Kymera Therapeutics, Inc. · NASDAQ:KYMR

Kymera Therapeutics — Investor Day (December 2021)

105 slides from Kymera Therapeutics's investor day presentation, Dec 16, 2021

1. Slide 1: Kymera 2021 R&D Day

   Kymera 2021 R&D Day December 16, 2021 KYMERA R&D DAY - December 16th, 2021

2. Slide 2: Forward-looking Statements

   Forward-looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA) and other federal securities laws. These statements include information about our current and future prospects and our operations and fi

3. Slide 3: Kymera 2021 R&D Day - Nello Mainolfi

   Kymera 2021 R&D Day Nello Mainolfi, Ph.D., Founder, President and CEO , Kymera KYMERA R&D DAY - December 16th, 2021

4. Slide 4: Proteome Editing is the New Frontier of Medicine

   Proteome Editing is the New Frontier of Medicine Genome Proteome Essentially static Changes based on internal (genetic) and external Encodes (epigenetic) events Alterations are Alterations are responsible responsible for some for all diseases diseases Editing is irreversible Editing is reversible ©2

5. Slide 5: Proteome Editing with Targeted Protein Degradation

   Proteome Editing with Targeted Protein Degradation A Nobel Prize (2004) Inspired Technology Targeted Small Expanded Opportunities Disease-causing Molecule 1 Target Protein 2 Protein Degraders • Small molecule binds to E3 and target protein to effect its degradation Degrader • Small Molecule only nee

6. Slide 6: Expanding Druggable Proteome with Targeted Protein Degradation

   Expanding Druggable Proteome with Targeted Protein Degradation All therapeutic Undrugged Opportunity Cell/Gene Therapy modalities to date Drugged Traditional Small only drug up to 20% Molecule Antibody Antisense of proteome RNAi Kymera is expanding the drugged proteome with Targeted Protein Degradat

7. Slide 7: Exponential Clinical Pipeline Growth of Degraders

   Exponential Clinical Pipeline Growth of Degraders Targeted Protein Degradation Drugs FDA Drugs in Clinical Approved Development Degraders 4 >15 Existing Modalities 2010 2020 2030 Therapeutic Modality Drugs FDA Approved • Elucidation of MOA of thalidomide circa 2010 Small molecule inhibitor >2000 has

8. Slide 8: Today's Speakers

   Today’s Speakers Bruce Nello Jared Naimish Ashwin Juliet Chris Jacobs, CFA, MBA Mainolfi, PhD Gollob, MD Patel, MD Gollerkeri, MD Williams, PhD De Savi, PhD CFO Founder, President CMO SVP, Head of Global SVP, Head of SVP, Head VP, Head of Drug and CEO Development, Development of Biology Discovery Im

9. Slide 9: Today's Agenda

   Today’s Agenda Introduction to Kymera Nello Mainolfi, Ph.D. Founder and Chief Executive Officer, Kymera Clinical Stage Pipeline • IRAK4 Degrader KT-474 Ph1 HV study: SAD/MAD data Jared Gollob, M.D., Chief Medical Officer, Kymera • KT-474 Development in Immuno-inflammatory Diseases Naimish Patel, M.D

10. Slide 10: Our Vision

    OUR VISION is to be a disease- and technology-agnostic, fully integrated global biopharmaceutical company, using targeted protein degradation to deliver medicines that will transform patients’ lives ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 10

11. Slide 11: Introduction to Kymera

    Introduction to Kymera • Leader in Targeted Protein Degradation (TPD) • Building a fully-integrated, global biotech company • Initial focus in Immunology/Inflammation and Oncology, but already a disease-agnostic platform • Accelerating forward integration through key strategic partnerships • Establi

12. Slide 12: Kymera's Pipeline of Novel Protein Degraders

    Kymera’s Pipeline of Novel Protein Degraders Pathway Program Indication(s) Discovery IND Enabling Phase 1 Phases 2/3 Next Milestone Rights* Multiple Immuno- Patients POB KT-474 IRAK4 inflammatory Diseases: mid-22 HS, AD, RA Multiple molecules staged as others potential back ups if needed IL-1R/TLR I

13. Slide 13: Kymera's Differentiated Approach to TPD

    Kymera’s Differentiated Approach to TPD TARGET TPD INNOVATION PLATFORM CLINICAL SELECTION “FIRSTS” Unique approach Significantly Innovative clinical Kymera has Serious focused on differentiated trial designs for accomplished several commitment to undrugged or not investments degrader “firsts” in TPD

14. Slide 14: Our People & Culture

    Our People & Culture To build a thriving, high-performing and diverse organization that enables leaders and teams to do their best work every day and propels us to boldly innovate and transform treatment paradigms for serious diseases Differentiated Experience We fully engage our people by creating

15. Slide 15: Our First 5 Years, a Foundation for the Future

    Our First 5 Years, a Foundation for the Future Drug Development First First In Vitro First Novel First Transcription Third Degradation of First In Vivo E3 DC First FIRST FIRST Factor Cleared IND Founded Novel Target Degradation Degradation KT-474 IND POM POB Degrader IND in 2021 2016 2017 2018 2019

