amelenodor (ABBV-113) / LianBio, AbbVie - LARVOL DELTA

DIFFERENTIAL MODULATION OF INFLAMMATORY CYTOKINE PROFILES AMONG EARLY RESPONDERS AND NON-RESPONDERS IN A PHASE 1B STUDY OF THE NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN, LEUCINE RICH REPEAT CONTAINING X1 (NLRX1) AGONIST NX-13 IN ULCERATIVE COLITIS (UEGW 2024) - P1, P2 | "Broad changes in tissue cytokine expression were specifically observed in patients that responded to NX-13- after 4 weeks of treatment, compared to non-responders. These changes mirror those seen in preclinical mouse colitis models where a broad array of cytokines is reduced1. The early onset of cytokine shifts associated with clinical response to NX-13 at week 4 is notable and will be assessed in the ongoing phase 2 NEXUS study in patients with moderate to severe UC."

P1 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CXCL8 • IFNG • IL10 • IL12A • IL17A • IL4 • IL6 • NLRC5 • TNFA

Study to Evaluate the Clinical Activity and Safety of Oral NX-13 in Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Landos Biopharma Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

ROLE OF NLRX1 AGONIST NX-13 IN REDUCING VISCERAL HYPERSENSITIVITY IN PRECLINICAL GASTROINTESTINAL INFLAMMATION (DDW 2024) - "Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase human NEXUS trial in patients with UC."

Preclinical • Anesthesia • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pain • Ulcerative Colitis

THE EFFECT OF NLRX1 ACTIVATION ON EOSINOPHILS IN ULCERATIVE COLITIS AND INFLAMMATION: TRANSLATIONAL LEARNINGS ACROSS DISEASES AND FROM MOUSE TO HUMAN (DDW 2024) - "Studies of NLRX1 agonists (gut-selective NX-13 & systemic LABP-73) in diverse disease models identified novel cellular targets of NLRX1 activation. Neutrophil and eosinophil infiltration were reduced in UC patients treated with the gut selective NLRX1 agonist, NX-13, and was coupled with better clinical outcomes. The effect of NX-13 on eosinophils will be evaluated further in the ongoing phase 2 NEXUS trial in patients with UC."

Preclinical • Asthma • Eosinophilia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Pulmonary Disease • Respiratory Diseases • Ulcerative Colitis

AbbVie Completes Acquisition of Landos Biopharma (PRNewswire) - "AbbVie...announced today that it has completed its acquisition of Landos Biopharma, Inc. (NASDAQ: LABP). With the completion of the acquisition, Landos is now part of AbbVie. Landos' lead investigational asset is NX-13, a first-in-class, oral NLRX1 agonist (a member of the NOD-like receptor family), which is currently in Phase 2 for the treatment of moderate to severe UC (NEXUS study; NCT05785715)."

M&A • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

NX-13: “NX-13 was well-tolerated & shows promising signs of clinical improvement in active UC“; Ulcerative colitis (Landos Biopharma) - Corporate Presentation

P1 data • Inflammatory Bowel Disease • Ulcerative Colitis

NX-13: Topline data from P2 trial (NCT05785715) for moderate to severe ulcerative colitis in Q4 2024 (Landos Biopharma) - Corporate Presentation

P2 data • Inflammatory Bowel Disease • Ulcerative Colitis

AbbVie to Acquire Landos Biopharma, Further Strengthening its Portfolio in Inflammatory and Autoimmune Diseases (GlobeNewswire) - "AbbVie Inc...announced a definitive agreement under which AbbVie will acquire Landos, a clinical stage biopharmaceutical company focused on the development of novel, oral therapeutics for patients with autoimmune diseases. Landos’ lead investigational asset is NX-13, a first-in-class, oral NLRX1 agonist (a member of the NOD-like receptor family) with a bimodal mechanism of action (MOA), which is anti-inflammatory and facilitates epithelial repair....The randomized controlled Phase 2 NEXUS clinical trial evaluating NX-13 in UC is currently enrolling patients in the United States and Europe (NCT05785715)."

Enrollment status • M&A • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Landos Biopharma Provides Business Update and Reports Fourth Quarter and Full Year 2023 Results (GlobeNewswire) - "Landos Biopharma, Inc...provided a business update and reported financial results for the fourth quarter and the full year ended December 31, 2023...Research and development expenses were $3.1 million for the fourth quarter of 2023, compared to $3.4 million for the fourth quarter of 2022. The decrease was primarily attributable to reduced clinical activities due to the wind down of the omilancor and LABP-104 programs and a reduction in NX-13 Phase 1b clinical trial expenses, partially offset by the initiation of the NX-13 Phase 2 trial; Research and development expenses were $12.0 million for the full year ended December 31, 2023, compared to $25.7 million for the full year ended December 31, 2022. The decrease was primarily attributable to reduced clinical activities due to the wind down of the omilancor and LABP-104 programs and a reduction in NX-13 Phase 1b clinical trial expenses, partially offset by the initiation of the NX-13 Phase 2 trial."

Commercial • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease • Lupus • Rheumatoid Arthritis • Ulcerative Colitis

The Effect of NLRX1 Activation on Eosinophils in Ulcerative Colitis and Inflammation: Translational Learnings Across Diseases and from Mouse to Human (ECCO-IBD 2024) - "Studies of NLRX1 agonists (gut-selective NX-13 & systemic LABP-73) in diverse disease models identified novel cellular targets of NLRX1 activation...2 L Peyrin-Biroulet, et al. JCC (17) Supp"

Preclinical • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Role of NLRX1 Agonist NX-13 in Reducing Visceral Hypersensitivity in Preclinical Gastrointestinal Inflammation (ECCO-IBD 2024) - "JCC (14)Supp 4 Wils et al. J Clin Med 11(15)"

Preclinical • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

The Immunometabolic Bimodal Mechanism of NLRX1 Agonist NX-13 in a Pig Model of Ulcerative Colitis (ECCO-IBD 2024) - "These results align with previous murine results and observations in the phase 1b clinical program. Therefore, they can be used to generate additional mechanistic hypotheses for translational studies in the ongoing NEXUS phase 2 trial in moderate to severe UC."

Preclinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL23A • IL6 • NLRP3

Translating Pharmacokinetic and Efficacy Outcomes of NLRX1 Agonist NX-13: Contrasting a Pig Model and a Human Phase 1b Clinical Trial in Ulcerative Colitis (ECCO-IBD 2024) - "2 Peyrin-Biroulet, et al. JCC (17) Supp."

Clinical • P1 data • PK/PD data • Preclinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Modulation of Immunometabolism via NLRX1 or PLXDC2: Novel Bimodal Mechanisms for the Treatment of Inflammatory Bowel Diseases (ECCO-IBD 2024) - "Results NX-13, a novel NLRX1 agonist, resulted in regulation of cellular metabolism: activation of mitochondrial genes such as mt - nd3 & odgh , and concomitant down-regulation of glucose uptake by murine T cells (Fig1A)...LABP-69 also reduced superoxide levels in BMDM...J Immunol 203(12) 3 Tubau-Juni et al. J Immunol 206(Supp)"

Immunology • Inflammation • Inflammatory Bowel Disease • IFNG • NLRC5 • TNFA

Landos Biopharma to Present New Data on Immunometabolism at the 19th Annual Congress of the European Crohn’s and Colitis Organisation (GlobeNewswire) - "Landos Biopharma, Inc...announced that six abstracts were accepted for poster presentation at the 19th Annual Congress of the European Crohn’s and Colitis Organisation (ECCO). The abstracts highlight new and additional data on immunometabolism modulation by activating NLRX1 and PLXDC2 with novel agonists such as NX-13 and LABP-69. The ECCO congress will take place February 21-24, 2024 in Stockholm, Sweden....NX-13 is currently in a Phase 2 proof-of-concept trial...The Company expects to report topline results in the fourth quarter of 2024."

P1 data • Preclinical • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Landos Biopharma Publishes Results of NX-13 Phase 1b Study in Ulcerative Colitis in Journal of Crohn’s and Colitis (GlobeNewswire) - P1 | N=39 | NCT04862741 | Sponsor: Landos Biopharma Inc. | "Landos Biopharma, Inc...announced a peer-reviewed publication describing the safety, tolerability, pharmacokinetic and clinical efficacy results for the NX-13 Phase 1b trial in patients with ulcerative colitis (UC) in the Journal of Crohn’s and Colitis....NX-13 was found to be well tolerated in all patients studied. No deaths or severe adverse events were reported and all adverse events were mild to moderate. The majority of patients treated with NX-13 for four weeks showed consistent and rapid clinical improvement in total Mayo score and in symptoms relief (as measured by rectal bleeding and stool frequency). Additionally, the endoscopic improvement observed correlated closely with symptoms improvement....Phase 2 proof-of-concept study (NCT05785715) with top-line results expected in the fourth quarter of 2024."

