Kymera Results Presentation Deck

Made public by

sourced by PitchSend

28 of 68

Creator

Kymeratx logo
Kymeratx

Category

Healthcare

Published

December 2022

Slides

Transcriptions

#1KT-474 HS and AD Clinical Data and Oncology Pipeline Update Company Webcast KYMERA December 14, 2022#2Forward-looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA) and other federal securities laws. These statements include information about our current and future prospects and our operations and financial results, which are based on currently available information. All statements other than statements of historical facts contained in this presentation, including express or implied statements regarding our strategy, future financial condition, future operations, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. 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 our strategy, business plans and objectives for our programs; plans and timelines for the clinical development of our product candidates, including the therapeutic potential, clinical benefits and safety thereof; expectations regarding timing, success and data announcements of current ongoing clinical trials; the ability to initiate new clinical programs; the initiation, timing, progress and results of our current and future clinical trials and current and future preclinical studies and clinical trials 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. You should not rely upon forward-looking statements as predictions of future events. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Any forward-looking statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements includin without limitation, risks associated with: the impact of COVID-19 on countries or regions in which we have operations or do business, as well as on the timing and anticipated results of our current and future preclinical studies and clinical trials, supply chain, strategy and future operations; the delay of any current and future preclinical studies or clinical trials or the development of our drug candidates; the risk that the results of current preclinical studies and clinical trials may not be predictive of future results in connection with current or future clinical trials, including those for KT-474, KT-333 and KT-413; Our ability to successfully demonstrate the safety and efficacy of our drug candidates; the timing and outcome of our planned interactions with regulatory authorities; obtaining, maintaining and protecting our intellectual property; and our relationships with its existing and future collaboration partners. 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, except as required by law. As a result of these risks and others, including those set forth in our most recent and future filings with the Securities and Exchange Commission, 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 Ⓒ2022 KYMERA THERAPEUTICS, INC. PAGE 2#3KYMERA PRESENTATION AGENDA 1. Welcome 2. Oncology Update IRAKIMID (KT-413) STAT3 (KT-333) ● ● 3. IRAK4 Update ● KT-474 HS and AD Patient Cohort 4. Q&A 15' 35' 40'#4Kymera is a 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 KYMERA ©2022 KYMERA THERAPEUTICS, INC. Introduction to Kymera Key accomplishments to date: Since 2016 founding, advanced 4 clinical stage programs and developed a deep pipeline positioned to deliver ≥1 IND/year ● ● ● ● Unique target selection strategy based on using TPD to unlock high value, undrugged targets First to advance degraders (KT-474) in healthy volunteers and patients with HS and AD, demonstrating degrader vs. small molecule inhibitors (SMI) biological differentiation, and potential best in class profile in I/I Demonstrated fidelity of translation of PK, PD and safety across three clinical programs in I/I and oncology patients • Well capitalized with $596 million of cash as of 9/30/22 positioning Kymera to accelerate and expand clinical impact in areas with large clinical and commercial opportunities PAGE 4#5Pathway Program IL-1R/TLR JAK/STAT p53 Collaboration Discovery Pipeline IRAK4 IRAKIMID (IRAK4, Ikaros, Aiolos) STAT3 STAT3 MDM2 Confidential Kymera's Pipeline of Novel Protein Degraders Indication(s) Immuno-inflammatory Diseases: HS, AD, RA, others MYD88MT Tumors Liquid & Solid Tumors Autoimmune & Fibrotic Diseases Liquid & Solid Tumors Confidential Several Discovery Programs Discovery IND Enabling 6 Undisclosed Programs KT-474 Multiple molecules staged as potential back ups if needed 0 KT-413 KT-333 KT-253 Phase 1 Collaboration *Option to participate equally in the development and commercialization of Sanofi-partnered programs in the US. RA: Rheumatoid arthritis, AD: Atopic Dermatitis, HS: Hidradenitis suppurativa KYMERA ©2022 KYMERA THERAPEUTICS, INC. Multiple programs in immune-inflammatory and oncology indications anticipated to deliver ≥ 1 IND/year 6 targets in 5 disease areas outside of immunology-inflammation and oncology Phase 2 = Oncology Next Milestones Phase 2 Start 2023 Clinical Activity 2023 Clinical Activity 2023 Phase 1 Start 2023 ≥ 1 DC Annually = Immunology-Inflammation Rights* KYMERA sanofi KYMERA KYMERA KYMERA KYMERA KYMERA sanofi KYMERA VERTEX PAGE 5#6Oncology KT-333 and KT-413 Phase 1 trials in dose escalation phase Both molecules demonstrating PK/PD consistent with pre-clinical models No dose-limiting toxicities observed to date KT-253 IND cleared; Phase 