Slide 1: KT-621 / STAT6 Degrader Phase 1 Healthy Volunteer Results
June 2, 2025 KT-621 / STAT6 Degrader Phase 1 Healthy Volunteer Results Revolutionizing Immunology with Oral Small Molecule Degrader Medicines
Slide 2: Agenda
Agenda Introduction Justine Koenigsberg Vice President, Investor Relations Revolutionizing Immunology with Oral Medicines Nello Mainolfi, PhD Founder, President and Chief Executive Officer KT-621 Phase 1 Healthy Volunteer Data Jared Gollob, MD Chief Medical Officer Question and Answer Session 2
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
Slide 4: Revolutionizing Immunology with Oral Medicines
Revolutionizing Immunology with Oral Medicines Nello Mainolfi, PhD, Founder, President and CEO 4
Slide 5: Kymera: Revolutionizing Immunology with Oral Medicines
Kymera: Revolutionizing Immunology with Oral Medicines • Targeted Protein Degradation (TPD) leader • Best-in-industry capabilities in hit finding and optimization of oral degraders • Unique target selection strategy pursuing traditionally undrugged targets in highly validated pathways • Portfolio po
Slide 6: A Proven Track Record of Reproducible Innovation
A Proven Track Record of Reproducible Innovation Productive, Reproducible and Scalable Innovation Engine for High Value Immunology Targets Technology Leader High Productivity Capabilities and know-how to 9 development candidates develop highly potent/specific oral 5 INDs degraders for undrugged prot
Slide 7: Unique Target Selection Strategy Drives Best-In-Class Pipeline
Unique Target Selection Strategy Drives Best-In-Class Pipeline Strong STAT6 Large clinical/ genetic/clinical commercial validation opportunities Undrugged or Clear path to inadequately IRF5 early clinical drugged IRAK4 differentiation targets FOCUS ON FIRST- AND BEST-IN-CLASS OPPORTUNITIES 7
Slide 8: Building a Best-In-Industry Oral Immunology Pipeline
Building a Best-In-Industry Oral Immunology Pipeline Potential Upcoming 2025 1H 2026 Indications Milestones Immunology – Oral Small Molecule Degraders Phase 1 Healthy Volunteer Results AD, Asthma, Ph2b AD STAT6 COPD, PN, Ph1b AD Data: 4Q25 Ph1 HV Ph1b AD Ph2b AD Start: 4Q25 CRSwNP, EoE, KT-621 BP, C
Slide 9: Immunology: A Large, Underserved Market
Immunology: A Large, Underserved Market Oral Degraders with ~160M Total Patients Across Key Immunologic Diseases1 Biologics-Like Profiles Advanced Therapies: ~5M (3%) Can Disrupt the Immunology Market >$100B >$500B? • ∼5M patients (3% of Non-Advanced total diagnosed) are Therapies: • ∼ 97% of the on
Slide 10: Small Molecule Oral Degraders Can Transform Immunology
Small Molecule Oral Degraders Can Transform Immunology Potentially Superior Profile to Injectable Biologics and Traditional Small Molecule Inhibitors (SMIs) Biologics can have several limitations, making orals preferred by most patients • Expensive, challenging to prescribe/reimburse • Immunogenicit
Slide 11: STAT6: An Ideal Immunology Target
STAT6: An Ideal Immunology Target STAT6 TRANSCRIPTION FACTOR Strong genetic/clinical validation Undrugged or inadequately drugged targets Large clinical/commercial opportunities Clear path to early clinical differentiation 11
Slide 12: STAT6: Highly Validated Genetically and Clinically
STRONG STAT6: Highly Validated Genetically and Clinically GENETIC/ CLINICAL VALIDATION STAT6 is the Key Signaling Node for IL-4 and IL-13 STAT6 TRANSCRIPTION • STAT6 is the obligate and specific transcription factor for IL-4/IL-13, FACTOR which only signal through STAT6 • STAT6 targeting should phen
Slide 13: Only STAT6 Degradation Has the Potential to Lead to Dupilumab-Like Pathway Inhibition
Only STAT6 Degradation Has the Potential to UNDRUGGED OR INADEQUATELY Lead to Dupilumab-Like Pathway Inhibition DRUGGED • STAT6, long pursued immunology “holy-grail” target, has remained undrugged before KT-621 SMI • Most oral approaches centered around small molecule inhibitors (SMIs), which have s
Slide 14: Building a STAT6 Franchise That Will Serve All Patients with Th2 Inflammation
