#1KYMERA INVENTING NEW MEDICINES WITH TARGETED PROTEIN DEGRADATION August 2020#2Legal Disclaimer This presentation is not a prospectus and is not an offer to sell, nor a solicitation of an offer to buy, securities. We have filed a registration statement on Form 5-1 (including a preliminary prospectus) with the Securities and Exchange Commission (the "SEC") for the offering to which this communication relates. The registration statement has not yet become effective. Before you invest, you should read the preliminary prospectus and the other documents we file with the SEC for more complete information about us and this offering. You can obtain these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the preliminary prospectus may be obtained from Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014; BofA Securities by telephone at 1-800-294-1322 or by email at [email protected]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY, 11717, Attention: Prospectus Department, by telephone at (833) 297-2926; Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017, by telephone at (212) 518-5548, or by email at [email protected]. This presentation contains forward-looking statements and 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 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 "aim," "anticipate," "assume," "believe," "contemplate," "continue," "could," "design," "due," "estimate," "expect," "goal," "intend," "may," "objective," "plan," "predict," "positioned," "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. These forward-looking statements include statements about the initiation, timing, progress and results of our future clinical trials and current and future preclinical studies of our product candidates and of our research and development programs; our plans to develop and commercialize our current product candidates and any future product candidates and the implementation of our business model and strategic plans for our business, current product candidates and any future product candidates. 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. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise. As a result of these risks and others, actual results could vary significantly from those anticipated in this presentation, and our financial condition and results of operations could be materially adversely affected. This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. 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 has 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. KYMERA#3Issuer Ticker / Exchange Offering Size Concurrent Private Placement Price Range Gross Proceeds Over-Allotment Option Expected Pricing Use of Proceeds Lock-Up Period Bookrunners KYMERA Offering Summary Kymera Therapeutics, Inc. KYMR/ Nasdaq Global Market 7,360,000 shares of common stock (100% Primary) **500,000 shares of common stock, with the option to purchase ~75,000 additional shares if the over- allotment option is exercised in full $16 - $18 per share ~$134MM (at midpoint of price range, includes $8.5MM in proceeds from concurrent private placement and excluding option to purchase additional shares) 15% (100% primary) Thursday, August 20th (Post-market close) * Development of the IRAK4 program Development of the IRAKIMID program • Development of the STAT3 program . Continued expansion of the platform technology, preclinical studies for research stage programs, working capital and other general corporate purposes 180 days for the Company, directors, officers and substantially all other pre-IPO share and option holders Morgan Stanley, BofA Securities, Cowen, Guggenheim Securities#4KYMERA K Investment Highlights Mission to discover, develop & commercialize transformative therapies using targeted protein degradation (TPD) Leading targeted protein degradation platform investing in unique capabilities of our proprietary discovery platform, Pegasus Focus on un-drugged or inadequately-drugged targets in clinically validated biological pathways that TPD can potentially unlock >>> Robust internal pipeline focused on Oncology and Immunology with three programs projected to enter the clinic in 2021: IRAK4, IRAKIMID and STAT3 Leveraging synergies in biopharma collaborations with Vertex and Sanofi to date, to increase disease and patient impact Experienced management team of leading scientific