1 trial expected to commence in early 2023 ● ● ● Presentation Summary KT-474 Part C cohort complete: data supportive of promising clinical and market opportunities in HS and AD PK/PD in patients in line with healthy volunteers with broad impact on disease relevant cytokines in blood and skin of HS and AD patients ● KT-474 generally well-tolerated; QTc spontaneously returned to normal baseline during the dosing period Clinical endpoints suggest promising potential in both HS and AD, supporting targeting IRAK4 and clear differentiation of degrader versus small molecule inhibitors Sanofi officially committed to advance KT-474 into Phase 2 clinical trials, initially in HS and AD KYMERA ©2022 KYMERA THERAPEUTICS, INC. ● PAGE 6#7KYMERA STAT3 (KT-333)#8● ● ● ● STAT3 Degraders In Oncology: KT-333 High degree of validation of JAK-STAT pathway in oncology and immuno-oncology supported by >25k publications Traditionally undrugged target First-in-class opportunity to address STAT3 driven pathology across large and diverse indications STAT3 Has Unique Tumor Cell Intrinsic and Extrinsic Mechanisms Intrinsic: Hyperactivation of STAT3 via either receptor signaling, or hotspot mutations promotes gene expression programs involved with survival, proliferation, stemness and metastasis of tumor cells Opportunities in STAT3-dep. malignancies (e.g., T cell maligs., DLBCL, AML) and drug resistant tumors (e.g., TKI res. oncogene- driven solids) KYMERA Ⓒ2022 KYMERA THERAPEUTICS, INC. Prevalence Incidence ~13k ~6.5k ~30k ~2.6k ~4.5k <1k Solid Tumors, PD-1 Combo (e.g. Stage IV MSI-H CRC) ~30k ~5k Source: Bionest, SEER. GlobalData; ROW includes EU, UK, Japan and China. Extrinsic: STAT3 promotes the differentiation and activity of immunosuppressive and endothelial cells, resulting in an immunosuppressive tumor microenvironment Peripheral T-cell lymphoma (PTCL) Large granular lymphocyte leukemia (LGL-L) Opportunities in multiple heme and solid tumor indications that are not responsive to immune checkpoint inhibitors Cutaneous T-cell lymphoma (CTCL) Cytokine Receptor JAK JAK U.S. Growth Factor Receptor P P STAT3 SRC STAT3 STAT3 STAT3 STAT3 # P R.O.W. Prevalence Incidence ~27k ~15k ~67k ~6k ~24k ~3k ~78k ~20k Adrenergic Receptor PAGE 8#9Tumor Volume (mm³) Mean, +SEM KT-333 Highly Active on Intermittent Dosing Regimens Complete Tumor Regressions Associated with Robust STAT3 KD for ~48h in Preclinical Models 3000 2000 1000- 0 SU-DHL-1 Weekly Dosing Vehicle KT-333, 5 mg/kg, QW KT-333, 10 mg/kg, QW [ITHH HH 10 5 15 Days (Post-randomization) HH 20 KYMERA ©2022 KYMERA THERAPEUTICS, INC. 25 Dose- and degradation-dependent tumor growth inhibition observed with once-weekly dosing in ALK+ ALCL 10 mg/kg sufficient to drive full tumor regression in SU-DHL- 1 that was durable for multiple weeks after the last dose (on day 14) 100000 KT-333 Concentration (ng/ml or ng/g) 10000 1000 100 10 Preclinical PK/PD •Tumor PK 48 Plasma PK 96 Time (hr) 144 Tumor PD 192 240 150 100 50 -0 Based on preclinical model (STAT3 dependent ALK+ ALCL), target PD >90% STAT3 KD for ~48 hours to achieve robust anti-tumor activity % of Vehicle Control PAGE 9#10KT-333: Phase 1, Multicenter, Dose-Escalation and Expansion Trial to Evaluate KT-333 in Adult Patients with PTCL, CTCL, LGL-L, and Solid Tumors 0.05 Primary Dec. 2022: Currently enrolling Key Objectives Secondary 0.10 ● ● ● Phase 1a (n up to 40) R/R Lymphoma/Leukemia or Solid Tumors Regimen: mg/kg IV Infusion weekly 0.20 0.40 DLX Predicted clinically efficacious doses Phase 1a Safety/Tolerability and MTD and RP2D PK Parameters of KT-333 Preliminary Estimates of Activity Exploratory PD Effects of KT-333 MTD: Maximum Tolerated Dose. RP2D: Recommended Phase 2 Dose. ORR: Overall Response Rate KYMERA ©2022 KYMERA THERAPEUTICS, INC. ● ● MTD/RP2D Expansion* ● Phase 1b (n=40) Cohort 1: PTCL n=20 Phase 1b • Safety/Tolerability at RP2D in Patients with Lymphoma/Leukemia and Solid Tumors Cohort 2: CTCL n=20 PD Effects of KT-333 Cohort 3: LGL-L n=20 Cohort 4: Solid Tumors n=20 Preliminary Clinical Activity (ORR, DOR, PFS, DCR, OS) PK Parameters of KT-333 PAGE 10#11Interim Safety Data Summary Dose Level 1 • 4 patients at Dose Level 1 (DL1, 0.05 mg/kg) ● ● All 4 patients heavily pretreated (≥3 prior lines) 3 solid tumor 1 CTCL No DLTS, no treatment-related SAEs, no AEs leading to discontinuation KYMERA ©2022 KYMERA THERAPEUTICS, INC. PAGE 11#12Plasma KT-333 Concentration (ng/mL) Mean (± SE) Summary of PK Data From 4 Patients Enrolled in DL1 400 300 200 100 0 0 2 H 4 6 8 KYMERA ©2022 KYMERA THERAPEUTICS, INC. Week 1 Time (h) 24 PK Parameter Cmax (ng/mL) AUC (ng.h/mL) Vd (L/kg) CL (L/h/kg) t₁/2 (h) DL1 → 0.05 mg/kg Week 1 (n = 4) 306 (30.9%) 1550 (66.4%) 0.278 (17.5%) 0.0450 (62.5%) 6.25 (78.8%) PAGE 12#13● ● STAT3 Degradation in Blood at Dose Level 1 (DL1: 0.05 mpk) Consistent with Prediction from Preclinical Modeling Mean % Change from C1D1 Predose STAT3 (fmol/µg) -20 -40 -60 -80- Clinical PD in PBMC by MS Method: Targeted MS n = 4 subjects -100+ 0 24 48 72 96 120 144 168 192 216 240 264 Hours Post Infusion KT-333 0.05 mpk KT-333 0.05 mpk Subject ID KYMERA ©2022 KYMERA THERAPEUTICS, INC. DL1-1 DL1-2 DL1-3 DL1-4 Mean Max Degradation* Post-doses 1&2 (Range) -79.8 % (-75.6 % to -84.1 %) -67.8 % (-73.5 % to -62.0 %) -50.0 % (-47.4% to -52.6 %) -66.7 % (-47.7% to -85.8 %) Cohort Average *Max degradation as measured across