study: SAD/MAD data KT-474 Development in Immuno-inflammatory Diseases ● ● IRAKIMID Degrader KT-413 Update and Clinical Plans STAT3 Degrader KT-333 Update and Clinical Plans STAT3 Degraders in Immune-inflammation and Fibrosis Break Discovery Pipeline Principles and MDM2, New Degrader Program in Development Today's Agenda Expanding the Drugged Proteome: Kymera's Platform Kymera 2026 Vision Q&A KYMERA ©2021 KYMERA THERAPEUTICS, INC. Nello Mainolfi, Ph.D. Founder and Chief Executive Officer, Kymera Jared Gollob, M.D., Chief Medical Officer, Kymera Naimish Patel, M.D., SVP, Head of Global Development, Immunology and Inflammation, Sanofi Genzyme Ashwin Gollerkeri, M.D., SVP, Head of Development, Kymera Juliet Williams, Ph.D., SVP, Head of Biology, Kymera Chris De Savi, Ph.D., VP, Drug Discovery, Kymera Nello Mainolfi, Ph.D. Founder and Chief Executive Officer, Kymera Nello Mainolfi, Ph.D., Founder and Chief Executive Officer, Kymera Jared Gollob, M.D., Chief Medical Officer, Kymera Bruce Jacobs, CFA, MBA Chief Financial Officer, Kymera KYMERA R&D DAY - December 16th, 2021 PAGE 9#10KYMERA EST. 2016 KYMERA ©2021 KYMERA THERAPEUTICS, INC. OUR VISION is to be a disease- and technology-agnostic, fully integrated global biopharmaceutical company, using targeted protein degradation to deliver medicines that will transform patients' lives KYMERA R&D DAY - December 16th, 2021 PAGE 10#11KYMERA KYMERA ©2021 KYMERA THERAPEUTICS, INC. Introduction to Kymera ● ● ● ● ● ● Leader in Targeted Protein Degradation (TPD) Building a fully-integrated, global biotech company and Oncology, but Initial focus in Immunology/Inflammation already a disease-agnostic platform Accelerating forward integration through key strategic partnerships Establishing many "firsts" for TPD with initial programs Three programs in/entering the clinic and a deep pipeline positioned to deliver ≥1 IND/year Focused on continued innovation in platform and discovery Well capitalized with $611 million of cash* KYMERA R&D DAY - December 16th, 2021 * Based on reported cash at September 30, 2021 PAGE 11#12Pathway Program IL-1R/TLR JAK/STAT p53 Collaboration Discovery Pipeline Collaboration IRAK4 IRAKIMID (IRAK4, Ikaros, Aiolos) STAT3 STAT3 MDM2 Confidential Kymera's Pipeline of Novel Protein Degraders Indication(s) Multiple Immuno- inflammatory Diseases: HS, AD, RA others MYD88MT Tumors Liquid & Solid Tumors Autoimmune & Fibrotic Diseases Liquid & Solid Tumors Confidential Several Discovery Programs 6 Undisclosed Programs Discovery KYMERA ©2021 KYMERA THERAPEUTICS, INC. IND Enabling Multiple molecules staged as potential back ups if needed 00 KT-474 KT-253 KT-413 KT-333 Phase 1 *Option to participate equally in the development and commercialization of Sanofi-partnered programs in the US Multiple programs in immune-inflammatory and oncology indications to deliver ≥ 1 IND/year 6 targets in 5 disease areas outside of immunology-inflammation and oncology KYMERA R&D DAY - December 16th, 2021 Phases 2/3 = Oncology NEW Next Milestone Rights* KYMERA Patients POB mid-22 POM: 2022 POM: 2022 IND: 2H22 ≥ 1 DC: 2H22 = Immunology-Inflammation SANOFI KYMERA KYMERA KYMERA KYMERA K SANOFI KYMERA VERTEX PAGE 12#13TARGET SELECTION Unique approach focused on undrugged or not fully drugged targets with broad indication potentials KYMERA Kymera's Differentiated Approach to TPD TPD "FIRSTS" PLATFORM Significantly differentiated investments Tissue- selective E3 Ligases Enabling a whole new generation of clinical programs ©2021 KYMERA THERAPEUTICS, INC. New Molecular Glue Approach Novel strategy to address undrugged/ un-ligandable targets Innovative clinical trial designs for degrader development Absolute IRAK4 Levels Mean (SE) [fmol/ug Protein] 2.0 1.5 1.0 0.5 CLINICAL 0.0 1 2 3 4 Day 14 Kymera has accomplished several "firsts" in TPD % Remaining on Study 100 KYMERA R&D DAY - December 16th, 2021 40 0 7 14 21 42 Day Post Tumor Implant KT-474/ IRAK4 FIRST randomized, placebo- controlled trial in healthy volunteers 28 35 49 56 63 KT-333/ STAT3 FIRST Hetero- bifunctional degrader against an undrugged transcription factor in clinic INNOVATION Serious commitment to constant evolution of our science G PAGE 13#14Our People & Culture To build a thriving, high-performing and diverse organization that enables leaders and teams to do their best work every day and propels us to boldly innovate and transform treatment paradigms for serious diseases Organizational Strategy We are building a company that is scalable, flexible and with a clear view of what's needed to be a fully integrated, commercial organization. Core Values Through rigorous science, trust, tenacity and resilience, this team of collaborative pioneers create transformative medicines for patients. KYMERA ©2021 KYMERA THERAPEUTICS, INC. Differentiated Experience We fully engage our people by creating experiences that empower them to be their best selves and inspire how we live and work. KYMERA EST. 2016 KYMERA R&D DAY - December 16th, 2021 Culture Of Belonging We recognize and celebrate everyone's unique contributions and experiences. People + Leadership Our people bring depth of knowledge, accomplishments and creative ideas to move challenging work forward. PAGE 14#15Founded 2016 Seed gsk KYMERA Our First 5 Years, a Foundation for the Future Drug Development First In Vitro First Novel Degradation of First In Vivo E3 Novel Target Degradation Degradation 2017 Series A ©2021 KYMERA THERAPEUTICS, INC. 2018 Series B First KYMERA DC First FIRST FIRST EST. 2016 KT-474 IND POM 2019 VERTEX 2020 Series C Financing and Partnerships KYMERA R&D DAY - December 16th, 2021 SANOFI First Transcription Factor POB Degrader IND 2021 IPO FO Molecular Glue Discovery with: A-ALPHA BIO Third Cleared IND in 2021 T NYU W UNIVERSITY of WASHINGTON PAGE 15#16KYMERA ©2021 KYMERA THERAPEUTICS, INC. ● ● Why TPD is uniquely poised to transform treatment paradigms Who we are and what we have accomplished so far Rationale for our strategy and approach to TPD Power of the Kymera drug development engine ● R&D Day Objectives ● What we have delivered in 2021 How we are evolving our pipeline, our platform and all TPD Our vision for the company we are building KYMERA R&D DAY - December 16th, 2021 PAGE 16#17Clinical Pipeline KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#18Agenda IRAK4 Degrader KT-474 Ph1 HV study: SAD/MAD data IRAKIMID Degrader KT-413 Update and Clinical Plans • STAT3 Degrader KT-333 Update and Clinical Plans • STAT3 Degraders in Immune-inflammation and Fibrosis KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 18#19Safety, PK and PD from SAD and MAD Dose Portion of KT-474 Phase 1 Trial in Healthy Volunteers Jared Gollob, M.D., Chief Medical Officer, Kymera KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#20IRAK4 Targeting: Degrader Advantage, Clinical Validation, and Human Genetics De-risking Degrader Advantage Inhibitor IRAK3 TLRs (TLR 2,4,5,7,8,9) signaling NFkB IL-1R/TLR Pathway IL-1 a/B, IL-18, IL-33, IL-36 $ Myddosome IKKS MyD88 IRAK4 IRAK1 IRAK2 TRAF6 c-Jun IL-1R KYMERA ©2021 KYMERA THERAPEUTICS, INC. JNK/p38 MINITAT secreted TNF-a, IFN-y, IL-1B, IL-6, IL-8, IL-10, IL-12, IL-17, IL-23 Scaffolding Role JNK/p38 NFkB IRAK4 Degrader Kinase Role KYMERA R&D DAY - December 16th, 2021 IRF5/7 Clinical Pathway Validation IL-1a/IL-13: Rheumatoid Arthritis, CAPS, Hidradenitis Suppurativa IL-1α: Atopic Dermatitis IL-1ß: Gout; CANTOS Outcomes Data in Atherosclerosis and Lung Cancer IL-18: Macrophage Activation Syndrome IL-36: Generalized Pustular Psoriasis, Atopic Dermatitis IRAK4 SMI: Rheumatoid Arthritis Human Genetics Adult humans with IRAK4 Null Mutation are healthy IRAK4 degrader has potential to achieve a broad, well-tolerated anti-inflammatory effect, providing multiple development opportunities in autoimmune inflammatory diseases PAGE 20#21● ● ● ● ● ● Development Opportunities for IRAK4 Degrader in Inflammation Potential for Broad Activity Across Th1-Th17 and Th2 Diseases KT-474 IL-1R/TLR Lupus IBD Gout Psoriasis IRAK4 OC Th1-Th17/Neutrophils Hidradenitis Suppurativa Rheumatoid Arthritis ● ● ● ● Th2/Eosinophils Atopic Dermatitis Asthma COPD CRSWNP $150B drug sales Source: EvaluatePharma; GlobalData; Dash. Allied Market Research. 2021; Koto. Modern Rheumatology. 2021; Ahn. JAMA Otolaryngol Head Neck Surg. 2016; UC: Ulcerative Colitis; CD: Crohn's Disease. KYMERA ©2021 KYMERA THERAPEUTICS, INC. Combined global Indication AD HS RA SLE IBD Gout Psoriasis Asthma COPD CRSWNP ● 2021 Prevalence US/EU5/JP ~82.5 M ~785 K ~385 K ~580 K ~3.2 M ~18.2 M ~15.8 M ~87.3 M ~61.7 M ~20.4 M Small Molecule Inhibitors o o KYMERA R&D DAY - December 16th, 2021 2021 Global Sales Limitations of Current Therapies Anti-Cytokine/Cytokine Receptor Antibodies o Target only 1-2 cytokines o Require injection $5,760 M $1,106 M $27,634 M $1,333 M $21,710 M $1,319 M $23,268 M $15,664 M $9,960 M $2,622 M Limited pathway blockade (IRAK4 SMI) Safety issues (JAK family) PAGE 21#22IRAK4 protein levels overexpressed in HS patient skin lesions IRAK4+ Cells per mm² 9000 6000 3000 Protein Expression 0 0.4 0.3 0.2 0.1 0.0 Immunofluorescence (IF) Lesion 3 IRAK4 Protein Expression in Autoimmune Diseases Upregulation in Skin of HS Patients Compared to Healthy Subjects 0.0084 Lesion 0.00016 2.6e-05 1.6e-07 Mass Spectrometry (MS) Peri-lesion Non-lesion Healthy 3.9e-06 8 0.0003 1.2e-05 0.34 t Peri-lesion Non-lesion Healthy KYMERA ©2021 KYMERA THERAPEUTICS, INC. Histology H&E IF Stain Nuclear IRAK4 Morphology Mask Epidermal Keratinocytes Dermal Immune cells IRAK4 expression is upregulated in dermis and epidermis of HS patients relative to healthy subject skin Lesion Peri-lesion Non-lesion Healthy subject KYMERA R&D DAY - December 16th, 2021 IRAK4+ Cells per mm² IRAK4+ Cells per mm² 6000- 4000- 2000- 9000 6000 3000 0 Dermal Immune Cells Lesion % 0.35 Lesion 0.00046 Epidermal Keratinocytes 0.47 Peri-lesion Non-lesion Healthy 4e-05 0.43 .8 0.011 