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Tuesday Poster Session

Category: IBD

P3607 - The Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat Containing X1 Agonist NX-13 Demonstrates Rapid Symptomatic and Biomarkers Improvement in Ulcerative Colitis: Results in a Phase 1b Study

Tuesday, October 24, 2023
10:30 AM – 4:00 PM PT
Location: Exhibit Hall
Marla C. Dubinsky, MD1, Laurent Peyrin-Biroulet, MD, PhD2, Brian G. Feagan, MD3, Andres Yarur, MD4, Simon Lichtiger, MD5, Rebecca Mosig, PhD6, Fabio A. Cataldi, MD6, Jean-Frederic Colombel, MD7
1Mount Sinai Kravis Children’s Hospital, New York, NY; 2Last Inserm U954 and CHU de Nancy, Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; 3Western University, London, ON, Canada; 4Cedars-Sinai Medical Center, Los Angeles, CA; 5Landos Biopharma, Inc., Blacksburg, VA; 6Landos Biopharma, Blacksburg, VA; 7Icahn School of Medicine at Mount Sinai, New York, NY

Introduction: Activation of NLRX1 reduces cellular oxidative stress and decreases effector immune responses. NX-13 is a first-in-class, orally active, gut selective NLRX1 agonist with low systemic exposure. In preclinical IBD models, NX-13 reduced inflammatory responses and disease severity. NX-13 was well tolerated in phase 1 trials and topline results were reported previously.1 Herein, we present data supporting rapid improvement in symptoms within 2 weeks of treatment.

Methods: In this double-blind, placebo-controlled trial, 36 patients with UC (Total Mayo Score [MCS] 4-10; Mayo endoscopic subscore [MES] 2-3) were randomly assigned to NX-13 250mg Immediate Release (IR), 500mg IR, 500mg Delayed Release (DR) or Placebo QD for 4 weeks. Biologic exposed patients, stable 5-ASA and corticosteroids (oral ≤20mg/day prednisone or equivalent) were permitted. Stool Frequency (SFS), Rectal Bleeding Score (RBS) and FCP were collected using daily diaries and at in-person visits at baseline, week 2 and week 4.

Results: Symptom Improvement (SI), Symptom Resolution (SR), and Total Symptom Remission (TSR) rates were calculated and are defined in Table 1. Early Symptom Improvement in RBS or SFS was observed by NX-13 patients within 48 hours with a clear demarcation after just 2 weeks of treatment, versus placebo (Table 1, Fig1). The greatest response was seen in the 250mg IR group with 9 patients showing Symptom Improvement and 5 in Total Symptomatic Remission at week 2. 500mg IR and DR dosed patients also responded with about half of patients showing Symptom Improvement at 2 weeks. RBS and SFS in the IR groups continued to improve to 4 weeks, with an additional 5 patients reaching SI or TSR. NX-13 IR patients also demonstrated rapid decreases in FCP levels with normalization rates of 20% (500mg IR) and 36% (250mg IR) at 2 weeks increasing to 40% (500mg IR) and 46% (250mg IR) at 4 weeks.

Discussion: In patients with UC, once-daily NX-13 demonstrated rapid onset of action within 48 hours. Distinct Symptom Improvement of RBS, SFS and/or FCP at week 2, and continued to improve to week 4. This novel mechanism of action with the potential to provide fast clinical improvement is under evaluation in a proof-of-concept study (NCT05785715).

Figure: Figure 1: Early onset of improvement in the Rectal Bleeding Score at 2 and 4 weeks in NX-13 treated patients.


Disclosures:
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.
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.
Brian Feagan: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Allianthera – Consultant. Amgen – Advisory Committee/Board Member, Consultant. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. Baxter – Consultant. BioJamp – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Boston Pharma – Consultant. Bristol Myers Squibb – Consultant. Celgene/BMS – Advisory Committee/Board Member, Consultant. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring Pharmaceuticals – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Advisory Committee/Board Member, Consultant. Gilead – Consultant. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, stock shareholder. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Advisory Committee/Board Member, Consultant. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. LifeSci Capital – Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Consultant. Morphic Therapeutics – Advisory Committee/Board Member, Consultant. Mylan – Consultant. Novartis – Advisory Committee/Board Member. OM Pharma – Consultant. Origo BioPharma – Advisory Committee/Board Member, Consultant. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Play to Know AG – Consultant. Progenity – Advisory Committee/Board Member, Consultant. Prometheus Therapeutics and Diagnostics – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill Biopharma – Consultant. Redx – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Teva – Advisory Committee/Board Member, Consultant. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Advisory Committee/Board Member, Consultant. UCB Pharma – Consultant. VHSquared Ltd. – Consultant. Viatris – Consultant. Western University, Alimentiv Inc – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.
Andres Yarur: BMS – Consultant, Speakers Bureau. Boehringer Ingelheim – Consultant. Pfizer – Consultant. Takeda – 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).
Jean-Frederic Colombel: AbbVie – Consultant, Grant/Research Support, lecture fees. Allergan – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. AnaptysBio – Consultant. Arena Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, Speakers Bureau. Celgene Corporation – Consultant. Celltrion – Consultant. Eli Lilly – Consultant. Enterome – Consultant. Ferring Pharmaceuticals – Consultant, Speakers Bureau. Galmed Research – Consultant. Genentech (Roche) – Consultant. Gilead – Consultant. Glaxo Smith Kline – Consultant. Immunic – Consultant. Imtbio – Consultant. Inotrem – Consultant. Intestinal Biotech Development – Stock Options. Invea – Consultant. Ipsen – Consultant. Iterative Scopes – Consultant. Janssen Pharmaceuticals – Consultant, Grant/Research Support. Kaleido Biosciences – Consultant. Landos – Consultant. LimmaTech Biologics AG – Consultant. Medimmune – Consultant. Merck – Consultant. Microba Life Science – Consultant. Novartis – Consultant. O Mass – Consultant. Otsuka Pharmaceutical – Consultant. Pfizer – Consultant. Prometheus – Consultant. Protagonis Therapeutics – Consultant. Sanofi – Consultant. Seres – Consultant. Shire – Consultant, Speakers Bureau. Takeda – Consultant, Grant/Research Support, lecture fees. Teva – Consultant. TiGenix – Consultant. Viela Bio – Consultant. Vifor – Consultant.


Marla C. Dubinsky, MD1, Laurent Peyrin-Biroulet, MD, PhD2, Brian G. Feagan, MD3, Andres Yarur, MD4, Simon Lichtiger, MD5, Rebecca Mosig, PhD6, Fabio A. Cataldi, MD6, Jean-Frederic Colombel, MD7. P3607 - The Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat Containing X1 Agonist NX-13 Demonstrates Rapid Symptomatic and Biomarkers Improvement in Ulcerative Colitis: Results in a Phase 1b Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.