Building a STAT6 Franchise That Will Serve All LARGE CLINICAL &COMMERCIAL Patients with Th2 Inflammation OPPORTUNITIES Patient DERMATOLOGY Numbers1 AD 42M CSU 4.5M Total Potential Patient Impact: Mild PN 305K BP 166K >130M 46.5% Only 1% Treated with Systemic GASTROENTEROLOGY patients1 Advanced Thera
Slide 15: KT-621 Development Plan Enables Efficient Path to Registration
KT-621 Development Plan Enables Efficient Path CLEAR PATH TO EARLY CLINICAL to Registration Across All Th2 Diseases DIFFERENTIATION Initial Parallel Phase 2b Trials in Moderate/Severe Atopic Dermatitis (AD) and Asthma are Expected to Support Subsequent Phase 3 Trials Across Multiple Dermatology, GI
Slide 16: KT-621: Compelling Preclinical Package
KT-621: Compelling Preclinical Package Exquisite Selectivity Highly Potent Robust Degradation Excellent Preclinical Efficacy Full inhibition of IL-4/IL-13 pathways KT-621 can degrade STAT6 90% STAT6 degradation leads to Complete STAT6 degradation selectivity more potent than dupilumab in all relevan
Slide 17: Phase 1 Healthy Volunteer Exceeded Study Objectives
Phase 1 Healthy Volunteer Exceeded Study Objectives Clinical Data Continues to Support a Dupilumab-like Profile KT-621 Healthy Volunteer KT-621 Healthy Volunteer Endpoint Objectives Data STAT6 Degradation in Blood 90%+ Complete STAT6 Degradation in Skin 90%+ Complete Well tolerated 16-fold above the
Slide 18: Phase 1 Healthy Volunteer Data Surpass Target Product Profile
Phase 1 Healthy Volunteer Data Surpass Target Product Profile (TPP) and Underscore Significant Potential of KT-621 Phase 1 HV Goals Exceeded Conclusions / Next Steps ✓ Potent Degradation • KT-6 profile surpasses Kymera’s T with compelling • >90% STAT6 degradation in blood in all doses above 1.5 mg p
Slide 19: KT-621/STAT6 Degrader: Dupilumab-like Activity in a Pill
KT-621/STAT6 Degrader: Dupilumab-like Activity in a Pill Phase 1 Healthy Volunteer Data Jared Gollob, MD, Chief Medical Officer 19
Slide 20: Agenda
Agenda • Trial Description • Demographics • Pharmacokinetics (PK) • SAD Degradation • MAD Degradation • Th2 Biomarkers • Safety 20
Slide 21: KT-621: Phase 1a SAD and MAD Healthy Volunteer Trial
KT-621: Phase 1a SAD and MAD Healthy Volunteer Trial Randomized, Double-blind, Placebo-controlled SAD and MAD in 118 Healthy Volunteers Part A Part B Single Ascending Dose Multiple Ascending Dose Primary (SAD) (MAD) • Safety & tolerability of 14x daily doses escalating single and 800 mg 200 mg multi
Slide 22: SAD/MAD Demographics
SAD/MAD Demographics Generally Well-Balanced Across Placebo and Treatment Arms SAD 1-6: SAD 1-6: MAD 1-6: MAD 1-6: PBO KT-621 PBO KT-621 (n=12) (n=36) (n=18) (n=52) Gender, n (%) Female 7 (58.3) 11 (30.6) 0 5 (9.6) Male 5 (41.7) 25 (69.4) 18 (100) 47 (90.4) Age, years, median (range) 34.5 (20, 50) 3
Slide 23: KT-621: Favorable PK Profile After Single and Multiple Dosing
SAD & MAD KT-621: Favorable PK Profile After Single and Multiple Dosing Steady-State (Day 14) Single Dose PK Profiles 6.25 mg SD n=6 Multi-Dose PK Profiles 1.5 mg QD n=9 25 mg SD n=6 12.5 mg QD n=7 KT-621 Plasma Concentration (ng/mL) KT-621 Plasma Concentration (ng/mL) 75 mg SD n=6 25 mg QD n=9 200
Slide 24: Single Doses Achieved Rapid, Deep and Prolonged STAT6 Degradation in Blood
SAD Single Doses of KT-621 Achieved Rapid, Deep and Prolonged STAT6 Degradation in Blood Absolute STAT6 Levels1 Mean Percent Change from Baseline in STAT6 1.5 Placebo n=12 100 Placebo n=12 6.25 mg SD n=6 6.25 mg SD n=6 25 mg SD n=6 25 mg SD n=6 Change from Baseline in STAT6 75 mg SD n=6 75 mg SD n=6
Slide 25: Single Dose Achieved >90% STAT6 Degradation in Blood Across All Dose Levels
SAD Single Dose Administration of KT-621 Achieved >90% STAT6 Degradation in Blood Across All Dose Levels >95% Mean STAT6 Degradation Achieved at Doses of 75 mg or Greater 20 Placebo Mean (±SE) Percent Change from Baseline in STAT6 6.25 mg SD 0 25 mg SD -20 75 mg SD -40 200 mg SD 400 mg SD -60 800 mg
Slide 26: Multiple Daily Doses Rapidly Achieved Complete STAT6 Degradation in Blood
