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Tuesday Poster Session

Category: IBD

P3644 - Rapid Symptomatic Relief Is Correlated with Early Endoscopic Response to the Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat Containing X1 (Nlrx1) Agonist Nx-13 in Ulcerative Colitis in a Phase 1b Study

Tuesday, October 24, 2023
10:30 AM – 4:00 PM PT
Location: Exhibit Hall

    Presenting Author(s)

  • Andres J. Yarur, MD

    Associate Professor of Medicine
    Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center
    Los Angeles, CA

Andres Yarur, MD1, Laurent Peyrin-Biroulet, MD, PhD2, Remo Panaccione, MD3, Marla C. Dubinsky, MD4, Simon Lichtiger, MD5, Rebecca Mosig, PhD6, Fabio A. Cataldi, MD6, Stefan Schreiber, MD7
1Cedars-Sinai Medical Center, Los Angeles, CA; 2Last Inserm U954 and CHU de Nancy, Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; 3University of Calgary, Calgary, AB, Canada; 4Mount Sinai Kravis Children’s Hospital, New York, NY; 5Landos Biopharma, Inc., Blacksburg, VA; 6Landos Biopharma, Blacksburg, VA; 7University Hospital Schleswig Holstein, Kiel, Schleswig-Holstein, Germany

Introduction: NLRX1 is an immunometabolic mitochondrial protein whose activation reduces oxidative stress to decrease inflammation. NX-13 is a novel, first-in-class, orally active and gut selective NLRX1 agonist with low systemic exposure. In animal studies of IBD, NX-13 reduced inflammatory responses and overall disease severity. A phase 1a study showed NX-13 to be well tolerated. The aim of this analysis was to assess the association between the onset of clinical improvement with early endoscopic response after the 4 weeks of NX-13 treatment.

Methods: In this double-blind, placebo-controlled trial, 36 patients with active UC (Total Mayo Score 4-10; Mayo Endoscopic Subscore [MES] 2-3) were randomized to receive NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks. Stable 5-ASAs and corticosteroids (oral ≤20mg/day prednisone or equivalent) were permitted. Stool Frequency (SFS) and Rectal Bleeding Scores (RBS) were collected at baseline, week 2 and week 4. MES was centrally read in a blinded manner at screening and week 4. A blinded pathologist performed Geboes scoring.

Results: Symptom Improvement, Endoscopic Response, Endoscopic Remission, and Histologic Remission rates were calculated and are defined in Table 1. No placebo patients achieved Endoscopic Response. More than half of NX-13 dosed patients with Symptom Improvement at week 2 progressed to achieve rapid Endoscopic Response after only 4 weeks, with 26% in complete Endoscopic Remission in this short trial (Table 1). Histologic Remission was also more common in patients with Symptom Improvement. Sub analysis of the Symptom Improvement group highlighted patients with early, isolated SFS improvement (n=4) had the greatest rates of Endoscopic Response (100%), Endoscopic Remission (75%), and Histologic Remission (75%) (Fig1). Patients with RBS Improvements also responded endoscopically and histologically better than patients without symptom improvement. Conversely, nearly all Endoscopic Responders showed early Symptom Improvement (10/11) at week 2. Further, all 5 of the Endoscopic Remitters had symptomatic improvement at week 2.

Discussion: : Patients with active UC starting treatment with NX-13 that achieved fast onset of Symptom Improvement were more likely to achieve associated rapid Endoscopic Response and Remission. This novel MOA with good safety paired with promising efficacy results will be further evaluated in a proof-of-concept study (NCT05785715).

Figure: Figure 1: Endoscopic Outcomes at week 4 were correlated with Symptom Improvement by week 2.


