latiglutenase (IMGX003) / Entero Therap - LARVOL DELTA

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

Efficacy and Safety of Latiglutinase In Celiac Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ACG 2024) - "Three RCTs involving 253 patients were analyzed (Table 1). No significant difference was observed between latiglutenase and placebo in the villus height to crypt depth ratio (MD: 0.05, 95% CI [-0.41, 0.51], P = 0.82) (Figure 1-A) or intraepithelial lymphocyte densities (MD: -11.82, 95% CI [-28.41, 4.78], P = 0.16) (Figure 1-B). Additionally, there were no significant differences in overall AEs (RR: 0.99, 95% CI [0.81, 1.21], P = 0.90), medication-related AEs (RR: 1.33, 95% CI [0.71, 2.49], P = 0.37), or gastrointestinal-related AEs (RR: 1.05, 95% CI [0.82, 1.34], P = 0.70) (Figure 1-C)."

Retrospective data • Review • Celiac Disease • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Mucositis • Pain

Efficacy and Safety of Latiglutenase in the Treatment of Celiac Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. (PubMed, Am J Ther) - No abstract available

Clinical • Journal • Retrospective data • Review • Celiac Disease • Immunology

Prospective, Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Symptomatic CD Patients (clinicaltrials.gov) - P2 | N=84 | Terminated | Sponsor: Entero Therapeutics | N=120 ➔ 84 | Active, not recruiting ➔ Terminated; Due to low enrollment related to Covid.

Enrollment change • Trial termination • Celiac Disease • Immunology

A COMPOSITE MUCOSAL SCALE FOR CELIAC DISEASE ENCOMPASSING BOTH MORPHOLOGY AND INFLAMMATION (DDW 2024) - P2, P2a, P2b | "For the gluten-challenge IMGX003-NCCIH-17 1 (NCT03585478) trial we observed an effect size and p-value (ANCOVA) of 0...[ ] Oberhuber G. Histopathology of celiac disease. Biomed Pharmacother 000;54:368-37 ."

Celiac Disease • Immunology • Inflammation

DYNAMICS OF SEROLOGIC CHANGE TO GLUTEN IN CELIAC DISEASE PATIENTS (DDW 2024) - P2 | "Method The test results reported here are from two recent celiac disease trials IMGX003-NCCIH-17 1 (NCT03585478) and IMGX003-NIAID-18 1 (NCT04 43551)...There is a strong correlation by both measurements as evidenced by a Pearson coefficient R = 0. 8584."

Clinical • Celiac Disease • Immunology

Celiac disease: Hope for new treatments beyond a gluten-free diet. (PubMed, Clin Nutr) - "Despite significant efforts, no treatment has yet completed a phase III clinical trial. Future studies will likely focus on the use of supplemental drugs in conjunction to a GFD, with ALV003 and ZED-1227 currently being the most promising therapeutic options."

Journal • Review • Celiac Disease • Immunology • Inflammation

A Composite Morphometric Duodenal Biopsy Mucosal Scale for Celiac Disease Encompassing both Morphology and Inflammation. (PubMed, Clin Gastroenterol Hepatol) - "The composite VCIEL scale combining Vh:Cd and IEL values appears to improve accuracy and statistical precision compared to either component alone."

Biopsy • Journal • Celiac Disease • Immunology • Inflammation

Study of Latiglutenase in T1D/CD Patients (clinicaltrials.gov) - P2 | N=13 | Terminated | Sponsor: Immunogenics, LLC | N=40 ➔ 13 | Trial completion date: Jun 2024 ➔ Dec 2022 | Recruiting ➔ Terminated | Trial primary completion date: Apr 2024 ➔ Dec 2022; Covid-19 interruptions and enrollment challenges

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Prospective, Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Symptomatic CD Patients (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Immunogenics, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: May 2023 ➔ Dec 2023 | Trial primary completion date: May 2023 ➔ Dec 2023

Enrollment closed • Trial completion date • Trial primary completion date • Celiac Disease • Immunology

A COMPOSITE QUANTITATIVE HISTOLOGY SCALE BASED ON VH:CD AND IEL (DDW 2023) - P2, P2b | "Results Our first example is for our recently completed gluten challenge study (CeliacShield, NCT03585478) using a 1,200 mg dose of latiglutenase...[3] Oberhuber G. Histopathology of celiac disease. Biomed Pharmacother 2000;54:368–372."

Celiac Disease • Immunology

MEASURING GLUTEN IN A CLINICAL TRIAL SETTING - EXPERIENCES WITH LATIGLUTENASE, AN ORAL THERAPY IN DEVELOPMENT FOR CELIAC DISEASE (DDW 2023) - "The lack of a universally accepted reference standard for gluten provides complications for assessing gluten content; semi-quant urine assays to study GIP are extremely useful; new evidence studying the urinary peptidome suggests more gluten-based biomarkers may prove useful to study a potential therapy’s mechanism of action. Our LC/MS targeted quantitative assay provides an interesting approach to further probe in-vivo gluten digestion products in urine from CeD vs non CeD."

Clinical • Celiac Disease • Immunology

LATIGLUTENASE – AN EFFECTIVE ORAL THERAPY IN DEVELOPMENT FOR THE TREATMENT OF CELIAC DISEASE: EXPLORING THE BENEFITS AND CHALLENGES OF ADMINISTERING AND MEASURING GLUTEN IN A CLINICAL TRIAL SETTING (UEGW 2022) - P2 | " Our observations from this study in concert with current knowledge in food science and drug development clinical trial results provide the following insights: care and attention should be given to the analytical methodology used to determine the gluten content of the particular food articles used in a clinical gluten challenge. A lack of a universally accepted reference standard for gluten provides complications for assessing the accurate gluten content in some foods; semi-quantitative urinary assays to study GIP are extremely useful; new evidence directed to studying the urinary peptidome suggests more gluten-based biomarkers may be useful to study a potential therapy’s mechanism of action. Our LC-MS/MS targeted quantitative assay provided a more sensitive approach to further probe in-vivo gluten digestion products and further validated the latiglutenase mechanism of action."

Clinical • Celiac Disease • Immunology

Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients with Celiac Disease Exposed to a Gluten Challenge. (PubMed, Gastroenterology) - P2 | "The 3 x 2-week trend-line significance for these symptoms, respectively, were p = .014, .030 and .002 IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity. gov number NCT03585478."

Journal • Celiac Disease • Gastrointestinal Disorder • Immunology • Inflammation • Pain

Study of Latiglutenase in T1D/CD Patients (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Immunogenics, LLC | N=30 ➔ 40 | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Apr 2023 ➔ Apr 2024

Enrollment change • Trial completion date • Trial primary completion date • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Prospective, Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Symptomatic CD Patients (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Immunogenics, LLC | Trial completion date: Feb 2022 ➔ May 2023 | Trial primary completion date: Dec 2021 ➔ May 2023

Trial completion date • Trial primary completion date • Celiac Disease • Immunology

CELIACSHIELDTM GLUTEN CHALLENGE STUDY – LATIGLUTENASE PROTECTS THE MUCOSA AND ATTENUATES SYMPTOMS OF CELIAC DISEASE (DDW 2022) - P2 | "Measurements of GIPs in urine showed reduction of gluten of >90% for latiglutenase vs. placebo. Serology measurements for TTG-IgA, DGP-IgG and DGP-IgG all showed worsening for placebo and improvement for latiglutenase groups relative to baseline.We further acknowledge the valuable contributions of Ana Ramos, Vasiliy Loskutov, Irina Horwath, and Isabel Hujoel."

Celiac Disease • Immunology • Pain

GLUTEN IN URINE MEASUREMENTS VALIDATE LATIGLUTENASE MECHANISM OF ACTION IN CELIACSHIELD GLUTEN CHALLENGE STUDY (DDW 2022) - P2 | "To test this assumption, we correlated GIP in urine to histologic change as measured by villous height to crypt depth ratio (Vh:Cd) and observed a statistically significant trend (p = 0.012). Though suggestive of non-compliance we cannot rule out at this time possible pharmacokinetic effects."

Celiac Disease • Immunology

[VIRTUAL] CELIACSHIELDTM GLUTEN-CHALLENGE STUDY – LATIGLUTENASE PROTECTS THE MUCOSA AND ATTENUATES SYMPTOMS IN CELIAC DISEASE PATIENTS (UEGW 2021) - P2 | "Latigluenase continues to show efficacy in the degradation of gluten in the stomach of patients with CeD. By measuring changes in histology, serology, commonly reported symptoms and GIPs in urine, data confirm the correlation of various biological signatures and successfully support endpoints to clinical support endpoints to clinical outcome measures of attenuation of CeD-related symptoms while maintaining a histologic architecture. Latiglutenase is an orally administered therapeutic drug candidate for the treatment of CeD in patients who follow and maintain a strict gluten-free diet."

