Genentech, a member of the Roche group, will partner with Xencor to develop and commercialize its novel IL-15 cytokine therapeutics—including its most advanced preclinical cytokine program, the cancer candidate XmAb®24306, the companies said today, through a collaboration that could generate more than $280 million for Xencor.

Xencor could see even more money if the companies develop additional IL-15 drug candidates. The collaboration includes a two-year research program to discover such potential therapies, including ones targeted to specific immune cell populations.

Genentech has agreed to pay $120 million upfront, and up to $160 million in payments tied to each program that advances into Phase III clinical trials, starting with the XmAb24306 program.

“We believe cytokine therapy will play an important role in the treatment of a wide range of diseases, including cancer,” James Sabry, MD, PhD, global head of Pharma Partnering, Roche, said in a statement. “This collaboration with Xencor will further enhance our understanding of a critical immune activation pathway and may present a potential new way to use the immune system to target cancer.”

XmAb24306 is an IL-15/IL-15Rα cytokine complex engineered with Xencor’s bispecific Fc domain and Xtend™ Fc technology.

IL-15 is a highly active cytokine which, when pre-complexed with IL-15 receptor alpha (IL-15Rα), is designed to bind to IL-15Rβγ and stimulate the expansion and activation of natural killer (NK) cells and cytotoxic T cells, but with reduced regulatory T-cell activation compared to IL-2.

Xencor’s IL-15 bispecific cytokine platform is intended to provide a more druggable version of IL-15 with potentially superior tolerability, slower receptor-mediated clearance, and a prolonged half-life.

The platform is intended for development with a wide range of combination agents due to its proposed mechanism of activating tumor-killing immune cells, according to Xencor.

Combination strategy

“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 president and CEO Bassil Dahiyat, PhD, said in a statement.

“This partnership with Genentech accelerates our immuno-oncology work by enabling the exploration of novel XmAb24306 combinations with Genentech’s leading oncology portfolio and our growing internal pipeline of bispecific antibodies,” Dahiyat added.

Xencor’s pipeline includes 12 candidates engineered with its XmAb® technology that are in clinical development, either internally or with collaboration partners. The company’s partners include Novartis, Amgen, MorphoSys, CSL, Alexion, and Boehringer Ingelheim.

Xencor’s internal programs include: obexelimab (XmAb5871) in Phase II for the treatment of IgG4-related disease, and also for the treatment of systemic lupus erythematosus; XmAb7195 in Phase I for the treatment of asthma and allergic diseases; XmAb14045 in Phase I for acute myeloid leukemia; XmAb13676 in Phase I for B-cell malignancies; XmAb18087 in Phase I for the treatment of neuroendocrine tumors and gastrointestinal stromal tumors; XmAb20717 in Phase I for advanced solid tumors.

In addition to XmAb24306, Xencor has two other preclinical candidates in development for cancer indications, XmAb22841 and XmAb23104.

According to a Xencor regulatory filing, for each new IL-15 cytokine product that emerges from the research program and advances into Phase I clinical trials, Genentech has agreed to also pay Xencor a $20 million development milestone payment—with an additional up to $160 million in clinical milestone payments for each product that advances to Phase III trials.

Xencor is eligible to receive a 45% share of net profits for sales of XmAb24306 and other collaboration products, while also sharing in the net losses at the same percentage rate. The companies also agreed to jointly share development and commercialization costs at the same percentage rate, while Genentech would bear launch costs entirely. The profit/cost share is subject to ratchet at Xencor’s discretion and convertible to a royalty under certain circumstances, the company disclosed.

The collaboration is expected to close in the first half of 2019, subject to customary conditions that include clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

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