Kymera Therapeutics, Inc. · NASDAQ:KYMR

Kymera Therapeutics — Investor Day (January 2024)

75 slides from Kymera Therapeutics's investor day presentation, Jan 4, 2024

  1. Slide 1: 2024 Immunology R&D Day

    2024 IMMUNOLOGY R&D DAY January 4, 2024 ©2023 KYMERA THERAPEUTICS, INC. PAGE 1

  2. Slide 2: Welcome

    Welcome Justine Koenigsberg Vice President, Investor Relations 2

  3. Slide 3: Forward Looking Statements

    Forward 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

  4. Slide 4: Agenda

    Agenda Welcome 10:00 - 10:05 Justine Koenigsberg, Vice President, Investor Relations Revolutionizing Immunology with Small Molecule Oral Degraders 10:05 - 10:25 Nello Mainolfi, Ph.D., Founder, President and CEO Paving the Way: KT-474, a First-in-Class Oral IRAK4 Degrader 10:25 - 10:35 Jared Gollob,

  5. Slide 5: Revolutionizing Immunology with Small Molecule Oral Degraders

    Revolutionizing Immunology with Small Molecule Oral Degraders Nello Mainolfi, Ph.D., Founder, President and CEO 5

  6. Slide 6: Mission

    Mission Build a global medicines company that harnesses novel modalities to revolutionize healthcare

  7. Slide 7: What I Will Cover

    What I Will Cover • Targeted Protein Degradation: Harnessing a Game-Changing Novel Modality • Demonstrating Reproducible and Scalable Clinical Innovation • Our Target Selection Strategy • Why Oral Degraders in Immunology • Our Two New Programs 7

  8. Slide 8: Harnessing a Game-Changing, Novel Modality

    Harnessing a Game-Changing, Novel Modality Kymera, a Leader in Targeted Protein Degradation DEGRADER • Focused on unlocking high value, undrugged targets using TPD • Highly productive and reproducible platform for discovery of DISEASE- innovative medicines E3 CAUSING LIGASE PROTEIN • Leading platfor

  9. Slide 9: Target Selection Strategy

    Target Selection Strategy Focus on First- or Best-in-Class Opportunities Undrugged or Inadequately Strong Genetic/Pathway Clear Path to Early Clinical Large Clinical/Commercial Drugged targets Validation Differentiation Opportunities Small Molecule Inhibitor Degrader TRANSCRIPTION AREAS OF APPROVED

  10. Slide 10: Demonstrating Reproducible and Scalable Clinical Innovation

    Demonstrating Reproducible and Scalable Clinical Innovation IRAK4 IRAK4 Degradation leads to Early POC STAT3 Degradation Leads to Major Response STAT3 KT-474 in HS and AD in cHL Patient KT-333 IRAK4 Levels Reduction of AN Counts in HS Patients STAT3 Levels 700 Bone Lesion Size Reduction in cHL Patie

  11. Slide 11: Building a Global Medicines Company

    Building a Global Medicines Company Pioneering a Demonstrating Delivering a new generation new modality early POC of medicines 2016-2020 2021-2023 2024-2028 0 Mean % Change (+/- S.E. of -10 -20 -19.9 Mean) -45.4 -27.4 -30 -31.6 -40.6 -40 -46.1 -50 -49.6 -50.7 -60 0 7 14 21 28 35 42 Day Focused on un

  12. Slide 12: The Opportunity in Immunology

    The Opportunity in Immunology Immune- Orals inflammation is a $250B WW Oncology market1 spanning multiple $171B therapeutic areas. Other $81B $250B Immune- $156B Immunology inflammation $40B Infectious Disease $72B Injectables $131B dominate, CNS comprising >75% of Cardio- the established Metabolic

  13. Slide 13: Why Small Molecule Oral Degraders in Immunology

    Why Small Molecule Oral Degraders in Immunology Key pathways/cytokines Oral Degraders Can Offer validated as drivers of many diseases in I&I Biologic-like Efficacy in a Pill Biologics blocking these Patients on Biologics that pathways/cytokines have Would Switch to Orals1 revolutionized treatment Bi

