#1INVENTING NEW MEDICINES WITH TARGETED PROTEIN DEGRADATION KYMERA December 2023#2Forward-looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. These statements include, but are not limited to, implied and express statements about our strategy, business plans and objectives for our programs; plans and timelines for the preclinical and clinical development of our product candidates, including the therapeutic potential, clinical benefits and safety profiles of such product candidates; expectations regarding timing, success and data announcements of ongoing preclinical studies and clinical trials; our ability to initiate new clinical programs, including plans to submit investigational new drug (IND) applications; the initiation, timing, progress and results of our current and future preclinical studies and clinical trials of our current and prospective product candidates; our plans to develop and commercialize our current and any future product candidates and the implementation of our business model and strategic plans for our business, current and any future product candidates. 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. In some cases, you can identify forward-looking statements by terminology such as "anticipate," "assume," "believe," "could," "estimate," "expect," "goal," "intend," "may," "milestones," "objective," "plan," "predict," "potential," "seek," "should," "target," "will," "would" and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. You should not rely upon forward-looking statements as predictions of future events and actual results or events could differ materially from the plans, intentions and expectations disclosed herein. Any forward-looking statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements including, without limitation, risks associated with: the timing and anticipated results of our current and future preclinical studies and clinical trials, supply chain, strategy and future operations; the delay of any current and future preclinical studies or clinical trials or the development of our drug candidates; the risk that the results of prior preclinical studies and clinical trials may not be predictive of future results in connection with current or future preclinical studies and clinical trials, including those for KT- 474/SAR444656, KT-333 and KT-253; our ability to successfully demonstrate the safety and efficacy of our drug candidates; the timing and outcome of any interactions with regulatory authorities; obtaining, maintaining and protecting our intellectual property; our relationships with existing and future collaboration partners; the impacts of current macroeconomic and geopolitical events. In addition, any forward-looking statements represent Kymera's views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera explicitly disclaims any obligation to update any forward-looking statements, except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. As a result of these risks and others, including those set forth in our filings with the SEC, actual results could vary significantly from those anticipated in this presentation, and our financial condition and results of operations could be materially adversely affected. Certain information contained in this presentation and statements made orally during this presentation relate to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party studies, publications, surveys and other data to be reliable as of the date of the presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent sources have evaluated the reasonableness or accuracy of the Company's internal estimates or research, and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. KYMERA ©2023 KYMERA THERAPEUTICS, INC. PAGE 2#3KYMERA Recognized leader in Targeted Protein Degradation (TPD) Building a fully-integrated, global biotech company Focusing on I/I and some areas of Oncology, with disease- agnostic potential Accelerating forward integration through key strategic partnerships KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. ● Overview Focused on unlocking high value, undrugged targets using TPD Advanced four programs to clinical stage to date, first degrader program in I/I with IRAK4 demonstrating degrader differentiation Demonstrated fidelity of translation of PK, PD and safety across four clinical programs in both immunology and oncology Demonstrated clinical activity in three programs in immunology and oncology Initiated two Phase 2 trials for KT-474/SAR444656, in potential blockbuster indications (HS & AD) with Sanofi Highly productive discovery engine delivering multiple INDs/year with expanding focus in I/I Well-capitalized with $435m of cash as of September 30, 2023, enabling expansion of clinical impact into areas with large clinical and commercial opportunities PAGE 3#4KYMERA KYMERA Recent Accomplishments Dosed first patients in KT-474 Phase 2 clinical trials in Hidradenitis Suppurativa and Atopic Dermatitis • Resulted in combined $55m from Sanofi in development milestones Published KT-474 Phase 1 study results in Nature Medicine; first clinical publication in TPD Demonstrated initial KT-333 anti-tumor activity in Phase 1 clinical trial; results presented at ASH 2023 Demonstrated proof-of-mechanism in KT-253 and initial antitumor activity in first patient cohort without typical MDM2 hematologic toxicity Cash runway guidance into first half of 2026 ©2023 KYMERA THERAPEUTICS, INC. PAGE 4#5TARGET SELECTION Kymera: A Differentiated Approach to TPD Undrugged (UD) or inadequately drugged (ID) targets UD Transcription Factors (e.g. STAT3) KYMERA ID Degrader Advantage Over SMI (e.g. IRAK4, MDM2) Strong genetic validation within clinically validated pathway ©2023 KYMERA THERAPEUTICS, INC. PLATFORM Significantly differentiated investments Tissue- selective E3 Ligases Enabling a whole new generation of clinical programs New Molecular Glue Approach Novel strategy to address undrugged/ unligandable targets CLINICAL TRANSLATION Fidelity of translation of PK, PD and safety in 4 programs in immunology and oncology 0 Percent Change from Baseline IRAK4 -20 -40 -60 -80 % Change from C1D1 Predose (Mean ± SEM) -100 -20 0 4 8 12 16 20 24 28 32 36 40 -40 -60 -80- -100 KT-333 1 MAD PART C Cycle 1 weeks 1 & 2 T T T T 2 3 4 5 6 7 8 9 10 11 12 Days in Study PAGE 5#6Clinical and Near-Term Clinical Pipeline of Novel Protein Degraders Immunology Programs IRAK4* Transcription Factor IL4/13 Pathway Scaffolding Kinase STAT3 Oncology Programs STAT3 MDM2 Potential Indication(s) HS, AD, RA, Other AD, Asthma, COPD, EoE, PN Psoriasis, IBD, Lupus, Other Autoimmune & Fibrotic Diseases Potential Indication(s) PTCL, LGL-L, CTCL, Solid Tumors Liquid & Solid Tumors Preclinical Phase 1 KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. KT-474 - Hidradenitis Suppurativa KT-474 - Atopic Dermatitis 00 Preclinical KT-333 KT-253 Phase 2 Phase 1 Phase 2 *KT-474 partnered with Sanofi, with Kymera option to participate equally in the development and commercialization in the United States. Phase 3 Phase 3 Upcoming Milestones Topline HS Data 1H 2025 Topline AD Data 1H 2025 R&D Day January 2024 R&D Day January 2024 R&D Day January 2024 Upcoming Milestones Phase 1a results: 2024 Phase 1a results: 2024 Rights with sanofi KYMERA KYMERA KYMERA Rights KYMERA KYMERA PAGE 6#7KYMERA IRAK4#8Degrading IRAK4: Best Approach to Block IL-1R/TLR driven Inflammation 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 IRAK 1 IRAK2 TRAF6 c-Jun KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. IL-1R JNK/p38 secreted TNF-a, IFN-Y, IL-1B, IL-6, IL-8, IL-10, IL-12, IL-17, IL-23 Degrader Advantage Inhibitor Scaffolding Role JNK/p38 NFkB IRAK4 Degrader Kinase Role IRF5/7 Clinical Pathway Validation IL-1a/IL-1ß: 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 8#9● ● ● ● ● IRAK4 Degrader Best-in-Class Potential in Immune-inflammation Potential for Broad Activity Across Th1-Th17 and Th2 Diseases KT-474 Lupus IBD Gout Psoriasis IL-1R/TLR ↓ IRAK4 Th1-Th17/Neutrophils Hidradenitis Suppurativa Rheumatoid Arthritis ● ● Th2/Eosinophils Atopic Dermatitis Asthma COPD CRSWNP Combined global drug sales ~$120B Source: 1. GlobalData; 2. Evaluate Pharma;.3. Ahn. JAMA Otolaryngol Head Neck Surg. 2016; 4. Dash. Allied Market Research 2021 KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. Indication AD HS RA SLE IBD Gout Psoriasis Asthma COPD CRSWNP 2022 Prevalence¹ (US/EU5/JP) 98 M 785 K 6.4 M 550 K 3.1 M 20.3 M 15.8 M 86.8 M 61.9 M 20.4 M³ 2022 Global Sales² $8.6 B $1.0 B¹ $27.9 B $1.8 B $23.6 B $1.1 M $24.6 B $17.7 B $9.6 B $2.6 B4 Limitations of Current Therapies Anti-Cytokine/Cytokine Receptor Antibodies Target only 1-2 cytokines Require injection • Small Molecule Inhibitors o Limited pathway blockade (IRAK4 SMI) Safety issues (JAK family) PAGE 9#10● ● ● ● ● KT-474 Phase 1 Data Supports Phase 2 Advancement Healthy Volunteers (HV), SAD and MAD Evaluated safety, tolerability and pharmacokinetics in 132 healthy volunteers SAD: oral doses of 25-1600 mg MAD: escalating doses up to 200 mg were administered for 14 consecutive days Robust ( >95%) and sustained IRAK4 degradation with single and multiple daily doses Broad inhibition of ex vivo TLR-mediated cytokine induction Generally well-tolerated across all dose groups KYMERA ©2023 KYMERA THERAPEUTICS, INC. ● ● ● ● HS and AD Patient Cohort Open label study in 21 patients with HS and AD Dose: 75 mg QD with food (equivalent exposure to 100 mg fasted), administered for 28 consecutive days Safety, PK and PD comparable to healthy volunteers Robust IRAK4 degradation in blood and skin with associated systemic anti-inflammatory effect in HS and AD patients Promising clinical activity observed in HS and AD PAGE 10#11Mean (± SE) Percent IRAK4 Change from Baseline 50 -20 -40 -60 -80 -100 ● ● KT-474 Healthy Volunteer Study: Robust and Sustained IRAK4 Degradation Leading to Broad Cytokine Impact 1 2 3 4 Mean % Reduction of IRAK4 (Daily oral doses for 14 days) 7 Dosing period 14 Day 17 21 KYMERA ©2023 KYMERA THERAPEUTICS, INC. Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD 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) 50-200 mgs approached Lower Limit of Quantitation (LLOQ) 28 Ex Vivo Inhibition of 9 Disease-Relevant Cytokines, Day 7-14 R848 (TLR7/8) Stimulation Placebo (n = 9) 50 mg QD (n = 9) 100 mg QD (n = 8-9*) Pbo 50 mg QD 200 100 -50 -100 IFNY IL10 IL6 >500% -62% 15% -85% -59% 35% -18% IL8 IL10 IL12 -53% -5% -28% -23% 100 mg -68% QD Mean values > 200% have been replaced by 200 for visualization purposes *n=8 for LPS, n=9 for R848 2% -32% -50% 3% -58% -72% IL17 107% -24% -46% IRAK4 MAD TNFa -7% -21% -59% PAGE 11#12Percent Change from Baseline IRAK4 PK/PD Correlation in Blood (Plasma/Monocytes) (FLOW) 3 ng/mL threshold -20 -40 -60 -80 -100 0 KT-474 Plasma PK and IRAK4 Degradation in HS and AD Patients Dosed for 28 Days are Comparable to HV High KT-474 Exposure in HS and AD Patients Skin 1000 MAD PART C 4 8 12 16 20 24 28 32 36 40 KT-474 Ctrough/ng/mL KT-474 concentrations in plasma lead to same level of IRAK4 degradation in HV (n=48) and HS/AD (n=20) patients Concentrations above 3 ng/mL lead to same level of degradation (>80%) in HV and Patients IRAK4 Levels in Blood (PBMC) in Patients at Day 28 (MS) KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. Mean (± SE) Absolute IRAK4 Levels by MS [fmol/µg protein] 1.00- 0.75 0.50 0.25 0.00 Day 28 HS and AD Patients IRAK4 Levels at Day 28 (n=4) near LLOQ protein) ន Mean (+SE) IRAK4 Levels in Skin (fmol/µg N Mean 400 0.0 Mean (± SE) KT-474 Concentrations [ng/mL for Plasma, ng/g for Skin] 300 0 Reduced IRAK4 in Skin Lesions of AD and HS Patients 0.3- Plasma Day 28 Skin Day 28 ‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒ MAD Healthy Subjects (Baseline) 46 0.12 AD Patients HS Patients (Baseline) (Baseline) 7 0.22 11 0.24 AD Patients (Day 28) 6 0.1 IRAK4 Patients ‒‒‒‒‒‒‒‒ HS Patients (Day 28) 9 0.11 PAGE 12#13Disease-Relevant Genes Downregulated in Skin Lesions in ≥ 50% of Evaluable* AD (N=7) and HS (N=10) Patients at Day 28 (RNAseq) Substantial downregulation of many disease relevant genes in both HS and AD patients Downregulation exceeded 90% for many genes Broad anti-inflammatory signature with downregulation of genes responsible for: KYMERA IL1 family cytokines Th1 Th17 Th2 Innate immunity AD HS ©2023 KYMERA THERAPEUTICS, INC. CXCL1 AD-3- AD-6- AD-7- AD-4- AD-5- AD-2- AD-1- HS-3- HS-8- HS-2- HS-5 HS-4- HS-12- HS-9- HS-1- HS-6- HS-7- HS-12 HS-7 IFNG HS-3- HS-8 HS-5 HS-1 HS-9 HS-2 HS-4 HS-6- -7.5 CSF3 -7.5 0 log2(fold change) -5.0 -2.5 0.0 log2 (fold change) 2.5 0.0 IL2RB AD-6- AD-3- AD-2- AD-7- AD-1- AD-4- AD-5- GZMB HS-5- HS-2 HS-3- HS-8- HS-12- HS-6- HS-7 HS-4 HS-9- HS-1 -3 HS-8- HS-1- HS-3- HS-4 HS-5 HS-7 HS-9- HS-12- HS-6- HS-2- -7.5 IL1B log2(fold change) -5.0 -2.5 log2 (fold change) log2(fold change) flog2(fold change): -1 = 50% decrease, -2 = 75% decrease, -3 = 87.5% decrease -2.5 log2(fold change) -5.0 0.0 2.5 IL5 AD-4- AD-5- AD-1- AD-3- AD-7- AD-2- AD-6- IL8 HS-5- HS-4- HS-8 HS-1 HS-3- HS-12- HS-7 HS-9 HS-6 HS-2- HS-12 HS-5- HS-3- HS-4 HS-1 HS-8 HS-7 HS-9- HS-6- HS-2- -5.0 IL36A -7.5 0 log2(fold change) -2.5 0.0 log2(fold change) 2.5 5.0 0.0 NLRP3 AD-3- AD-5- AD-2- AD-4- AD-7- AD-1- AD-6- IL2RA HS-4- HS-5- HS-3- HS-8- HS-2- HS-1- HS-9- HS-12- HS-6- HS-7- -4 -2 IL17A HS-5- HS-8- HS-3- HS-4- HS-1 HS-7- HS-2- HS-12- HS-9- HS-6- 0 log2(fold change) -2 log2(fold change) 0 4 -5.0 -2.5 log2 (fold change) log2(fold change) *Evaluable patients for whom the samples were of sufficient quality for analysis. IRAK4 Patients PAGE 13#14Mean % Change (+/- S.E. of mean) 0 -10 -20 -30 -40 -50 -60 0 KT-474 HS: Significant Reductions in AN Counts Leading to HISCR Responses and Significant Reductions in Pain and Pruritis 7 Mean % Change in Total AN Counts Over Time -27.4 -19.9 14 All HS Patients (N=12)* Moderate to Severe (N=10) -49.6 21 Day -31.6 28 -45.4 -40.6 35 -46.1 -50.7 42 KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. % of HISCR Responders (80% CI) 80 70 8 50 9 30 20 10 0 0 7 HISCR50 Responders 30 14 25 21 Day 30 28 25 50 42 35 50 42 42 *One patient is censored for Day 35 and Day 42 since the patient started on ustekinumab, steroids and abx on Day 34. Mean % Change (+/- S.E. of Mean) Mean % Change (+/- S.E. of Mean) Mean % Change in Average Pain Over Past Week -10 -20 -30 -40 -50 -60 -70 -80 0 -10 -20 -50 -60 -70 -80 -30 -29.1 -40 -90 0 -100 -26.9 0 7 -23.4 7 -38.7 -17 14 -41.7 -40.1 -56.1 21 Day Mean % Change in Worst Pruritus Over Past Week -26.1 F-41.9 14 -48.6 -64.6 -24 28 -67.8 21 Day -53.8 -65.7 -48.6 28 35 -59.7 -62.3 -60.1 -60.4 42 35 -53.6 -61.6 IRAK4 Patients -68.4 42 PAGE 14#15● ● ● ● KT-474 Showed Meaningful Signs of Clinical Activity in HS, Comparing Favorably to Placebo Benchmarks and SOC AN Count reductions most profound in moderate and severe patients Highly competitive HISCR response rates continued to improve after cessation of dosing Pain and pruritus response rates and reductions significantly higher than placebo and SOC benchmarks Physician Global Assessment (PGA) scores improved in 5 of 12 patients, including 1 moderate disease patient with full disease clearance, and stable in the others ΔΑΝ Count AN Count 0/1/2 HiSCR50 HiSCR75 Pain NRS30 Responder KT-474 Part C (All/Moderate to Severe) Day 28 Day 42 -32% / -50% 42% / 50% 25% / 30% 8% / 10% 50% / 60% -46% / -51% 33% / 40% 42% / 50% 25% / 30% 50% / 60% Placebo Benchmarks Week 4 -15%¹ 24 to 26%3 19 to 30% 3,4 5%4 18 to 23% 3,5 Adalimumab Phase 2 and 3 Week 4 -31%¹ 28 to 47%2,3 29 to 51% 3,4 20%4 IRAK4 Patients 39 to 58%2,3,5 The Adalimumab clinical trial was conducted by other parties in a similar patient population with different enrollment criteria from Part 1C of our Phase 1 clinical trial evaluating KT-474. Results do not reflect a head-to-head trial and are shown for illustrative purposes only. ¹Kimball AB, et al. Ann Intern Med 2012;157:846-55; 2Morita A, et al. J Dermatol 2021;48:3-13; ³Kimball AB, et al. NEJM 2016;375:422-434;4Glatt S et al. JAMA Dermatol 2021;157:1279-88; 5Scheinfeld, et al. Derm Online J 2016:22 KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. PAGE 15#16Mean % Change in EASI Score (+/-S.E. of Mean) -10 20 -30 -40 -50 -60 KT-474 AD: Significant Reduction in EASI Score and Pruritus KYMERA 0 Mean % Change in EASI Score Over Time (N=7) 0 7 14 -17.9 21 Day -37.1 28 35 -27.6 -36.4 ©2023 KYMERA THERAPEUTICS, INC. 42 Mean % Change (+/-S.E. of Mean) 10 -10 -20 -40 -50 -70 -80 0 Mean % Change of Worst Pruritus Over Time (N=7) -5.8 H 7 -6.6 -32.1 14 -33.3 -43 | H H -35.6 -44.6 -51.2 21 Day 28 Past Week Past 24 Hours -38.9 -44.6 35 -51.9 -62.9 42 % of Pruritis Responders (80% CI) 100 90 80 70 50 30 20 10 O Patients with ≥4 Unit Reduction from Baseline in Worst Pruritus (N=7) 0 7 29 14 43 29 21 Day 71 Past Week Past 24 Hours 57 28 57 43 35 IRAK4 Patients 71 57 42 PAGE 16#17● ● ● KT-474 Showed Meaningful Signs of Clinical Activity in AD, Comparing Favorably to Placebo Benchmarks and SOC Encouraging initial EASI score reductions sustained after cessation of dosing Peak pruritus reductions, and responder rates, significantly greater than placebo and SOC benchmarks Investigator Global Assessment (IGA) scores improved in 2 of 7 patients and remained