Immune cell modulators are a novel therapeutic class with the potential to deliver differentiated outcomes in autoimmune and inflammatory diseases including dermatology, gastroenterology, and rheumatology
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Checkpoint agonists “hit the brakes” to restore immune balance and deliver differentiated outcomes
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Rosnilimab (PD-1 agonist) targets PD-1+ T cells through 3 MOAs:
- Deplete PD-1high Teff cells
- Deplete PD-1high Tfh/Tph cells
- Agonize PD-1int Teff cells
ANB032 (BTLA agonist) modulates activated immune cells:
- Agonize T cells (Th1, Th2, Th17, Th22)
- Modulate dendritic cells
- Agonize B cells
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Membrane-proximal binding epitope and optimized Fc receptor binding affinity enables tight immune synapse and best-in-class potency
Rosnilimab, a Novel PD-1 Agonist Monoclonal Antibody, Inhibits Peripheral T Cell Proliferation and Cytokine Secretion and Reduces Circulating PD-1 High Expressing CD4 and CD8 T Cells: Results from a Phase 1 Healthy Volunteer Clinical Trial
Kenneth Luu, Martin E. Dahl, Eric Hare, Cailin Sibley, Paul Lizzul and Bruce Randazzo
Optimizing PD-1 Agonist Signaling with Membrane-Proximal Binding of Rosnilimab, a Clinical Stage PD-1 Agonist IgG1 Antibody
Stephen Parmley, Benjamin Szlyk, Richard Frank, Matthew Hsu, Polina Brodsky, Cailin Sibley, Paul Lizzul, Martin Dahl
Rosnilimab, a Novel PD-1 Agonist Monoclonal Antibody, Demonstrated Modulation of Peripheral T cell Activity and Reduction of Circulating PD-1 high Expressing CD4 and CD8 T cells in a Phase 1 Healthy Volunteer Clinical Trial
Martin E. Dahl, Eric Hare, Kenneth Luu, Bruce Randazzo and Paul Lizzul
PD-1 and PD-1 ligands: from discovery to clinical application
Taku Okazaki and Tasuku Honjo
21st Century Center of Excellence Formation and Department of Immunology and Genomic Medicine, Graduate School of
Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan
Discovery of a PD-1 Checkpoint Agonist Antibody for Autoimmune / Inflammatory Disease
Marilyn R. Kehry, Gerald Manorek, Janean Fisher, Natasha Del Cid, Allison Rooks, Laurence Altobell III, Gregory Gold, Morena Shaw, Robert Morse, Margaret Marino, Jessie-Farah Fecteau, and Stephen Parmley
A Phase 2b, Randomized, Double blind, Placebo controlled, Global Study to Evaluate the Efficacy and Safety of ANB032 in the Treatment of Moderate to Severe Atopic Dermatitis
Benjamin Ehst1, Jonathan Silverberg2, Paul Lizzul3, Kenneth Luu3, Jocelyne Papacharalambous3, Priya Raina3, Bruce Randazzo3, Cailin Sibley3, Emma Guttman-Yassky4
1Oregon Medical Research Center, Portland, OR, USA; 2The George Washington University School of Medicine and Health Sciences, Washington DC, USA; 3AnaptysBio, San Diego, CA, USA; 4Icahn School of Medicine at Mount Sinai, New York, NY, USA
ANB032, a Novel BTLA Agonist Monoclonal Antibody, Inhibits T Cell Proliferation, Reduces Inflammatory Cytokines, and Down Modulates BTLA Expression on Circulating T and B Cells: Results from a First-in-Human Phase 1 Study
Ken Luu, Bruce Randazzo, Eric Hare, Matthew Hsu, Chris Haines, Martin Dahl, Cailin Sibley, Paul Lizzul
ANB032, a Novel BTLA Agonist Monoclonal Antibody, Inhibits T Cell Proliferation, Reduces Inflammatory Cytokines, and Down Modulates BTLA Expression on Circulating T and B Cells: Results from a First-in-Human Phase 1 Study
Ken Luu, Bruce Randazzo, Eric Hare, Matthew Hsu, Chris Haines, Martin Dahl, Cailin Sibley, Paul Lizzul