  14. Slide 14: Revolutionizing Immunology with Oral Degraders: Our IRAK4 Example

    Revolutionizing Immunology with Oral Degraders Our IRAK4 Example IRAK4 BEST-IN-PATHWAY MECHANISM SCAFFOLDING KINASE IL-1R/TLR Pathway Cytokines Clinical pathway validation > IL-1, IL-18, IL-33, IL-36 biologics TLR IL-1, IL-18, > IRAK4 null adults: healthy Agonists IL-33, IL-36 Human genetics TLRs IL

  15. Slide 15: What We Have Learned from KT-474

    Revolutionizing Immunology with Oral Degraders WHAT WE HAVE LEARNED FROM KT -474 Strong Early Signs PK/PD of Clinical Correlation Activity Differentiated Safety vs. SMI IRAK4 SCAFFOLDING KINASE 15

  16. Slide 16: KT-474: Fidelity of Translation from Preclinical to Clinical Profile

    KT-474: Fidelity of Translation from Preclinical to Clinical Profile Predicted % IRAK4 Reduction from Baseline Human PBMC After Oral Dosing QD 0 –20 on Day 14 (mean (+s.e.)) from Baseline in PBMC Percent IRAK4 Change –40 –60 –80 DC85 = 3 ng/mL –92% –95% –98% –96% –100 Placebo 25 mg 50 mg 100 mg 200

  17. Slide 17: Our Two New Programs

    Revolutionizing Immunology with Small Molecule Oral Degraders Our Two New Programs SPECIFIC IL-4/13 SPECIFIC IL-23/IFN TRANSCRIPTION FACTOR SCAFFOLDING KINASE STAT6 TYK2 17

  18. Slide 18: STAT6 Degrader: Dupilumab-like Activity in a Pill

    STAT6 Degrader: Dupilumab-like Activity in a Pill STAT6 BEST-IN-PATHWAY MECHANISM TRANSCRIPTION FACTOR IL-4/13 Pathway Type I IL-4 Type II IL-4 Clinical pathway validation > Dupilumab Receptor Receptor IL-4 IL-4 IL-13 Gain of function variants cause IL-4Rα γc IL-4Rα IL-13Rα1 Human genetics > severe

  19. Slide 19: STAT6: Significant Potential Across Multiple I&I Indications

    STAT6: Significant Potential Across Multiple I&I Indications Dupixent1 (dupilumab) Global Sales, MARKET USD Billions OPPORTUNITY 25,000 $19.8 Total IL-4/IL-13 biologics2 sales expected 20,000 to double by 2029 • >$10B in 2023 +12.4% • >$23B by 2029 Sales Value 15,000 CAGR Currently approved indicati

  20. Slide 20: TYK2 Degrader: Degrading a Proven Target for a Best-in-Class Profile

    TYK2 Degrader: Degrading a Proven Target for a Best-in-Class Profile TYK2 BEST-IN-PATHWAY MECHANISM SCAFFOLDING KINASE IL-23 biologics (ustekinumab), IL-12/23/IFN Pathways Clinical pathway validation > TYK2 inhibitor (deucravacitinib) approved, others Type I interferons IL-23 IL-12 LOF variant is pr

  21. Slide 21: TYK2: Significant Potential Across Multiple I&I Indications

    TYK2: Significant Potential Across Multiple I&I Indications MARKET IL-23 and Type I IFN Annual Market OPPORTUNITY USD Billions 30,000 $26.9 Total IL-23 and Type I IFN 25,000 biologics1 sales expected to grow >6% by over $9B by 2029 CAGR • ~$18B in 2022 20,000 $17.7 • ~$27B by 2029 Sales Value 15,000

  22. Slide 22: Kymera Immunology Oral Degrader Portfolio

    Kymera Immunology Oral Degrader Portfolio Complementary, First-in-class Mechanisms IRAK4 STAT6 TYK2 SCAFFOLDING TRANSCRIPTION SCAFFOLDING KINASE FACTOR KINASE IL-1R/TLR Pathway IL-4/13 Pathway IL-12/23/IFN Pathways Cytokines Type I IL-4 Type II IL-4 TLR Type I IL-1, IL-18, Receptor Receptor Agonists

  23. Slide 23: Industry-leading Oral Immunology Pipeline

    Industry-leading Oral Immunology Pipeline Three Fundamental Immune-inflammatory Pathways with Large Market Potential High value undrugged/ Next generation oral Building the industry- inadequately drugged drugs with potential leading oral targets best-in-class profiles immunology portfolio IRAK4 (KT-