stable in the others AEASI APeak Pruritus NRS Peak Pruritus NRS Responder (week/24hrs) KT-474 Part C Day 28 -37% -52% 57%/71% Day 42 -36% -63% 57%/71% Placebo Benchmarks Week 4 -12 to -25%* -11%1 4 to 17%** Dupilumab Phase 3 Week 4 -52%¹ -34%¹ IRAK4 Patients 23 to 40%¹,2 *Range from 7 different Phase 2 and Phase 3 trials; **Range from 10 different Phase 2 and Phase 3 trials; ¹Simpson EL, et al. NEJM 2016;375:2335-2348; 2Bieber T, et al. NEJM 2021;384:1101-1112; The Dupilumab clinical trial was conducted by other parties in a similar patient population with different enrollment criteria from Part 1C of our Phase 1 clinical trial evaluating KT-474. Results do not reflect a head-to-head trial and are shown for illustrative purposes only KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. PAGE 17#18● ● ● Adverse Events Related to KT-474 (Occurring in >1 Patient) Adverse Event (Preferred Term) KYMERA Headache Fatigue Diarrhea # of Patients 6 Ⓒ2023 KYMERA THERAPEUTICS, INC. 4 2 Severity (# of Pts) Mild (5) Severe (1) Mild (4) Mild (2) Outcome (# of Pts) Recovered (6) Recovered (4) No SAEs, no drug-related infections, and no AEs observed leading to dose interruption or discontinuation No QTc-related AEs observed Recovered (2) QTc declines to baseline with continued dosing and sustained plasma exposure through Day 28 Profile is maintained through day 42 upon cessation of dosing after Day 28 IRAK4 Patients PAGE 18#19● Phase 1 results in healthy volunteers and patients support Phase 2 advancement Sanofi responsible for program development costs Kymera retains option (before Phase 3) for cost and profit sharing First development milestones achieved in Q4 2023 $55 million combined milestones for first patients dosed in HS and AD trials Topline data from two ongoing trials expected 1H 2025 Kymera and Sanofi evaluating opportunities to expand indications beyond HS and AD ● KT-474: Oral Agent with Potential to Achieve Broad, Well-Tolerated Anti-Inflammatory Effect in Multiple Diseases ● KYMERA ©2023 KYMERA THERAPEUTICS, INC. PAGE 19#20KT-474/SAR444656: Hidradenitis Suppurativa (ZEN) Design: Double blind, placebo-controlled, 2-arm randomized trial; KT-474 oral tablet or placebo once-daily Enrollment: up to 99 subjects Duration: 16 weeks on therapy + 4 weeks of follow up Primary Outcome Measure: Percent change from baseline in total abscess and inflammatory nodule (AN) count Select Secondary Outcome Measures: ● ● ● ● ● Ongoing Phase 2 Trials in HS and AD Atopic Dermatitis (ADVANTA) Design: Double blind, placebo-controlled, 3-arm randomized trial; KT-474 dose 1 oral tablet, KT-474 dose 2 oral tablet or placebo once-daily Enrollment: up to 115 subjects Duration: 16 weeks on therapy + 4 weeks of follow up Primary Outcome Measure: Percent change from baseline in EASI Proportion of patients achieving HiSCR50, AN Count ≤2 Absolute change from baseline in IHS4 Proportion of patients with improvement in Hurley Stage, AN50 Change from baseline in reported daily worst pain HS-Skin Pain-NRS Proportion of participants achieving at least 30% reduction and at least 1 unit reduction in daily worst pain using HS-Skin Pain-NRS Primary Completion (Estimated): February 2025 Select Secondary Outcome Measures: Proportion of participants with vIGA-AD of 0 or 1 and a reduction from baseline of 22 points Proportion of participants achieving EASI-50 EASI-75 EASI-90 Proportion of participants with reduction of weekly average of daily PP-NRS by 24 points from baseline ● ● Percent change from baseline in weekly average of daily PP-NRS Absolute change from baseline in weekly average of daily PP-NRS Primary Completion (Estimated): January 2025 Additional information on the Phase 2 studies can be found at www.clinical trials.gov; identifier NCT06028230 (HS) and NCT06058156 (AD); Study Sponsor: Sanofi sanofi KYMERA HISCR50: Hidradenitis Suppurativa Clinical Response 50 | IHS4: International Hidradenitis Suppurativa Severity Score System | HS-Skin Pain-NRS: HS-Skin Pain-Numerical Rating Scale EASI: The Eczema Area and Severity Index; vIGA-AD: validated Investigational Global Assessment; PP-NRS: Peak Pruritus Numeric Rating Scale KYMERA ©2023 KYMERA THERAPEUTICS, INC. PAGE 20#21KYMERA STAT3#22● • KT-333 is a potent highly selective heterobifunctional small molecule degrader of STAT3 ● ● ● KT-333: STAT3 Degrader in Oncology 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 Opportunities in STAT3-dep. malignancies (e.g., T cell maligs., DLBCL, AML) and drug resistant tumors (e.g., TKI res. oncogene-driven solids) KYMERA Prevalence Incidence ~75k ~4-8k ~30k ~3k ~4.5k <1k Solid Tumors, PD-1 Combo (e.g. Stage IV MSI-H CRC) ~30k ~5k Source: Bionest, NCI, SEER. GlobalData, LLS; ROW includes EU, UK, Japan and China. STAT3 Has Unique Tumor Cell Intrinsic and Extrinsic Mechanisms 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 ©2023 KYMERA THERAPEUTICS, INC. Peripheral T-cell lymphoma (PTCL) Potential Clinical Activity Based on Preclinical Data: Single agent activity in heme (i.e. CTCL, PTCL, LGL-L); potential activity in solid tumors in combination Cutaneous T-cell lymphoma (CTCL) Large granular lymphocyte leukemia (LGL-L) 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 Cytokine Growth Factor Receptor Receptor JAK JAK U.S. P P STAT3 SRC STAT3 STAT3 STAT3 STAT3 # P R.O.W. Prevalence Incidence ~27k ~15k ~67k ~6k ~24k ~3k ~78k ~20k Adrenergic Receptor PAGE 22#23Durable Anti-Tumor Activity of STAT3 Degradation as a Single Agent in Preclinical Models of T cell Lymphoma Tumor Volume (mm³) +SEM Mean, 100000 KT-333 Concentration (ng/ml or ng/g) 10000 1000 100 10 3000 1 2000 1000 0 Complete Tumor Regressions Associated with >90% STAT3 KD for ~48h Achieved with Intermittent Dosing of KT-333 Vehicle