
Nuvectis switches focus

Nuvectis's effective discontinuation of NXP800 – the molecule apparently still has a theoretical chance of being taken forward in endometrial and prostate cancers – thins the industry pipeline of GCN2 inhibitors to three clinical projects. These include DCC-2812, the Deciphera-originated molecule recently taken into phase 1 by Ono, which acquired Deciphera for $2.4bn last year. Nuvectis on Thursday said it was stopping development of NXP800 in ovarian cancer after seeing just two unconfirmed partial responses among 13 evaluable subjects with Arid1a-mutated disease given a target dose of 75mg/day. The study earlier highlighted a risk of thrombocytopenia, and while this was apparently later managed with intermittent dosing that didn't broaden NXP800's therapeutic window. Nuvectis, whose stock fell 8% even though the NXP800 setback was hardly surprising, now turns to NXP900, which it calls a small-molecule inhibitor of YES1/SRC signalling, and which is in phase 1 dose escalation. Some comfort for others working on GCN2 is that Nuvectis has been vague about NXP800's precise mechanism. The molecule was licensed from the UK's Institute for Cancer Research, which coded it CCT361814 and called it an inhibitor of the HSF1 pathway, activating an unfolded protein response and altering androgen receptor and E2F function.
Industry projects targeting GCN2
Project | Company | Mechanism | Status |
---|---|---|---|
DCC-2812/ DP-9149 | Ono (ex Deciphera) | GCN2 activator | Ph1 in GI cancers |
APL-4098 | Apollo Therapeutics | GCN2 inhibitor | Ph1/2 in AML |
HC-7366 | HiberCell | GCN2 modulator | Ph1 in AML (solid tumour trial terminated) |
NXP800/ CCT361814 | Nuvectis (ex ICR) | GCN2 activator | Ph1 in ARID1a-mutated, platinum resistant ovarian carcinoma discontinued; possible utility in endometrial & prostate cancers |
AST-05X | Aston Science | GCN2 inhibitor | Preclinical poster at AACR 2024 |
DA-4507 | Dong-A ST | GCN2 inhibitor | Preclinical poster at SITC 2022 |
DP-9024 | Ono (ex Deciphera) | PERK/GCN2 inhibitor | Preclinical poster at AACR 2023 |
CRD-099 | Chordia Therapeutics | HRI/PERK/GCN2 inhibitor | Preclinical poster at AACR 2025 |
Source: OncologyPipeline.