Disclosures:
Andres Yarur: BMS – Consultant, Speakers Bureau. Boehringer Ingelheim – Consultant. Pfizer – Consultant. Takeda – Consultant.
Laurent Peyrin-Biroulet: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Allergan – personal fees. Alma – personal fees. Amgen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Applied Molecular Transport – personal fees. Arena – personal fees. Biogaran – Advisory Committee/Board Member, Consultant, Speakers Bureau. Biogen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant, Speakers Bureau. Bristol Myers Squibb – personal fees. Celgene – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. CTMA – Stock Options. Eli Lilly – Advisory Committee/Board Member, Consultant, Speakers Bureau. Enterome – personal fees. Enthera – personal fees. Ferring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Forward Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Fresenius – personal fees. Genentech – Advisory Committee/Board Member, Consultant, Speakers Bureau. Gilead – personal fees. H.A.C. Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Hikma – personal fees. Hospira/Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Index Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Lycera – Advisory Committee/Board Member, Consultant, Speakers Bureau. Merck – Advisory Committee/Board Member, Consultant, Speakers Bureau. Mitsubishi – Advisory Committee/Board Member, Consultant, Speakers Bureau. MSD – Grant/Research Support, personal fees. Mylan – personal fees. Nestlé – personal fees. Norgine – Advisory Committee/Board Member, Consultant, Speakers Bureau. Oppilan Pharma – personal fees. OSE Immunotherapeutics – personal fees. Pfizer – personal fees. Pharmacosmos – personal fees. Roche – personal fees. Samsung Bioepis – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sterna – personal fees. Sublimity Therapeutics – personal fees. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Theravance – Advisory Committee/Board Member, Consultant, Speakers Bureau. Tillots – Advisory Committee/Board Member, Consultant, Speakers Bureau. Vifor – Advisory Committee/Board Member, Consultant, Speakers Bureau.
Remo Panaccione: Abbivax – Consultant. Abbott – Consultant. AbbVie – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena – Consultant. AstraZeneca – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Celltrion – Consultant. Cosmos Technology – Consultant. Eisai – Consultant. Elan – Consultant. Eli Lilly – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. JAMP Bio – Consultant. Janssen – Consultant. Merck – Consultant. Mylan – Consultant. Novartis – Consultant. Oppilan Pharma – Consultant. Organon – Consultant. Pandion Pharma – Consultant. Pendopharm – Consultant. Pfizer Inc – Consultant. Progenity – Consultant. Prometheus – Consultant. Protagonist Therapeutics – Consultant. Roche – Consultant. Sandoz – Consultant. Satisfai Health – Consultant. Shire – Consultant. Sublimity Therapeutics – Consultant. Takeda Pharmaceuticals – Consultant. Theravance Biopharma – Consultant. Trellus – Consultant. UCB – Consultant. Ventyx – Consultant. Viatris – Consultant.
Marla Dubinsky: AbbVie – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant. Astra Zeneca – Consultant. Celgene – Consultant. Genentech Inc. – Consultant. Gilead Sciences – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Consultant. Pfizer – Consultant, Grant/Research Support. Prometheus Biosciences – Consultant, Grant/Research Support. Prometheus Labs – Consultant, Grant/Research Support. Takeda – Consultant, Licensing fees. Thabor – Consultant. Trellus Health – Stock-publicly held company(excluding mutual/index funds). UCB Pharma – Consultant.
Simon Lichtiger: Landos Biopharma – Consultant, Employee, Stock-publicly held company(excluding mutual/index funds).
Rebecca Mosig: Landos Biopharma – Employee, Stock Options.
Fabio Cataldi: Landos Biopharma – Employee, Stock-publicly held company(excluding mutual/index funds).
Stefan Schreiber: AbbVie – Consultant, Speakers Bureau. Arena – Consultant. Biogen – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb, – Consultant, Speakers Bureau. Celgene – Consultant. Celltrion – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant, Speakers Bureau. Falk Pharma – Consultant, Speakers Bureau. Fresenius – Consultant. Galapagos/Gilead – Consultant, Speakers Bureau. Hikma – Consultant, Speakers Bureau. IMAB – Advisory Committee/Board Member, Consultant. Janssen – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Mylan – Advisory Committee/Board Member, Consultant. Pfizer – Consultant, Speakers Bureau. Protagonist – Consultant. Provention Bio – Consultant. Takeda – Consultant, Speakers Bureau. Theravance – Consultant.


Andres Yarur, MD1, Laurent Peyrin-Biroulet, MD, PhD2, Remo Panaccione, MD3, Marla C. Dubinsky, MD4, Simon Lichtiger, MD5, Rebecca Mosig, PhD6, Fabio A. Cataldi, MD6, Stefan Schreiber, MD7. P3644 - Rapid Symptomatic Relief Is Correlated with Early Endoscopic Response to the Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat Containing X1 (Nlrx1) Agonist Nx-13 in Ulcerative Colitis in a Phase 1b Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.