NewLink Genetics Corporation, a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, has started first in human phase I clinical trial of NLG919. This is NewLink's second IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor that will initially be tested in patients with recurrent advanced solid tumours.

NLG919 is a small-molecule, orally bioavailable, immune checkpoint inhibitor designed to counteract a fundamental mechanism by which tumors evade immune-mediated destruction.

NLG919 represents a novel class of compounds in NewLink's IDO pathway platform. This platform includes indoximod, NewLink's most advanced IDO pathway inhibitor, which is currently in Phase 2 clinical development for the treatment of breast cancer.

"NLG919 represents a second category of IDO pathway inhibitors to enter clinical development. It has demonstrated encouraging preclinical activity on its own, and interesting synergy in combination with indoximod, our most advanced IDO product candidate. By combining multiple immune checkpoint inhibitors, such as those targeting PD-1, CTLA-4 and IDO, we have the potential to provide more effective treatment options," commented Dr Charles Link, chairman and chief executive officer of NewLink. "IDO pathway inhibitors harness key mechanisms of the immune system to enhance the body's ability to fight cancer and boost the effect of other therapies. We believe the addition of NLG919 to our pipeline further solidifies NewLink as a leader in the field of IDO pathway inhibition."

The phase I dose-escalation study is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and initial evidence of activity of NLG919 as determined by overall response rates in up to 36 patients with recurrent advanced solid malignancies.

In preclinical studies, NLG919 has demonstrated encouraging activity in solid tumor models and shown that IDO pathway inhibition is critical to reversal of the local immune suppression which impairs immunological detection and destruction of tumors. NewLink has shown that NLG919 inhibits the IDO pathway by a complementary, yet different mechanism of action than indoximod. Furthermore, preclinical data showing that the combined activity of different checkpoint inhibitors, including distinct IDO inhibitors such as NLG919 and indoximod as well as other agents targeting the PD-1 and CTLA-4 pathways, can function synergistically against cancer.

IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitors represent a key class of immune checkpoint inhibitors and a potential breakthrough approach to cancer therapy. This approach uses anti-tolerogenic, small molecule drug candidates intended to counteract a key mechanism by which tumours evade immune-mediated destruction. IDO is an enzyme that regulates immune response by suppressing T-cell function and enabling local tumour immune escape.

Recent studies have demonstrated that IDO is overexpressed in many cancers, both within tumour cells as a direct defense against T-cell attack, and also within antigen presenting cells in tumor draining lymph nodes whereby IDO promotes peripheral tolerance to tumours. When hijacked by developing cancers in this manner, IDO may facilitate the survival, growth, invasion, and metastasis of malignant cells that might otherwise be recognized and attacked by the immune system. NLG919 is currently in phase I clinical development in patients with recurrent advanced solid tumours. In addition to NLG919, indoximod, NewLink's most advanced IDO pathway inhibitor, is in phase II clinical studies for the treatment of breast cancer. NewLink has an active drug discovery programme focused on the IDO pathway.