16. Slide 16: R&D Day Objectives

    R&D Day Objectives • Why TPD is uniquely poised to transform treatment paradigms • Who we are and what we have accomplished so far • Rationale for our strategy and approach to TPD • Power of the Kymera drug development engine • What we have delivered in 2021 • How we are evolving our pipeline, our p

17. Slide 17: Clinical Pipeline

    Clinical Pipeline KYMERA R&D DAY - December 16th, 2021

18. Slide 18: Agenda

    Agenda • IRAK4 Degrader KT-474 Ph1 HV study: SAD/MAD data • IRAKIMiD Degrader KT-413 Update and Clinical Plans • STAT3 Degrader KT-333 Update and Clinical Plans • STAT3 Degraders in Immune-inflammation and Fibrosis ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 18

19. Slide 19: Safety, PK and PD from SAD and MAD Dose Portion of KT-474 Phase 1

    Safety, PK and PD from SAD and MAD Dose Portion of KT-474 Phase 1 Trial in Healthy Volunteers Jared Gollob, M.D., Chief Medical Officer, Kymera KYMERA R&D DAY - December 16th, 2021

20. Slide 20: IRAK4 Targeting: Degrader Advantage, Clinical Validation, Human Genetics

    IRAK4 Targeting: Degrader Advantage, Clinical Validation, and Human Genetics De-risking IL-1R/TLR Pathway Degrader Advantage secreted Inhibitor signaling IL-1α/β, IL-18, TNF-α, IFN-γ, IRAK4 IL-33, IL-36 IL-1β, IL-6, Scaffolding Kinase IL-8, IL-10, Role Role IL-12, IL-17, TLRs IL-23 (TLR 2,4,5,7,8,9)

21. Slide 21: Development Opportunities for IRAK4 Degrader in Inflammation

    Development Opportunities for IRAK4 Degrader in Inflammation Potential for Broad Activity Across Th1-Th17 and Th2 Diseases 2021 Prevalence Indication 2021 Global Sales US/EU5/JP KT-474 AD ~82.5 M $5,760 M HS ~785 K $1,106 M RA ~385 K $27,634 M SLE ~580 K $1,333 M IBD ~3.2 M $21,710 M Gout ~18.2 M $1

22. Slide 22: IRAK4 Protein Expression in Autoimmune Diseases

    IRAK4 Protein Expression in Autoimmune Diseases Upregulation in Skin of HS Patients Compared to Healthy Subjects IRAK4 protein levels overexpressed in IRAK4 expression is upregulated in dermis and epidermis of HS patients relative HS patient skin lesions to healthy subject skin Dermal Immune Cells I

23. Slide 23: Proinflammatory Transcripts Upregulated and Correlate with IRAK4 in HS Skin

    Multiple Proinflammatory Transcripts Are Upregulated and Correlate with IRAK4 Protein Levels in HS Skin Lesions • Upregulation of TLRs, IL-1β/IL-36, MYD88, and multiple additional drivers of inflammation that all correlate with IRAK4 protein expression • Highlights potential of IRAK4 targeting to tr

24. Slide 24: KT-474: Potent and Specific IRAK4 Degradation Superior to Kinase Inhibition

    KT-474: Potent and Specific IRAK4 Degradation with Impact on Cytokines Superior to Kinase Inhibition Degradation and Selectivity Superiority over SM kinase Inhibitor 10xDC90 24hr • KT-474 DC50 = 2.1 nM in LPS + IL-1β  IL-6 3 human immune cells 2.5 • KT-474 only degraded IRAK4 in human immune cells

25. Slide 25: KT-474 Superior to IRAK4 Inhibitor Across Preclinical Models

    KT-474 is Superior to IRAK4 Small Molecule Inhibitor (SMI) Across Multiple Preclinical Immune-inflammatory In Vivo Models rmIL-33 Intradermal rhIL-36αβγ Intradermal Th17-mediated Multiple Challenge Model Challenge Model Sclerosis Model In vivo IRAK4 IL-5 in In vivo IRAK4 In vivo IRAK4 Ear Degradatio

26. Slide 26: KT-474 Phase 1 Trial Design Includes HV and Patients

    KT-474 Phase 1 Trial Design Includes HV and Patients Double-blind, Placebo-controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) trial Endpoints Three-part Phase 1 Design Primary • Safety & tolerability Secondary/ 1 2 3 • Pharmacokinetic measures Exploratory (half-life, bioavaila

27. Slide 27: SAD/MAD Enrollment Status and Demographics

    SAD/MAD Enrollment Status and Demographics SAD 1-7 (n=57) MAD 1-4 (n=48) Gender, n Female 29 9 Male 28 39 Median age, years (range) 38.0 (20-55) 37.5 (20-55) Ethnicity • Hispanic or Latino 42 34 • Black or African American 8 8 • Non-Hispanic or Latino- White 5 6 • Asian 2 0 ©2021 KYMERA THERAPEUTICS

28. Slide 28: KT-474 Achieved >95% IRAK4 Degradation After Single Dose

    KT-474 Achieved >95% IRAK4 Degradation After Single Dose Percent IRAK4 Reduction in PBMC at 48 Hours Post-Dose Using Mass Spectrometry Median Mean IRAK4 N IRAK4 p value Change Change Placebo 13 -1% -2% -- 25 mg 6 -26% -39% 0.1 75 mg 6 -73% -75% <0.0001 150 mg 6 -81% -82% <0.0001 300 mg 6 -84% -89% <

