To create its XmAb antibody engineering platform, Xencor precisely alters the Fc domain — the stem of the 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 throughout a broad portfolio of 18 proprietary and partnered therapeutic antibody and cytokine programs in clinical development for the treatment of cancer, autoimmune disorders and infectious disease.
Partnering
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 by simply changing a few amino acids in the 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 nine programs in clinical trials and numerous preclinical programs that use XmAb Fc domains for bispecific structure, higher cytotoxicity, longer half-life or improved stability.
Please direct partnering inquiries to: collaborate@xencor.com
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 adult patients with paroxysmal nocturnal hemoglobinuria (PNH) and for the treatment of patients with atypical hemolytic uremic syndrome (aHUS).
MorphoSys licensed worldwide rights for Monjuvi® (tafasitamab-cxix), a B-cell targeting antibody with an XmAb Cytotoxic Fc Domain. The U.S. Food and Drug Administration approved Monjuvi as a CD19-directed cytolytic antibody indicated 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. Additionally, the European Medicines Agency has validated the Marketing Authorization Application for tafasitamab, which seeks approval of tafasitamab in combination with lenalidomide, followed by tafasitamab monotherapy, for the treatment of adult patients with r/r DLBCL, including DLBCL arising from low grade lymphoma, who are not candidates for ASCT.
Xencor discovered and developed tafasitamab through Phase 1 clinical trials.
Xencor and Genentech, a member of the Roche Group, are co-developing XmAb24306/RG6323 and other potential novel IL15 cytokine therapeutics. XmAb24306 is an IL15/IL15Rα cytokine complex engineered with Xencor’s bispecific Fc domain and Xtend™ Fc technology. Additionally, the companies have engaged in a two-year research program to discover new IL15 drug candidates, including ones targeted to specific immune cell populations. The companies are will share development costs and profits. Genentech will commercialize medicines worldwide, and Xencor has the option to co-promote in the United States. XmAb24306 is being evaluated in a Phase 1 study in patients with solid tumors, as a single agent and in combination with atezolizumab.
Novartis has licensed ex-U.S. commercial rights and entered a collaboration for the worldwide development of vibecotamab and has entered into a collaboration to use XmAb bispecific Fc domains across four Novartis programs; Novartis also licensed various XmAb Fc domains to optimize the performance of therapeutic antibodies.
Amgen licensed worldwide rights to use XmAb bispecific Fc domains in multiple programs. Amgen is developing AMG 509, a STEAP1 x CD3 XmAb 2+1 bispecific antibody, for patients with prostate cancer and Ewing sarcoma. A Phase 1 study of AMG 509 in patients with metastatic castration-resistant prostate cancer (mCRPC) is ongoing.