- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio
Enrollment closed, Phase classification, Enrollment change, Trial primary completion date, Combination therapy: KB-LANRA- 1001: A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - Dec 27, 2023
P1/2, N=24, Active, not recruiting,
NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC. Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2 | N=100 --> 24 | Trial primary completion date: Nov 2023 --> May 2024
- |||||||||| Combined Single Cell Flow Cytometry and Imaging Analyses Reveal Immunomodulatory Effects Exerted By Targeted Phospho-SYK Inhibitors with Elevated Sensitivity in NPM1 Mutated AML (Halls G-H (San Diego Convention Center)) - Nov 3, 2023 - Abstract #ASH2023ASH_6504;
P1b/2
Entospletinib (ENTO) and lanraplenib (LANRA) are inhibitors of spleen tyrosine kinase (SYK); the latter is a next-generation SYK inhibitor and is currently being evaluated in combination with gilteritinib (GILT) in patients with relapsed or refractory FLT3-mutated AML (NCT05028751)...Two different AML patient cohorts were assessed by ex vivo treatment with ENTO, LANRA and combinations of LANRA (trametinib, gilteritinib (GILT), aPD-1) over a range of time points (2h, 4h, 3d and 9d) and readouts for cellular phenotype (e.g., differentiation state, immune cell populations) and functional readouts (pSYK, viability) for each cohort were analyzed by HP-FC and sc-MI and associated with available mutation information (bulk gene and single cell RNA sequencing)...These support studies investigating the use of pSYK inhibitors in combination with other therapies to reduce tumor burden, and as an improved line of treatment for AML. Acknowledgements: We are appreciative of the patients and families for their time and participation.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Xospata (gilteritinib) / Astellas
KB-LANRA 1001: A PHASE 1B/2 STUDY ON SAFETY, PK, PD, AND PRELIMINARY EFFICACY OF THE SELECTIVE SYK INHIBITOR LANRAPLENIB IN COMBINATION WITH THE FLT3 INHIBITOR GILTERITINIB, IN FLT3-MUTATED R/R AML () - May 12, 2023 - Abstract #EHA2023EHA_2669;
P1b/2
Eligible pts must have documented FLT3 mutation from a reference lab, and can have received prior therapy with a FLT3 inhibitor (including midostaurin, gilteritinib, quizartinib, or ceronlanib). Accrual is ongoing.
- |||||||||| entospletinib (GS-9973) / Kronos Bio
Responses in patients with AML and treated with entospletinib monotherapy. () - Apr 26, 2023 - Abstract #ASCO2023ASCO_6110;
P1b/2
We are testing Lanraplenib, a next-generation SYK inhibitor with enhanced selectivity, and more favorable pharmacologic properties in combination in genetically defined subsets of AML (NCT05028751). Clinical trial information: NCT02343939.
- |||||||||| Immunohistological pattern-stratification opens the door for reliabletargeted treatment strategies in cutaneous lupus erythematosus (Ito Hall, University of Tokyo) - Apr 13, 2023 - Abstract #ISID2023ISID_2364;
This study demonstrates that > 90% of CLE patients might be prone to betreated with at least one targeted drug, which were developed for the treatment of SLE oris in clinical studies for CLE. These drugs include belimumab (anti-Blys/ B cells) andanifrolumab (anti-IFNabR), which have already been approved for the treatment of SLEby FDA and EMA, but also anti-pDCs drugs (BIIB059 (anti-BDCA2); Daxdilimab (AntiILT7)) and inhibitors of the JAK/STAT pathway (Tofacitinib (JAK), Lanraplenib &Filgotinib (JAK/SYK), Deucravacitinib (TYK2), which block IFN-mediatedinflammatory pathways.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, entospletinib (GS-9973) / Kronos Bio
Influence of efflux and uptake transporters on the pharmacokinetics of the SYK inhibitors entospletinib and lanraplenib (Hall Bordeaux) - Jan 31, 2023 - Abstract #ESMOTAT2023ESMO_TAT_190;
Conclusions ABC transporters play an important role in the brain disposition of entospletinib and lanraplenib, although they have only a slight impact on the plasma exposure of entospletinib. The role for the OATP uptake transporters seems to be less prominent for both drugs, but they might be involved in the tissue disposition of lanraplenib, but not of entospletinib.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, entospletinib (GS-9973) / Kronos Bio
Journal: Neutrophil-specific Syk expression is crucial for skin disease in experimental epidermolysis bullosa acquisita. (Pubmed Central) - Jan 15, 2023
Entospletinib and lanraplenib, two second generation, Syk-specific inhibitors effectively abrogated IC-induced responses of human neutrophils and decreased the anti-C7 antibody-initiated, neutrophil-mediated ex vivo dermal-epidermal separation in human skin samples. Taken together, these results point to a crucial role for Syk in neutrophils in the development and progression of epidermolysis bullosa acquisita and suggest Syk inhibition as a potential therapeutic strategy.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Tavalisse (fostamatinib) / Rigel, Kissei
The impact of Syk-inhibition on 5B9 monoclonal HIT antibody-mediated procoagulant platelet formation (#229) (Harmony 2 (C2)) - Jan 7, 2023 - Abstract #GTH2023GTH_175;