29. Slide 29: Ex Vivo Cytokine Stimulation Methodology

    Ex Vivo Cytokine Stimulation: Methodology in KT-474 Phase 1 Trial Impact of KT-474 on TLR- stimulated Cytokine/Chemokine 1 2 3 4 Production Blood Draw Overnight Plasma Cytokine/Chemokine Cytokines/Chemokines Pre-/Post-Dose Incubation Isolation Measurement (37°) TNF-α, IFN-γ, TLRs IL-1β, IL-6, IL-8,

30. Slide 30: Broad and Deep Inhibition of Disease Relevant Cytokines

    Broad and Deep Inhibition of Disease Relevant Cytokines Effect Against LPS (TLR4)- or R848 (TLR7/8)-Stimulated Cytokine Induction in Whole Blood LPS R848 Placebo (n = 14) SAD 63 (n = 6) SAD 73 (n = 6) IFNγ IL1β IL6 IL8 IL10 IL12 IL17 IL23 TNFα IFNγ IL1β IL6 IL8 IL10 IL12 IL17 TNFα Pbo 80% 27% 16% 19

31. Slide 31: KT-474 Demonstrates Broadest Anti-inflammatory Effect

    KT-474 Demonstrates Broadest Anti-inflammatory Effect Compared to Other Clinical Agents Inhibition of Ex Vivo Disease Relevant Cytokine/Chemokine Stimulation by Anti-Inflammatory Agents in Ph1 Studies Agent/Stimulus Target IFNγ TNFα IL-1β IL-6 IL-8 IL-17 IL-12 IL-23 IL-10 KT-474/LPS IRAK4 (degrader)

32. Slide 32: Blinded SAD Safety Summary

    Blinded SAD Safety Summary n=8 per cohort (6 drug/2 placebo) Possibly or Probably Treatment-Related AEs* • No SAEs (>1 Subject) • Treatment-related AEs AE Term #Subjects Severity Cohort observed only in SAD 5 and SAD 6; all were self-limiting and Moderate SAD 5, SAD 6 resolved (x2) Headache 4 • No t

33. Slide 33: MAD Study: Once Daily Dosing Resulted in High Steady-State Exposures

    MAD Study: Once Daily Dosing Resulted in High Steady-State Exposures Steady-State (Day 14) PK Parameters 25 mg QD 50 mg QD 100 mg QD 200 mg QD PK Parameter (n = 9) (n = 9) (n = 9) (n = 9) Cmax (ng/mL) 8.20 (34.5) 12.0 (39.1) 16.1 (32.0) 25.2 (26.7) 8.00 8.00 8.00 8.00 tmax (h)a (4.0 – 8.0) (8.0 – 8.

34. Slide 34: Near Complete and Sustained IRAK4 Degradation with Multiple Daily Doses

    KT-474 Achieved Near Complete and Sustained IRAK4 Degradation with Multiple Daily Oral Doses (14 Days) Absolute IRAK4 Levels Mean % Reduction of IRAK4 * * * Data beyond day 14 pending • Detected by mass spectrometry in circulating PBMC • Steady state IRAK4 reduction achieved between Days 7 and 14 •

35. Slide 35: Lower Daily Doses Achieved >98% IRAK4 Degradation

    Lower Daily Doses of KT-474 Achieved >98% IRAK4 Degradation (MS) Plateau in IRAK4 Reduction after 14 days in PBMC after 100 mg Percent IRAK4 Reduction in PBMC by Mass Spectrometry Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD (n=12) (n=9) (n=9) (n=9) (n=

36. Slide 36: KT-474 Achieved >90% Degradation in Monocytes

    KT-474 Achieved >90% Degradation in Monocytes at ≥ 100 mg (FLOW) Maximal Degradation in Monocytes in MAD4/200mg at Day 14 Percent IRAK4 Reduction in Lymphocytes Percent IRAK4 Reduction in Monocytes Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD Placebo 25 mg QD 50 mg QD 100 mg QD 200 mg QD Placebo 25

37. Slide 37: High Skin Exposures Exceeding Plasma

    Once Daily Dosing (14 Days) Resulted in High Skin Exposures Exceeding Plasma KT-474 Levels in Skin Substantially Larger Skin vs Plasma Exposures at Ctrough ng/mL (plasma) 25 mg QD 50 mg QD 100 mg QD 200 mg QD ng/g (skin) (n=9) (n=9) (n=9) (n=9) • Increasing exposures through Day 14 Plasma Day 7 3.21

38. Slide 38: KT-474 Reduced IRAK4 to Near LLOQ in the Skin

    KT-474 MAD4/200mg Reduced IRAK4 to Near LLOQ in the Skin (MS) IRAK4 Levels in Skin vs PBMC at Day 14 Absolute IRAK4 Levels in Skin of KT-474 treatment Baseline levels 5- to 10- fold lower than PBMC * LLOQ LLOQ * Data beyond day 14 pending • Baseline IRAK4 levels in skin substantially lower compared

39. Slide 39: Substantial IRAK4 Degradation in Dermis and Epidermis

    Substantial IRAK4 Degradation in Skin Observed in Dermis and Epidermis IRAK4 = Red Epidermis Dermis Predose Day 14 Day 28 (recovery) Pan cytokeratin (panCK) is used as the epidermal marker Representative images from subject in 50 mg cohort ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16

