Future Therapies for Celiac Disease

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.

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.

Enteralia Bioscience is a healthcare and pharmaceutical company formed in 2021 from Nemysis Limited. Enteralia is developing E40, an oral enzyme that effectively breaks down gluten even in absence of pepsin. E40 was originally discovered in soil and is now produced through recombinant technology. E40 has the potential to become a first-in-class, first line pharmaceutical option for celiac disease and other gluten-related disorders. Read more about Enteralia.

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 (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 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’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.

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 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 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.

Equillium, a clinical-stage biotechnology company that acquired Bioniz Therapeutics in February 2022, is conducting a phase 1 study to evaluate the safety and tolerability of EQ102. EQ102 is a first-in-class, bi-specific cytokine inhibitor and part of Equillium’s proprietary Multi-Cytokine Platform. EQ102 may be an optimal approach to treating patients with celiac disease as it inhibits the natural biological synergy of cytokines IL-15 and IL-21 that drive cytotoxic T cell responses in gastrointestinal inflammation. Read more about Equillium.

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 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.

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, 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 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. The Celiac Disease Foundation is currently recruiting for the TEV-CeD Study, a phase 1b clinical trial evaluating the safety and tolerability of TEV-53408 in people with celiac disease. See if you qualify.

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 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 SynCeD Study, a phase 2a clinical trial testing the ability of KAN-101 to protect the gut from gluten-induced damage. See if you qualify.

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 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.

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.

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.

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 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.

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 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.

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.