A Phase 2b, Randomized, Double blind, Placebo controlled, Multicenter, Global Study to Evaluate the Efficacy and Safety of ANB032 in the Treatment of Subjects with Moderate to Severe Atopic Dermatitis
Jonathan Silverberg1, Benjamin Ehst2, Bart Burington 3*, Paul Lizzul 3, Kenneth Luu 3, Jocelyne Papacharalambous 3, Priya Raina 3, Bruce Randazzo 3, Cailin Sibley 3, Emma Guttman Yassky 4
1The George Washington University School of Medicine and Health Sciences, Washington DC, USA; 2Oregon Medical Research Center, Portland, OR, USA; 3AnaptysBio, Inc., San Diego, CA, USA; 4Icahn School of Medicine at Mount Sinai, New York, NY, USA
ANB032, a novel BTLA agonist monoclonal antibody, inhibited T cell proliferation, reduced inflammatory cytokines, and down modulated BTLA expression on circulating T and B cells in Phase 1, progresses into a Phase 2 study in atopic dermatitis
Kenneth Luu, Bruce Randazzo, Jihao Zhou, Eric Hare, Matthew Hsu, Chris Haines, Martin Dahl, Cailin Sibley, Paul F. Lizzul; AnaptysBio, Inc., San Diego, CA
BTLA signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa
Caroline Stienne, Richard Virgen-Slane, Lisa Elme´ n, …, Kenneth M. Murphy,
Carl F. Ware, John R. Sedy
ANB032, a Novel BTLA/HVEM Therapeutic Antibody, Inhibited T cells Derived from Atopic Dermatitis Patients In-vitro
Matthew Hsu, Stephanie Baguley, Tyson Chase, Justin Choi, Jennifer Michaels, Safak Yalcin, Eric Hare, Gerald Manorek, April Fraley, Gregory Gold, Robert Morse, Margaret Marino, JingUeiVerkade, Stephen Parmley and Martin Dahl.
Soluble BTLA (sBTLA) is Induced Following Targeting of BTLA In-vivo by ANB032, a Novel BTLA/HVEM Modulator Therapeutic Antibody for The Treatment of Autoimmune Disease
Martin E. Dahl, Tyson Chase, Stephanie Baguley, Eric Hare, Gerald Manorek, Kristine Storey, April Fraley, Gregory Gold, Robert Morse, Margaret Marino, Scott Lashbrook, Justin Choi, JingUei Verkade, Yu-yu Ren and Stephen Parmley,
Discovery and Characterization of ANB032, a Novel BTLA/HVEM Checkpoint Modulator for Autoimmune/Inflammatory Disease
Martin E. Dahl, Jean da Silva, Gerald Manorek, Natasha Del Cid, April Fraley, Gregory Gold, Robert Morse, Margaret Marino, JingUei Verkade, Yu-yu Ren, Janean Young, Paul Fisher,
Stephen Parmley and Marilyn R. Kehry. AnaptysBio, Inc., San Diego, CA
Discovery of a novel high affinity anti-human CD122 antagonist monoclonal antibody (ANB033) that abrogates IL-2 and IL-15 signaling for the treatment of T cell-mediated inflammatory and autoimmune diseases
Eric Hare, Chris Haines, Matthew Hsu, Jack Manorek, Cheryl Schendel, Pejman Soroosh, Stephen Parmley, Martin Dahl*; AnaptysBio, Inc., San Diego, CA, USA
Imsidolimab, an Anti-IL-36 Receptor Monoclonal Antibody for the Treatment of Generalised Pustular Psoriasis: Results from the Phase 2 GALLOP Trial
Warren et al. British Journal of Dermatology. 2023 Apr 30. https://doi.org/10.1093/bjd/ljad083
Imsidolimab, an Anti-IL-36 Receptor Monoclonal Antibody, in the Treatment of Generalized Pustular Psoriasis: Results from a Phase 2 Trial
Gudjonsson et al. 2021 Oct. Presented at 2021 European Academy of Dermatology and Venereology Annual Congress.
A Phase 1 Study of ANB019, an Anti-Interleukin-36-Receptor (IL-36R) Monoclonal Antibody, in Healthy Volunteers
Khanskaya et al. 2018 May. Poster presented at the 2018 European Academy of Allergy and Clinical Immunology (EAACI) Congress.
IL-36 in psoriasis
Towne et al. Curr Opin Pharmacol. 2012 Aug;12(4):486-90. doi:10.1016/j.coph.2012.02.009
IL-36: a potential psoriasis target?
