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NEW TREATMENTS FOR BLADDER CANCER HAVE BEEN EXTREMELY SCARCE OVER THE PAST DECADES. HOWEVER, THE CONTINUED RISE OF CHECKPOINT INHIBITOR IMMUNOTHERAPIES MAY BE PROVIDING A NEW BREAKTHROUGH FOR METASTATIC DISEASE. NEW DEVELOPMENTS IN THE NEXT GENERATION OF IMMUNO-ONCOLOGY MODELS ARE ALSO UP AND COMING THANKS TO AN EXTENDED ALLIANCE BETWEEN CROWN BIOSCIENCE AND THE NATIONAL RESOURCE CENTER FOR MUTANT MICE.

Over many years of research, bladder cancer has proven to be a particularly difficult cancer type to develop new treatment options for. No new drugs for the disease in general have been FDA approved in the last 10 years, and for subtypes such as metastatic urothelial bladder cancer (UBC) there have been no major treatment advances for as long as 30 years. This has been reflected in patient survival rates – the overall 5-year relative survival rate has stagnated at around 77% for 10 years, with the 5-year survival of patients with distant metastases as low as 6%.

Hopefully, change is on the horizon as anti-PD-1/PD-L1 immunotherapies start to make their mark on this cancer type. Following approval in advanced melanoma last year for Keytruda® and Opdivo®, these agents are still a hot immuno-oncology topic, with potential FDA approvals appearing shortly for lung cancer. Another agent in this drug class is MPDL3280A, an anti-PD-L1 antibody being developed by Genentech/Roche, which has Breakthrough Therapy Designation in both NSCLC and metastatic bladder cancer, with impressive Phase I results reported last year in metastatic UBC.

The study (reported in Nature) looked at 68 metastatic UBC patients treated with MPDL3280A, who had all previously failed chemotherapy and had been given only 6 to 8 months to live. Objective response rates were impressive for patients with tumors expressing PD-L1 (as confirmed by immunohistochemistry score 2 or 3), with 52% of patients experiencing tumor shrinkage at 12 weeks, and patients with a positive response to treatment having prolonged benefits. Two of these patients had a complete response, with no signs of cancer after therapy. Even some patients with little/no PD-L1 on their tumors (IHC score 0 or 1) showed a response – objective response rate amongst these patients was 11%. Following on from these results and a suitable safety profile, a Phase II trial has been started with this agent in further advanced bladder cancer patients, which is currently recruiting subjects.

This is potentially great news for patients with late stage bladder cancer, who have waited a long time for new therapeutic options, and we hope that Phase II testing onwards is successful. Immunotherapy is proving to be a highly successful oncology field, providing both potential patient benefits and commercial success for the pharmaceutical industry. Major obstacles to developing new immunotherapeutics have included a lack of experimental immunotherapy models with a functioning immune system. At Crown Bioscience we have a range of immunotherapy research platforms already available for preclinical drug development, including platforms of mouse immunity and platforms of human immunity. All of these platforms can be used to study anti-PD-1/PD-L1 molecules e.g. a selection of our syngenic models across a variety of cancer types (including melanoma, breast, and colon cancer) have already been trialed with these agents with a range of responses seen.

Crown Bioscience are also committed to developing the next generation of cancer immunotherapy models, which has been solidified by our expanded strategic partnership with the National Resource Center for Mutant Mice (NRCMM) and its commercial branch Nanjing Biotech Innovation Corporation (NBIC), in Nanjing, Jiangsu Province, China. The immediate focus of our expanded partnership (which was announced last week) is to build and validate novel experimental immuno-oncology models for cancer immunotherapy research, by leveraging the proprietary technologies of both institutions.

For example, the NRCMM specialize in genetically engineered mouse models (GEMM), many of which mimic human cancers. Our partnership allows Crown Bioscience to further develop GEMM-based oncology platforms including MuPrime™, which is comprised of allografts of spontaneous murine tumors (from sources including GEMMs), studied in mice with complete immunocompetency. Similar to GEMM, the tumor lines have never been manipulated or adapted to grow in vitro, mirroring original mouse tumor histopathology and genetic profiles, with different differentiation phenotypes, rich microenvironments, and cancer stem cell driven disease. Our collaboration with the NRCMM further strengthens our leading position as the oncology translational medicine partner for drug discovery organizations worldwide.

Contact us at busdev@crownbio.com to talk to our experts about how Crown Bioscience can drive forward your immunotherapy research today.