  24. Slide 24: What to Expect Today

    WHAT TO EXPECT TODAY Vision for our I/I portfolio and Kymera’s unique ability to capitalize on power of TPD Update on IRAK4 program Detailed overview of STAT6 and TYK2 programs • Clinical opportunities • Degrader advantage • Compelling preclinical data package • Timelines to clinic

  25. Slide 25: Paving the Way: KT-474, a First-in-Class IRAK4 Oral Degrader

    Paving the Way: KT-474, a First- in-Class IRAK4 Oral Degrader Jared Gollob, M.D., Chief Medical Officer 25

  26. Slide 26: IRAK4: What We Will Cover

    IRAK4: What We Will Cover • Pathway Biology and Validation • Clinical Development/Commercial Opportunities • Degrader Profile and Advantage • Our Clinical Data and Fidelity of Translation • Our Ongoing Phase 2 Studies 26

  27. Slide 27: IRAK4 Biology and Target Rationale

    IRAK4 Biology and Target Rationale IRAK4 SCAFFOLDING KINASE Target Rationale IL-1R/TLR Pathway • IRAK4 is an obligate node in IL-1R/TLR signaling, and its Cytokines TLR degradation is the only approach to fully block the pathway Agonists IL-1, IL-18, IL-33, IL-36 TLRs IL-1R Human Genetics • Adult hu

  28. Slide 28: IL-1R/TLR Pathway Potential Impact Across Multiple Immune-Inflammatory Diseases

    IL-1R/TLR Pathway Potential Impact Across Multiple Immune- Inflammatory Diseases DERMATOLOGY RESPIRATORY GI RHEUMATOLOGY Atopic RA Asthma CD Dermatitis COPD HS UC SLE Total Potential Patient Impact1: >150M patients Numerous indication IRAK4 degradation leading to Oral degrader medicines opportunitie

  29. Slide 29: IRAK4 Degrader Advantage

    IRAK4 Degrader Advantage Only Degrader Can Fully Block Inflammation Preclinical Data (Kymera IRAK4 Backgrounder) LPS + IL-1b → IL-6 • IRAK4 KO is able to block TLR activation unlike the kinase dead rescue Cytokines TLR • IRAK4 scaffolding function is critical in IL-1, IL-18, Agonists IL-33, IL-36 My

  30. Slide 30: KT-474: Selective and Potent IRAK4 Degrader Active in Multiple Cell Types

    KT-474: Selective and Potent IRAK4 Degrader Active in Multiple Cell Types Selectivity in PBMC KT-474 selectively degrades Potency in Blood and Skin Cells IRAK4 in human immune KT-474 Degradation Across Immune Cell Types cells at concentration 10-fold above the DC90 Potent degradation in PBMC subsets

  31. Slide 31: Initial Clinical Focus for KT-474: Moderate to Severe HS and AD

    Initial Clinical Focus for KT-474: Moderate to Severe HS and AD Hidradenitis Suppurativa (HS) Atopic Dermatitis (AD) Chronic and debilitating skin disease with painful nodules, Chronic inflammatory skin disease with scaly, dry, erythematous abscesses and draining fistulae/tunnels lesions; intense it

  32. Slide 32: KT-474 Phase 1: Compelling Data and Early POC in HS and AD

    KT-474 Phase 1: Compelling Data and Early POC in HS and AD Healthy Volunteers (HV): HS and AD Patient Cohort SAD and MAD • Evaluated safety, tolerability and • Open label study in 21 patients with HS and pharmacokinetics in 105 healthy volunteers AD • SAD: Oral doses of 25-1600 mg • Dose: 75 mg QD w

  33. Slide 33: Near-Complete Degradation and Broad Cytokine Impact in Healthy Volunteers

    Near-Complete Degradation and Broad Cytokine Impact in Healthy Volunteers Mean % Reduction of IRAK4 Ex Vivo Inhibition of 9 Disease-Relevant (Daily oral doses for 14 days) Cytokines, Day 7-14 R848 (TLR7/8) Stimulation IFNγ IL1β IL6 IL8 IL10 IL12 IL17 TNFα Pbo >500% 15% 35% -5% -23% 3% 107% -7% 50 mg

  34. Slide 34: High Skin Exposure and Degradation in Skin of HS and AD Patients

    High Skin Exposure and Degradation in Skin of HS and AD Patients High KT-474 Exposure in HS and AD Patients Skin Reduced IRAK4 in Skin Lesions of AD and HS Patients MAD Healthy AD Patients HS Patients AD Patients HS Patients Plasma Day 28 N=21 Subjects (Baseline) (Baseline) (Day 28) (Day 28) Skin Da