Raison et al. Expert Rev Dermatol. 2012 7(6):503-505. doi:10.1586/EDM.12.65
Interleukin-36–Receptor Antagonist Deficiency and Generalized Pustular Psoriasis
Marrakchi et al. N Engl J Med. 2011 Aug 18;365(7):620-8. doi:10.1056/NEJMoa1013068
Mutations in IL36RN/IL1F5 Are Associated with the Severe Episodic Inflammatory Skin Disease Known as Generalized Pustular Psoriasis
Onoufriadis et al. Am J Hum Genet. 2011 Sep 9;89(3):432-7. doi:10.1016/j.ajhg.2011.07.022
The Majority of Generalized Pustular Psoriasis without Psoriasis Vulgaris Is Caused by Deficiency of Interleukin-36 Receptor Antagonist
Sugiura et al. J Invest Dermatol. 2013 Nov;133(11):2514-21. doi:10.1038/jid.2013.230
IL-1F5, -F6, -F8, and -F9: A Novel IL-1 Family Signaling System That Is Active in Psoriasis and Promotes Keratinocyte Antimicrobial Peptide Expression
Johnston et al. J Immunol. 2011 Feb 15;186(4):2613-22. doi:10.4049/jimmunol.1003162
Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation
Blumberg et al. J Exp Med. 2007 Oct 29;204(11):2603-14. doi:10.1084/jem.20070157
Coupling mammalian cell surface display with somatic hypermutation for the discovery and maturation of human antibodies
Bowers et al. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20455-60. doi:10.1073/pnas.1114010108
Mammalian cell display for the discovery and optimization of antibody therapeutics
Bowers et al. Methods. 2014 Jan 1;65(1):44-56. doi:10.1016/j.ymeth.2013.06.010
Humanization of Antibodies Using Heavy Chain Complementarity-determining Region 3 Grafting Coupled with in Vitro Somatic Hypermutation
Bowers et al. J Biol Chem. 2013 Mar 15;288(11):7688-96. doi:10.1074/jbc.M112.445502
High Affinity Humanized Antibodies without Making Hybridomas; Immunization Paired with Mammalian Cell Display and In Vitro Somatic Hypermutation
McConnell et al. PLOS ONE. 2012;7(11):e49458. doi:10.1371/journal.pone.0049458
AID-induced insertions and deletions complement point mutations to massively expand the diversity created by somatic hypermutation of antibodies
Verdino et al. Poster presented at Keystone Symposium on Antibodies as Drugs 2015.
The Biochemistry of Somatic Hypermutation
Peled et al. Annu Rev Immunol. J Exp Med. 2005 May 2;201(9):1467-78. doi:10.1146/annurev.immunol.26.021607.090236
Intricate targeting of immunoglobulin somatic hypermutation maximizes the efficiency of affinity maturation
Zheng et al. J Exp Med. 2005 May 2;201(9):1467-78. doi:10.1084/jem.20042483
Generation and iterative affinity maturation of antibodies in vitro using hypermutating B-cell lines
Cumbers et al. Nat Biotechnol. 2002 Nov;20(11):1129-34. doi:10.1038/nbt752
Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models
Kumar et al. MAbs. 2021 July 13(1):e1954136. doi:10.1080/19420862.2021.1954136.
Identification and characterization of TSR-042, a novel anti-PD-1 therapeutic antibody
Laken et al. Poster presented at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics 2016.
Discovery of TSR-022, a novel, potent anti-TIM-3 therapeutic antibody
Laken et al. Poster presented at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics 2016.
Targeting PD-1, TIM-3 and LAG-3 in Combination for Improved Immunotherapy Combinations
Kehry et al. Poster presented at AACR Annual Meeting 2015.
Generation of anti-LAG-3 monoclonal antibodies for use in immunotherapy combinations
Jun et al. Poster presented at Keystone Symposium on Antibodies as Drugs 2015.
Identification and Characterization of a Potent Anti-Human Tim-3 Antagonist
Correia et al. Poster presented at AACR Special Conference on Tumor Immunology and Immunotherapy 2014.
Generation of antagonistic anti-TIM-3 and LAG-3 monoclonal antibodies for potential novel immunotherapy combinations
Jun et al. Poster presented at AACR Annual Meeting 2014.