timepoints sampled -66.0 % Observed STAT3 degradation of 50-80% in PBMCs at Dose Level 1 is consistent with the range predicted for tumor based on preclinical modeling of SUDHL1 xenograft PK-PD data Maximal degradation in DL1 patients is observed between 24-96 hours post infusion in Cycle 1 weeks 1 & 2, with recovery of STAT3 levels between doses, as seen in preclinical models PAGE 13#14● ● ● ● Demonstration of Initial Proof-of-Mechanism (POM) for KT-333 Accrual to first dose level completed STAT3 degradation in blood at first dose level consistent with preclinical predictions, with mean maximum degradation following first 2 doses of Cycle 1 averaging 66%, with maximum knockdown of up to 86% At least 48h of target degradation observed that in preclinical species led to robust antitumor activity in STAT3 sensitive preclinical models DL1 level generally well-tolerated with no DLTS or treatment-related SAEs DL2 currently enrolling patients DL3-4 expected to be clinically active doses KYMERA ©2022 KYMERA THERAPEUTICS, INC. PAGE 14#15KYMERA IRAKIMID (KT-413)#16IRAKIMiDs are Potent Degraders of IRAK4 and IMID Substrates Targeting Redundant Pro-survival Pathways in MYD88MT DLBCL Single-agent therapies targeting activated NFkB signaling in DLBCL show limited activity • Redundant NFKB pathway activation and downregulation of Type 1 IFN common in MYD88MT lymphoma • Simultaneous degradation of IRAK4 and IMiD substrates Ikaros and Aiolos shows synergistic activity in MYD88MT models MYD88 MT DLBCL Prevalence ~8k U.S. ~9k ~2k Incidence 2.8 / 100k MYD88 MT Waldenström's Macroglobulinemia MYD88 MT PCNS Lymphoma Source: Bionest and Global Data. ROW includes E.U., U.K. and Japan. 0.3/ 100k 0.6/ 100k KYMERA ©2022 KYMERA THERAPEUTICS, INC. R.O.W. Prevalence Incidence 1.2/ 100k ~10k ~26k ~10k 0.7/ 100k 0.6/ 100k TLRs JNK * AP1 Pathway P IL-1R MYD88MYD88 IRAK4 IRAK4 IRAK1 IRAK1 * TRAF6 TRAF6 P IKKy IKKBIKKa NFkB Pathway PROLIFERATION & SURVIVAL B Cell Receptor BTK CARD11 MALT1 BCL10 * A20 * IRF4 Autoantigens * CD79A/B Ikaros Aiolos IRF7 IFN IFNAR1/2 IFN Pathway IFITS Pathway-activating alterations in DLBCL Adapted from Yang et al. (2012) Cancer Cell 21, 6, pp723-737 PAGE 16#17KT-413 Highly Active on Intermittent Dosing in Preclinical Models Complete Tumor Regressions Associated with Robust IRAK4 and Ikaros/Aiolos Degradation for ~72h +SEM Tumor Volume (mm³) Mean, 2500 2000 1500 1000 500 Drug (Day 33) IV vehicle CC-220, 3 mg/kg, PO, QD x 21 KT-413, 10 mg/kg, IV, D1,2,21,22 7 14 21 28 Days After Start of Treatment CC-220 KT-413 10 mg/kg T/C% (REG%) 9 (94) CR 0 5 PR KYMERA ©2022 KYMERA THERAPEUTICS, INC. 0 2 35 SD 0 0 In the OCI-LY10 MYD88MT xenograft model, intermittent dosing of KT-413 induced strong antitumor activity, including complete regressions. Superior activity compared to IMID CC-220 alone PD 7 0 10000 KT-413 Concentration (ng/ml or ng/g) 1000 100 10 •Tumor PK 48 HAH Plasma PK H IRAK4 Ikaros HH HH 96 Time (hr) 144 192 HHHHH I 240 150 100 50 Single 10 mg/kg dose showed extended tumor exposure and strong degradation of both IRAK4 and IMID substrates that was maintained for least 72hr in preclinical models Target PD 80-90% Ikaros KD and 50-70% IRAK4 KD in tumor for ≥72 hrs to achieve robust anti-tumor activity % of Vehicle Control PAGE 17#18KT-413: Phase 1, Multicenter, Dose-Escalation and Expansion Trials to Evaluate KT-413 in Patients with R/R DLBCL 0.16 0.32 Key Objectives Primary ● Ⓡ ● Phase 1a (n up to 40) R/R B-cell NHL Dec. 2022: Currently enrolling 0.51 0.82 Regimen: mg/kg IV Infusion q 3 weeks Predicted clinically efficacious doses Secondary Exploratory PD Effects of KT-413 MTD: Maximum Tolerated Dose. RP2D: Recommended Phase 2 Dose. ORR: Overall Response Rate KYMERA ©2022 KYMERA THERAPEUTICS, INC. DLX Phase 1a Safety/Tolerability and MTD and RP2D PK Parameters of KT-413 Preliminary Estimates of Activity ● ● ● MTD/RP2D Expansion * *Additional 3-6 pts for a total of 9 patients dosed at MTD Phase 1b (n=40) R/R DLBCL PD Effects of KT-413 Cohort 1: MYD88MT n=20 Cohort 2: MYD88WT n=20 Phase 1b Safety/Tolerability at RP2D in Patients with DLBCL Preliminary Clinical Activity (ORR, DOR, PFS, DCR, OS) PK Parameters of KT-413 PAGE 18#19● ● Interim Safety Data Summary Dose Levels 1-2 All patients with heavily pretreated B-cell lymphoma (up to 3 prior lines of therapy) Follicular lymphoma, DLBCL (all wild-type MYD88) No DLTS, no treatment-related SAES or AEs leading to discontinuation, no neutropenia in first two dose levels KYMERA ©2022 KYMERA THERAPEUTICS, INC. PAGE 19#20Plasma KT-413 Concentration (ng/mL) Plasma PK Showing Dose-Proportional Increase in Exposure 300 100 30 10 0 4 8 12 Cycle 1 Plasma PK 24 KYMERA ©2022 KYMERA THERAPEUTICS, INC. Time (h) 48 DL1: 0.16 mg/kg DL2: 0.32 mg/kg 72 PK Parameter Cmax (ng/mL) AUC inf (ng.h/mL) Vd (L/kg) CL (L/h/kg) t₁/2 (h) 0.16 0.32 mg/kg mg/kg (DL1) (DL2) Cycle 1 140 1360 10.1 0.118 59.3 Cycle 1 493 3490 3.99 0.092 30.2 PAGE 20#21At least 72h of Target Degradation Observed with Once Every Three-week Dosing Target Degradation in PBMC by FLOW Cycle 2 DL1 0.16mg/kg IRAK4 Percent Change from Baseline Ikaros Degradation Profile of IRAK4, Ikaros and Aiolos in DL1/DL2 Consistent with Preclinical Models in Blood and Tumor Aiolos Percent Change DL2 0.32mg/kg 100- 50- 0 -50- -100 0 -20- -40- -60- -80- -100 200 150 100 50 50. -50 -100 0 0 2 0 2 24 96 192 15 0 Hours Days Cycle 