Combos

NewLink grabs the AACR spotlight with IDO pathway, Keytruda combo — shares blitzed

Attendees, speakers and awardees during AACR’s 2017 Opening Ceremony © AACR/Todd Buchanan 2017


WASHINGTON, DC — Researchers at NewLink Genetics are in the spotlight at AACR this morning with data showing that their pair-up of the biotech’s IDO pathway inhibitor indoximod with Merck’s Keytruda significantly pushed up response rates over what the PD-1 checkpoint alone normally produces for advanced melanoma.

The historical percentage response rate for Keytruda alone in this field is in the low 30s, but for all the 60 evaluable patients in the study the ORR was 52% — including hard-to-tread ocular melanoma cases. If you leave out the ocular (eye) patients, the success ratio rises to 59%, with a disease control rate of 80%. And the researchers say the safety profile for the combo looked similar to Keytruda alone, which will help the biotech start making the case that it can add a therapy to a checkpoint without pushing toxicity, the way a CTLA-4 drug like Yervoy would.

A group of critics on Twitter hit the data quickly Tuesday morning, though, questioning the results and driving the stock down 22% in early trading.

NewLink $NLNK is unusual in this field. The biotech — which was hammered in 2016 with the failure of its pancreatic cancer vaccine — partnered with Genentech in 2014 on GDC-0919, a specific IDO enzymatic inhibitor. Genentech has that program under its wing after paying $150 million upfront with more than a billion dollars promised in milestones.

Charles Link

NewLink CEO Chuck Link describes indoximod as its wholly-owned IDO pathway inhibitor, separate from the enzymatic specific group, which includes Incyte’s leading epacadostat, now headed into a full slate of late-stage combinations with Keytruda (Merck) and Opdivo (Bristol-Myers).

“Indoximod is a drug we’re trying to fully understand,” Link tells me. The drug acts on both dendritic cells and T cells, he says, allowing the T cells to replicate in fighting cancer. It does not bind with the kind of specificity that characterizes the enzymatic class.

The next step is to push ahead into a registration study. The latest data comes from a Phase II that does not have a control arm, which will be remedied in the late-stage trial. And Link says he expects the study to get underway later this year.

Link wasn’t ready to provide an estimate of when the data will read out. That might depend on a variety of things, he says, including some design elements that might allow for an early cut of the results that could be taken to the FDA in search of an accelerated approval.

Time will tell.

IDO inhibition came into full focus during the last few days as Incyte surged on its late-stage development plans. Behind the leaders you’ll find a host of early-stage efforts underway, and Link believes that there may be a future for combining IDO pathway and IDO enzyme inhibitors.

What Incyte, NewLink and all the other players are wondering is if an IDO/PD-1 or IDO/PD-L1 checkpoint can do as well as a checkpoint match-up using a CTLA-4. Those CTLA-4s are effective, but well known for a harsh toxicity that makes them hard to tolerate. And that would have major implications not only for Yervoy’s future, but also combos like AstraZeneca’s durvalumab and tremelimumab, a CTLA-4 that occupies a central role in the pharma giant’s plans to leap from last place into the forefront, presuming they can get a relatively quick OK as the fifth in a series.


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RAPS Regulatory Convergence 2017