KT-579 / Kymera Therap - LARVOL DELTA

First-in-class Oral IRF5 Degrader, KT-579, Demonstrates Significant Activity Alone or in the Presence of Background Therapies in Preclinical Lupus Models (ACR Convergence 2026) - "Background therapy maintenance includes hydroxychloroquine (HCQ) while aiming to minimize chronic glucocorticoid or steroid use. Collectively, the preclinical data reported here indicate that KT-579 single agent therapeutic activity can robustly inhibit human disease relevant biomarkers and disease progression in translational models, independent of background therapy. These findings position KT-579 as a novel, first-in-class, oral therapeutic agent with the potential to transform the treatment landscape and reduce background therapeutic burden in SLE and other autoimmune diseases."

Preclinical • Immunology • Inflammatory Arthritis • Lupus • IRF5 • TLR7 • TLR8

Enrollment is ongoing in the KT-579 Phase 1 clinical trial in healthy volunteers, with data expected in the fourth quarter of 2026. (GlobeNewswire) - "The Company plans to initiate a Phase 1b patient proof-of-concept trial in lupus soon after the completion of the healthy volunteer trial."

New P1 trial • P1 data • Immunology • Lupus

Kymera Therapeutics Inc…presented preclinical data for KT-579, an oral IRF5 degrader being developed for lupus treatment (Investing.com) - "In preclinical studies, KT-579 demonstrated activity in lupus patient-derived cells and multiple disease models. The compound selectively degraded IRF5, blocked TLR-induced IRF5 nuclear translocation, and reduced inflammatory mediators including Type I interferon and pro-inflammatory cytokines...In animal studies, KT-579 showed dose-dependent IRF5 degradation and inhibition of TLR7- and TLR9-induced cytokine release, including TNFα, IL-6, IL-12 and IFNβ...A Phase 1 healthy volunteer trial is currently ongoing. The study is evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of KT-579 compared to placebo. The company expects to report data from the trial in the second half of 2026...Following the healthy volunteer study, Kymera plans to initiate a patient proof-of-concept trial, likely in lupus."

P1 data • Preclinical • Immunology

Firts-in-Class Oral IR5 Degrader, KT-579, Demonstrates Selective and Potent In vitro and In vivo Activity in Human Cellular Assays and Mouse Models of Lupus (EULAR 2026) - "Conclusions We report here the first potent, selective, oral IRF5 degrader, KT-579, that inhibits in vitro and in vivo activity in endosomal TLR induced immune responses in human SLE patient derived cells and in lupus mouse models, demonstrating superior or similar activity to existing standards of care agents. These findings position KT-579 as a potential first-in-class approach capable of broadly modulating pathogenic pathways in SLE and other autoimmune diseases."

IO biomarker • Preclinical • Immunology • Inflammatory Arthritis • Lupus • Nephrology • Renal Disease • Targeted Protein Degradation • IFNB1 • IL12A • IL23A • IL6 • IRF5 • TLR7 • TLR8 • TLR9 • TNFA • TYK2

Potent and Selective First-in-Class Oral IRF5 Degrader, KT-579, Inhibits Endosomal TLR-induced Responses in SLE Derived PBMCs and Significantly Reduces Disease Activity in the MRL.lpr Mouse Lupus Model (FOCIS 2026) - "In the MRL.lpr lupus model, KT-579 doses achieving >85% degradation led to significant reduction of proteinuria and 100% survival through end of study, reduction of both anti-dsDNA and anti-Sm autoantibodies in plasma, and reduction of IgG deposition in kidney, with results superior to active comparators including a TLR7/8 small molecule inhibitor. These findings position KT-579 as a novel, first-in-class, oral IRF degrader with the potential to transform the treatment landscape of lupus and multiple autoimmune diseases driven by IRF5 dysregulation."

IO biomarker • Preclinical • Immunology • Inflammatory Arthritis • Lupus • IFNB1 • IL12A • IL6 • IRF5 • TLR7 • TLR8 • TLR9 • TNFA

Business Highlights, Recent Developments and Upcoming Milestones (GlobeNewswire) - "...Company commenced dosing in the BREADTH Phase 2b clinical trial...Recruitment is ongoing, with data expected to be reported in late 2027...In May 2026, the Company will present on KT-621 at multiple medical meetings, including a late-breaking oral presentation at the Society of Investigative Dermatology...the Company will have a featured oral presentation at the American Thoracic Society (ATS) Annual Meeting Respiratory Innovation Summit focused on the potential of KT-621 to transform treatment paradigms in respiratory care....The Company expects to report data from the trial in the second half of 2026...Building on KT-579’s preclinical profile, the Company plans to present new data further characterizing its activity across autoimmune disease models, including IBD at Digestive Disease Week (DDW) in May, as well as lupus at the European Alliance of Associations for Rheumatology (EULAR) Congress and the Federation of Clinical Immunology Societies (FOCIS)..."

