Therapy Areas: Autoimmune
Takeda Enters Collaboration and Licensing Agreement with Zedira, Dr. Falk Pharma to Develop First-in-Class Celiac Disease Therapy
20 October 2022 - - Japan-based pharmaceutical company Takeda (TSX: 4502) (NYSE: TAK), Germany-based biotechnology company Zedira and Dr. Falk Pharma GmbH have forged a collaboration and licensing agreement to develop ZED1227/TAK-227, a Phase 2b investigational therapy for the treatment of celiac disease, the companies said.

TAK-227 is a potential first-in-class therapy designed to prevent the immune response to gluten in celiac disease, a serious autoimmune disease where the ingestion of gluten leads to inflammation and damage to the small intestine.

There are currently no approved therapies for the treatment of celiac disease.

TAK-227 (ZED1227)1 is a selective, oral small molecule designed to inhibit tissue transglutaminase, an enzyme that generates immunogenic gluten peptide fragments upon the breakdown of gluten in the stomach and intestinal tissue.

TAK-227 targets the dysregulated transglutaminase to prevent mucosal damage in the small intestine by preventing the body's immune response to gluten, a disease process mediated by activation of gluten-specific T cells.

A Phase 2a proof-of-concept study published in the New England Journal of Medicine previously demonstrated a protective effect of TAK-227 on the duodenal mucosa and symptoms during a six-week gluten challenge.

The compound was also found to be safe and well tolerated.

Under the terms of the agreement, Takeda and Dr. Falk Pharma will conduct global clinical studies for TAK-227 in celiac disease. Takeda will receive an exclusive license to develop and commercialize TAK-227 in the United States and other territories outside of Europe, Canada, Australia and China.

Zedira and Dr. Falk Pharma will receive an upfront payment and are eligible to receive potential development, regulatory and commercial milestones, as well as royalties on net sales.

Originally discovered by Zedira, Dr. Falk Pharma licensed the European rights to ZED1227 from Zedira in 2011 and assumed responsibility for preclinical and clinical development of the program.

Takeda is advancing a portfolio of investigational therapies for the potential treatment of celiac disease. In addition to TAK-227, Takeda is developing two other investigational celiac disease therapies that recently entered Phase 2 clinical trials.

TAK-062 is a potential best-in-class, highly potent glutenase a protein that degrades ingested gluten that was computationally engineered to treat celiac disease.

TAK-101 is a potential first-in-class, immune-modifying nanoparticle containing gliadin proteins designed to promote immune tolerance to gluten in celiac disease by preventing gliadin-specific T-cell activation.

Celiac disease is a systemic, immune-mediated disorder characterized by chronic enteropathic inflammation, and precipitated by exposure to dietary gluten in genetically predisposed individuals.

Global prevalence of celiac disease is ~1%, with highest rates in women, in relatives of individuals with celiac disease, and in those with other immune-mediated disorders; prevalence of celiac disease is increasing worldwide, yet many cases remain undetected or not formally diagnosed.

The amount of daily tolerable gluten varies widely among individuals with celiac disease. Although some can tolerate >50 mg/day, others develop mucosal abnormalities with gluten consumption of 10 mg/day, and mucosal damage has been associated with chronic exposures of as little as 1 mg/day.

Celiac disease can cause symptoms, including abdominal pain, diarrhea, nausea, and vomiting. Long-term complications of celiac disease may include malnutrition, accelerated osteoporosis, nervous system problems and problems related to reproduction.

There is no approved therapy for celiac disease. The only available management option for patients is maintaining a gluten-free diet, which involves strict, lifelong avoidance of exposure to gluten proteins from wheat, barley, and rye, which is not always effective.

Zedira GmbH is a Darmstadt (Germany) based biotech company has a focus on celiac disease and other transglutaminase-linked conditions in the areas of autoimmunity, fibrotic diseases, and thrombosis.

The company develops, produces, and markets specialty reagents and kits for research and development as well as for clinical diagnostics.

Zedira established a pipeline of drug candidates adapted to specific indications based on a series of patented synthetic transglutaminase blockers. ZED1227 is the first direct-acting transglutaminase inhibitor in clinical development.

Zedira is a portfolio company of the German High-Tech Gründerfonds.

Dr. Falk Pharma GmbH has been developing and marketing innovative medicines to treat a range of gastrointestinal disorders like inflammatory bowel disease or eosinophilic esophagitis as well as hepatobiliary disorders such as primary biliary cholangitis for over 60 years.

Dr. Falk Pharma GmbH employs approximately 990 individuals globally, thereof 218 in Freiburg.