rosmantuzumab (OMP-131R10) / Mereo Biopharma - LARVOL DELTA

RSPO3 regulates the radioresistance of Non-Small cell lung cancer cells via NLRP3 Inflammasome-Mediated pyroptosis. (PubMed, Radiother Oncol) - "The findings demonstrated that RSPO3 plays a crucial role in regulating NSCLC radioresistance via NLRP3 mediated pyroptosis. Targeting the RSPO3-NLRP3 inflammasome axis may offer a potential therapeutic strategy to enhance the efficacy of radiotherapy for NSCLC patients."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NLRP3 • RSPO1 • RSPO3 • SPON1

Targeting the Wnt signaling pathway through R-spondin 3 identifies an anti-fibrosis treatment strategy for multiple organs. (PubMed, PLoS One) - "Specifically, an anti-RSPO3 antibody, OMP-131R10, when dosed therapeutically, attenuated fibrosis in carbon tetrachloride (CCl4)-induced liver fibrosis, bleomycin-induced pulmonary and skin fibrosis models. Finally, RSPO3 was found to be highly elevated in the active lesions of fibrotic tissues in mouse models of fibrosis and in patients with idiopathic pulmonary fibrosis (IPF) and nonalcoholic steatohepatitis (NASH). Together these data provide an anti-fibrotic strategy for targeting the Wnt/β-catenin pathway through RSPO3 blockade and support that OMP-131R10 could be an important therapeutic agent for fibrosis."

Journal • Fibrosis • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Oncology • Respiratory Diseases

Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia. (PubMed, Cancer Cell) - "RSPO receptor, LGR4, is epigenetically upregulated and works through cooperation with HOXA9, a poor prognostic predictor. Blocking the RSPO3-LGR4 interaction by clinical-grade anti-RSPO3 antibody (OMP-131R10/rosmantuzumab) impairs self-renewal and induces differentiation in AML patient-derived xenografts but does not affect normal hematopoietic stem cells, providing a therapeutic opportunity for HOXA9-dependent leukemia."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • RSPO2

R-SPONDIN3 antagonism sensitizes colorectal cancer to taxane treatment (AACR 2017) - " Anti-RSPO3 was highly effective in combination with nab-paclitaxel in a CRC model with an RSPO3 translocation and RSPO3 overexpression. Anti-RSPO3 (OMP-131R10) was active in the majority of CRC PDX models tested when combined with taxane treatment. These CRC models harbored mutations in APC and β-catenin. This data indicates that RSPO3 inhibition is an effective means to target the mutated Wnt pathway in CRC, and that antagonizing RSPO3 in combination with paclitaxel may improve survival for CRC patients."

Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Graft versus Host Disease • Oncology • Pancreatic Cancer

OncoMed provides update on navicixizumab partnership (GlobeNewswire) - "OncoMed Pharmaceuticals...announced that Celgene has notified OncoMed that due to strategic product portfolio considerations Celgene has decided not to exercise its option to license OncoMed’s bispecific antibody navicixizumab (OMP-305B83). Celgene continues to retain its options to license OncoMed’s etigilimab (OMP-313M32) and rosmantuzumab (anti-RSPO3, OMP-131R10) under the collaboration. OncoMed and Celgene are working to formalize the termination of the collaboration agreement with respect to navicixizumab, and OncoMed expects to retain worldwide rights to navicixizumab....Interim Phase 1b data [from navicixizumab in combination with paclitaxel in patients with platinum-resistant late-stage ovarian cancer] will be presented in a poster presentation on October 20, 2018 at the [ESMO 2018]."

Licensing / partnership • P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

RheumNow podcast – Eat your veggies (4.19.19) (RheumNow) - "Dr. Jack Cush reviews the news and journal articles from the past week on RheumNow.com....AC&R reports on a VA study of Temporal Arter (3,057 Bxs - 306 [10%]were Bx+). Positive TAB significantly increased w/ Bxlength >3.0 cm (OR 1.58), B/L Bx (OR 1.83), age >71 yrs. Prednisone use (up to42 days prior) did not influence TAB results."

Review • Video