0.0033 0.0021 Peri-lesion Non-lesion Healthy Alavi et al., Society for Investigative Dermatology Annual Meeting, 2021 PAGE 22#23Multiple Proinflammatory Transcripts Are Upregulated and Correlate with IRAK4 Protein Levels in HS Skin Lesions Chemokines Cellular Cytotoxicity Cytokines & Cytokine Signaling Cytokine Receptors TLRs Myddosome Inflammasome Prostaglandins KYMERA Lesion -1 Peri-lesion Non-lesion Scaled Expression 0 Healthy 1 CCL2 CCL20 CSF3 CXCL1 CXCL2 CXCL6 CXCL8 CXCL11 CXCL13 GZMB PRF1 IFNG IL10 IL1B IL32 IL36G IL6 IRF7 SOCS3 TNF IL2RA IL2RB IL18RAP MYD88 TLR1 TLR2 TLR3 TLR4 TLR6 TLR8 TLR9 NLRP3 PTGS2 ©2021 KYMERA THERAPEUTICS, INC. Chemokines Cytokines & Cytokine Signaling Cytokine Receptors Cellular Cytotoxicity TLRs Myddosome IRAK4 Lesion Correlation VS. Non-lesion IF MS Inflammasome Prostaglandins CCL2 CCL20 CSF3 CXCL1 CXCL2 CXCL6 CXCL8 CXCL11 CXCL13 IFNG IL10 IL1B IL32 IL36G IL6 IRF7 SOCS3 TNF IL2RA IL2RB IL18RAP GZMB PRF1 MYD88 TLR1 TLR2 TLR3 TLR4 TLR6 TLR8 TLR9 Spearman correlation log₂ (fold change) NLRP3 PTGS2 IF: immunofluorescence; MS: mass spectrometry KYMERA R&D DAY - December 16th, 2021 1.0 0.5 0.0 -0.5 -1.0 0 Upregulation of TLRs, IL-13/IL-36, MYD88, and multiple additional drivers of inflammation that all correlate with IRAK4 protein expression Highlights potential of IRAK4 targeting to treat diseases like HS characterized by marked pleiotropic inflammation Alavi et al., Society for Investigative Dermatology Annual Meeting, 2021 PAGE 23#24Pvalue (-log 10) 3 2.5 1.5 1 0.5 0 -2 KT-474: Potent and Specific IRAK4 Degradation with Impact on Cytokines Superior to Kinase Inhibition Degradation and Selectivity 10xDC90 IRAK4 -1.5 -1 -0.5 0 KYMERA 0.5 1 24hr pval=0.05 1.5 2 Protein Level Fold Change (log2) ©2021 KYMERA THERAPEUTICS, INC. ● KT-474 DC50 = 2.1 nM in human immune cells ● • KT-474 only degraded IRAK4 in human immune cells at concentration 10- fold above the DC90 ● KT-474 better able to inhibit IL-6 under both LPS and LPS + IL-1ẞ than clinically active IRAK4 SM kinase inhibitor PF-06550833 KYMERA R&D DAY - December 16th, 2021 150 100 50 Superiority over SM kinase Inhibitor LPS + IL-1B → IL-6 HA -4 HA Legend Compound 101 -2 e Log[Compound] (nM) 0 IRAK4 Degrader Negative control IRAK4 SMI (PF-06550833) IL-6 IC50 (nM) 0.8 450 N/A PAGE 24#25pg/ML 80- 60 40 20 0 KT-474 is Superior to IRAK4 Small Molecule Inhibitor (SMI) Across Multiple Preclinical Immune-inflammatory In Vivo Models In vivo IRAK4 Degradation in Whole Blood Naive rmlL-33 Intradermal Challenge Model Vehicle Degrader 15 mg/kg * Degrader 50 mg/kg Degrader 150 mg/kg **** SMI 30 mg/kg Dexamethasone mg/kg % of Vehicle Control 150 100 50 0 IL-5 in Ear Tissues Naive Vehicle Degrader 15 mg/kg Degrader 50 mg/kg SMI 30 mg/kg Degrader 150 mg/kg Dexamethasone mg/kg % of Vehicle Control KYMERA ©2021 KYMERA THERAPEUTICS, INC. 150 100 50 rhlL-36aßy Intradermal Challenge Model In vivo IRAK4 Degradation in Whole Blood Naive Vehicle Der 15 mg/kg 50 mg/kg Degrader 150 mg/kg l 30 mg/kg Dexamethasone mg/kg 100 80 40 20 0 Naive Degrader Ear Thickness 15e Degrader 50 mg/kg 40 € g/kg Dexamethasone mg/kg 120 KYMERA R&D DAY - December 16th, 2021 100 80 60 40 20 Th17-mediated Multiple Sclerosis Model In vivo IRAK4 Degradation in Whole Blood Naive Vehicle Degrader 150 mg/kg SMI 30 mg/kg FTY720 3 mg/kg EAE Clinical Scores 4 3- 1 0- 5 MOG-EAR¹ + Vehicle + Degrader 150 mg/kg SMI 30 mg/kg +FTY720 3 mg/kg 10 Treatment Vehicle Degrader 150 mg/kg SMI 30 mg/kg FTY720 3 mg/kg 15 20 25 30 Day Mean Max Score +/- SD p value 3.40 +/-0.54 2.69 +/- 0.52 3.07 +/-0.42 2.70 +/- 1.28 IRAK4 knockdown of ≥85% in whole blood achieved anti-inflammatory effect comparable to potent corticosteroids or approved standard of care drugs in these models as well as in models of TLR4 (MSU-Gout) or TLR7/8 (Imiquimod-Psoriasis) activation that was superior to IRAK4 small molecule inhibitor 1. Myelin Oligodendrocyte Glycoprotein-induced Experimental Autoimmune Encephalomyelitis (MOG-EAR) Model 0.0018 0.0822 0.0271 PAGE 25#26KT-474 Phase 1 Trial Design Includes HV and Patients Double-blind, placebo-controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) trial Endpoints Three-part Phase 1 Design 1 SAD Portion Healthy Volunteers • 7 cohorts (up to 56 adult healthy subjects) 8 per cohort (6:2 randomization) Single dosing (starting dose 25 mg) 2 MAD Portion Healthy Volunteers 5 cohorts (up to 60 adult healthy subjects) 12 per cohort (9:3 randomization) • 14x daily doses (starting dose 25 mg) KYMERA ©2021 KYMERA THERAPEUTICS, INC. 3 MAD Portion Patient Cohort • 1 cohort (up to 20 AD and HS patients) Open-label 14x daily doses Primary Secondary/ Exploratory SAD & MAD Exploratory SAD & MAD Exploratory MAD Only KYMERA R&D DAY - December 16th, 2021 ● ● Pharmacokinetic measures (half-life, bioavailability) • IRAK4 knockdown in PBMC ● ● Safety & tolerability ● Ex vivo response of whole blood to TLR agonists (SAD & MAD) and IL-1B (MAD only) IRAK4 knockdown in skin biopsies Proinflammatory cytokine and chemokine levels in skin biopsies (Patients only) Plasma C-reactive protein (HV and Patients) and cytokine levels (Patients only) PAGE 26#27Gender, n Female Male Median age, years (range) Ethnicity Hispanic or Latino • Black or African American Non-Hispanic or Latino- White ● SAD/MAD Enrollment Status and Demographics ● Asian KYMERA ©2021 KYMERA THERAPEUTICS, INC. SAD 1-7 (n=57) MAD 1-4 (n=48) 29 28 38.0 (20-55) 42 8 5 2 KYMERA R&D DAY - December 16th, 2021 9 39 37.5 (20-55) लॅ०७० 34 8 6 PAGE 27#28Mean (± SE) Percent IRAK4 Change from Baseline at 48hr 20 -20 -40 -60 -80 -100 KT-474 Achieved >95% IRAK4 Degradation After Single Dose + Placebo Percent IRAK4 Reduction in PBMC at 48 Hours Post-Dose Using Mass Spectrometry Median IRAK4 Change -2% 25 mg SD 75 mg SD 300 mg SD 150 mg SD |||| KYMERA ©2021 KYMERA THERAPEUTICS, INC. 600 mg SD 1600 mg SD 1000 mg SD N Placebo 13 KYMERA R&D DAY - December 16th, 2021 25 mg 75 mg 150 mg 300 mg 600 mg 1000 mg 1600 mg * p-values relative to placebo 6 6 6 6 7 5 Mean IRAK4 Change 6 -1% -26% -73% -81% -84% -96% -93% -95% -39% -75% -82% -89% -96% -94% -95% p value 0.1 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 PAGE 28#29Ex Vivo Cytokine Stimulation: Methodology in KT-474 Phase 1 Trial Impact of KT-474 on TLR- stimulated Cytokine/Chemokine NH₂ TLRs T KT-474 KYMERA Production MyD88 IRAK4 IRAK1 IRAK2 TRAF6 140 Cytokines/Chemokines PBMCs ©2021 KYMERA THERAPEUTICS, INC. 1 Blood Draw Pre-/Post-Dose R848 or LPS TruCulture Tube 2 Overnight Incubation (37°) 8888 KYMERA R&D DAY - December 16th, 2021 3 Plasma Isolation 4 Cytokine/Chemokine Measurement TNF-a, IFN-y, IL-13, IL-6, IL-8, IL-10, IL-12, IL-17, IL-23 PAGE 29#30Pbo 100 50 -50 -100 SAD 6 85-93% Degr* SAD 7 89-95% Degr* Broad and Deep Inhibition of Disease Relevant Cytokines Effect Against LPS (TLR4)- or R848 (TLR7/8)-Stimulated Cytokine Induction in Whole Blood IFNY IL13 80% -51% -42% 27% IL6 IL8 16% 19% *Mean IRAK4 degradation in PBMC at 24-48h 30% -58%¹ -46%² -72%¹ -67%² IL10 IL12 IL17 IL23 TNFa 29% KYMERA ©2021 KYMERA THERAPEUTICS, INC. -45%² 19% LPS -40%² 22% -54%² -68%¹ -62%¹ -81%¹ -83%¹ -35%² -43%² -45%² Placebo (n = 14) 24% SAD 63 (n = 6) -31% SAD 7³ (n = 6) Mean (+SE) Maximum % Change from Baseline at 24 - 48 Hours Pbo SAD 6 -42%² SAD 7 1 = p value < 0.01; 2= p value < 0.05 350 200 150 100 50 -50 -100 IFNY 40% -78% -97%² KYMERA R&D DAY - December 16th, 2021 HA IL1B IL6 -12% -4% IL8 185% -78%¹ -60%¹ -33% IL10 19% IL12 -7% IL17 4% -45% -80%¹ -60%¹ R848 TNFa -8% -61% -92%¹ -88%¹ -54% -89%¹ -93%¹ -79%¹ -88%² 3Ex vivo cytokine assay was performed at 48h nadir (maximal degradation) only in cohorts 6-7 PAGE 30#31KT-474 Demonstrates Broadest Anti-inflammatory Effect Compared to Other Clinical Agents Agent/Stimulus Target IFNY IRAK4 (degrader) ✓ ✓ KT-474/LPS KT-474/R848 CA-4948/R848 GS-5718/R848 ATI-450/LPS ATI-450/IL-13 LY2775240/LPS Iberdomide/LPS JNJ-61803534/ T cell activation Inhibition of Ex Vivo Disease Relevant Cytokine/Chemokine Stimulation by Anti-Inflammatory Agents in Ph1 Studies TNFa IL-1B IL-6 IL-8 IL-17 ✓ ✓ * Non-selective IRAK4 (degrader) IRAK4* (inhibitor) IRAK4 (inhibitor) MK2 MK2 PDE4 Ikaros/ Aiolos RORY ✓ ✓ KYMERA ©2021 KYMERA THERAPEUTICS, INC. ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ IL-12 ✓ ✓ IL-23 ✓ IL-10 ✓ Iberdomide: Schafer PH, et al. Ann Rheum Dis 2018;77:1516-1523; LY2775240: Patel DR, et al. Clin Transl Sci. 2021;14:1037-1048; JNJ61803534: Xue X, et al. Sci Rep 2021;11:11066- 80; MK2: Aclaris 2021 Company Overview; CA-4948: Booher RN, et al. ASH Annual Meeting 2018, Poster #4168; GS-5718: Roedder S, et al. ACR Convergence 2021, Poster #0185 KYMERA R&D DAY - December 16th, 2021 PAGE 31#32• No SAEs Treatment-related AEs observed only in SAD 5 and SAD 6; all were self-limiting and resolved ● KYMERA No treatment-related AEs in SAD 7 • No significant ECG changes Blinded SAD Safety Summary n=8 per cohort (6 drug/2 placebo) ©2021 KYMERA THERAPEUTICS, INC. * Possibly or Probably Treatment-Related AES* (>1 Subject) #Subjects Severity AE Term Headache Nausea per investigator assessment 4 2 KYMERA R&D DAY - December 16th, 2021 Moderate (x2) Mild (x2) Mild (x2) Cohort SAD 5, SAD 6 SAD 5 SAD 6 PAGE 32#33MAD Study: Once Daily Dosing Resulted in High Steady-State Exposures Plasma KT-474 Concentration (ng/mL) Mean (± SD) 40 30 20 10 0 04 12 Day 1 ● KYMERA 24 HOA 4 HIGI HO T 48 72 144 312 316 Time (h) 320 ©2021 KYMERA THERAPEUTICS, INC. Day 14 324 25 mg QD 50 mg QD 100 mg QD 200 mg QD 336 PK Parameter Cmax (ng/mL) Steady-State (Day 14) PK Parameters 25 mg QD (n = 9) 50 mg QD (n = 9) 12.0 (39.1) 100 mg QD (n = 9) 16.1 (32.0) 8.20 (34.5) tmax AUC24 (ng*h/mL) Ctrough (ng/mL) Day 14/1 Ratio Cmax (h)a 8.00 (4.0 - 8.0) 153 (30.8) 5.03 (30.3) KYMERA R&D DAY - December 16th, 2021 3.73 (47.1) 8.00 (8.0 - 8.0) 224 (39.4) High steady-state exposures with QD dosing, 3- to 4-fold increase in exposure on Day 14 Day 14 Ctrough in range where >90% IRAK4 