KT-333, 5 mg/kg, QW KT-333, 10 mg/kg, QW 0 5 15 Days (Post-randomization) 10 48 20 Tumor PK Plasma PK → Tumor PD 192 25 240 96 144 Time (hr) KYMERA ©2023 KYMERA THERAPEUTICS, INC. 100 150 in vivo PD 50 ALK+ ALCL 0 SU-DHL-1 % of Vehicle Control STAT3 MFI Disease Severity Score* + N 15000 10000 5000- 0 Vehicle (n=3) KTX-115 30 mpk, QW 4-weeks ON/1-week OFF (n=4) 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 Duration of Treatment (Weeks) Vehicle (n=3) KTX-115, 30 mpk, QW x 3 (n=3) STAT3 Degradation Results in Disease Amelioration in a CTCL Preclinical Model with Potent Degradation of STAT3 in CD4+ T Cell-of-Origin Circulating CD4 T Cells wt Stat3Cstopfl/+ CD4Cre STAT3 MFI in vivo PD Lymph Node CD4 T Cells 15000 ||||||| 10000 5000 0 wt Stat3Cstopfl/+ CD4Cre CTCL GEMM Fanok et al. (2018) Collaboration with NYU STAT3 MFI 25000 20000 15000 10000- 64th ASHⓇ Annual Meeting and Exposition 0 Skin CD4 T Cells 5000 O wt 8 Stat3Cstopfl/+ CD4Cre PAGE 23#24STAT3 Degradation Elicits an IFNy Gene Signature in TME and Sensitizes Solid Tumor Mouse Models to PD-1 Inhibition IFNY mRNA Signature Predictive of Clinical Responses to Anti-PD-1 (Pembrolizumab) Expression Score IFNY, and Expanded Immune Gene Signature 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 IFN-Y ID01 CXCL10 CXCL9 HLA-DRA STAT1 IFNG IFNY Signature Nonresponder Responder Ayers et. al. JCI 2017 (Merck) KYMERA ©2023 KYMERA THERAPEUTICS, INC. IFNy mRNA Signature in TME Elicited by STAT3 Degradation in Preclinical Model Tumor Column (mm³) Log(Count) Log(Count) 3000 2000 1000- 200- 70 3000- 1000 300 Vehicle •-KTX-201 q2d Stat 1 5 vehicle Cxc19 vehicle GEP 10 Days 15 KTX-201 KTX-201 20 Log(Count) Log(Count) Log(Count) 100- 50- 2000- 1000- 500- 50- 30- Ifny Vehicle KTX-201 Cxcl10 vehicle Ido1 KTX-201 vehicle KTX-201 On treatment Day 11; n-6/grp STAT3 Degrader Sensitizes CT-26 Model to Anti-PD-1 via Activation of Anti-tumor Immunity Tumor Volume (mm³) 4000 3000 2000 1000 Lead-in aPD1 Day -2 0 04 Tx start CT-26 Vehicle (PBS + Isotype Ab) KTX-201 5 mg/kg Q2d IP + Isotype Ab Anti-PD1 10 mg/kg BIW IP + PBS Combination Rechallenged age-matched naïve control 20 Tx end 40 Tx Days end CT-26 rechallenge 60 80 PAGE 24#25KT-333: Phase 1, Multicenter, Dose-Escalation and Expansion Trial to Evaluate KT-333 in Adult Patients with PTCL, CTCL, LGL-L, and Solid Tumors Phase 1b Dose Expansion Opportunities Phase 1a Dose Escalation & MTD/RP2D Expansion (n=~45) Solid Tumor/ Lymphoma DL1 Primary Key Objectives Secondary DL2 Exploratory DL3 LGL- L/T-PLL ● ● ● ● DL4 DL3 KT-333 IV Weekly in 28-day Cycles DL5 DL4 DLX Phase 1a Safety/Tolerability and MTD and RP2D PK Parameters of KT-333 Preliminary Estimates of Activity PD Effects of KT-333 MTD/RP2D Expansion Lymphoma/Solid tumor and LGL- L/T-PLL MTD: Maximum Tolerated Dose. RP2D: Recommended Phase 2 Dose. ORR: Overall Response Rate KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. ● ● ● Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell Lymphoma (CTCL) Large Granular Lymphocytic Leukemia (LGL-L) Advanced Solid Tumors Phase 1b Safety/Tolerability at RP2D in Patients with Lymphoma/Leukemia and Solid Tumors Preliminary Clinical Activity (ORR, DOR, PFS, DCR, OS) PK Parameters of KT-333 PD Effects of KT-333 PAGE 25#26KYMERA Remaining Slides Describe Data From ASH23 Poster Presentation (Data Cut-off of October 18, 2023) ©2023 KYMERA THERAPEUTICS, INC. PAGE 26#27● 29 patients were treated across 5 dose levels 7 patients remain active • KYMERA Discontinuations were primarily related to disease progression and investigator discretion Two patients discontinued for adverse event Age (years) Median (min, max) KT-333 Phase 1a: Patient Demographics Sex (n, (%)) Male ECOG (n, (%)) 0 1 Prior Anti-Cancer Therapy ≥3 Dose Level 1 0.05 mg/kg (n=4) 64.5 (57, 70) 3 (75.0) 1 (25.0) 3 (75.0) 4 (100) 3 (75.0) 1 (25.0) Dose Level 2 0.1 mg/kg (n=4) Ⓒ2023 KYMERA THERAPEUTICS, INC. 63.5 (59, 74) 1 (25.0) 4 (100) 4 (100) Dose Level 3 0.2 mg/kg (n=5) 2 (50.0) 1 (25.0) 1 (25.0) 69.0 (40,76) 3 (60.0) 2 (40.0) 3 (60.0) 5 (100) Dose Levl 4 0.4 mg/kg (n=11) 66.0 (42, 81) 5 (100) 9 (81.8) 4 (36.4) 7 (63.6) 9 (81.8) Dose Level 5 0.7 mg/kg (n=5) 61.0 (30, 69) 5 (100) 3 (60.0) 2 (40.0) 7 (63.6) 3 (27.3) 4 (80.0) Tumor Type Solid Tumor+ PTCLO CTCL T-Cell LGL-L B-Cell Lymphoma Hodgkin's 1 (9.1) + = anal; appendiceal; cholangiocarcinoma; colon adenocarcinoma; colorectal (4); duodenal; endometrial; head and neck (3); ovarian, pancreatic (2), peritoneal, rectal and renal; = anaplastic T-cell lymphoma; Data cut-off: 18 October 2023 2 (40.0) Overall (N=29) 65.0 (30, 81) 2 (40.0) 1 (20.0) 21 (72.4) 10 (34.5) 19 (65.5) 25 (86.2) 19 (65.5) 1 (3.4) 5 (17.2) 2 (6.9) 1 (3.4) 1 (3.4) PAGE 27#28● ● ● Overall, KT-333 well tolerated with primarily Gr. 1-2 AEs 2 DLTs observed (Gr. 3 stomatitis, Gr. 3 arthralgia) both in LGL-L patients at DL5; No DLTs in solid tumor/lymphoma patients at any dose level ■ Led to protocol amendment to assess safety/MTD in solid tumor and lymphoma patients separately from leukemic patients (LGL-L, T-PLL) Solid tumor/lymphoma- currently at DL5 with plan to continue dose escalation as planned LGL-L/T-PLL- currently at DL3 with max escalation to DL4 Most common related AEs across all patients (n=29), n (%): Stomatitis, 6 (21%) ALT increase, 3 (10%)* AST increase, 2 (7%)* Related Grade 3 AEs**: 1 pt each: Stomatitis, arthralgia, weight decreased ● ● ● ● KT-333 Safety Summary *all Gr 1; **no Gr 4 or Gr 5 related AEs KYMERA ©2023 KYMERA THERAPEUTICS, INC. PAGE 28#29Response and Stable Disease Observed Across Multiple Tumor Types During Dose Escalation of KT-333 Tumor Type CTCL PTCL LGL-L CHL Solid Tumors # With ≥ 1 Assessment LO KYMERA ©2023 KYMERA THERAPEUTICS, INC. 1 2 1 12 Best Response 2 PR 1 SD 2 PD 