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- R289 / Rigel
R289, a Dual Irak 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower-Risk Myelodysplastic Syndrome (LR-MDS): Initial Results from a Phase 1b Study (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5789;
P1b
R835 is a selective dual inhibitor of IRAK 1/4 that blocks TLR4 and IL-1R-dependent cytokine release in vitro and in vivo...Those with del (5q) must be R/R to lenalidomide...Prior therapies included luspatercept [n=15 (79%)], hypomethylating agent (HMA) [n=15 (79%)]...Further evaluation of 250 mg BID and a 500/250 mg daily split dose is ongoing. An expansion cohort is planned to confirm a recommended phase 2 dose.
- R289 / Rigel
Phase 1b trial of IRAK 1/4 inhibition for low-risk myelodysplastic syndrome refractory/resistant to prior therapies. (Hall A; Poster Bd #: 147a) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1226;
P1b
Statistical analyses will be primarily descriptive. The trial is currently ongoing at 9 US sites.
- | R 835 / Rigel
Journal: Integrative Multi-omics Analysis Identifies Genetic Variants Contributing to Non-syndromic Cleft Lip with or without Cleft Palate. (Pubmed Central) - Apr 1, 2024
Our study identified five SNPs (rs7218002, rs835367, rs77022994, rs961470 and rs17314727) and three susceptibility genes (NTN1, FGGY and LINC01135) associated with NSCL/P. These findings contribute to a better understanding of the genetic factors involved.
- R289 / Rigel
Phase 1b Trial of Irak 1/4 Inhibition for Low-Risk Myelodysplastic Syndrome Refractory/Resistant to Prior Therapies: A Trial in Progress (Halls G-H (San Diego Convention Center)) - Nov 3, 2023 - Abstract #ASH2023ASH_4183;
P1b
The trial is currently recruiting at 9 US sites. The study has enrolled 7 patients in the dose escalation phase.
- zimlovisertib (PF-06650833) / Pfizer, R 835 / Rigel
R851, a Potent Second Generation IRAK1 and IRAK4 Inhibitor Suppresses IL-6 in Vitro and in Vivo for the Treatment of Rheumatoid Arthritis (Poster Hall; in person) - Sep 23, 2023 - Abstract #ACRConvergence2023ACR_Convergence_2897;
The increased potency in whole blood assays is believed to be driven by a reduction in protein binding. We predict that R851 will require a significantly lower exposures for efficacy in humans which should position this molecule for a chronic condition like rheumatoid arthritis.
- | R 835 / Rigel
Journal: CD147 rs8259T>A Variant Confers Susceptibility to COVID-19 Infection within the Mexican Population. (Pubmed Central) - Aug 26, 2023
We predict that R851 will require a significantly lower exposures for efficacy in humans which should position this molecule for a chronic condition like rheumatoid arthritis. Our results suggest that the CD147 rs8259T>A variant is a risk factor for COVID-19.
- R289 / Rigel
PHASE 1B CLINICAL STUDY OF IRAK 1/4 INHIBITION FOR LOW-RISK MYELODYSPLASTIC SYNDROMES REFRACTORY/RESISTANT TO PRIOR THERAPIES: A TRIAL IN PROGRESS () - May 12, 2023 - Abstract #EHA2023EHA_2919;
P1b
R289 is a prodrug that is converted to the active drug R835 in the gastrointestinal (GI) tract. Phase I, Myelodysplastic syndrome, Kinase inhibitor, MDS
- R289 / Rigel
Phase 1b clinical study of IRAK 1/4 inhibition for low-risk myelodysplastic syndromes refractory/resistant to prior therapies. (Available On Demand; Poster Bd # 209a) - Apr 26, 2023 - Abstract #ASCO2023ASCO_860;
P1b
The trial is currently recruiting at 8 US sites. Clinical trial information: NCT05308264.
- | R 835 / Rigel
Journal: Comparative genomic and phenotypic analyses of the virulence potential in Shiga toxin-producing Escherichia coli O121:H7 and O121:H10. (Pubmed Central) - Dec 13, 2022
In fact, the O121:H7 strain RM8082 appeared to cause minimal cytotoxicity to Vero cells. Our study demonstrated distinct evolutionary lineages among the strains of serotypes O121:H19, O121:H10, and O121:H7 and suggested reduced virulence potentials in STEC strains of O121:H10 and O121:H7.