degradation is expected Steady-state reached by Day 7 of dosing 7.28 (35.1) 2.64 (26.3) 8.00 (8.0 - 12) 314 (29.9) 9.81 (30.1) Day 14/1 Ratio AUC 4.01 (41.2) 2.97 (23.2) Geometric Mean (%CV) reported for all parameters, except tmax where median (range) are presented Day 14/1 Ratio represents fold change in exposure from Day 1 to Day 14 2.92 (37.7) 3.29 (38.9) 200 mg QD (n = 9) 25.2 (26.7) 8.00 (8.0 - 12) 498 (24.0) 18.8 (32.6) 3.51 (34.7) 4.22 (28.8) PAGE 33#34KT-474 Achieved Near Complete and Sustained IRAK4 Degradation with Multiple Daily Oral Doses (14 Days) Absolute IRAK4 Levels Mean % Reduction of IRAK4 Absolute IRAK4 Levels Mean (SE)[fmol/µg protein] ● 1.5 ● 1.0 0.5 0.0 1 2 3 4 7 14 Day 17 KYMERA ©2021 KYMERA THERAPEUTICS, INC. 21 Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD* 28 Mean (± SE) Percent IRAK4 Change from Baseline 50 -20 -40 -60 -80 • Detected by mass spectrometry in circulating PBMC Steady state IRAK4 reduction achieved between Days 7 and 14 Recovery towards baseline by Day 28 (2 weeks after last dose) MAD 2 through 4 approached Lower Limit of Quantitation (LLOQ) -100 1 2 3 4 * Data beyond day 14 pending KYMERA R&D DAY - December 16th, 2021 7 14 Day 17 21 Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD* 28 PAGE 34#35Lower Daily Doses of KT-474 Achieved >98% IRAK4 Degradation (MS) Plateau in IRAK4 Reduction after 14 days in PBMC after 100 mg Percent IRAK4 Reduction in PBMC by Mass Spectrometry KYMERA Mean (± SE) Percent IRAK4 Change from Baseline 20 O -20 -40 -60 -80 -100 Mean Day 7 Mean Day 14 p value* ©2021 KYMERA THERAPEUTICS, INC. Day 7 Placebo (n=12) -9% -23% 25 mg QD (n=9) -87% -92% <0.0001 Day 14 50 mg QD (n=9) -93% -95% 100 mg QD (n=9) -97% -98% <0.0001 <0.0001 KYMERA R&D DAY - December 16th, 2021 Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD 200 mg QD (n=9) -95% -96% <0.0001 * p-values relative to placebo PAGE 35#36KT-474 Achieved >90% Degradation in Monocytes at ≥ 100 mg (FLOW) Maximal Degradation in Monocytes in MAD4/200mg at Day 14 Percent IRAK4 Reduction in Lymphocytes Percent IRAK4 Reduction in Monocytes Mean (± SE) Percent IRAK4 Change from Baseline Mean Day 7 * 20 O -20 -40 -60 -80 -100 Placebo (n=12) -17% Day 7 25 mg QD 50 mg QD (n=9) (n=9) -83% Mean Day 14 p-value* p-values relative to placebo KYMERA ©2021 KYMERA THERAPEUTICS, INC. -29% -86% -88% <0.0001 -87% <0.0001 Day 14 100 mg QD 200 mg QD (n=9) (n=9) -85% -87% <0.0001 -84% -92% <0.0001 Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD Mean Day 7 Mean Day 14 p-value* Mean (± SE) Percent IRAK4 Change from Baseline 20 O -20 -40- -60- -80 -100- Placebo (n=12) -16% KYMERA R&D DAY - December 16th, 2021 -21% Day 7 25 mg QD (n=9) -81% -83% <0.0001 50 mg QD (n=9) -90% -87% <0.0001 Day 14 100 mg QD 200 mg QD (n=9) (n=9) -93% -92% <0.0001 -90% -94% <0.0001 PAGE 36#37Skin KT-474 Concentration (ng/g) Mean (± SD) 400 Once Daily Dosing (14 Days) Resulted in High Skin Exposures Exceeding Plasma 300- 200 100 ● ● KT-474 Levels in Skin 7 14 Day 25 mg QD 50 mg QD Ctrough concentrations shown for Days 1, 7 and 14. KYMERA ©2021 KYMERA THERAPEUTICS, INC. 100 mg QD A 200 mg QD T 28 Increasing exposures through Day 14 Ctrough levels in skin ~10-14 fold higher than plasma on Day 14 Substantially Larger Skin vs Plasma Exposures at Ctrough [ng/mL for Plasma, ng/g for Skin] Mean (± SD) Concentration 150- 100 50 ng/mL (plasma) ng/g (skin) Plasma Day 7 Plasma Day 14 Skin Day 7 Skin Day 14 Plasma Day 7 Plasma Day 14 Skin Day 7 Skin Day 14 KYMERA R&D DAY - December 16th, 2021 25 mg QD (n=9) 3.21 4.72 21.5 44.5 50 mg QD (n=9) 7.15 8.49 40.2 94.2 100 mg QD (n=9) 11.9 11.6 53.5 93.7 H 200 mg QD (n=9) 18.2 17.4 80.9 238 PAGE 37#38KT-474 MAD4/200mg Reduced IRAK4 to Near LLOQ in the Skin (MS) IRAK4 Levels in Skin vs PBMC at Day 14 of KT-474 treatment Mean (± SE) Absolute IRAK4 Levels [fmol/µg protein] 0.20 0.15 0.10 0.05 0.00 KYMERA 1 Baseline levels 5- to 10- fold lower than PBMC ● Absolute IRAK4 Levels in Skin ● ● 7 * 14 Day Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD ©2021 KYMERA THERAPEUTICS, INC. LLOQ Mean (± SE) Absolute IRAK4 Levels [fmol/µg protein] 0.6 0.4 0.2 0.0 28 * Data beyond day 14 pending • Baseline IRAK4 levels in skin substantially lower compared to PBMC Dose-dependent IRAK4 degradation in skin by mass spectrometry Steady-state degradation not yet reached at day 14 Mean IRAK4 levels at 200 mg dose nearing LLOQ by Day 14, with knockdown up to 90% at 200 mg Comparable degradation in PBMC shows that effect of KT-474 is independent of baseline expression level Placebo 25 mg QD 50 mg QD KYMERA R&D DAY - December 16th, 2021 100 mg QD Plasma Skin 200 mg QD LLOQ PAGE 38#39Substantial IRAK4 Degradation in Skin Observed in Dermis and Epidermis IRAK4 = Red KYMERA Predose DAPI/IRAK4 DAPIIRAK4/panCK Pan cytokeratin (panCK) is used as the epidermal marker Day 14 ©2021 KYMERA THERAPEUTICS, INC. Representative images from subject in 50 mg cohort Day 28 (recovery) KYMERA R&D DAY - December 16th, 2021 PAGE 39#40Ex Vivo Inhibition of 9 Disease-Relevant Cytokines, Day 7-14 Results through MAD3 Showed Dose-Dependent Effect Tracking with Extent of Monocyte IRAK4 Degradation Pbo 200 50 mg QD 100 -50 -100 100 mg QD IFNY IL10 IL6 IL8 116% -39% 15% IL10 IL12 IL17 IL23 357% 292% -5% -10% 880% -11% 72% 91% LPS -27% 4% 81% 2% -2% -48% -63% -54% -46% -49% -42% -28% -58% TNFa 70% 40% -57% 50 mg QD: 93-95% PBMC degradation at Day 7-10; 87-90% Monocyte degradation at Day 7-14 100 mg QD: 97-98% PBMC degradation at Day 7-10; 92-93% Monocyte degradation at Day 7-14 KYMERA ©2021 KYMERA THERAPEUTICS, INC. Placebo (n = 9) 50 mg QD (n = 9) 100 mg QD (n = 8-9*) Pbo 50 mg QD 100 mg QD 200 100 0 -50 -100 IFNY >500% -62% -85% KYMERA R&D DAY - December 16th, 2021 H IL1B 15% -59% -68% IL6 35% -18% -53% +4 IL8 -5% -28% -32% IL10 -23% 2% -50% IL12 3% -58% -72% R848 IL17 107% -24% -46% TNFa -7% -21% -59% *n=8 for LPS, n=9 for R848 Mean values > 200% have been replaced by 200 for visualization purposes PAGE 40#41• No SAEs • Treatment-related AEs were self-limiting and resolved • No ECG changes, including QTc KYMERA Blinded MAD Safety Summary n=12 per cohort (9 drug/3 placebo) ©2021 KYMERA THERAPEUTICS, INC. Possibly or Probably Treatment-Related AES* (>1 Subject) #Subjects ** AEs Headache Palpitations** Nausea 6 KYMERA R&D DAY - December 16th, 2021 3 2 Severity Moderate, Mild Mild Mild (x3) Mild (x3) Mild (x2) Cohort MAD2 per investigator assessment; all were considered possibly-related, single, transient self-reported episodes during 21 days of in-patient observation in Phase 1 unit; not associated with any objective findings and did not lead to interruption in dosing MAD 3 MAD 4 MAD 2, MAD 4 (x2) MAD 2 PAGE 41#42● Summary of Phase 1 KT-474 SAD/MAD Healthy volunteer SAD dose escalation completed; MAD enrolled through Cohort 4 (200 mg), with proof of mechanism (IRAK4 degradation) and proof of biology (broad inhibition of cytokine induction) established in SAD and at substantially lower doses in MAD Marked reduction of IRAK4 protein in blood and skin to near LLOQ of highly quantitative and sensitive mass spectrometry assay achieved at a dose of 100-200 mg daily x 14 days Strong and broad inhibition of whole blood ex vivo cytokine induction in MAD comparable to what was seen at highest SAD dose (1600 mg) demonstrated in association with >90% IRAK4 reduction in monocytes at 100 mg daily dose ● ● While cytokine results at 200 mg not currently available, even greater inhibition anticipated at that dose given the substantial increase in plasma exposure and tissue degradation (e.g. skin) and 94% IRAK4 reduction in monocytes High sensitivity CRP levels in plasma too noisy over time to detect meaningful changes Prolonged suppression of IRAK4 in blood and skin for at least 14-21 days with KT-474 multi- dosing shown to be safe and well-tolerated On track to initiate open-label cohort in HS and AD patients in Q1 next year with data read-out planned for mid-year, followed thereafter by start of Phase 2 studies in multiple indications KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 42#43KT-474 Development in Immuno-inflammatory Diseases Naimish Patel, M.D. - SVP, Head of Global Development, Immunology and Inflammation, Sanofi Genzyme KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#44Naimish Patel Global Head of Development, Immunology & Inflammation SANOFI#45Sanofi's approach to R&D Pathways Deep understanding of disease pathways SANOFI Patients Relentless patient focuS Expanding capabilities 3 Platforms Expanded tools for drug discovery 45#46Sanofi - Rich Immunology portfolio extending to other TAs Dermatology DupixentⓇ Amlitelimab(2) Rilzabrutinib SAR444727 topical BTKi SAR444656(1) IRAK4 degrader SAR443726 Anti IL13/OX40L nanob. SAR443122(3) RIPK1i *THOR809 SANOFI Respiratory DupixentⓇ Itepekimab Rilzabrutinib *anti-IL-13-TSLP NANOBODYⓇ GI DupixentⓇ *Bispecific NANOBODYⓇ Type 2 Type 2+ mixed Gl: gastrointestinal; TCE: T cell engager; NKCE: NK cell engager Rheumatology *= preclinical All assets except for Dupixent®, Libtayo®, Sarclisa®, AubagioⓇ (3) and LemtradaⓇ are under investigation and are not approved by (4) Rilzabrutinib Anti-CD40L mAb(4) Autoantibody KevzaraⓇ *Bispecific NANOBODYⓇ any regulators (1) (2) Hematology Neurology Sutimlimab Rilzabrutinib Isatuximab SAR445088 Complement C1s inh Immunoregulatory (5) Developed in collaboration with Kymera (KT474) (6) Anti-OX40L mAb, formerly known as KY1005/SAR445229 (7) In collaboration with Denali (8) In collaboration with Immunext AubagioⓇ Tolebrutinib Anti-CD40L mAb(4) SAR445088 Complement C1s inh. LemtradaⓇ SAR443820(3) RIPK1i Th1/Th17 Oncology LibtayoⓇ SarclisaⓇ SAR442257 CD38xCD28xCD3 SAR444245(6) Non-alpha IL-2 SAR445419(7) K-NK. SAR439459 Anti-TGFb mAB *NKCE(8) Immunostimulatory Pending closure of Kiadis acquisition Formerly known as THOR707 Formerly known KDS1001 (Kiadis) In collaboration with Innate Pharma 46#47IRAK4 is a key initiator of Type 2 and Type 17 inflammation of mucosal tissues via TLRS and IL-1 family receptors Upstream initiation Downstream effects Tissue effects Amplification Virus Bacteria Allergens Epithelial Injury becobet IL-33 Activation TLR SANOFI APC IL-1 a/B, IL-36 IRAK4 signaling Tho Th2 Th17 I I IL-5 IL-4, IL-13 Differentiation in bone marrow Th cells T helper cells; IgE: Immunoglobulin E Source: https://www.type2inflammation.com/science-cytokines Amplification Class switching IL-6 IL-17 Eosinophil Th2 B cell IgE Trafficking to tissues Neutrophil Mucus secretion, hyperplasia, collagen deposition Immunity. 