LONDON - Ona Therapeutics SL has raised €30 million (US$33.9 million) in a series A round, providing the means to advance a new method of treating metastases by blocking the lipid metabolism of cancer cells.
The approach rests on preclinical research showing that increased expression of the fatty acid receptor CD36 on the surface of subsets of cancer cells plays a critical role in initiating metastases, in animal models of oral squamous cell carcinoma and other solid tumors.
Neutralizing CD36 inhibits those cells and has the potential to treat multiple types of metastatic cancers, according to Valerie Vanhooren, co-founder and CEO of Barcelona, Spain-based Ono. “Our research demonstrates that the survival of metastatic cells is linked to the intake of certain saturated fats, and if we block the capacity for intake of these fats, we significantly reduce the cells’ metastatic potential,” she said.
“We now have a lead panel of antibodies and are figuring out which is the best. We will then move on to IND-enabling studies,” Vanhooren told BioWorld.
The series A will fund a 150-patient phase I/II dose-ranging basket trial, in which the lead antibody will be tested in a number of solid tumor metastases. It is expected the trial will begin in 2023.
Ona’s seed investor, Asabys Partners, which put in €1.5 million to form the company in May 2019, followed on. The round attracted new investors Alta Life Sciences, Bpifrance’s Innobio2 fund, Belgian investor Fund+ and Ysios Capital. “We are very proud to raise such a big round with this international syndicate,” Vanhooren said.
Ona’s co-founder, Salvador Aznar-Benitah, of the Catalan Institution for Research and Advanced Studies, laid the scientific foundations for the company after identifying a subpopulation of slow-growing cells in oral tumors. Transcriptome analysis of samples of those cells isolated from tumors of several patients showed differential expression of 69 genes known to be related to metastasis formation and lipid distribution and translocation, compared to other tumor cells.
One of those was the CD36 gene. Aznar-Benitah showed that promoting overexpression of CD36 in cell lines and patient-derived cells with a low metastatic potential, significantly increased the ability of those cell to migrate and form metastases.
Conversely, depletion of CD36 expression greatly reduced metastasis to lymph nodes, in some cases blocking the process completely. Neither under- nor overexpression had any effect on the growth of primary tumors.
The subpopulation of oral tumor cells that expressed CD36 also expressed higher levels of three key enzymes that are involved in the oxidation of fatty acids. It is suggested that enables the cells to generate the high amount of energy needed to migrate and anchor at sites distant from the primary tumor.
Supporting that, when mice fed a high-fat diet were infected with patient-derived oral cancer cells, they developed much larger lymph node metastases, and the number of CD36-positive cells was greater in both primary tumors and metastases.
Administering anti-CD36 antibodies to mice with human oral cancer xenografts completely prevented the formation of metastases, while metastases that had already formed were reduced in size.
Vanhooren said that while the original research, published in Nature in December 2016, is in oral cancers, neutralizing CD36 expression has been shown to be effective in breast, ovarian and melanoma metastases. “It works in a number of mouse models,” she said.
CD36 has been targeted in a number of other cancer clinical trials, but in general those have focused CD36 binding to thrombosporin-1, to promote apoptosis of cancer cells. “Our approach is a little bit different from other companies,” said Vanhooren. “We’re blocking lipid metabolism.”