  35. Slide 35: Robust Clinical Impact in HS After Only Days of Dosing

    Robust Clinical Impact in HS After Only 28 Days of Dosing Mean % Change in Average 80 HiSCR50 Responders 0 Pain Over Past Week 70 -10 Mean % Change (+/- S.E. of Mean) % of HiSCR Responders (80% CI) Moderate to Severe (N=10) Moderate to Severe (N=10) 60 -20 50 -27 50 50 -30 40 -40 -39 30 30 30 -50 -5

  36. Slide 36: Robust Clinical Impact in AD After Only Days of Dosing

    Robust Clinical Impact in AD After Only 28 Days of Dosing Mean % Change in EASI Mean % Change of Worst Pruritus 0 0 10 Score Over Time (N=7) Over Time (N=7) 0 Mean % Change (+/-S.E. of Mean) Mean % Change (+/-S.E. of Mean) -10 -6 -7 -10 -18 -20 -20 -28 -30 -33 -37 -32 -36 -30 -40 -39 -43 -45 -52 -36

  37. Slide 37: KT-474/SAR444656: Positioned for Clinical Success

    KT-474/SAR444656: Positioned for Clinical Success Phase 2 HS Trial Phase 2 AD Trial (ZEN) (ADVANTA) • Double-blind, placebo-controlled • Double-blind, placebo-controlled • Up to 99 patients, dosed for 16 • Up to 115 patients, dosed for 16 weeks weeks • 1 KT-474 dose arm, 1 placebo arm • 2 KT-474 dos

  38. Slide 38: Oral IRAK4 Degrader: KT-474

    Oral IRAK4 Degrader: KT-474 A best-in-pathway broad oral anti-inflammatory agent for multiple inflammatory diseases Validated Biology Competitive Profile KT-474 Progress/Next Steps Mediates signaling through IL-1 Potential for Broad Activity Phase 1 complete: and toll-like receptors Across Th1-Th17

  39. Slide 39: Dupilumab-like Activity in a Pill: KT-621, a First-in-class Oral STAT6 Degrader

    Dupilumab-like activity in a pill: KT-621, a First-in-class Oral STAT6 Degrader Amy Wang, Ph.D., Senior Director, Biology Project Lead 39

  40. Slide 40: What We Will Cover

    What We Will Cover • STAT6 Biology and Target Rationale • Clinical Development/Commercial Opportunities • Degrader Advantage • Preclinical Data • Next Steps 40

  41. Slide 41: STAT6 Biology and Target Rationale

    STAT6 Biology and Target Rationale STAT6 TRANSCRIPTION FACTOR Target Biology and rationale • STAT6 is the specific transcription factor required for IL-4 and IL-13 Type I IL-4 Receptor Type II IL-4 Receptor cytokine signaling • STAT6 regulated cytokines are clinically validated targets for allergic

  42. Slide 42: Oral STAT6 Degraders Can Transform Treatment Paradigm in Multiple Indications

    Oral STAT6 Degraders Can Transform Treatment Paradigm in Multiple Indications De-risked by Dupilumab DERMATOLOGY RESPIRATORY ENT GI Atopic Asthma Dermatitis CRSwNP EoE COPD PN Total Potential Patient Impact1: >150M patients Numerous indication STAT6 degradation leading to Oral degrader medicines opp

  43. Slide 43: STAT6 Degrader Advantage

    STAT6 Degrader Advantage Type I IL-4 Receptor Type II IL-4 Receptor Tralokinumab • STAT6 is the specific and Dupilumab Dupilumab Lebrikizumab essential transcription factor in IL-4 IL-4 IL-13 the IL-4/13 pathway Degrader IL-4Rα γc IL-4Rα IL-13Rα1 STAT6 • Occupancy based approaches (e.g., SMI) unlike

  44. Slide 44: KT-621: A Picomolar Degrader of STAT6

    KT-621: A Picomolar Degrader of STAT6 Consistent Degradation Across All Disease Relevant Cell Types Evaluated STAT6 Degradation in Hematopoietic Cells Human Primary Cell Type KT-621, DC50 (pM) Hematopoietic cell (all TH2 diseases) Human PBMC 13 Human CD3 T cell 36 Blood Human CD14 monocyte 60 Human

