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    DRUG CLASS:

    IRAK-4 degrader

    Related drugs:
    14d
    ADVANTA: Phase 2 Study of SAR444656 in Adult Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov)
    P2, N=200, Recruiting, Sanofi | N=115 --> 200 | Trial completion date: Feb 2025 --> Aug 2026 | Trial primary completion date: Jan 2025 --> Jul 2026
    Enrollment change • Trial completion date • Trial primary completion date
    14d
    ZEN: A Phase 2 Study to Evaluate the Efficacy and Safety of SAR444656 Compared With Placebo in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov)
    P2, N=156, Recruiting, Sanofi | N=99 --> 156 | Trial completion date: Mar 2025 --> Jul 2026 | Trial primary completion date: Feb 2025 --> Jun 2026
    Enrollment change • Trial completion date • Trial primary completion date
    3ms
    Discovery of KT-474─a Potent, Selective, and Orally Bioavailable IRAK4 Degrader for the Treatment of Autoimmune Diseases. (PubMed, J Med Chem)
    This molecule successfully completed phase I studies in healthy adult volunteers and patients with atopic dermatitis or hidradenitis suppurativa. Phase II clinical trials in both of these indications have been initiated.
    Journal
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    IL1R1 (Interleukin 1 receptor, type I) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    5ms
    Discovery of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates Targeting MYD88 Mutant Diffuse Large B-Cell Lymphoma. (PubMed, J Med Chem)
    KT-413 achieves concurrent degradation of these proteins by functioning as both a heterobifunctional degrader and a molecular glue. Based on the demonstrated activity and safety of KT-413 in preclinical studies, a phase 1 clinical trial in B-cell lymphomas, including MYD88 mutant ABC DLBCL, is currently underway.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    |
    KT-413
    5ms
    Unveiling the role of HACE1 in cervical cancer: implications for human papillomavirus infection and prognosis. (PubMed, Transl Cancer Res)
    From The Cancer Genome Atlas Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) and Gene Expression Omnibus (GEO, GSE6791) datasets, we obtained RNA-Seq profiles and associated clinical information...Our study reveals that HACE1 upregulation is associated with cervical cancer, particularly in HPV-positive patients. HACE1 emerges as an independent prognostic factor, linked to unfavorable outcomes.
    Journal
    |
    UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    5ms
    A Single and Multiple Ascending Dose Trial of LT-002-158 in Healthy Adult Volunteers (clinicaltrials.gov)
    P1, N=82, Not yet recruiting, Shanghai Leadingtac Pharmaceutical Co., Ltd. | Initiation date: Jan 2024 --> Jun 2024
    Trial initiation date
    10ms
    ADVANTA: Phase 2 Study of SAR444656 in Adult Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov)
    P2, N=115, Recruiting, Sanofi | Trial completion date: May 2026 --> Feb 2025 | Trial primary completion date: Apr 2026 --> Jan 2025
    Trial completion date • Trial primary completion date
    10ms
    ZEN: A Phase 2 Study to Evaluate the Efficacy and Safety of SAR444656 Compared With Placebo in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov)
    P2, N=99, Recruiting, Sanofi | Trial completion date: Sep 2026 --> Mar 2025 | Trial primary completion date: Aug 2026 --> Feb 2025
    Trial completion date • Trial primary completion date
    10ms
    ZEN: A Phase 2 Study to Evaluate the Efficacy and Safety of SAR444656 Compared With Placebo in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov)
    P2, N=99, Recruiting, Sanofi | Trial completion date: Mar 2025 --> Sep 2026 | Trial primary completion date: Feb 2025 --> Aug 2026
    Trial completion date • Trial primary completion date
    10ms
    ADVANTA: Phase 2 Study of SAR444656 in Adult Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov)
    P2, N=115, Recruiting, Sanofi | Trial completion date: Feb 2025 --> May 2026 | Trial primary completion date: Jan 2025 --> Apr 2026
    Trial completion date • Trial primary completion date
    11ms
    Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL (clinicaltrials.gov)
    P1, N=80, Suspended, Kymera Therapeutics, Inc.
    Trial completion date • Trial primary completion date
    |
    KT-413
    11ms
    ZEN: A Phase 2 Study to Evaluate the Efficacy and Safety of SAR444656 Compared With Placebo in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov)
    P2, N=99, Recruiting, Sanofi | Not yet recruiting --> Recruiting
    Enrollment open
    11ms
    ADVANTA: Phase 2 Study of SAR444656 in Adult Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov)
    P2, N=115, Recruiting, Sanofi | Not yet recruiting --> Recruiting
    Enrollment open
    12ms
    Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL (clinicaltrials.gov)
    P1, N=80, Suspended, Kymera Therapeutics, Inc. | Recruiting --> Suspended
    Trial suspension
    |
    KT-413
    over1year
    PHASE 1 TRIAL OF KT-413, A DEGRADER OF IRAK4 AND IMID SUBSTRATES, IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN’S LYMPHOMAS (ICML 2023)
    Initial clinical data with KT-413 demonstrate degradation of IRAK4 and Ikaros/Aiolos in PBMC and tumor. It is anticipated that higher doses will achieve the predicted degradation profile in tumors that may confer clinical benefit in MYD88-mutant patients. Dose escalation is ongoing, and analyses from additional patients will be presented at the meeting.
    Clinical • P1 data
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • IRF4 (Interferon regulatory factor 4) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    |
    MYD88 mutation • MYD88 wild-type
    |
    KT-413
    almost2years
    Phase 1 Study of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates, in Adult Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (ASH 2022)
    Furthermore, based on new genetic classifications, co-mutations in MYD88 and CD79 (C5 and MCD subgroups) are associated with an inferior survival after standard R-CHOP. Enrollment in the Phase 1a portion of the KT413-DL-101 study is ongoing. NCT05233033.
    Clinical • P1 data • IO biomarker
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • IRF4 (Interferon regulatory factor 4) • IL1R1 (Interleukin 1 receptor, type I) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    |
    MYD88 mutation • MYD88 mutation + CD79B mutation • MYD88 wild-type
    |
    Rituxan (rituximab) • KT-413
    2years
    Precision Targeting of MYD88 Mutant DLBCL Using the Novel Combination of Irakimids and BCL2 Inhibition (ASH 2022)
    Background: Based on new genetic classifications, co-mutations in MYD88 and CD79B (C5 and MCD subgroups) are associated with an inferior survival after standard R-CHOP. Preclinical studies highlight the potential of IRAKIMiDs as a therapeutic approach for the treatment of MYD88MT DLBCL. KTX-582 demonstrates preferential activity in MYD88MT ABC-DLBCL. Single agent venetoclax demonstrated varying potency in ABC-DLBCL cell lines, irrespective of MYD88 mutational status.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IKZF1 (IKAROS Family Zinc Finger 1) • CD79B (CD79b Molecule) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    |
    MYD88 mutation • BCL2 expression • CD79B mutation • MYD88 mutation + CD79B mutation • MYD88 wild-type
    |
    Venclexta (venetoclax) • Rituxan (rituximab) • KT-413 • KTX-582