Slide 1: KT-621, Oral STAT6 Degrader, Phase 1b Results
KT-621, Oral STAT6 Degrader, Phase 1b Results 1
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 BroADen Phase 1b Data Jared Gollob, MD Chief Medical Officer Closing Remarks Nello Mainolfi, PhD Founder
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 • Leader in Targeted Protein Degradation (TPD) • Unique target selection strategy pursuing traditionally undrugged targets in highly validated pathways • Best-in-industry capabilities in hit finding and optimization of oral degraders Strategical
Slide 6: Immunology Remains a Large Underserved Market
Immunology Remains a Large Underserved Market Millions of Patients Do Not Have Access to Advanced Systemic Therapies Untreated ~62M (39%) ~160M Advanced Therapies >$100B PATIENTS ~5M (3%) IN ANNUAL SALES DIAGNOSED WITH FOR ADVANCED IMMUNOLOGICAL THERAPIES2 DISEASES1 Non-Advanced Therapies ~90M (58%)
Slide 7: Advanced Systemic Therapies Are Mostly Injectable Biologics
Advanced Systemic Therapies Are Mostly Injectable Biologics Biologics Have Numerous Limitations, Making Orals Preferred by Most Patients • Inconvenient, burdensome, >90% and often painful for patients WOULD SWITCH TO AN ORAL • Immunogenicity risks OPTION1 • In-office injection training costs HCPs va
Slide 8: Small Molecule Oral Degraders Can Transform Treatment of Diseases
Small Molecule Oral Degraders Can Transform Treatment of Diseases Oral Drugs with Biologics-like Activity Unlike Traditional Small Molecule Inhibitors (SMI), Degraders Allow for Continuous, Complete Pathway Blockade TYPICAL PK OF ORAL DRUGS PD OF DEGRADERS VS SMI SMI Suppression Drug (follows exposu
Slide 9: STAT6 Transcription Factor, Highly Validated but Undrugged Target
STAT6 Transcription Factor, Highly Validated but Undrugged Target STAT6 • STAT6 is the specific transcription factor in TRANSCRIPTION the IL-4/IL-13 pathway FACTOR • IL-4/IL-13 pathway is clinically validated by Dupilumab IL-4 Dupilumab IL-4 IL-13 dupilumab across multiple Type 2 allergic IL-4Rα γC
Slide 10: STAT6 Opportunity to Serve Millions of Patients with Type 2 Inflammation
STAT6 Opportunity to Serve Millions of Patients with Type 2 Inflammation DERMATOLOGY PATIENTS1 AD 43M CSU 4.4M PN 305K >140M <2M BP 166K GASTROENTEROLOGY TOTAL EoE 1.6M TREATED WITH POTENTIAL SYSTEMIC ADVANCED RESPIRATORY THERAPIES2 PATIENT IMPACT1 Asthma 55M COPD 34M CRSwNP 2.8M An oral STAT6 degra
Slide 11: KT-621: Compelling Preclinical Profile
KT-621: Compelling Preclinical Profile Preclinical Package Suggests Potential for Dupilumab-like Activity in a Pill Full Inhibition of IL-4/IL-13 Excellent Preclinical Exquisite Robust Degradation Pathways, More Potent Activity Comparable or Selectivity in Relevant Cell Types than Dupilumab Superior
Slide 12: KT-621: Compelling Clinical Profile
KT-621: Compelling Clinical Profile KT-621 Phase 1 Healthy Volunteer Data Suggests Potential for Dupilumab-like Activity in a Pill Robust STAT6 Degradation in Blood and Reductions in Multiple Disease-Relevant Skin Following Low Daily Oral Doses Type 2 Biomarkers 100 Serum TARC1 with Serum Eotaxin-32
Slide 13: KT-621 Development Plan Enables Efficient Path to Registration
KT-621 Development Plan Enables Efficient Path to Registration Across All Type 2 Diseases Ph3 Ph2b AD Dose Ph3: AD (Initial), Dose Ranging EoE, CSU, PN, BP Ongoing Data expected by Mid-2027 Ph1 HV Ph1b AD SAD-MAD Single Arm, Open Label ✓ Complete ✓ Today’s Release Ph3 Ph2b Asthma Dose Ph3: Asthma (I
