Phase 1:
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 conditions that currently have no approved treatment, including celiac disease. Calypso is currently conducting a phase 1b clinical trial to test the safety and tolerability of CALY-002 in healthy volunteers and volunteers with celiac disease. Read more about Calypso.
Chugai Pharmaceutical Co., DONQ52
Chugai is conducting a phase 1 clinical trial for DONQ52, an investigational medication designed to target an immune complex known to cause celiac disease symptoms. DONQ52 is expected to also protect the small intestine against damage caused by gluten exposure. Read more about Chugai.
GlaxoSmithKline (GSK), GSK3915393 - Discontinued
TRIAL DISCONTINUED February 1, 2023: Read more about this. GlaxoSmithKline (GSK) conducted 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. By inhibiting TG2, this drug had the potential to minimize the autoimmune response that results in intestinal inflammation and disease development in celiac disease patients. Unfortunately, after completing the phase 1 study in 2021, GSK dropped the celiac disease drug candidate from its clinical development pipeline. Read the press release here.
Immunic Therapeutics, IMU-856
Immunic is a clinical-stage biotechnology company developing treatment options for chronic inflammatory and autoimmune diseases, including IMU-856, a small molecule modulator that targets a protein involved in the regulation of intestinal barrier function and regeneration of bowel epithelium. 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. In May 2023, Immunic announced positive results from its phase 1b clinical trial in patients with celiac disease. IMU-856 was observed to be safe and well-tolerated in this trial and demonstrated positive results in four key dimensions of the disease’s pathophysiology: histology, disease symptoms, biomarkers, and nutrient absorption. Immunic is currently preparing for a phase 2b clinical trial in patients with 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 moreabout 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.
Teva, TEV-53408
Teva Pharmaceuticals is currently testing TEV-53408, an investigational antibody designed to block interleukin 15 (IL-15). In people with celiac disease, gluten consumption results in the production of IL-15 which triggers intestinal inflammation, leading to destruction of intestinal cells. Teva is conducting a phase 1b clinical trial evaluating the safety and tolerability of TEV-53408 in people with celiac disease. Read more about Teva.
Phase 2:
Amgen and Provention Bio, a Sanofi Company, PRV-015 (formerly AMG 714)
Provention Bio, a Sanofi Company, 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 recently completed recruitment for the 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.
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. The Celiac Disease Foundation is now recruiting for the ACeD-it Study, a phase 1b/2 clinical trial evaluating the safety and tolerability of KAN-101 in people with celiac disease, and the SynCeD Study, a phase 2a clinical trial testing the ability of KAN-101 to protect the gut from gluten-induced damage.
Entero Therapeutics, Latiglutenase
Entero is developing latiglutenase, 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. Entero plans to initiate a phase 3 trial in the second half of 2024 to assess 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 Entero.
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.
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 analysisrevealed 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, 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. Takeda is currently conducting a phase 2 clinical trial evaluating the safety and effectiveness of TAK-062 in those with celiac disease on a gluten-free diet. Read more about Takeda.
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 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.
Takeda Pharmaceuticals, Dr. Falk Pharma, and Zedira, TAK-227/ZED1227
TAK-227 (ZED1227) is a selective, oral small molecule designed to inhibit tissue transglutaminase (TG2) to prevent mucosal damage in the small intestine by preventing the body’s immune response to gluten. A phase 2a proof-of-concept gluten-challenge study revealed that TAK-227 successfully reduced gluten-induced duodenal mucosal damage in people with celiac disease. In October 2022, Takeda announced a collaboration and licensing agreement to continue phase 2b development of TAK-227 in partnership with Zedira and Dr. Falk Pharma. Read more about Takeda.
Topas Therapeutics, TPM502
Topas Therapeutics is a clinical-stage biotechnology company with a mission to deliver novel, disease-modifying treatments for autoimmune and inflammatory diseases. Topas is developing antigen-specific proprietary nanoparticles, called TPCs (Topas Particle Conjugates), which harness the natural mechanisms of the liver to promote antigen-specific immune tolerance without broadly suppressing the immune response. Topas is currently conducting a phase 2a clinical trial testing TPM502 for the treatment of celiac disease. Read more about Topas.
