Kymera Therapeutics, Inc. · NASDAQ:KYMR
Kymera Therapeutics — Corporate Update (June 2021)
20 slides from Kymera Therapeutics's corporate update, Jun 28, 2021
Slide 1: KT-474 Phase 1 Clinical Trial Update
WITH TARGETED PROTEIN DEGRADATION June 28, 2021 INVENTING NEW MEDICINES KT-474 Phase 1 Clinical Trial Update Exhibit 99.2
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
Slide 3: Kymera: A Leading TPD Company
Kymera: A Leading TPD Company VISION KEY PARTNERSHIPS INITIAL FOCUS FIRST-IN-CLASS Fully integrated, disease agnostic protein degrader medicine company Immune inflammation (I/I) and oncology CLINICAL PIPELINE PROOF-OF-BIOLOGY WELL-POSITIONED First to show placebo-controlled degrader proof-of-mechani
Slide 4: Kymera's Pipeline of Novel Protein Degraders
Discovery Pre-Clinical Phases 1-3 JAK/STAT STAT3 Liquid & Solid Tumors Ph1: 4Q21 STAT3 Autoimmune & Fibrotic Diseases IL-1R/TLR IRAK4 Atopic Dermatitis, Hidradenitis Suppurativa, Rheumatoid Arthritis, others Rights1 Next Milestone POB: 4Q21 Indication(s) Program Pathway IRAKIMiD (IRAK4, Ikaros, Aiol
Slide 5: Near-Term Milestones Provide Significant Opportunity
Near-Term Milestones Provide Significant Opportunity Liquid & Solid Tumors IRAK4 AD, HS, RA, others Indication(s) Program IRAKIMiD (IRAK4, Ikaros, Aiolos) MYD88MT DLBCL Discovery Programs & Platform Expected Upcoming Milestones Initiated SAD portion of Phase 1 trial in healthy volunteers (Feb 2021)
Slide 6: IRAK4 Degrader KT-474
IRAK4 Degrader KT-474
Slide 7: IRAK4 Targeting: Clinical Validation, Human Genetics De-risking and Degrader Advantage
IRAK4 Targeting: Clinical Validation, Human Genetics De-risking and Degrader Advantage IL-1R/TLR Pathway IL1-Ra/IL-1β : Rheumatologic Diseases IL-1a: Atopic Dermatitis IL-1β: CANTOS Data, Atherosclerosis, Lung Cancer IL-18: Macrophage Activation Syndrome IL-36: Generalized Pustular Psoriasis IRAK4 S
Slide 8: KT-474 Opportunity
Atopic Dermatitis (AD) Rheumatoid Arthritis (RA) Hidradenitis Suppurativa (HS) Additional Opportunities KT-474 Opportunity Immune-inflammatory disorders collectively impacting millions of patients in the U.S. Total Prevalence (U.S.) >1.3M >16.0M >325K Chronic, pruritic inflammatory skin disease Larg
Slide 9: KT-474: Potent and Specific IRAK4 Degradation Superior to Kinase Inhibition
KT-474: Potent and Specific IRAK4 Degradation Superior to Kinase Inhibition KT-474 DC50 = 2.1 nM in human immune cells KT-474 only degraded IRAK4 in human immune cells at concentration 10-fold above the DC90 KT-474 better able to inhibit IL-6 under both LPS and LPS + IL-1B than clinically active IRA
Slide 10: 85% IRAK4 Degradation Sufficient for Maximal In Vivo Efficacy in Preclinical Models
85% IRAK4 Degradation Sufficient for Maximal In Vivo Efficacy in Preclinical Models Ability to inhibit topical skin thickening induced by imiquimod was measured in a mouse model of psoriasis Orally dosed KT-474 inhibited thickening, a reflection of local and systemic inflammation, comparable to a to
Slide 11: KT-474 in Dog: Multi-dosing Required to Achieve Target Degradation
Dog Single Ascending Dose (SAD) IRAK4 Knockdown at Day 1 Dog Multiple Ascending Dose (MAD) IRAK4 Knockdown at Day 7 KT-474 in Dog: Multi-dosing Required to Achieve Target Degradation Orally-administered KT-474 achieves >85% knockdown of IRAK4 at Day 7 with repeat dosing in MAD study Multiple doses (
Slide 12: KT-474 Interim Phase 1 SAD Results
KT-474 Interim Phase 1 SAD Results
Slide 13: KT-474 Phase 1 Trial Design
KT-474 Phase 1 Trial Design Double-blind, Placebo-controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) trial 1 SAD Portion Healthy Volunteers 2 MAD Portion Healthy Volunteers 3 MAD Portion Patient Cohort Safety & tolerability 5 cohorts (up to 60 adult healthy subjects) 12 per co
Slide 14: KT-474 Phase 1 Trial Goals
KT-474 Phase 1 Trial Goals Establishing proof-of-mechanism and proof-of-biology Oral Bioavailability and Proof-of-Mechanism Efficacious plasma exposures that are safe and well-tolerated Proof-of-mechanism with IRAK4 knockdown following single KT-474 dose Predictable PK/PD supporting oral daily dosin
Slide 15: KT-474 Interim Phase 1 Healthy Volunteer SAD Overview
KT-474 Interim Phase 1 Healthy Volunteer SAD Overview Interim Results (Cohorts 1-4) Dosing Pharmacokinetic (PK) Features Safety & Tolerability 32 subjects randomized 24 subjects administered KT-474 8 subjects administered placebo Single dose administration of oral KT-474 tablet Dose levels (mg): 25
Slide 16: KT-474 Achieved Profound IRAK4 Degradation after Single Oral Dose
KT-474 Achieved Profound IRAK4 Degradation after Single Oral Dose that Lasted for at Least 6 Days Measured by mass spectrometry in circulating PBMC IRAK4 levels nadired at 48-72 hours IRAK4 reduction lasted for at least 144h (6 days post-dose) in all dose groups Absolute IRAK4 Levels Mean % Reductio
Slide 17: IRAK4 Degradation >85% Achieved Following Single KT-474 Dose
Percent IRAK4 Reduction in PBMC at 48 Hours Post-Dose using Mass Spectrometry Placebo (n=8) Cohort 1 (n=6) Cohort 2 (n=6) Cohort 3 (n=6) Cohort 4 (n=6) KT-474 dose - 25 mg 75 mg 150 mg 300 mg Mean IRAK4 Change +3% -38% -71% -78% -84% Median IRAK4 Change +16% -41% -71% -78% -90% p value* 0.0057 <0.00
Slide 18: Interim Results from Phase 1 Healthy Volunteer SAD Summary and Next Steps
Interim Results from Phase 1 Healthy Volunteer SAD Summary and Next Steps KT-474 interim Phase 1 results demonstrate degrader proof-of-mechanism, first time for TPD in a placebo-controlled study Median IRAK4 reduction of 90% (p<0.0001 vs placebo) and maximum reduction of 94% at 48 hours following si
Slide 19: KT-474 Development Plan
2020 2021 2022 2023 KT-474 Development Plan . 1. Estimated clinical development timeline. Non-Interventional Study Phase 1 HV SAD Phase 2 Trials (Sanofi-sponsored)1 Interim Data Updated Results HV POB Patient POB IND Final Results Interim Results HV MAD Patient Cohort SAD dosing initiated 1Q21 SAD/M
Slide 20: Thank You
THANK YOU investors@kymeratx.com media@kymeratx.com inquiries@kymeratx.com