Slide 14: BroADen KT-621 Phase 1b AD Study Surpassed Objectives
BroADen KT-621 Phase 1b AD Study Surpassed Objectives Effects on All Type 2 Biomarkers and Clinical Endpoints Were in Line with or in Some Cases Numerically Exceeded Published Data for Dupilumab at Week 4 BroADen Endpoints Phase 1b Results Highlights ü Strong fidelity of translation from Phase 1a he
Slide 15: KT-621: Phase 1b Atopic Dermatitis Trial Results
KT-621: Phase 1b Atopic Dermatitis Trial Results Jared Gollob, MD Chief Medical Officer 15
Slide 16: Agenda
Agenda • Atopic Dermatitis Overview • Trial Design • Demographics/Baseline Characteristics • STAT6 Degradation • Type 2 Inflammation Biomarkers • Clinical Endpoints • Safety 16
Slide 17: Atopic Dermatitis: Intensely Pruritic, Chronic and Underserved Disease
Atopic Dermatitis: Intensely Pruritic, Chronic and Underserved Disease Opportunity Exists to Transform the Treatment Paradigm • Chronic inflammatory disease that causes inflamed and irritated skin, making it itchy and painful • Majority of patients have disease onset as children and carry the diseas
Slide 18: Design Phase 1b in Moderate to Severe Atopic Dermatitis Patients
Design • Single arm, open label • 22 patients Phase 1b in Moderate to Severe • Oral, once daily dose for 28 days Atopic Dermatitis Patients • 14-day follow-up after dosing completed Baseline entry criteria: • Adult, moderate to severe AD patients Dosing • Two sequential dose cohorts EASI ≥16 • 100 m
Slide 19: BroADen Phase 1b Demographics
BroADen Phase 1b Demographics Generally Well-Balanced Across Treatment Cohorts 100 mg 200 mg Overall (n=10) (n=12) (n=22) Gender, n (%) Female 6 (60) 7 (58.3) 13 (59.1) Male 4 (40) 5 (41.7) 9 (40.9) Age, years, mean (SD) 30.1 (8.5) 33.0 (11.4) 31.7 (10.1) BMI, kg/m2, mean (SD) 32.8 (11.5) 30.8 (9.2)
Slide 20: BroADen Phase 1b Baseline Disease Characteristics
BroADen Phase 1b Baseline Disease Characteristics Generally Well-Balanced Across Treatment Cohorts 100 mg 200 mg Overall (n=10) (n=12) (n=22) vIGA-AD, n (%) Moderate (3) 6 (60) 6 (50) 12 (54.5) Severe (4) 4 (40) 6 (50) 10 (45.5) EASI Score, mean (SD) 23.5 (7.5) 26.1 (9) 24.9 (8.3) Other Disease Char
Slide 21: STAT6 Degradation
STAT6 Degradation apeutics,Inc. |KYMERA 21
Slide 22: Achieved Deep STAT6 Degradation in Blood
KT-621 Achieved Deep STAT6 Degradation in Blood Degradation Maintained for 28 Days Across Both Dose Cohorts Median % Change from Baseline in STAT6 Method: Flow Cytometry % STAT6 Change from Baseline • Median STAT6 degradation of 98% in blood in both dose groups after 4 KT-621 100 mg QD (n = 8) Media
Slide 23: Achieved Deep STAT6 Degradation in Skin
KT-621 Achieved Deep STAT6 Degradation in Skin Median % Change from Baseline in STAT6 Method: Targeted Mass Spec • Median STAT6 degradation of 94% in % STAT6 Change from Baseline skin in both dose groups after 4 weeks of treatment using targeted Mass Spec Median (Q1, Q3) • Deep skin degradation with
Slide 24: Type 2 Biomarkers
Type 2 Biomarkers apeutics,Inc. |KYMERA 24
Slide 25: Disease-Relevant Biomarkers of Type 2 Inflammation
Disease-Relevant Biomarkers of Type 2 Inflammation Eotaxin-3 TARC (CCL17) IgE IL-31 FeNO (CCL26) • TARC drives • Eotaxin-3 drives • IgE activates mast cells and • IL-31 is a key pruritogenic • FeNO (fractional exhaled chemotaxis of CCR4- chemotaxis of CCR3- basophils to release Type 2 cytokine produ
Slide 26: Higher Baseline TARC Levels Associated with Greater TARC Reductions Across Dupilumab Studies
