Kymera Therapeutics, Inc. · NASDAQ:KYMR
Kymera Therapeutics — Investor Day (May 2025)
52 slides from Kymera Therapeutics's investor day presentation, May 9, 2025
Slide 1: Oral Medicines with Biologics-like Activity
May 9, 2025 Oral Medicines with Biologics-like Activity Immunology Innovation Day
Slide 2: Agenda
Agenda Kymera’s Immunology Strategy Nello Mainolfi, PhD, Founder, President and Chief Executive Officer STAT6 (KT-621) Update Jared Gollob, MD, Chief Medical Officer IRF5 (KT-579): Drugging a Genetically Validated Target Veronica Campbell, Senior Director, Immunology Question and Answer Session
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: Kymera's Immunology Strategy
Kymera’s Immunology Strategy Nello Mainolfi, PhD Founder, President and CEO 4
Slide 5: Revolutionizing Immunology: Oral Drugs with Biologics-Like Efficacy
Revolutionizing Immunology: Oral Drugs with Biologics-Like Efficacy Science-driven Clinical Stage Organization with Industry-leading Oral Immunology Pipeline • Targeted Protein Degradation (TPD) leader • Best-in-industry capabilities in hit finding and optimization of oral degraders • Unique target
Slide 6: Clear Vision and History of Strong Execution
Clear Vision and History of Strong Execution VISION EXECUTION IMPACT • Reinventing the treatment of human • Delivered 5 new investigational • Dosed >300 healthy volunteers/patients to disease as a fully integrated degrader drugs into the clinic date across clinical pipeline commercial global biotech
Slide 7: Targeted Protein Degradation
Targeted Protein Degradation New Modality Expanding the Range of Treatable Disease Targeted Protein Degradation can unlock the undrugged proteome Existing modalities have limitations that restrict their application leaving millions of patients without adequate treatment options. Heterobifunctional D
Slide 8: 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 9: 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 Biologics can have several limitations, making orals preferred by most patients • Expensive, challenging to prescribe/reimburse • Immunogenicity 75% •
Slide 10: Kymera, Industry Leader at Developing Oral Degrader Drugs
Kymera, Industry Leader at Developing Oral Degrader Drugs Established Drug Discovery Engine to Address Historically Undrugged/Inadequately Drugged Proteins Key Capabilities Proven Results • Productivity Fragment Cysteine Virtual DEL -based Covalent HTS ASMS Screen Screen Screening Kymera has deliver
Slide 11: Unique Target Selection Strategy Drives Best-In-Class Pipeline
Unique Target Selection Strategy Drives Best-In-Class Pipeline Undrugged or Clear path to inadequately STAT6 early clinical drugged differentiation targets Strong IRF5 IRAK4 Large clinical/ genetic/clinical commercial validation opportunities FOCUS ON FIRST- AND BEST-IN-CLASS OPPORTUNITIES 11
Slide 12: Complementary First-in-Class Mechanisms in Highly Validated Pathways
Complementary First-in-Class Mechanisms in Highly Validated Pathways STAT6 IRF5 IRAK4 TRANSCRIPTION TRANSCRIPTION SCAFFOLDING FACTOR FACTOR KINASE IL-4/13 Pathway Type I IFN, cytokines (TNFα, IL- IL-1R/TLR Pathway 6, IL-12/23) and autoantibodies Type I IL-4 Type II IL-4 TLR Cytokines Receptor Recept
Slide 13: Addressing Major Immunology Indications
