Spanish researchers have outlined a new therapeutic route to attack tumor stem cells in patients with leukemia. The Cancer Molecular Therapy Research Unit UITM-CaixaResearch of the Vall d’Hebron Institute of Oncology (VHIO) It is the only center in the world where the phase 1 clinical trial is being carried out SERONCO-1 which is evaluating for the first time in patients a new compound called AOP208 (formerly LB-208), initially developed by Leukos Biotecha spin-off of Josep Carreras Leukemia Research Institutewhich works through a new mechanism of action never explored before in oncology, what is known as ‘first-in-class’.
The new compound blocks a protein on the surface of the cancer stem cell, the serotonin 1B receptorwhich in oncological cells adopts a particular conformation and controls metabolic pathways whose blocking may be essential to treat the root cause of the disease. The compound is administered orally and was initially designed and developed by Leukos Biotech based on research carried out by doctor Ruth Risueño since 2012 at the Josep Carreras Leukemia Research Institute with the support of the Josep Carreras Foundation against Leukemia.
«We wanted to find a new way to attack cancer stem cells, since they are responsible for the initiation, maintenance of the tumor and the appearance of recurrences, 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. Since there was no suitable molecule that could block the receiver, At Leukos we implemented a chemical development program that allowed us to reach the AOP208 molecule. Now we are delighted to begin a clinical trial and take our compound to the next level for the benefit of leukemia patients and some solid tumors,” says Risueño, also scientific director of Leukos Biotech.
Thanks to the phase 1 clinical trial SERONCO-1, led by Dr. Irene Branamedical oncologist at the Vall d’Hebron University Hospital and head of the VHIO Head and Neck Tumors Group at the UITM-CaixaResearch, a first patient has been able to receive this innovative drug.
The clinical trial is being carried out in collaboration with Leukos Biotech with partial funding from the Ministry of Science and Innovation of Spain through the RETOS Public-Private Collaboration Program (CPP2021-008715).
“Treating the first patient with AOP208 in the trial represents a significant step toward understanding the safety and tolerability of the drug,” he explains. Brana. Remember that “all the drugs that we test on patients in a clinical trial have previously demonstrated efficacy in preclinical models, but now we must demonstrate, first, that it is safe in humans and second, that this antitumor activity also occurs in the patient.”
Applicable in solid tumors such as breast and lung tumors
Christoph Kladechief scientific officer at AOP Health, highlights the need to investigate new approaches in cancer therapy. «AOP208 targets a receptor on cancer stem cells that has not been the focus of cancer therapy until now, making it an investigational drug ‘first-in-class’ in oncology. “This pathway may have a role in several types of leukemia and also in several solid tumors, including breast and lung cancer.”
Based on the safety and active dose information expected from the SERONCO-1 trial in patients with advanced solid tumors, AOP Health will conduct a second clinical trial on this compound in patients with acute myeloid leukemia, a cancer that currently has a dismal prognosis.
The drug is being evaluated in clinical phases in international collaboration with AOP Health. SERONCO-1, promoted by Leukos Biotech with the support of AOP Health, is the first trial of the global program. Leukos and AOP closed a licensing and collaboration agreement in 2022 to facilitate the development of the product for the benefit of leukemia and other tumor patients on a global scale.
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