NewLink's IDO inhibitor score sheet reads one fail, one modest pass

breast cancer
Indoximod fails breast cancer trial; mixed views remain on follow-up GDC-0919.

NewLink Genetics has been hit by another setback in its immuno-oncology pipeline after IDO inhibitor indoximod failed to show any benefit in a metastatic breast cancer trial.

The Ames, Indiana-based biotech said the phase 2 study didn't meet its primary objectives of improving overall survival, progression-free survival or the objective response rate when added to standard therapy with taxane drugs in the trial, which enrolled patients with advanced HER2-negative breast cancer.

Lead investigator Hatem Soliman, M.D., of the H. Lee Moffitt Cancer Center and Research Institute in Florida commented: "As demonstrated by multiple studies that have been reported since the start of this clinical trial, breast cancer unfortunately remains a challenging disease in immuno-oncology."

The result is a fresh blow for NewLink, which has been in the doldrums since it revealed a pancreatic cancer vaccine failed a phase 3 trial last year, with patients receiving placebo actually living longer than those on its algenpantucel-L candidate. The finding cast serious doubts on the future of the company's HyperAcute platform cancer vaccine platform, which was subsequently parked by the company as it focused on its IDO inhibitor candidates.

The indoximod disappointment sparked a steady decline in NewLink's shares that was not helped by some more clinical news on the firm's IDO portfolio that emerged at ASCO over the weekend.

NewLink presented data on a follow-up IDO inhibitor—navoximod (GDC-0919)—in combination with Roche's PD-L1 inhibitor Tecentriq (atezolizumab) in 61 patients with advanced solid tumors, with a 10% overall response rate that according to analysts at Jefferies "seemingly does not meaningfully differentiate to PD-(L)1 alone."

Their overall take is that the drug's performance was "disappointing," although other analysts had a different take.

On a slightly more positive note, Leerink said the study suggests the drug, which is partnered with Roche/Genentech, seems to be safe and consistent with Incyte's rival IDO inhibitor epacadostat which also had new data on display at ASCO. They concluded the results "seemed too immature to draw conclusions on efficacy ... given the heterogeneous patient population enrolled, which consisted mostly of IO-insensitive tumor types."

Going further, analysts at Baird say the profile of GDC-0919 is encouraging given that the drug's dosing had not been optimized and the patient population had been heavily pretreated. They think there could be good news for the company's IDO portfolio from additional phase 2 trials in pancreatic cancer and acute myeloid leukemia in the coming months, and say indoximod is on course to start a phase 3 trial in melanoma before the end of the year.

NewLink will be reporting data at ASCO later today on the combination of indoximod and prostate cancer vaccine Provenge, which it says shows a significant improvement in progression-free survival (10 months versus 4 months).

Overall, the picture for the company looks a little gloomy at the moment however, with shares down more than 8% in premarket trading, and 11% by midday.