2019 Apr 16;50(4):778-795 I I I I I I I I Allergens Maladaptation Degranulate Mast cell Basophil CARBUROOO Asthma COPD Airway obstruction & hyperreactivity Skin thickening, itch & inflammation Atopic Dermatitis Hidradenitis Sup. Cut. Lupus Colonic mucosal inflammation Ulcerative Colitis Crohn's Disease#48First-in-class IRAK4(¹) oral protein degrader SAR444656 or KT-474 ● ● Degradation of IRAK4 protein abolishes its kinase activity and scaffold function ● IRAK4 protein degrader SAR444656 inhibits pNFkB and pro-inflammatory cytokines • Potential for oral immunology ● pathway drug across multiple indications Targeting early initiation steps may afford possibility of early intervention and disease modification IRAK4 Kinase Inhibitor SANOFI Inactive Kinase P IRF5/7 TLRs IRAK4 MyD88 IRAK4 scaffold function P NFkB | T IL1/IL18/IL33/IL36 IRAK4 Protein Degrader (SAR444656) Inactive Kinase Disabled scaffold function P IRF5/7 I I I IFNa/B, inflammatory cytokines (IL-6, TNFa) & mediators pNFkB (S536) Log2 (stim./unstim.) IL-6 (% control) 3 2 150- 100- 50- 0 -6 Mean (± SE) Percent IRAK4 Change from Baseline at 48hr 20 (SAR444656) * -20 -40 -60 -80 Potent inhibition of pNFkB in PBMC Kinase Negative Inhibitor -100 Degrader Control Potent Inhibition of TLR+IL1 induced cytokines in PBMC + -4 -2 0 Log (concentration, nM) Placebo Potent IRAK4 degradation in Human (PBMC) 25 mg SD 75 mg SD 150 mg SD CIXIO 300 mg SD *Significant dij *** IRAK4 expression is below level of quantification Degrader (SAR444656) Negative Control Kinase Inhibition 600 mg SD 1000 mg SD T 2 1600 mg SD Entered the clinic in 2021; Initial indications: Atopic Dermatitis and Hidradenitis Suppurativa IRAK4 is an asset under investigation and is not approved by any regulators, also called SAR444656 (1) IRAK4 protein degrader in collaboration with Kymera, also known as KT474 48#49IRAKIMID Degrader KT-413 Update and Clinical Plans Ashwin Gollerkeri, M.D., SVP, Head of Development, Kymera KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#50IRAKIMiDs are Potent Degraders of IRAK4 and IMID Substrates Targeting Redundant Pro-survival Pathways in MYD88MT DLBCL Single-agent therapies that target activated NFkB signaling in DLBCL show limited activity in preclinical or clinical settings • Redundant NFKB pathway activation and downregulation of Type 1 IFN is common in MYD88MT lymphoma, supporting need to seek combination therapies Targeting simultaneous degradation of IRAK4 and IMID substrates Ikaros and Aiolos shows synergistic activity in MYD88MT models, supporting this targeted combination IMiD Degrader CRBN IMiD (E3 Ligase) Binder IMID Substrates Degradation KYMERA IRAKIMID Degrader IMID CRBN (E3 Ligase) Binder IMID Substrates AND IRAK4 Degradation ©2021 KYMERA THERAPEUTICS, INC. IRAK4 Binder TLRs JNK AP1 Pathway P IL-1R MYD88MYD88 IRAK4 IRAK4 IRAK1 IRAK1 TRAF6 TRAF6 P IKKy IKKBIKKa KYMERA R&D DAY - December 16th, 2021 NFkB Pathway PROLIFERATION & SURVIVAL B Cell Receptor BTK CARD11 MALT1 BCL10 * A20 * IRF4 Autoantigens * CD79A/B Ikaros Aiolos ➡IRF7 IFN IFNAR1/2 IFN Pathway IFITS Pathway activating alterations in DLBCL Adapted from Yang et al. (2012) Cancer Cell 21, 6, pp723-737 PAGE 50#51IRAKIMID: First Precision Medicine in MYD-88 Mutated Cancers MYD88 is mutated in ≥ 25% of DLBCL patients, the most common subtype of non-Hodgkin's lymphoma MYD88-mutant DLBCL Waldenström's Macroglobulinemia Primary Central Nervous System Lymphoma KYMERA Patient Impact¹ ~8k US ~37k ROW* per year ~10k US ~26k ROW* per year ~3k US ~12k ROW* per year *EU, UK, Japan, China ©2021 KYMERA THERAPEUTICS, INC. ● • SOC in relapsed/refractory DLBCL, which includes CAR-T therapy, anti- body drug conjugates (ADC), and anti-CD19 and CD20 compounds, are associated with ORR of 40-80% There are no treatments indicated specifically in MYD88 mutant DLBCL ● ● ● DLBCL 5-year survival rate is ~64%, and MYD88 mutations are associated with poorer survival following frontline R-CHOP chemotherapy ● MYD88 is mutated in approximately 90% of Waldenström's macroglobulinemia (WM) cases. Standard therapy includes ibrutinib-based or zanubrutinib with overall response rates of 80-90% and major response rates (≥ partial response) of approximately 73% MYD88 is mutated in approximately 70% of primary central nervous system lymphoma (PCNSL) Standard therapy in 1L includes high-dose (HD) methotrexate combinations result in overall response rates (ORR) of 53-87%, complete response (CR) in 23-49%, and 2-year PFS rates of 36-61%. Approximately 20-30% of patients with PCNSL experience tumor progression within first 6 months of treatment. ¹Bionest • There is no standard of care therapy in relapsed disease KYMERA R&D DAY - December 16th, 2021 PAGE 51#52● ● KT-413 is a Potent Degrader of IRAK4 and IMID Substrates with Potent Activity in MYD88MT Cell lines KT-413 selectively degrades both IRAK4 and IMiD substrates which leads to a profound antitumor effect in vitro and in vivo KT-413 is more active in MYD88MT DLBCL cells than the clinically active IMiD, CC- 220, and IRAK4-selective degrader, KTX-545 KYMERA ©2021 KYMERA THERAPEUTICS, INC. Fraction of DMSO IRAK4 DC50 Ikaros DC50 = 2 nM Aiolos DC50 = 2 nM 1.00 0.75 0.50 0.25 0.00 KT-413 = T -2 6 nM OCI-Ly10 (MYD88L265P) KT-413 CC220 KTX-545 OCI-Ly-10 (MYD88MT DLBCL) EC50 = 1 nM -1 Log [compound], μM 1 KYMERA R&D DAY - December 16th, 2021 CTG (% Growth Inhibition) Fraction of DMSO 100 80 60 40 O 1.00 0.75 0.50 0.25 0.00 0.1 H HKH -3 1 HH SUDHL2 (MYD885222R) Concentration (nM) 10 HOW KT-413 CC220 KTX-545 HH HH K -2 -1 0 Log [compound], µM IRAK4 Ikaros Aiolos CTG 100 1 ▶ 100 -80 -60 40 -20 -0 Degradation (% Control) PAGE 52#53In the OCI-LY10 MYD88MT xenograft model, intermittent dosing of KT-413 induced strong antitumor activity, including complete or partial regressions. ● KT-413 is Highly Active on Intermittent Dosing Regimens Superior Anti-tumor activity OCI-Ly-10 Tumor Volume Superior activity compared to the clinically active IRAK4-inhibitor CA-4948 or the IMID CC-220 alone Single 10 mg/kg dose showed extended tumor exposure and strong degradation of both IRAK4 and IMID substrates that was maintained for least 72hr KYMERA Single 10 mg/kg dose Q3W had robust anti-tumor activity ©2021 KYMERA THERAPEUTICS, INC. Tumor Volume (mm³) Mean, ± SEM 2500 2000 1500 1000 500 0 0 7 14 21 28 Days After the Start of Treatment 10000 1000- 100- 10- 1- Plasma 48 35 IV Vehicle CA-4948, 150 mg/kg, PO, QD x 37 CC-220, 3 mg/kg, PO, QD x 21 KT-413,5 mg/kg, IV, D1,2,15,16 → KT-413, 10 mg/kg, IV, D1,2,21,22 KYMERA R&D DAY - December 16th, 2021 Tumor Drug (day 33) CA-4948 CC-220 KT-413 5mg/kg KT-413 10 mg/kg IRAK4 96 144 Time (hr) Post Single-dose Ikaros 192 240 T/C% (REG%) 9 9 (14) (94) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 CR 0 0 1 5 PR SD 0 O 0 2 O 0 3 0 PD 7 7 3 0 PAGE 53#54Tumor Volume (mm³) 2400 2200 2000 1800 1600 1400 1200 1000 800 600 400 200 0 0 KYMERA KT-413 Has Strong Activity in Combination in MYD88MT OCI-Ly10 Xenografts with BTK Inhibitor Vehicle Ibrutinib, 12.5 mg/kg, PO, QD x 21 KT-413,3 mg/kg, IV, D1, 2, 15, 16 Ibrutinib + KT-413 5 10 15 20 25 30 Days after the Start of Treatment • KT-413 administered on intermittent schedules leads to strong regressions in combination with the BTK inhibitor Ibrutinib 35 40 Tumor Volume (mm³) ©2021 KYMERA THERAPEUTICS, INC. 2400 2200 2000 1800 1600 1400 1200 1000 800 600 400 200 0 0 with BCL-2 Inhibitor Vehicle, PO, QD x 21 Venetoclax, 50 mg/kg, PO, QD x 21 KT-413,3 mg/kg, IV, D1, 2, 15, 16 Venetoclax + KT-413 5 10 15 20 25 30 35 40 Days after the Start of Treatment • KT-413 administered on intermittent schedules leads to deep and durable regressions in combination with the BCL-2 inhibitor, Venetoclax Tumor Volume (mm³) KYMERA R&D DAY - December 16th, 2021 3000 2500 2000 1500 1000 500- 0 10 with Rituxan Data support potential for KT-413 in combination in earlier lines of therapy Vehicle Rituxan, 10 mg/kg, IP, BIW KT-413,3 mg/kg, IV, D1,2,8,22,23 Rituxan + KT-413 20 30 40 50 60 70 Days after the Start of Treatment 80 • KT-413 administered on intermittent schedules leads to deep and durable regressions in combination with Rituxan 90 PAGE 54#55Key Eligibility Criteria: R/R B-cell lymphoma Ⓡ ● KT-413: Clinical Study Design and Objectives Primary Objective: • To evaluate safety, PK/PD in Ⓡ > 2 prior systemic regimens Ineligible or refused CAR-T or ASCT ● Study Endpoints: Primary: Safety, tolerability, MTD/RP2D Secondary: PK, preliminary efficacy Exploratory: Target MYD88 mutant and MYD88 wild-type R/R DLBCL (IRAK4/Ikaros/Aiolos) knockdown and downstream effects in PBMC, and tumor KYMERA ©2021 KYMERA THERAPEUTICS, INC. DL1 Phase 1a Dose Escalation & MTD/RP2D Expansion DL2 DLX Protocol Amendment KT-413 + SOC Combo MTD/RP2D Expansion Protocol Amendment DL1-DLX DL1 DLx→ KYMERA R&D DAY - December 16th, 2021 MTD/RP2D Expansion MTD/RP2D Expansion Phase 1b Dose Expansion MyD88MT DLBCL ≥2 prior regimens MyD88WT DLBCL ≥2 prior regimens Waldenström's Macroglobulinemia Primary CNS Lymphoma Combination Expansion Combination Expansion PAGE 55#56KYMERA KT-413 Registration Strategies Phase 2 open label study patients Phase 3 randomized KT-413 in combo vs SOC Waldenstrom's: 1st (AA) Approval: Phase 2 open label 2nd (Full) approval: Phase 3 KT-413 vs BTK 1st line PCNSL: Phase 2 open label study ©2021 KYMERA