40. Slide 40: Ex Vivo Inhibition of Disease-Relevant Cytokines, Day 7-14

    Ex Vivo Inhibition of 9 Disease-Relevant Cytokines, Day 7-14 Results through MAD3 Showed Dose-Dependent Effect Tracking with Extent of Monocyte IRAK4 Degradation LPS R848 Placebo (n = 9) 50 mg QD (n = 9) 100 mg QD (n = 8-9*) IFNγ IL1β IL6 IL8 IL10 IL12 IL17 IL23 TNFα IFNγ IL1β IL6 IL8 IL10 IL12 IL17

41. Slide 41: Blinded MAD Safety Summary

    Blinded MAD Safety Summary n=12 per cohort (9 drug/3 placebo) Possibly or Probably Treatment-Related AEs* (>1 Subject) AEs #Subjects Severity Cohort Moderate, • No SAEs MAD2 Mild • Treatment-related AEs Headache 6 Mild MAD 3 were self-limiting and Mild (x3) MAD 4 resolved MAD 2, • No ECG changes, Pa

42. Slide 42: Summary of Phase 1 KT-474 SAD/MAD

    Summary of Phase 1 KT-474 SAD/MAD • Healthy volunteer SAD dose escalation completed; MAD enrolled through Cohort 4 (200 mg), with proof of mechanism (IRAK4 degradation) and proof of biology (broad inhibition of cytokine induction) established in SAD and at substantially lower doses in MAD • Marked r

43. Slide 43: KT-474 Development in Immuno-inflammatory Diseases

    KT-474 Development in Immuno-inflammatory Diseases Naimish Patel, M.D. - SVP, Head of Global Development, Immunology and Inflammation, Sanofi Genzyme KYMERA R&D DAY - December 16th, 2021

44. Slide 44: Naimish Patel

    Naimish Patel Global Head of Development, Immunology & Inflammation

45. Slide 45: Sanofi's approach to R&D

    Sanofi's approach to R&D Pathways Patients Platforms Deep understanding Relentless Expanded tools for of disease pathways patient focus drug discovery Expanding capabilities 45

46. Slide 46: Sanofi - Rich Immunology portfolio extending to other TAs

    Sanofi - Rich Immunology portfolio extending to other TAs Dermatology Respiratory GI Rheumatology Hematology Neurology Oncology Dupixent® Dupixent® Dupixent® Kevzara® Sutimlimab Aubagio® Libtayo® *Bispecific Amlitelimab(2) Itepekimab Rilzabrutinib Rilzabrutinib Tolebrutinib Sarclisa® NANOBODY® Anti-

47. Slide 47: IRAK4 is a key initiator of Type 2 and Type 17 inflammation

    IRAK4 is a key initiator of Type 2 and Type 17 inflammation of mucosal tissues via TLRs and IL-1 family receptors Upstream initiation Tissue effects Downstream effects Activation Amplification Maladaptation Asthma Virus Bacteria Allergens Epithelial Injury COPD Differentiation IL-5 in bone marrow Eo

48. Slide 48: First-in-class IRAK4 oral protein degrader SAR444656 or KT-474

    First-in-class IRAK4(1) oral protein degrader SAR444656 or KT-474 Potent inhibition of pNFkB in PBMC NF-kB S536 Kinase 33 Negative Inhibitor Log2(stim./unstim.) Degrader Control pNFkB (S536) (SAR444656) Avg (log2ratio) 22 • Degradation of IRAK4 protein TLRs IL1/IL18/IL33/IL36 ** abolishes its kinase

49. Slide 49: IRAKIMiD Degrader KT-413 Update and Clinical Plans

    IRAKIMiD Degrader KT-413 Update and Clinical Plans Ashwin Gollerkeri, M.D., SVP, Head of Development, Kymera KYMERA R&D DAY - December 16th, 2021

50. Slide 50: IRAKIMiDs are Potent Degraders of IRAK4 and IMiD Substrates

    IRAKIMiDs are Potent Degraders of IRAK4 and IMiD Substrates Targeting Redundant Pro-survival Pathways in MYD88MT DLBCL • Single-agent therapies that target activated NFκB Autoantigens signaling in DLBCL show limited activity in preclinical TLRs IL-1R B Cell Receptor or clinical settings IFNAR1/2 • R

51. Slide 51: IRAKIMiD: First Precision Medicine in MYD88 Mutated Cancers

    IRAKIMiD: First Precision Medicine in MYD-88 Mutated Cancers Patient Impact1 • MYD88 is mutated in ≥ 25% of DLBCL patients, the most common subtype of non-Hodgkin’s lymphoma ~8k US • DLBCL 5-year survival rate is ~64%, and MYD88 mutations are associated with poorer survival following frontline R-CHO

52. Slide 52: KT-413 Potent Degrader with Activity in MYD88MT Cell Lines

    KT-413 is a Potent Degrader of IRAK4 and IMiD Substrates with Potent Activity in MYD88MT Cell lines • KT-413 selectively degrades KT-413 both IRAK4 and IMiD IRAK4 DC50 = 6 nM substrates which leads to a OCI-Ly-10 Ikaros DC50 = 2 nM (MYD88MT DLBCL) profound antitumor effect in EC50 = 1 nM vitro and i

