To create its XmAb protein engineering platform, Xencor precisely alters an Fc domain — the stem of an antibody structure — to significantly enhance natural functions and performance. In some cases, these modifications create entirely new therapeutic mechanisms of action.
Xencor’s optimized Fc domains can plug-and-play into nearly any antibody. XmAb Fc domains provide enhanced performance or new structures, like cytokine-Fc fusions, throughout a broad portfolio of more than 20 proprietary and partnered therapeutic antibody and cytokine programs in clinical development for the treatment of cancer, autoimmune disorders and infectious disease.
Partners Broaden the Pipeline of XmAb Drug Candidates
The plug-and-play nature of Xencor’s XmAb technology enables the rapid creation of more powerful, more effective antibodies and cytokines by simply changing a few amino acids in an antibody’s Fc domain to the amino acids identified by our structure-based design. Typically two amino acids are changed to create the XmAb Fc domain and dramatically enhance the biological function of the antibody. Xencor’s growing pipeline is based on this plug-and-play approach to creating differentiated antibody drug candidates.
Xencor extends the use of the XmAb technology through licenses of these high-performance Fc domains to partners interested in therapeutic targets outside of Xencor’s areas of focus. Currently, partners are advancing clinical-stage and preclinical programs that use XmAb Fc domains for bispecific structure, higher cytotoxicity, longer half-life or improved stability. When our partners access our plug-and-play XmAb Bispecific Fc Domain to create novel drug candidates, we may conduct limited research and development to create potential candidates for further development and commercialization by our partners.
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Alexion is using Xencor’s Xtend™ Fc domain to enhance the half-life of Ultomiris® (ravulizumab-cwvz). Ultomiris has received marketing authorizations in global markets for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH), for certain patients with atypical hemolytic uremic syndrome (aHUS) and for certain patients with generalized myasthenia gravis (gMG). Alexion is also evaluating Ultomiris in a broad development program across additional hematology and neurology indications. In May 2023, Ultomiris was approved in the EU and Japan for the treatment of certain adult patients with neuromyelitis optica spectrum disorder (NMOSD).
In 2010, Xencor licensed exclusive worldwide rights to develop and commercialize tafasitamab to MorphoSys AG. In the United States, Monjuvi® ( tafasitamab-cxix) is approved by the FDA in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). In Europe, Minjuvi® (tafasitamab) received conditional approval, in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for ASCT. Minjuvi and Monjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S., and marketed by Incyte under the brand name Minjuvi in the EU.
Xencor discovered tafasitamab and developed it through Phase 1 clinical trials.
Xencor and Genentech, a member of the Roche Group, are co-developing XmAb306/RG6323. XmAb306 is an IL15/IL15Rα cytokine complex engineered with Xencor’s bispecific Fc domain and Xtend™ Fc technology. Genentech is conducting a Phase 1 study of XmAb306 as a single agent and in combination with atezolizumab in patients with advanced solid tumors. Genentech has initiated two additional Phase 1 studies, evaluating XmAb306 in patients with relapsed/refractory multiple myeloma, either in combination with daratumumab (anti-CD38 antibody) or in combination with cevostamab (FcRH5 x CD3 bispecific antibody).
Amgen licensed rights to the XmAb bispecific Fc domain, and Xencor applied the technology to create xaluritamig (AMG 509), a STEAP1 x CD3 XmAb 2+1 bispecific antibody, for patients with prostate cancer. STEAP1 is a a challenging membrane target with limited extracellular exposure. Amgen is conducting a Phase 1 study of xaluritamig in patients with metastatic castration-resistant prostate cancer (mCRPC).