For a while, IDO inhibitors were believed to be the hot new area for cancer drugs. Then in April, Merck & Co. and Incyte had a catastrophic failure with a combination trial of Merck’s Keytruda and Incyte’s IDO inhibitor epacadostat in late-stage melanoma. Incyte abandoned the study, which forced NewLink Genetics to re-evaluate its own IDOi, indoximod. And it had looked like NewLInk was abandoning its efforts as well. But now they have announced, with company restructuring and layoffs, they are refocusing on indoximod.
Terry Chrisomalis, writing for Seeking Alpha, says, “The translation believed to be true was just because Incyte’s drug failed, that NewLink’s drug would also. I’m happy to say that NewLink has chosen to advance its IDO inhibitor drug indoximod, despite the failure of epacadostat. I agree with that … for two reasons.”
His rationale is that, first, although indoximod targets the IDO pathway, it does it differently than epacadostat. And in a Phase II trial reported at the ASCO 2018 Annual Meeting in June, the results were positive, although the study design has some issues, namely no placebo control. Nonetheless, the drug with a checkpoint inhibitor showed an overall response rate (ORR) of 55.7 percent and a complete response rate of 18.6 percent.
Chrisomalis also points out that the Phase II trial had enrolled 15 patients that had uveal melanoma, which may have skewed the data downward for the primary indication. “If we take that into account,” he writes, “then it’s quite possible that the numbers that NewLink received for its melanoma study should be higher. Why would that be the case? That’s because uveal melanoma is not only an intraocular malignancy, but it is a tougher form of melanoma to treat.”
NewLink had cut about a third of its headcount and reorganized its executive management team. With all the changes, the company indicates it expects to spend around $40 million a year, which will allow them to keep the doors open into the second half of 2021. But this is a company whose stock traded at about $55 per share three years ago and is now trading for about $3.78. It’s clearly struggling.
About a year ago, NewLink had a collaboration with Roche for another IDO inhibitor called navoximod, but when it failed to impress in the clinic, Roche wrote it off. And a year before that, NewLink restructured after its pancreatic cancer vaccine failed.
In a filing with the U.S. Securities and Exchange Commission (SEC), the company reported that its chief financial officer Jack Henneman had resigned his job to become chief administrative officer in preparation for leaving the company later this year. He will be replaced by Carl Langren. He has been acting as the vice president of finance since 2011. Chief commercial officer Brian Wiley left the company in the last week.
It also stated that on July 26, the company laid off 25 employees, or about 30 percent of staff.
The indoximod program will focus on recurrent pediatric brain tumors, front-line treatment of diffuse intrinsic pontine glioma (DIPG), and front-line treatment of acute myeloid leukemia (AML). It will also work to advance a prodrug of indoximod called NLG802, which has shown efficacy in preclinical studies. “Indoximod’s unique mechanism of action has shown promising activity against multiple cancers and in combination with checkpoint inhibitors, radiation, chemotherapy, and vaccines,” said Charles Link, Jr., chairman and chief executive officer of NewLink in a statement. “We intend to focus on near-term opportunities where additional data can validate the importance of indoximod in areas of high unmet need.”
A Product Manager with expertise in pharma marketing and sales operations