TAK-101 / Cour Pharma, Takeda - LARVOL DELTA

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

Evolving Therapy for Celiac Disease. (PubMed, Front Pediatr) - "Examples include HLA-DQ2 blockers that prevent presentation of gluten derived- antigens by dendritic cells to T cells, immune- tolerizing therapies like the vaccine Nexvax2 and TIMP-Glia, cathepsin inhibitors, immunosuppressants like corticosteroids, azathioprine etc., and anti-cytokine agents targeting TNF-α and interleukin-15. Overall, although many therapies being explored are still in the pre-clinical phase, some like the zonulin antagonist, immune tolerizing therapies and glutenases have reached phase II/III clinical trials. While these potential options appear exciting, currently they may at best be used to supplement rather than supplant the GFD."

Journal • Review

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

Clinical • Enrollment open

Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease (clinicaltrials.gov) - P1; N=22; Active, not recruiting; Sponsor: COUR Pharmaceutical Development Company, Inc.; Trial primary completion date: Nov 2018 ➔ May 2019

Clinical • Trial primary completion date