  45. Slide 45: KT-621: Exquisite Degradation Selectivity for STAT6

    KT-621: Exquisite Degradation Selectivity for STAT6 Complete STAT6 degradation selectivity in human PBMC proteome at 100 x DC90 No other STATs are degraded to any extent 45

  46. Slide 46: KT-621: Exquisite Pathway Selectivity for STAT6

    KT-621: Exquisite Pathway Selectivity for STAT6 No Impact on Any Other STAT Pathway Observed STAT6 STAT assays KT-621, IC50 (nM) IL-13 Induced pSTAT6 in Human PBMC IFN-α induced pSTAT1 > 1000 IFN-α induced pSTAT2 > 1000 IL-10 induced pSTAT3 > 1000 IL-12 induced pSTAT4 > 1000 IL-2 induced pSTAT5 > 10

  47. Slide 47: KT-621 Fully Blocks IL-4/13 Pathway, More Potently than Dupilumab

    KT-621 Fully Blocks IL-4/13 Pathway, More Potently than Dupilumab KT-621 Dupilumab Cellular Functional Assay IC50 (pM) IC50 (pM) Serum Th2 biomarker, chemoattractant for Th2 IL-4 TARC release in human PBMC 62 194 TARC cell IL-13 TARC release in human PBMC 43 113 B cell activation marker, correlates

  48. Slide 48: KT-621 Achieves Dose Dependent Deep Degradation of STAT6 in vivo

    KT-621 Achieves Dose Dependent Deep Degradation of STAT6 in vivo with Low Oral Doses STAT6 Degradation in Dog Blood post 7 days of KT-621 QD Oral Dosing 0 STAT6 % Change from Baseline KT-621 potently degrades STAT6 across multiple preclinical species -50 KT-621 can degrade STAT6 to depletion with lo

  49. Slide 49: KT-621 Degrades STAT6 in Disease Relevant Tissues in NHP

    KT-621 Degrades STAT6 in Disease Relevant Tissues in NHP STAT6 Degradation in NHP Tissues post 14 days of KT-621 10 mpk QD Oral Dosing 0 STAT6 % Change from Baseline Deep degradation of STAT6 in NHP after 14 days of daily oral dosing -50 STAT6 is degraded in key disease- relevant tissues: blood, spl

  50. Slide 50: KT-621 Has Comparable in vivo Efficacy to Dupilumab in MC903 AD Model

    KT-621 Has Comparable in vivo Efficacy to IL-4Rα Saturating Dose of Dupilumab in the MC903 Atopic Dermatitis Model STAT6 Degradation in Mouse Spleen Total Serum IgE An atopic dermatitis model induced by topical application of low- calcemic vitamin D3 analog MC903 with prominent Th2 inflammation in t

  51. Slide 51: KT-621 Efficacy vs Dupilumab in Intranasal HDM Asthma Model

    KT-621 Has Comparable or Superior in vivo Efficacy to IL-4Rα Saturating Dose of Dupilumab in the Intranasal HDM Asthma Model A lung inflammation model induced by intranasal house dust mite administration with dominant Th2 inflammation in the IL4/IL4RA humanized mice (Le Floc’h et al. Allergy. 2020)

  52. Slide 52: Oral STAT6 Degrader: KT-621

    Oral STAT6 Degrader: KT-621 Dupilumab-like efficacy with oral small molecule profile Validated Biology Competitive Profile KT-621, FIH: 2H 2024 Specific and essential WW IL-4/IL-13 biologic market Full IL-4 and IL-13 functional transcription factor in IL-4 and currently $10B+ annually inhibition wit

  53. Slide 53: Degrading a Proven Target: KT-294, a First-in-Class Oral TYK2 Degrader

    Degrading a Proven Target: KT-294, a First-in-Class Oral TYK2 Degrader Juliet Williams, Ph.D., Head of Research 53

  54. Slide 54: What We Will Cover

    What We Will Cover • TYK2 Biology and Target Rationale • Clinical Development/Commercial Opportunities • Degrader Advantage • Preclinical Data • Next Steps 54

  55. Slide 55: TYK2 Biology and Target Rationale

    TYK2 Biology and Target Rationale TYK2 SCAFFOLDING KINASE Target Biology and Rationale Ustekinumab • TYK2 is a member of the JAK family required for Type I IFN, IL- Anifrolumab Risankizumab 12 and IL-23 cytokine signaling • TYK2 regulated cytokines are clinically validated targets for autoimmune and