Addressing Major Immunology Indications Orals with Biologics-Like Activity to Transform Immunology Immune Classes & Dermatology Respiratory GI Rheumatology Indications AD HS CSU PN BP Asthma COPD CRSwNP IBD EoE RA SLE SSc jörgren’s DM STAT6 KT-621 IRF5 KT-579 IRAK4 KT-4741 Synergies and know-how acr
Slide 14: Oral Degraders with Biologics-like Efficacy Can Transform Immunology
Oral Degraders with Biologics-like Efficacy Can Transform Immunology Existing Therapies Address 10% or Less of Diagnosed Patients1 STAT6 IRF5 IRAK4 TRANSCRIPTION FACTOR TRANSCRIPTION FACTOR SCAFFOLDING KINASE Key Indications: AD, Asthma, COPD, Key Indications: SLE, RA, UC, CD, Key Indications2: HS,
Slide 15: Pipeline with Clear Line of Sight to Large Value Creation
Pipeline with Clear Line of Sight to Large Value Creation Potential Upcoming 2025 1H 2026 Indications Milestones Immunology – Oral Small Molecule Degraders Phase 1 HV Results Ph1 HV Data: June AD, Asthma, Ph2b AD STAT6 COPD, PN, Ph1b AD Data: 4Q25 Ph1 HV Ph1b AD Ph2b AD Start: 4Q25 CRSwNP, EoE, KT-6
Slide 16: STAT6 (KT-621): Dupilumab-like Activity in a Pill
STAT6 (KT-621): Dupilumab-like Activity in a Pill Jared Gollob, MD Chief Medical Officer 16
Slide 17: STAT6 Degrader: Opportunity for Dupilumab-Like Activity in a Pill
STAT6 Degrader: Opportunity for Dupilumab-Like Activity in a Pill STAT6 Highly Validated but Undrugged Target TRANSCRIPTION FACTOR • IL-4/IL-13 pathway highly validated by dupilumab (IL-4Rα mAb): approved in 7 Th2 allergic indications, >$15B of yearly sales IL-4/13 Pathway • STAT6 is the specific tr
Slide 18: Oral STAT6 Degraders Can Transform the Treatment Paradigm
Oral STAT6 Degraders Can Transform the Treatment Paradigm in Multiple Indications De-risked by Dupilumab Patient Patient DERMATOLOGY RESPIRATORY Numbers1 Numbers1 AD 55M Asthma 43M CSU 4.5M COPD COPD 34M 34M PN 305K CRSwNP CRSwNP 166K 2.8M BP 166K GASTROENTEROLOGY Total Potential Patient Impact: EoE
Slide 19: KT-621: Kymera's First-in-Class STAT6 Degrader
KT-6 : Kymera’s First-in-Class STAT6 Degrader Excellent Degradation Potency and Selectivity Complete STAT6 degradation selectivity in Picomolar potency and consistent Complete STAT6 Degradation Selectivity Picomolar Potency and degradation Consistent across Degradation all disease relevant cell huma
Slide 20: KT-621 Has Preclinical Activity Comparable or Superior to Dupilumab
KT-621 Has Preclinical Activity Comparable or Superior to Dupilumab KT-621 Fully Blocks IL-4/13 Pathway KT-621 Blocks Th2 Inflammation in Vivo in Human Th2 Functional Assays Equal to/Better than a Saturating Dose with IC50’s Lower than Dupilumab of Dupilumab in Mouse HDM Asthma Model1 IL-13 Induced
Slide 21: KT-621 Degrades STAT6 at Low Oral Doses in All Relevant Tissues
KT-621 Degrades STAT6 at Low Oral Doses in All Relevant Tissues Dose Responsive STAT6 Degradation in Dog Blood STAT6 Degradation in All Relevant Tissues in NHP Post 7 Days of KT-621 QD Oral Dosing Post 14 Days of KT-621 (10 mpk QD) Oral Dosing 0 0 STAT6 % Change from Baseline STAT6 % Change from Bas
Slide 22: KT-621 Development Plan Enables Efficient Path to Registration
KT-621 Development Plan Enables Efficient Path to Registration Across all Th2 Diseases 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 and Respiratory Indications Ph2b AD Ph3 AD, C
Slide 23: KT-621: Phase 1a Trial
KT-621: Phase 1a Trial Double-blind, Placebo-controlled SAD and MAD in Healthy Volunteers • Safety & tolerability of June 2025 Part A Primary escalating single and Single Ascending Dose multiple doses of KT-621 Phase 1 Healthy (SAD) Volunteer Data Secondary • Pharmacokinetic measures Key trial aim i