53. Slide 53: KT-413 is Highly Active on Intermittent Dosing Regimens

    KT-413 is Highly Active on Intermittent Dosing Regimens Superior Anti-tumor activity OCI-Ly-10 Tumor Volume • In the OCI-LY10 MYD88MT xenograft model, intermittent dosing of KT-413 induced strong antitumor activity, including Drug (day 33) T/C% CR PR SD PD (REG%) complete or partial regressions. CA-

54. Slide 54: KT-413 Strong Activity in Combination in OCI-Ly10 Xenografts

    KT-413 Has Strong Activity in Combination in MYD88MT OCI-Ly10 Xenografts with BTK Inhibitor with BCL-2 Inhibitor with Rituxan • KT-413 administered on • KT-413 administered on • KT-413 administered on intermittent schedules leads intermittent schedules leads intermittent schedules leads to strong re

55. Slide 55: KT-413: Clinical Study Design and Objectives

    KT-413: Clinical Study Design and Objectives Phase 1a Phase 1b Key Eligibility Criteria: Dose Escalation & MTD/RP2D Dose Expansion R/R B-cell lymphoma Expansion • ≥ 2 prior systemic regimens • Ineligible or refused CAR-T or MyD88MT DLBCL ASCT MTD/RP2D ≥2 prior regimens DLx Expansion Primary Objectiv

56. Slide 56: KT-413 Registration Strategies

    KT-413 Registration Strategies Phase 2 open label study patients First US Approval (Accelerated) 3rd Line R/R MYD88mut Phase 3 randomized KT-413 DLBCL in combo vs SOC Second US Approval (Full) Waldenstrom’s: 2nd Line R/R MYD88mut 1st (AA) Approval: DLBCL + SOC Phase 2 open label 2nd (Full) approval:

57. Slide 57: KT-413 Potential to be First Precision Medicine in DLBCL

    IRAKIMiD Degrader KT-413 has Potential to be First Precision Medicine in DLBCL to Target a Genetically-defined Population (MYD88MT) • Profound antitumor activity in preclinical models both in single agent and combination • Clinical strategy in place to enable accelerated approval: Monotherapy • MYD8

58. Slide 58: STAT3 Degrader KT-333 Update and Clinical Plans

    STAT3 Degrader KT-333 Update and Clinical Plans Ashwin Gollerkeri, M.D., SVP, Head of Development, Kymera R&D Day KYMERA R&D DAY - December 16th, 2021 December 16, 2021

59. Slide 59: STAT3 Has Unique Tumor Cell Intrinsic and Extrinsic Mechanisms

    STAT3 Has Unique Tumor Cell Intrinsic and Extrinsic Mechanisms Survival, proliferation, Tumor Cell Intrinsic STAT3 as a Target EMT, stemness • Hyperactivation of STAT3 via either Cytokine Growth Factor Adrenergic receptor signaling, or hotspot mutations Receptor Receptor Receptor Cancer promotes gen

60. Slide 60: First-in-class Opportunity to Address STAT3-driven Pathology

    First-in-class Opportunity to Address STAT3-driven Pathology Across Diverse indications Patient Impact (Global)1 • Abnormal activation of JAK/STAT pathway occurs in nearly all T-cell Peripheral T-cell ~13k US lymphomas • STAT3 is most frequent mutation among JAK/STAT pathway Lymphoma (PTCL) ~27k ROW

61. Slide 61: KT-333 Demonstrates Highly Selective Degradation of STAT3

    KT-333 Demonstrates Highly Selective Degradation of STAT3 Change in Protein Levels 10× DC95 at 8h in SU-DHL-1 • Deep mass spectrometry-based proteomics to assess STAT3 selectivity performed • In hPBMC and SU-DHL-1 cancer line (shown), treatment with KT-333 degrader led to selective degradation of on

62. Slide 62: Full and Durable Regressions Across Preclinical Tumor Models

    Full and Durable Regressions Across Multiple in vivo Preclinical Tumor Models • Mice bearing STAT3- SU-DHL-1 SUP-M2 dependent ALK+ ALCL SU- Weekly Dosing Weekly Dosing DHL-1 or SUP-M2 tumor xenografts dosed with STAT3 degrader • Dose- and degradation dependent tumor growth inhibition observed with o

63. Slide 63: STAT3 Degrader Sensitization of Tumors to Anti PD-1

    STAT3 Degrader’s Role in Immuno-Oncology: Sensitization of Tumors to Anti PD-1 IFNγ-dependent Gene Signature Induced by STAT3 STAT3 Degradation and Anti-PD-1 Synergy Degrader Monotherapy in CT-26 Tumors • KTX-201 synergizes with anti-PD-1 leading to 60% complete responses in CT- 26 model CT-26: Veh

64. Slide 64: KT-333: Clinical Study Design and Objectives

    KT-333: Clinical Study Design and Objectives Phase 1a Key Eligibility Criteria: Phase 1b Dose Escalation & MTD/RP2D R/R B-cell lymphoma Dose Expansion • ≥ 2 prior systemic regimens Expansion • Ineligible or refused CAR-T or ASCT PTCL Advanced solid tumors MTD/RP2D ≥1 prior systemic regimens • ≥ 2 pr

