Novartis has struck a deal with Artios Pharma to access DNA damage response (DDR) targets with the potential to enhance its radioligand therapies. Artios, which is run by some of the people behind pioneering DDR drug Lynparza, is set to get $20 million upfront and up to $1.3 billion in milestones in return for the targets.
During the three-year collaboration, Artios and Novartis will discover and validate up to three targets for exclusive worldwide use by the Swiss Big Pharma company. The goal is to find targets that add to the potential of Novartis’ radioligand therapies.
Cancer cells are prone to DNA damage because of the speed at which they replicate but there are fundamental DNA repair mechanisms that fix the problems. Some of the repair mechanisms can be upregulated in cancer cells. Radioligands and certain other therapies work by damaging DNA. If the DNA damage hits a pathway that is upregulated, then you get resistance.
Artios is working to understand the DNA repair factors that are important to Novartis’ radioligands to discover DDR targets that enhance their efficacy. “Are there targets that if we knock out those DNA repair factors [and] processes that we would enhance in certain tumors ... the effectiveness of these radioligands? It's a combination of two things coming together ... and really sensitizing the tumor better to that style of damage,” Artios CEO Niall Martin said.
Novartis has built up its radiopharmaceutical business in recent years through in-house investment and the acquisitions of Advanced Accelerator Applications and Endocyte for, respectively, $3.9 billion and $2.1 billion. The strategy is beginning to bear fruit, with Novartis reporting last month that the drug at the heart of the Endocyte buyout had hit the mark in a phase 3 prostate cancer trial.
Other research groups see DDR and radiopharmaceuticals as complementary approaches. DDR drugs such as AstraZeneca’s Lynparza work by stopping an enzyme from repairing breaks in DNA. As such, DNA-damaging agents, such as radioligand therapy, could combine well with DDR therapies.
That thinking has led to studies that are evaluating the effects of giving radium Ra 223 dichloride in combination with the PARP inhibitors Lynparza and GlaxoSmithKline’s Zejula. PARP inhibitors put the DDR space on the map but Artios is founded on the belief there are rich pickings beyond that first, concept-validating target.
Artios’ C-suite features Niall Martin and Graeme Smith, both of who worked on Lynparza at KuDOS Pharmaceuticals. AstraZeneca bought KuDOS for $210 million but Martin and Smith both retained an interest in DDR. Martin took up the Artios CEO post in 2016 and Smith, after a stint at AstraZeneca, joined as chief scientific officer the next year.
The appointments positioned Martin and Smith to work on inhibitors of DDR enzymes beyond PARP, including DNA polymerase theta and DNA nucleases. Artios’ expertise in the area attracted Novartis Venture Fund, which contributed to a $84 million series B round, in 2018 and has now led to a deal with the Swiss Big Pharma itself.
In a statement, Martin said the collaboration “is an ideal fit” as it “maximizes the application of our platform to areas beyond our current focus as we independently advance our pipeline of novel DDR candidates.” Artios retains full control of its ATR inhibitor ART0380 and pol theta prospect ART4215.
The deal comes a few months after Merck KGaA committed to $30 million in upfront and near-term payments to work with Artios on compounds against up to eight targets. Merck is on the hook for up to $860 million in milestones per target.