THERAPEUTICS, INC. First US Approval (Accelerated) 3rd Line R/R MYD88mut DLBCL Second US Approval (Full) 2nd Line R/R MYD88mut DLBCL + SOC Additional Label Expansions Waldenstrom's, PCNSL, 1st line + SOC DLBCL, Wild Type DLBCL, etc. KYMERA R&D DAY - December 16th, 2021 PAGE 56#57IRAKIMID Degrader KT-413 has Potential to be First Precision Medicine in DLBCL to Target a Genetically-defined Population (MYD88MT) Profound antitumor activity in preclinical models both in single agent and combination • Clinical strategy in place to enable accelerated approval: KYMERA Monotherapy MYD88MT DLBCL for most direct path to registration Other MYD88MT lymphomas of interest include PCNSL, WM Combinations With SOC agents in MYD88MT DLBCL to enable earlier line therapy ● ● ● ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 57#58STAT3 Degrader KT-333 Update and Clinical Plans Ashwin Gollerkeri, M.D., SVP, Head of Development, Kymera KYMERA R&D Day KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016 December 16, 2021#59STAT3 Has Unique Tumor Cell Intrinsic and Extrinsic Mechanisms Survival, proliferation, EMT, stemness ● STAT3 as a Target Growth Factor Receptor Cytokine Receptor JAK JAK P P SRC STAT3 STAT3 STAT3 P P STAT3 STAT3 NAMO Adrenergic Receptor W High degree of validation of JAK-STAT pathway in oncology and immuno- oncology supported by >25k publications Traditionally undrugged target First-in-class opportunity to address STAT3 driven pathology across large and diverse indications KYMERA ©2021 KYMERA THERAPEUTICS, INC. Cancer Cells P P STAT3 STAT3 Cytokines (e.g., IL-6, IL-10, VEGF) Myeloid Cells (Macrophages, MDSCs) Tregs Immature DCs PD-L1 P STAT3 Endothelial Cells Vascularization Immune- suppression KYMERA R&D DAY - December 16th, 2021 ● Tumor Cell Intrinsic Hyperactivation of STAT3 via either receptor signaling, or hotspot mutations promotes gene expression programs involved with survival, proliferation, stemness and metastasis of tumor cells Opportunities in STAT3-dependent malignancies (e.g., T cell malignancies, DLBCL, AML) and drug resistant tumors (e.g., TKI resistant oncogene-driven solid tumors) Tumor Cell Extrinsic STAT3 promotes the differentiation and activity of immunosuppressive and endothelial cells, resulting in an immunosuppressive tumor microenvironment. Opportunities in multiple heme and solid tumor indications that are not responsive to immune checkpoint inhibitors. PAGE 59#60First-in-class Opportunity to Address STAT3-driven Pathology Across Diverse indications Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell Lymphoma (CTCL) Large Granular Lymphocytic Leukemia (LGL-L) Solid Tumors PD-1 Combo: e.g. Stage IV CRC - MSI-H Patient Impact (Global)¹ ~13k US ~27k ROW* per year ~30k US ~67k ROW* per year ~4.5k US ~25k ROW* per year ~26k US ~96k ROW* per year *EU, UK, Japan, China KYMERA ©2021 KYMERA THERAPEUTICS, INC. ● • STAT3 is most frequent mutation among JAK/STAT pathway Standard therapies in relapsed/refractory PTCL including result in ORRs ~25%, CR rate of ~10% and mDOR of approximately 9 months ● ● Abnormal activation of JAK/STAT pathway occurs in nearly all T-cell lymphomas ● Advanced stages of disease associated with constitutively activated STAT3 Standard therapies in relapsed/refractory CTCL result in ORRs of ~30% with few CRs and mPFS of 5-8 months STAT3 mutations in up to 70% cases Constitutively active STAT signaling in nearly all cases No approved agents in LGL-L; SOC in 1L which includes methotrexate and cyclophosphamide result in ORRs ~60% No SOC in ≥2L STAT3 decreases inflammatory state in tumor, degradation of STAT3 sensitizes to PD1/L1 activity • PD1 inhibitors approved as single agents or in combination with CTLA4 inhibitor in 1L and in later lines following chemotherapy in patients with metastatic MSI-H CRC ¹Bionest KYMERA R&D DAY - December 16th, 2021 PAGE 60#61KT-333 Demonstrates Highly Selective Degradation of STAT3 KYMERA Deep mass spectrometry-based proteomics to assess STAT3 selectivity performed In hPBMC and SU-DHL-1 cancer line (shown), treatment with KT-333 degrader led to selective degradation of only STAT3 protein ©2021 KYMERA THERAPEUTICS, INC. -Log10(p-Value) 8 t 2 0 Change in Protein Levels 10x DC95 at 8h in SU-DHL-1 STAT3 O KYMERA R&D DAY - December 16th, 2021 STAT6 STAT4 STAT5A STAT2 STAT5B STAT1 T -2.5 2.5 Log2(300nM KT-333/DMSO) 0.0 PAGE 61#62Full and Durable Regressions Across Multiple in vivo Preclinical Tumor Models Mice bearing STAT3- dependent ALK+ ALCL SU- DHL-1 or SUP-M2 tumor xenografts dosed with STAT3 degrader Dose- and degradation dependent tumor growth inhibition observed with once- a-week dosing 10 mg/kg sufficient to drive full tumor regression in SU- DHL- 1 that was durable for multiple weeks after the last dose (on day 14) KYMERA ©2021 KYMERA THERAPEUTICS, INC. Tumor Volume (mm³) Mean, ± SEM 3000 2000 1000 SU-DHL-1 Weekly Dosing - - Vehicle KT-333, 5 mg/kg QW KT-333, 10 mg/kg QW KT-333, 15 mg/kg QW KT-333, 45 mg/kg QW 01 10 5 15 Days (Post-randomization) 20 KYMERA R&D DAY - December 16th, 2021 25 Tumor Volume (mm³) Mean, ± SEM 3000 2000 1000 SUP-M2 Weekly Dosing Vehicle KT-333, 10 mg/kg QW KT-333,20 mg/kg QW KT-333, 30 mg/kg QW 20 40 Days (Post-randomization) 60 PAGE 62#63Counts 150 100 50- IFNy-dependent Gene Signature Induced by STAT3 Degrader Monotherapy in CT-26 Tumors Infy Vehicle KTX-201 250 150- 100 50 0- Stat1 HIH Vehicle STAT3 Degrader's Role in Immuno-Oncology: Sensitization of Tumors to Anti PD-1 • STAT3 degradation remodels the CT-26 TME to be more immune-favorable with upregulation of anti-tumor immunity genes previously identified as predictors of clinical response to pembrolizumab in KTX-201 2000 1500- 1000 500 0₁ Cxcl10 HA Vehicle KTX-201 4000 3000 IFN-Y ID01 CXCL10 CXCL9 HLA-DRA STAT1 IFNG 2000- 1000 Cxcl9 +To KYMERA ©2021 KYMERA THERAPEUTICS, INC. Vehicle CT-26: Veh or KTX-201 25 mg/kg q2D IP; n-6/grp; t = Day 11 KTX-201 Expression score 60 Ido1 2.8- 2.6- 2.4- 2.2- 2.0- 1.8- 1.6- 1.4- 1.2- 1.0- 0.8 40 IFN-y and Expanded Immune Gene Signature B Vehicle Nonresponder KTX-201 IFN-y signature Responder Source: Ayers et al., JCI, 2017 STAT3 Degradation and Anti-PD-1 Synergy KTX-201 synergizes with anti-PD-1 leading to 60% complete responses in CT- 26 model Complete responders reject tumor rechallenge demonstrating development of long-term immune memory Combination extends survival KYMERA R&D DAY - December 16th, 2021 Tumor Volume (mm³) Tumor Volume (mm³) % Remaining on Study 5000 4000 3000 2000 1000 0 5000 4000 3000 2000 1000 100 80 60- 0 40- 20 0 0 7 20 20 Days Days 14 40 Anti-PD1 n=10 Vehicle 2000 n=10 1/10 CRs 40 21 28 5000 60 4000 3000 1000 0 5000 4000 3000 2000 1000 35 0 0 0 42 Day Post Tumor Implant 20 20 49 KTX-201 n=10 T 56 40 Days Combination n=10 6/10 CRs CT-26 rechallenge 60 40 Days 63 60 80 Vehicle KTX-201 Anti-PD1 Combination PAGE 63#64Key Eligibility Criteria: R/R B-cell lymphoma •> 2 prior systemic regimens Ineligible or refused CAR-T or ASCT Advanced solid tumors > 2 prior systemic regimens or no available SOC ● ● KT-333: Clinical Study Design and Objectives Primary Objective: To evaluate safety, PK/PD in PTCL, CTCL, LGL-L and solid tumors ● Study Endpoints: Primary: Safety, tolerability, ● ● MTD/RP2D Secondary: PK, preliminary efficacy Exploratory: STAT3 knockdown and downstream effects in PBMC and tumor KYMERA ©2021 KYMERA THERAPEUTICS, INC. DL1 Phase 1a Dose Escalation & MTD/RP2D Expansion DL2 DLx Protocol Amendment KT-333 + SOC Combo MTD/RP2D Lymphoma Expansion MTD/RP2D Solid Tumor Expansion DL1-DLX DL1 DLx→ KYMERA R&D DAY - December 16th, 2021 MTD/RP2D Expansion MTD/RP2D Expansion Phase 1b Dose Expansion PTCL ≥1 prior systemic regimens CTCL ≥1 prior systemic regimens LGL-L ≥1 prior systemic regimens Solid Tumors Combination Expansion Combination Expansion PAGE 64#65KT-333 Accelerated and Full Approval Strategies Across Several Indications ≥2nd Line R/R PTCL (or CTCL)- KT-333 monotherapy First US Approval [Accelerated] (Phase 2 single arm study) KYMERA 1st Line PTCL (or CTCL)- KT-333 monotherapy or combo with SOC FULL Approval (Phase 3 Study) ©2021 KYMERA THERAPEUTICS, INC. LGL-L KT-333 monotherapy FULL Approval (Phase 2 single arm study) KYMERA R&D DAY - December 16th, 2021 Solid Tumor CRC MSI-H (e.g.) – PD1 inhibitor refractory KT-333 + PD1 inhibitor FULL Approval (Phase 2/3 randomized study) 1st Line KT-333 combo with PD-1 inhibitor FULL Approval (Phase 3 Study) PAGE 65#66STAT3 Degrader KT-333, First-in-class Opportunity to Address STAT3-driven Pathology Across Diverse Indications • First heterobifunctional degrader against an undrugged target in the clinic • Profound single agent activity in liquid tumor and promising combo activity with anti-PD1 in liquid and solid tumors. Clinical development strategy includes direct registrational path in STAT3 pathway activated heme malignancies Opportunity for expansion into solid tumors in combination with immune checkpoint inhibitors KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 66#67STAT3 Degraders in Immune-Inflammation and Fibrosis Ashwin Gollerkeri, M.D., SVP, Head of Development, Kymera KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#68Role of STAT3 in Inflammatory Processes STAT3 is activated by multiple tyrosine kinases and plays a critical role in the signaling of cytokines, hormones, and growth factors including IL-6, IL-21, IL-11, OSM, TGF-B, VEGF STAT3 gain-of-function mutations lead to a poly- autoimmunity with clinical manifestations that include interstitial lung disease (ILD), arthritis, scleroderma and eczema Increased STAT3 activation is associated with disease severity in chronic inflammation including SSC, RA, AS, MS, IBD, Psoriasis STAT3 activation is also implicated in conditions defined by intense stromal remodeling in the absence of overt inflammation, e.g. IPF, PAH, NAFLD, and Diabetic Kidney Disease KYMERA ©2021 KYMERA THERAPEUTICS, INC. Leukocyte Activation