Takeda Pharmaceutical today further bolstered its pipeline in one of its key therapeutic areas, gastroenterology, by acquiring an exclusive global license to develop and commercialize COUR Pharmaceutical Development’s mid-stage candidate CNP-101 after the potential first-in-class treatment for celiac disease generated positive Phase IIa results. The deal could generate more than $420 million for the Chicago biotech, which has partnered with the Japanese pharma giant for several years.

CNP-101 (formerly TIMP-GLIA) is an immune modifying nanoparticle containing gliadin proteins. The candidate uses COUR’s proprietary immune modifying nanoparticles, which are designed to bind inflammatory cells to initiate tolerogenic immune reprogramming. The interior core can be loaded with disease-specific antigen—such as gliadin proteins, in the case of CNP-101—to induce tolerance in celiac disease and other autoimmune conditions.

The license deal comes nearly four years since Takeda and COUR launched a research and development partnership of undisclosed value in December 2015 that was designed to develop novel immune-modulating therapies for the potential treatment of celiac disease, using COUR’s Tolerizing Immune Modifying nanoParticle (TIMP) platform. The underlying technology was acquired from Northwestern University and draws from more than 30 years of research by the laboratory of Stephen D. Miller, PhD, the Judy E. Guggenheim research professor of microbiology-immunology.

“Our collaboration with COUR has shown, for the first time, that it is possible to induce specific immune tolerance to a foreign antigen in autoimmune diseases such as celiac disease,” Asit Parikh MD, PhD, head, gastroenterology therapeutic area unit at Takeda, said in a statement. “With our expertise in inflammatory diseases, Takeda is well positioned to further develop TAK-101 in pursuit of providing the first approved treatment option for patients with celiac disease.”

Gastroenterology is one of Takeda’s three main therapeutic areas of focus, along with oncology and neuroscience, though the pharma’s pipeline also includes plasma-derived therapies, vaccines, and rare disease treatments. Takeda has made moves in recent months to bolster its gastroenterology pipeline.

In August, for example, Takeda inked a potentially more than $1.2 billion collaboration with Sosei Heptares to discover, develop, and commercialize small molecules and biologics designed to modulate G protein-coupled receptor (GPCR) targets—focusing on unspecified “high-priority” gastrointestinal GPCR targets to be nominated by Takeda, with the potential to expand into other therapeutic areas.

Positive proof of concept

Takeda said it inked the license agreement with COUR after CNP-101 generated positive results in a Phase IIa proof-of-concept study whose results were presented today as a late-breaking abstract at UEG Week 2019, being held in Barcelona, Spain. The trial was intended to highlight the potential for CNP-101 to prevent gluten-induced immune activation in patients with celiac disease. Of 34 patients who were randomized and treated, 28 completed the 14-day gluten challenge per protocol, while the other six discontinued due to gluten-related symptoms.

Takeda and COUR said CNP-101 met the trial’s primary endpoint of change from baseline in interferon-gamma (IFN-γ) spot forming units (SFUs) at day 6 after gluten challenge using a gliadin-specific enzyme-linked immunospot (ELISpot) assay. The test is designed to be a direct measure of gluten-specific systemic T cell activation in celiac disease; the blocking of that response suggested that people with celiac disease could be protected from the effects of gluten exposure.

CNP-101 generated a mean change from baseline in IFN-γ ELISpot SFUs of 17.57 with placebo and 2.10 with CNP-101. The study also showed better protection from small intestinal mucosal damage with deterioration of 0.18 with TAK-101, compared with 0.63 with placebo.

“The placebo group showed the expected, highly significant, increase in IFN-γ SFU during GC. This GC-induced gliadin-depend[e]nt T cell response was substantially reduced by CNP-101 pre-treatment,” according to COUR’s presentation. “To our knowledge, this is the first clinical trial to demonstrate induction of antigen-specific immune tolerance in any autoimmune disease.”

Added COUR co-founder, president, and CEO John J. Puisis: “We are encouraged by the data from this first human proof-of-concept study of our proprietary nanoparticle platform designed to reprogram the immune system.”

Dose-ranging study planned

Takeda will rename CNP-101 as TAK-101, and said it intends to launch a dose-ranging study to further explore the drug’s potential for treating patients with celiac disease on a gluten-free diet, with the results to inform future registrational trials.

In return for the licensing rights, Takeda agreed to pay COUR up to $420 million in future payments, and royalties on sales of any commercialized products resulting from the license.

When Takeda and COUR launched their partnership in 2015, they disclosed that COUR was to receive upfront and milestone payments from Takeda leading to an exclusive option by Takeda to acquire a global license to the TIMP-GLIA program after the completion of the Phase IIa clinical trial. Takeda also agreed to pay COUR royalties on sales of any successful commercialized products resulting from the partnership. Takeda also received the option to collaborate on up to three additional TIMP compounds each with development, regulatory, and sales milestones and royalties on sales.

“As Takeda assumes responsibility for the celiac disease program, COUR will focus on advancing our pipeline of therapies for a variety of other immune disorders ranging from multiple sclerosis to peanut allergy,” Puisis added.