More IDO Issues: NewLink Drops Pancreatic Cancer Indication For Indoximod
Executive Summary
NewLink has scrapped plans to explore its IDO inhibitor in pancreatic cancer – more bad news for a drug class that has suffered several setbacks recently.
NewLink Genetics Corp. has “deprioritized” pancreatic cancer and will not proceed with a planned Phase II study testing its lead product indoximod with AstraZeneca PLC's Imfinzi (durvalumab), the company said during its first-quarter earnings announcement.
This follows on from news last month that NewLink had halted the Phase III Indigo301 study of indoximod in combination with PD-1 inhibitors for patients with advanced melanoma. NewLink plans to evaluate an alternative trial design for this Phase III program. However, Jefferies analysts said in an April 15 note that they expected NewLink to pivot away from melanoma given the low likelihood of success with IDO inhibitors in this indication.
NewLink emphasized during its May 3 earnings call that indoximod had demonstrated encouraging clinical data in several cancer indications, and that its decision not to go ahead with studies in pancreatic cancer was due to pipeline prioritization.
After completing a review of its clinical programs, NewLink expects to substantially reduce the rate at which the company is using cash. Also through the review process NewLink aims to identify indoximod programs that it will not take forward.
“Because of the situation that we're in currently, we have to rank the things that we think are most important and most probable to hit within the budget and timeline that we have to be able to show proof of concept for indoximod in a definitive way,” Charles Link, chair and CEO of the company, said during NewLink’s Q1 earnings call.
“Our decision is that doing a trial in combination with another checkpoint blockade is probably not the optimal first place for us to go to look for final proof of concept,” Link said.
Indoximod, an investigational, orally available small molecule targeting the IDO pathway, was in clinical development for melanoma, pancreatic cancer, acute myelogenous leukemia, brain cancer and solid tumors.
Link said the company was looking for “the easiest, most cost-effective path to validation” for indoximod. “We want to take time and be very purposeful and thoughtful about those decisions,” he said.
When NewLink halted the Phase III trial in melanoma, Jefferies analysts suggested the company might focus on diffuse intrinsic pontine glioma (DIPG), a type of brain cancer, as a first indication for indoximod. A Phase II trial is expected for indoximod in DIPG, but the analysts said "if the Phase II trial design is single-arm as expected, concerns will remain as to how indoximod performance extrapolates to randomized pivotal studies."
IDO Issues
Indoleamine 2,3-dioxygenase (IDO1) is an enzyme that plays an important part in immune response. Despite promising early data and a rush into broad late-stage trials, the class has disappointed as more data rolls in.
Just this month, immuno-oncology giant Bristol-Myers Squibb Co. said it had terminated three Phase III studies for its in-house IDO inhibitor, BMS-986205, in melanoma, head and neck, and lung cancer. (Also see "A Wake For IDO: Bristol Ends Registrational Trials Of High-Priced Flexus Drug" - Scrip, 30 Apr, 2018.)
Furthermore, on April 6, Incyte Corp. and Merck & Co. Inc. announced the combination of Keytruda (pembrolizumab) and epacadostat failed against the Keytruda monotherapy comparator arm in the Phase III ECHO-201/KEYNOTE-252 study of 700 patients with metastatic melanoma. (Also see "Incyte/Merck's ECHO-301 Failure Casts More Shadow On IDO Space" - Scrip, 6 Apr, 2018.)
NewLink’s Q1 Performance
NewLink ended the quarter on March 31, 2018, with cash and cash equivalents totaling $143.9m versus $158.7m for the year ending December 31, 2017. R&D expenses for the first three months of 2017 were $20.3m, the company noted, an increase of $4.6m from $15.7m for the same period in 2017.
Net loss for the first three months of the year was $18.3m compared to net loss of $20.9m for the same period in 2017.