innovators#5Nello Mainolfi, PhD Founder, President & Chief Executive Officer • Global project leader and co-inventor of LNP023- first SM factor B inhibitor • Inventor of LHA510- first topical SM for wet AMD & NOVARTIS KYMERA Richard Chesworth, PhD Chief Scientific Officer Head of Research and key contributor to the discovery and development of Tazverik Over 20 years of pharma and biotech experience CEpizyme Leadership Team Jared Gollob, MD Chief Medical Officer Development lead for Onpattro, First FDA approved RNAI medicine at ALNY 2 Alnylam Bruce Jacobs, CFA, MBA Chief Financial Officer Over 25 years in health care financial services, equity research and investment banking. WESTFIELD CAPITAL MANAGEMENT Karen Martin, PhD, JD Brian Albarran, PhD, MBA VP, Strategy VP, Head of Intellectual Property & Operations Over 15 years in intellectual property law, patent portfolio development, licensing, transactions, post-grant practice, litigation Takeda • Head of Cl; PTL for dostarlimab (anti-PD-1) • Over 14 years in R&D, BD, strategy consulting. and operations TESARO Paige Cochran VP, Human Resources Over 25 years of HR experience for both private and public high-growth companies in life science and technology verticals microchips#6~$400M Raised Capital raised since inception, equally split between equity sales and partnership upfronts ~$300M+ On Hand Current cash and cash equivalents (includes upfront from Sanofi collaboration) Cash runway beyond early 2025 Current expected cash runway based on operational plans, IPO and concurrent private placements, excludes any milestones from collaborations KYMERA Financial Highlights ATLASVENTURE Series A/B (~$96M Raised) AMGEN' Ventures Pfizer Ventures 和天 Academic Collaborators LILLYVENTURES HATTERAS SANOFI VENTURES BESSEMER UCSF MERCK VERTEX Yale MAYO CLINIC Series C: March 2020 (~89M Raised) BVF WELLINGTON MANAGEMENT" BlackRock Janus Henderson -INVESTORS COLUMBIA UNIVERSITY Redmile Group UNIVERSITY OF CAMBRIDGE BainCapital LIFE SCIENCES ROCK SPRINGS CAPITAL LOGOS CAPITAL Radboud University#7VERTEX Vertex collaboration signed May 2019 - $70 million total, including $50 million upfront cash and $20 million equity investment Collaboration covers up to 6 targets in disease areas outside of Kymera's core areas of focus in oncology and inflammation. Financial terms: Strategic Collaborations Eligible for >$1 billion in payments Development, regulatory, and commercial milestones; option exercise payments Tiered royalties on future net sales on any products from collaboration Vertex option at DC and bears all clinical, regulatory and other . KYMERA H i SANOFI Sanofi collaboration signed July 2020 $150 million upfront payment + potential milestones of over $2 billion and tiered royalties Collaboration covers two programs: IRAK4 program in immune-inflammatory disease Second earlier-stage program Financial terms: Upfront payment + development, regulatory, and commercial milestones Tiered royalties on future net sales on any products from collaboration Kymera advances IRAK4 through Phase 1; Sanofi performs/funds all other clinical work Kymera retains U.S. opt-in rights for both programs: - Kymera decision before phase 3 to co-develop and co-promote Under opt-in, companies equally share development costs and profits/losses in the US Kymera retains all rights to IRAK4 in oncology#8Co-opting a Naturally Occurring Process to Regulate Protein Levels 1 2 3 KYMERA E3 ligase recognizes protein Ubiquitin chain transferred Protein is marked for elimination Broad Opportunity Only Binding Site Required Efficient Catalytic Targeted Protein Degradation Biology Prolonged Impact Targeted Protein Degradation E3 1 Disease-causing Target Protein Degrader E2 Peptides from Degraded Protein Ubiquitin 3 Proteasome 2 Targeted Small Molecule Protein Degraders Ubiquitin Chain#9KYMERA Targeted Protein Degradation Next Potential Breakthrough Modality to Expand Drugged Proteome Human Proteome Targeted Protein Degradation 2020 KYMERA THERAPEUTICK, INC Un-Drugged Opportunity Drugged Undruggable Targets Scaffold, transcript factor, multiple funct Efficient Development / Manufacturing Systemic Exposure Oral Bioavailability Traditional Small Molecule Existing Modalities X X Antibody X #4 BB Antisense ✔ RNAI Cell/Gene Therapy#10KYMERA PEGASUS PLATFORM#11KYMERA E3 Ligase Whole-Body Atlas E3 Ligase Binders