OSM, IL-6, IL-27 Tissue Remodeling and Fibrosis KYMERA R&D DAY - December 16th, 2021 OSM, IL-6 Endothelial Activation STAT3 IL-6, LIF, IL-11 Stromal Cell Activation IL-6, IL-21, LIF, IL-11 T Cell and Macrophage Differentiation Leukocyte Recruitment and Retention Do o C Chemokine Production (e.g. CCL2, CCL11, CXCL10) Adhesion Molecule Expression (e.g. ICAM-1, VCAM-1) Cytokine Production (e.g. IL-6) Epithelial Regeneration and Cancer PAGE 68#69STAT3 Degraders Have Applicability in Serious Inflammatory and Fibrotic Diseases Systemic Sclerosis (SSc) Idiopathic Pulmonary Fibrosis (IPF) Atopic Dermatitis (AD) moderate-to- severe Rheumatoid Arthritis (RA) Patient Impact¹ ~85k US ~200K ROW* per year ~80k US ~180k ROW* per year ~12m ~60m ROW* per year ~2m US ~17m ROW* per year *EU, UK, Japan, China KYMERA ©2021 KYMERA THERAPEUTICS, INC. Fibrosis / Interstitial Lung Disease Autoimmune Increased STAT3 and pSTAT3 observed in SSc skin and lung biopsies • Aberrant IL6/JAK/STAT3 gene signature in biopsies from SSc patients Tocilizumab no effect on mRSS but change from baseline in FVC at week 48 (observed FVC and %pFVC) in patients with SSC/ILD ● ● ● ● STAT3 dependent cytokines (e.g. IL-11) upregulated in lung of IPF patients and are associated with disease severity IL-6/gp130 stimulation is mitogenic for IPF fibroblasts but no normal fibroblasts SoC reduces the annual rate of FVC decline STAT3 GoF pat ts exhibits signs of dermatitis TSLP receptor activates STAT3 Pruritis is linked to mechanical and IL-31R activation of STAT3 Fibrotic changes associated with AD is associated with STAT3 activation STAT3 mRNA and pSTAT3 are significantly higher in blood of RA patients STAT3 target genes (BCL3, SOCS3 and PIM1) are upregulated in early RA Constitutive STAT3 phosphorylation in circulating CD4+ T cells correlates to IL-6 levels in recent-onset RA ~30% of SoC therapies in moderate to severe RA achieve ACR70 at week 52 ¹Bionest KYMERA R&D DAY - December 16th, 2021 PAGE 69#70In Vivo Tight Skin Model (Fibrosis) TSK + Mice (BIW Dosing) Dermal Thickness (Fold Change) 15 Gel Contraction (%) 10- 80 60 Our STAT3 Degraders Robustly Reduce Disease in Models of Systemic Sclerosis, Arthritis and CNS Inflammation 40 20 Wild-type Cellular Fibrosis Model TGF-B Stimulated SSC Fibroblasts (72h) O Vehicle +TGF-B, Vehicle T +TGF-B, 2 nM KT-6955 2 mg/kg KT-6955 7 mg/kg KT-6955 +TGF-B, 10 nM KT-6955 KYMERA ©2021 KYMERA THERAPEUTICS, INC. Sum of Scores Clinical Scores 12- 10 ∞06+ 4 O 3 N Pathology Score 1 In Vivo CIA Model (RA) Collagen-induced Arthritis (BIW Dosing) Vehicle 2 mg/kg KT-6955 →7 mg/kg KT-6955 → 20 mg/kg KT-6955 30 mg/kg Tofacitinib 0 20 22 24 26 Naive Vehicle 2 mg/kg KT-6955 7 mg/kg KT-6955 20 mg/kg KT-6955 28 Day 30 32 Periosteal Bone Width (µM) 150 Periosteal Bone Growth 100 50 Naive 34 Vehicle + 36 2 mg/kg KT-6955 7 mg/kg KT-6955 20 mg/kg KT-6955 KYMERA R&D DAY - December 16th, 2021 Clinical Scores 4 3 N 1 0 In Vivo MS Model Experimental Autoimmune Encephalomyelitis (BIW Dosing) 6 Treatment 8 Vehicle 1 mg/kg KT- 6955 Vehicle 1 mg/kg KT-6955 3 mg/kg KT-6955 10 mg/kg KT-6955 3 mg/kg KT- 6955 10 mg/kg KT- 6955 10 12 14 16 EAE Incidence (%) 100.0% 66.7% 16.7% 18 20 22 24 26 Day 0.0% Median Day of Onset 13.0 23.0 >28.0* >28.0* 28 30 End Score (+/-SD) 2.71 +/-0.69 0.75 +/- 0.92 0.29 +/-0.69 0.00 +/- 0.00 PAGE 70#71Program will continue following a short break KYMERA#72Discovery Pipeline Principles Juliet Williams, Ph.D., SVP, Head of Biology, Kymera KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#73Drug Development Philosophy E KYMERA Unmet Medical Need Validated Biology Undrugged Node Precision Medicine Approach ©2021 KYMERA THERAPEUTICS, INC. How We Select Our Targets Target Types ID UD TR Inadequately Drugged Targets with Clear Degrader Advantage e.g. IRAK4 Undrugged Targets by any other technology e.g. STAT3 Clinically Validated Targets Enabled by E3 Ligase Tissue Restricted Expression KYMERA R&D DAY - December 16th, 2021 Oncology: ● Therapeutic Profile Clear patient stratification Clear single agent activity with potential for expansion with combos Multiple addressable unmet needs Immunology: Address key unmet needs providing game ● changing oral therapies Key validated signaling pathways with clear degrader advantage Other Disease Areas: Enabled by E3 ligase differential expression Key insights from biology and technology expansion Some areas enabled by collaborations PAGE 73#74ID UN TR KYMERA Kymera's Roadmap to Deliver ≥ 1 IND per Year Strategy Inadequately Drugged Undrugged Tissue- Restricted Program IRAK4 IRAKIMID MDM2 2-3 new targets per year STAT3 2-4 new targets per year 3-5 target pairs per year ©2021 KYMERA THERAPEUTICS, INC. Asset(s) 2021 2022 2023 2024 2025 2026 KT-474 KT-413 KT-253 KT-333 IND IND IND IND KYMERA R&D DAY - December 16th, 2021 Multi-IND Potential Multi-IND Potential Multi-IND Potential PAGE 74#75KT-253, a First-in-Class MDM2 Degrader in Development for Solid and Liquid Tumors Juliet Williams, Ph.D., SVP, Head of Biology, Kymera KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#76DNA Damage p53 Stressors Hypoxia # MDM2 is the E3 Ligase that Modulates P53, the Largest Tumor Suppressor p53 Oncogenes MDM2 p53 ub ub ub MDM2 Tumor Suppression KYMERA ©2021 KYMERA THERAPEUTICS, INC. Other p53 Degradation p53 Targets Feedback Loop Cell Cycle Arrest (p21, Ptprv) Apoptosis (Noxa, Bax, Puma) ● Cancer Genetics p53 is NOT mutated in almost 50% of tumors • MDM2 overexpression and amplification can ● inactivate p53 ● Large opportunity in wide variety of cancers Dependency of p53WT cells on MDM2 MDM2 CRISPR Sensitivity Score 0.6 0.4 0.2 0 -0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4 -1.6 -1.8 -2 -2.2 KYMERA R&D DAY - December 16th, 2021 p53MUT p53WT Graph generated with data obtained from DepMap.org Cell Line PAGE 76#77DNA Damage MDM2 Degradation, Not Inhibition, Efficiently Restores p53 p53 Stressors Hypoxia # Inhibitor I MDM2 T Degrader p53 Oncogenes ub ub ub p53 MDM2 Tumor Suppression KYMERA ©2021 KYMERA THERAPEUTICS, INC. Other p53 Degradation p53 Targets Feedback Loop Cell Cycle Arrest (p21, Ptprv) Apoptosis (Noxa, Bax, Puma) Clinical Validation • MDM2 small molecule inhibitors of MDM2/p53 interaction show activity in the clinic.. ...but they induce MDM2 feedback loop resulting in limited impact on pathway Degrader Advantage • MDM2 degraders, by removing the protein, can overcome the p53-dependent feedback loop that upregulates MDM2 ● MDM2 degrader can induce an acute apoptotic response in tumor cells, increasing efficacy and therapeutic index vs a small molecule inhibitor KYMERA R&D DAY - December 16th, 2021 PAGE 77#78Kymera's MDM-2 Degrader Development Candidate, KT-253 is Superior to MDM2/p53 Small Molecule Inhibitors KT-253 is a potent MDM2 degrader % MDM2 Remaining Company 300 250 200 150 100 80 60 40 20 0 KT-253 + DS-3032 Baseline 100000 0.0001 MDM2-HiBiT 0.001 0.01 Compound 0.1 Concentration, μM DC50=0.4nM Clinical stage RS4-11 IC50 (nM) (AML Cell Killing) MDM2-HiBiT, DC50 (nM) (Degradation) 10 KT-253, unlike SMI's such as DS- 3032, strongly stabilizes p53... p53 MSD, 2h 3000 100 80- 60 40- CO 20 DMSO -20 2500 2000 1500- 1000 500- 0- 0.00001 KT-253 Kymera IND enabling 0.3 0.4 KT-253 DS-3032 0.0001 0.001 0.01 Concentration, μM DS-3032 Sankyo/Rain Ph II / combo AML 67 10 RG7388 Roche Ph II / III 220 ... which leads to superior tumor cell killing (pM range) KYMERA R&D DAY - December 16th, 2021 TO000'0 KT-253 DS-3032 620 SAR405838 Sanofi Paused 0.0001 RS4;11, 24h CTG 0.001 0.01 0.1 Concentration, μM HDM201 Novartis PhI/II 163 DMSO 10 AMG-232 Amgen/Kartos Multiple Ph II; combo AML 280 KT-253 is >200-fold more potent in tumor cell killing assays than SMI's due to to its mechanism of action Proteomics show selective degradation of KT-253 KYMERA ©2021 KYMERA THERAPEUTICS, INC. PAGE 78#79KT-253, Unlike Small Molecule Inhibitors, Overcome the MDM2 and p53 Autoregulatory Feedback Loop Degrader Overcomes MDM2 Feedback Loop KT-253, IC90 KYMERA Oh DMSO 2h 24h 4h 24h DMSO MDM2 levels are kept at undetectable levels with MDM2 degrader KT-253, leading to p53 stabilization DS-3032, IC90 Oh DMSO 2h 24h 4h 24h DMSO MDM2 ACTB ©2021 KYMERA THERAPEUTICS, INC. MDM2 ACTB MDM2 levels are increased by the small molecule inhibitor (feedback loop), impairing p53 stabilization KYMERA R&D DAY - December 16th, 2021 p53 Inhibitor 1 MDM2 T Degrader p53 ub p53 ub ub T MDM2 p53 Degradation Feedback Loop p53 Targets PAGE 79#80Short Term Exposure to MDM2 Degrader, but not SMI, is Sufficient to Commit Cells to Undergo Apoptosis Caspase 3_7/CTG Signal ● 20000 10000 3000 2000 1000 0 04 KT-253 1000 nM 100 nM 10 nM 1 nM 24 Time, hrs 48 Caspase 3_7/CTG Signal KYMERA ©2021 KYMERA THERAPEUTICS, INC. 20000 10000 3000 2000 1000 0- 04 DS-3032 1000 nM 100 nM 10 nM 1 nM 24 Time, hrs 48 Treatment Washout KYMERA R&D DAY - December 16th, 2021 Oh 4h | | P53 Levels by MSD Caspase Activity 24h Į 4 hr target coverage by KT-253 is sufficient to induce apoptosis in contrast to SMIS Supports hypothesis that intermittent dosing schedule of KT-253 can drive efficacy while increasing therapeutic index Cells Allowed to Recover 48h Į PAGE 80#81Tumor Volume (mm³) Mean, ± SEM Single Dose of KT-253 Leads to Sustained Tumor Regression Single Dose of KT-253 Achieves Sustained Tumor Regression MDM2 Degradation (KT-253, 1 mg/kg) Leads to Fast Increase in p53, p21, and PUMA (Key Apoptotic Biomarker) Rs4:11 XGs 3000- 2000 1000- 0- Vehicle KT-253, 1 mg/kg KT-253, 3 mg/kg KT-253, 10 mg/kg 20 40 Days (Post-randomization) 60 KYMERA ©2021 KYMERA THERAPEUTICS, INC. % Ratio (Relative to ACTB) 800 600 400 200 p53 1 3 6 24 48 Time, hrs Oh % Ratio (Relative to ACTB) 800 KYMERA R&D DAY - December 16th, 2021 600 400 200 p21 -F--Oh 1 3 6 24 48 Time, hrs % Ratio (Relative to ACTB) 300- 200- Clinical equivalent doses of small molecule inhibitors have no significant in vivo impact in these xenograft models 100 PUMA I -- Oh T 1 3 