KT-621 / Kymera Therap - LARVOL DELTA

Potent and Selective Oral STAT6 Degrader, KT-621, Inhibits IL-4 and IL-13 Functions in Human Cells and Blocks TH2 Inflammation in a House Dust Mite Model of Asthma (ATS 2025) - "Dupilumab, an injectable monoclonal antibody that blocks IL-4/IL-13 signaling, is an approved therapy for multiple atopic/allergic diseases. STAT6 degradation is a potential novel oral approach for blocking the IL-4/IL-13 signaling pathways involved in TH2 inflammation. These data demonstrate the potential of KT-621 for the treatment of asthma, chronic obstructive pulmonary disease (COPD), and other allergic diseases with best-in-pathway potential given its biologics-like activity profile and oral bioavailability. KT-621 is currently in Phase 1 clinical testing."

Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • IL13 • IL4 • IL4R • STAT6

BroADen: Safety, PK, PD, and Clinical Activity of Orally Administered KT-621 in Adult Patients With Atopic Dermatitis (AD) (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Kymera Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

BroADen: Safety, PK, PD, and Clinical Activity of Orally Administered KT-621 in Adult Patients With Atopic Dermatitis (AD) (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Kymera Therapeutics, Inc.

New P1 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Kymera Therapeutics Announces First Patient Dosed in BROADEN Phase 1b Atopic Dermatitis Clinical Trial of KT-621, a First-in-Class Oral STAT6 Degrader (GlobeNewswire) - "Kymera Therapeutics, Inc...announced that it recently initiated dosing in its BroADen Phase 1b clinical trial evaluating KT-621, an oral, highly selective, potent degrader of STAT6, in patients with moderate to severe atopic dermatitis (AD). The Company expects to report data from the BroADen trial in the fourth quarter of 2025. Additionally, the Company has completed SAD/MAD dosing and follow-up in the KT-621 Phase 1 healthy volunteer trial with data to be reported in June 2025."

P1 data • Trial status • Atopic Dermatitis

Kymera Therapeutics Announces Fourth Quarter and Full Year 2024 Financial Results and Provides a Business Update (GlobeNewswire) - "KT-621 (STAT6) Phase 1 healthy volunteer trial ongoing, complete SAD/MAD data expected in June 2025....The Company plans to initiate a Phase 1b trial in moderate to severe AD patients in the second quarter of 2025, with data expected to be reported in the fourth quarter of 2025....Two parallel Phase 2b studies in AD and asthma patients are planned to begin in the fourth quarter of 2025 and first quarter of 2026, respectively."

New P1 trial • New P2b trial • P1 data • Asthma • Atopic Dermatitis

Kymera Therapeutics Outlines Key 2025 Objectives and Strategy to Advance Industry Leading Portfolio of Oral Immunology Programs (GlobeNewswire) - "Key upcoming KT-621 milestones: Complete KT-621 Phase 1 healthy volunteer clinical trial and report data in the second quarter of 2025. Advance KT-621 into a Phase 1b clinical trial in AD patients in the second quarter of 2025 and report data in the fourth quarter of 2025. Initiate KT-621 Phase 2b clinical trial in AD in the fourth quarter of 2025, followed by a Phase 2b clinical trial in asthma in early 2026. Key upcoming KT-295 milestones: File KT-295 IND and initiate dosing in the Phase 1 healthy volunteer clinical trial in the second quarter of 2025, with Phase 1 data expected in the fourth quarter of 2025."

IND • New P1 trial • New P2b trial • P1 data • Asthma • Atopic Dermatitis • Inflammatory Bowel Disease • Psoriasis

Kymera Therapeutics Announces Third Quarter 2024 Financial Results and Provides a Business Update (GlobeNewswire) - "In October, Kymera initiated dosing in the Phase 1 healthy volunteer clinical trial evaluating single and multiple ascending doses of KT-621, a potent and selective oral degrader of STAT6. The Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of KT-621 compared to placebo. The Company expects to report Phase 1 data in the first half of 2025....Hidradenitis Suppurativa (ZEN trial): The study has been expanded from 99 to 156 patients. Previously, the trial included one active dose of KT-474 as well as placebo. The study will now include an additional dose. The estimated primary completion date for the ZEN trial is now in the first half of 2026.; Atopic Dermatitis (ADVANTA Trial): The study has been expanded from 115 to 200 patients. Previously, the trial included two active doses of KT-474 as well as placebo. The study will now include an additional dose. The estimated primary completion date for the ADVANTA trial is now in the middle of 2026."

P1 data • Trial completion date • Trial status • Atopic Dermatitis • Dermatitis • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation

First-in-human Study of Orally Administered KT-621 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Kymera Therapeutics, Inc.

New P1 trial • STAT6

POTENT AND SELECTIVE ORAL STAT6 DEGRADER KT-621 INHIBITS IL-4/IL-13 IN MOUSE MODELS OF ASTHMA (ACAAI 2024) - " KT-621 potently and selectively degraded STAT6 and fully blocked IL-4/IL-13 in various disease-relevant human primary immune and tissue cells with picomolar potencies comparable or superior to dupilumab, a therapeutic antibody blocking IL-4/IL-13. STAT6 degradation is a novel oral approach for blocking the IL-4/IL-13 pathways for the potential treatment of multiple allergic diseases."

