Just four months after cutting back R&D to focus on cancer and pain, Finland’s Orion has reaped the benefit. Today’s licensing deal with Merck & Co covering ODM-208, a mid-stage prostate cancer project, is this year’s second biggest by up-front value.

The tie-up shows Merck getting further into prostate cancer – the US group already boasts a mutation-defined label for Lynparza here – while the less well-known Orion builds on Nubeqa, a Bayer-partnered drug sold for non-metastatic disease. It is likely that the trigger for the $290m deal, beyond Orion flagging ODM-208 in its R&D overhaul, was data revealed at February’s Asco-GU conference.

This meeting featured results of Cypides, a first-in-human study of ODM-208, in 44 metastatic castration-resistant prostate cancer patients, all of whom had progressed on Zytiga and/or Xtandi. 32% achieved a PSA decrease of 50% or more, a number that rose to 68% in a subgroup with a mutation in the androgen receptor ligand-binding domain.

ODM-208 acts by inhibiting cytochrome P450 11A1, an enzyme involved in steroid production. It is thought that in prostate cancer the androgen receptor axis remains open even after Zytiga or Xtandi treatment, and it can become reactivated by non-androgenic steroid hormones.

ODM-208 is said to shut down steroid biosynthesis entirely, thus inhibiting prostate cancer progression. Evaluate Pharma reveals no other oncology work on CYP11A1 inhibition. Angion Pharma is active in cytochrome P450 inhibition, and had looked preclinically at the CYP17 inhibitor ANG-3279 in prostate cancer, but this is now discontinued; Angion is now developing CYP11B2 inhibitors, though not for cancer.

Either way, Merck has clearly been persuaded of the potential of the anti-steroid approach. It has given Orion $290m for co-development rights to ODM-208 and other CYP11A1 inhibitors, and retains an option to take out a global, exclusive licence.

Merck/Astrazeneca’s Lynparza is already carving out a place in castrate-resistant prostate cancer, thanks to its unusually broad US label allowing use in second-line patients with any HRR mutation. However, a Lynparza/Keytruda combo failed the Keylynk-010 prostate cancer study in March.

Merck clearly sees prostate as the place to be, however, and Orion had signalled its intention to build a presence here when it cut back investments in neuroscience and inhaled drug delivery, to focus on cancer and pain. The Finnish group cited Nubeqa and ODM-208 as reasons for optimism.

The former drug, licensed to Bayer, is approved for non-metastatic, castrate-resistant prostate cancer, and a second niche, hormone-sensitive prostate cancer, has opened up thanks to positive data from the Arasens trial published in the NEJM this year.

True, Zytiga is already available in the latter setting, and Xtandi in both, but the sellside still expects Nubeqa to become a blockbuster by 2026, according to Evaluate Pharma consensus. ODM-208 does not yet feature in most analysts’ models, a fact both companies will hope changes soon.

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