Taken together, these results point to a crucial role for Syk in neutrophils in the development and progression of epidermolysis bullosa acquisita and suggest Syk inhibition as a potential therapeutic strategy. Furthermore, experiments with the Syk inhibitors fostamatinib (R406) and lanraplenib revealed that the formation of procoagulant PLTs seems to be dependent on Syk mediated PLT activating signaling mechanisms, as preincubation of PLTs with these Syk inhibitors resulted in significant inhibition of Ab-induced procoagulant PLT formation (IC50: 14.35
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, entospletinib (GS-9973) / Kronos Bio
Enhanced utility of AI/ML methods during lead optimization by inclusion of 3D ligand information (S401a (McCormick Place Convention Center)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_10241;
This includes an effort to retrospectively re-identify drug candidate molecules based on data from an intermediate stage of the project which illustrates the use of chemical space constraints and the application of evolutionary pressure within GTD. Additionally, a study of how the GTD system can blend features from alternate chemical series with the Gilead lead series shows some of the unique ways GTD applies AI/ML to drug discovery.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead
Clinical, P2 data, Journal: Filgotinib or Lanraplenib in Moderate to Severe Cutaneous Lupus Erythematosus: A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study. (Pubmed Central) - Jun 4, 2022
P2
Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated.
- |||||||||| SYK INHIBITION DRIVES DEEP RESPONSES IN A BIOMARKER GUIDED SUBSET OF AML ALONE AND IN RATIONAL COMBINATIONS () - May 13, 2022 - Abstract #EHA2022EHA_741;
P1b/2, P3
Finally, robust synergy across a range of LANRA concentrations was found when paired with venetoclax and gilteritinib...The highly predictive response for SYK inhibition with concurrent NPM1 m/ FLT3 -ITD mutations and synergy with gilteritinib observed in patient derived models is supportive of its clinical evaluation in combination with a FLT3 inhibitor. Our work supports the rationale for an ongoing Phase 1b/2 study of LANRA in combination with gilteritinib in patients with R/R FLT3 -mutated AML.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Xospata (gilteritinib) / Astellas, entospletinib (GS-9973) / Kronos Bio
PHARMACOLOGICAL INHIBITION OF SYK CONFERS ANTI-PROLIFERATIVE AND NOVEL ANTI-TUMOR IMMUNE RESPONSES IN AML () - May 13, 2022 - Abstract #EHA2022EHA_692;
P1/2, P1b/
The selective, orally bioavailable SYK inhibitor entospletinib (ENTO) has demonstrated clinical activity and tolerability in HOXA9/MEIS1- driven AML...Lanraplenib (LANRA) is a next-generation SYK inhibitor with similar potency and selectivity to ENTO but with more favorable pharmacologic properties that is currently being evaluated in combination with gilteritinib in pts with relapsed or refractory FLT3 -mutated AML (NCT05028751)...Our studies illustrate that ENTO and LANRA may restore T-cell proliferation in a subset of AML pts with dysfunctional T-cell responses, suggesting a novel mechanism of action. Additional studies are required to fully understand the mechanism of SYK-mediated antitumor immune responses in AML.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Velexbru (tirabrutinib) / Ono Pharma, Gilead, Jyseleca (filgotinib) / Galapagos, Gilead
P2 data, Journal: Safety and Efficacy of Filgotinib, Lanraplenib, and Tirabrutinib in Sjögren's Syndrome: Randomised, Phase 2, Double-Blind, Placebo-Controlled Study. (Pubmed Central) - Apr 5, 2022
P2
Three drugs with disparate mechanisms were tested, but no significant differences vs placebo in primary or secondary endpoints were observed. These results may be considered hypothesis-generating, given the drug tolerability, subgroup analysis, and biomarker findings.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio
Journal: Identification of CDK1 as a candidate marker in cutaneous squamous cell carcinoma by integrated bioinformatics analysis. (Pubmed Central) - Feb 5, 2022
The GSE117247, GSE32979, and GSE98767 datasets comprising a total of 32 cSCC samples and 31 normal skin tissue samples were obtained from the National Center for Biotechnology Information Gene Expression Omnibus database...CDK1 is a gene closely related to the occurrence and development of cSCC, which may play an important role. Bioinformatics analysis shows that it is involved in the important pathway of the pathogenesis of cSCC, and may be recognized and applied as a new biomarker in the future diagnosis and treatment of cSCC.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Gilead
Clinical, P2 data, Journal: Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. (Pubmed Central) - Sep 2, 2021
P2
The number of patients treated in this study was small, and only limited conclusions can be drawn. There may be a therapeutic benefit with filgotinib treatment, which may support future investigations with filgotinib or other JAK inhibitors in patients with LMN.