P1 data • P2b data • Preclinical • Asthma • Immunology • Inflammatory Bowel Disease • Lupus • Respiratory Diseases

In February 2026, the Company, after IND-clearance from the FDA, commenced dosing in the first-in-human KT-579 Phase 1 clinical trial in healthy volunteers. (GlobeNewswire) - "The Phase 1 study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of orally administered KT-579 compared to placebo. The key study aim is to show that KT-579 can robustly degrade IRF5 in blood at doses that are safe and well-tolerated. The functional impact of IRF5 degradation on the induction of Type I interferons, proinflammatory cytokines, and inflammatory pathway gene transcripts by TLR 7/8/9 agonists will also be assessed with whole blood ex vivo stimulation assays. The Company expects to report data from the trial in the second half of 2026."

First-in-human • IND • P1 data • Trial status • Immunology

First-in-human Study of Orally Administered KT-579 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Kymera Therapeutics, Inc.

First-in-human • New P1 trial

Kymera Therapeutics Outlines Key 2026 Objectives... (The Manila Times) - "Key Upcoming KT-579 Milestones: Initiate the first-in-human Phase 1 healthy volunteer trial in the first quarter of 2026, with data expected to be reported in the second half of 2026...KT-485/SAR447971, a selective, potent, oral IRAK4 degrader, is being advanced in collaboration with Sanofi for immuno-inflammatory diseases, with a Phase 1 clinical trial expected to initiate in 2026....The Company intends to advance at least one new development candidate towards IND for a first-in-class, oral immunology program in 2026."

First-in-human • New P1 trial • P1 data • Pipeline update • Immunology • Inflammation

Kymera Therapeutics Presents New Preclinical Data for KT-579, a First-in-Class, Oral IRF5 Degrader, at the American College of Rheumatology Annual Meeting (GlobeNewswire) - "The findings show that by selectively targeting and degrading IRF5, a master regulator of immune responses, KT-579 offers a novel oral approach to suppress multiple pro-inflammatory pathways implicated in diseases such as lupus and rheumatoid arthritis (RA)....The Company intends to initiate Phase 1 testing for KT-579 in early 2026."

New P1 trial • Preclinical • Lupus • Rheumatoid Arthritis

Potent and Selective Oral IRF5 Degrader, KT 579, Blocks Pro-Inflammatory Cytokines and Reduces Joint Swelling in a Mouse Model of Rheumatoid Arthritis (ACR Convergence 2025) - "KT-579 was tested in the antigen-induced arthritis (AIA) mouse model of RA and compared to the JAK inhibitor, tofacitinib. We report here the first selective, potent, oral IRF5 degrader that can sufficiently deplete IRF5 and impact myeloid cell effector function by potently inhibiting pro-inflammatory cytokines found to be critical in amplifying inflammatory responses, including cytokines that promote Th1 and Th17 T cell responses, and can reduce joint swelling in a mouse model of RA. These findings support KT-579 as a novel therapeutic agent with the potential to be a first-in-class oral therapy for the treatment of RA and other autoimmune diseases."

Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • CXCL1 • IL12A • IL1B • IL23A • IL6 • IRF5 • TLR4 • TLR7 • TLR8 • TNFA

Potent and Selective Oral IRF5 Degrader, KT-579, Demonstrates In Vitro and In Vivo Activity Comparable or Superior to Approved or Clinically Active Agents in Human Cellular Assays and Lupus Efficacy Models (ACR Convergence 2025) - "We report here the first potent, selective, oral IRF5 degrader development candidate, KT-579, which depletes IRF5 in human primary cells, SLE patient derived cells, and lupus disease models, demonstrating superior activity to existing standards of care agents. These findings position KT-579 as a novel, first-in-class, oral therapeutic agent with the potential to transform the treatment landscape of lupus and multiple autoimmune diseases driven by IRF5 dysregulation."

Preclinical • Immunology • Inflammatory Arthritis • Lupus • Renal Disease • Targeted Protein Degradation • IL12A • IL23A • IL6 • IRF5 • TLR7 • TLR8 • TLR9 • TNFA

Kymera Therapeutics Announces Second Quarter 2025 Financial Results and Provides a Business Update (The Manila Times) - "KT-579 IND-enabling studies are ongoing. The Company intends to advance the program into Phase 1 testing in early 2026. Additional new data from preclinical animal models in lupus and RA will be shared in two posters at the American College of Rheumatology (ACR) Annual Meeting..."

New P1 trial • Preclinical • Lupus • Rheumatoid Arthritis

Kymera Therapeutics Expands Industry Leading Immunology Pipeline with New First-in-Class, Oral IRF5 Degrader Program with Potential to Address Multiple Immuno-Inflammatory Diseases (GlobeNewswire) - "KT-579, a potent, selective, oral degrader of IRF5 with an excellent profile in preclinical safety studies, has demonstrated activity comparable or superior to approved and clinically active drugs in multiple efficacy animal models of lupus and RA; IND-enabling studies are ongoing with Phase 1 testing expected to begin in early 2026."

New P1 trial • Preclinical • Immunology • Lupus • Rheumatoid Arthritis