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DRUG CLASS:

IRAK-4 degrader

Related drugs:
4ms
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
4ms
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
4ms
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
4ms
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
4ms
Trial completion date • Trial primary completion date
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KT-413
5ms
Enrollment open
6ms
Trial suspension
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KT-413
1year
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
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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)
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MYD88 mutation • MYD88 wild-type
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KT-413
over1year
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
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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)
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MYD88 mutation • MYD88 mutation + CD79B mutation • MYD88 wild-type
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Rituxan (rituximab) • KT-413
over1year
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
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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)
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MYD88 mutation • BCL2 expression • CD79B mutation • MYD88 mutation + CD79B mutation • MYD88 wild-type
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Venclexta (venetoclax) • Rituxan (rituximab) • KT-413 • KTX-582