1 2 24 96 192 15 0 2 Hours Days 24 Hours 2 24 192 15 Hours Days 96 192 15 Days A 2 0 24 192 15 Hours Days 24 192 15 Hours Days KYMERA ©2022 KYMERA THERAPEUTICS, INC. ● Dose Level DL1 DL2 Dose Level DL1 DL2 Dose Level DL1 DL2 Cycle 1 -16% -27% Cycle 1 -84% -92% Cycle 1 -93% -100% Cycle 2 0 -40% Cycle 2 -88% -95% Cycle 2 - 91% -100% Up to 40% KD of IRAK4 and 95/100% KD of Ikaros and Aiolos in PBMC at DL1-2 Target Knockdown in Tumor by Targeted MS Percent Change from Baseline at C3D4 104-002: 0.16mg/kg Mean* SEM % Change 40 20 O -20 -40 -60 -80- -100 -41% -66% -27% Ikaros Aiolos IRAK4 *Mean is from 2-3 peptides measured for each analyte PAGE 21#22● First two dose levels completed PK and PD profiles in DL1 and DL2 consistent with preclinical data supporting once every three-week dosing regimen Up to 95/100% KD of Ikaros/Aiolos and 40% KD of IRAK4 in blood Consistent degradation in blood and tumor At least 72h target degradation observed, a profile that in preclinical species led to robust antitumor activity in MYD88 mutant tumors ● ● Demonstration of Initial POM for KT-413 ● First 2 dose levels generally well-tolerated with no DLTs, treatment-related SAEs or neutropenia observed DL3 currently enrolling patients DL3/4 expected to be clinically active doses KYMERA ©2022 KYMERA THERAPEUTICS, INC. PAGE 22#23KYMERA IRAK4 (KT-474)#24TLRs (TLR 2,4,5,7,8,9) IRAK3 signaling NFkB Myddosome IL-1R/TLR Pathway IL-1 a/B, IL-18, IL-33, IL-36 IKKS Degrading IRAK4 Superior Approach to Block IL-1R/TLR-driven Inflammation MyD88 IRAK4 IRAK 1 IRAK2 TRAF6 c-Jun KYMERA Ⓒ2022 KYMERA THERAPEUTICS, INC. IL-1R JNK/p38 secreted TNF-a, IFN-Y, IL-1B, IL-6, IL-8, IL-10, IL-12, IL-17, IL-23 Degrader Advantage Inhibitor Scaffolding Role JNK/p38 NFkB IRAK4 Degrader Kinase Role IRF5/7 Clinical Pathway Validation IL-1a/IL-1ß: Rheumatoid Arthritis, CAPS, Hidradenitis Suppurativa IL-1α: Atopic Dermatitis IL-1ß: Gout; CANTOS Outcomes Data in Atherosclerosis and Lung Cancer IL-18: Macrophage Activation Syndrome IL-36: Generalized Pustular Psoriasis, Atopic Dermatitis IRAK4 SMI: Rheumatoid Arthritis Human Genetics Adult humans with IRAK4 Null Mutation have no clinical phenotype IRAK4 degrader has potential to achieve a broad, well-tolerated anti-inflammatory effect, providing multiple development opportunities in autoimmune inflammatory diseases PAGE 24#25IRAK4 Scaffolding Function is Critical in Myddosome Formation and Pathway Signaling IL-1R (or TLRs) IRAK4 Degradation but Not Inhibition is Required to block IL1R/TLR Pathway MyD88 Recruitment IRAK4 Recruitment/ MyD88 Limitation IRAK1 Recruitment IRAK4 scaffolding role functions to limit MYD88 oligomer size and trigger myddosome formation Source: Deliz-Aguirre, et al. J. Cell Biol., 2021 KYMERA ©2022 KYMERA THERAPEUTICS, INC. IRAK4 Degradation, but not Kinase Inhibition, can Block TLR- induced NF-KB Translocation B Cell CpG-B → IL-6 % IL6 (Control) %Phos-NF-kBp65/Control 150 100 50- 0 0.1 150 100 50 O IC50-18 NM 500 |PF-06550833 IRAK4 Degrader 1 10 Dose (nM) PF-06550833 IRAK4 Degrader 125 31.25 7.8125 1.953125 Dose (nM) 100 0.488281 1000 0.12207 150 100 50 0 -6 IRAK4 Degradation, but not Kinase Inhibition, can block IL1R+TLR activation LPS + IL-18 → IL-6 HA ▶ -4 HA 101 -2 Log[Compound] (nM) Compound IRAK4 Degrader Negative Control IRAK4 SMI (PF-06550833) 2 IL-6 IC50 (NM) 0.8 450 N/A PAGE 25#26● ● ● ● ● IRAK4 Degrader Best-in-class Potential in Immune-inflammation Potential for Broad Activity Across Th1-Th17 and Th2 Diseases KT-474 Lupus IBD Gout Psoriasis IL-1R/TLR ↓ IRAK4 Th1-Th17/Neutrophils Hidradenitis Suppurativa Rheumatoid Arthritis ● ● Th2/Eosinophils Atopic Dermatitis Asthma COPD CRSWNP $150B drug sales Combined global Source: EvaluatePharma; GlobalData; Dash. Allied Market Research. 2021; Koto. Modern Rheumatology. 2021; Ahn. JAMA Otolaryngol Head Neck Surg. 2016; UC: Ulcerative Colitis; CD: Crohn's Disease. KYMERA Ⓒ2022 KYMERA THERAPEUTICS, INC. Indication AD HS RA SLE IBD Gout Psoriasis Asthma COPD CRSWNP 2021 Prevalence US/EU5/JP ~82.5 M ~785 K ~4.6 M ~580 K ~3.2 M ~18.2 M ~15.8 M ~87.3 M ~61.7 M ~20.4 M 2021 Global Sales • Small Molecule Inhibitors o $5,760 M $1,106 M $27,634 M $1,333 M $21,710 M $1,319 M $23,268 M $15,664 M $9,960 M $2,622 M Limitations of Current Therapies Anti-Cytokine/Cytokine Receptor Antibodies Target only 1-2 cytokines Require injection Limited pathway blockade (IRAK4 SMI) Safety issues (JAK family) PAGE 26#27KT-474 Phase 1 Trial Design Double-blind, placebo-controlled SAD and MAD in Adult HV; Open Label Patient Cohort in HS & AD Patients Parts A & B Healthy Volunteers (HV) SAD and MAD Todays' Focus Part C HS and AD Patients 9 SAD cohorts - 8 subjects per cohort (6:2 randomization) including 2 food-effect cohorts - 72 adult healthy subjects dosed Single dose (25-1600 mg) 5 MAD cohorts - 12 subjects per cohort (9:3 randomization) 60 adult healthy subjects dosed 14x daily doses (25-200 mg, MAD 1-4); 5x twice-weekly doses (200 mg, MAD5) - 1 cohort 21 HS and AD patients 75 mg (fed state) (~equivalent exposure to 100mg fasted MAD cohort dose level) Open-label 28x daily doses KYMERA ©2022 KYMERA THERAPEUTICS, INC. ● ● ● ● Summary of Key Findings in MAD IRAK4 degradation of 80-90% in PBMC using Flow Cytometry; reduction to near lower limit of quantification with Mass Spectrometry Associated with up to 85% inhibition of multiple disease-relevant cytokines