Takeda, Zedira and Dr. Falk Pharma GmbH have entered a collaboration and licensing agreement to develop ZED1227/TAK-227, a Phase 2b investigational therapy for the treatment of celiac disease.
 
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.
 
“The continued development of TAK-227 in partnership with Zedira and Dr. Falk Pharma has the potential to offer a meaningful benefit to patients with celiac disease who suffer from symptoms and ongoing intestinal injury despite maintaining a gluten-free diet,” said Chinwe Ukomadu, M.D., Ph.D., head, Gastroenterology Therapeutic Area Unit at Takeda. “With three novel programs now in the clinic, Takeda is at the forefront of developing transformative therapies for celiac disease and is advancing multiple therapies for patients living with this challenging lifelong autoimmune condition.”

About TAK-227 (ZED1227)

TAK-227 (ZED1227)¹ is a selective, oral small molecule designed to inhibit tissue transglutaminase (TG2), 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.² The compound was also found to be safe and well tolerated.
 
“Patients with celiac disease urgently need appropriate therapeutic options to manage the significant negative impacts of the disease on health and daily quality of life,” said Roland Greinwald, Ph.D., Managing Director Medicine & Pharmaceutics at Dr. Falk Pharma.
 
Martin Hils, Ph.D., CEO at Zedira, added, “Takeda’s R&D expertise in gastroenterology, commercial footprint, and its strong commitment to develop therapies to treat celiac disease, make it an ideal partner to help us bring TAK-227 to patients.”

Terms of the Agreement

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.
 
References:
¹ Büchold C, Hils M, Gerlach U, Weber J, Pelzer C, Heil A, Aeschlimann D, Pasternack R. Features of ZED1227: The First-In-Class Tissue Transglutaminase Inhibitor Undergoing Clinical Evaluation for the Treatment of Celiac Disease. Cells. 2022; 11(10):1667. https://doi.org/10.3390/cells11101667
² Schuppan D, Mäki M, Lundin KEA, Isola J, Friesing-Sosnik T, Taavela J, Popp A, Koskenpato J, Langhorst J, Hovde Ø, Lähdeaho ML, Fusco S, Schumann M, Török HP, Kupcinskas J, Zopf Y, Lohse AW, Scheinin M, Kull K, Biedermann L, Byrnes V, Stallmach A, Jahnsen J, Zeitz J, Mohrbacher R, Greinwald R; CEC-3 Trial Group. A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease. N Engl J Med. 2021 Jul 1;385(1):35-45. doi: 10.1056/NEJMoa2032441. PMID: 34192430.