Artios Pharma Limited (Artios), a biotech company established with the help and expertise of Francis Crick Institute scientist Simon Boulton, has secured an additional $86m (£65m) to advance its first-in-class small molecule DNA repair programmes into the clinic. The company was founded in 2016 as a spinout from Cancer Research UK’s Commercial Partnerships team with seed funding from SV Health Investors.
Artios is developing treatments to prevent cancer cells from repairing their DNA when it gets damaged. Many cancers can’t survive without ‘back-up’ DNA repair mechanisms, so compounds that block these pathways could form the basis of the next generation of cancer therapies – either alone or in combination with chemotherapy, radiotherapy or immunotherapy drugs.
Faults in normal DNA repair processes can cause tumours to develop and grow, but even cancer cells need DNA repair mechanisms to survive. Cancers become reliant on these back-up DNA repair processes as they develop but these changes can also become an Achilles’ heel. Blocking these back-up repair pathways can kill cancer cells without damaging healthy cells, making them an exciting avenue for new cancer therapies.
From lab to clinic
“By targeting cancer’s Achilles’ heel, we have a unique opportunity to develop a new class of treatments that could bring real benefit to patients in the next decade,” says Simon Boulton, Senior Group Leader at the Crick and Senior Vice President for Science Strategy at Artios. “The new investment will help us to advance our new DNA repair inhibitor drugs, taking us from basic science to the first human trials.”
Blocking DNA repair is already the basis of a drug called olaparib, which was recently approved to treat breast and ovarian cancers in women with BRCA mutations. Olaparib and other related inhibitors stop a protein in our cells known as poly-ADP ribose polymerase (PARP) from repairing damaged DNA. Cancer cells with BRCA gene faults already have a poor repair system, so blocking PARP with drugs like olaparib kills cancer cells by stopping them from repairing themselves.
Clinical trials are currently investigating whether PARP inhibitors could work in ovarian and breast cancers that have other DNA repair mutations beyond the BRCA gene fault, as well as in other types of cancer. However, even if these are successful, new strategies are needed to prevent treatment resistance and exploit other DNA repair mechanisms in different cancers that are not sensitive to PARP inhibitors.
Beyond PARP inhibitors
Artios is developing a new type of drug to block a protein called Pol-theta, which normally functions as a back-up DNA repair pathway. Importantly, Pol-theta is largely dispensable for repair in normal cells, but it becomes essential in cancer cells, particularly those that have lost other DNA repair pathways. Hence, Pol-theta inhibitors could be used to selectively kill cancer cells that have become reliant on Pol-theta for DNA repair.
Preclinical work has also shown that loss of Pol-theta makes cancer cells more vulnerable to radiotherapy without effecting normal cells. Around 40% of cancer patients are treated with radiotherapy, so if these results translate to patients they could have a significant impact.
“There’s nothing else in the market or even conceptually that can do this, so we think Pol-theta inhibitors could be a game-changer in cancer therapy,” says Simon. “As Pol-theta inhibitors work in a different way to PARP inhibitors, they could potentially be used in combination approaches to improve treatment outcomes and prevent resistance.”
Tony Hickson, Cancer Research UK’s chief business officer, said: “We’re thrilled to see the continued success of Artios, one of a number of very successful new companies formed by Cancer Research UK over recent years with the help of the charity’s Commercial Partnerships Team. Our unique partnership allows us to provide a solid research foundation for developing new treatments that could bring real impact to cancer patients.
“Through Artios, in collaboration with the Cancer Research UK Therapeutic Discovery Laboratory, discoveries from Cancer Research UK’s network of world-leading scientists are being turned into the latest treatments to selectively kill cancer cells. These innovative therapies, that target the way cancer cells repair damaged DNA, have the potential to work alone or even make treatments like chemotherapy and radiotherapy more effective.”
The new financing, which was significantly oversubscribed, was led by Andera Partners (formerly EdRIP) and LSP (Life Sciences Partners), with participation by additional new investors Pfizer Ventures and Novartis Venture Fund (NVF). Artios’ existing shareholders Arix Bioscience, who are now Artios’ largest shareholder, SV Health Investors, Merck Ventures, IP Group plc and AbbVie Ventures also participated in the fundraise.