and chemokines in ex vivo TLR stimulation assay at 100 mg dose Dose-dependent IRAK4 degradation in skin of >50% Generally well tolerated at doses up to 200 mg with no SAEs Non-adverse, self-limiting QTcF prolongation in 10-20 msec range was neither dose- nor exposure-dependent Primary Secondary/ Exploratory ● Safety & tolerability Pharmacokinetic measures (half-life, bioavailability) IRAK4 knockdown in PBMC and skin Change in systemic inflammatory biomarkers and proinflammatory gene transcripts in skin Ex vivo response of whole blood to TLR agonists Clinical endpoints: EASI (AD), Total AN Count (HS), symptom scores and global assessments PAGE 27#28KT-474 Part C: Demographics/Disposition KYMERA#29Gender, n Female Male Median age, years (range) Race/Ethnicity White / Hispanic, Latino White / Non-Hispanic, Latino Black / Hispanic, Latin Black / Non-Hispanic, Latino Other* *Native American or Alaskan Native/ Hispanic, Latino Patient Demographics KYMERA ©2022 KYMERA THERAPEUTICS, INC. HS (n=13) 10 3 40 (21-53) 7 1 0 50 0 AD (n=8) 3 5 31 (23-55) 6 0 1 COL 0 1 PAGE 29#30Disease Severity Mild Moderate Severe Very Severe Extent of Disease AN Count Fistula Count Pain-NRS* Pruritus-NRS* EASI Score Baseline Disease Characteristics HS (n=13) (HS-PGA) Patients with any prior Therapy, n (%) Antibiotics/Antibacterials** Corticosteroids Adalimumab 10 1 2 Mean (min, max) 8 (5, 18) 4 (0, 15) 7 (3, 10) 5 (0, 10) 8 (62) 6 (46) 0 3 (23)² 1 (8)* AD (n=8) (VIGA-AD) 1 5 2 ! Mean (min, max) 8 (4, 10) 17.6 (4.4, 52.3) 7 (88) 1 (13) 7 (88) 0 0 Other Biologics includes 2 pts with very severe disease; *worst score over past week **includes clindamycin and chlorhexidine *1 patient with very severe disease received infliximab and bimekizumab (and adalimumab) AD=Atopic Dermatitis; AN=Abscess and Inflammatory Nodule Count; EASI-Eczema Area and Severity Index; HS-hidradenitis suppurativa; Min-minimum; Max=maximum; Pain-NRS-Skin Pain Numerical Rating Score; Pruritus-NRS-Peak Pruritus Numerical Rating Score; PGA-Physicians Global Assessment; IGA=Investigator Global Assessment KYMERA ©2022 KYMERA THERAPEUTICS, INC. PAGE 30#313 Enrolled patients Primary reason for Treatment Completion Completed Withdrawal by patient Withdrew treatment after 4 doses for personal reasons ** Withdrew treatment after 5 doses for personal reasons KYMERA Patient Disposition ©2022 KYMERA THERAPEUTICS, INC. HS 13 12 • 9 Moderate 1 Severe • 2 Very Severe ● 1* AD 8 7 • 1 Mild ● • 4 Moderate 2 Severe 1** Total 21 19 2 PAGE 31#32KYMERA KT-474 PK and Degradation#33KT-474 Concentration (ng/mL) Mean (+ SE) 20 15 10 5 C ● D1 D1-H6 ● KT-474 Plasma PK and IRAK4 Degradation in Patients Dosed for 28 Days is Comparable to HV Part C KT-474 Plasma PK n = 19 after Day 4; 2 patients discontinued treatment D4 D4-H6 D7-H6 D7 D11 D11-H6 D14 D14-H6 D21 D21-H6 D28 D28-H6 Mean Day 14 Cmax (MAD3: 100 mg QD) Mean Day 14 Ctrough (MAD3: 100 mg QD) KT-474 PK at the 75 mg QD dose (fed state) in patients is comparable to 100 mg QD (fasted state) in HV D31 KYMERA ©2022 KYMERA THERAPEUTICS, INC. 3 ng/mL threshold D35 D42 Mean Cmax and Ctrough levels at steady state in Part C are in line with MAD3 levels at Day 14 Mean half-life of 44 hours is within the range observed in MAD (34-59 hours) Percent Change from Baseline IRAK4 0 -20- -40- -60- -80 -100- PK/PD Correlation in Plasma/Monocytes (FLOW) 0 4 3 ng/mL threshold MAD PART C 8 12 16 20 24 28 32 36 40 KT-474 Ctrough/ng/mL KT-474 concentrations in plasma lead to same level of IRAK4 degradation in HV (n=48) and HS/AD (n=20) patients Concentrations above 3 ng/mL lead to same level of degradation (>80%) in HV and Patients protein] Mean (± SE) Absolute IRAK4 Levels by MS [fmol/µg IRAK4 Levels in PBMC in Patients at Day 28 (MS) 1.00- 0.75 0.50 0.25 0.00 Day 28 HS and AD Patients IRAK4 Levels at Day 28 (n=4) near LLOQ PAGE 33#34Skin PK: KT-474 Has High Skin Concentration In Patients at Day 28 Higher than MAD3 HV n=11 for Day 28 and n=10 for Day 42 KT-474 Concentration (ng/g) Mean (± SE) 500 KYMERA ©2022 KYMERA THERAPEUTICS, INC. 400 300 200 100 0 Part C: 75 mg QD (fed)* Day 28 386 (± 103) Day 42 135 (± 33.8) PAGE 34#35KT-474 Reduced IRAK4 in Skin Lesions of AD and HS Patients on Day 28 to at Least Same Level as Healthy Subjects KYMERA Mean (+SE) IRAK4 Levels in Skin (fmol/µg protein) N Mean (± SE) 0.3 0.2 0.1 0.0 MAD Healthy Subjects (Baseline) 46 0.123 (± 0.01) ©2022 KYMERA THERAPEUTICS, INC. ‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒ AD Patients (Baseline) 7 0.216 (± 0.06) HS Patients (Baseline) 11 0.236 (± 0.05) AD Patients (Day 28) 6 0.103 (+ 0.05) ‒‒‒‒‒‒‒‒‒‒‒ ‒‒‒‒‒‒‒‒‒‒ HS Patients (Day 28) 9 0.112 (± 0.03) PAGE 35#36KYMERA KT-474 Safety#37Adverse Events Related to Study Drug (Occurring in > 1 Patient) Adverse Event (Preferred Term) Headache Fatigue Diarrhea # of Patients KYMERA Ⓒ2022 KYMERA THERAPEUTICS, INC. 6 4 2 Severity (# of Pts) Mild (5) Severe (1) Mild (4) Mild (2) Outcome (# of Pts) Recovered (6) Recovered (4) Recovered (2) No SAEs, no drug-related infections, and no AEs observed leading to dose interruption or discontinuation PAGE 37#38● ● ● QTc Prolongation Spontaneously Resolves to Baseline by Day 28 AQTCF in Part C is in the range observed in MAD3 (100 mg QD) up to Day 14 Declines to baseline with continued dosing and sustained plasma exposure through Day 28 Profile is maintained through day 42 upon cessation