Toolbox Ternary Complex Modeling Quantitative System Pharmacology Model Proprietary Chemistry Proprietary Pegasus TPD Platform Key Capabilities Identification of the expression profiles of the approximately 600 unique E3 ligases to match a target protein with the appropriate E3 ligase based on expression, distribution, intracellular localization, and biology. Leveraging the E3 Ligase Whole-Body Atlas, a toolbox of proprietary ligands designed to bind to novel E3 ligases to design protein degraders with specific degradation profiles for different target disease states. Characterization of ternary complex with both structural biology and biophysical techniques feeds a ternary complex modeling tool to optimize the development of highly efficient, and selective degrader therapeutics. A model to measure and predict the 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. Expertise in proprietary chemistry enables the design and optimizes both E3 and target protein binders and convert them into degraders with optimal pharmaceutical properties tailored to specific patient populations and diseases. Proprietary Chemistry E3 Ligase Whole-Body Atlas VPEGASUS Quantitative System Pharmacology Model Ternary Complex Modeling E3 Ligase Binders Toolbar#12KYMERA E3 Ligase Whole-Body Atlas Toolbox Ternary Complex System Pharmacology Model Proprietary Chemistry Pegasus E3 Ligase Whole-Body Atlas 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 - Vision to develop tissue selective or tissue restricted degraders to enable novel therapeutics opportunities E3 LIGASES TARGETS CRBN CULAA DDB1 XIAP LIGASE 1 LIGASE 2 LIGASE 3 LIGASE 4 O RNF114 (MOA) IN YOU DCAF16 LIGASE S LIGASE 6 LIGASE T LIGASE B LIGASE 9 LIGASE TO STATS IRAKA TARGET 1 TARGET 2 TARGET: Abundand 000000000 00000 TONSIL LIVER SPLEEN STOMACH BRAIN LUNG TESTIS TISSUES DUODENUM SMALL INTESTINE URINARY BLADDER HEART ESOPHAGUS THYROID GALL BLADDER ENDOMETRIUM COLON KIDNEY FALLOPIAN TUBE SMOOTH MUSCLE PROSTATE APPENDIX PANCREAS OVARY RECTUM PLACENTA ADIPOSE TISSUE BO HAWAT SALIVARY GLAND ADRENAL GLAND UNDISCLOSED Ubiquitous Restrictive Selective#13KYMERA E3 Ligase Whole-Body E3 Ligase Binders Toolbox Ternary Complex Modeling Quantitative System Pharmacology Proprietary Chemistry H H 1 V Pegasus E3 Ligase Binders Toolbox E3 Ligase Whole Body Atlas queried to identify a tissue sparing E3 ligase based on target protein unwanted pharmacology (i.e. bone marrow for a particular target of interest) A Bone marrow sparing E3 ligase identified Screening and optimization lead to a novel binder to a previously unliganded E3 ligase (E3 ligase binders toolbox) A novel degrader based on a bone marrow sparing E3 ligase demonstrated target degradation This E3 Ligase is Not Expressed in Bone Marrow Concentration (M) 400- 100 % Target 150 Ligand Identification TPD with Bone Marrow Sparing Novel E3 Ligase 75- 50 10 Cereblon A Novel E3 H Log Compound) (M) Bone marrow: CD34+ from five donors 5 Target Target Protein DC (M) DTH: (8)#14KYMERA Whole Body Binders Toolbox Ternary Complex Modeling Quantitative System Pharmacology Model Proprietary Pegasus Ternary Complex Modeling / Quantitative System Pharmacology Model Refined understanding of each parameter impacting degradation profiles . Modeling predicts how relative E3 ligase and protein concentrations impact degradation Designed to solve complex equations to accurately translate PK/PD into optimal human dosing Example 1: Target vs E3 Ligase Concentration Range Leads to Suboptimal Ternary Complex and Degradation Temary Complex Degrader Concentration Example 2: Target vs E3 Ligase Concentration Range Leads to Optimal Ternary Complex and Degradation TERNARY COMPLEX Degrader Concentration = DEGRADATION |||#15Jo KYMERA Whole-Body Toolbox Ternary Complex Modeling Quantitative System Model Proprietary Chemistry Utilize comprehensive strategies for identification of starting ligands that bind to E3 ligases and proteins of interest Identify compounds with preferred physiochemical properties conducive to achieving the optimized target product profile • In silico drug discovery to accelerate hit finding and optimization Readily accessible and diverse library of preferred linkers to connect binders to the E3 ligase and the target Enables rational degrader design and optimization, and ability to improve molecular properties Characteristic