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May 15, 2018

Genentech Terminates IDO Inhibitor Partnership with NewLink

  • Genentech, a member of the Roche Group, has terminated its four-year-old collaboration with NewLink Genetics to discover next-generation combination IDO-TDO (indoleamine-pyrrole 2,3-dioxygenase–tryptophan-2,3-dioxygenase) therapy compounds, nearly a year after the Roche subsidiary returned to NewLink rights to the cancer candidate GDC-0919 (navoximod).

    The collaboration had been expected to generate more than $1.15 billion for NewLink when launched in October 2014, with Genentech paying NewLink $150 million upfront.

    At the time, the companies reasoned that IDO pathway inhibitors represented a breakthrough approach to cancer therapy, as did treatments that combined IDO with TDO-specific inhibitors.

    The companies cited earlier studies showing that the IDO pathway was active both within tumor cells as a direct defense against T-cell attack and within antigen-presenting cells in tumor-draining lymph nodes.

    However, that thinking changed following a series of clinical trial setbacks experienced by Genentech/NewLink and other developers of IDO inhibitor treatments.

    In June 2017, Genentech returned its GDC-0919 rights to NewLink, while agreeing to continue partnering with NewLink on discovering IDO-TDO treatment candidates.

    That decision came almost a week after NewLink acknowledged that a Phase II study of another IDO inhibitor, indoximod, plus taxane chemotherapy—either docetaxel or paclitaxel—failed to meet its primary endpoints of a statistically significant difference in progression-free survival (PFS) compared with placebo plus taxane chemotherapy in patients with metastatic breast cancer.

    In a regulatory filing today, NewLink disclosed that on May 10, it received notice from Genentech that it will terminate their collaboration effective in 180 days.

    As a result, NewLink said, it will regain rights to IDO inhibitors, and receive from Genentech an “exclusive, worldwide, royalty-bearing, sublicensable license, under certain Genentech intellectual property, to research, develop, manufacture, and commercialize such next-generation compounds.” NewLink said it will be required to pay Genentech a low single-digit royalty on any sales of the compounds should it proceed to develop and commercialize them.

    Also as a result of the termination, Genentech must assign to NewLink data arising from research that Genentech conducted on IDO inhibitors, NewLink added.

  • Retreat from IDO Inhibitors

    Genentech follows the pattern of other biopharma giants in retreating from IDO inhibitor development.

    On April 6, Incyte and Merck & Co. halted the Phase III ECHO-301/KEYNOTE-252 study (NCT02752074) assessing the combination of Incyte’s lead cancer immunotherapy candidate, the IDO1 inhibitor epacadostat (INCB024360), with Merck’s marketed blockbuster cancer immunotherapy Keytruda® (pembrolizumab) in melanoma.

    The combination missed its first primary endpoint of improving PFS in the overall population compared to Keytruda monotherapy, the companies acknowledged.

    Later last month, Bristol-Myers Squibb (BMS) halted two Phase III trials of its IDO1 inhibitor BMS-986205, which it acquired when it bought Flexus Biosciences for up-to-$1.25 billion in 2015, in combination with its blockbuster cancer immunotherapy Opdivo® (nivolumab) in head-and-neck cancer (NCT03386838), and in non-small-cell lung cancer (NCT03417037).

    “Business objectives have changes,” BMS stated on the pages for both trials on

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