TAK-101 / Cour Pharma, Takeda - LARVOL DELTA

TAK-101 IMMUNOMODULATION OF THE GLIADIN RECALL RESPONSE IN HLA-DQ8 MICE – (SINGLE CELL) TRANSCRIPTOMIC STUDIES (UEGW 2025) - "B cells appear to be important for the immunomodulation of the adaptive gliadin immune response by TAK-101."

Immunomodulating • Preclinical • Celiac Disease • Immunology • IL17A • IL22 • IL6 • TNFA

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

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2 | N=83 | Active, not recruiting | Sponsor: Takeda | N=17 ➔ 83

Enrollment change • Celiac Disease • Immunology

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting | N=90 ➔ 17

Enrollment change • Enrollment closed • Celiac Disease • Immunology

TAK-101 IMMUNOMODULATION OF THE GLIADIN RECALL RESPONSE IN HLA-DQ8 MICE: TREATMENT EFFECT DURATION AND MECHANISTIC STUDIES (DDW 2024) - "TAK-101 induced a sustained tolerance effect in HLA-DQ8 mice. B cells appear to be important in immunomodulation of the gliadin recall response by TAK-101."

Immunomodulating • Preclinical • Celiac Disease • Immunology • IL17A

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Takeda | Active, not recruiting ➔ Recruiting | Trial completion date: Jan 2026 ➔ Oct 2025 | Trial primary completion date: Jan 2026 ➔ Oct 2025

Enrollment open • Trial completion date • Trial primary completion date • Celiac Disease • Immunology • IFNG

Antigen-specific CD4+ Tregs induced by tolerogenic immune modifying nanoparticles (TIMP) inhibit antigen-specific CD8+ T cell responses (IMMUNOLOGY 2024) - "Dysglycemic RIP-mOVA mice were treated with TIMP-OVA323 induced a long-lived return to normoglycemia, which was shown to be dependent upon CD4+ Tregs. Taken together, these results show that TIMP-induced tolerance to a single CD4+ T cell epitope within a complex protein activates Ag-specific Tregs capable of inhibiting responses to a dominant CD8 T cell epitope within that protein."

Celiac Disease • Diabetes • Immunology • Metabolic Disorders • CD4 • CD8

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2 | N=108 | Active, not recruiting | Sponsor: Takeda | Trial completion date: May 2024 ➔ Jan 2026 | Trial primary completion date: Jan 2024 ➔ Jan 2026

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

QUALIFICATION OF A MACHINE LEARNING APPROACH FOR THE ANALYSIS OF HIGH-DIMENSION IMMUNE-PROFILING DATA IN CELIAC DISEASE (DDW 2023) - P=N/A, P2 | "ML allowed an independent method to be used to confirm findings by manual gating and to gain insight into the cellular changes that occur after gluten exposure and treatment with a potential immune tolerance therapy for CeD (TAK-101)... The qualification of the FlowSOM ML process suggests it is a viable approach to interrogate high-dimension datasets. ML may be used as a complementary approach secondary to hypothesis-driven manual gating to confirm immune subset findings and to yield deeper cell subset characterization not evident with traditional approaches."

IO biomarker • Machine learning • Celiac Disease • Immunology • CD38 • CD4 • CD8

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2 | N=108 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed • Celiac Disease • Immunology • IFNG • IL2

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Celiac Disease • Immunology • IFNG • IL2

Tolerogenic Immune-Modifying Nanoparticles Encapsulating Multiple Recombinant Pancreatic β Cell Proteins Prevent Onset and Progression of Type 1 Diabetes in Nonobese Diabetic Mice. (PubMed, J Immunol) - "Blockade of T1D following CNP-T1D tolerization was characterized by regulatory T cell induction and a significant decrease in both peri-insulitis and immune cell infiltration into pancreatic islets. As we have recently published that CNP treatment is both safe and induced Ag-specific tolerance in a phase 1/2a celiac disease clinical trial, Ag-specific tolerance induced by nanoparticles encapsulating multiple diabetogenic proteins is a promising approach to T1D treatment."

Journal • Preclinical • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus • CD4 • CD8

Tolerogenic Immune Modifying Nanoparticles (TIMP) Encapsulating Multiple Diabetogenic Epitopes Prevent Onset of Type 1 Diabetes in NOD Mice (IMMUNOLOGY 2022) - "We have recently published that CNP treatment is both safe and induces Ag-specific tolerance in Phase I/IIa celiac disease clinical trials. Therefore, utilization of this technology including multiple diabetogenic proteins is a promising Ag-specific tolerance approach to T1D treatment."