1 PD Not Evaluable 1 PR 4 SD* 8 PD *Mucoepidermoid carcinoma of parotid gland (C7+), sinonasal adenocarcinoma (C5), cholangiocarcinoma (C3), renal cell cancer (C3+) Dose Level DL2+4 DL4 DL1+5 DL2 DL5 DL4 DL3+4 DL1-5 Summary: Disease control in 3 of 5 CTCL patients including 2 PR's and 1 SD; 1 PR in cHL, demonstrating single agent activity in liquid tumors supported by preclinical data In solid tumors, where preclinically no strong single agent activity was observed, a pattern of more prolonged SD in H&N tumors was seen with overall 4 patients with SD PAGE 29#30Maximum Degradation of STAT3 in PBMCs Per Cohort (min, max; N) Dose Level 0.05 mg/kg 0.1 mg/kg 0.2 mg/kg 0.4 mg/kg 0.7 mg/kg % Change from C1D1 Predose (Mean) ● ● Cycle 1 D1-D12 -69.9% (-52.6%, -84.1%; 4) -73.5% (-65.5%, -80.7%; 3) -81.5% (-72.3%*, -90.4%; 4) -84.0% (-68.1%, -95.9%*; 11) -82.7% (-72.3%, -92.2%*; 4) 0 -20 -40- -60 Robust STAT3 Degradation in PBMCs and Tumor -80- -100 DL1 DL2 Cycle 2 D29-D37 N/A -79.5% (-64.8%, -91.0%*; 3) -81.0% (-67.3%, -88.6%; 3) -84.0% (-68.3%, -94.2%*; 9) -76.3% (-66.4%, -84.1%; 4) * BLOQ Per Patient (min, max; N) Cycle 1 (D1-D12) DL3 DL4 3 ㅎㅎ DL5 DL2 KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. ● DL3 % change in STAT3 represents mean percent change of 2 STAT3 peptides from baseline, measured using targeted mass spectrometry. Cycle 2 (D29-D37) DL4 DL5 O BLOQ 90% Deg. KT-333 Leads to Marked Reductions in STAT3, pSTAT3 in Tumor Tissue from a CTCL Patient Baseline KT-333 Treated (C1D9; 24 hr Post Dose) % Biomarker Positive of Total DAPI+ Cells 100 80 60 40 20 0 H&E 2mm 2mm ning D9 Screening STAT3/DAPI Screening STAT3 and pSTAT3 % Positive Cells are Reduced Entire Tumor Section C1D9 Screening STAT3 C1D9 Screening D9 CD3+ Compartment CD9 STAT3/CD3 Screening pSTAT3/DAPI pSTAT3 % STAT3+ % pSTAT3+ STAT3+ % CD3+ % STAT3+ CD3+ % pSTAT3+ STAT3+ CD3+ Summary Strong proof-of-mechanism for KT-333 with up to 96% maximum degradation of STAT3 in PBMCs STAT3 and pSTAT3 positive cells reduced by 69% and 87% in tumor 69% & 87% respectively in the post treatment tumor biopsy compared to screening PAGE 30#31% Change from C1D1 Predose (Mean ± SEM) 400 300 200 400 300 200 200 100 50 0- -25 STAT3 Degradation Elicits IFN-y Response Gene Signature in Blood and Tumor Blood CXCL9 mRNA 2 3 4 5 6 7 8 CXCL10 mRNA KYMERA 2 3 4 5 6 STAT1 mRNA 1 2 3 4 5 ● 6 7 7 9 10 11 12 8 9 10 11 12 A Time Course of Transcriptional Induction of Select IFNy Stimulated Genes Post KT-333 Infusion 8 9 10 11 12 A 29 30 31 32 33 34 35 36 37 29 30 31 32 33 34 35 36 37 29 30 31 32 33 34 35 36 37 A Days in Study % Change from C1D1 Predose (Mean ± SEM) 300- ©2023 KYMERA THERAPEUTICS, INC. 200 100 50 0 -25 100 50- 0- -25 -50 200 100 50 0 -25 -50 -75 IDO1 mRNA 2 3 LAG3 mRNA 1 4 5 6 7 2 3 4 5 6 PD-L1 mRNA 2 3 4 5 6 7 7 8 9 10 11 12 8 9 10 11 12 29 30 31 32 33 34 35 36 37 8 A 29 30 31 32 33 34 35 36 37 9 10 11 12 Days in Study 29 30 31 32 33 34 35 36 37 DL2 DL3 DL4 DL5 A KT-333 IV + Tumor Change from Screening (%) 300 200 100 0 -50 Enrichment Score 0.4 11 0.2 0.0 KT-333 Leads to Induction of IFNY Pathway Response and Downregulation of SOCS3 in a CTCL Tumor CXCL10 JO Post KT-333 Treatment (C1D9) CXCL9 STAT1 10000 IFN y Response Pathway 20000 IDO1 Rank LAG3 Summary: Induction of IFN-y signature in tumor by KT-333 consistent with preclinical findings where effect in syngeneic solid tumor model associated with enhanced response to anti-PD-1 30000 SOCS3 40000 PAGE 31#32KT-333: Desired Translation of PK, PD and Safety As of October 18, 2023 data cutoff (ASH): Disease control in 3 of 5 CTCL patients including 2 PR's and 1 SD; 1 PR in Hodgkin's lymphoma; supports activity in liquid tumors consistent with preclinical data Tumor biopsy, consistent with preclinical findings, demonstrates induction of IFN-y signature with potential to synergize with anti-PD-1 KT-333 generally well tolerated with primarily Grade 1-2 AEs 2 DLTS observed (Gr. 3 stomatitis/arthralgia), both in LGL-L patients at DL5; additional leukemia patients being enrolled at DL3-4 No DLTs in solid tumor/lymphoma patients at any dose level; enrollment continuing at DL5 Next steps: Complete Phase 1a dose escalation in 2024 to inform expansion cohort strategies KYMERA ©2023 KYMERA THERAPEUTICS, INC. First-in-Class Opportunity to Address STAT3-Driven Pathology Across Diverse Indications First heterobifunctional degrader against an undrugged target in the clinic Clinical development strategy includes monotherapy direct registrational path in STAT3 dependent T cell malignancies Opportunity for expansion into solid tumors in combination with immune checkpoint inhibitors to be informed by preclinical data and planned analysis of TME remodeling in solid tumor biopsies from ongoing trial PAGE 32#33KYMERA MDM2#34KT-253: Potent MDM2 Degrader and Best-in-Class p53 Stabilizer • KT-253 is a novel, highly potent and selective heterobifunctional MDM2 degrader • MDM2 is the E3 ligase that modulates p53, the largest tumor suppressor • 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 Benefits of MDM2 Degradation • KT-253, unlike small molecule inhibitors, overcomes the feedback loop which up-regulates MDM2 production and in doing so more effectively stabilizes the tumor suppressor p53 • Broad franchise opportunities available for this mechanism (over 50% of tumors are p53 WT); focused on indications with specific sensitivity to degrader mechanism, through a biomarker strategy Clinical Activity Based on Preclinical Data: Strong antitumor activity in a wide variety of heme and solid tumors with an emerging signature (undisclosed) KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. MDM2 CRISPR Sensitivity Score 0.6 Dependency of p53WT cells on MDM2 0.4 0.2 O -0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4 -1.6 -1.8 -2 -2.2 DNA Damage p53 p53MUT p53WT Hypoxia Stressors MDM2 Graph generated with data obtained from DepMap.org p53 Cell Line Oncogenes p53 ub ub MDM2 Tumor Suppression Other p53 Targets CE p53 Degradation Feedback Loop Cell Cycle Arrest (p21, Ptprv) Apoptosis (Noxa, Bax, Puma) PAGE 34#35KT-253 is a potent MDM2 degrader % MDM2 Remaining KT-253 is Superior to MDM2/p53 Small Molecule Inhibitors KT-253, unlike SMI's such as DS- 3032, strongly stabilizes p53... ... which leads to superior tumor cell killing (pM range) p53 MSD, 2h RS4;11, 24h CTG Company 300 250- 200 150 100 80 60 40 20 0 Clinical stage RS4-11 IC50 KT-253 DS-3032 Baseline 0.00001 0.0001 MDM2-HiBiT 0.001 0.01 Compound 1 Concentration, μM (nM) (AML Cell Killing) MDM2-HiBiT, DC50 (nM) (Degradation) DC50=0.4nM Ox 60 CD 40- 20 DMSO 3000- 2500- 0.3 0.4 2000 1500- 1000 KT-253 Kymera Phl 500- ¹0000¹0 KT-253 -DS-3032 0.0001 0.001 0.01 Concentration, μM DS-3032 Sankyo/Rain Ph II / combo AML 67 RG7388 Roche Ph II / III 220 100 80- -20 10000'0 KT-253 DS-3032 0.0001 SAR405838 Sanofi Paused 620 0.001 0.01 Concentration, μM HDM201 Novartis PhI/II 163 DMSO AMG-232 Amgen/Kartos Multiple Ph II 280 KT-253 is >200-fold more potent in tumor cell killing assays than SMIs due to its mechanism of action Proteomics show selective degradation of KT-253 KYMERA Ⓒ2023 KYMERA THERAPEUTICS, INC. PAGE 35#36Relative Quantification (% Vehicle, p53/ACTB) KT-253 Potently Degrades MDM2 leading to Pathway Impact and Antitumor Activity Superior to SMI in ALL and AML Models e 2000 1500- 1000 500 0 MDM2 Degradation Leads to Superior P53 Upregulation vs SMI %MDM2 Remaining (Norm. to Vehicle, ACTB) 18 24 250- 200- 150- 100- 50- MDM2 Protein Levels 1h post dosing p53 Protein Levels 6% 1 8 24 1 8 24 1 8 24 1 8 24 Time (Hours) 8% Relative Quantification (% Vehicle, GDF15/IPO8) 10000 8000 6000 4000 2000 0 KYMERA ©2023 KYMERA THERAPEUTICS, INC. Vehicle KT-253 3 mg/kg SD KT-253 1 mg/kg SD DS-3032 30 mg/kg QDx3 DS-3032 100 mg/kg QDx3 GDF15 Protein Levels p53 Activation 1 8 24 1 8 24 18 24 1 8 24 Time (Hours) 1 8 24 Targeted proteomic analysis of RS4;11 tumors demonstrates robust degradation of MDM2 one hour post dosing and associated pathway activation biomarkers including p53 and GDF15 MDM2 Degradation Leads to Superior Antitumor Responses in AML and ALL Preclinical Models Tumor Volume (mm³) Mean ± SEM Tumor Volume (mm³) Mean ± SEM 2500 2000 1500 1000- 500 O 2500 2000 1500 0 1000- 500- 0 0 7 14 Days Post Treatment 21 7 14 Days Post Treatment 21 28 28 RS4;11 Vehicle KT-253 3 mg/kg IV, SD KT-253 1 mg/kg IV, SD DS-3032 30 mg/kg PO, 3 on/11 off DS-3032 100 mg/kg PO, 3 on/11 off MV4;11 Vehicle KT-253 3 mg/kg IV, SD KT-253 1 mg/kg IV, QWx3 -DS-3032 30 mg/kg PO, 3 on/11 off DS-3032 100 mg/kg PO, 3 on/11 off Sustained tumor regressions in RS4;11 (ALL) and MV4;11 (AML) CDX models after a single 3 mg/kg KT-253 dose No efficacy observed with clinically relevant dosing regimen of SM (DS-3032) PAGE 36#37● DLX ● ● KT-253 Phase 1a: Study Design and Arm A Enrollment Status Dose Level 1 0.05 mg/kg (n=3) Dose Level 2 0.1 mg/kg (n=4) Dose Level 3 0.17 mg/kg (n=2) ● Solid Tumors/Lymphoma DLXH1 Pharmacologically Active Dose in ST/L DLx+2 Phase 1a DLY DLn DLy+1 R/R high-grade Myeloid Malignancies/ALL DLY +2 Clinical Trial Design Arm A: R/R Solid Tumors and Lymphomas 9 patients enrolled across first three dose levels Arm B: R/R high-grade Myeloid Malignancies/ALL Enrollment initiated MTD/RP2D DLn Regimen: IV infusion once every 3 weeks Initial Results: Arm A (Data cut-off: October 20, 2023) Robust PD in blood in first two dose cohorts (POM) Antitumor activity in dose level 1 • No DLTs or hematological toxicity KYMERA ©2023 KYMERA THERAPEUTICS, INC. MTD/RP2D Arm A Enrollment Age (years) Mean (range) Gender n, (%) Female Male # of Prior Therapies n, (%) 2-3 >3 Mean (range) Tumor type n, (%) Merkel Cell Carcinoma Fibromyxoid Sarcoma Uveal Melanoma Rectal Prostate Adenoid Cystic Renal Cell Osteosarcoma KT-253 Cycles Received Mean (range) 57.3 (42, 66) 2 (66.7) 1 (33.3) 1 (33.3) 1 (33.3) 4.3 (1,9) 1 (33.3) 1 (33.3) 1 (33.3) 4.7 (2-6) 64.3 (55, 74) 2 (50.0) 2 (50.0) 0 4 (100) 6.8 (4, 9) 1 (25.0) 1 (25.0) 1 (25.0) 1 (25.0) 1.3 (1-2) 50 (43, 57) 1 (50.0) 1 (50.0) 2 (100) O 2.5 (2, 3) 1 (50.0) 1 (50.0) 1 (NA) Overall (N=9) 58.8 (42, 74) 5 (55.6) 4 (44.4) 3 (33.3) 5 (55.5) 5.0 (1,9) 1 (11.1) 1 (11.1) 2 (22.2) 1 (11.1) 1 (11.1) 1 (11.1) 1 (11.1) 1 (11.1) 2.3 (1-6) PAGE 37#38Upregulation of Plasma GDF-15 Shows MDM2 Target Engagement by KT-253 at Dose Levels 1 and 2 GDF-15 is Downstream Biomarker of p53 Upregulation Following MDM2 Degradation P53 Stabilization KYMERA p53 Blood MDM2 KT-253 p53 KIAD MDM2 Degradation ©2023 KYMERA THERAPEUTICS, INC. Upregulation of p53 Targets Genes GDF-15- ELISA Cycle 1 Plasma Exposure and Fold-Change in GDF-15 Levels (Mean ± SEM) Dose Level DL1: 0.05 mg/kg (n = 3) DL2: 0.10 mg/kg (n = 4) Plasma GDF-15 levels (Fold Change Over Pre-dose Baseline) 25 20 15 *Max fold increase over pre-dose baseline up to D4 post-infusion; **n=3 10 AUC (ng.h/mL) 5 353 ± 236 D1 609 ± 67.3 Cmax (ng/ml) 180 ± 116 Kinetics of Plasma GDF-15 Upregulation in Subject on DL1 Cycle 1 387 ± 24.0 Max Fold Increase in Plasma GDF-15* Pre-dose baseline 10-fold 4.7 30-fold ± 19** D4 D2 D1 Time Points: Oh, 2h, 3h, 7h from Start of Infusion D8 PAGE 38#390 KT-253: Initial Clinical Activity Demonstrated in Phase 1a 23 21 42 Lesion 1 Pre-Treatment Lesion 2 Pre-Treatment 63 KYMERA ©2023 KYMERA THERAPEUTICS, INC. Days on Study - Dose Level 1 (0.05 mg/kg) 84 107 * 105 Post-Cycle 2 Post-Cycle 2 133 126 Merkel Cell Carcinoma Fibromyxoid Sarcoma Uveal Melanoma 147 Ongoing Discontinued (Progressive Disease) Partial Response Stable Disease *Patient