Slide 24: KT-621: BroADen Phase 1b Trial
KT-621: BroADen Phase 1b Trial Single Arm, Open Label in Atopic Dermatitis Patients • Single arm, open label 4Q 2025 Design • ~20 patients Adult, Moderate to Phase 1b AD • Daily dose for 28 days; Severe AD Patients 14-day safety follow-up Patient Data Baseline entry criteria: EA I ≥ 6; • Single dose
Slide 25: KT-621 Summary
KT-621 Summary Dupilumab-like Activity in a Pill KT-621 is the first • In preclinical in vitro and in • STAT6 degradation was well-tolerated highly selective and vivo studies, it is equal or in multiple preclinical safety studies at potent STAT6 superior to dupilumab >40x efficacious concentration d
Slide 26: IRF5 (KT-579): Drugging a Genetically Validated Transcription Factor
IRF5 (KT-579): Drugging a Genetically Validated Transcription Factor with an Oral Degrader Veronica Campbell Senior Director, Immunology 26
Slide 27: IRF5: Agenda
IRF5: Agenda • Value proposition • Biological function, genetics and clinical validation • Opportunity in I&I • KT-579: A highly potent and selective IRF5 degrader • In vitro and in vivo data • Next steps 27
Slide 28: KT-579: a First-in-Class IRF5 Oral Degrader
KT-579: a First-in-Class IRF5 Oral Degrader • A potent, selective, oral IRF5 degrader with broad potential utility across multiple diseases • Robust activity in: • Primary human cells KT-579 • Lupus patient donor cells IRF5 • In vivo models of Lupus and RA • Well-tolerated in safety studies up to Pr
Slide 29: IRF5: Targeting a Genetically Validated Undrugged Transcription Factor
IRF5: Targeting a Genetically Validated Undrugged Transcription Factor IRF5 MASTER An Undrugged Transcription Factor, Master Regulator of REGULATOR Immunity TLR Agonists • IRF5 regulates pro-inflammatory cytokines, Type I IFN production and Dectin1/2 autoantibody production in a cell and activation-
Slide 30: IRF5: Master Regulator of Innate and Adaptive Immune Responses
IRF5: Master Regulator of Innate and Adaptive Immune Responses M1 DCs Monocytes B cells Macrophages IRF5 Expression and Activation • IRF5 is selectively expressed and activated in specific cell types: Dendritic Cells (DCs), Monocytes, Macrophages, and B cells • IRF5 is activated by pattern recogniti
Slide 31: IRF5 Genetically Validated in Multiple Autoimmune Diseases
IRF5 Genetically Validated in Multiple Autoimmune Diseases Human Genetics Mouse IRF5 KO Studies • Multiple GWAS studies identify IRF5 as an autoimmune • KO mice are viable and fertile; with normal B cell susceptibility gene1 development • IRF5 risk haplotypes and hyperactivated IRF5 levels in • IRF5
Slide 32: Stimuli and Cell Specific IRF5 Activation in Clinically Validated Pathways
Stimuli and Cell Specific IRF5 Activation in Clinically Validated Pathways IRF5 degradation has the potential to selectively block inflammation and restore immune regulation by inhibiting pro-inflammatory cytokines, Type I IFN and autoantibody production Activation by: TLR2, -4, -5, -7, -8, -9, Dect
Slide 33: IRF5: A Novel Mechanism in High Unmet Need Indications in I&I
IRF5: A Novel Mechanism in High Unmet Need Indications in I&I Patient Patient RHEUMATOLOGY GI Numbers Numbers RA 4.7M UC 1.9M Lupus1 1.2M CD 1.5M Sjögren's 765K SSc 200K Total Potential Patient Impact2: DM >100K >10M patients IRF5 functional risk variants associate with increased susceptibility to m
