First patient in the world treated with a new therapeutic strategy to target cancer stem cells
A new drug originally developed by Leukos Biotech S.L., a spin-off of the Josep Carreras Leukemia Research Institute, in collaboration with AOP Health, is being tested for the first time on patients at the UITM-CaixaResearch of the Vall d’Hebron Institute of Oncology (VHIO) in the SERONCO-1 phase 1 trial to evaluate its safety in patients with advanced solid tumors. The drug AOP208 blocks a particular conformation of the serotonin 1b receptor on the membrane of cancer stem cells, which controls metabolic pathways whose blockade may be crucial for the initiation and development of the tumor.
The new compound called AOP208, initially developed by Leukos Biotech, a spin-off of the Josep Carreras Leukemia Research Institute, has been tested for the first time in patients at the Molecular Cancer Therapy Unit (UITM-CaixaResearch) of the Vall d’Hebron Institute of Oncology (VHIO). AOP208 (formerly LB-208) operates through a new mechanism of action never before explored in oncology, what is called a “first-in-class” drug.
The drug is being evaluated in clinical phases in an international collaboration with the Austrian pharmaceutical company AOP Health. SERONCO-1, sponsored by Leukos Biotech with the support of AOP Health, is the first trial of the global program. In 2022, Leukos and AOP entered into a licensing and collaboration agreement to facilitate the global development of the product for the benefit of leukemia and other tumor patients.
Focus on a promising target
The new compound, AOP208, blocks a protein on the surface of the cancer stem cell, the serotonin 1B receptor, which in cancer cells adopts a particular conformation and controls metabolic pathways whose blockade may be crucial to treating the root cause of the disease. The compound is administered orally and was initially designed and developed by Leukos Biotech based on research conducted by Dr. Ruth Risueño since 2012 at the Josep Carreras Leukemia Research Institute with the support of the Josep Carreras Foundation against Leukemia.
Dr. Risueño, who acts also as scientific director of Leukos Biotech, explains: “We wanted to find a new way to attack cancer stem cells, as they are responsible for initiation and maintenance of the tumor, and also for the occurrence of relapses, a serious problem particularly in some leukemias. Our work at the Josep Carreras Leukemia Research Institute demonstrated that the serotonin 1b receptor is key to this process in leukemic stem cells. As there was no suitable molecule to block the receptor, Leukos implemented a chemical development program that allowed us to select the AOP208 molecule. We are now excited to start a clinical trial and take our compound to the next level for the benefit of leukemia patients and some solid tumors.”
First patient treated with AOP208
The first patient in the world to receive this innovative drug has done so through the SERONCO-1 phase 1 clinical trial, led by Dr. Irene Braña, medical oncologist at Vall d’Hebron University Hospital and head of the Head and Neck Tumor Group at VHIO, at the UITM-CaixaResearch, the early-phase clinical trials unit of VHIO and the only center participating in this study. This trial is being conducted in collaboration with Leukos Biotech with partial funding from the Spanish Ministry of Science and Innovation through the Public-Private Partnership Collaboration Program RETOS (CPP2021-008715).
“The treatment of the first patient with AOP208 in the trial represents a significant step toward understanding the safety and tolerability of the drug,” explains Dr. Irene Braña.
“All the drugs we test in patients in a clinical trial have previously demonstrated efficacy in preclinical models, but now we must first prove that it is safe in humans and second, that this antitumor activity also occurs in the patient,” she adds.
A first-in-class drug with potential in leukemia and several solid tumors
Research into new approaches in cancer therapy is urgently needed, emphasizes Dr. Christoph Klade, Chief Scientific Officer of AOP Health: “AOP208 targets a receptor in cancer stem cells that has not been the focus of cancer therapy until now, making it a first-in-class investigational drug in oncology. This pathway may play a role in several types of leukemia and also in several solid tumors, including breast and lung cancer.”
Thanks to the safety and active dose information expected from the SERONCO-1 trial, AOP Health will conduct a second clinical trial on AOP208 in patients with acute myeloid leukemia, a cancer that currently has a dismal prognosis.