of dosing after Day 28 No QTc-related AEs observed AQTcF QTcF Mean MAD3 Part C MAD3 Part C n=9 for MAD3 and n=20 for Part C, except day 14 (n=19) KYMERA ©2022 KYMERA THERAPEUTICS, INC. Baseline 395 Change from Baseline QTcF (ms) Mean (± 90% CI) 403 20 15 10 5 O -5 Day 7 17 15 411 419 Day 14 13 12 408 416 Day 21 5.9 -- 410 MAD3 PART C Day 28 1.6 405 PAGE 38#39KYMERA KT-474 Pharmacodynamics#40* Maximum % Change from Baseline -20 - -40- -60 - -80 -100 - HV (MAD3) Up to 98% Inhibition of 9 Disease-Relevant Cytokines Ex Vivo in both HS and AD Patients |'||||| peppe IFNY IL10 IL12 IL17 IL1b IL23 IL6 IL8 TNFa -67% -45% -47% -20% -64% -54% AD -95% -98% -76% KYMERA LPS HS -36% -52% -84% -8% -44% -31% -50% -59% -57% -49% -60% -83% -63% -95% -70% -85% -74% Ⓒ2022 KYMERA THERAPEUTICS, INC. -41% MAD 3 Healthy Subjects 100 mg QD (n = 9) Part C AD Patients (n=7) Plots show median of the maximum change from baseline between Days 7-14 in MAD3, and Days 14-28 in Part C Part C HS Patients (n=9) Maximum % Change from Baseline -20- -40- -60- -80- -100- HV (MAD3) AD HS IFNY IL10 IL12 IL17 IL1b -87% -95% -76% -50% -71% -55% -67% -64% 0% -72% IL6 -54% -81% -74% -35% -69% -46% -57% -50% IL8 -33% -48% -43% R848 TNFa -62% -62% -54% PAGE 40#41In Vivo Inhibition of Disease-Relevant Plasma Cytokines and Acute Phase Reactants by KT-474 in HS/AD Patients IL-6 Analyte IL-6t CRPt IL-1B SAAT Mean Max* AD Mean Max* HS (n) (n) -56% (3) ΝΑ -36% (7) -51% (4) *Max % reduction through Day 42 +Analysis performed only on patients with values >ULN at baseline IL-6, IL-13 and CRP are high sensitivity assays KYMERA ©2022 KYMERA THERAPEUTICS, INC. -63% (8) -58% (5) -48% (8) -41% (10) Percent Change from Baseline 50 O -50 0 7 ed 14 TICH 28 Days + 35 AD (N=3) HS (N=8) 42 PAGE 41#42Disease-Relevant Genes Downregulated in Skin Lesions in ≥ 50% of Evaluable* AD (N=7) and HS (N=10) Patients at Day 28 (RNAseq) • Substantial downregulation of many disease relevant genes in both HS and AD patients Downregulation exceeded 90% for many genes Broad anti-inflammatory signature with downregulation of genes responsible for: KYMERA IL1 family cytokines Th1 Th17 Th2 Innate immunity AD HS CXCL1 ©2022 KYMERA THERAPEUTICS, INC. AD-3- AD-6- AD-7- AD-4- AD-5- AD-2- AD-1- IFNG HS-3- HS-8 HS-2- HS-5- HS-4- HS-12- HS-9- HS-1 HS-6 HS-7 -7.5 CSF3 HS-3- HS-8- HS-5 HS-1- HS-9 HS-2 HS-4- HS-6- HS-12- HS-7- 0 log2(fold change) -5.0 -7.5 -2.5 0.0 log2 (fold change) 2.5 IL2RB 0.0 AD-6- AD-3- AD-2- AD-7- AD-1- AD-4- AD-5- GZMB HS-5- HS-2- HS-3- HS-8- HS-12- HS-6- HS-7- HS-4- HS-9- HS-1- -3 HS-8- HS-1- HS-3- HS-4- HS-5- HS-7- HS-9- HS-12- HS-6- HS-2- -7.5 IL1B -5.0 -2.5 log2 (fold change) log2 (fold change) tlog2(fold change): -1 = 50% decrease, -2 = 75% decrease, -3 = 87.5% decrease log2(fold change) -5.0 -2.5 log2(fold change) 0.0 6 2.5 IL5 AD-4- AD-5- AD-1- AD-3- AD-7- AD-2- AD-6- IL8 HS-5 HS-4 HS-8 HS-1- HS-3- HS-12- HS-7 HS-9 HS-6 HS-2 -5.0 IL36A HS-5- HS-3 HS-4 HS-1 HS-8 HS-7 HS-9- HS-6 HS-2 HS-12- 0 -7.5 log2(fold change) -2.5 0.0 log2 (fold change) 2.5 5.0 0.0 NLRP3 AD-3- AD-5- AD-2- AD-4- AD-7- AD-1- AD-6- IL2RA HS-4- HS-5 HS-3- HS-8- HS-2- HS-1- HS-9- HS-12 HS-6 HS-7 -2 IL17A HS-5- HS-8- HS-3- HS-4- HS-1- HS-7- HS-2- HS-12- HS-9- HS-6- 0 2 log2(fold change) -5.0 -2.5 log2 (fold change) log2(fold change) *Evaluable patients for whom the samples were of sufficient quality for analysis. 0 log2(fold change) PAGE 42#43KT-474 Part C: Clinical Endpoints KYMERA#44Included as Exploratory Endpoints Skin lesions and global assessments performed on Days 1, 14, 28, 35 and 42 Symptom scores performed at additional time points ● AD ● ● HS ● ● Clinical Endpoints Change from baseline in Eczema Area and Severity Index (EASI) Peak pruritus NRS Investigator Global Assessment (VIGA-AD) Additional ad hoc analysis included: Peak Pruritus NRS Response (≥4-point improvement from baseline) Change from baseline in Total Abscess and Inflammatory Nodule (AN) count Skin pain Numerical Rating Scale (NRS) Peak pruritus NRS HS-Physician's Global Assessment (HS-PGA) Additional ad hoc analyses included: ANO/1/2 Response, HiSCR50, HiSCR75, and Pain NRS30 KYMERA ©2022 KYMERA THERAPEUTICS, INC. PAGE 44#45KYMERA AD Clinical Endpoints#46Mean EASI Score (+/-S.E. of Mean) 25 23 21 19 17 15 13 11 9 7 5 Mean EASI Score Over Time (N=7) 18.9 EASI Score: Mean 37% and Max 76% Reduction 7 14 15.3 21 Day KYMERA ©2022 KYMERA THERAPEUTICS, INC. 12.5 28 35 13.6 12.2 42 Mean % Change in EASI Score (+/-S.E. of Mean) Mean % Change in EASI Score Over Time (N=7) -10 -20 -30 -40 -50 -60 0 7 14 -17.9 21 Day -37.1 28 35 -27.6 -36.4 42 PAGE 46#47Mean % Change (+/-S.E. of Mean) -10 -20 -30 -40 -50 -60 -70 -80 O -5.8 KYMERA TF 7 Mean % Change in Peak Pruritus Over Time (N=7) -6.6 Peak Pruritus NRS: Mean 52 to 63% Reduction Peak Pruritus NRS Responders: 57 to 71% -32.1 14 -34.6 -43 -35.6 -51.2 21 Day I ©2022 KYMERA THERAPEUTICS, INC. -44.6 28 Past 24 Hours ➡Past Week -38.9 -44.6 35 -51.9 -62.9 42 % of Peak Pruritis Responders (80% CI) 100 90 80 70 60 50 40 30 20 10 0 0 % of Patients with 24 Unit Reduction from Baseline in Peak Pruritus (N=7) 7 29 14 43 Past 24 Hours 29 21 Day 71 57 28 Past Weel 57 35 43 71 57 42 PAGE 47#48KYMERA 7 # of Patients by AD-IGA Score N + 0 ● Investigator's Global Assessment (VIGA-AD) 2 4 1 Baseline VIGA-AD Score Over Time (n=7) Ⓒ2022 KYMERA THERAPEUTICS, INC. 1 4 2 Day 14 1 4 2 Day 28 ■Mild Moderate Severe IGA scores remained stable or improved in all patients 1 4 2 Day 35 1 3 3 Day 42 PAGE 48#49Percent Change from Baseline ● ● 51-year-old Hispanic/Latino male with severe AD (VIGA-AD) and EASI score of 28.2 at baseline Previously treated with topical betamethasone 2018-2020 Efficacy Endpoints IGA-AD Score EASI Score (% Change) Peak Pruritis NRS - past week (% Change) 150 125 100. 