Slide 34: KT-579 Preclinical Characterization
KT-579 Preclinical Characterization Human Primary Cells (Healthy) SLE Patient Samples In Vivo Disease Models ✓ Degradation and selectivity Inhibition of: ✓ Inhibition of pro-inflammatory cytokines in vivo ✓ Pro-inflammatory cytokines ✓ Pro-inflammatory cytokines ✓ MRL/lpr Lupus model inhibition ✓ Ty
Slide 35: KT-579 Preclinical Characterization
KT-579 Preclinical Characterization Human Primary Cells (Healthy) SLE Patient Samples In Vivo Disease Models ✓ Degradation and selectivity Inhibition of: ✓ Inhibition of pro-inflammatory cytokines in vivo ✓ Pro-inflammatory cytokines ✓ Pro-inflammatory cytokines ✓ MRL/lpr Lupus model inhibition ✓ Ty
Slide 36: KT-579: An Exquisitely Selective and Picomolar Oral IRF5 Degrader
KT-579: An Exquisitely Selective and Picomolar Oral IRF5 Degrader Equipotent Degradation in Relevant KT-579: 10xDC90 in hPBMCs @ 24 hrs Equipotent Degradation in relevant hPBMC subsets @ hPBMC Subsets @ 24hrs 24hrs Cell Subsets KT-579 DC50 (nM) PBMC 0.8 Selectivity Binding and Cellular Assays KT-579
Slide 37: KT-579 Selectively Depletes IRF5 Downstream of TLR Activation
KT-579 Selectively Depletes IRF5 Downstream of TLR Activation IRF5 IRF3 IRF7 IRF5 is Mostly in Unstimulated Control Cytoplasm IRF5 degradation in human monocytes IRF5 selectively depletes Translocated R848 (TLR7/8) TLR7/8 induced IRF5 into Nucleus 2h nuclear translocation, while sparing IRF7 and IRF
Slide 38: KT-579 Potently Inhibits Production of Key Pro-Inflammatory Cytokines and Type I IFN
KT-579 Potently Inhibits Production of Key Pro-Inflammatory Cytokines and Type I IFN in Human Primary Cellular Assays HuMonocytes + R848 HuMonocytes + ssRNA40 Cytokine KT-579 IL12p40 Production Biology Receptor Stim Cell IFNβ Production Readout DC50 (nM) N-3 donors N-2 donors TLR8 ssRNA40 Monocytes
Slide 39: KT-579 Dampens Type I IFN Downstream Response
KT-579 Dampens Type I IFN Downstream Response Impact on Type I Response Following TLR8 Activation Inhibition of Select Downstream Interferon-Stimulated Genes (ISGs) ssRNA40 (TLR8) Stim KT-579 Afimetoran DMSO RSAD2 IFIT1 Log(2) fold change KT-579 blocks Type I IFN dependent genes at least as KT-579 i
Slide 40: KT-579 Preclinical Characterization
KT-579 Preclinical Characterization Primary Cells SLE Patient Samples In Vivo Disease Models ✓ Degradation and selectivity Inhibition of: ✓ Inhibition of pro-inflammatory cytokines in vivo ✓ Pro-inflammatory cytokines ✓ Pro-inflammatory cytokines ✓ MRL/lpr Lupus model inhibition ✓ Type-I IFN ✓ NZBW1
Slide 41: KT-579 Effectively Blocks Pro-inflammatory Cytokines and Type I IFN Induction in SLE Patient Samples
KT-579 Effectively Blocks Pro-inflammatory Cytokines and Type I IFN Induction in SLE Patient Samples Pro-inflammatory Cytokines Type I IFN TNFα IL-12p40 IL-6 IL-1β IFNβ Degrader Treatment (100nM) for 24h, Followed by 24h of R848 (TLR7/8) Stimulation KT-579 inhibits pro-inflammatory cytokines and Typ
Slide 42: KT-579 Significantly Inhibits IgG Levels in Human SLE Patient Samples
KT-579 Significantly Inhibits IgG Levels in Human SLE Patient Samples KT-579 Inhibits IgG Levels After TLR9 Activation (CpG-B) Total IgG IgG1 IgG2 IgG3 IgG4 7-day B cell culture with CpG-B (TLR9) + 100nM degrader treatment KT-579 reduces TLR9 (CpG-B) induced plasmablast differentiation and inhibits
