Genentech has paid $120 million upfront to secure global rights to IL-15 cytokine therapeutics in preclinical development at Xencor. The upfront sets the Roche subsidiary up to incorporate the candidates into its immuno-oncology combination strategy.
Xencor is pursuing IL-15, an immune signaling protein, in the belief it can stimulate natural killer and cytotoxic T cells without triggering the simultaneous surge in regulatory T cell activity associated with the targeting of IL-2. That prospect has attracted multiple drug development shops, including Eli Lilly and Novartis, but Xencor thinks its technology can deliver better tolerability and a longer half life.
In preclinical tests, XmAb24306, Xencor’s lead IL-15/IL-15Rα cytokine complex, triggered sustained in vivo proliferation of lymphocytes, suggesting its Fc domain technologies can enable less burdensome dosing schedules.
That idea and Xencor’s other claims about the potential of XmAb24306 remain clinically untested. But Genentech has seen enough potential in the early-stage data to pay $120 million for worldwide rights to the lead candidate and other IL-15 prospects that may emerge from Xencor’s pipeline.
Genentech is also on the hook for $160 million in clinical development milestones per program. The Roche subsidiary will hand over another $20 million for each additional, as-yet-unidentified program that emerges from Xencor’s pipeline and enters human testing. Genentech will pay 55% of the cost of developing and commercializing the drugs, and take the same share of any profits or losses.
For Xencor, the money is only a part of the allure of the deal. Teaming up with Genentech also gives Xencor the chance to explore the use of IL-15 drugs in combination with other anti-cancer therapies.
“A wide-ranging combination strategy will be critical to realize the potential of IL-15 bispecific cytokines such as XmAb24306, so we plan to explore our cytokines with a broad spectrum of leading commercial-stage and investigational cancer therapies,” Xencor CEO Bassil Dahiyat said in a statement.
Researchers have proposed pairing IL-15 drugs with treatments that address immunosuppression or stimulate distinct pathways. Potential partners for XmAb24306 include chemotherapeutic agents, immune checkpoint inhibitors and anti-CD40 antibodies. Roche’s portfolio and pipeline features multiple drugs that fit the bill, including anti-PD-L1 checkpoint inhibitor Tecentriq and CD40 agonist selicrelumab.
The agreement gives Xencor the right to perform clinical trials of assets covered by the Genentech collaboration in combination with other therapeutic agents. Through these and other trials, Xencor and Genentech will work to realize the long-recognized therapeutic potential of IL-15.
A National Cancer Institute workshop ranked IL-15 as the top immunotherapy prospect in the 2000s but researchers initially struggled to overcome the short in vivo half lives of candidates. Researchers have worked to overcome that limitation, in Xencor’s case by engineering L15/IL15R heterodimeric Fc fusions, leading to the proliferation of assets in preclinical and early-phase development.