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 15 programs in clinical trials and numerous preclinical programs that use XmAb Fc domains for bispecific structure, higher cytotoxicity, longer half-life or improved stability.
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Alexion is using Xencor’s Xtend™ Fc domain to enhance the half-life of Ultomiris® (ravulizumab-cwvz), approved in the United States, the European Union and Japan for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) and for the treatment of patients with atypical hemolytic uremic syndrome (aHUS). Ultomiris is approved in the United States for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.
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.
In November 2020, Xencor entered a strategic clinical collaboration with MorphoSys and Incyte to investigate the chemotherapy-free triple combination of plamotamab, tafasitamab and lenalidomide in patients with relapsed or refractory DLBCL, first-line DLBCL and relapsed or refractory follicular lymphoma (FL). We plan to initiate the first of these studies, in patients with relapsed or refractory DLBCL, an aggressive type of NHL, in late 2021 or early 2022.
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 and other potential novel IL15 cytokine therapeutics. XmAb306 is an IL15/IL15Rα cytokine complex engineered with Xencor’s bispecific Fc domain and Xtend™ Fc technology. The companies are sharing development costs and profits. Genentech will commercialize medicines worldwide, and Xencor has the option to co-promote in the United States. XmAb306 is being evaluated in a Phase 1 study in patients with solid tumors, as a single agent, in combination with atezolizumab and in combination with daratumumab.
Novartis is developing an undisclosed XmAb bispecific antibody candidate in a Phase 1 clinical study. Novartis has also licensed various XmAb Fc domains to optimize the performance of therapeutic antibodies, and as of the second quarter of 2021, Xencor received a development milestone related to IND-enabling activities for an undisclosed program using XmAb Fc technologies.
Amgen licensed rights to the XmAb bispecific Fc domain and applied the technology to create AMG 509, a STEAP1 x CD3 XmAb 2+1 bispecific antibody, for patients with prostate cancer. A Phase 1 study of AMG 509 in patients with metastatic castration-resistant prostate cancer (mCRPC) is ongoing.