V Pegasus Proprietary Chemistry Potency Human in vitro clearance Membrane permeability In vivo clearance Bioavailability Metric Whole Blood IRAK4 DC (nM) HLM (mL/min/mg) Permeability (A/B; x10 cm/s) Mouse CL (mL/min/kg) Mouse PO PK (%F) Compound A (1 Generation) 280 96 0.4 177 Compound B (2nd Generation) 17 3 <-15 40#16Rheumatic Diseases UNMET MEDICAL NEED Many unmet medical needs across various cancers and rheumatological, dermatological disorders KYMERA Rheumatologic THE LANCET -10: CANTOS Data Atherosclerosis, OURNAL MEDICINE Lung Cancer Allergy Clinical L-18: Macrophage Immunology Activation Syndrome IL-IR Drug Development Principles IL-1R/TLR Pathway FAMA Mycen IL-1 IL-18 IL-33 IL-36 VALIDATED BIOLOGY Clinically validated areas: oncology. immunology, fibrosis MYDS8 Mutations: Home One Generalized Pustular Psoriasis Atopic Dermatitis SCIENTIFIC REPORTS NEW ENGLAND Allergy Clinical Immunology AAD UN-DRUGGED NODE Key un-drugged or inadequately drugged nodes that TPD can unlock IL-6R: IL-6: Multicentric Rheumatoid Castleman's Arthritis Disease ACTEMRA sylvant JAK1/2: Myelofibrosis Jakafi Ⓒ JAK3: Alopecia Areata Pfizer IL-AR 20 JAK SAK JAK-STAT Pathway PRECISION MEDICINE APPROACH JAK Targeted to a genetically defined patient population JAK STATE STATS STATE STATS STAT3: Activating Mutations ATE genetics TYK2 JOURNAL MEDICINE TYKZ: Autoimmune Disease NEW ENGLAND JOURNAL MEDICINE STATS ASO AZD9150 in Oncology Journal for ImmunoTherapy of Cancer STAT3: Activation (pSTAT3) Blood Cancer Journal#17Robust Pipeline of Targeted Protein Degraders for Un-drugged Targets Pathway IL-1R/TLR JAK/STAT Program IRAKA KYMERA IRAKIMID (IRAKA, Ikaros, Alolos) STAT3 Indication(s) HS, AD, RA MYD-88MT DLBCL Liquid & Solid Tumors Discovery Pre-Clinical KT-474 Phase 1 Phase 2 - Oncology = Inflammation/Immunology "Kymera will have the option to participate equally in the development of Sanofi-partnered programs in the US during clinical development Phase 3 Next Milestone Ph1: 1H 21 Ph1: 2H '21 Ph1: 2H '21 Leveraging the capabilities of our Pegasus platform, we are also advancing: • Multiple wholly-owned degrader programs in immunology-inflammation and genetically defined oncology indications . Multiple programs across several disease indications with our partners: Vertex and Sanofi Rights KYMERA SANOFI KYMERA KYMERA#18KYMERA IRAK4#19IRAK4 Biology and Degrader Rationale • IRAK4 is a key component of myddosome protein complex Myddosome involved in innate immunity that mediates signals through IL-1R and TLRs • IL-1R/TLR signaling through the myddosome complex is dependent on IRAK4 kinase and scaffolding functions • Degrading IRAK4 we believe can provide a single oral small molecule solution to many diseases impacted by this pathway KYMERA Indications/Timeline AD, Hidradenitis Suppurativa (HS), RA Current: IND enabling studies Expected IND submission: 1H 2021 Expected P1: 1H 2021 Kinase Domain IL-1 Family Cytokines: IL-1a/B, IL-18, IL-33, IL-36 IL-1R KINASE DEPENDENT Inhibitor IRAKA Kinase Catalytic Activity JNK/p38 Cytokines MyDB8 IRAK4 T IRAK4 Degrader T TLRs Scaffolding NFkB TLR Agonists KINASE INDEPENDENT Death Domain#20% IRAK4 (Control) + SEM KYMERA 150 100 50- KT-474: Specific IRAK4 Degradation Degradation in Human Monocytes KT-474 KT-5653 (Negative Control) Log [Compound] (µM) • Calculated DC50 of 2.1 nM and E3 ligase dependent degradation of IRAK4 in human immune cells IRAK4 was only protein of over 10,000 to be degraded by KT-474 in human immune cells at concentration 10-fold above the DC p-value (-Log 10) 3. 2.5 2 1.5 0.5 0 Selectivity in Human PBMC 10xDC RAKA 24hr -2 -1.5 -1 -0.5 0 0.5 1 1.5 2 Protein Level Fold Change (Log2)#21IRAK4 Degradation Superior to Kinase Inhibition in Cytokine Production - Functional activity of KT- 474 assessed by measuring pro- inflammatory cytokine levels upon activation . Cells pre-treated with KT-474, a negative control, and two small molecule IRAK4 kinase inhibitors KT-474 better able to inhibit IL-6 under both LPS and R848 than clinically active IRAK4 SM kinase inhibitor PF-06550833 KYMERA 9-71% 150 100- 50 -8 Legend LPS → IL-6 Log [Compound] (uM) Compound KT-474 Negative control IRAK4 SMI (PF-06550833) IRAK4 SMI (other) IL-6 IC (nm) 3 335 N/A N/A 9-71% 150 100 50 -8 R848 → IL-6 -2 Log [Compound] (µM) Legend Compound KT-474 IRAK4 SMI (PF-06550833) IRAK4 SMI (other) IL-6 IC (nM) 0.7 