discontinued from study 64-year-old male, diagnosed with Merkel cell carcinoma (rare and aggressive skin cancer) in 2019 Received 6 prior regimens including treatment with pembrolizumab, atezolizumab, nivolumab and ipilimumab Confirmed partial response after 4 cycles of KT-253, including resolution of skin metastasis; treatment continuing PAGE 39#40As of October 20, 2023 No dose-limiting toxicities across dose levels 1-3 Adverse events related to KT-253 and observed in at least 2 patients Nausea (n=3): Grade 1 (n=2) and Grade 2 (n=1) Diarrhea (n=2): All Grade 1 ● ● ● ● ● ● Serious adverse events (SAEs) deemed related to KT-253: Hypotension (n=1): Grade 3, occurred during cycle 4 Due to decreased oral intake; resolved with treatment including IV fluids Patient remains on study without dose reduction or recurrence of hypotension No thrombocytopenia or neutropenia even after 6 cycles of KT-253 ● KT-253 Phase 1a: Safety Update ● ● KYMERA ©2023 KYMERA THERAPEUTICS, INC. PAGE 40#41● ● ● ● KT-253: Emerging Clinical Data Support Therapeutic Hypothesis for MDM2 Degrader KT-253, unlike SMIs, overcomes the feedback loop which up-regulates MDM2 production and in doing so more effectively stabilizes the tumor suppressor p53 KT-253 inhibits tumor cell growth with picomolar activity and is more than 200-fold more potent than clinically active MDM2 SMIs, enabling intermittent dosing to improve therapeutic index Interim Phase 1a data from Arm A show evidence of target engagement and p53 pathway activation and initial signs of antitumor activity without DLTS including typical hematological toxicity Arm B (high grade myeloid malignancies including AML) enrollment initiated Additional clinical and preclinical data supporting biomarker-based patient selection strategy to be disclosed in 2024 KYMERA ©2023 KYMERA THERAPEUTICS, INC. First-in-class Opportunity to Address p53 WT Tumors Across a Variety of Tumor Types First degrader against a clinically proven but inadequately drugged target, MDM2 Profound single agent activity in preclinical liquid and solid tumor models and initial evidence of antitumor activity in patients in Phase 1a Clinical development strategy includes accelerated registration path in p53 WT tumors with high sensitivity to degrader mechanism such as AML, lymphomas and solid tumors PAGE 41#42Immunology Oncology KYMERA Upcoming Milestones and Events KT-474/SAR444656 Pipeline Update KT-333 KT-253 ©2023 KYMERA THERAPEUTICS, INC. ● Estimated enrollment completion in Phase 2 HS & AD trials in 4Q 2024 Topline data expected for both studies in 1H 2025 Virtual Immunology R&D Day: January 4, 2024 Complete Phase 1a trial in 1H 2024 Phase 1 data at medical meeting in 2024 Patient stratification and development strategy in 2024 Phase 1 data at medical meeting in 2024 PAGE 42#43KYMERA NASDAQ: KYMR www.kymeratx.com @Kymera TX For additional information contact: [email protected] [email protected] [email protected]#44KYMERA Appendix#45Preferred Term Nausea ALT increased AST increased Constipation Fatigue Stomatitis Anemia Number of Patients with Adverse Event Occurring in ≥15 Patients Overall (n, (%) Dose Level 1 0.05 mg/kg (n=4) Dose Level 2 0.1 mg/kg (n=4) All Related Dose Level 3 0.2 mg/kg (n=5) All Related Dose Level 4 0.4 mg/kg (n=11) All Related 3 (27.3) 1 (9.1) Dose Level 5 0.7 mg/kg (n=5)a All Related Related All 1 (25.0) 1 (25.0) 3 (60.0) 2 (40.0) 4 (36.4) 3 (27.3) 2 (50.0) KT-333: Overall Safety Profile 2 (50.0) 1 (25.0) 1 (25.0) 2 (50.0) 2 (40.0) 2 (40.0) 1 (20.0) KYMERA ©2023 KYMERA THERAPEUTICS, INC. 1 (20.0) 1 (20.0) 3 (27.3) 3 (27.3) 2 (18.2) 3 (27.3) 2 (18.2) 2 (18.2) 1 (9.1) 3 (27.3) 1 (9.1) 1 (9.1) Abdominal pain 2 (50.0) 1 (25.0) a At the time of data cut off DL5 was still open to enrollment in patients with solid tumors and lymphoma diagnosis with an expected enrollment total of n=6 b All Grade 1 2 (40.0) 2 (40.0) 1 (20.0) 3 (60.0) 1 (20.0) 2 (40.0) Overall (N=29) All 8 (27.6) 8 (27.6) 7 (24.1) 1 (20.0) 7 (24.1) 7 (24.1) 3 (60.0) 7 (24.1) 6 (20.7) 5 (17.2) Related 1 (3.4) 3 (10.3)b 2 (6.9)b 1 (3.4) 2 (6.9) 6 (20.7) 1 (3.4) 1 (3.4) Summary: At the time of the data cut-off (October 18, 2023), KT-333 was well tolerated, with primarily grade 1 and 2 AEs; 2 DLTs observed in LGL-L patients at DL5, no DLTs in solid/lymphomas at any dose level PAGE 45#46● Partial Response and Stable Disease Observed Across Multiple Tumor Types During Dose Escalation of KT-333 ASH Poster Presentation (Data Cut-off of October 18, 2023) ● Overall Response in Evaluable Patients* Non-CTCL Lymphoma/ Hodgkin's (n=3) Partial Response Stable Disease Progression of Disease 1 0 CTCL (n=5) 2 1 Solid Tumor (n=12) 0 4 KYMERA ©2023 KYMERA THERAPEUTICS, INC. 2 2 8 * Two LGL-L patients at DL5 not included as they were not evaluable for response assessment at time of KT- 333 discontinuation Duration on Treatment for Patients with Response of SD or Better Hodgkin's CTCL CTCL CTCL HNC1 HNC2 Cholangiocarcinoma Renal ¥ Ongoing Disease Progression Partial Response Stable Disease C8 Summary: Disease control in 3 of 5 CTCL patients including 2 PR's and 1 PR in cHL demonstrate activity in liquid tumors supported by preclinical data DL2 DL3 DL4 C2 C3 C4 C5 C6 C7 * Received steroids during 1st week of C1 to treat symptoms arising from Szezary Syndrome ¥ Discontinued d/t AE (Gr. 2 squamous cell carcinoma of skin) HNC1 = Mucoepidermoid carcinoma of parotid gland Discontinued d/t Pl discretion (stable disease at discontinuation) HNC2 = Sinonasal adenocarcinoma Stable disease observed in 4 solid tumor patients to date with potential pattern of more prolonged SD in H&N tumors Enrollment moving forward to continue enriching for tumor types potentially responsive to monotherapy or anti-PD-1 combination PAGE 46