Slide 43: KT-579 Preclinical Characterization
KT-579 Preclinical Characterization Primary Cells SLE Patient Samples In Vivo Disease Models ✓ Degradation and selectivity Inhibition of: ✓ Inhibition of pro-inflammatory cytokines in vivo ✓ Pro-inflammatory cytokines ✓ Pro-inflammatory cytokines ✓ MRL/lpr Lupus model inhibition ✓ Type-I IFN ✓ NZBW1
Slide 44: KT-579 Effectively Blocks Circulating Cytokines In Mouse Model
KT-579 Effectively Blocks Circulating Cytokines In Mouse Model1 IRF5 Degradation in Mouse Spleen KT-579 Leads to Significant Dose-dependent Inhibition of TLR7-R848 Following 4 Days of Oral Dosing and TLR9-CpG-B Cytokine Production in Mouse TLR7-R848 TLR9-CpGB-SL01 0% 17% 14% 53% 79% 89% 90% M5049=TL
Slide 45: KT-579 Demonstrated Generally Better Outcomes in MRL/lpr Model of Lupus
KT-579 Demonstrated Generally Better Outcomes than Approved or Clinically Active Drugs in MRL/Ipr1 Model of Lupus Proteinuria Survival # #Total Treatment survival Vehicle 10/15 * ** KT-579 50 mg/kg, p.o. 15/15 *** KT-579 200 mg/kg, p.o. 15/15 **** Afimetoran, 10 mg/kg, p.o. 14/15 Deucravacitinib, 30
Slide 46: IRF5 Degradation Demonstrated Better Outcomes in NZBW1 Mouse Lupus Model
IRF5 Degradation Demonstrated Generally Better Outcomes than Approved or Clinically Active Drugs in NZBW1 Spontaneous1 Mouse Lupus Model Early, Sustained and Complete Superior Activity Reducing Decreased Proteinuria Reduction in Anti-dsDNA Abs Anti-dsDNA at Week 37 **** **** *** *** # ** ** ****p<0.
Slide 47: KT-579 Reduces Joint Swelling in a Mouse Model of RA
KT-579 Reduces Joint Swelling in a Mouse Model of RA Treatment with KT-579 Leads to Significant Reduction in Joint Reduction in Circulating IL-12 Levels and Infiltrating Swelling Comparable to Tofacitinib in the AIA1 Mouse Model of RA Synovial IFNy+ Th1 Cells IL-12p40 Serum Levels Day 2 IFNγ+ CD4+ T
Slide 48: KT-579 Potently Degrades at Low Oral Doses in NHP with an Excellent Safety Profile
KT-579 Potently Degrades at Low Oral Doses in NHP with an Excellent Safety Profile IRF5 Degradation in NHP Blood Post 7 Days of KT-579 QD Oral Dosing 0 IRF5 % Change from Baseline 24hrs After Last Dose • KT-579 potently degrades IRF5 across multiple preclinical species with low oral doses -50 • KT-5
Slide 49: IRF5 Program Executive Summary
IRF5 Program Executive Summary Vision: KT-579 is a first-in-class, oral IRF5 degrader to target debilitating diseases driven by Type 1 interferon, pro-inflammatory cytokines (TNFα, IL-1b, IL-6, IL-12p40, IL-23) and autoantibodies such as LE, jögren’s disease, dermatomyositis, RA, IBD and potentially
Slide 50: Pipeline with Clear Line of Sight to Large Value Creation
Pipeline with Clear Line of Sight to Large Value Creation Potential Upcoming 2025 1H 2026 Indications Milestones Immunology – Oral Small Molecule Degraders Phase 1 HV Results Ph1 HV Data: June AD, Asthma, Ph2b AD STAT6 COPD, PN, Ph1b AD Data: 4Q25 Ph1 HV Ph1b AD Ph2b AD Start: 4Q25 CRSwNP, EoE, KT-6
Slide 51: A Powerful Strategy for Patients
A Powerful Strategy for Patients Harnessing the powerful mechanism of Demonstrated consistent and TPD to develop innovative, differentiated compelling preclinical packages medicines that address critical health across our immunology programs problems in immunology Established unique capabilities to
Slide 52: Thank You Q&A
Thank You Q&A KYMERA THERAPEUTICS 500 North Beacon Street, 4th Floor Watertown, MA 02472