65. Slide 65: KT-333 Accelerated and Full Approval Strategies

    KT-333 Accelerated and Full Approval Strategies Across Several Indications ≥2nd Line R/R PTCL Solid Tumor (or CTCL)- LGL-L KT-333 monotherapy CRC MSI-H (e.g.) – PD1 KT-333 monotherapy inhibitor refractory KT-333 + PD1 inhibitor First US Approval FULL Approval [Accelerated] (Phase 2 single arm study)

66. Slide 66: STAT3 Degrader KT-333, First-in-class Opportunity

    STAT3 Degrader KT-333, First-in-class Opportunity to Address STAT3-driven Pathology Across Diverse Indications • First heterobifunctional degrader against an undrugged target in the clinic • Profound single agent activity in liquid tumor and promising combo activity with anti-PD1 in liquid and solid

67. Slide 67: STAT3 Degraders in Immune-Inflammation and Fibrosis

    STAT3 Degraders in Immune-Inflammation and Fibrosis Ashwin Gollerkeri, M.D., SVP, Head of Development, Kymera KYMERA R&D DAY - December 16th, 2021

68. Slide 68: Role of STAT3 in Inflammatory Processes

    Role of STAT3 in Inflammatory Processes Leukocyte Recruitment and • STAT3 is activated by multiple tyrosine kinases Retention and plays a critical role in the signaling of Endothelial Leukocyte Activation cytokines, hormones, and growth factors​ Activation including IL-6, IL-21, IL-11, OSM, TGF-β, V

69. Slide 69: STAT3 Degraders in Serious Inflammatory and Fibrotic Diseases

    STAT3 Degraders Have Applicability in Serious Inflammatory and Fibrotic Diseases Patient Impact1 Fibrosis / Interstitial Lung Disease ~85k US • Increased STAT3 and pSTAT3 observed in SSc skin and lung biopsies Systemic Sclerosis • Aberrant IL6/JAK/STAT3 gene signature in biopsies from SSc patients (

70. Slide 70: STAT3 Degraders Reduce Disease in Fibrosis, Arthritis and CNS Models

    Our STAT3 Degraders Robustly Reduce Disease in Models of Systemic Sclerosis, Arthritis and CNS Inflammation In Vivo Tight Skin Model (Fibrosis) In Vivo CIA Model (RA) In Vivo MS Model TSK ± Mice (BIW Dosing) Collagen-induced Experimental Autoimmune Arthritis (BIW Dosing) Encephalomyelitis (BIW Dosin

71. Slide 71: Program will continue following a short break

    Program will continue following a short break

72. Slide 72: Discovery Pipeline Principles

    Discovery Pipeline Principles Juliet Williams, Ph.D., SVP, Head of Biology, Kymera KYMERA R&D DAY - December 16th, 2021

73. Slide 73: How We Select Our Targets

    How We Select Our Targets Drug Development Target Types Therapeutic Profile Philosophy Oncology: Inadequately Drugged • Clear patient stratification Unmet Targets with Clear • Clear single agent activity with potential ID Medical Degrader Advantage for expansion with combos Need e.g. IRAK4 • Multipl

74. Slide 74: Kymera's Roadmap to Deliver ≥1 IND per Year

    Kymera’s Roadmap to Deliver ≥ 1 IND per Year Strategy Program Asset(s) 2021 2022 2023 2024 2025 2026 IRAK4 KT-474 IND ID Inadequately IRAKIMiD KT-413 IND Drugged MDM2 KT-253 IND 2-3 new targets per year - Multi-IND Potential STAT3 KT-333 IND UN Undrugged 2-4 new targets per year - Multi-IND Potentia

75. Slide 75: KT-253, a First-in-Class MDM2 Degrader

    KT-253, a First-in-Class MDM2 Degrader in Development for Solid and Liquid Tumors Juliet Williams, Ph.D., SVP, Head of Biology, Kymera KYMERA R&D DAY - December 16th, 2021

76. Slide 76: MDM2 is the E3 Ligase that Modulates p53

    MDM2 is the E3 Ligase that Modulates P53, the Largest Tumor Suppressor Stressors Cancer Genetics DNA • p53 is NOT mutated in almost 50% of Damage Hypoxia Oncogenes Other tumors • MDM2 overexpression and amplification can ub inactivate p53 ub ub • Large opportunity in wide variety of cancers p53 MDM2

77. Slide 77: MDM2 Degradation, Not Inhibition, Efficiently Restores p53

    MDM2 Degradation, Not Inhibition, Efficiently Restores p53 Stressors Clinical Validation DNA Damage Hypoxia Oncogenes Other • MDM2 small molecule inhibitors of MDM2/p53 interaction show activity in the clinic.. Inhibitor ub ub • …but they induce MDM2 feedback loop ub resulting in limited impact on p

78. Slide 78: KT-253 is Superior to MDM2/p53 Small Molecule Inhibitors

    Kymera’s MDM-2 Degrader Development Candidate, KT-253 is Superior to MDM2/p53 Small Molecule Inhibitors KT-253 is a potent MDM2 degrader KT-253, unlike SMI’s such as DS- … which leads to superior 3032, strongly stabilizes p53… tumor cell killing (pM range) MDM2-HiBiT p53 MSD, 2h RS4;11, 24h CTG Comp

