BAY1830839 / Bayer - LARVOL DELTA

The oral IRAK4-Inhibitors Zabedosertib (BAY1834845) and BAY1830839 suppress immune complex induced interferon-α production by plasmacytoid dendritic cells in a dose dependent manner (EULAR 2025) - "In addition, we asked if the IRAK4 effect is additive to hydroxychloroquine (HCQ), which most patients with SLE receive as standard of care. Both IRAK4 inhibitors investigated in the present study efficiently suppressed the IFN-a production in an in vitro SLE model system. Moreover, both drugs enhanced the pharmacological effect of HCQ. BAY1830839 and BAY1834845 should therefore be further explored as therapeutic options for oral treatment of patients with SLE and CLE."

Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD14 • CXCL8 • IFNA1 • IL6 • IRAK4 • TLR7 • TLR9 • TNFA

The oral IRAK4 inhibitors zabedosertib and BAY1830839 suppress local and systemic immune responses in a randomized trial in healthy male volunteers. (PubMed, Clin Transl Sci) - "Localized skin inflammation was induced by topical application of imiquimod (IMQ) cream for 3 days, starting at Day 3 of treatment. Both IRAK4 inhibitors significantly suppressed the serum TNF-α and IL-6 responses (≥80% suppression vs. placebo, p < 0.05) and inhibited C-reactive protein, procalcitonin, and IL-8 responses to intravenous LPS. This study demonstrated the pharmacological effectiveness of BAY1834845 and BAY1830839 in suppressing systemically and locally induced inflammatory responses in the same range as prednisolone, underlining the potential value of these IRAK4 inhibitors as future therapies for dermatological or other immune-mediated inflammatory diseases."

Journal • Dermatitis • Dermatology • Inflammation • CRP • CXCL8 • IL6 • IRAK4 • TNFA

Discovery of IRAK4 Inhibitors BAY1834845 (Zabedosertib) and BAY1830839. (PubMed, J Med Chem) - "By exploiting binding site features distinct to IRAK4 using an in-house docking model, liabilities of the original hit could surprisingly be overcome to confer both candidates with a unique combination of good potency and selectivity. Favorable DMPK profiles and activity in animal inflammation models led to the selection of these two compounds for clinical development in patients."

Journal • Inflammation • IRAK4

An innovative phase 1b trial demonstrating proof-of-pharmacology for two novel IRAK4-inhibitors using a local (Imiquimod) and systemic (LPS) driven immune response (ISID 2023) - "CONTROL ID: 3888739. This study demonstrated the effectiveness of the orally administered IRAK4-specific inhibitors BAY 1834845 and BAY 1830839 in suppressing the systemic and local inflammatory response upon specific topical or systemic challenges. The results suggest that both tested IRAK4-inhibitors showed pharmacodynamic responses upon IMQ- and LPS-challenges with a similar effect size as prednisolone."

P1 data • Dermatitis • Dermatology • Inflammation • CXCL8 • IL6 • IRAK4 • TNFA

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=67 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

Trial completion

A Trial to Learn How BAY1834845 and BAY1830839 Affect Inflammation When Taken by Mouth Twice a Day for 7 Days in a Row in Healthy Male Participants (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

Trial completion • Immunology • Inflammation • CRP • IL6 • TNFA

A Trial to Learn How BAY1834845 and BAY1830839 Affect Inflammation When Taken by Mouth Twice a Day for 7 Days in a Row in Healthy Male Participants (clinicaltrials.gov) - P1; N=50; Active, not recruiting; Sponsor: Bayer; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Immunology • Inflammation • CRP • IL6 • TNFA

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=67; Active, not recruiting; Sponsor: Bayer; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Trial to Learn How BAY1834845 and BAY1830839 Affect Inflammation When Taken by Mouth Twice a Day for 7 Days in a Row in Healthy Male Participants (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: Bayer

New P1 trial • Immunology • Inflammation • CRP • IL6 • TNFA

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Bayer; Active, not recruiting ➔ Recruiting; Trial primary completion date: Apr 2021 ➔ Dec 2021

Clinical • Enrollment open • Trial primary completion date

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=57; Active, not recruiting; Sponsor: Bayer; Trial completion date: Jun 2021 ➔ Jan 2022

Clinical • Trial completion date

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=52; Active, not recruiting; Sponsor: Bayer; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

[VIRTUAL] Targeting MYD88-Mutant DLBCL with IRAKIMiDs: A Comparison to IRAK4 Kinase Inhibition and Evaluation of Synergy with Rational Combinations (ASH 2020) - "Methods : MYD88-mutant (n=4) and wild type (n=4) DLBCL cell lines were exposed to a panel of single agents (KTX-475, KTX-582, BAY1830839, CA-4948, CC-220, lenalidomide, pomalidomide, ibrutinib, umbralisib, venetoclax) in order to establish the drug concentration:cytotoxicity effect relationship. Our data thus far demonstrate improved efficacy of IRAKIMiDs compared to IRAK4 kinase inhibitors or IMiDs alone in vitro, as well as synergy with other active agents in combination regimens. A promising lead IRAKIMiD candidate has been identified, with initiation of a first-in-human clinical trial in B-cell lymphomas planned for 2021."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IKZF1 • IRF4 • MYD88

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Bayer; Trial completion date: Aug 2020 ➔ Feb 2021; Trial primary completion date: Jul 2020 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Bayer; Trial completion date: Mar 2020 ➔ Aug 2020

Trial completion date

BAY1830839: First in Man, Single Dose Escalation, Safety & Tolerability and Pharmacokinetics (clinicaltrials.gov) - P1; N=64; Completed; Sponsor: Bayer; Active, not recruiting ➔ Completed

Clinical • Trial completion

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Bayer; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants (clinicaltrials.gov) - P1; N=50; Not yet recruiting; Sponsor: Bayer

Clinical • New P1 trial

BAY1830839: First in Man, Single Dose Escalation, Safety & Tolerability and Pharmacokinetics (clinicaltrials.gov) - P1; N=64; Active, not recruiting; Sponsor: Bayer; Recruiting ➔ Active, not recruiting

Enrollment closed