40 20 0 -20 -40- Plasma Cytokines 0 7 BL Severe 28.2 14 IL-1B IL-6 Percent Change from Baseline Day 28 Moderate 14 (-50) 1 (-75) 0- -25- -50- AD Case Study: Patient AD-3 Improvement in Disease Severity from Severe to Mild -75- -100- 21 28 35 42 49 Day KYMERA ©2022 KYMERA THERAPEUTICS, INC. Day 35 Moderate 16.45 (-42) 1 (-75) Day 42 Mild 9.2 (-67) 1 (-75) Skin Inflammation Biomarkers* (RNAseq) IL5 TNF NLRP3 CXCL1 CCL3 CXCL8 IL1B PTGS2 *Changes at D28 Day 1 - BL =1mm ADT =1mm Day 42 PAGE 49#50● ● KT-474 Showed Meaningful Signs of Clinical Activity in AD, Comparing Favorably to Placebo Benchmarks and SOC Summary Results Mean EASI score reduction up to 37%, with maximum reduction of up to 76% Mean peak pruritus NRS reduction of 52 to 63% Peak pruritus NRS Responder rate of 57 to 71% Investigator Global Assessment (IGA) scores improved in 2 of 7 patients and remained stable in the others AEASI APeak Pruritus NRS KT-474 Part C -37% -52 to -63% Placebo Benchmarks Week 4 -12 to -25%* 57 to 71% -11%¹ Peak Pruritus NRS Responder *Range from 7 different Phase 2 and Phase 3 trials; **Range from 10 different Phase 2 and Phase 3 trials; ¹Simpson EL, et al. NEJM 2016;375:2335-2348; 2Bieber T, et al. NEJM 2021;384:1101-1112; The Dupilumab clinical trial was conducted by other parties in a similar patient population with different enrollment criteria from Part 1C of our Phase 1 clinical trial evaluating KT-474. Results do not reflect a head-to-head trial and are shown for illustrative purposes only KYMERA Ⓒ2022 KYMERA THERAPEUTICS, INC. ** Dupilumab Phase 3 Week 4 -52%¹ -34%¹ 4 to 17%* 23 to 40%¹,2 PAGE 50#51KYMERA HS Clinical Endpoints#52Mean % Change in AN Count (+/- S.E. of Mean) Mean % Change in Total AN Count Over Time 0 -10 -20 -30 -40 -50 -60 AN Count: Mean 46 to 51% and Max 100% Reduction AN 0/1/2 Responders: 42 to 50% Response Rate KYMERA 7 -27.4 -All HS (n=12)* 14 -19.9 -49.6 21 Day -31.6 28 Ⓒ2022 KYMERA THERAPEUTICS, INC. -45.4 -Moderate to Severe (n=10) -40.6 -46.1 35 -50.7 42 *One patient is censored for Day 35 and Day 42 since the patient started on ustekinumab, steroids and abx on Day 34. % of Patients with AN 0/1/2 (80% CI) 80 70 60 50 40 30 20 10 0 0 % of Patients with AN Count 0/1/2 7 20 14 17 All HS (n=12) 21 Day 50 28 42 50 35 42 Moderate to Severe (n=10) 40 33 42 PAGE 52#53% of HISCR Responders (80% CI) KYMERA 80 70 60 50 40 30 20 10 O HISCR50: 42 to 50% Response Rate 7 ©2022 KYMERA THERAPEUTICS, INC. 30 % of Patients with HiSCR50 14 25 All HS (n=12) 21 Day 30 Moderate to Severe (n=10) 28 25 50 35 42 50 42 42 PAGE 53#54Mean % Change in Pain (+/- S.E. of Mean) 0 -10 -20 -30 -40 -50 -60 -70 -80 KYMERA 0 Mean % Change in Worst Pain Over Past Week -17.5 I 7 -14.6 -36 14 Pain NRS: Mean 49 to 55% Reduction Pain NRS30: 50 to 60% Response Rate All HS (N=12)* -31.2 -47.5 -40 21 Day -55.2 28 -46 Ⓒ2022 KYMERA THERAPEUTICS, INC. -43.5 -48.8 -49.3 -52.2 35 Moderate to Severe (N=10) 42 *One patient is censored for Day 35 and Day 42 since the patient started on ustekinumab, steroids and abx on Day 34. % of Pain NRS30 Responders (80% CI) % of Patients with ≥30% and ≥1 Unit Reduction in Worst Skin Pain Over the Past Week 100 90 80 70 60 50 40 30 20 10 O 0 20 7 17 50 14 42 70 All HS patients (N=12) 58 21 Day 60 50 28 60 35 50 60 50 42 Moderate to Severe (N=10) PAGE 54#55Mean % Change in Peak Pruritus (+/- S.E. of Mean) 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 KYMERA 0 Peak Pruritus NRS: Mean 62 to 68% Reduction -29.1 7 Mean % Change in Peak Pruritus Over Past Week -17 -41.7 Ⓒ2022 KYMERA THERAPEUTICS, INC. 14 -26.1 -41.9 -All HS (N=12)* *One patient is censored for Day 35 and Day 42 since the patient started on ustekinumab, steroids and abx on Day 34. -24 21 Day -67.8 28 Moderate to Severe (N=10) -48.6 -62.3 35 -53.6 -61.6T -68.4 42 PAGE 55#56# of Patients by HS-PGA Score 12 10 00 2 O 2 1 9 HS-PGA Score Over Time (N=12*) Baseline 2 1 6 2 Physician's Global Assessment (HS-PGA) 1 Day 14 ■Clear ■Minimal ■Mild 2 1 5 3 1 1 1 4 3 KYMERA ©2022 KYMERA THERAPEUTICS, INC. 1 1 Day 28 Day 35 Moderate ■Severe ■Very Severe 1 1 4 1 Day 42 # of Patients by HS-PGA Score OHN W AUT a 5 *One patient is censored for Day 35 and Day 42 since the patient started on ustekinumab, steroids and abx on Day 34. 