Higher Baseline TARC Levels Associated with Greater TARC Reductions Across Dupilumab Studies Dupilumab data Median Median % Change from Baseline in Serum TARC Dupilumab Median Baseline Time of TARC Studies1 TARC % Change Measurement Median Baseline TARC (pg/mL) 1000 2000 3000 4000 5000 EOE POC 293 -
Slide 27: Higher Baseline TARC Associated with Greater Reductions Across Dupilumab and KT-621 Studies
Higher Baseline TARC Levels Associated with Greater TARC Reductions Across Dupilumab and KT-621 Studies KT-621 Ph1b AD 100 mg Dupilumab data KT-621 Ph1b AD 200 mg Median Median % Change from Baseline in Serum TARC Dupilumab & Median Baseline Time of TARC KT-621 Studies1,2 TARC % Change Measurement M
Slide 28: Similar TARC Reductions with KT-621 and Dupilumab at Similar Baseline Levels
Similar TARC Reductions with KT-621 and Dupilumab When Selecting for Similar Baseline TARC Levels KT-621 TARC BL < 1600 pg/mL Dupilumab data KT-621 Overall KT-621 TARC BL ≥ 1600 pg/mL Median Median % Change from Baseline in Serum TARC Dupilumab & Median Baseline Time of TARC KT-621 Studies1,2 TARC %
Slide 29: Achieved Median TARC Reduction of 74% in Patients with Comparable TARC Levels
KT-621 Achieved Median TARC Reduction of 74% in Patients with TARC Levels Comparable to Dupilumab AD Studies Stratified by Baseline TARC Stratified by Median Baseline TARC Stratified by Dose (1600 pg/mL) (800 pg/mL) Median % Change from Baseline in Median % Change from Baseline in Median % Change fr
Slide 30: Achieved Median Serum Eotaxin-3 Reduction of up to 73%
KT-621 Achieved Median Serum Eotaxin-3 Reduction of up to 73% Median % Change from Baseline in Eotaxin-3 KT-621 100 mg QD (n=7) Median % Change from Baseline KT-621 200 mg QD (n=11) in Serum Eotaxin-3 (Q1, Q3) • Rapid and robust median Eotaxin-3 reduction in both dose groups • Reduction exceeds the
Slide 31: Achieved Median Serum IgE Reduction of up to 14%
KT-621 Achieved Median Serum IgE Reduction of up to 14% Median % Change from Baseline in IgE Median % Change from Baseline KT-621 100 mg QD (n=10) in Serum Total IgE (Q1, Q3) KT-621 200 mg QD (n=12) • IgE reduction comparable to dupilumab data in AD studies at week 41 • More robust IgE reduction oft
Slide 32: Achieved Robust Serum IL-31 Reduction of up to 56%
KT-621 Achieved Robust Serum IL-31 Reduction of up to 56% Median % Change from Baseline in IL-31 KT-621 100 mg QD (n=8) Median % Change from Baseline KT-621 200 mg QD (n=8) in Serum IL-31 (Q1, Q3) • Robust reduction of pruritogenic cytokine IL-31 in both dose groups • First known demonstration of IL
Slide 33: Achieved up to 33% Reduction in FeNO in AD Patients
KT-621 Achieved up to 33% Reduction in FeNO in AD Patients Median % Change from Baseline in FeNO 40 KT-621 100 mg QD (n=10)1 KT-621 200 mg QD (n=12)2 20 Median % Change from Baseline 0 in FeNO (Q1, Q3) • Rapid and robust median FeNO -20 reduction in both dose groups -40 • First known demonstration o
Slide 34: Skin Biomarker Changes
Skin Biomarker Changes apeutics,Inc. |KYMERA 34
Slide 35: Significantly Downregulated Core Type 2 Inflammation Gene Set in Skin Lesions
KT-621 Significantly Downregulated Core Type 2 Inflammation Gene Set in Skin Lesions of AD Patients p < 0.01 KT-621 (n=18) Dupilumab2 (n=23) • Genes in signature1: • CCL26/Eotaxin-3 Signature Score • CCL17/TARC • CCL18/PARC • CCL13/MCP-4 • Changes in transcriptome comparable to published data for du
Slide 36: Significantly Downregulated AD Disease-relevant Gene Set in Skin Lesions