P1 data • P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

The Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of the NLRX1 agonist NX-13 in Active Ulcerative Colitis: Results of a Phase 1b Study. (PubMed, J Crohns Colitis) - P1 | "NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741."

Clinical • Journal • P1 data • PK/PD data • Atrial Fibrillation • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Landos Biopharma Provides Company Update and Reports Third Quarter 2023 Results (Yahoo Finance) - "The NEXUS trial of NX-13 remains on track as the Company continues to recruit, screen and randomize patients for the trial. 20 sites in the United States and Europe have been activated....Research and development expenses were $3.1 million for the third quarter of 2023, compared to $4.9 million for the third quarter of 2022. The decrease was primarily attributable to the wind down of omilancor and LABP-104 clinical trials and a reduction in NX-13 Phase 1b clinical trial costs, partially offset by initiation of the NEXUS trial."

Commercial • Trial status • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

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) - P2 | "Stable 5-ASAs and corticosteroids (oral ≤20mg/day prednisone or equivalent) were permitted. 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)."

P1 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • NLRC5

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) - P2 | "Biologic exposed patients, stable 5-ASA and corticosteroids (oral ≤20mg/day prednisone or equivalent) were permitted. 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."

Biomarker • P1 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • NLRC5

Target Engagement and Pharmacodynamic Molecular Mechanism Evaluation in a Phase 1b Study of the Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat Containing X1 (NLRX1) Agonist NX-13 in Ulcerative Colitis (ACG 2023) - P2 | "All NX-13 treated groups showed target engagement through mean positive increases in NLRX1 expression versus placebo at week 4, with more pronounced upregulation observed in responding patients (Fig1A). Placebo patients’ NLRX1 levels did not increase (Fig1A). Gene expression profiles after 4 weeks of NX-13 or placebo treatment showed upregulation of the mitochondrial metabolism gene MT-ND3 (Fig1B) with downstream reductions in HIF1α and NLRP3 (Fig1C) expression in the NX-13 IR groups."

P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • HIF1A • IL1B • NLRC5 • NLRP3

Landos Biopharma to Present at the American College of Gastroenterology 2023 Annual Scientific Meeting (GlobeNewswire) - "Landos Biopharma, Inc...announced that it will present additional findings from its Phase 1b study of NX-13 for the treatment of ulcerative colitis (UC), including detailed results on the rapid symptomatic relief and improvement in multiple clinical biomarkers observed in the study, at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting, being held October 20-25 in Vancouver, Canada....The Company continues to actively recruit, screen and randomize patients for the NEXUS trial, with topline results expected by the fourth quarter of 2024."

P1 data • P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

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: RESULTS IN A PHASE 1B STUDY (UEGW 2023) - P2 | "Stable 5-ASAs and corticosteroids (oral ≤20mg/day prednisone or equivalent) were permitted. 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 and tolerability paired with promising efficacy results will be further evaluated in a phase 2 proof-of-concept study (NCT05785715)."

P1 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • NLRC5

TARGET ENGAGEMENT AND PHARMACODYNAMIC MOLECULAR MECHANISM EVALUATION IN A PHASE 1B STUDY OF THE NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN, LEUCINE RICH REPEAT CONTAINING X1 (NLRX1) AGONIST NX-13 IN ULCERATIVE COLITIS (UEGW 2023) - P2 | "Treatment with NX-13 induced upregulation of its target, NLRX1, as well as downstream immunometabolic signaling consistent with preclinical MOA studies. Most importantly, target engagement parallels clinical benefit. This novel mechanism of action warrants further study and is currently being evaluated in a phase 2 proof of concept study (NCT05785715)."

P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • DERL1 • HIF1A • IL1B • NLRC5 • NLRP3

THE NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN, LEUCINE RICH REPEAT CONTAINING X1 (NLRX1) AGONIST NX-13 DEMONSTRATES RAPID SYMPTOMATIC AND BIOMARKERS IMPROVEMENT IN ULCERATIVE COLITIS: RESULTS IN A PHASE 1B STUDY (UEGW 2023) - P2 | "Biologic exposed patients, stable 5'ASAs and corticosteroids dose (oral ≤20mg/day prednisone or equivalent) were permitted. In patients with active UC, once-daily NX-13 demonstrated rapid onset of action within 48 hours. Distinct Symptom Improvement of RBS, SFS and/or FCP at 2 weeks of treatment and continued to improve to week 4. This novel mechanism of action with the potential to provide fast symptomatic relief is under evaluation in a proof-of-concept study (NCT05785715)."

Biomarker • P1 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • NLRC5