Programs
CD3 Bispecific Antibodies
XmAb® 2+1 Bispecific Antibodies
Tumor Microenvironment Activating Bispecific Antibodies
Engineered Cytokines
Preclinical-stage Platforms
Immune Inhibitor Antibodies
Plamotamab (CD20 x CD3 Bispecific Antibody)
Patel, K., et al. 2019, American Society of Hematology (poster).
Preliminary Safety and Anti-Tumor Activity of XmAb13676, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia
Chu, S. Y., et al. 2014, Blood (poster) 124(21), 3111.
Immunotherapy with long-lived anti-CD20 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human B cell lines and of circulating and lymphoid B cells in monkeys: a potential therapy for B cell lymphomas and leukemias.
Vibecotamab (CD123 x CD3 Bispecific Antibody)
Ravandi, F., et al. 2020, American Society of Hematology (presentation).
Complete Responses in Relapsed/ Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of Vibecotamab(XmAb®14045), a CD123 x CD3 T Cell-Engaging Bispecific Antibody; Results of a Phase 1 Study
Ravandi, F., et al. 2018, American Society of Hematology (presentation).
Complete Responses in Relapsed/ Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of XmAb®14045, a CD123 x CD3 T Cell-Engaging Bispecific Antibody: Initial Results of a Phase 1 Study
Chu, S. Y., et al. 2014, Blood (poster) 124(21), 2316.
Immunotherapy with long-lived anti-CD123 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human AML cell lines and of CD123+ cells in monkeys: a potential therapy for acute myelogenous leukemia.
Tidutamab (SSTR2 x CD3 Bispecific Antibody)
El-Rayes, et al. 2020, NANETS (poster).
Preliminary Safety, PK/PD, and Antitumor Activity of XmAb18087, an SSTR2 x CD3 Bispecific Antibody, in Patients With Advanced Neuroendocrine Tumors
Lee, S-H., et al. 2017, AACR Annual Meeting (poster).
Anti-SSTR2 × anti-CD3 bispecific antibody induces potent killing of human tumor cells in vitro and in mice, and stimulates target-dependent T cell activation in monkeys: a potential immunotherapy for neuroendocrine tumors
XmAb®819 (ENPP3 x CD3 Bispecific Antibody)
Nisthal, A., et al. 2020, American Association for Cancer Research (poster).
XmAb30819, an XmAb®2+1 ENPP3 x CD3 bispecific antibody for RCC, demonstrates safety and efficacy in in vivo preclinical studies
Additional XmAb® 2+1 Bispecific Antibody Progrms
Nisthal, A., et al. 2020, American Association for Cancer Research (poster).
Affinity tuned XmAb®2+1 PSMA x CD3 bispecific antibodies demonstrate selective activity in prostate cancer models
Zeng, V. G., et al. 2020, American Association for Cancer Research (poster).
Affinity tuned XmAb® 2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell-dependent cellular cytotoxicity of human ovarian cancer cells
XmAb®717 (PD-1 x CTLA-4 Bispecific Antibody)
Shum, E., et al. 2020, Society for Immunotherapy of Cancer (poster).
Preliminary Safety, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of XmAb®20717, a PD-1 x CTLA-4 Bispecific Antibody, in Patients With Advanced Solid Tumors
Hedvat, M., et al. 2018, Society for Immunotherapy of Cancer (poster).
Simultaneous checkpoint – costimulatory or checkpoint – checkpoint receptor targeting with bispecific antibodies promotes enhanced human T cell activation
Hedvat, M., et al. 2018, American Association for Cancer Research (poster).
Simultaneous checkpoint-checkpoint or checkpoint-costimulatory receptor targeting with bispecific antibodies promotes enhanced human T cell activation
Hedvat, M., et al. 2017, Society for Immunotherapy of Cancer (poster).
Dual Blockade of PD1 and CTLA4 with Bispecific Antibody XmAb20717 Promotes Human T Cell Activation and Proliferation
Hedvat, M., et al. 2016, J Immunother Cancer (poster) 4(Suppl 1):82.