- | R 835 / Rigel
Journal: Effect modification of greenness on the association between heat and mortality: A multi-city multi-country study. (Pubmed Central) - Oct 19, 2022
Our study demonstrated distinct evolutionary lineages among the strains of serotypes O121:H19, O121:H10, and O121:H7 and suggested reduced virulence potentials in STEC strains of O121:H10 and O121:H7. Our findings can inform communities on the potential health benefits of greenspaces in the urban environment and mitigation measures regarding the impacts of climate change.
- | R 835 / Rigel
Journal: Associations of maternal anthropometrics with newborn anogenital distance and the 2:4 digit ratio. (Pubmed Central) - Sep 10, 2022
Our findings can inform communities on the potential health benefits of greenspaces in the urban environment and mitigation measures regarding the impacts of climate change. Increased maternal weight and adiposity before and in early pregnancy may lengthen the female AGD, which warrants further investigation.
- R 835 / Rigel
[VIRTUAL] CELL-TYPE SPECIFIC REGULATION OF IL-1R SIGNALING BY R835, A DUAL IRAK1/4 INHIBITOR () - May 22, 2020 - Abstract #EULAR2020EULAR_2992;
In endothelial cells, as in myeloid cells, the kinase activity of IRAK1 and IRAK4 is required for the activation of all downstream signaling. Unexpectedly, in human fibroblasts, IRAK1/4 kinase activity appears to primarily regulate the JNK pathway, and not the NFkB pathway.
- R 835 / Rigel
[VIRTUAL] R835, A NOVEL IRAK1/4 DUAL INHIBITOR IN CLINICAL DEVELOPMENT, BLOCKS TOLL-LIKE RECEPTOR 4 (TLR4) SIGNALING IN HUMAN AND MOUSE (Poster View) - May 22, 2020 - Abstract #EULAR2020EULAR_1532;
In a recent phase 1 study, R835 substantially reduced the increase of serum cytokines after an intravenous LPS challenge in healthy volunteers. Importantly, this shows that the pharmacological inhibition of IRAK1/4 pathway by R835 in humans mirrors the results obtained in mice.
- R 835 / Rigel
[VIRTUAL] FIRST-INHUMAN STUDY OF SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF IRAK1/4 INHIBITOR R835 IN HEALTHY SUBJECTS (Poster View) - May 22, 2020 - Abstract #EULAR2020EULAR_1442;
The most common AEs were headache and gastrointestinal disturbance. For both of the formulations tested, the PK of R835 was linear and exposure was dose proportional with rapid steady-state attainment following BID administration.
- R 835 / Rigel
[VIRTUAL] PRECLINICAL EFFICACY OF R835, A NOVEL IRAK1/4 DUAL INHIBITOR, IN RODENT MODELS OF JOINT INFLAMMATION (Wollheim) - Mar 4, 2020 - Abstract #EULAR2020EULAR_214;
R835 is a promising clinical candidate for the treatment of a range of cytokine-driven rheumatological diseases. R835 has proven to have desirable pharmacokinetic properties, was well tolerated and suppressed LPS-induced serum cytokines in healthy volunteers in a recent phase 1 study.
- R 835 / Rigel
[VIRTUAL] TARGETING IRAK1 AND 4 SIGNALING WITH R835, A NOVEL ORAL SMALL MOLECULE INHIBITOR: A POTENTIAL NEW TREATMENT FOR SYSTEMIC LUPUS ERYTHEMATOSUS (Dequeker) - Mar 4, 2020 - Abstract #EULAR2020EULAR_150;
R835 has proven to have desirable pharmacokinetic properties, was well tolerated and suppressed LPS-induced serum cytokines in healthy volunteers in a recent phase 1 study. To our knowledge, R835 is the first dual IRAK1/4 inhibitor to enter clinical development and provides an attractive approach to treat a range of autoimmune and rheumatic diseases, including lupus.