6 24 48 Time, hrs PAGE 81#82MDM2 Dependency Seen Across a Large Subset of Tumor Types Large Franchise Potential in Liquid and Solid Tumors MDM2 CRISPR Sensitivity Score 0.6 0.4 0.2 0 -0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4 -1.6 -1.8 -2 -2.2 Dependency of p53WT Cell Lines on MDM2 p53MUT p53WT Graph generated with data obtained from DepMap.org Cell Line Tumor Types: Uveal melanoma, Bile Duct, Bladder, Bone, Brain, Breast, Colon, Endometrial/Uterine, Gastric, Kidney, Liver, Lung, Ovarian, Pancreatic, Rhabdoid, Sarcoma, Leukemia, Lymphoma KYMERA ©2021 KYMERA THERAPEUTICS, INC. % Growth Inhibition (CTG) MDM2 Degrader Superior to SMI Across Cell Line Panel Heme & Solid Cell Lines 100 80 60 40 20 O -20 0.00001 KT-253 DS-3032 KYMERA R&D DAY - December 16th, 2021 0.0001 0.001 0.01 0.1 DMSO 10 Concentration, μM p53WT cell lines sensitive: ALL, AML, DLBCL, Uveal Melanoma p53 mutant cell lines were not sensitive to KT-253 or DS-3032 as expected PAGE 82#83TCGA Oliner, et al. 2015 KYMERA Focus on Indications Where MDM2 Degradation Leads to Acute Apoptotic Response p53 WT in >50% of Tumors ● ● ● ● ● ● • AML ● ● Mesothelioma Melanoma DLBCL Prostate cancer ● Cholangiocarcinoma Cervical cancer Renal cell cancer Uveal melanoma Thyroid cancer Liposarcoma HCC Breast cancer ©2021 KYMERA THERAPEUTICS, INC. MOA-specific Sensitivity (Biomarker-based) ● ● AML Uveal Melanoma ● Lymphomas Others will be disclosed in upcoming medical meetings KYMERA KYMERA R&D DAY - December 16th, 2021 ● ● ● ● ● MDM2 Amplification Liposarcoma (87%) Sarcoma (19%) Glioblastoma multiforme (7%) Bladder (3%) Cholangiocarcinoma (3%) TCGA Donehower, et al. 2020 PAGE 83#84KT-253 is a Potent MDM2 Degrader and a Best-in-Class p53 Stabilizer with Potential to Treat Numerous p53 WT Tumors ● ● ● ● ● KT-253 inhibits tumor cell growth with picomolar potency and is more than 200-fold more potent than clinically active MDM2 small molecule inhibitors KT-253, unlike small molecule inhibitors, blocks the feedback loop which up-regulates MDM2 production and in doing so more effectively stabilizes the tumor suppressor p53 Short term high exposures of KT-253 are enough to induce apoptosis in cell lines and in vivo xenografts, which ensures high activity and improved therapeutic index vs SMI's Broad franchise opportunities available for this mechanism (p53 WT is present in >50% tumors), Kymera is focused on indications with specific sensitivity to degrader mechanism, such as AML, Uveal melanoma and others through a biomarker strategy Projected IND filing in 2022 KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 84#85Expanding the Drugged Proteome: Kymera's Platform Chris De Savi, Ph.D., VP, Head of Drug Discovery, Kymera KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#86Targeted Protein Degradation Human Proteome KYMERA Targeted Protein Degradation Next Potential Breakthrough Modality to Expand Drugged Proteome ✓ ✓ ✓ ✓ Undrugged Opportunity ©2021 KYMERA THERAPEUTICS, INC. Drugged Traditional Small Molecule Undruggable Targets Scaffold, transcript factor, multiple functions Efficient Development / Manufacturing Systemic Exposure Oral Bioavailability KYMERA R&D DAY - December 16th, 2021 Existing Modalities Antibody 044 Antisense X X X Cell/Gene Therapy RNAi PAGE 86#87ID We Want to Drug All Target Classes C Inadequately Drugged Targets with Clear Degrader Advantage Small molecule binders exist but unable to drug target fully e.g. IRAK4, MDM2... KYMERA Heterobifunctional Degraders ©2021 KYMERA THERAPEUTICS, INC. Expanding the Druggable Proteome with TPD UD Undrugged Targets No other technology can drug Ligandable Proteins e.g. STAT3... Heterobifunctional Degraders Un-ligandable Proteins e.g. other transcription factors Molecular Glues KYMERA R&D DAY - December 16th, 2021 Clinically Validated Targets TR Enabled by E3 Ligase Tissue Restricted Expression On target unwanted pharmacology limits clinical application Į E3-1 E3-2 Tissue sparing or selective E3 ligases eliminate unwanted toxicity and allow full clinical potential PAGE 87#88NEW Expanded E3 Ligase Toolbox Understanding Degradation (PK/PD) Across Tissue Types Proprietary Chemistry Center for Molecular Glue Discovery KYMERA Proprietary PegasusTM TPD Platform Key Capabilities E3 ligase Whole-Body Atlas: Identification of the expression profiles of ~600 unique E3 ligases Match target protein with appropriate E3 ligase based on expression, distribution, intracellular localization, and biology through a machine learning based algorithm Toolbox of proprietary ligands leverages the E3 Ligase Whole-Body Atlas Quantitative System Pharmacology Model measures and predicts diverse sets of parameters that impact protein levels Based on understanding of PK/PD, both in vitro and in vivo, and across different tissues and cell types Comprehensive hit finding technologies toolbox Proprietary chemistry expertise enables the design and optimization of both E3 ligases and target protein binders, Al enabled optimization Ability to convert into degraders with optimal pharmaceutical properties Identification of novel E3 ligases, beyond CRBN, that enable degradation of high value "undrugged and un-ligandable" proteins through small molecule interactions Established collaborations with A-Alpha Bio and two academic organizations in the US to enable this novel and differentiated approach to molecular glues discovery UD Undrugged Targets ID Inadequately Drugged Targets with Clear Degrader Advantage ©2021 KYMERA THERAPEUTICS, INC. TR Clinically Validated Targets Enabled by E3 Ligase Tissue Restricted Expression KYMERA R&D DAY - December 16th, 2021 DISCOVERY IMPACT BY TARGET TYPE ID UD ID UD ID UD UD TR TR TR PAGE 88#89TR Clinically Validated Targets Unlocked by E3 Ligase Differential Expression On target unwanted pharmacology limits clinical application ● Novel E3 Ligases to Drug a New Generation of Targets ● KYMERA Focused on determining the expression profiles of ~600 unique E3 ligases Patterns mapped in both disease and healthy contexts • Ability to match a target protein with appropriate E3 ligase based on expression and biology via a machine learning algorithm Vision to develop tissue-selective or tissue-restricted degraders to nable novel therapeutic opportunities ©2021 KYMERA THERAPEUTICS, INC. E3 LIGASES TARGETS CRBN CUL4A DDB1 XIAP LIGASE 1 LIGASE 2 LIGASE 3 LIGASE 4 RNF114 Mol. wt (kDa) DCAF 16 LIGASE 5 LIGASE 6 LIGASE 7 LIGASE 8 LIGASE 9 LIGASE 10 STAT3 IRAK4 TARGET 1 TARGET 2 TARGET 3 Increasing Abundance ooooooooº 000000 O 0000 TONSIL LIVER SPLEEN STOMACH BRAIN LUNG TESTIS DUODENUM KYMERA R&D DAY - December 16th, 2021 • ● SMALL INTESTINE. URINARY BLADDER... ESOPHAGUS GALL BLADDER TISSUES HEART THYROID ENDOMETRIUM NO FALLOPIAN TUBE. 6 KIDNEY SMOOTH MUSCLE PROSTATE APPENDIX PANCREAS OVARY PLACENTA •-. - RECTUM ADIPOSE TISSUE LYMPH NODE SALIVARY GLAND ADRENAL GLAND UNDISCLOSED Ubiquitous Restrictive Selective Source: Kymera's Proprietary E3 Expression Atlas PAGE 89#90Kymera has Engaged a Broadly Expressed Protein in Only One Cell Type Using a Tissue Selective E3 Ligase Protein Kymera Has Identified an E3 Ligase that is Expressed Almost Exclusively in One Cell Population CRBN Ligase X Biological Replicates Protein Expression Profile (Proprietary E3 Atlas) Target Cells 1 23 Cell #1 1 2 3 Cell #2 Log 10 Tox Cell Types 1 2 3 Cell #3 Concentration Estimate [nM] KYMERA ©2021 KYMERA THERAPEUTICS, INC. 1 2 3 Cell #4 1 2 1 2 3 Cell #5 Ligand Identification and Optimization Small Molecule Ligand Bound to a Tissue-selective E3 Ligase KYMERA R&D DAY - December 16th, 2021 Lead Compound Affinity K = < 1 uM Leads to an Active Ternary Complex with a Protein of Interest Relative Signal 1.0 0.5 0.0 AUC 1.133 Bmax=1109 nM -9 -8 -7 -6 -5 -4 Log[Compound], M PAGE 90#91Tissue-Selective Degradation Drives Increase of Therapeutic Index Kymera has characterized an E3 ligase that is expressed broadly but NOT in ONE blood cell type ● A clinically validated oncology target has dose limiting toxicity driven by on-target ● pharmacology in the same blood cell type where this E3 ligase is absent/very low E3 Ligase is Almost Absent in One Blood Cell Type KYMERA Tumor Cells Blood Cells ©2021 KYMERA THERAPEUTICS, INC. Donor Donor 2 B-actin This program is projected to nominate a development candidate in 2022 E3 Ligase Optimization and Degrader Program Percentage Control (%) Percentage Control (%) 100 50- Blood Cell Viability (%) O 100 50 100- 50 0 0 0 KYMERA R&D DAY - December 16th, 2021 In Cancer Cell 2 3 Log₁0 [Concentration (nM)] In Blood Cell 1 1 --● POI Degradation 2 3 Log₁0 [Concentration (nM)] In Vivo POI Degrader POI SMI 4 Kymera's degrader using this E3 ligase degrades target in cancer cells Kymera's degrader using this E3 ligase DOES NOT degrade target in one blood cell type In a pharmacologically active dose in vivo a degrader allows blood cells to survive while SMI leads to substantial cell death POI = protein target of interest PAGE 91#92Criteria • Availability of ● Approaches ● Virtual Screen ● A Comprehensive Hit Finding Toolbox Rapidly Enables New Ligand Discovery Against All Target Classes structure or homology model DB ~8 million purchasable cpds Cloud enables screen < 24hrs Al to improve enrichment KYMERA H ● DEL Criteria High quality protein Ideal QC profile (single-species by SEC; <5% aggregation by DLS) ©2021 KYMERA THERAPEUTICS, INC. Criteria Availability of high quality (crystallization-grade) Ⓡ Fragment-Based Screen ● Approaches SPR, NMR X-ray LC/MS (covalent) ● protein Robust crystallization system Cysteine Covalent Screening Criteria Proteins have reactive cysteines • Approaches • Covalent fragment screening on recombinant protein • Whole cell covalent fragment screening KYMERA R&D DAY - December 16th, 2021 HTS Criteria Available high- throughput assay format Approaches Focused library Diversity set ● IM) ASMS Criteria • Availability of high- quality protein PAGE 92#93Successful Examples of Fragment and Covalent Screens Fragment Based Virtual Optimization X-ray with Fragment Fragment bound X-ray structure Rational design to explore SAR In silico library evaluation & synthesis Rational design to optimize library hits KYMERA HTRF IC50 > 1mM IC50 < 30 μM IC50 < 5 μM IC 50 = < 0.1 μM μΜ MW <400 clogP 0.7 Total # of virtual compounds evaluated Total # of crystal structures Total # of compounds made ©2021 KYMERA THERAPEUTICS, INC. X-ray with Optimized Ligand 40K 18 195 cell_line Covalent Ligand E3 Ligase Hit Finding HCT116 PaTu-8988T HCT116 PaTu-8988T HCT116 PaTu-8988T HCT116 HCT116 CL1 CL26 KYMERA R&D DAY - December 16th, 2021 CL51 CL76 CL101 CL126 AC23 ligand CR < 2 CR >= 2 and CR < 4 CR >= 4 NA AC48 AC73 ACB AC123 AC148 7 128 137 176 Novel covalent ligand to bone marrow-sparing E3 ligase for multiple oncology programs PAGE 93#94Kymera Can Develop Degraders with Predictable Drug-Like Properties Pre-clinical Optimization of Degraders Leads to High Oral Bioavailability Across Pre-clinical Species Ternary Complex Modeling (TCM) Harnessing the power of cloud computing and Al to evaluate millions of TCM models DMPK Properties HLM / RLM (uL/min/mg) P. (10-6 cm/s) / Efflux Ratio app Rat Cl (mL/min/kg) / Vdss / F% Dog Cl (mL/min/kg) / Vdss / F% Monkey Cl (mL/min/kg) / Vdss / F% KYMERA ©2021 KYMERA THERAPEUTICS, INC. ${ Molecular Chameleonicity Accurately capturing the chameleonic nature of degraders to predict ADME/PK profile Degrader 1 317 / 193 ND / ND ND ND ND Degrader 2 74 / 22 6.0 / 1.3 35/9/8 69 / 19 / 9 129 / 16 / 1 KYMERA R&D DAY - December 16th, 2021 Al-driven Insights Leveraging deep-learning to derive design insights from in silico and in vitro data Degrader 3 <12/<12 14/21 19/7/14 15/11/58 33 / 16 / 45 Degrader 4 <12 / <12 4.3 / 2.0 7/3/18 6/4/60 9/6/62 PAGE 94#95Mechanistic Modeling Allowed Kymera to Accurately Predict Human PK and PD from Preclinical Dog Data for Clinical Candidate KT-474 Mechanistic PK/PD Modeling Describes the MoA of TPD Drug IV, SC, PO Ka PD (R) Target Protein 84 Tissue Keo EC50 Cp Ct d.R Plasma Kel PK Elimination PD dt Ksyn Kdeg = ksyn — kdeg (1 + EmaxxCt BCSo+Ct R KYMERA ©2021 KYMERA THERAPEUTICS, INC. % IRAK4 100 80 60 40 20 100 80 60 40 20 Preclinical Species Models for PK/PD KT-474 in Dog Ⓡ 0.3 mg/kg D2001 0 48 96 144 192 240 288 10 mg/kg D5001 0 0 48 96 144 192 240 288 0 0.3 mg/kg 0.3 mg/kg D2501 as.factor(dose) 1 mg/kg 10 mg/kg 3 mg/kg 1 mg/kg D3001 48 96 144 192 240 288 10 mg/kg D5501 48 96 144 192 240 288 • 0 48 96 144 192 240 288 Time (h) ● 3 mg/kg D4001 1 mg/kg D3501 0 48 96 144 192 240 288 0 48 96 144 192 240 288 0 48 96 144 192 240 288 KYMERA R&D DAY - December 16th, 2021 3 mg/kg D4501 Predicted % IRAK4 Reduction from Baseline Model Predicts Human PK/PD 0 20 40 60 80 85 K 100 0.01 DC85= 3 ng/mL 0.1 10 Plasma KT-474 Ctrough (ng/mL) 1 Dog Human 100 PAGE 95#96UD Rationally Designing Molecular Glues to Drug Historically Undrugged/Unligandable Targets To drug all genetically validated but undrugged and un-ligandable proteins through the discovery of novel E3 ligases and small molecule glues Undrugged Targets No other technology can drug Ligandable Proteins e.g.STAT3 Un-ligandable Proteins e.g. other transcription Heterobifunctional Degraders factors Molecular Glues KYMERA ©2021 KYMERA THERAPEUTICS, INC. Our Approach: We are NOT iterating on CRBN/IMID Scaffold Identifying the best matched pairs between targets of interests and E3 ligases exploiting natural affinity augmented with small molecule glues ● ● ● Established a platform that uses high content genetic-based screens, structural insights, biological pathways deconvolution, degron discovery, computational knowledge expansion Multiple programs in discovery stage Strategic partnerships with: @ A-ALPHA BIO W UNIVERSITY of WASHINGTON KYMERA R&D DAY - December 16th, 2021 NYU PAGE 96#97● ● ● ● ● ● Expanding the Druggable Proteome with TPD Kymera intends to drug all target classes using targeted protein degradation A comprehensive hit finding toolbox with key Al and machine learning inputs has been developed to identify ligands against novel E3 and undrugged targets Our capabilities have evolved to accurately predict human active doses and compound properties We have developed know-how and technologies to drug inadequately drugged targets such as IRAK4 and MDM2, undrugged targets such as STAT3 and have for the first time in TPD drugged targets in a tissue selective manner using our E3 ligase toolbox. Kymera has established a new discovery unit to identify new molecular glue degrader drugs focused on undrugged/un-ligandable high value protein targets Multiple strategic collaborations have been established to enable MG Discovery KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 97#98Kymera 2026 Vision Nello Mainolfi, Ph.D., Founder and CEO, Kymeral KYMERA KYMERA R&D DAY - December 16th, 2021 5 KYMERA EST. 2016#99● ● ● ● Our first 5 years; pipeline and platform investments Three compelling clinical programs with large franchise potential: IRAK4, KT-474 - Ph1 data de-risks profile for best-in-class oral drug in broad immune-inflammatory indications IRAKIMID, KT-413 - Potential for first therapeutics for genetically defined subtype of DLBCL, IND cleared STAT3, KT-333 - First specific degrader against a transcription factor with large franchise potentials, IND cleared Significant investment in our discovery pipeline: MDM2, KT-253 - Best in class P-53 stabilizer for liquid and solid tumors, IND in 2022 Commitment to at least 1 new IND/year, yearly disclosure of new development program(s) Commitment to innovation for our platform and pipeline: ● ● ● ● ● ● What We Showed You Today ● First tissue restricted E3 ligase in vivo POC, leading to tissue sparing biology Novel approach to molecular glue for undrugged/unligandable targets Goal of drugging all target classes in the cell KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 99#100Pathway Program IL-1R/TLR JAK/STAT p53 Collaboration Discovery Pipeline Collaboration IRAK4 IRAKIMID (IRAK4, Ikaros, Aiolos) STAT3 STAT3 MDM2 Confidential Indication(s) Multiple Immuno- inflammatory Diseases: HS, AD, RA others MYD88MT Tumors Liquid & Solid Tumors Autoimmune & Fibrotic Diseases Liquid & Solid Tumors Confidential Several Discovery Programs 6 Undisclosed Programs Kymera's Pipeline Today KYMERA ©2021 KYMERA THERAPEUTICS, INC. Discovery IND Enabling Multiple molecules staged as potential back ups if needed KT-474 10 KT-413 KT-253 KT-333 Phase 1 *Option to participate equally in the development and commercialization of Sanofi-partnered programs in the US Multiple programs in immune-inflammatory and oncology indications to deliver ≥ 1 IND/year 6 targets in 5 disease areas outside of immunology-inflammation and oncology KYMERA R&D DAY - December 16th, 2021 Phases 2/3 = Oncology NEW Next Milestone Rights* KYMERA Patients POB mid-22 POM: 2022 POM: 2022 IND: 2H22 ≥ 1 DC: 2H22 = Immunology-Inflammation SANOFI KYMERA KYMERA KYMERA KYMERA K SANOFI KYMERA VERTEX PAGE 100#101● ● ● ● What We Expect in 2022 Completion of Ph1 patient cohort for KT-474 and transition to Sanofi Proof of mechanism in patients for KT-413 and KT-333 oncology Ph1 studies IND filing for KT-253 First tissue restricted E3 ligase enabled program in development Continued growth of team and capabilities Expanded recognition as a leader in TPD with a disruptive innovation engine across the biotech sector Multiple scientific contributions in medical meetings and in peer reviewed publications Continued investment in providing our employees, collaborator and partners the best experience KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 101#102Our 5-year Vision: Where Kymera Will Be in 2026 A fully-integrated biotech company with a disease KYMERA and technology agnostic pipeline and capabilities Path to NDA for at least 1 program Disease and technology- agnostic pipeline and capabilities At least 8 clinical stage programs across different development stages and disease areas Expand technology platform to wholistically address undrugged proteome KYMERA ©2021 KYMERA THERAPEUTICS, INC. Pipeline positioned to deliver at least 1 new IND per year Continued commitment to innovation and first- in-class science and medicines KYMERA R&D DAY - December 16th, 2021 Clinical proof-of-concept established in tissue- selective/restricted degradation and undrugged targets Commercial organization build up in progress PAGE 102#103Pathway IL-1R/TLR JAK/STAT p53 Discovery Pipeline KYMERA What Kymera's Clinical Pipeline Could Look Like in 2026 Program IRAK4 IRAKIMID (IRAK4, Ikaros, Aiolos) STAT3 STAT3 MDM2 Indication(s) HS, AD, RA others MYD88MT DLBCL, Waldenstrom's, others Liquid & Solid Tumors Autoimmune & Fibrotic Diseases Liquid & Solid Tumors Tissue Sparing Biology Several Discovery Programs ©2021 KYMERA THERAPEUTICS, INC. Discovery IND Enabling KT-474 KT-413 KT-253 KT-333 Phase 1 Phases 2/3 Multiple programs in immune-inflammatory and oncology indications to deliver ≥ 1 IND/year KYMERA R&D DAY - December 16th, 2021 = Oncology Rights* KYMERA SANOFI KYMERA KYMERA KYMERA KYMERA KYMERA KYMERA KYMERA KYMERA KYMERA = Immunology-Inflammation PAGE 103#104What We Hope You Will Take from Today • Targeted Protein Degradation is positioned to transform drug development ● landscape Kymera is a medicine focused company with recognized leadership in TPD • We employ a novel and differentiated scientific strategy and approach around target selection, drug development and platform investments We are committed to innovation, execution and to the pursuit of real step change in treatment paradigms There is much we have accomplished since our founding, but even more we expect to deliver in 2022 and beyond We have a very ambitious but achievable vision for the company KYMERA ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 104#105KYMERA EST. 2016 Thank you Q&A UN COLUMBIA BENCH 89