Dual blockade of PD-1 and CTLA-4 with bispecific antibodies promotes human T cell activation and proliferation.
Bernett, M. J., et al. 2016, J Immunother Cancer (poster) 4(Suppl 1):82
Multiple bispecific checkpoint combinations enhance T cell activity.
XmAb®841 (CTLA-4 x LAG-3 Bispecfic Antibody)
Hedvat, M., et al. 2018, Society for Immunotherapy of Cancer (poster).
Simultaneous checkpoint – costimulatory or checkpoint – checkpoint receptor targeting with bispecific antibodies promotes enhanced human T cell activation
Hedvat, M., et al. 2018, American Association for Cancer Research (poster).
Simultaneous checkpoint-checkpoint or checkpoint-costimulatory receptor targeting with bispecific antibodies promotes enhanced human T cell activation
Bernett, M. J., et al. 2016, J Immunother Cancer (poster) 4(Suppl 1):82
Multiple bispecific checkpoint combinations enhance T cell activity.
XmAb®104 (PD-1 x ICOS Bispecific Antibody)
Hedvat, M., et al. 2018, Society for Immunotherapy of Cancer (poster).
Simultaneous checkpoint – costimulatory or checkpoint – checkpoint receptor targeting with bispecific antibodies promotes enhanced human T cell activation
Hedvat, M., et al. 2018, American Association for Cancer Research (poster).
Simultaneous checkpoint-checkpoint or checkpoint-costimulatory receptor targeting with bispecific antibodies promotes enhanced human T cell activation
Moore, G. L., et al. 2017, Society for Immunotherapy of Cancer (poster).
Anti-PD1 x anti-ICOS bispecific antibody XmAb23104 brings together PD1 blockade and ICOS costimulation to promote human T cell activation and proliferation
Moore, G. L., et al. 2017, American Association for Cancer Research (poster).
Combination of PD1 blockade and T cell costimulation by bispecfic antibodies promotes human T cell activation and proliferation
XmAb®306 (IL15/IL15Rα-Fc Cytokine)
Bernett, M. J., et al. 2018, Society for Immunotherapy of Cancer (poster).
An IL15/IL15Rα heterodimeric Fc-fusion engineered for reduced potency demonstrates an optimal balance of in vivo activity and exposure
Bernett, M. J., et al. 2018, American Association for Cancer Research (poster).
Potency-reduced IL15/IL15Rα heterodimeric Fc-fusions display enhanced in vivo activity through increased exposure
Bernett, M. J., et al. 2017, American Association for Cancer Research (poster).
IL15/IL15Rα heterodimeric Fc-fusions with extended half-lives
XmAb®564 (IL2-Fc Cytokine)
Varma, R., et al. 2018, American Society of Hematology (poster).
Regulatory T cell selective IL-2-Fc fusion proteins for the treatment of autoimmune disease
IL12-Fc Program
Bernett, M. J., et al. 2020, Society for Immunotherapy of Cancer (poster).
Potency-reduced and extended half-life IL12 heterodimeric Fc-fusions exhibit strong anti-tumor activity with potentially improved therapeutic index compared to native IL12 agents
Varma, R., et al. 2020, American Association for Cancer Research (poster).
Potency-reduced IL12 heterodimeric Fc-fusions exhibit strong anti-tumor activity
CD28 Bispecific Antibody Platform
Hedvat, M., et al. 2020, Society for Immunotherapy of Cancer (poster).
Tumor-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors
TGFβ Bispecific Antibody Platform
Moore, G. L., et al. 2020, Society for Immunotherapy of Cancer (poster).
PD1 x TGFβR2 bispecifics selectively block TGFβR2 on PD1-positive T cells, promote T cell activation, and elicit an anti-tumor response in solid tumors
Obexelimab (Anti-CD19 Antibody)
Merrill, J. T., et al. 2018, American College of Rheumatology (poster).
Top-line Results of a Phase 2, Double-blind, Randomized, Placebo-Controlled Study of a Reversible B Cell Inhibitor, XmAb®5871, in Systemic Lupus Erythematosus (SLE)
Stone, J. H., et al. 2017, American College of Rheumatology (presentation).
Final Results of an Open Label Phase 2 Study of a Reversible B Cell Inhibitor, XmAb®5871,in IgG4-Related Disease
Stone, J. H., et al. 2017, EULAR (presentation).
Interim Results of a Phase 2 Study of XmAb®5871, a Reversible B Cell Inhibitor, in IgG4-Related Disease
Stone, J. H., et al. 2016, American College of Rheumatology (presentation).
Preliminary Data from the Ongoing Open-Label XmAb5871 Phase 2 Pilot Study in IgG4-Related Disease
Jaraczewska-Baumann, M., et al. 2015, EULAR (poster).
A Phase 1b/2a Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of XmAb®5871 in Patients with Rheumatoid Arthritis
Szili, D., et al. 2014, mAbs 6(4):991-999.
Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19.
Chu, S. Y., et al. 2014, Arthritis Rheumatol 66(5):1153-64.
Suppression of rheumatoid arthritis B cells by XmAb5871, an anti-CD19 antibody that coengages B cell antigen receptor complex and Fcγ receptor IIb inhibitory receptor.
Horton, H. M., et al. 2011, J Immunol 186(7):4223-33.
Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus.
Chu, S. Y., et al. 2008, Mol Immunol 45(15):3926-33.
Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcγRIIb with Fc-engineered antibodies.
Fc Technology
- Bispecific Fc Domain
- Cytotoxic Fc Domain
- Immune Inhibitor Fc Domain
- Xtend™ Fc Domain
- XmAb® Core Technology
- Reviews
Bispecific Fc Domain
Moore, G.L., Bautista, C., Pong, E., Nguyen, D.H., Jacinto, J., Eivazi, A., Muchhal, U.S., Karki, S., Chu, S.Y., and Lazar, G.A. 2011. A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens. mAbs 3(6): 546-557
Chu, S. Y., Lee, S., Rashid, R., Chen, H., Chan, E. W., Phung, S., Pong, E., Endo, N. A., Miranda, Y., Bonzon, C., Leung, I. W., Muchhal, U. S., Moore, G. L., Bernett, M. J., Szymkowski, D. E., and Desjarlais, J. R. 2014. Immunotherapy with long-lived anti-CD20 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human B cell lines and of circulating and lymphoid B cells in monkeys: a potential therapy for B cell lymphomas and leukemias. Blood 124(21), 3111
Chu, S. Y., Miranda, Y., Phung, S., Chen, H., Rashid, R., Endo, N. A., Chan, E. W., Pong, E., Bonzon, C., Muchhal, U. S., Leung, I. W., Bernett, M. J., Moore, G. L., Szymkowski, D. E., and Desjarlais, J. R. 2014. Immunotherapy with long-lived anti-CD38 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human myeloma cell lines and CD38+ cells in monkeys: a potential therapy for multiple myeloma. Blood (poster) 124(21), 4727
Chu, S. Y., Pong, E., Chen, H., Phung, S., Chan, E. W., Endo, N. A., Rashid, R., Bonzon, C., Leung, I. W., Muchhal, U. S., Moore, G. L., Bernett, M. J., Szymkowski, D. E., and Desjarlais, J. R. 2014. Immunotherapy with long-lived anti-CD123 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human AML cell lines and of CD123+ cells in monkeys: a potential therapy for acute myelogenous leukemia. Blood 124(21), 2316
