Advantages of immune cell modulation in the treatment of autoimmune and inflammatory diseases

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

  • Checkpoint agonists “hit the brakes” to restore immune balance​ and deliver differentiated outcomes

  • 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
  • Membrane-proximal binding epitope and optimized Fc receptor binding affinity enables tight immune synapse and best-in-class potency

Teff=T effector cells; Tph cells=Peripheral helper cells; Tfh cells=Follicular helper cells.

Publications

Rosnilimab

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 T. Frank, Matthew Hsu, Polina Brodsky, Cailin Sibley, Paul Lizzul, and Martin Dahl

Anti–PD-1 antibodies recognizing the membrane proximal region are PD-1 agonists that can downregulate inflammatory diseases

Kensuke Suzuki and Tasuku Honjo

Department of Immunology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe 650-0047, Japan

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

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

ANB032

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

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

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

ANB033

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

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

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

Technology Platform

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

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

Immuno-Oncology

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.