KT-621 Significantly Downregulated AD Disease-relevant Gene Set in Skin Lesions of AD Patients p < 0.01 KT-621 (n=18) • Genes in signature1: Dupilumab2 (n=23) • CCL26/Eotaxin-3 (Type 2) • CCL17/TARC (Type 2) • CCL18/PARC (Type 2) • CCL13/MCP-4 (Type 2) Signature Score • CXCL1/GRO-⍺ (Th17) • PI3/Pept
Slide 37: Clinical Endpoints
Clinical Endpoints apeutics, Inc. |KYMERA 37
Slide 38: Achieved 63% Overall Mean Reduction in EASI
KT-621 Achieved 63% Overall Mean Reduction in EASI Mean % Change from Baseline in EASI Mean (±SE) Percent Change from 0 KT-621 100 mg QD (n=10)1 Baseline in EASI Score KT-621 200 mg QD (n=12) • KT-621 achieved rapid and robust -20 KT-621 Overall (n=22)1 mean EASI reduction in both dose cohorts -40 •
Slide 39: Achieved Consistent EASI Reduction Across All Patient Subgroups
KT-621 Achieved Consistent EASI Reduction Across All Patient Subgroups, Regardless of Baseline TARC/EASI Mean % Change in EASI: Stratified by Baseline TARC Mean % Change in EASI: Stratified by Baseline EASI Mean (±SE) Percent Change from Mean (±SE) Percent Change from 0 0 BL TARC ≥ 1600 pg/mL (n=6)1
Slide 40: Achieved Robust Clinical Improvement Across EASI-50, EASI-75, and vIGA-AD 0/1
KT-621 Achieved Robust Clinical Improvement Across EASI-50, EASI-75, and vIGA-AD 0/1 Measures EASI-50 and EASI-75 vIGA-AD 0/1 Responders 100 KT-621 100 mg QD (n=9) 50 KT-621 200 mg QD (n=12) 83% KT-621 Overall (n=21) 80 76% 40 67% Responders (%) Responders (%) 60 30 22% 40 20 19% 33% 17% 29% 25% 20
Slide 41: Achieved 48% Overall Mean Reduction in SCORAD
KT-621 Achieved 48% Overall Mean Reduction in SCORAD Mean % Change in Total SCORAD Total SCORAD 10 Mean (±SE) Percent Change from 0 Baseline in Total SCORAD KT-621 100 mg QD (n=10)1 • SCORAD is a validated composite -10 KT-621 200 mg QD (n=12) measure of AD severity, integrating -20 KT-621 Overall (
Slide 42: Achieved Robust and Consistent Reductions in Itch
KT-621 Achieved Robust and Consistent Reductions in Itch Across Independent Clinical Measures Mean % Change in Peak Pruritus NRS Mean % Change in SCORAD Itch Mean (±SE) Percent Change from Mean (±SE) Percent Change from 20 20 Baseline in Peak Pruritus NRS 10 KT-621 100 mg QD (n=10) 10 KT-621 100 mg
Slide 43: Achieved Consistent Reduction of Peak Pruritus NRS Across Subgroups
KT-621 Achieved Consistent Reduction of Peak Pruritus NRS Across All Patient Subgroups, Regardless of Baseline TARC/EASI Mean % Change in PPNRS: Stratified by Baseline TARC Mean % Change in PPNRS: Stratified by Baseline EASI BL TARC ≥ 1600 pg/mL (n=6) BL EASI ≥ 22 (n=12) Mean (±SE) Percent Change fr
Slide 44: Achieved 76% Overall Mean Reduction in SCORAD-Sleeplessness
KT-621 Achieved 76% Overall Mean Reduction in SCORAD- Sleeplessness Mean % Change in SCORAD - Sleeplessness KT-621 100 mg QD (n=9)1 Baseline in SCORAD - Sleeplessness 20 KT-621 200 mg QD (n=11) Mean (±SE) Percent Change from 10 KT-621 Overall (n=20)1 0 -10 • SCORAD-Sleeplessness is a validated -20 m
Slide 45: Achieved Robust Improvement in Patient Quality of Life (POEM)
KT-621 Achieved Robust Improvement in Patient Quality of Life (POEM) 2 Mean Point Change in POEM POEM Responders (Improvement ≥4 Points) Baseline in POEM Score (Points) KT-621 100 mg QD (n=10) 0 KT-621 200 mg QD (n=12) Mean (±SE) Change from -2 100 KT-621 Overall (n=22) -4 MCID -6 80 75% 73% 70% -8
Slide 46: Achieved Robust Improvement in Patient Quality of Life (DLQI)
