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The UK firm Artios Pharma raised a huge Series C round last week in one of many efforts to develop cancer drugs that target the DNA repair systems of our cells. Artios Pharma bagged €129M (£110M) last week in a venture capital round led by the US-based firms Omega Funds and TCG X. The proceeds will bankroll the clinical development of Artios’ lead cancer drug in phase I in addition to the launch of clinical trials of its second program in late 2021. Artios develops DNA damage response (DDR) inhibitors, a class of drugs that kill cancer cells by sabotaging their ability to repair damage to their DNA. Artios’ CEO, Niall Martin, played a role in the development of AstraZeneca’s Lynparza -- a blockbuster DDR inhibitor for ovarian cancer that targets a protein called PARP. This year has been eventful for Artios, which has landed no less than two potentially lucrative big pharma collaborations. The first was with Merck KGaA in January, in which Artios could earn up to €5.7B as it co-discovers new DDR targets with the German giant. The second deal, worth up to €1.1B, was signed with Novartis, which seeks DDR targets that can prevent cancer from becoming resistant to therapies that break the DNA of tumor cells with radiation. “Artios’ DDR programs have been validated by large pharma partnerships which speak to the promise of their science and strategy,” stated Chen Yu, Founding Managing Partner of TCG X, last week. DDR inhibitors have been heralded as a game-changer for multiple cancers compared to traditional therapies, promising more precisely targeted treatments, better tolerance, and improved survival for patients. While PARP is the most established DDR target, newer inhibitors in development take aim at other protein targets including ATM, DNA-PK, ATR, and Pol theta. Merck KGaA is currently pushing ahead several ATR inhibitors in phase I. Artios’ most advanced program has its crosshairs on ATR, while its second focuses on Pol theta. Other efforts to uncover new DDR targets include a €10M seed round raised last year by the Swiss startup FoRx Therapeutics along with big pharma collaborations in North America including Bristol Myers Squibb with the Canadian firm Repare Therapeutics, and GSK with the US company IDEAYA. “The DDR class is an expanding therapeutic field with potential to be a fundamental part of the standard of care in many cancer subtypes, alone or in combination with immunotherapy, chemotherapy, or radiotherapy,” said Andree Blaukat, Head of Merck’s translational innovation platform in oncology and immuno-oncology. Another big push in the field focuses on stopping tumors from becoming resistant to common DDR inhibitors. In January, the Hungarian startup Turbine nailed €5.7M in a pre-Series A round. The company uses computational simulations and artificial intelligence to discover drugs that can overcome resistance to PARP inhibitors. Meanwhile, the French biotech Onxeo aims to smash tumor resistance to PARP inhibitors with a drug that misdirects the tumor cell’s DNA repair machinery rather than directly blocking it. According to interim results from a phase Ib trial in November, the drug combined with chemotherapy showed signs of controlling tumors where other treatments had failed. In April, Onxeo raised almost €10M in a share offering to fund the drug’s clinical development. All of these DDR developments are taking place amid big clinical trial disruption caused by the Covid-19 pandemic, said Ruth Plummer, Director of the Sir Bobby Robson Cancer Trials Centre in the UK. “The huge impact on the field from the Covid-19 pandemic is that worldwide trial recruitment has slowed, and even stopped in a number of centers, such that the timelines for all studies to complete has lengthened,” she told me. “In addition, many universities have had to stop laboratory science work, and many of the DDR inhibitors in development have come out of key academia and industry partnerships, so again there will have been a slowing to movement forwards in the field.” Nonetheless, Klaus Edvardsen, Senior Vice President and Global Head Oncology Development at Merck, remains confident that the industry can ride out the storm. “Our most important objective remains ensuring the safety and wellbeing of the patients participating in our clinical trials, and continuity in treatment and care of these patients,” Edvardsen told me. “Overall, we have mitigated the impact of Covid-19 on our DDR research and development activities and are committed to our timelines, which remain on track.” Cover image from Elena Resko. This article was first published on 19/01/2021 and has since been updated by Jonathan Smith to include recent developments in the DDR inhibitor field.

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