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Trial completion: Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN) (clinicaltrials.gov) - Feb 10, 2020
P2, N=9, Completed,
Lanraplenib is currently under clinical evaluation in multiple autoimmune indications. Active, not recruiting --> Completed
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Trial completion: Study to Evaluate Safety and Efficacy of Filgotinib and Lanraplenib in Females With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - Jan 21, 2020
P2, N=47, Completed,
Active, not recruiting --> Completed Active, not recruiting --> Completed
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Trial completion date, Trial primary completion date: Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN) (clinicaltrials.gov) - Oct 15, 2019
P2, N=9, Active, not recruiting,
Active, not recruiting --> Completed Trial completion date: May 2020 --> Feb 2020 | Trial primary completion date: Aug 2019 --> May 2019
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Velexbru (tirabrutinib) / Ono Pharma, Gilead, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Trial completion: Study to Assess Safety and Efficacy of Filgotinib, Lanraplenib and Tirabrutinib in Adults With Active Sjogren's Syndrome (clinicaltrials.gov) - Oct 9, 2019
P2, N=152, Completed,
Trial completion date: May 2020 --> Feb 2020 | Trial primary completion date: Aug 2019 --> May 2019 Active, not recruiting --> Completed
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Trial completion date, Trial primary completion date: Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN) (clinicaltrials.gov) - May 2, 2019
P2, N=9, Active, not recruiting,
Active, not recruiting --> Completed Trial completion date: Apr 2021 --> May 2020 | Trial primary completion date: Jul 2020 --> Aug 2019
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Enrollment closed: Study to Evaluate Safety and Efficacy of Filgotinib and Lanraplenib in Females With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - Feb 21, 2019
P2, N=47, Active, not recruiting,
Trial completion date: Apr 2021 --> May 2020 | Trial primary completion date: Jul 2020 --> Aug 2019 Recruiting --> Active, not recruiting
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Enrollment closed, Enrollment change: Study to Evaluate the Safety and Efficacy of Filgotinib and Lanraplenib in Adults With Lupus Membranous Nephropathy (LMN) (clinicaltrials.gov) - Feb 8, 2019
P2, N=9, Active, not recruiting,
Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting | N=32 --> 9
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Velexbru (tirabrutinib) / Ono Pharma, Gilead, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Enrollment closed: Study to Assess Safety and Efficacy of Filgotinib, Lanraplenib and Tirabrutinib in Adults With Active Sjogren's Syndrome (clinicaltrials.gov) - Oct 26, 2018
P2, N=152, Active, not recruiting,
Recruiting --> Completed | N=60 --> 35 Recruiting --> Active, not recruiting
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Trial completion date, Trial primary completion date: Study to Evaluate Safety and Efficacy of Filgotinib and Lanraplenib in Females With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - Oct 11, 2018
P2, N=50, Recruiting,
Recruiting --> Active, not recruiting Trial completion date: Jul 2019 --> Jan 2020 | Trial primary completion date: Oct 2018 --> Mar 2019
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio, Velexbru (tirabrutinib) / Ono Pharma, Gilead, Jyseleca (filgotinib) / Galapagos, Gilead, SOBI
Trial completion date, Trial primary completion date: Study to Assess Safety and Efficacy of Filgotinib, Lanraplenib and Tirabrutinib in Adults With Active Sjogren's Syndrome (clinicaltrials.gov) - Apr 26, 2018
P2, N=140, Recruiting,
Trial completion date: Jul 2019 --> Jan 2020 | Trial primary completion date: Oct 2018 --> Mar 2019 Trial completion date: May 2019 --> Dec 2019 | Trial primary completion date: Aug 2018 --> Mar 2019
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio
Trial completion date, Trial primary completion date: Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function (clinicaltrials.gov) - Apr 5, 2018
P1, N=60, Recruiting,
Trial completion date: May 2019 --> Dec 2019 | Trial primary completion date: Aug 2018 --> Mar 2019 Trial completion date: Jun 2018 --> Oct 2018 | Trial primary completion date: Jun 2018 --> Oct 2018
- |||||||||| lanraplenib (GS-9876) / Gilead, Galapagos, Kronos Bio
Trial primary completion date: Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function (clinicaltrials.gov) - Nov 27, 2017
P1, N=60, Recruiting,
Trial completion date: Jun 2018 --> Oct 2018 | Trial primary completion date: Jun 2018 --> Oct 2018 Trial primary completion date: Dec 2017 --> Jun 2018
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