Preclinical • Asthma • Immunology • Inflammation • Respiratory Diseases • Targeted Protein Degradation • IL13 • IL4 • IL4R • STAT6

Kymera Therapeutics Announces Dosing of First Participant in Phase 1 Clinical Trial of KT-621, a First-in-Class Oral STAT6 Degrader, for the Treatment of TH2 Immuno-Inflammatory Diseases (GlobeNewswire) - "Kymera Therapeutics, Inc...today announced that it recently initiated dosing in the Phase 1 clinical trial in the US evaluating KT-621, a potent, selective, oral degrader of STAT6, in adult healthy volunteers. The Company expects to report Phase 1 data in the first half of 2025....The Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered KT-621 in healthy volunteers. The study includes double-blind, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) cohorts."

P1 data • Trial status • Immunology • Inflammation

Potent and selective oral STAT6 degrader, KT-621, inhibits IL-4 and IL-13 functions in human cells and blocks TH2 inflammation in vivo (EADV 2024) - "We also compared the efficacy of KT-621 to dupilumab in vivo in an MC903 induced atopic dermatitis model and a HDM induced asthma model in the IL4/IL4RA humanized mice. STAT6 degradation is a potential novel oral approach for blocking the IL-4/IL-13 pathways. These data demonstrate the potential of KT-621 for the treatment of atopic dermatitis and other allergic diseases with best- in-pathway potential given its biologics-like activity profile and oral bioavailability. KT-621 is expected to be in a human Phase 1 trial in the second half of 2024."

Preclinical • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Inflammation • Respiratory Diseases • Targeted Protein Degradation • IL13 • IL4 • IL4R • STAT6

Kymera Therapeutics Announces FDA Clearance of Investigational New Drug Application for KT-621, a First-in-Class, Oral STAT6 Degrader (GlobeNewswire) - "Kymera Therapeutics...announced the clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for KT-621, a potent, selective, oral degrader of STAT6. The Company expects to initiate dosing in a Phase 1 clinical trial in healthy volunteers in October 2024 and to report data from the Phase 1 study in the first half of 2025....The Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of KT-621 compared to placebo."

IND • New P1 trial • Immunology

Kymera Therapeutics Presents Preclinical Data for KT-621, a Potent, Selective, First-In-Class, Oral STAT6 Degrader at the EADV Congress (GlobeNewswire) - "Kymera Therapeutics, Inc...announced the presentation of preclinical data for KT-621, a potent, selective, oral degrader of STAT6, an essential transcription factor that is a central driver of TH2 inflammation....In preclinical studies, KT-621 was exquisitely selective for STAT6 over other STAT proteins and fully blocked the function of IL-4/IL-13, critical cytokines in allergic and atopic inflammation, in key human TH2 cellular assays with picomolar potency that was comparable or superior to dupilumab. In addition, at low daily oral doses, preclinical studies with KT-621 demonstrated near full in vivo STAT6 degradation in disease-relevant tissues and was well-tolerated. In an MC903-induced atopic dermatitis mouse model, orally administered KT-621 demonstrated robust degradation of STAT6 in vivo and marked reduction of total serum IgE comparable to the activity of the IL-4RA saturating dose of dupilumab."

Preclinical • Atopic Dermatitis • Dermatitis • Immunology

Kymera Therapeutics Presents New Preclinical Data for KT-621, a First-In-Class, Oral STAT6 Degrader at the ATS Annual Meeting (GlobeNewswire) - "The featured data demonstrate activity of KT-621 comparable to a saturating dose of the IL-4Rα antibody, dupilumab, in an asthma efficacy model which demonstrated that KT-621 robustly inhibited all the tested cytokines, chemokines, and cell infiltrates involved in TH2 inflammation in asthma....Kymera intends to initiate Phase 1 testing for KT-621 in the second half of 2024 and expects data from the Phase 1 trial to be reported in the first half of 2025....KT-621 preclinical data was also presented at Digestive Disease Week in Washington, D.C. The data demonstrated reversal of IL-13 stimulatory effects on esophageal smooth muscle cells, an important cell type involved in the pathophysiology of eosinophilic esophagitis. The company plans to share additional preclinical data for KT-621 at upcoming medical meetings in 2024."

New P1 trial • P1 data • Preclinical • Asthma • Eosinophilic Esophagitis

Kymera Therapeutics Presents Preclinical Data for STAT6 and TYK2 First-In-Class, Oral Degrader Immunology Programs at the American Academy of Dermatology Annual Meeting (GlobeNewswire) - "Based on the results generated to date, Kymera intends to initiate Phase 1 testing for KT-621 and KT-294 in the in the second half of 2024 and the first half of 2025, respectively. Data from both Phase 1 trials are expected to be reported in 2025....The findings presented today demonstrate that in preclinical studies, KT-621...was exquisitely selective for STAT6 over other STATs and fully blocked IL-4/IL-13 functions in key human TH2 cellular assays with picomolar potency that was superior to dupilumab....Additionally, in preclinical studies, KT-294...demonstrated picomolar degradation potency and potent inhibition of the IL-23, IL-12 and Type I IFN pathways, showing its potential to recapitulate the biology of human TYK2 loss-of-function profile."

New P1 trial • P1 data • Preclinical • Atopic Dermatitis • Immunology