  56. Slide 56: Patient Impact of TYK2: Potential Best-In-Class Opportunity in I&I

    Patient Impact of TYK2: Potential Best-In-Class Opportunity in I&I DERMATOLOGY GASTROENTEROLOGY RHEUMATOLOGY CNS CD PsA Plaque MS Psoriasis UC SLE Total Potential Patient Impact1: > 20M patients Numerous indication TYK2 degradation, differentiated from Oral degrader medicines opportunities across mu

  57. Slide 57: TYK2 Degrader Advantage

    TYK2 Degrader Advantage Only TYK2 Degraders Can Reach Biologics-like Activity • TYK2 has a well-established scaffolding Ustekinumab function that is responsible for cytokine Anifrolumab Risankizumab receptor surface expression and Degrader activation • Unlike SMIs, only TYK2 degradation Type I IL-23

  58. Slide 58: TYK2 Has Well-Established Scaffolding Function

    TYK2 Has Well-Established Scaffolding Function • TYK2 complete deficiency severely impairs IL-23, Type I IFN, and IL-12 signaling but spares IL-10 in humans • TYK2 scaffolding functions are demonstrated by differential pathway inhibitions in complete TYK2 deficiency vs a kinase dead variant in human

  59. Slide 59: KT-294, a Highly Selective Picomolar TYK2 Degrader

    KT-294, a Highly Selective Picomolar TYK2 Degrader, Recapitulates TYK2 Human Deficiency Biology Fully Inhibits of Type I IFN and IL-12/23 and Spares IL-10/22 KT-294 Cellular Degradation/Functional Assay Selective TYK2 Degradation by KT-294 in DC50/IC50 (nM) hPBMC Proteome at 10x DC90 Human PBMC degr

  60. Slide 60: KT-294, Unlike Deucravacitinib, Does not Inhibit IL-10

    KT-294, Unlike Allosteric TYK2 Inhibitor Deucravacitinib, Does not Inhibit IL-10 IL-10 has essential roles in intestinal homeostasis • Loss of function mutations of the IL-10 pathway cause early onset refractory colitis in humans Deucravacitinib inhibits IL-10 through JAK1 • Deucra JAK1 Ki = 0.33 nM

  61. Slide 61: Superior Inhibition of Type I IFN Pathway by KT-294 vs TAK-279

    Superior Inhibition of Type I IFN Pathway and Innate Immunity by KT-294 vs TAK-279 21-gene IFN⍺ Signature Score 12-gene Innate Signature Score was Measured by RNAseq was Measured by RNAseq SG15 IFI6 IFI27 SPATS2L LY6E IFI44L Mean inhibition DEFB1 by KT-294 ISG15 OAS3 Mean inhibition OAS1 DSP by KT-2

  62. Slide 62: KT-294 Achieved Dose Dependent Deep Degradation of TYK2 in vivo

    KT-294 Achieved Dose Dependent Deep Degradation of TYK2 in vivo with Low Oral Doses TYK2 Degradation in NHP Blood Post 7 days of KT-294 QD Oral Dosing 0 TYK2 % Change from Baseline KT-294 potently degrades TYK2 across multiple preclinical species In NHP, KT-294 can degrade TYK2 to depletion with low

  63. Slide 63: TYK2 SMI's Do Not Reach Maximal Target Engagement

    TYK2 SMI’s Do Not Reach Maximal Target Engagement Clinical Efficacy In Psoriasis is Target Engagement Dependent 100 90 80 30mg TYK2 degrader 70-80% inh. average (LOF phenotype) PASI 75 (%)* @ Wk 10 - 16 70 6mg Opportunity 60 50-60% inh. average 50 91 40 67 30 56 20 10 0 IL-23 p19 Deucravacitinib TAK

  64. Slide 64: Biological and Clinical Differentiation

    Biological and Clinical Differentiation KT-294, unlike TYK2 SMI, can replicate the TYK2 deficient phenotype and result: potent Type I IFN, IL- TYK2 Clinical Deucravacitinib TAK-279 KT-294 12/23 inhibition fully while sparing IL-10 Opportunities IL12/23, IFN, IL10 IL12/23, ~IFN IL12/23, IFN WITH FOLL