79. Slide 79: KT-253 Overcomes the MDM2 and p53 Feedback Loop

    KT-253, Unlike Small Molecule Inhibitors, Overcome the MDM2 and p53 Autoregulatory Feedback Loop Degrader Overcomes MDM2 Feedback Loop KT-253, IC90 0h 24h DMSO 2h 4h 24h DMSO Inhibitor ub ub MDM2 ub p53 ACTB MDM2 p53 Degradation MDM2 levels are kept at undetectable levels with MDM2 degrader KT-253,

80. Slide 80: Short Term Exposure to MDM2 Degrader Commits Cells to Apoptosis

    Short Term Exposure to MDM2 Degrader, but not SMI, is Sufficient to Commit Cells to Undergo Apoptosis KT-253 DS-3032 Caspase Activity Treatment Washout 0h 4h 24h 48h P53 Levels Cells Allowed by MSD to Recover • 4 hr target coverage by KT-253 is sufficient to induce apoptosis in contrast to SMIs • Su

81. Slide 81: Single Dose of KT-253 Leads to Sustained Tumor Regression

    Single Dose of KT-253 Leads to Sustained Tumor Regression Single Dose of KT-253 Achieves MDM2 Degradation (KT-253, 1 mg/kg) Leads to Fast Increase Sustained Tumor Regression in p53, p21, and PUMA (Key Apoptotic Biomarker) Rs4;11 XGs p53 p21 PUMA • Clinical equivalent doses of small molecule inhibito

82. Slide 82: MDM2 Dependency Seen Across a Large Subset of Tumor Types

    MDM2 Dependency Seen Across a Large Subset of Tumor Types Large Franchise Potential in Liquid and Solid Tumors Dependency of p53WT Cell Lines MDM2 Degrader Superior to SMI on MDM2 Across Cell Line Panel 0.6 Heme & Solid Cell Lines 0.4 MDM2 CRISPR Sensitivity Score 0.2 0 -0.2 -0.4 -0.6 -0.8 -1 -1.2 -

83. Slide 83: Focus on Indications Where MDM2 Degradation Leads to Apoptosis

    Focus on Indications Where MDM2 Degradation Leads to Acute Apoptotic Response p53 WT in >50% MOA-specific MDM2 of Tumors Sensitivity Amplification • Mesothelioma (Biomarker-based) • Melanoma • DLBCL • AML • Liposarcoma (87%) • Prostate cancer • Uveal Melanoma • Sarcoma (19%) • Cholangiocarcinoma • L

84. Slide 84: KT-253 is a Potent MDM2 Degrader and Best-in-Class p53 Stabilizer

    KT-253 is a Potent MDM2 Degrader and a Best-in-Class p53 Stabilizer with Potential to Treat Numerous p53 WT Tumors • KT-253 inhibits tumor cell growth with picomolar potency and is more than 200-fold more potent than clinically active MDM2 small molecule inhibitors • KT-253, unlike small molecule in

85. Slide 85: Expanding the Drugged Proteome: Kymera's Platform

    Expanding the Drugged Proteome: Kymera’s Platform Chris De Savi, Ph.D., VP, Head of Drug Discovery, Kymera KYMERA R&D DAY - December 16th, 2021

86. Slide 86: Targeted Protein Degradation: Next Potential Breakthrough Modality

    Targeted Protein Degradation Next Potential Breakthrough Modality to Expand Drugged Proteome Targeted Protein Degradation Human Proteome Existing Modalities Undrugged Opportunity Drugged Cell/Gene Traditional Small Therapy Molecule Antibody Antisense RNAi Undruggable Targets ✓ Scaffold, transcript f

87. Slide 87: We Want to Drug All Target Classes

    We Want to Drug All Target Classes Expanding the Druggable Proteome with TPD Inadequately Drugged Clinically Validated Targets Undrugged Targets ID Targets with Clear UD No other technology can drug TR Enabled by E3 Ligase Tissue Degrader Advantage Restricted Expression Small molecule binders exist

88. Slide 88: Proprietary Pegasus TPD Platform

    Proprietary PegasusTM TPD Platform Key Capabilities DISCOVERY IMPACT BY TARGET TYPE • E3 ligase Whole-Body Atlas: Identification of the expression profiles of ~600 unique E3 ligases Expanded E3 • Match target protein with appropriate E3 ligase based on expression, distribution, intracellular Ligase

89. Slide 89: Novel E3 Ligases to Drug a New Generation of Targets

    Novel E3 Ligases to Drug a New Generation of Targets TR Clinically Validated Targets Unlocked by E3 Ligase Differential Expression On target unwanted pharmacology limits clinical application • Focused on determining the expression profiles of ~600 unique E3 ligases • Patterns mapped in both disease

90. Slide 90: Engaging a Broadly Expressed Protein in One Cell Type Using Tissue Selective E3

    Kymera has Engaged a Broadly Expressed Protein in Only One Cell Type Using a Tissue Selective E3 Ligase Kymera Has Identified an E3 Ligase Small Molecule Ligand Bound that is Expressed Almost to a Tissue-selective E3 Ligase Exclusively in One Cell Population Lead Compound Protein Expression Profile

