NewLink Genetics Pursues Dual Cancer Immunotherapy Platforms

Harnessing multiple components of the immune system to fight cancer is the focus of NewLink Genetics’ clinical pipeline. The company’s HyperAcute immunotherapy platform stimulates the patient’s immune system to recognize and attack cancer cells, while its IDO pathway inhibitor platform targets a key immune checkpoint and disrupts mechanisms that cancerous tumors could use to evade a patient’s immune system.

NewLink’s most advanced product candidates in the HyperAcute immunotherapy arena include algenpantucel-L and tergenpumatucel-L. The agents are made up of human cancer cells that are tumor specific, but not patient specific. The cancer cells have been altered so that they express the carbohydrate alpha-gal. Humans exhibit a pre-existing immunity to this carbohydrate and the resulting immune response results in a rapid and powerful reaction to seek out and destroy the cancer cells by the body’s immune system. By taking advantage of this immune response, NewLink hopes to marshal a patient’s own immune system to attack his own cancer cells.

The company says algenpantucel-L and tergenpumatucel-L use intact whole cells rather than cell fragments or purified proteins, and the immunotherapies do not require tissue from individual patients.

Algenpantucel-L is being evaluated in two phase III clinical trials. IMPRESS involves 722 patients with surgically resected pancreatic cancer and PILLAR involves patients with locally advanced pancreatic cancer.

Tergenpumatucel-L is in phase II/III clinical development and NewLink is actively recruiting patients with non-small cell lung cancer (NSCLC) to participate in upcoming trials.

In September 2013, the NewLink researchers presented data at the 2013 European Cancer Congress (abstract 2503). For both algenpantucel-L and tergenpumatucel- L, the researchers reported greater than expected responses to salvage chemotherapy:

• Three pancreatic cancer patients exhibited durable complete responses (12-36 months) after subsequent salvage chemotherapy after progressing on algenpantucel-L.
• Sixteen NSCLC patients were followed after subsequent salvage chemotherapy after progressing on tergenpumatucel-L. Among those, five (31%) achieved partial responses and four (25%) achieved stable disease.
• Algenpantucel-L and tergenpumatucel- L each produced immunologic responses associated with improved survival, supporting the efficacy of HyperAcute immunotherapy.

Newlink’s IDO pathway platform comprises a class of smallmolecule immune checkpoint inhibitors with similar mechanisms as the CTLA-4- and PD-1-targeting antibodies. The IDO pathway inhibitor platform has two drug candidates currently in development. The first, indoximod, is currently in phase II development for a range of solid tumors. NewLink’s second IDO pathway inhibitor, NLG919, is expected to enter clinical development by the end of 2013.

NewLink Genetics Pipeline