Roche and Novartis, two companies with a notable presence in prostate cancer, are making new bets on treating this disease, advancing new projects, GDC-1261 and INR731 respectively, into their first-in-human studies. For now, however, there are no clues as to how either of these molecules acts.
This work wasn’t disclosed in either company’s recent first-quarter financials update, and has instead come to light in new listings on the clinicaltrials.gov registry. These also show two other secret assets, Novartis’s ERW316 and Hansoh’s HS-10587, moving into phase 1, though an educated guess can be made as to the mechanisms of these two projects.
In prostate cancer Novartis is a prominent player, and beyond its marketed anti-PSMA radiopharmaceutical Pluvicto its pipeline includes clinical assets against the androgen receptor (with a degrader), EZH1/2 and GRPR. To these efforts INR731 is now being added, with a first-in-human trial starting later this month in the metastatic castration-resistant setting, either as monotherapy or in combination with AR pathway inhibition.
Roche also has an AR degrader in its pipeline, with an asset licensed from Jemincare, and is testing its approved breast cancer drug Itovebi in prostate cancer too. Its newcomer, GDC-1261, is now in phase 1, apparently as monotherapy only; the clinicaltrials.gov listing doesn’t specify the metastatic prostate cancer setting being pursued here.
Small molecules
Meanwhile, Novartis’s ERW316 appears to be a CDK2 inhibitor, given that its first-in-human trial tests it in cancers in which ER-positive HER2-negative breast, and CCNE1-amplified tumours, are specifically called out.
That’s identical to the first-in-human study of another Novartis molecule, GVV858, which went into the clinic last December. It’s not immediately clear whether there’s any similarity between ERW316 and GVV858, or why Novartis would necessarily want to develop two separate assets acting on CDK2.
Hansoh’s HS-10587 also appears to be a small molecule, judging by the participation criteria for its new phase 1 study. This requires patients’ tumours to have MTAP deletion, suggesting that this molecule is a PRMT5 or MAT2A inhibitor, in common with the likes of Tango’s vopimetostat or Ideaya’s IDE397 respectively, for instance.
Recently disclosed first-in-human studies*
Away from small molecules, Akeso is advancing a trispecific MAb, AK150, that hits ILT2, ILT4 and CSF1R. Targeting ILT2/4, also known as LILRB1/2 respectively, has caused headaches, with Merck & Co handing MK-4830 back to Agenus, Sanofi giving up on Biond Biologics’ BND-22, and Pfizer canning PF-07826390; no company other than Akeso appears to be trying to hit CSF1R as well, however.
Hardly a week seems to go by without a new in vivo Car-T project going into human trials, and this time it’s Iaso’s anti-CD19 asset IASO207. At last year’s ASH conference Iaso presented a technology for generating Car-T cells in vivo, using an engineered third-generation lentiviral vector; projects profiled here included IASO206 (anti-BCMA) and IASO208 (CD20) as well as IASO207.
And another cell therapy newly into the clinic is BlueShpere’s BSB-2002, an engineered T-cell receptor targeting NPM1. BlueSphere is a private US biotech that raised $105m in a 2021 series B. BSB-2002 seems to be the second asset it’s taken into the clinic since being founded in 2017, with BCB-2001, which targets the minor histocompatibility antigen HA-1, starting phase 1 last year.
