NewLink Genetics said today it has agreed to license its IDO pathway inhibitor NLG919 to Genentech and launch a research collaboration with the Roche subsidiary to discover next generation combination IDO-TDO therapy compounds, in a deal that could yield the licensor more than $1.15 billion.

The companies reason that Indoleamine-pyrrole 2,3-dioxygenase (IDO) pathway inhibitors represent another breakthrough approach to cancer therapy as do recently-developed antibodies targeting CTLA-4, PD-1, and PD-L1.

The IDO pathway regulates immune response by suppressing T-cell activation which enables local tumor immune escape. NewLink has cited recent studies, which have demonstrated that the IDO pathway is active both within tumor cells as a direct defense against T-cell attack, and within antigen presenting cells in tumor-draining lymph nodes, where the pathway promotes peripheral tolerance to tumor-associated antigens (TAAs).

NewLink says the IDO pathway may facilitate the survival, growth, invasion and metastasis of malignant cells, whose expression of tumor-associated antigens (TAAs) might otherwise be recognized and attacked by the immune system. NewLink has several active development programs aimed at synthesizing IDO pathway inhibitors, as well as programs that use tryptophan-2,3-dioxygenase (TDO) specific inhibitors, for potential use in anti-cancer compounds either as monotherapy or in combination with IDO inhibition.

Roche has an anti-PD-L1 or “Programed Death Ligand-1” compound in development, MPDL3280A. On May 31, Roche trumpeted positive Phase I results for MPDL3280A, saying that the compound shrank tumors in 43% (13 out of 30) patients previously treated for metastatic urothelial bladder cancer (UBC) whose tumors were characterized as PD-L1 positive. Based on these data, the FDA granted a breakthrough therapy designation to MPDL3280A, which is being studied alone or in combination therapies in 10 Phase I or Phase II trials now recruiting patients, according to

“We are intrigued by the biology of the IDO and TDO compounds and are very interested in the potential to combine them with Genentech's portfolio of novel therapies,” James Sabry, svp and global head of Genentech partnering, said in a statement.

Under the companies’ exclusive worldwide license agreement, NewLink will continue to pursue development activities associated with NLG919 in combination with its HyperAcute vaccine platform, designed to elicit an antitumor response by prompting the immune system to attack a patient’s own cancer cells.

NewLink is in a pair of Phase III trials for the HyperAcute immunotherapy Algenpantucel-L for pancreatic cancer, its lead product. Algenpantucel-L consists of 2 pancreatic cancer cell lines (HAPa-1 and HAPa-2) that have been genetically modified to express alpha-gal carbohydrates on cell surface molecules.

Genentech agreed to fund future research, development, manufacturing, and commercialization costs. Genentech also agreed to provide funding to for support of the research collaboration with NewLink, which will retain the option for co-promotion rights for NLG919 and potential next generation IDO/TDO compounds in the U.S.

In return, Genentech agreed to pay NewLink $150 million upfront, and more than $1 billion in payments tied to undisclosed milestones, as well as escalating double-digit royalties on potential commercial sales of multiple products by Genentech.

“This alliance enables us to accelerate and expand development of NLG919 while we continue to advance our other promising clinical and preclinical development programs,” stated Charles J. Link, Jr., M.D., NewLink’s chairman and CEO.

The completion of the agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

The collaboration with NewLink marks Genentech’s second billion-dollar deal since July, when it acquired Seragon Pharmaceuticals for up to $1.725 billion. That deal was designed to complement Genentech’s breast cancer products and R&D with a portfolio led by an early-stage clinical candidate for hormone receptor-positive breast cancer.

The Genentech deal marks the first time in recent weeks that NewLink has made headlines outside of its Ebola program. NewLink is among U.S. and Canadian partners that starting today was to ship 800 vials of donated Ebola vaccine candidate to the World Health Organisation in Geneva, according to an Oct. 18 announcement by the government of Canada. The vials contain the vaccine candidate VSV-EBOV, developed by the Public Health Agency of Canada (PHAC), and licensed by PHAC NewLink subsidiary to BioProtection Systems.

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