Moore, G. L., Lee, S., Schubbert, S., Miranda, Y., Rashid, R., Pong, E., Phung, S., Chan, E. W., Chen, H., Endo, N., Ardila, M. C., Bernett, M. J., Chu, S., Leung, I. W., Muchhal, U., Bonzon, C., Szymkowski, D. E., and Desjarlais, J. 2015. Tuning T cell affinity improves efficacy and safety of anti-CD38 × anti-CD3 bispecific antibodies in monkeys – a potential therapy for multiple myeloma. Blood (poster) 126(23), 1798
Chu, S.Y., Pong, E., Schubbert, S., Rashid, R., Chen, S., Chan, E., Phung, S., Endo, N.A., Ardilla, M.C., Bonzon, C., Leung, I.W.L., Muchhal, U.S., Moore, G.L., Bernett, M.J., Avery, K.A., Desjarlais, J.R. and Szymkowski, D.E. 2016. Immunotherapy with anti-PSMA x anti-CD3 bispecific antibody stimulates potent killing of a human prostate cancer cell line and target-mediated T cell activation in monekys: a potential therapy for prostate cancer. Cancer Res 76(14)Suppl
Bernett, M.J., Bonzon, C., Rashid, R., Varma, R., Avery, K.N, Leung. I.W.L., Chu. S.Y., Muchhal, U.S., Moore, G.L., and Desjarlais, J.R. 2017. IL15/IL15Rα heterodimeric Fc-fusions with extended half-lives. AACR Annual Meeting IL15/IL15Rα
Lee, S-H., Chu, S.Y., Rashid, R., Phung, S., Leung, I., Muchhal, U.S., Moore, G.L., Bernett, M.J., Schubbert, S., Ardila, C., Bonzon, C., Foster, P., Szymkowski, D.E., and Desjarlais, J.R. 2017. Anti-SSTR2 × anti-CD3 bispecific antibody induces potent killing of human tumor cells in vitro and in mice, and stimulates target-dependent T cell activation in monkeys: a potential immunotherapy for neuroendocrine tumors. AACR Annual Meeting (poster)
Moore, G.L., Hedvat, M., Bernett, M.J., Varma, R., Schubbert, S., Bonzon, C., Avery, K.A., Rashid, R., Nisthal, A., Bogaert, L., Leung, I.W.L., Chu, S.Y., Muchhal, U.S., and Desjarlais, J.R. 2017. Combination of PD1 blockade and T cell costimulation by bispecific antibodies promotes human T cell activation and proliferation. AACR Annual Meeting (poster)
Nisthal, A., Bernett, M.J., Moore, G.L., Hedvat, M., Bonzon, C., Chu, S.Y., Rashid, R., Avery, K., Umesh, U.S. and Desjarlais, J.R. 2016. Mulitple bispesific combinations promote T cell activation. IBC’s Antibody Engineering & Therapeutics Conference (poster)
Moore, G.L., Bernett, M.J., Rashid, R., Pong, E.W., Nguyen, D.H., Jacinto, J., Eivazi, A., Nisthal, A., Diaz, J.E., Chu, S.Y., Muchhal, U.S. and Desjarlais, J.R. 2019. A robust heterodimeric Fc platform engineered for efficient development of bispecific antibodies of multiple formats. Methods. 154:38-50
Cytotoxic Fc Domain
Lazar, G.A., Dang, W., Karki, S., Vafa, O., Peng, J.S., Hyun, L., Chan, C., Chung, H.S., Eivazi, A., Yoder, S.C., Vielmetter, J., Carmichael, D.F., Hayes, R.J., and Dahiyat, B.I. 2006 Engineered antibody Fc variants with enhanced effector function. PNAS 103(11), 4005-4010
Lawrence, C. E., Hammond, P. W., Zalevsky, J., Horton, H., Chu, S., Karki, S., Desjarlais, J. R., and Carmichael, D. F. 2007 XmAb™2513, an Fc engineered humanized anti-CD30 monoclonal antibody, has potent in vitro and in vivo activities, and has the potential for treating hematologic malignancies. Blood (poster) 110(11), 2340
Horton, H.M., Bernett, M.J., Pong, E., Peipp, M., Karki, S., Chu, S.Y., Richards, J.O., Vostiar, I., Joyce, P.F., Repp, R., Desjarlais, J.R., and Zhukovsky, E.A. 2008 Potent in vitro and in vivo activity of an Fc-engineered anti-CD19. Cancer Res 68(19):8049-8057
Lawrence, C. E., Zalevsky, J., Horton, H., Leung, I., Chu, S., Karki, S., Zhukovsky, E., Desjarlais, J. R., & Carmichael, D. F. 2008 XmAb®5574, an Fc engineered humanized anti-CD19 monoclonal antibody, has potent in vitro and in vivo activities, and has the potential for treating B cell malignancies. Blood (poster) 112(11), 2621
Zalevsky, J., Leung, I.W., Karki, S., Chu, S.Y., Zhukovsky, E.A., Desjarlais, J.R., Carmichael, D.F., and Lawrence, C.E. 2009 The impact of Fc engineering on an anti-CD19 antibody: increased Fcγ receptor affinity enhances B-cell clearing in nonhuman primates. Blood 113:3735-3743
Awan, F.T., Lapalombella, R., Trotta, R., Butchar, J.P., Yu, B., Benson, D.M., Roda, J.M., Cheney, C., Mo, X., Lehman, A., Jones, J., Flynn, J., Jarjoura, D., Desjarlais, J.R., Tridandapani, S., Caligiuri, M.A., Muthusamy, N., and Byrd, J.C. 2010 CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain–engineered monoclonal antibody. Blood 115(6): 1204-1213
Horton, H. M., Bernett, M. J., Peipp, M., Pong, E., Karki, S., Chu, S. Y., Richards, J. O., Chen, H., Repp, R., Desjarlais, J. R., and Zhukovsky, E. A. 2010 Fc-engineered anti-CD40 antibody enhances multiple effector functions and exhibits potent in vitro and in vivo antitumor activity against hematologic malignancies. Blood 116(16), 3004-3012
Kellner, C., Zhukovsky, E.A., Pötzke, A., Brüggemann, M., Schrauder, A., Schrappe, M., Kneba, M., Repp, R., Humpe, A., Gramatzki, M., and Peipp, M. 2013 The Fc-engineered CD19 antibody MOR208 (XmAb5574) induces natural killer cell-mediated lysis of acute lymphoblastic leukemia cells from pediatric and adult patients. Leukemia 27:1595-1598
Woyach, J.A., Awan, F., Flinn, I.W., Berdeja, J.G., Wiley, E., Mansoor, S., Huang, Y., Lozanski, G., Foster, P.A., and Byrd, J.C. 2014 A phase I trial of the Fc engineered CD19 antibody XmAb®5574(MOR00208) demonstrates safety and preliminary efficacy in relapsed chronic lymphocytic leukemia. Blood 124(24): 3553–3560
Immune Inhibitor Fc Domain
Chu, S.Y., Vostiar, I., Karki, S., Moore, G.L., Lazar, G.A., Pong, E., Joyce, P.F., Szymkowski, D.E., and Desjarlais, J.R. 2008 Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcγRIIb with Fc-engineered antibodies. Mol Immunol 45(15):3926-33
Horton, H.M., Chu, S.Y., Ortiz, E.C., Pong, E., Cemerski, S., Leung, I.W., Jacob, N., Zalevsky, J., Desjarlais, J.R., Stohl, W., and Szymkowski, D.E. 2011 Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus. J Immunol 186(7):4223-33
Chu, S.Y., Yeter, K., Kotha, R., Pong, E., Miranda, Y., Phung, S., Chen, H., Lee, S.H., Leung, I., Bonzon, C., Desjarlais, J.R., Stohl, W., and Szymkowski, D.E. 2014 Suppression of rheumatoid arthritis B cells by XmAb5871, an anti-CD19 antibody that coengages B cell antigen receptor complex and Fcγ receptor IIb inhibitory receptor. Arthritis Rheumatol 66(5):1153-64
Szili, D., Cserhalmi, M., Bankó, Z., Nagy, G., Szymkowski, D.E., and Sármay, G. 2014 Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19. mAbs 6(4):991-999
Xtend™ Fc Domain
Zalevsky, J., Chamberlain, A.K., Horton, H.M., Karki, S., Leung, I.W., Sproule, T.J., Lazar, G.A., Roopenian, D.C., and Desjarlais, J.R. 2010 Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157-9
Bernett, M.J., Chu, S.Y., Leung, I., Moore, G.L., Lee, S.H., Pong, E., Chen, H., Phung, S., Muchhal, U.S., Horton, H.M., Lazar, G.A., Desjarlais, J.R., and Szymkowski, D.E. 2013 Immune suppression in cynomolgus monkeys by XPro9523: an improved CTLA4-Ig fusion with enhanced binding to CD80, CD86 and neonatal Fc receptor FcRn. mAbs 5(3):384-96
Saunders, K.O., Pegu, A., Georgiev, I.S., Zeng, M., Joyce, M.G., Yang, Z.Y., Ko, S.Y., Chen, X., Schmidt, S.D., Haase, A.T., Todd, J.P., Bao, S., Kwong, P.D., Rao, S.S., Mascola, J.R., and Nabel, G.J. 2015 Sustained delivery of a broadly neutralizing antibody in nonhuman primates confers long-term protection against simian/human immunodeficiency virus infection. J. Virol. 89(11):5895-5903
Nnane, I.P., Han, C., Jiao, Q., Tam, S.H., Davis, H.M., and Xu, Z. 2017 Modification of the Fc region of a human anti-oncostatin M monoclonal antibody for higher affinity to FcRn receptor and extension of half-life in cynomolgus monkeys. Basic Clin Pharmacol Toxicol doi:10.1111/bcpt.12761
XmAb® Core Technology
Lazar, G.A., Desjarlais, J.R., Jacinto, J., Karki, S., and Hammond P.W. 2007 A molecular immunology approach to antibody humanization and functional optimization. Mol Immunol 44, 1986-1998
Bernett, M.J., Karki, S., Moore, G.L., Leung, I.W., Chen, H., Pong, E., Nguyen, D.H., Jacinto, J., Zalevsky, J., Muchhal, U.S., Desjarlais, J.R., and Lazar, G.A. 2008 Engineering fully human monoclonal antibodies from murine variable regions. J Mol Biol 396(5):1474-90
Richards, J.O., Karki, S., Lazar, G.A., Chen, H., Dang, W., and Desjarlais, J.R. 2008 Optimization of antibody binding to FcγRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 7(8):2517-27
Moore, G.L., Chen, H., Karki, S., and Lazar, G.A. 2010 Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. mAbs 2(2):181-189
Cemerski, S., Chu, S.Y., Moore, G.L., Muchhal, U.S., Desjaralis, J.R., and Szymkowski, D.E. 2012 Suppression of mast cell degranulation through a dual-targeting tandem IgE–IgG Fc domain biologic engineered to bind with high affinity to FcγRIIb. Immunol Lett 143(1):34-43
Reviews
Desjarlais, J.R., Lazar, G.A., Zhukovsky, E.A., and Chu, S.Y. 2007. Optimizing engagement of the immune system by anti-tumor antibodies: an engineer’s perspective. Drug Discov Today 12(21-22): 898-910
Desjarlais, J.R., and Lazar, G.A. 2011. Modulation of antibody effector function. Exp Cell Res 317(9)1278-1285
Sondermann, P., and Szymkowksi, D.E. 2016. Harnessing Fc receptor biology in the design of therapeutic antibodies. Curr Opin Immunol 40:78-87
Clynes, R.A. and Desjarlais, J.R. 2019. Redirected T cell cytotoxicity in cancer therapy. Annu Rev Med. 70:437-450
CONTACT US
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