First in China: Reindeer Medical GPRC5D CAR-T clinical initiation

2022-05-28 0 By

▎ ArmstrongOn February 2, 2022, Reindeer Medical enrolled 18 patients with relapsed/refractory multiple myeloma or lymphoma in a phase I clinical trial of GPRC5D CAR-T at ClinicalTrials.gov.Reindeer Medical’s r&d pipeline is as follows. The most advanced is BCMA CAR-T, jointly developed with Cinda Bio.The GPRC5D CAR-T has not been updated to the pipeline.Scientists at Memorial Sloan-Kathryn and Urich found that 65 percent of multiple myeloma patients had GPRC5D expression above the 50 percent threshold.More importantly, GPRC5D is independently expressed with BCMA and is not correlated with BCMA, so it has excellent potential therapeutic value.Memorial Sloan Kathryn center and Uruc developed CAR-T therapies targeting GPRC5D, focusing on optimized antibody cloning and spacer sequences (terminal, medium, and long).The optimized GPRC5D CAR-T showed similar activity to BCMA CAR-T and remained effective against BCMA negative tumors, again suggesting that the two targets did not overlap and had independent clinical value.The Memorial Sloan Kathryn Center is in phase I clinical development with Uricol’S GPRC5D CAR-T, and Uricol is also developing BCMA/GPRC5D dual targeted CAR-T therapy.Johnson & Johnson focuses on the development of GPRC5D/CD3 dual antibody Talquetamab. Johnson & Johnson’s BCMA/CD3 dual antibody and GPRC5D/CD3 dual antibody are both constructed using Genmab’s Duobody technology platform.As a seventh-order transmembrane protein (GPCR), GPRC5D has a very complex structure, which poses great challenges for antibody preparation and activity analysis.Alcock made the full-length protein of GPRC5D expressed in lactation, and has developed an antibody drug for the discovery and production of antibodies.() In just a few years, multiple myeloma has entered the era of small molecule drugs into the era of large molecule drugs. CD38 antibody has entered the first-line therapy, and Johnson & Johnson’s Darzalex sales reached $6 billion last year.BCMA targets ADC and CAR-T have been marketed, and Johnson & Johnson BCMA/CD3 dual antibody has also submitted its application for marketing.GPRC5D target becomes another important new target in multiple myeloma after CD38 and BCMA.