5 49#22IRAK4 Degradation Superior to Kinase Inhibition in Intracellular Signaling KYMERA Phosphorylation events upon TLR activations monitored using flow cytometry KT-474 inhibited pro- inflammatory phosphorylation events in a superior manner to small-molecule inhibitors including clinically active PF-compound Unstim Ctrl R848 (TLR7/8) IRAKASMI IRAKA SMI (other) (PF-06550833) LPS (TLR4) IRAKASMI IRAK4 SMI (other) (PF-06550833)#23IRAK4 Degradation In Vivo Active in Preclinical Mouse Psoriasis Model IL-1R/TLR driven Ability to inhibit topical skin thickening induced by imiquimod was measured in a mouse model of psoriasis • Orally dosed KT-474 inhibited thickening, a reflection of local and systemic inflammation, comparable to a topic corticosteroid after 2 or 4 days of dosing * Inhibition shown at doses achieving at least 60-70% IRAK4 knockdown in skin and spleen KYMERA & Ear thickness (µm) D % IRAK4 (Control) + SEM % IRAK4 (Control) + SEM 150 150 $% IMQ Skin Spleen#24IRAK4 Degradation In Vivo Active in Preclinical Mouse Gout Model IL-1R driven • Neutrophil recruitment and inflammasome dependent cytokine production measured upon activation with injected urate crystals in mouse + KT-474 blocked neutrophil infiltration and IL-18 production at doses and exposures resulting in 80% or greater IRAK4 reduction in the spleen Dose (mpk) BID Plasma [KT-474] µM KYMERA 0.87 Spleen [KT-474] µM 10.89 30 66% 100 80% 300 86% Inhibition of disease activity achieved with 80% degradation of IRAK4 in spleen 18 IRAK4 KD Percent 100 80 8 40 MSU Vehicle Neutrophils KT-474 30 mg/kg, PO BID ****p<0.0001 KT-474 100 mg/kg. PO BID KT-474 300 mg/kg, PO BID Total pg 500 400 200 100 IL-13 in Exudate MSU Vehicle KT-474 30 mg/kg, PO BID **p<0.001 KT-474 100 mg/kg. PO BID KT-474 300 mg/kg, PO BID#25KT-474: Close to Complete IRAK4 Degradation and Well Tolerated in Preclinical Non-rodent Model • Orally-administered KT-474 evaluated in a 14-day non- GLP tox and PKPD study in rodent and non-rodents (shown). • Almost complete knockdown demonstrated across multiple tissues at multiple doses Compound well-tolerated at all doses up to 600 mg/kg for rodents and 100 mg/kg for non-rodents KYMERA % IRAK4 (Control) % IRAK4 (Control) 150- 50 150- 100 0 0 PBMC 10 30 Dose (mg/kg/day) Kidney Dose (mg/kg/day) % IRAK4 (Control) % IRAK4 (Control) 150- 150 100 10 Skin Dose (mg/kg/day) Liver # 100 Dose (mg/kg/day) % IRAK4 (Control) % IRAK4 (Control) 150- 50 10 150- 2 Spleen Dose (mg/kg/day) Lymph Node 0 10 Dose (mg/kg/day) Vehicle 10mg/kg/day 30 mg/kg/day 100 mg/kg/day *- Below level of quantification#26Target Date H1 2020 H2 2020/H1 2021 • HS: n=30 AD: n=10 NI Study Single-site non-interventional study • Whole blood, plasma and skin biopsies collected at single time point Milestones Study Start Data readouts from skin and blood KYMERA • Biomarker endpoints in blood and skin: IRAK4, cytokines, acute phase reactants IND KT-474 Development Plan Phase 1 NHV SAD/MAD Target Date Milestones H1 2021 IND Filing and Study Start H2 2021 NHV SAD/MAD data H2 2021 Patient cohort in MAD • Randomized, pbo-controlled, dose escalation study • SAD and MAD (14 daily doses) • Up to 100 adult healthy volunteers Primary endpoint: Safety • Secondary endpoints: PK and PD (POB) • IRAK4 levels in blood and skin • Levels of pro-inflammatory cytokines • Ex-vivo stimulation of PBMC • Plasma levels of hsCRP • Small patient cohort of top MAD dose to confirm PKPD POB Phase 2 Target Date Milestones 2022 Clinical POC • Randomized, pbo-controlled, study in pts in indications such as HS, AD, RA POC#27KYMERA IRAKIMID#28MYD88 mutation drives differentiation and proliferation in subset of B cell lymphomas Selective kinase inhibitors do not affect viability Degraders are effective in this context IMiDs downregulate IRF4, increasing IFN signaling and further suppressing NFkB activation IRAKIMID A Combo in a Single Molecule Inhibiting both MYD88 and IRF4-dependent NFkB and activating IFN signaling drive cell death in MYD88-mutant lymphomas and leads to full and durable responses in vivo KYMERA Indications/Timeline MYD88-mutant Diffuse Large B Cell Lymphoma Current: Preclinical development Expected IND submission: 2H 2021 Expected P1: 2H 2021 IRAK4 Degrader S JNK IL-1R UVERDAFTAND GRARATARS RAK IRAK AP1 Pathway KKK Pathway NFKB Pathway 8 Cell Receptor CL10 TK CD79A/B* IRFA PROLIFERATION & SURVIVAL Adapted from Yang et al. (2012) Cancer Cell 21, 6. pp723-737 *Oncogenic driver mutations IRAK4+ Ikaros/Aiolos IMIDS Baros Nucles IFN IFNAR1/2 IFN Pathway#29KYMERA Degradation of IRAK4, Ikaros and Aiolos Correlates to Cell Killing IMID Degrader CRBN IMD Rinder Degradation of ID Substrates IRAKIMID Degrader CRBN iped IMD Binder Degradation of IMID Substrates and A IRAKA - IRAK4, Ikaros and Aiolos degradation measured in MYD-88- mutated OCI-Ly10 cells after 24 h of drug exposure - IRAK4 DC50=4 nM • Ikaros/Aiolos DC5o = 2/2 nM Degradation correlates with cell killing effects IC50=31 nM % Cell Death 100- 50 0 10000'0 0.0001 0.001 0.01 0.1 % Cell Death Aiolos Ikaros IRAK4 10 -50 100 0 100 IRAKIMID Degrader Concentration (µM) % Degradation#30IRAKIMID Superior to IRAK4 Inhibition and IMID Single Agents MYD88-mutated ABC- DLBCL cell lines OCI-Ly10 and SUDHL2 evaluated in a 4-day viability assay - Activity of IRAKIMID compared to an IMID compound alone and IRAK4 kinase inhibitor alone assessed + IRAKIMID degrader (ICso 31 nM) significantly more selective and efficient than IRAK4 SM kinase inhibitor or a third generation clinically active IMID CC-122 in cell viability KYMERA % Viability (4D CTG) 100- 75- 50 OCI-Ly10 Log [Compound] (μM) % Viability (4D CTG) 100 IRAK4 KI CC122 75 50 25 IRAKIMID Degrader SUDHL2 Log [Compound] (μM)#31* Mice carrying MYD-88 mutated OCI-Ly10 xenografts treated with daily IRAKIMID doses (5 and 25 mg/kg) Tumor Regressions from Substantial Degradation of IRAK4 and IMID Substrates in Preclinical Xenograft Model • Dose-dependent degradation of IRAK4, Ikaros/Aiolos observed, and more than 80% degradation associated with onset of regression # Data support hypothesis that superior single-agent anti-tumor activity driven by downregulation of both MYD88 and IRF4 pathways KYMERA Tumor Volume (mm³) 1500 1000 500 0 Vehicle, QD x 21 days IRAKMID 5 mg/kg, QD x 21 days IRAKMID 25 mg/kg, QD x 21 days 7 Days 21 28 100 8 Target Degradation (% Control) 80 40 IRAK4 Ikaros Aiolos 5 25 IRAKIMID Degrader Dose (mg/kg)#32Lead IRAKIMID Selective for MYD88 Tumors Irrespective of Co-mutations • Lead IRAKIMID degrader is a selective and efficient degrader of both IRAK4 and the IMiD substrates IRAK4 DC50 = 8 nM Ikaros/Aiolos DC5o = 2 nM Degradation leads to cell viability effects preferentially in MYD88- mutant lines irrespective of other mutational status KYMERA - Data support potential for broadly targeting tumors harboring MYD88 mutations Model OCI-LY10 TMD8 SUDHL-2 OC-LY19 U2932 MYD88 L265P mut L265P mut $222R mut Wild type Wild type CD79A/B mut mut Co-mutations TNFAIP3 mut IRF4 mut BCL6 mut mut IRAKIMID (ICM) 0.008 0.022 0.013#33Tumor Regressions from Intermittent Dosing In Preclinical Xenograft Model Both PO and IV • Mice carrying MYD-88 mutated OCI-Ly10 xenografts treated with lead IRAKIMID dosed orally (left) and IV (right) -IRAKIMID induced complete tumor regressions • Responses were seen with different routes of administration and schedules . Durable responses suggest potential for infrequent dosing KYMERA Tumor volume (mm³) Vehicle PO, QD x 7 days Lead IRAKIMID Degrader 10 mg/kg. D1, 4, 8, 11 Lead IRAKIMID Degrader 30 mg/kg. D1, 4,8 2500 2000- 1500- 1000 500 0 7 14 21 28 35 Days Tumor volume (mm³) → IV Vehicle Lead IRAKIMID Degrader 3 mg/kg, D1,4,8,11 Lead IRAKIMID Degrader 6 mg/kg, D1,4,8 2500 2000 1500 1000 500 0 7 14 21 28 35 Days#34KYMERA IND IRAKIMID Development in MYD88 Mutant DLBCL Target Date H2 2021 H2 2022 Phase 1 B Cell Lymphomas Milestones IND and Study Start Clinical POC • Multi-center dose escalation study (US) B cell lymphomas • Safety, tolerability, PK and PD (POB) and preliminary clinical activity • P1b Expansion cohort in DLBCL (MYD88-mut and-wt) with and without CNS involvement at MTD • Option to amend protocol to explore select combinations . Clinical and biomarker endpoints POC#35KYMERA STAT3#36STAT3 Biology and Degrader Rationale . STAT3 is a traditionally largely undrugged transcription factor activated through cytokine and growth factor receptors via JAKS and non-JAKS mediated mechanisms High degree of validation of JAK-STAT pathway in oncology and immuno-oncology supported also by numerous publications - STAT3 plays a role in tumor biology, evasion of immune surveillance and inflammation/fibrosis - No known drugs specifically affect STAT3 broadly across all relevant cell types . First in class opportunity to address STAT3 driven pathology across large and diverse indications KYMERA Indications/Timeline Hematological Malignancies/Solid Tumors and Autoimmune/Fibrosis Current: Preclinical development Expected IND submission: 2H 2021 Expected P1: 2H21 IL-6 IL-6R JAK JAK GPRC JAK TLRs JAK STAT3 STAT3 STAT3 STAT3 ❤ JAK TYK2#37CANCER 1/1 FIBROSIS Liquid Tumors Solid Tumors Autoimmune Fibrosis KYMERA STAT3 Disease Impact in Oncology & Autoimmunity Genetically-defined STAT3 mutation and/or hyperactivation ALCL, T-LGL leukemia, NK/T-cell lymphoma nasal type STAT3 activation and dependency DLBCL, AML, multiple myeloma Cell Intrinsic: STAT3 role in EMT/TKI resistance Combinations in TKI/chemotherapy resistant settings Cell Extrinsic: STAT3 role in 10 T-cell infiltrated tumors. Combinations with immune-modulators STAT3 GOF syndrome Genetically-defined STAT3 mutation characterized by enteropathy, arthritis, dermatitis, lung disease Immune-inflammatory Systemic sclerosis, atopic dermatitis, rheumatoid arthritis, Crohn's disease/ulcerative colitis Chronic inflammation / fibrosis Idiopathic pulmonary fibrosis, CKD/renal fibrosis Survival, proliferation, EMT, stemness Cancer Cells STATS Cytokines (e.g., IL-6, IL-10, VEGF) STATS Myeloid Cells (Macrophages, MDSCS) Tregs Immature DCs PD-L1 STATS Endothelial Cells Vascularization#38CANCER FIBROSIS Liquid Tumors Solid Tumors Autoimmune KYMERA Fibrosis Highly Specific Degradation of STAT3 • Deep mass spectrometry-based proteomics to assess STAT3 specificity performed i hPBMC and tumor cells (SU-DHL-1) treated with Kymera's STAT3 degrader • STAT3 was the only protein to be degraded with statistical significance Data demonstrate highly selective degradation profile p-value (-Log 10) L 3.5 inn 5 1 0.5 DC90 hPBMCs "STAT3 STAT3-85701 CO 24hr pval-0.05 1 2 Protein Level Fold Change (Log2) p-value (-Log 10) m 1.5 0.5 DC90 SU-DHL-1 STAT3 STAT3-A5701 Bhr 1 Protein Level Fold Change (Log2) STAT Family Members: STAT1, STAT2, STAT3, STAT4, STATSA, STATSB, STAT6#39CANCER FIBROSIS Liquid Tumors KYMERA Autoimmune Fibrosis STAT3 Protein (% Control) STAT3 Degradation 150 125- 100 50 STAT3 Degradation and Downstream Effects Across Tumor Cells 25 -SU-DHL-1 SUP-MZ 0 1 2 3 Log [STAT3 Degrader] (nM) • STAT3 protein levels measured in two STAT3-dependent cell lines • STAT3 degrader decreased levels of STAT3 by greater than 95% with DC so of 15nM and 86 nM, respectively Gene Transcription Effects mRNA Levels (% Control) 125 100 75 50- 25 Socs3 +Myc 0 1 2 3 Log (STAT3 Degrader] (n) Expression of STAT3 downstream target genes in SU-DHL-1 cells measured Treatment with STAT3 degrader for 24 hours led to significant downregulation of STAT3 target genes, including SOCS3 (ICS = 36 nM) and MYC (IC=37 nM) Growth Inhibition (% Control) Cell Viability Effects 125 100- 75- 50 25- -SU-DHL-1 SUP-M2 -1 0 1 2 3 4 Log [STAT3 Degrader] (nM) 5 Impact of STAT3 degradation on viability of lymphoma cells measured . Inhibited growth of SU-DHL-1 and SUP- M2 cells with IC50 values of 64 and 105 nM, respectively#40CANCER FIBROSIS Liquid Tumors o pro Autoimmune Fibrosis # Full and Durable Regressions Across Multiple in vivo Preclinical Tumor Models Mice bearing STAT3-dependent ALK+ ALCL SU-DHL-1 (above) and STAT3-driven ALK+ ALCL xenograft model SUP-M2 (below) tumors dosed with STAT3 degrader Dose and degradation dependent tumor growth inhibition observed with once a week IV dosing 30 mg/kg sufficient to drive full tumor regression that was durable for multiple weeks after the last dose KYMERA ©2020 KYMERA THERAPEUTICS, INC. Tumor Volume (mm²) Tumor Volume (mm³) 2000 1000 2000- 1000 10 Days Days STAT3 Degrader 5 mg/kg. QW →STAT3 Degrader 10 mg/kg, QW →STAT3 Degrader 25 mg/kg. QW STAT3 Degrader 50 mg/kg. QW Vehicle STAT3 Degrader 30 mg/kg, QW#41CANCER FIBROSIS Solid Tumors KYMERA Autoimmune SIROURES STAT3 Degradation as Resistant Mechanism in Solid Tumors - STAT3 is activated across a wide range of cancer cells in response to TKI's and chemotherapies, eventually leading to resistance and disease progression. . For example, when EGFR mutant (but not WT) NSCLC cell line H1650 was treated with erlotinib, upregulation of p-STAT3 was observed, which was reversed by STAT3 degrader Treatment with Erlotinib (1uM) Treatment with STAT3 Degrader (1 µM) p-STAT3 (Y705) STAT3 Actin X X X X > ✓ ✓ X X ✓ ✓#42CANCER FIBROSIS Solid Tumors KYMERA Autoimmune Fibrosis PD-L1 mRNA Levels (% Control) PD-L1 Downregulation PD-L1 mRNA in SU-DHL-1 cells PD-L1 mRNA in SUP-M2 cells 150 125- 100 75 STAT3 Degradation in Tumor Microenvironment 50- 2 3 Log [STAT3 Degrader] (nM) Treatment of cells with Kymera's STAT3 degrader reduced transcription of PD-L1 mRNA STAT3 degradation may reverse a key tumor intrinsic mechanism for immune suppression Increased Inflammation in Tumor Associated Immune Cells Log2-Fold Change STAT 3 Degrader vs DMSO Immune Markers CD1B TLR8 LILRA1- LILR82- IL21R- FCGR2A S100A12- $100A8 CD14- MSAASA CD163 STODAS IL-6: 1hr 6hr Signaling Cytokines Survival/Proliferation CCL25 CSF1 TNF- ICOSLG- IL23A- IL17A- CCR7- TMEM173- CXCL1- JAK3- SERPINA2 IL10 CXCL13 IL-6: 1hr 6hr IRF8 NOTCHI MYC AREG IL-6: 1hr 6hr STAT3 degrader blocked IL-6-induced increases in gene expression in hPBMC Data suggest degradation of STAT3 reverses expression of genes contributing to immune suppression#43CANCER FIBROSIS shown pos KYMERA Autoimmune Fibrosis STAT3 Degrader In Vivo Active in Preclinical PD-1/L-1 Refractory Solid Tumor Models • Kymera's STAT3 degrader assessed in colorectal cancers (CT-26) known to be refractory to approved immunotherapies STAT3 degrader significantly reduced tumor growth when administered every two days Analysis of tumors showed synergistic modulation of immune cells (M2/M1 and T cells) within the tumor microenvironment to favor an anti-tumor response Tumor Volume (mm³) mean 3500 3000 2500 2000 1500 1000 500 Vehicle STAT3 Degrader 25 mg/kg, q2d 5 10 Days HH 1.5 20 % Population % Population Macrophages (M1/M2) 100 9 80 9 8 M1 T Cells CD8+ Vehicle STAT3 Degrader Vehicle STAT3 Degrader#44V FIBROSIS STAT3 Degrader Active in T Cell Activation Preclinical In Vivo Model Multiple Sclerosis Model KYMERA shown in Solid Tumors Autoimmune Fibrosis * A preclinical model of experimental autoimmune encephalomyelitis (T cell activation) was used to evaluate STAT3 degradation Kymera STAT3 Degrader completely prevented onset of the disease in mice % Incidence of Disease 100 75 50 25 0 10 15 Days 20 Vehicle Dexamethasone, PO, QD STAT3 Degrader 10 mg/kg STAT3 Degrader 25 mg/kg Normal (non-immunized) 25#45STAT3 Degrader Clinical Development Plan in Liquid and Solid Tumors KYMERA IND Target Date H2 2021 H2 2022 Phase 1 Liquid and Solid Tumors • Multi-center dose escalation study -R/R B patients Milestones IND and Study Start Clinical POC • Safety, tolerability, PK and PD (POB) and preliminary clinical activity • P1b Expansion cohort in liquid and solid tumors separately • Option to amend protocol to explore select combinations . Clinical and biomarker endpoints POC#46KYMERA HIGHLIGHTS AND MILESTONES#47IL-1R / TLR JAK / STAT Internal Sanofi-partnered" Program KYMERA IRAK4* IRAKIMID (IRAK4, Ikaros, Aiolos) STAT3 Various Undisclosed Vertex-partnered Undisclosed Indication HS, AD, RA MYD88MT DLBCL Liquid and Solid Tumors Upcoming Catalysts H1 Phase 1 Start 2021 POB Phase 1 Start Phase 1 Start HI Phase 2 Start POB POB 2022 H₂ POC Immunology-inflammation POC *Kymera will have the option to participate in the development and commercialization of Sanofi-partnered programs in the US during clinical development Multiple degrader programs in immune-inflammatory and genetically defined oncology indications with DC/IND nominations in this timeframe Oncology Research and development of degraders against an undisclosed target Research and development of degraders against up to 6 targets in disease areas outside of our core strategic focus of immunology-inflammation and oncology#48KYMERA Investment Highlights Mission to discover, develop & commercialize transformative therapies using targeted protein degradation (TPD) Leading targeted protein degradation platform investing in unique capabilities of our proprietary discovery platform, Pegasus Focus on un-drugged or inadequately-drugged targets in clinically validated biological pathways that TPD can potentially unlock >>> Robust internal pipeline focused on Oncology and Immunology with three programs projected to enter the clinic in 2021: IRAK4, IRAKIMID and STAT3 Leveraging synergies in biopharma collaborations with Vertex and Sanofi to date, to increase disease and patient impact Experienced management team of leading scientific innovators#49KYMERA THANK YOU August 2020