MAD Multiple Daily Doses of KT-621 Rapidly (8hr) Achieved Complete STAT6 Degradation in Blood Mean Absolute STAT6 Levels1 Mean Percent Change from Baseline in STAT6 Placebo n=18 200 Placebo n=18 1.5 mg QD n=9 150 1.5 mg QD n=9 Mean (±SE) Percent Change from 100 12.5 mg QD n=7 12.5 mg QD n=7 1.0 50 2
Slide 27: Multiple Daily Doses Achieved >90% STAT6 Degradation in Blood
MAD Multiple Daily Doses of KT-621 Achieved >90% STAT6 Degradation in Blood at All Dose Levels Above 1.5 mg Complete Degradation Achieved at Doses of 50 mg or Greater 100 Mean (±SE) Percent Change Placebo n=18 from Baseline in STAT6 1.5 mg QD n=9 12.5 mg QD n=7 25 mg QD n=9 0 50 mg QD n=9 100 mg QD
Slide 28: Multiple Daily Doses Achieved Complete STAT6 Degradation in Skin
MAD Multiple Daily Doses of KT-621 Achieved Complete STAT6 Degradation in Skin Mean Absolute STAT6 Levels1 Mean Percent Change from Baseline in STAT6 0.3 Placebo n=17 100 Placebo n=17 1.5 mg QD n=7 1.5 mg QD n=7 Mean (SE±) Percent Change 12.5 mg QD n=7 12.5 mg QD n=7 from Baseline in STAT6 25 mg QD
Slide 29: Complete STAT6 Degradation in Skin at All Doses ≥5 mg
MAD Multiple Daily Doses of KT-621 Achieved Complete STAT6 Degradation in Skin at All Doses ≥5 mg Mean (±SE) Percent Change from Baseline in STAT6 0 Placebo n=17 1.5 mg QD n=7 12.5 mg QD n=7 25 mg QD n=8 -50 50 mg QD n=9 100 mg QD n=9 200 mg QD n=9 -100 7 14 7 14 7 14 7 14 7 14 7 14 7 14 Day Mean% C
Slide 30: Th2 Biomarkers
Th2 Biomarkers \ ©2025 Kymera Therapeutics ,KYMERA 30
Slide 31: TARC, IgE, and Eotaxin-3: Validated Biomarkers of Th2 Biology
TARC, IgE, and Eotaxin-3: Validated Biomarkers of Th2 Biology Not Typically Elevated in HV Subjects Without Th2-Driven Disease1 TARC (CCL17) Immunoglobulin E (IgE) Eotaxin-3 (CCL26) • TARC is the chemokine responsible • IgE activates mast and basophil cells to • The chemokine responsible for for che
Slide 32: TARC and IgE Assessment in Dupilumab Healthy Volunteer Study
TARC and IgE Assessment in Dupilumab Healthy Volunteer Study Dupilumab Decreased TARC up to 35% in a High Variability and Minimal Changes Non-Dose Dependent Manner in Healthy in IgE after 1-4 Week Volunteers from Baseline in TARC Days from Baseline in IgE Median % Change Median % Change Days Li et a
Slide 33: Multiple Daily Doses Achieved Up to 37% Median TARC Reduction
MAD Multiple Daily Doses of KT-621 Achieved Up to 37% Median TARC Reduction Median Percent Change from Mean Percent Change from Baseline in Serum TARC1 Baseline in Serum TARC1 Median % Mean % Placebo n=18 Day 14 Change Change Percent Change from Baseline in TARC 1.5 mg QD n=9 in TARC in TARC 20 20 1
Slide 34: High Variability and Minimal Changes in IgE with Multiple Daily Oral Doses
MAD High Variability and Minimal Changes in IgE with Multiple Daily Oral Doses of KT-621 Median % Change from Mean % Change from Baseline in IgE1 Baseline in IgE1 Median% Mean % 10 10 Placebo n=18 Day 14 Change Change In IgE In IgE Percent Change from Baseline in IgE 1.5 mg QD n=9 12.5 mg QD n=7 Pla
Slide 35: Multiple Daily Doses Achieved Up to 63% Median Eotaxin-3 Reduction
MAD Multiple Daily Doses of KT-621 Achieved Up to 63% Median Eotaxin-3 Reduction Median Percent Change from Mean Percent Change from Baseline in Serum Eotaxin-31 Baseline in Serum Eotaxin-31 Median % Mean % Percent Change from Baseline in Eotaxin-3 Placebo n=18 Day 14 Change Change 20 20 1.5 mg QD n
Slide 36: Healthy Volunteer SAD/MAD Safety Summary
SAD & MAD Healthy Volunteer SAD/MAD Safety Summary KT-621 Well Tolerated Across All Doses Evaluated Undifferentiated from Placebo TRAEs by Preferred Term: SAD Cohort • No SAEs SAD 1-6: SAD 1-6: AE Term (severity) PBO KT-621 • No Severe AEs (n=12) (n=36) • No dose dependent pattern in the TEAEs Heada
Slide 37: Phase 1 Healthy Volunteer Data Surpass Target Product Profile
Phase 1 Healthy Volunteer Data Surpass Target Product Profile (TPP) and Underscore Significant Potential of KT-621 Phase 1 HV Goals Exceeded Conclusions / Next Steps ✓ Potent Degradation • KT-6 profile surpasses Kymera’s T with compelling • >90% STAT6 degradation in blood in all doses above 1.5 mg p
Slide 38: Thank You Q&A
Thank You Q&A To ask a question, raise your virtual hand