larazotide (AT1001) / 9 Meters Biopharma - LARVOL DELTA

Evaluation of Larazotide as a Non-Dietary Pharmacological Option for Patients With Celiac Disease: A Meta-Analysis (ACG 2025) - "Out of 99 screened articles, only 4 met the inclusion criteria, encompassing 633 patients. All studies administered a gluten challenge using capsules containing 2.5–2.7 g/day of gluten in both arms. Analysis of the lactulose-to-mannitol (LAMA) urinary excretion ratio revealed no significant difference between Larazotide and placebo (MD: 0.15, 95% CI: -0.56 to 0.25, p = 0.46)."

Retrospective data • Celiac Disease • Gastrointestinal Disorder • Immunology

Larazotide Acetate Protects the Intestinal Mucosal Barrier from Anoxia/Reoxygenation Injury via Various Cellular Mechanisms. (PubMed, Biomedicines) - " LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with "leaky gut" and mucosal injury."

Journal • Celiac Disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Reperfusion Injury

Is There a Future Without Gluten Restrictions for Celiac Patients? Update on Current Treatments. (PubMed, Nutrients) - "These include gluten-degrading enzymes (e.g., AN-PEP, Latiglutenase, Zamaglutenase), gluten-sequestering agents (e.g., AGY-010, BL-7010), modulators of intestinal permeability (e.g., Larazotide acetate, IMU-856), immune-modulating agents (e.g., ZED1227, AMG 714, EQ102), and strategies for immune tolerization (e.g., TAK-101, KAN-101, Nexvax2). Continued research is essential to validate efficacy, optimize dosing, and ensure safety in broader patient populations. Here, we provide a comprehensive overview of the therapeutic landscape for CeD, analyze the main strengths and limitations of each treatment and highlight promising directions for future management of CeD, altogether evidencing the urgent need to develop effective alternatives for these patients."

Journal • Review • Allergy • Celiac Disease • Immunology

Antibacterial hyaluronic acid hydrogel with sustained release of larazotide as effective colitis treatment. (PubMed, J Control Release) - "It repaired tight junctions (ZO-1, occluding and claudin-5), restored mucus production (MUC2), and rebalanced gut microbiota. HSMP-LA hydrogel might offer a synergistic strategy to combat colitis via halting the vicious dysbiosis-mucus-epithelial barrier disorders cycle."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • CLDN5 • IL10 • MUC2 • TJP1

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Massachusetts General Hospital | N=48 ➔ 150 | Trial primary completion date: Mar 2026 ➔ Jul 2026

Enrollment change • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide. (PubMed, Sci Transl Med) - "Children treated with larazotide displayed faster resolution of gastrointestinal symptoms, faster clearance of spike antigen, and a faster return to usual activities. Our findings suggest that larazotide treatment may be safe in children and may improve resolution of symptoms when used as an adjuvant therapy for MISC."

Clinical • Journal • Cardiovascular • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pain • Respiratory Diseases • IFNG • IL6

Coeliac disease and the intestinal barrier: mechanisms of disruption and strategies for restoration. (PubMed, Gut) - "We also review comprehensively the therapies targeting barrier integrity and normalising intestinal permeability, including particular diets and supplements, and experimental and improved medications including larazotide acetate and IMU-856. Finally, we highlight the need for reliable biomarkers for evaluating increased permeability in coeliac disease and advocate for further research on therapies which normalise barrier function, particularly as a strategy to maintain remission."

Journal • Review • Celiac Disease • Gastrointestinal Disorder • Immunology

Preventive effects of Larazotide acetate (AT-1001) on non-alcoholic fatty liver diseases (NAFLD) in a mouse model. (PubMed, Pediatr Neonatol) - No abstract available

Journal • Preclinical • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease

New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review. (PubMed, Healthcare (Basel)) - "For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent...Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated...For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments...Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric..."

Journal • Review • Autoimmune Hepatitis • Celiac Disease • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder • Hepatitis B • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Pediatrics • Transplantation • IL13 • IL5 • TGM2 • TSLP

LARAZOTIDE ACETATE: ANALYSIS OF A PHASE # STUDY FOR PERSISTENT SYMPTOMS IN PATIENTS WITH CELIAC DISEASE (DDW 2025) - No abstract available

Clinical • Celiac Disease • Immunology

The PAR2 Antagonist Larazotide Can Mitigate Acute Histamine-Stimulated Epithelial Barrier Disruption in Keratinocytes: A Potential Adjunct Treatment for Atopic Dermatitis. (PubMed, JID Innov) - "Larazotide may be beneficial as a topical therapeutic for AD; however, the permeability properties of the short-peptide larazotide through the uppers layers of the epidermis is currently unknown. In conclusion, the protease-activated receptor 2 antagonist larazotide has a protective effect on keratinocyte monolayers and may be useful as an adjunct therapeutic agent to enhance barrier function and promote epidermal healing in AD."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Elucidating the Significance of Zonulin in the Pathogenesis of Chronic Inflammatory Disorders: Emphasis on Intestinal Barrier Function and Tight Junction Regulation. (PubMed, Curr Med Chem) - "Recent research has demonstrated the therapeutic potential of targeting zonulin, specifically through the use of larazotide acetate, a zonulin antagonist...Further research is needed to elucidate the precise mechanisms of action of zonulin antagonists and evaluate their efficacy and safety in clinical trials. A deeper understanding of the complex interplay among zonulin, intestinal permeability, and CIDs is crucial, paving the way for novel therapeutic strategies and personalized approaches to patient care."