91. Slide 91: Tissue-Selective Degradation Drives Increase of Therapeutic Index

    Tissue-Selective Degradation Drives Increase of Therapeutic Index In Cancer Cell • Kymera has Kymera’s degrader characterized an E3 ligase that is E3 Ligase is Almost using this E3 ligase degrades target in expressed broadly Absent in One cancer cells but NOT in ONE Blood Cell Type blood cell type B

92. Slide 92: A Comprehensive Hit Finding Toolbox

    A Comprehensive Hit Finding Toolbox Rapidly Enables New Ligand Discovery Against All Target Classes Fragment-Based Cysteine Covalent Virtual Screen DEL HTS ASMS Screen Screening Criteria Criteria Criteria Criteria Criteria Criteria • Availability of • High quality protein • Availability of high • Pr

93. Slide 93: Successful Examples of Fragment and Covalent Screens

    Successful Examples of Fragment and Covalent Screens Fragment Based Virtual Optimization Covalent Ligand E3 Ligase Hit Finding HTRF X-ray with Fragment Fragment bound IC50 > 1 mM X-ray structure Rational design to IC50 < 30 μM explore SAR X-ray with Optimized Ligand In silico library IC50 < 5 μM eva

94. Slide 94: Degraders with Predictable Drug-Like Properties

    Kymera Can Develop Degraders with Predictable Drug-Like Properties Pre-clinical Optimization of Degraders Leads to High Oral Bioavailability Across Pre-clinical Species Ternary Complex Modeling (TCM) Molecular Chameleonicity AI-driven Insights Harnessing the power of cloud Accurately capturing the c

95. Slide 95: Mechanistic Modeling Predicts Human PK and PD from Dog Data

    Mechanistic Modeling Allowed Kymera to Accurately Predict Human PK and PD from Preclinical Dog Data for Clinical Candidate KT-474 Mechanistic PK/PD Modeling Preclinical Species Models for PK/PD Model Predicts Human Describes the MoA of TPD KT-474 in Dog PK/PD ©2021 KYMERA THERAPEUTICS, INC. KYMERA R

96. Slide 96: Rationally Designing Molecular Glues

    Rationally Designing Molecular Glues to Drug Historically Undrugged/Unligandable Targets To drug all genetically validated but undrugged and un-ligandable proteins through the discovery of novel E3 ligases and small molecule glues Undrugged Targets Our Approach: UD No other technology can drug • We

97. Slide 97: Expanding the Druggable Proteome with TPD

    Expanding the Druggable Proteome with TPD • Kymera intends to drug all target classes using targeted protein degradation • A comprehensive hit finding toolbox with key AI and machine learning inputs has been developed to identify ligands against novel E3 and undrugged targets • Our capabilities have

98. Slide 98: Kymera 2026 Vision

    Kymera 2026 Vision Nello Mainolfi, Ph.D., Founder and CEO, Kymera KYMERA R&D DAY - December 16th, 2021

99. Slide 99: What We Showed You Today

    What We Showed You Today • Our first 5 years; pipeline and platform investments • Three compelling clinical programs with large franchise potential: • IRAK4, KT-474 – Ph1 data de-risks profile for best-in-class oral drug in broad immune-inflammatory indications • IRAKIMiD, KT-413 – Potential for fir

100. Slide 100: Kymera's Pipeline Today

     Kymera’s Pipeline Today Pathway Program Indication(s) Discovery IND Enabling Phase 1 Phases 2/3 Next Milestone Rights* Multiple Immuno- Patients POB KT-474 IRAK4 inflammatory Diseases: mid-22 HS, AD, RA Multiple molecules staged as others potential back ups if needed IL-1R/TLR IRAKIMiD (IRAK4, Ikaro

101. Slide 101: What We Expect in 2022

     What We Expect in 2022 • Completion of Ph1 patient cohort for KT-474 and transition to Sanofi • Proof of mechanism in patients for KT-413 and KT-333 oncology Ph1 studies • IND filing for KT-253 • First tissue restricted E3 ligase enabled program in development • Continued growth of team and capabili

102. Slide 102: Our 5-year Vision: Where Kymera Will Be in 2026

     Our 5-year Vision: Where Kymera Will Be in 2026 A fully-integrated biotech company with a disease and technology agnostic pipeline and capabilities Path to NDA At least 8 clinical Pipeline Clinical proof-of-concept for at least 1 stage programs positioned to established in tissue- program across dif

103. Slide 103: What Kymera's Clinical Pipeline Could Look Like in 2026

     What Kymera’s Clinical Pipeline Could Look Like in 2026 Pathway Program Indication(s) Discovery IND Enabling Phase 1 Phases 2/3 Rights* HS, AD, RA IRAK4 others KT-474 IL-1R/TLR IRAKIMiD MYD88MT DLBCL, (IRAK4, Ikaros, Aiolos) Waldenstrom’s, others KT-413 STAT3 Liquid & Solid Tumors KT-333 JAK/STAT Au

104. Slide 104: What We Hope You Will Take from Today

     What We Hope You Will Take from Today • Targeted Protein Degradation is positioned to transform drug development landscape • Kymera is a medicine focused company with recognized leadership in TPD • We employ a novel and differentiated scientific strategy and approach around target selection, drug de

105. Slide 105: Thank you Q&A

     Thank you Q&A ©2021 KYMERA THERAPEUTICS, INC. KYMERA R&D DAY - December 16th, 2021 PAGE 105

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