ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0455

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 Dahl, Eric Hare, Cailin Sibley, Paul Lizzul and Bruce Randazzo, AnaptysBio, San Diego, CA

Meeting: ACR Convergence 2023

Keywords: autoimmune diseases, rheumatoid arthritis, T Cell

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Sunday, November 12, 2023

Title: (0423–0459) RA – Treatments Poster I

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: PD-1 pathway mutations increase human susceptibility to multiple autoimmune diseases, and insufficient PD-1 signaling can lead to dysregulated T cell responses. By targeting natural immune regulatory mechanisms to modulate immune cells driving disease, there is an opportunity to dampen the inflammatory cycle and restore immune balance. Rosnilimab is a PD-1 agonist antibody designed to inhibit activated T cells for the treatment of inflammatory diseases, including rheumatoid arthritis (RA).The primary objective of this first-in-human (FIH), healthy volunteer (HV) Phase 1 study was to assess the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) of rosnilimab. Other objectives included the assessment of pharmacokinetic (PK) profile, immunogenicity, and translational pharmacodynamic (TPD) endpoints (e.g. PD-1 receptor occupancy (RO), reduction in various T cell populations and associated cytokine signaling).

Methods: This study was conducted at a single study center in the United States with 14 cohorts in SAD and 3 cohorts in MAD. Each cohort had 8 participants (6 active, 2 placebo (PBO)). Treatment cohorts were enrolled sequentially in each SAD/MAD phase. Intravenous (IV) and subcutaneous (SC) routes of administration were assessed in the SAD; SC route was assessed in the MAD.

Results: A total of 144 participants were enrolled; 90 randomized to the active SAD cohorts, 18 to the active MAD cohorts, and 30 and 6 randomized to the SAD and MAD PBO cohorts, respectively. All participants were assessed for safety and PD. Rosnilimab was well tolerated, with no dose-limiting toxicities or deaths. Two serious adverse events (SAEs) were reported in the SAD (obstructive pancreatitis in a PBO-dosed participant; COVID-19 infection in a rosnilimab-dosed participant leading to discontinuation; unrelated to treatment).No SAEs were reported in the MAD. TPD activity was rapid with sustained reduction in quantity and functional activity of PD-1+ T cells. Conventional T (Tcon) cells in the periphery expressing PD-1 were reduced, on average through Day 30 in the SAD where full RO was sustained following rosnilimab dosing, by ~50% in both CD4+ and CD8+ subsets, in a dose-dependent manner and in correlation with RO.This reduction was maximized on PD-1 high expressing T cells, ~90% reduction relative to baseline. There was no significant impact on the overall total T cell, Tcon or regulatory T (Treg) cell numbers, thereby resulting in an observed bias in favor of Treg:Tcon cell ratio post-dosing. An antigen-specific functional T cell assay measuring ex vivo interferon-gamma release in response to antigen challenge was inhibited up to ~90% relative to baseline within 30 days following a single dose. Rosnilimab has a favorable PK profile consistent with full RO, a two-week half-life, and exposure nearly dose-proportional in both IV and SC dosing.

Conclusion: Rosnilimab demonstrated favorable safety, PK, and TPD activity. These results demonstrate proof of mechanism in humans and support advancing rosnilimab into a phase 2b study in RA.


Disclosures: K. Luu: AnaptysBio, 3, 11; M. Dahl: AnaptysBio, 3, 11; E. Hare: AnaptysBio, 3, 11; C. Sibley: AnaptysBio, 3, 11; P. Lizzul: AnaptysBio, 3, 11; B. Randazzo: AnaptysBio, 3, 11.

To cite this abstract in AMA style:

Luu K, Dahl M, Hare E, Sibley C, Lizzul P, Randazzo B. 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 [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/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-p/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/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-p/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology