NewLink-Genentech deal could be worth more than $1bn
This article was originally published in Scrip
NewLink Genetics has been in the news recently for its experimental ebola vaccine, but the Ames, Iowa-based company's stock jumped 7.1% to $31.44 per share on 20 October based on a cancer immunotherapy deal with Genentech potentially worth more than $1bn.
Genentech, a member of the Roche Group, will give NewLink $150m up front and could pay out $1bn-plus in milestone fees for development of the indoleamine 2,3-dioxygenase (IDO) pathway inhibitor NLG919 and for a research collaboration to discover additional IDO and tryptophan 2,3-dioxygenase (TDO) inhibitors. The deal also gives NewLink escalating double-digit royalties on future product sales under the partnership.
Genentech will lead development of NLG919 and other compounds that may come out of the collaboration, but NewLink is entitled to research funding related to its work with Genentech. Commercialization will be led by Genentech, but NewLink has an option to co-promote NLG919 and other IDO/TDO inhibitors under the companies' agreement.
"This deal represents one of the richest deals in immune-oncology and provides validation of the IDO platform," Jefferies analyst Biren Amin said in a 20 October research note.
NewLink has spent the past several months touting opportunities to treat cancer with its IDO inhibitors in combination with other immunotherapy drugs, including programmed cell death-1 (PD-1) and PD-1 ligand (PDL-1) inhibitors (scripintelligence.com, 4 April 2014). However, the deal with Genentech did not include NewLink's lead IDO inhibitor indoximod, which is in Phase I and II trials for various tumor types; NLG919 is in Phase I to treat solid tumors.
Genentech plans to test NLG919 and other IDO/TDO inhibitors developed with NewLink in combination with its PDL-1 inhibitor MPDL3280A, its OX40 inhibitor MOXR0916 and other in-house immunotherapy candidates.
The Roche subsidiary previously revealed an interest in IDO inhibitors when it announced plans in July to test MPDL3280A for the treatment of non-small cell lung cancer (NSCLC) in combination with Incyte's IDO1 inhibitor INCB24360 (scripintelligence.com, 30 July 2014).
NewLink deal rationale
"We believe IDO is a compelling target for cancer immunotherapy. IDO is expressed by both tumor cells and immune cells, but regardless of its cell of residence in a given example, targeting IDO alters the levels of tryptophan and tryptophan metabolites that regulate the activities of T lymphocytes. Preclinical experiments have indicated the importance of IDO in controlling immunity in various settings, including cancer," Genentech senior vice president and global head of partnering James Sabry told Scrip.
Dr Sabry noted that IDO may facilitate cancer cell survival, growth, invasion and metastasis that the immune system might otherwise recognize and attack.
"NLG919, a dual acting investigational immunotherapy, is believed to regulate immune response by suppressing regulatory T cells function and activating effector T cells, enabling local tumor immune escape," he said.
The potential dual mechanism of action for NLG919 and its lack of expected toxicities in preclinical testing make a compelling case for studying the drug's activity in humans as part of immunotherapy combination regimens.
NewLink chairman and CEO Charles Link described Genentech as an "ideal collaborator" in the company's partnership announcement. Dr Link said cash received under the deal will expand the development of NLG919 and fund NewLink's own early-stage and clinical programs.
The company retained the right to develop NLG919 in combination with its HyperAcute vaccine platform, which includes the Phase III product candidate algenpantucel-L for pancreatic cancer; the Phase II candidates tergenpumatucel-L for NSCLC and dorgenmeltucel-L for melanoma; and the Phase I programs HyperAcute Prostate and HyperAcute Renal.
NewLink's ebola vaccine program recently was cleared for Phase I testing in light of the West African ebola crisis, but that technology was licensed from the Public Health Agency of Canada (scripintelligence.com, 14 October 2014).
IDO competition
Incyte has signed deals to test its IDO1 inhibitor INCB24360 in combination with Genentech's MPDL3280A, the Bristol-Myers Squibb PD-1 inhibitor Opdivo (nivolumab), Merck & Co's PD-1 inhibitor Keytruda (pembrolizumab) and AstraZeneca's PDL-1 inhibitor MEDI4736.
"While this enables the development of an IDO competitor," Jefferies analyst Thomas Wei said in a 20 October research note regarding Incyte, "we see the [Genentech-NewLink deal] news today as an overall net positive as it provides encouraging validation of IDO as a target and reinforces our favorable interpretation of Incyte's data for" INCB24360 in combination with the Bristol-Myers Squibb drug Yervoy (ipilimumab).
Data for the INCB24360/Yervoy combination which will be presented during the 56th Annual American Society for Hematology (ASH) Meeting and Exposition from 6 to 9 December in San Francisco.
The only other known IDO inhibitor in development, according to Sagient Research's BioMedTracker database, is the preclinical therapeutic cancer vaccine dCellVax from Bio-Matrix Scientific Group. Bio-Matrix recently submitted an investigational new drug (IND) application to the US FDA to test dCellVax in metastatic breast cancer.