City of Hope and Osel Announce Live Biotherapeutic Product CBM588 May Enhance Efficacy of Immunotherapy for Patients With Metastatic Kidney Cancer

City of Hope and Osel Announce Live Biotherapeutic Product CBM588 May Enhance Efficacy of Immunotherapy for Patients With Metastatic Kidney Cancer Additional Phase 1 clinical trial of CBM588 plus immune checkpoint and tyrosine kinase inhibitors to treat renal cell carcinoma ongoing February 28, 2022 — Los Angels, Calif. and Mountain View, Calif. — City of Hope, one of the largest cancer research and treatment organizations in the United States, and Osel Inc., a company developing live biotherapeutic products for modulation of the human microbiome, today announced Phase 1 trial data showing that use of the live biotherapeutic CBM588 ( Clostridium butyricum MIYAIRI 588® strain) plus immunotherapy medicine nivolumab/ipilimumab significantly improved progression-free survival in patients with metastatic kidney cancer when compared to use of nivolumab/ipilimumab alone. The study was published in Nature Medicine today. “Compared to microbiome modulation using fecal transplants, CBM588 given orally is potentially a more effective, reproducible, scalable and safer method to treat patients. We look forward to supporting the world-class team at City of Hope as they advance CBM588 in additional clinical trials.” Tweet this “To our knowledge, this is the first randomized clinical trial to demonstrate that a live bacterial product can modulate the gastrointestinal microbiome and enhance immunotherapy response in cancer patients. These results can help improve treatment options for patients with kidney cancer and is an important foundational step to bring about more effective targeted therapies for cancer treatment,” said Sumanta K. Pal, M.D., a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope and senior author of the study. CBM588 is a nonpathogenic bacteria that has multiple documented beneficial effects on the human microbiome. It produces short-chain fatty acids (mainly butyric acid), a well-known energy source for the lining of the GI tract, and has immunomodulatory properties. The bacterial strain appears to exert additional beneficial effects, including inhibiting pathogenic microorganisms and helping to restore the GI lining and decrease intestinal imbalance. Last summer, City of Hope granted an exclusive worldwide license to Osel for intellectual property on the novel use of CBM588 to enhance the efficacy of checkpoint inhibitors to treat cancer. In the clinical trial, 30 patients with metastatic kidney cancer (renal cell carcinoma) who had never received treatment before were randomized to receive either CBM588 orally in combination with nivolumab/ipilimumab or nivolumab/ipilimumab alone. Data showed a significant improvement in progression-free survival in patients treated with CBM588 plus nivolumab/ipilimumab (12.7 months) compared to nivolumab/ipilimumab alone (2.5 months). Additionally, use of CBM588 in combination therapy was linked to an increase in response rate when compared to use of nivolumab/ipilimumab therapy alone (58% vs. 20%). While there was no significant difference between the treatment groups in terms of the amount of the Bifidobacterium genus bacteria, patients who responded to the CBM588 with nivolumab/ipilimumab treatment had significant increases in the Bifidobacterium species. There were no significant differences in treatment-related toxicity reported between the two groups. “Over the last several years, the immunotherapy field has been closely studying how the GI microbiome can enhance immune checkpoint efficacy for the treatment of cancer,” said Thomas Parks, Ph.D., director of product development at Osel. “Compared to microbiome modulation using fecal transplants, CBM588 given orally is potentially a more effective, reproducible, scalable and safer method to treat patients. We look forward to supporting the world-class team at City of Hope as they advance CBM588 in additional clinical trials.” Osel licensed the rights for the pharmaceutical use of CBM588 in the United States, Canada and Europe from Miyarisan Pharmaceutical Co., Ltd. CBM588 is manufactured under GMP (good manufacturing practice) and marketed in Japan by Miyarisan Pharmaceutical as a prescription product known as MIYA-BM ( Clostridium butyricum MIYAIRI 588® strain) to treat GI indications. “City of Hope is currently conducting another Phase 1 clinical trial of CBM588 in combination with nivolumab and tyrosine kinase inhibitor cabozantinib for the treatment of advanced or metastatic kidney cancer,” said Pal, co-director of the Kidney Cancer Program at City of Hope. “We are working to open a large, randomized Phase 3 trial of CBM588 in the future.” Jeffrey Trent, Ph.D., Translational Genomics Research Institute ( TGen ) president and research director, a contributor to the study, said, “The field of microbiome research is exploding as evidenced by the clinical importance of this study, which points to the continued growth of clinical research and scientific understanding of the microbiome’s connection to disease and recovery.” TGen is an affiliate of City of Hope. Nazli Dizman, M.D., and Luis Meza, M.D., who were both postdoctoral fellows at City of Hope when the study was conducted, were lead researchers on the trial and co-primary authors. Funding for the study, “Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial ,” was provided by a grant from the Gateway for Cancer Research (Grant 449 ID: G-20-100). About City of Hope City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy . City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies, and numerous breakthrough cancer drugs are based on technology developed at the institution. Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHope TM , a wholly owned subsidiary, was launched in 2019, dedicated to serving employers and their health care partners by providing access to City of Hope’s exceptional cancer expertise. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nation’s “Best Hospitals” in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. For more information about City of Hope, follow us on Facebook , Twitter , YouTube or Instagram . About Osel, Inc. Osel Inc., a privately held biopharmaceutical company based in Mountain View, California, is focused on the development and commercialization of a portfolio of LBPs to prevent or treat medical conditions resulting from disruption of the human microbiome (dysbiosis). The company is a pioneer in the field of LBPs and is actively pursuing multiple indications in cancer and women’s health. Media Contact City of Hope: Zen Vuong Tel: (626) 409-9367 Email: [email protected] Osel: Michelle Linn Bioscribe Tel: (774) 696-3803 Email: [email protected]

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