Final Operational Milestone #5
Angiocrine Bioscience Inc., a clinical-stage biopharmaceutical company, completed enrollment of a Phase 1b/2a trial for the treatment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) undergoing high-dose chemotherapy and stem cell transplantation.
For patients with an aggressive-form of lymphoma, high-dose chemotherapy followed by stem cell transplantation can be curative. The high-dose chemotherapy eradicates cancer cells in the marrow, lymphatics and elsewhere. It also eliminates all blood stem cells in the marrow (healthy and malignant). Since blood stem cells are necessary for survival, patients are provided with their own blood stem cells (i.e., stem cell transplantation) the day after a week-long course of chemotherapy.
Beyond eradicating malignant and blood stem cells, the high-dose chemotherapy also causes widespread collateral injury to many other organs. This disables the organs’ vascular stem cell niches, the primary mechanism for the organs to repair themselves. Especially hard hit are organs that renew themselves on a daily basis, such as the oral-gastrointestinal (GI) tract and the bone marrow lining. With the repair mechanism (i.e., vascular stem cell niches) disabled, the mucosal lining of the oral-GI tract breaks down. This leads to the patient getting severely ill with oral-GI symptoms–painful mouth sores, making eating and drinking virtually impossible, and severe nausea, vomiting or diarrhea that are usually unresponsive to medication and require hospitalization. Despite stem cell transplantation, the bone marrow lining is also injured leading to delayed blood count recovery. Moreover, the tiny vessels that feed the vital organs can also be severely injured, which may lead to dysfunction of the lungs, kidneys, heart, liver and, more rarely, the brain. Collectively, these severe complications are called SRRT (severe regimen-related toxicities).
Despite the best available supportive care, SRRT occurs in approximately 50% of the patients undergoing high-dose chemotherapy stem cell transplantation. This rate increases to approximately 70% in older patients (older patients have more vulnerable vascular stem cell niches). The risk for life-threatening SRRT in the elderly are high enough that numerous patients are turned away each year from one of the few curative therapies for cancer—i.e., stem cell transplantation.
AB-205 is an experimental engineered-cell therapy intended to treat the injured vascular stem cell niches in multiple organs, and thereby, preventing or reducing the life-threatening complications known as SRRT. AB-205 is made with human endothelial cells that line the vessels in the umbilical cord tissue of a healthy newborn baby. In our body, the endothelial cells play a critical role in the development, ongoing functioning, and repairing of tissue and organs. Hence, AB-205 is an enhanced version of a human cell that was designed by nature to repair damaged organs and tissues.
In the Phase 1b/2a clinical trial with 42 lymphoma patients, AB-205 therapy demonstrated the reduction of oral/GI SRRT complications. Across all doses of AB-205, less than 10% of patients with lymphoma not affecting the brain or spinal cord reported severe side effects of oral mucositis, nausea, diarrhea or vomiting compared to a rate of 40-60% typically experienced by patients. In addition, the rate of severe infections was low which may reflect the accelerated repair of the oral and GI lining. Angiocrine Bioscience expects to initiate a single pivotal Phase 3 trial in 2021 in North America and Europe based on the positive Phase 1b/2a trial. The goal of the trial is to determine if treatment with AB-205 will help to prevent or decrease the severity and duration of SRRT, with focus on oral/GI SRRT, in lymphoma patients undergoing high-dose chemotherapy followed by stem cell transplantation compared to patients who do not receive AB-205 (and instead receive a placebo).
In September 2020, AB-205 was granted the Orphan Drug Designation from the US FDA. Two months later, in November 2020, the FDA granted AB-205 the Regenerative Medicine Advanced Therapy (RMAT) designation. Angiocrine was awarded a $6 million grant from CIRM in 2019 for the clinical development of AB-205.