Future Therapies for Celiac Disease

Allero is a biopharmaceutical company that develops next-generation immunotherapies for allergic and autoimmune disease patients, with a focus on food-related immune disorders. Their proprietary SOMIT (Specific OroMucosal ImmunoTherapy) technology is designed to induce long-lasting antigen-specific tolerance by delivering antigens directly to the oral mucosa with a mouth patch. Allero is currently developing their lead product for the treatment of celiac disease. Read more about Allero.

AMYRA is a biotech company that is developing a novel enzyme-based treatment for celiac disease. AMY02 aims to inhibit the toxic potential of gluten. It works by quickly and comprehensively degrading gluten immunogenic peptides during the digestion of gluten, inhibiting inflammations and long-term complications that occur in celiac patients whose diets are contaminated by gluten. Read more about AMYRA Biotech AG.

AnTolRx is a biotechnology company focused on revolutionizing the treatment of autoimmune diseases, including celiac disease. Their platform approach involves the development of novel therapeutics that selectively target pathogenic immune cells, utilizing specific antigens and molecules to actively promote immune tolerance. Their patented nanotechnology is designed to induce a strong anti-inflammatory signal and promote tolerance to a desired antigen. Read more about AnTolRx.

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 the 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.

IgY (Immunoglobulin-Y) is the most common type of antibody produced by the B cells in birds, reptiles, and amphibians, and has a long history of being used as therapeutic agents in humans. IgY for celiac disease contains antibodies that block the interaction of hypersensitive immune responses with microbial and protein components associated with celiac disease. IGY Life Sciences is researching the effectiveness of an oral therapeutic using a capsule-based format to deliver the antibodies directly to the small intestine where the inflammation takes place for better management of celiac disease. Read more about IGY Life Sciences.

IM Therapeutics’ approach to celiac disease is to identify and develop an oral small-molecule drug that blocks the function of HLA-DQ2, the major genetic risk factor for celiac disease. Their platform approach has identified candidate drugs that specifically block DQ2, and these lead compounds are undergoing further development and testing prior to use in patients. Read more about IM Therapeutics.

Imcyse is a clinical-stage biopharmaceutical company developing a new class of antigen-specific immunotherapies called Imotopes™. These synthetic peptides stimulate the body’s own immune system to specifically “delete” only the cells that drive abnormal immune attacks while leaving the rest of the immune system functioning normally. Imcyse is applying its Imotope™ technology for the treatment of various chronic autoimmune diseases, including celiac disease. Read more about Imcyse.

Parvus is developing a pipeline of novel Navacim™ candidates, which create disease-specific immune suppression while avoiding general immune suppression. Navacims reprogram disease-causing T cells to differentiate and expand into disease-regulating Treg cells to suppress the inflammatory immune response. Read more about Parvus.

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.

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.

Barinthus Biotherapeutics (formerly Vaccitech) is a clinical-stage biopharmaceutical company developing novel T cell immunotherapeutics that guide the immune system to overcome chronic infectious diseases, autoimmunity, and cancer. Barinthus Bio is developing VTP-1000 for the treatment of celiac disease. VTP-1000 is an antigen-specific immunotherapy utilizing Barinthus Bio’s SNAP Tolerance Platform to induce regulatory T cells to return the immune system to normal. The Celiac Disease Foundation is now recruiting for the AVALON Study, a phase 1 clinical trial evaluating the safety and tolerability of VTP-1000 in people with celiac disease. Read more about Barinthus Bio.

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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.

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.

Mozart Therapeutics is targeting the regulatory CD8 T cell network to counteract early events in the autoimmune inflammatory cascade. Mozart’s lead program, MTX-101, is a bispecific CD8 Treg Modulator that aims to restore the function of CD8 T cells in order to suppress and eliminate disease-causing immune cells. The initial therapeutic focus for MTX-101 is gastrointestinal autoimmune disorders, including celiac disease. Mozart Therapeutics is currently conducting a phase 1a/b clinical trial of MTX-101. Read more about Mozart.

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.

Dr. 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 the 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.

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.

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. Read more about Anokion.

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.

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 the Massachusetts General Hospital are conducting a double-blind, placebo-controlled trial to establish the safety and efficacy of Ritlecitinib to prevent gluten-induced symptoms in celiac disease patients. The results of this study will help investigators understand whether Ritlecitinib is a viable therapeutic option for patients with celiac disease. Read more about the study 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.

Amlitelimab is a fully human non-T cell depleting monoclonal antibody that blocks OX40-Ligand, a key immune regulator. It has the potential to be a first- or best-in-class treatment for a range of immune-mediated diseases and inflammatory disorders, such as celiac disease. Investigators are conducting a Phase 2a/b study to evaluate the efficacy and safety of Amlitelimab in adult participants with non-responsive celiac disease who are on a gluten-free diet. The study will assess the effect of Amlitelimab when compared to placebo to improve or reduce gluten-induced changes in the intestine. Read more about the study here.

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. 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 has recently concluded 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.