A researcher at ONA Therapeutics pipettes liquid in a laboratory

Research at ONA Therapeutics has focused on detailing how the company's system works at a molecular level.Credit: ONA Therapeutics

ONA Therapeutics in Barcelona, Spain, spun off from the Institute for Research in Biomedicine, Barcelona, and the Catalan Institution for Research and Advanced Studies, Barcelona, in 2019.

Since being a contender for The Spinoff Prize 2021, ONA Therapeutics in Barcelona, Spain, has selected a lead therapeutic candidate and begun pharmacology and toxicology studies. The company, which has also been longlisted for The Spinoff Prize 2023, has an eye on clinical trials in the coming years.

“We’ve matured into a real biotech,” says chief executive Valerie Vanhooren.

The company is a spin-off of the Institute for Research in Biomedicine (IRB) and the Catalan Institution for Research and Advanced Studies (ICREA), both in Barcelona.

IRB molecular biologist Aznar-Benitah founded the company with Vanhooren in 2019 to advance an antibody-drug strategy that his lab had shown could blunt the spread of cancer and reduce the burden of this metastasis in mice1. The company soon raised €30 million (US$33 million) in venture-capital funding, moved into a dedicated laboratory space, added world-leading specialists to its boards of directors and scientific advisers and grew to a 21-person research and development operation.

ONA scientists built on the pioneering discoveries of Aznar-Benitah’s team to further detail how the therapeutic approach works at a molecular level. They also made a humanized antibody to create the drug candidate ONA-046, which holds promise for treating deadly forms of advanced cancer.

“This approach has the potential to be more effective than traditional chemotherapy treatments, which often have limited success in treating metastatic cancer,” says Eduardo López-Collazo, a tumour immunologist at the Hospital La Paz Institute for Health Research in Madrid, who is not involved with the company.

Multipronged attack

ONA-046 is directed against a fatty-acid receptor, called CD36, that is found on the surface of many cells, including those that drive metastasis. On those cells, the receptor acts as a gullet for fat intake, helping to feed the voracious appetite of cancers in ways that fuel their invasiveness and migration. Aznar-Benitah and his colleagues have shown that CD36-targeted antibodies cut off this crucial wellspring of fat and trigger a kind of metabolic rewiring that ultimately proves lethal to cancer-propagating cells1,2.

But that’s not all the drug strategy seems to be doing. Other research teams have found that the same therapeutic approach helps to make drug-resistant cells vulnerable again to various anti-cancer agents3,4. As such, “I think their niche is going to be in therapy sensitization”, says Neil Bhowmick, a cancer biologist at Cedars-Sinai Medical Center in Los Angeles, California, who is not connected to ONA.

There’s also evidence that blocking CD36 augments the tumour-killing potential of anti-cancer immune cells. If that proves to be true, treatment with ONA-046 could help to shrink tumours both through direct effects on metastasis-initiating cells themselves and indirectly by enhancement of anti-cancer immune surveillance mechanisms.

“You have this double mode of action,” Vanhooren says. “That’s the beauty of it.”