CXCL3

iStock, Polinmr Incyte is abandoning its ALK2 blocker zilurgisertib, which it was trialing for myelofibrosis-associated anemia, while iTeos will deprioritize the development of inupadenant after it failed to meet the biotech’s clinical bar in a Phase II study of metastatic non-small cell lung cancer. The oncology space on Thursday lost two pipeline treatments after Incyte and iTeos Therapeutics announced that they were discontinuing the development of respective drug candidates following underwhelming readouts. Incyte revealed in an investor conference call on Thursday that it would no longer advance zilurgisertib, an investigational ALK2 inhibitor, in myelofibrosis-associated anemia, according to investor notes from William Blair and BMO Capital Markets. The company said it will continue to develop zilurgisertib in fibrodysplasia ossificans progressiva. The drug candidate was in very early stages of development for both indications, with the company still working on clinical proof-of-concept studies for the candidate before deciding to discontinue it. By blocking ALK2, zilurgisertib is designed to boost the production of the liver hormone hepcidin, in turn increasing plasma iron levels, promoting the production of red blood cells and suppressing ossification. The decision to discontinue zilurgisertib for myelofibrosis-associated anemia comes after the candidate’s “limited efficacy” in a Phase I trial, according to William Blair. Meanwhile, BMO Capital Markets noted that the move “adds to growing list of pipeline misses,” though the firm ultimately did not find this development surprising. In its third-quarter report in October, Incyte leadership had indicated that “zilurgisertib needed to be dosed higher than initially expected to see signs of more promising efficacy,” which could indicate weak overall activity, BMO analysts wrote. The discontinuation follows Incyte’s recently scrapping of MRGPRX4 antagonist INCB000547. The biotech announced last month that Phase II data for the candidate fell short of expectations and thus do not support further investment into its development. Incyte was developing INCB000547 for chronic pruritus. Joining Incyte’s cancer cut is iTeos, which on Thursday announced that it has “deprioritized” the development of its small molecule A2AR blocker inupadenant in metastatic non-small cell lung cancer (NSCLC) because the candidate “does not meet sufficient level of clinical activity to warrant further investment,” CEO Michel Detheux said in a statement. The decision was based on Phase II data showing that a combination regimen of inupadenant with carboplatin and pemetrexed yielded a 63.9% overall response rate in post-immunotherapy patients. Median progression-free survival (PFS) across all doses was 7.7 months. An exploratory analysis of the mid-stage trial also showed that inupadenant treatment restored normal levels of the CXCL3 chemokine, a biomarker known to be associated with clinical activity. Still, iTeos is funneling resources away from inupadenant and instead prioritizing the development of its other “differentiated, first- or best-in-class therapies,” Detheux said. It is not yet clear which candidates the biotech plans to focus on, though Detheux noted that the company will provide more details regarding its pipeline in 2025. Correction (Dec. 16): The original version of this article erroneously stated that Incyte is completely discontinuing development of zilurgisertib. In fact, the candidate is still in development for fibrodysplasia ossificans progressiva. BioSpace regrets the error.