Journal • Celiac Disease • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis

AT1001 for the Treatment of COVID-19 Related MIS-C (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: Massachusetts General Hospital | N=20 ➔ 12 | Trial completion date: Dec 2025 ➔ May 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ May 2024; Decline in MISC cases

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease • CRP • IL6

AT1001 for the Treatment of COVID-19 Related MIS-C (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Massachusetts General Hospital | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2022 ➔ Dec 2025 | Trial primary completion date: Sep 2022 ➔ Jun 2025

Phase classification • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • CRP • IL6

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Massachusetts General Hospital | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Novel Coronavirus Disease

Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats. (PubMed, Dig Dis Sci) - "Our findings show that LA reduces the increased intestinal permeability and intestinal damage by its effect on Zo in the AP model in rats, and decreases the frequency of bacterial translocation as a result of these positive effects."

Journal • Preclinical • Immunology • Inflammation • Pancreatitis • Systemic Inflammatory Response Syndrome • TJP1

Bromelain and ficin proteolytic effects on gliadin cytotoxicity and expression of genes involved in cell-tight junctions in Caco-2 cells. (PubMed, Amino Acids) - "Finally, we examined the effect of these treatments along with Larazotide Acetate on the expression of genes involved in cell-tight junctions, such as Occludin, Claudin 3, tight junction protein-1, and Zonulin in the Caco-2 cell line. Furthermore, the proteolytic effects of bromelain and ficin on gliadin indicated the expression of genes involved in cell-tight junctions was improved. This study confirms that bromelain and ficin mixture could be effective in improving the symptoms of CeD."

Journal • Celiac Disease • Immunology • CLDN3 • OCLN • TJP1

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2a | N=48 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions. (PubMed, Int J Mol Sci) - "In addition to focusing on the effect of microbiome on intestinal zonulin release, we also summarize potential pharmaceutical approaches to modulate zonulin-associated pathways with larazotide acetate and other zonulin receptor agonists or antagonists. The present review also addresses the emerging issues, including the use of misleading nomenclature or the unsolved questions about the exact protein sequence of zonulin."

Journal • Review • CNS Disorders

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2a | N=48 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2a trial • Infectious Disease • Novel Coronavirus Disease

Sex-dependent Lupus Blautia (Ruminococcus) gnavus strain induction of zonulin-mediated intestinal permeability and autoimmunity. (PubMed, Front Immunol) - "Strikingly, gut permeability was completely reversed by oral treatment with larazotide acetate, an octapeptide that is a specific molecular antagonist of zonulin. Taken together, these studies document a pathway by which RG strains from Lupus patients contribute to a leaky gut and features of autoimmunity implicated in the pathogenesis of flares of clinical Lupus disease."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Study to Evaluate the Efficacy and Safety of Larazotide Acetate for the Relief of CeD Symptoms (clinicaltrials.gov) - P3 | N=307 | Terminated | Sponsor: 9 Meters Biopharma, Inc. | N=630 ➔ 307 | Trial completion date: Dec 2021 ➔ Jul 2022 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2021 ➔ Jul 2022; Trial terminated by Sponsor

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Celiac Disease • Immunology

Modulation of the Intestinal Tight Junction Reduces Lung Fibrosis in an Animal Model for Idiopathic Pulmonary Fibrosis: The Role of Intestinal Microbiome Gut-Lung Axis in Idiopathic Pulmonary Fibrosis (ATS 2022) - "Methods - Forty-eight pathogen-free, 6-week old, female C57BL/6J mice were induced to develop pulmonary fibrosis by a single intratracheal administration of bleomycin (3.0 mg/kg). On the following 20 days, mice were administered once daily with larazotide orally (1 mg/kg), larazotide intratracheally (25 μg/mouse), vehicle (control) or dexamethasone (0.25 mg/kg, active control)...Conclusions - In an animal model for IPF, the tight-junction modulator larazotide administered orally reduced pulmonary fibrosis better than administered intratracheally, indicating that the gut microbiome may play an important role in pulmonary fibrosis. Therefore, intestinal tight junction modulators, such as larazotide, may have a role in the treatment of IPF via gut-lung axis."

Preclinical • Allergy • Asthma • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Fibrosis • Genetic Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series. (PubMed, Crit Care Explor) - "Larazotide appears safe and well-tolerated and may offer potential benefit as an adjuvant to immune-targeted therapies. Expansion of clinical trials is urgently needed to ascertain the clinical impact of larazotide on MIS-C."

Journal • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases