Currently, the only available treatment for a patient with celiac disease is a strict gluten-free diet. A lifelong diet completely free of gluten can be very costly and challenging. Many patients’ intestines don’t heal completely and they continue to suffer from symptoms, most often due to imperfect adherence to the gluten-free diet. Despite patients’ best efforts, accidental ingestion of gluten through cross-contamination continues to jeopardize their health and well-being. Future drug therapies are currently in development with the hope of reducing the burden of living with celiac disease and improving long-term health outcomes. Find out more below.

Pre-Clinical

AMYRA Biotech AG, AMY02

AMYRA is a biotech company that is developing a highly promising, novel, enzyme-based treatment for celiac disease, targeted to inhibit the toxic potential of gluten. Read more about AMYRA Biotech AG.

Circle33/Avaxia Biologics, AVX-176

Current research efforts at Avaxia are focused primarily on inflammatory diseases of the gastrointestinal tract. Avaxia has identified potential targets for antibodies that may improve celiac disease. Read more about Avaxia Biologics.

Equillium, EQ102

Equillium is a clinical-stage biotechnology company that acquired Bioniz Therapeutics in February 2022. EQ102 is a first-in-class, bi-specific cytokine inhibitor that selectively targets IL-15 and IL-21. EQ102 is ready for clinical development and Equillium expects to initiate a Phase 1 study in patients with celiac disease later this year. Read more about Equillium.

ExPharma/Nemysis, E40-02

ExPharma Limited is a medical foods development company that acquired Nemysis Limited. In May 2021, Nemysis announced the issuance of a Canadian patent for E40, a candidate for the development of a first-line treatment opposing gluten toxicity in celiac disease patients and gluten-sensitive conditions. Read more about ExPharma and Nemysis.

 

 

 

Mozart Therapeutics, CD8 Treg Cell Modulators

Mozart Therapeutics is developing CD8 T regulatory cell modulators for the treatment of celiac disease and other autoimmune disorders. In May 2022, Mozart researchers presented preclinical findings that revealed the potential of the targeted CD8 Treg modulators to reduce the inflammatory autoimmune response by eliminating disease-causing immune cells. Read more about Mozart Therapeutics.

Precigen ActoBio, ActoBiotics® AG017

Precigen ActoBio (formerly ActoBio Therapeutics) is an innovative clinical-stage biotechnology company focused on a new class of microbe-based therapeutic agents. Precigen ActoBio’s AG017 (ActoBiotics®) is an antigen-specific immunotherapy candidate based on the safe food-grade bacterium Lactococcus lactis, specifically engineered to express a gliadin peptide (a component of gluten) in combination with a cytokine (a protein that modifies the immune system). This investigational therapy has the potential to reverse gluten sensitivity. Precigen ActoBio is hoping to test AG017 for safety and efficacy in celiac disease patients. Read more about Precigen ActoBio.

Provid Pharmaceuticals

Provid focuses on synthetic and medicinal chemistry and is developing inhibitors of DQ2 and DQ8, the two genes associated with celiac disease. Read more about Provid Pharmaceuticals.

Selecta Biosciences, SVP

Selecta’s celiac disease program is focused on inducing immune tolerance by using their proprietary Synthetic Vaccine Particle (SVP™) platform to develop an immunotherapy for the treatment of celiac disease. Read more about Selecta Biosciences.

Phase 1:

Anokion, KAN-101

Anokion SA and its wholly owned subsidiary Kanyos Bio, Inc. developed KAN-101, an investigational treatment which targets the immune cells that drive celiac disease and leaves the otherwise healthy components of the immune system intact. KAN-101 acts by re-educating T cells, or tolerizing them, so they do not respond to gluten antigens. In January 2022, Anokion announced successful completion of its Phase 1 clinical trial, the ACeD Study. The Celiac Disease Foundation is proud to have been a major recruiter for this study. Anokion expects to launch enrollment for a Phase 2 clinical trial in the second half of 2022. Read more about Anokion.

 

Australian Institute of Tropical Health & Medicine (AITHM) at James Cook University, Hookworm Larvae

AITHM hopes to find a drug derived from hookworm larvae to treat gluten sensitivity. Hookworms may secrete anti-inflammatory proteins, which could be put in a pill and ultimately restore gluten tolerance. The most recently completed phase 1b trial involved applying hookworm larvae to participants’ skin, finding that hookworm-treated participants tended to have improved tolerance to low levels of gluten consumption. AITHM researchers are still investigating the biological samples they collected in this study and continuing their efforts to progress worm molecules as therapies. Read more about AITHM.

 

Calypso Biotech, CALY-002

Calypso Biotech is a biopharmaceutical company developing CALY-002, an antibody that inhibits the cytokine, Interleukin-15 (IL-15), which plays multiple roles in the immune system, especially in the gastrointestinal tract. CALY-002 may treat several gastrointestinal symptoms that currently have no approved treatment, including celiac disease. Read more about Calypso Biotech SA.

GlaxoSmithKline (GSK), GSK3915393

GlaxoSmithKline (GSK) is conducting a 3-part first time into human (FTIH) study for GSK3915393, an inhibitor of the enzyme Transglutaminase 2 (TG2) which triggers an inflammatory response to gluten exposure in people with celiac disease. Parts A and B of the study will evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending and repeat oral doses of GSK3915393 in healthy adult participants. Part C will evaluate the impact of co-administration of GSK3915393 with grapefruit juice and itraconazole on the PK of GSK3915393. By inhibiting TG2, this drug has the potential to minimize the autoimmune response that results in intestinal inflammation and disease development in celiac disease patients. Read more about GSK.

 

 

Immunic Therapeutics, IMU-856

Immunic is a clinical-stage biopharmaceutical company developing IMU-856, a small molecule modulator that targets a protein involved in the regulation of intestinal barrier function. The drug aims to restore intestinal barrier function and bowel wall architecture without compromising immune function in patients suffering from gastrointestinal diseases such as celiac disease. Read more about Immunic.

National Cancer Institute, Mayo Clinic, University of Chicago Medicine, Hu-Mik-Beta-1

Hu-Mik-Beta-1 is a monoclonal antibody that targets the cytokine receptor subunit IL-2/IL-15Rβ (CD122) as well as blocks IL-15 transpresentation. The antibody is being tested for the treatment of refractory celiac disease. Read more about Hu-Mik-Beta-1.

Nielsen Fernandez-Becker (Stanford University) and Protagonist Therapeutics, PTG-100

Nielsen Fernandez-Becker, head of the Celiac Disease Program at Stanford University, is collaborating with Protagonist Therapeutics to test the safety and efficacy of the drug PTG-100 in patients with celiac disease. PTG-100 is an oral peptide that blocks the function of alpha-4-beta-7 integrin, a cell receptor involved in the gastrointestinal inflammatory response. The goal of this phase 1b study is to learn whether PTG-100 can reduce or prevent inflammatory injury to the small intestine that occurs when people with celiac disease eat food products containing gluten. Read more about Nielsen Fernandez-Becker.

Takeda Pharmaceuticals, TAK-062

After a successful phase 1 proof-of-mechanism trial, Takeda acquired PvP Biologics and is continuing the development of TAK-062 (also known as Kuma062, formerly KumaMax). TAK-062 is a highly potent enzyme that is designed to recognize and break down the parts of gluten that trigger the immune reaction before those parts exit the stomach and reach the small intestine. Therefore, the immune response to gluten is expected to decrease, reducing the symptoms and intestinal damage associated with celiac disease. Takeda is planning a phase 2b efficacy and dose-ranging study of TAK-062 in celiac patients who maintain a gluten-free diet. Read more about Takeda.