Preclinical • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4 • CD8

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2; N=108; Not yet recruiting; Sponsor: Takeda; Trial completion date: Mar 2023 ➔ May 2024; Trial primary completion date: Dec 2022 ➔ Jan 2024

Clinical • Trial completion date • Trial primary completion date • Celiac Disease • Immunology • IFNG • IL2

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2; N=108; Not yet recruiting; Sponsor: Takeda; Initiation date: Apr 2021 ➔ Aug 2021

Clinical • Trial initiation date • Celiac Disease • Immunology • IFNG • IL2

TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study. (PubMed, Gastroenterology) - "TAK-101 was well tolerated and prevented gluten-induced immune activation in CeD. The findings from the present clinical trial suggest that antigen-specific tolerance was induced and represent a novel approach translatable to other immune-mediated diseases."

Clinical • Journal • Celiac Disease • Immunology • CD4 • IFNG

Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease. (PubMed, Gastroenterology) - "In mice with gliadin sensitivity, injection of TIMP-GLIA nanoparticles induced unresponsiveness to gliadin, and reduced markers of inflammation and enteropathy. This strategy might be developed for treatment of celiac disease."

Journal • Preclinical • Celiac Disease • Hematological Disorders • Immune Modulation • Immunology • Inflammation

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2; N=108; Not yet recruiting; Sponsor: Takeda; Trial completion date: Nov 2022 ➔ Mar 2023; Initiation date: Sep 2020 ➔ Apr 2021

Clinical • Trial completion date • Trial initiation date • Celiac Disease • Immunology • IFNG • IL2

Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet (clinicaltrials.gov) - P2; N=108; Not yet recruiting; Sponsor: Takeda

New P2 trial • Celiac Disease • Immunology • IFNG • IL2

Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease (clinicaltrials.gov) - P2; N=34; Completed; Sponsor: Takeda; Active, not recruiting ➔ Completed; N=51 ➔ 34

Clinical • Enrollment change • Trial completion • Celiac Disease • Immunology • CXCL8 • IFNG • IL10 • IL2 • IL4 • IL6

Treatment with Multiple-linked Myelin Peptides Encapsulated within Nanoparticles Induces Antigen-specific Tolerance in SJL/J Relapsing-remitting Experimental Autoimmune Encephalomyelitis. (IMMUNOLOGY 2020) - "Furthermore, treatment of SJL/J mice with multiple-linked myelin peptide TIMP significantly decreased TH17 cell responses and increased Tr1 cell responses. The present findings suggest that utilizing multiple-linked peptides may be clinically translatable for the treatment of autoimmune disease."

TAK-101 (TIMP-GLIA) PREVENTS GLUTEN CHALLENGE INDUCED IMMUNE ACTIVATION IN ADULTS WITH CELIAC DISEASE (DDW 2020) - "To our knowledge, this is the first clinical trial demonstrating non-autologous induction of antigen specific immune tolerance in any autoimmune disease. *TAK-101 previously labelled TIMP-GLIA (or CNP-101) for this study ** p-value by Wilcoxon rank-sum tes"

Clinical • Back Pain • Celiac Disease • CNS Disorders • Fatigue • Immunology • Inflammation • Inflammatory Bowel Disease • Pain • IFNG

CNP-101 PREVENTS GLUTEN CHALLENGE INDUCED IMMUNE ACTIVATION IN ADULTS WITH CELIAC DISEASE (UEGW 2019) - "In this Phase 2 proof of concept study, CNP-101 (TIMP-GLIA) was able to prevent gluten challenge induced immune activation in adults with CD. To our knowledge, this is the first clinical trial to demonstrate non-autologous induction of antigen specific immune tolerance in any autoimmune disease."

Clinical • Late-breaking abstract

Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease (clinicaltrials.gov) - P1; N=23; Completed; Sponsor: COUR Pharmaceutical Development Company, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease (clinicaltrials.gov) - P2; N=51; Active, not recruiting; Sponsor: COUR Pharmaceutical Development Company, Inc.; Recruiting ➔ Active, not recruiting; N=30 ➔ 51

Clinical • Enrollment change • Enrollment closed