  65. Slide 65: Oral TYK2 Degrader: KT-294

    Oral TYK2 Degrader: KT-294 Potential Best-in-Class Opportunity with Biologic-like Profile Validated Biology Competitive Profile KT-294, FIH: 1H 2025 IL-23 and Type 1 IFN-based biologic Degrades TYK2 in human cells with TYK2 is a member of the JAK family market currently ~$18B annually pM potency req

  66. Slide 66: Solving Big Problems with Small Molecules

    Solving Big Problems with Small Molecules Nello Mainolfi, Ph.D., Founder, President and CEO 66

  67. Slide 67: A Powerful Strategy That Puts Patients First

    A Powerful Strategy That Puts Patients First We focus on genetically validated targets/pathways that are either undrugged or inadequately drugged, where TPD is the best or the only solution With a growing understanding of the underlying biology and many key pathways/targets validated by biologics, I

  68. Slide 68: Revolutionizing Immunology with Small Molecule Oral Degraders

    Revolutionizing Immunology with Small Molecule Oral Degraders IRAK4 (KT-474) STAT6 (KT-621) TYK2 (KT-294) SCAFFOLDING TRANSCRIPTION SCAFFOLDING KINASE FACTOR KINASE Status • Phase 2 Trials in HS and AD • IND-Enabling • IND-Enabling with Sanofi Potential • AD, Asthma, COPD, CRSwNP, • IBD, PsO, PsA, L

  69. Slide 69: Kymera Immunology Oral Degrader Portfolio

    Kymera Immunology Oral Degrader Portfolio Complementary Mechanisms Each with Mega-blockbuster Potential Market Opportunity (2022 Sales) $1B $8B $2B $10B $16B $12B IRAK41: IL-1R/TLR pathway $28B Th1/17/Th2 biology $19B $16B HS SLE IL-4/13 pathway STAT6: Th2 biology AD Asthma TYK2: IL-23/IFN pathway C

  70. Slide 70: Immunology Pipeline with Clear Line of Sight to Large Value Creation

    Immunology Pipeline with Clear Line of Sight to Large Value Creation Potential 2024 2025 2026+ Upcoming Milestones Rights Indications Oral QD Small Molecule Degraders HS, AD, RA, HS Ph2 HS Late Development IRAK4* Ph2 HS & AD Data Asthma, 1H 2025 KT-474 IBD, other1 AD Ph2 AD Late Development 50/50 US

  71. Slide 71: Pipeline with Clear Line of Sight to Large Value Creation

    Pipeline with Clear Line of Sight to Large Value Creation Potential 2024 2025 2026+ Upcoming Milestones Rights Indications Immunology – Oral QD Small Molecule Degraders IRAK4* HS, AD, RA, HS Ph2 HS Late Development Ph2 HS & AD Data Asthma, 1H 2025 KT-474 IBD, other1 AD Ph2 AD Late Development 50/50

  72. Slide 72: 2024 Priorities

    2024 PRIORITIES • Completion of enrollment in IRAK4 oral degrader KT-474 Phase 2 trials in HS and AD by partner Sanofi (topline data 1H 2025) • Initiation of oral STAT6 degrader KT-621 Phase 1 • IND ready for oral TYK2 degrader KT-294 • Additional oncology proof-of-concept data for the STAT3 degrade

  73. Slide 73: Thank You Q&A

    Thank You Q&A investors@kymeratx.com media@kymeratx.com KYMERA THERAPEUTICS 200 Arsenal Yards Blvd., Suite 230 Watertown, MA 02472

  74. Slide 74: Abbreviations

    Abbreviations Ab Antibody FIH First-in-Human KO Knockout AD Atopic Dermatitis GDF15 Growth Differentiation Factor 15 LGL-L Large Granular Lymphocytic Leukemia AN Count Abscess and Inflammatory Nodule Count GI Gastrointestinal LOF Loss of Function CAGR Compound Annual Growth Rate GOF Gain of Function

  75. Slide 75: Abbreviations

    Abbreviations PsO Psoriasis UC Ulcerative Colitis pSTAT Signal Transducer and Activator of Transcription US United States PTCL Peripheral T-Cell Lymphoma vIGA Validated Investigator Global Assessment for AD QD Once a day WT Wildtype QoL Quality of Life WW Worldwide R&D Research and Development RA Rh

Kymera Therapeutics — Investor Day (January 2024) on 6ix