KT-621 Achieved Robust Improvement in Patient Quality of Life (DLQI) Mean Point Change in DLQI DLQI Responders (Improvement ≥ 4 points) 2 KT-621 100 mg QD (n=7) 0 100 KT-621 200 mg QD (n=11) Baseline in DLQI Score (Points) -2 KT-621 Overall (n=18) Mean (±SE) Change from -4 MCID 80 -6 64% Responders
Slide 47: Example of Clinical and Biomarker Response in Patient with Severe AD and Prior Dupilumab
Example of Clinical and Biomarker Response to KT-621 in BroADen Patient with Severe AD and Prior Dupilumab Treatment Pre and Day 29 Photos for EASI-75 Responder STAT6 Staining IHC Baseline Day 29 Baseline Day 29 % Change in EASI and Itch1 EASI SCORAD ITCH and PPNRS Percent Change from Baseline in Pe
Slide 48: Achieved Robust Impact on FeNO and ACQ-5 in AD Patients with Comorbid Asthma
KT-621 Achieved Robust Impact on FeNO and ACQ-5 in AD Patients with Comorbid Asthma ACQ-5 Responders Median % Change from Baseline in FeNO (n=4) Mean Point Change in ACQ-5 (n=4) (Improvement ≥ 0.5, n=4) Baseline in ACQ-5 Score (Points) 100 Median (Q1, Q3) Percent Change from 0.0 60 Mean (±SE) Change
Slide 49: Achieved Robust Impact on TNSS and RQLQ in AD Patients with Allergic Rhinitis
KT-621 Achieved Robust Impact on TNSS and RQLQ in AD Patients with Comorbid Allergic Rhinitis Mean Point Change TNSS Responders Mean Point Change RQLQ Responders in TNSS (n=7)1 (Improvement ≥ 0.55, n=7)1 in RQLQ (n=6)2 (Improvement ≥ 0.5, n=6)2 Baseline in RQLQ Score (Points) 100 100 Baseline in TNS
Slide 50: Demonstrated Robust Improvements Across All Key Clinical Efficacy Endpoints
KT-621 Demonstrated Robust Improvements Across All Key Clinical Efficacy Endpoints Results in Line With or in Some Cases Numerically Exceeded Published Data for Dupilumab at Week 4 KT-621 100 mg QD KT-621 200 mg QD KT-621 Overall Dupilumab 300 mg Q2W Day 29 (n=10) Day 29 (n=12) Day 29 (n=22) D28 Ph3
Slide 51: Safety
Safety apeutics,Inc. |KYMERA 51
Slide 52: BroADen Phase 1b Safety Summary
KT-621 BroADen Phase 1b Safety Summary • Well-tolerated with favorable safety at both 100 mg and 200 mg with a profile similar to what was observed in the Phase 1a healthy volunteer trial • No SAEs or Severe AEs • No dose-dependent pattern in the TEAEs • No related TEAEs or TEAEs leading to disconti
Slide 53: Positive BroADen Phase 1b Data Underscore Significant Potential of KT-621
Positive BroADen Phase 1b Data Underscore Significant Potential of KT- 621 in AD and Other Type 2 Allergic Diseases ü Once-a-day, Oral Dosing of KT-621 Achieved Deep STAT6 Degradation in Blood and Skin with Strong Translation from Healthy Volunteers ü Strong Effect on Disease-relevant Type 2 Inflamm
Slide 54: BroADen Phase 1b Summary
BroADen Phase 1b Summary Nello Mainolfi, PhD Founder, President and CEO 54
Slide 55: Kymera Completes the Clinical Translation of STAT6 Degradation
Kymera Completes the Clinical Translation of STAT6 Degradation Potential for Study Data “Dupilumab-in-a-pill” Profile Human Genetics STAT6 is a key driver of Type 2 inflammation ✓ Preclinical KT-621 degraded STAT6 and blocked IL-4/13 Type 2-driven inflammation in vitro/in vivo as effectively as dupi
Slide 56: Summary & Upcoming Milestones
BroADen Phase 1b Data Achieved Objectives and Underscore Significant Potential of KT-621 Summary & Upcoming Milestones • KT-621 BroADen AD patient data represent strong translation from Phase 1a healthy volunteer trial results • Results further validate KT-621’s oral, biologics-like profile with pot
Slide 57: Thank You Q&A
Thank You Q&A To ask a question, raise your virtual hand