 

 

Phase 2:

Amgen and Provention Bio, PRV-015 (formerly AMG 714)

Provention Bio licensed PRV-015 (formerly AMG 714) from Amgen in 2018. PRV-015 is an antibody that targets IL-15, a cytokine that has shown to be one of the key factors in the loss of tolerance to food antigens and is believed to be involved in celiac disease, refractory celiac disease (RCD), and other autoimmune conditions. The Celiac Disease Foundation is recruiting for Provention Bio’s PROACTIVE Celiac Study, a phase 2b study to test the safety and efficacy of PRV-015 in adult patients who are still experiencing celiac disease symptoms while on a gluten-free diet. See if you qualify.

Dr. Falk Pharma and Zedira, ZED1227

ZED1227 is the first direct-acting transglutaminase inhibitor in clinical development. Successful early clinical trials have shown efficacy, safety, and tolerability of the oral compound. Most recently, the completed phase 2a proof-of-concept gluten-challenge study revealed that ZED1227 successfully reduced gluten-induced duodenal mucosal damage in people with celiac disease. In November 2021, Dr. Falk Pharma and Zedira announced the start of the phase 2b real-life clinical trial in several European countries including Germany, Finland, and Norway to further evaluate the efficacy and tolerability of ZED1227. Read more about Dr. Falk and Zedira.

 

IGY Life Sciences, Vetanda Group Ltd., and The University of Alberta, AGY-010

Researchers from the University of Alberta and IGY have developed oral egg yolk anti-gliadin antibody (AGY), a novel treatment designed to neutralize the hidden gliadin in food. For baby chicks to fight off diseases, mother hens produce natural antibodies known as immunoglobulin yolk. In collaboration with IGY, the University of Alberta researchers developed egg yolk antibodies targeted at wheat proteins. Anti-gluten immunoglobulin yolk antibodies bind to problematic wheat proteins, making them harmless to those with celiac disease. A phase 2 trial is currently underway to test the safety and efficacy of an orally-administered capsule containing egg yolk with AGY in patients with celiac disease. Read more about Vetanda.

 

 

 

ImmunogenX, IMGX003 (Latiglutenase)

ImmunogenX is developing latiglutenase (IMGX003; formerly ALV003, Alvine Pharmaceuticals), a mixture of two gluten-specific enzymes that break down gluten proteins into small, harmless fragments. It is to be administered as a supplement to a gluten-free diet for the potential treatment of celiac disease. The technology has been extensively studied in phase 1 and phase 2 clinical trials, and has been shown to lessen gluten-induced intestinal mucosal injury, as well as improve symptoms in clinical trials. ImmunogenX is currently conducting an NIH-funded phase 2 study assessing the drink-based study medication latiglutenase and its ability to relieve common symptoms suffered by celiac disease patients after accidental gluten exposure. Read more about ImmunogenX.

ImmusanT, Nexvax2® - Discontinued

TRIAL DISCONTINUED June 25, 2019: Read more about this. ImmusanT is a clinical development-stage biotechnology company which developed Nexvax2®, a therapeutic vaccine candidate which was intended to potentially enable celiac disease patients to return to a normal diet. Booster shots of Nexvax2® were anticipated to offer periodic reinforcements of the treatment to establish a prolonged tolerance to gluten. Unfortunately, results from an interim analysis revealed Nexvax2 did not provide statistically meaningful protection from gluten exposure for celiac disease patients when compared with placebo. Read the press release here.

Oslo University Hospital, Teriflunomide

Investigators at Oslo University Hospital are currently testing the effects of teriflunomide on patients with celiac disease. Teriflunomide is an immunomodulatory agent, administered as an oral tablet, that is already in use for the treatment of multiple sclerosis. This phase 2a proof-of-concept study will test the effects of the drug on activation and efflux of gluten specific T cells using HLA-DQ:gluten tetramers. The goal of this study is to see if teriflunomide can inhibit the immune activation in celiac disease patients during a 3 day gluten challenge. Read more about celiac disease research at the University of Oslo.

Takeda Pharmaceuticals and Cour Pharmaceuticals, TAK-101

Takeda licensed TAK-101 (formerly CNP-101 or TIMP-GLIA) from Cour Pharmaceuticals in 2019. With TAK-101, the body’s immune system is reprogrammed to tolerate gluten as a non-threatening substance and then reverses the signs and symptoms of celiac disease without using immune suppressing drugs. By encapsulating a component of wheat in a small particle, Cour developed a “back door” approach, where the gluten is not recognized by the body’s immune system until it reaches the spleen, where immune tolerance can be generated. Takeda intends to initiate a Phase 2 dose-ranging study in June 2022 to further explore the potential of TAK-101 in the treatment of patients with celiac disease on a gluten-free diet. Read more about Takeda.

 

Phase 3:

9 Meters Biopharma, Larazotide - Discontinued

TRIAL DISCONTINUED June 21, 2022: Read more about this. 9 Meters (formerly known as Innovate Biopharmaceuticals) was evaluating larazotide, a tight junction regulator intended to reduce the symptoms of celiac disease by helping to restore “leaky” or open junctions to a normal state. 9 Meters aimed to introduce larazotide as an adjunctive therapy in tandem with a gluten-free diet in adults with celiac disease. Unfortunately, an interim analysis revealed that the additional number of patients needed to get clinically meaningful results between placebo and larazotide was too large to support trial continuation. 9 Meters plans to continue data analysis to determine if a subgroup of patients and/or symptoms may benefit from treatment with larazotide. Read the press release here.

Summary of Clinical Trial Phases
PhasePrimary goalDosePatient monitorTypical number of participantsnumber of participants Notes
PreclinicalTesting of drug in non-human subjects, to gather efficacy, toxicity and pharmacokinetic informationunrestrictedA graduate level researcher (Ph.D.)not applicable (in vitro and in vivo only)
Phase 0Pharmacokinetics particularly oral bioavailability and half-life of the drugvery small, subtherapeuticclinical researcher10 peopleoften skipped for phase I
Phase ITesting of drug on healthy volunteers for dose-rangingoften subtherapeutic, but with ascending dosesclinical researcher20-100determines whether drug is safe to check for efficacy
Phase IITesting of drug on patients to assess efficacy and safetytherapeutic doseclinical researcher100-300determines whether drug can have any efficacy; at this point, the drug is not presumed to have any therapeutic effect whatsoever
Phase IIITesting of drug on patients to assess efficacy, effectiveness and safetytherapeutic doseclinical researcher and personal physician1000-2000determines a drug’s therapeutic effect; at this point, the drug is presumed to have some effect
Phase IVPostmarketing surveillance – watching drug use in publictherapeutic dosepersonal physiciananyone seeking treatment from their physicianwatch drug’s long-term effect

Summary of Clinical Trial Phases

View table data

PhasePrimary goalDosePatient monitorTypical number of participantsnumber of participants Notes
PreclinicalTesting of drug in non-human subjects, to gather efficacy, toxicity and pharmacokinetic informationunrestrictedA graduate level researcher (Ph.D.)not applicable (in vitro and in vivo only)
Phase 0Pharmacokinetics particularly oral bioavailability and half-life of the drugvery small, subtherapeuticclinical researcher10 peopleoften skipped for phase I
Phase ITesting of drug on healthy volunteers for dose-rangingoften subtherapeutic, but with ascending dosesclinical researcher20-100determines whether drug is safe to check for efficacy
Phase IITesting of drug on patients to assess efficacy and safetytherapeutic doseclinical researcher100-300determines whether drug can have any efficacy; at this point, the drug is not presumed to have any therapeutic effect whatsoever
Phase IIITesting of drug on patients to assess efficacy, effectiveness and safetytherapeutic doseclinical researcher and personal physician1000-2000determines a drug’s therapeutic effect; at this point, the drug is presumed to have some effect
Phase IVPostmarketing surveillance – watching drug use in publictherapeutic dosepersonal physiciananyone seeking treatment from their physicianwatch drug’s long-term effect