GS-6791 / Gilead, Nurix Therap - LARVOL DELTA

Key cell cycle genes in cervical cancer and their potential role in neuromuscular complications: a bioinformatics perspective. (PubMed, Eur J Transl Myol) - "Gene expression profiles related to cervical cancer (GSE63514, GSE6791, GSE52903, and GSE9750) were retrieved from the GEO database...The specific genes associated with the cell cycle can act as prognostic biomarkers and may also have an influence in mediating neuromuscular complications due to their impact on mitotic control and molecular signaling pathways throughout the body. This latter aspect is helpful for the prognosis of cancer, including cervical cancer, as well as for the multidisciplinary treatment of neuromuscular symptoms that some cervical cancer patients may have."

Journal • Cervical Cancer • Oncology • Solid Tumor • CCNA2 • CDC20 • CDK1 • TOP2A

IRAK4 Degrader GS-6791 Inhibits IL-1 and IL-36 Driven Responses in Skin Epithelial Cell Systems and Demonstrates Efficacy in a Model of Dermatitis (EADV 2025) - "GS-6791 is a potent and selective oral IRAK4 degrader that demonstrates deep degradation of IRAK4 in primary basal and differentiated keratinocytes. IRAK4 degradation results in strong suppression of IL-1 and IL- 36-driven functional responses in vitro, reducing inflammatory cytokine secretion and downregulating keratinocyte genes linked to AD pathogenesis. GS-6791 also exhibits robust activity in vivo, suppressing IL-1- driven cytokines in a PD model and demonstrating efficacy in a mouse model of dermatitis."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Targeted Protein Degradation • IL1B • IL1R1 • IRAK4

Nurix Therapeutics Presents Preclinical Data from Novel IRAK4 Degrader, GS-6791, Demonstrating Potent Inhibition of IL-1 and IL-36 in Vitro and Efficacy in a Model of Dermatitis (GlobeNewswire) - "The findings support advancement of GS-6791 into clinical studies and are being presented at the European Academy of Dermatology and Venereology (EADV) Congress...The data show that GS-6791 mediates sustained degradation of IRAK4, resulting in robust inhibition of IL-1- and IL-36-driven responses in skin epithelial cell systems and significant disease reduction in a preclinical model of atopic dermatitis (AD)."

Preclinical • Atopic Dermatitis

Downregulation of ANKRD22 and its prognostic significance in squamous cell carcinoma of the cervix: a bioinformatics analysis based on public datasets. (PubMed, Transl Cancer Res) - "Gene expression profiles were obtained from GEO datasets (GSE63514, GSE6791), and RNA sequencing and clinical data were obtained from The Cancer Genome Atlas...ANKRD22 downregulation is associated with poor prognosis in SCC of the cervix. While these findings suggest prognostic relevance, further experimental studies are necessary to validate ANKRD22's clinical utility."

Journal • Cervical Cancer • Gynecology • Obstetrics • Oncology • Solid Tumor • Squamous Cell Carcinoma • ANKRD22

Upcoming Program Highlights: GS-6791 (previously NX-0479) (GlobeNewswire) - "GS-6791 (previously NX-0479): Nurix’s partner, Gilead, is responsible for conducting IND-enabling studies and advancing this program to clinical development, which Nurix anticipates in 2025."

Preclinical • Rheumatoid Arthritis

Nurix Announces FDA Clearance of IND Application for GS-6791/NX-0479 - a Novel IRAK4 Degrader for Inflammatory Conditions (Nurix Press Release) - "Nurix Therapeutics, Inc...announced today that the U.S. Food and Drug Administration (FDA) has cleared the IND for the IRAK4 degrader GS-6791/NX-0479, enabling the initiation of a Phase 1 trial, which is anticipated to begin in Q2 2025....GS-6791/NX-0479 has potential clinical applications across multiple blockbuster markets in inflammation, in both rheumatology and dermatology, including rheumatoid arthritis and atopic dermatitis....Nurix to receive a $5 million milestone payment from Gilead for FDA clearance of the IND, bringing the total amount received under the 2019 collaboration agreement to $135 million."

Commercial • IND • New P1 trial • Atopic Dermatitis • Dermatology • Inflammation • Rheumatoid Arthritis • Rheumatology

Nurix Therapeutics Reports Fourth Quarter and Fiscal Year 2024 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Upcoming Program Highlights:... (i) GS-6791 (previously NX-0479):...Nurix’s partner, Gilead, is responsible for conducting IND-enabling studies and advancing this program to clinical development, which Nurix anticipates in 2025; (ii) STAT6 degrader: In April 2024, Nurix announced an extension of the ongoing research program with Sanofi for STAT6 (signal transducer and activator of transcription 6), a key drug target in type 2 inflammation, with the goal of nominating a development candidate in the first year of the extended term. Nurix remains on track for this goal."