Clinical • Late-breaking abstract • Celiac Disease • Immunology • Pain

[VIRTUAL] CELIACSHIELDTM GLUTEN-CHALLENGE STUDY – LATIGLUTENASE PROTECTS THE MUCOSA AND ATTENUATES SYMPTOMS IN CELIAC DISEASE PATIENTS: Discussion (UEGW 2021) - No abstract available

Clinical • Celiac Disease • Immunology

[VIRTUAL] CELIACSHIELDTM GLUTEN CHALLENGE STUDY – GLUTEN IMMUNOGENIC PEPTIDE MEASUREMENTS IN URINE VALIDATE THE LATIGLUTENASE MECHANISM OF ACTION AND PROVIDE A MEASURE OF COMPLIANCE IN A CLINICAL TRIAL SETTING (UEGW 2021) - P2 | "Unique information from the semi-quantitative GIP in urine measurements was found to be particularly beneficial by illustrating how latiglutenase effectively degrades gluten in the stomach, as well as assessing the compliance of study subjects by tracking the biological signature of the presence of gluten during the course of a therapeutic clinical study. Future work will assess various other gluten peptides in urine(ref 2), specifically those not detected by a lateral flow immunochromatographic technique, using LC/MS to compare healthy vs CeD subjects.Further study of the pharmacokinetics of gluten ingestion and related in vivo digestion products as biomarkers, such as GIPs, is warranted and would provide helpful information to confirm suspected instances of non-compliance in gluten challenge studies. Additionally, this type of information may provide insight for researchers into how the immune systems of people with CeD and other autoimmune diseases are affected..."

Clinical • Celiac Disease • Immunology

[VIRTUAL] CELIACSHIELDTM GLUTEN CHALLENGE STUDY – GLUTEN IMMUNOGENIC PEPTIDE MEASUREMENTS IN URINE VALIDATE THE LATIGLUTENASE MECHANISM OF ACTION AND PROVIDE A MEASURE OF COMPLIANCE IN A CLINICAL TRIAL SETTING (UEGW 2021) - P2 | "Unique information from the semi-quantitative GIP in urine measurements was found to be particularly beneficial by illustrating how latiglutenase effectively degrades gluten in the stomach, as well as assessing the compliance of study subjects by tracking the biological signature of the presence of gluten during the course of a therapeutic clinical study. Future work will assess various other gluten peptides in urine(ref 2), specifically those not detected by a lateral flow immunochromatographic technique, using LC/MS to compare healthy vs CeD subjects.Further study of the pharmacokinetics of gluten ingestion and related in vivo digestion products as biomarkers, such as GIPs, is warranted and would provide helpful information to confirm suspected instances of non-compliance in gluten challenge studies. Additionally, this type of information may provide insight for researchers into how the immune systems of people with CeD and other autoimmune diseases are affected..."

Clinical • Celiac Disease • Immunology

[VIRTUAL] CELIACSHIELDTM GLUTEN CHALLENGE STUDY – GLUTEN IMMUNOGENIC PEPTIDE MEASUREMENTS IN URINE VALIDATE THE LATIGLUTENASE MECHANISM OF ACTION AND PROVIDE A MEASURE OF COMPLIANCE IN A CLINICAL TRIAL SETTING (UEGW 2021) - P2 | "Unique information from the semi-quantitative GIP in urine measurements was found to be particularly beneficial by illustrating how latiglutenase effectively degrades gluten in the stomach, as well as assessing the compliance of study subjects by tracking the biological signature of the presence of gluten during the course of a therapeutic clinical study. Future work will assess various other gluten peptides in urine(ref 2), specifically those not detected by a lateral flow immunochromatographic technique, using LC/MS to compare healthy vs CeD subjects.Further study of the pharmacokinetics of gluten ingestion and related in vivo digestion products as biomarkers, such as GIPs, is warranted and would provide helpful information to confirm suspected instances of non-compliance in gluten challenge studies. Additionally, this type of information may provide insight for researchers into how the immune systems of people with CeD and other autoimmune diseases are affected..."

Clinical • Celiac Disease • Immunology

Study of Latiglutenase in T1D/CD Patients (clinicaltrials.gov) - P2; N=30; Recruiting; Sponsor: Immunogenics, LLC; N=200 ➔ 30; Initiation date: Apr 2021 ➔ Oct 2021

Clinical • Enrollment change • Trial initiation date • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Latiglutenase as a Treatment for Celiac Disease (clinicaltrials.gov) - P2; N=79; Completed; Sponsor: Immunogenics, LLC; Trial primary completion date: Jan 2020 ➔ Jan 2021

Trial primary completion date • Celiac Disease • Immunology