Novartis will co-develop Xencor’s two T-cell-engaging XmAb bispecific antibodies targeting acute myeloid leukemia and B-cell malignancies as part of a broader collaboration that could generate up to up $150 million upfront for Xencor, the companies said today.

The two antibodies are XmAb®14045 for acute myeloid leukemia and XmAb®13676 for B-cell malignancies. Both are expected to begin clinical development this year.

Bispecific antibodies are engineered to recognize and target two different antigens, which makes them potentially more effective in targeting complex diseases than traditional monoclonal antibodies that target and bind to a single antigen. A T-cell-engaging bispecific antibody is designed to bind an antigen on a tumor cell with one arm and engage T cells capable of their destruction with the other.  

The companies agreed to share development costs for the worldwide development of XmAb14045 and XmAb13676, with Xencor maintaining U.S. commercialization rights and Novartis having commercialization rights in the rest of the world.

Novartis said the addition of Xencor's T-cell-engaging bispecific antibody programs expands its immuno-oncology portfolio—which includes novel checkpoint inhibitors, chimeric antigen receptor T-cell (CART) technology, myeloid cell targeting agents, the T-cell stimulating factor interleukin-15 (IL-15), stimulator of interferon genes (STING) agonists that enhance immune recognition of cancers, and adenosine receptor antagonists and transforming growth factor-β (TGF-β)-blocking antibodies that overcome immunosuppression in the tumor microenvironment.

At present, Novartis said, seven of these programs are in clinical phases, and five more are expected to enter the clinic individually and as combinations by year’s end.

Under the collaboration, Novartis also won additional rights to use Xencor’s XmAb antibody engineering platform to develop and commercialize four additional bispecific antibodies for targets to be selected by Novartis, with Xencor eligible to “opt in” to one of these programs in the U.S.

Novartis will also receive a worldwide nonexclusive license to use Xencor's XmAb Fc technologies in up to 10 molecules.

Novartis has agreed to pay Xencor $150 million upfront, as well as payments tied to achieving clinical, regulatory, and sales milestones for successful programs.

Xencor is also eligible to receive tiered, low double-digit royalties for sales of XmAb14045 and XmAb13676 outside of the U.S., and mid-single-digit tiered royalties for worldwide sales of the four proprietary Novartis bispecific molecules—unless Xencor exercises its right to “opt in” on development of one of these molecules and share in the costs and U.S. profit—as well as low single-digit royalties on Novartis molecules incorporating Xencor's XmAb Fc technology.

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