Clinical • Pipeline update • Immunology • Inflammation

Unveiling Biomarkers in Head and Neck Squamous Cell Carcinoma through Bioinformatics: The Role of SPP1 and KRT78. (PubMed, Int J Mol Sci) - "This study analyzed gene expression profiles from three datasets (GSE6791, GSE29330, and GSE58911) to identify differentially expressed genes (DEGs) in HNSCC...Remarkably, the expression levels of these hub genes correlated with tumor grade, clinical cancer stage, and poor prognosis in HNSCC. Our findings hold significant clinical potential for early diagnosis and the development of novel therapeutic targets for patients with HNSCC."

Biomarker • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Targeted Protein Degradation • SPP1

IRAK4 Degrader GS-6791 Inhibits TLR and IL-1R-Driven Inflammatory Signaling, and Ameliorates Disease in a Preclinical Arthritis Model (ACR Convergence 2024) - "Importantly, IRAK4 degradation ameliorated disease in a rat CIA efficacy model, effectuating dose-dependent reduction of ankle swelling and comparable reduction of joint pathology to a dexamethasone-treated control group. IRAK4 protein degradation by GS-6791 inhibited in vitro TLR and IL-1R-mediated cellular responses, with a differentiated profile from IRAK4 kinase inhibition in human B cells and RA synovial fibroblasts. Similarly, GS-6791 robustly inhibited pro-inflammatory signaling in vivo, triggered by both TLR ligands and IL-1-family cytokines. The striking efficacy of GS-6791 in a preclinical arthritis model supports the use of this treatment modality in RA and supports further evaluation in other TLR- or IL-1R-driven inflammatory indications."

Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • IL1B • IL1R1 • IRAK4 • TLR9

Nurix Therapeutics Presents Preclinical Data from Two Autoimmune and Inflammatory Disease Programs, NX-5948 and GS-6791, at ACR Convergence 2024 (GlobeNewswire) - "Nurix Therapeutics...today announced the presentation of preclinical data, including mechanism of action and relevant disease models, from two pipeline programs: NX-5948 and GS-6791. NX-5948 is Nurix’s proprietary, orally available, brain penetrant Bruton’s tyrosine kinase (BTK) degrader, which is being developed for the potential treatment of inflammation and autoimmune diseases in addition to its ongoing Phase 1b trial in patients with B-cell malignancies. GS-6791 is a selective, orally bioavailable degrader of interleukin-1 receptor-associated kinase 4 (IRAK4), which is being developed in collaboration with Gilead Sciences for the potential treatment of rheumatoid arthritis and other inflammatory diseases."

Preclinical • Immunology • Rheumatoid Arthritis

Analysis of Human Papillomavirus-Associated Cervical Cancer Differentially Expressed Genes and Identification of Prognostic Factors using Integrated Bioinformatics Approaches. (PubMed, Adv Biomed Res) - "Two gene expression profiles of GSE9750 and GSE6791, which included cervical cancer HPV-positive and -negative samples, were evaluated using the R limma package with established cut-off criteria of P value < 0.05 and; fold change| ≥ 1...In fact, the current study has the potential to give a distinct viewpoint on the molecular pathways linked to cervical cancer. Considering the potential importance of the hub genes, we recommend conducting in-depth wet lab research to determine their impact on the biological mechanisms of cervical cancer."

Biomarker • Journal • Cervical Cancer • Epstein-Barr Virus Infections • Hematological Malignancies • Human Papillomavirus Infection • Infectious Disease • Leukemia • Oncology • Solid Tumor • CDC45

Nurix Therapeutics Announces Presentations at ACR Convergence 2024, the Annual Meeting of the American College of Rheumatology (GlobeNewswire) - "Nurix Therapeutics, Inc...announced that preclinical data will be presented from NX-5948...and GS-6791/NX-0479, an IRAK4 degrader discovered in collaboration with Gilead Sciences and also in IND-enabling studies, in two posters at ACR Convergence 2024, the annual meeting of the American College of Rheumatology (ACR), being held November 14–19, 2024, in Washington, D.C."

Preclinical • Rheumatoid Arthritis

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 • Cervical Cancer • Gynecology • Human Papillomavirus Infection • Infectious Disease • Obstetrics • Oncology • Solid Tumor • Squamous Cell Carcinoma • Targeted Protein Degradation • UBR5