10 HS-PGA Score Over Time Moderate to Severe Patients (N=10) 1 9 Baseline Clear HS-PGA scores remained stable or improved in all patients Disease cleared in 1 patient with moderate disease at baseline 1 6 2 1 Day 14 Minimal 1 5 3 1 Day 28 1 4 3 1 1 Day 35 Mild Moderate ■Severe 1 4 1 Day 42 PAGE 56#57HS Case Study: Patient HS-3 Complete Clearing of Lesions and Symptoms in Patient with Moderate Disease at Baseline Day 1 - BL Day 42 45 year old Black Female with Moderate HS (HS- PGA); Baseline AN count = 7 Prior treatments: clindamycin (topical) and doxycycline Efficacy Endpoints HS-PGA Score AN Count (% Reduction) Skin Pain NRS - Worst, past week (% Change) Peak Pruritis NRS - past week (% Change) BL Moderate 7 7 6 Day 28 Day 35 Clear Clear 0 (-100) 0 (-100) 0 (-100) 0 (-100) 0 (-100) KYMERA ©2022 KYMERA THERAPEUTICS, INC. 0 (-100) Day 42 Clear 0 (-100) 0 (-100) 0 (-100) Percent change from baseline Area of swelling Beneath skin -25- -50- -75- -100- Resolution of Swelling Skin Inflammation Biomarkers* (RNAseq) '||| IIII CXCL8 IL1B PTGS2 IL36A IL17A IL5 CXCL1 GZMB IFNG *Changes at D28 PAGE 57#5839 year old Black Female with Moderate HS (HS-PGA); Baseline AN count = 5 Prior treatments: benzocaine ointment Efficacy Endpoints HS-PGA Score AN Count (% Reduction) Skin Pain NRS - Worst, past week (% Change) Peak Pruritis NRS - past week (% Change) HS Case Study: Patient HS-10 Improvement in Disease Severity from Moderate to Mild BL Moderate 5 8 10 Day 28 Mild 2 (-60) 3 (-63) KYMERA ©2022 KYMERA THERAPEUTICS, INC. 2 (-80) Day 35 Mild 2 (-60) 3 (-63) 0 (-100) Day 42 Mild 1 (-80) 1 (-88) 0 (-100) Day 1 - BL Percent Change from Baseline Multiple Ulcerated 40 Plasma Cytokines/Acute Phase Reactants 20 O -20 -40 -60- -80 Nodules O 7 14 21 28 Day Day 42 Clearing of Ulcerated Nodules 35 IL-1B SAA 42 49 PAGE 58#59● AN count of 0/1/2 response rate of 42 to 50% HISCR50 response rate of 42 to 50% HISCR75 response rate of 25 to 30% Pain NRS30 response in 50 to 60% and mean peak pruritis reduction of 62 to 68% Physician Global Assessment (PGA) scores improved in 5 of 12 patients, including 1 moderate disease patient with full disease clearance, and stable in the others KT-474 Part C Placebo Benchmarks Week 4 -15%¹ ΔΑΝ Count -46 to -51% AN Count 0/1/2 42 to 50% 24 to 26%3 28 to 47%2,3 HISCR50 42 to 50% 19 to 30% 3,4 5%4 29 to 51% 3,4 20%4 HISCR75 25 to 30% Pain NRS30 50 to 60% 18 to 23% 3,5 39 to 58%2,3,5 APeak Pruritus NRS -62 to -68% N/A N/A ¹Kimball AB, et al. Ann Intern Med 2012;157:846-55; 2Morita A, et al. J Dermatol 2021;48:3-13; ³Kimball AB, et al. NEJM 2016;375:422-434;4Glatt S et al. JAMA Dermatol 2021;157:1279-88; 5Scheinfeld, et al. Derm Online J 2016:22 The Adalimumab clinical trial was conducted by other parties in a similar patient population with different enrollment criteria from Part 1C of our KYMERA Phase 1 clinical trial evaluating KT-474. Results do not reflect a head-to-head trial and are shown for illustrative purposes only ● ● ● KT-474 Showed Meaningful Signs of Clinical Activity in HS, Comparing Favorably to Placebo Benchmarks and SOC Summary Results ● Mean total AN count reduction of 46 to 51%, with maximum reduction up to 100% ©2022 KYMERA THERAPEUTICS, INC. Adalimumab Phase 2 and 3 Week 4 -31%¹ PAGE 59#60KYMERA Conclusions / Summary#61● ● Part C Summary KT-474 administered to HS and AD patients at 75 mg QD for 28 days shown to have safety, PK and PD comparable to healthy volunteers Modest, non-adverse QTcF prolongation observed to spontaneously resolve back to baseline during final 2 weeks of dosing in HS and AD patients Robust degradation of IRAK4 in blood and skin was associated with systemic anti- inflammatory effect in HS and AD patients Promising clinical activity observed in HS and AD exceeding benchmark placebo rates and comparing favorably to SOC biologics Data presented here validate IRAK4 degradation as a potential best in class mechanism in inflammatory diseases and its superior clinical potential over SMI Results support advancing KT-474 into Phase 2 placebo-controlled trials, Sanofi has committed to start Ph2 clinical trials initially in HS and AD KYMERA ©2022 KYMERA THERAPEUTICS, INC. PAGE 61#62● ● ● Meeting Summary Kymera platform and discovery engine have been validated across several programs in patients with cancer and inflammatory diseases, with fidelity of translation of PK, PD and safety Kymera's unique target selection strategy, using TPD to drug undrugged targets, has been validated, with initial demonstration of IRAK4 degradation providing a biologically and clinically differentiated/superior profile than SMI KT-474 data positions this mechanism and drug as a potential best in class oral drug in HS, AD and a broader variety of immune-inflammatory diseases with large market opportunity potential The successful target selection strategy, molecular design, discovery and clinical execution and insights will allow acceleration and expansion of our pipeline in areas of high unmet need and large commercial opportunities ● In 2023 Kymera expects to share an expanded strategy to accelerate the path towards a disease agnostic global biotech KYMERA Ⓒ2022 KYMERA THERAPEUTICS, INC. PAGE 62#63KYMERA Q&A

Download to PowerPoint

Download presentation as an editable powerpoint.

Related

Fiscal 3Q Investor Presentation image

Fiscal 3Q Investor Presentation

Healthcare

FY23 Full-Year Results Presentation image

FY23 Full-Year Results Presentation

Healthcare

Healthcare Network P&L Statement and Expansion Projects image

Healthcare Network P&L Statement and Expansion Projects

Healthcare

Accreditation and Quality Assurance Overview image

Accreditation and Quality Assurance Overview

Healthcare

Investment Highlights image

Investment Highlights

Healthcare

Investor Presentation image

Investor Presentation

Healthcare

IDEAYA Biosciences Interim IDE397 Phase 1 Clinical Data and Q1 2022 Corporate Update image

IDEAYA Biosciences Interim IDE397 Phase 1 Clinical Data and Q1 2022 Corporate Update

Healthcare

BioAtla Investor Presentation Deck image

BioAtla Investor Presentation Deck

Healthcare