Takeda tees up $420M deal for celiac antidote, continuing R&D refocus
Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.
A dysfunctional digestive system, Arataeus concluded – an imbalance he attributed to a “heat” deficiency in a system he and other Greeks regarded as functioning similarly to an oven – and coined a term: coeliac disease, after the Greek word for abdomen.
Arataeus prescribed rest and fasting – to restore the heat – and for 2,000 years little changed for the autoimmune disease. Samuel Gee, the 19th-century physician who revived scientific study of the condition, figured diet was the answer; he just didn’t know which one. A banana-based diet, said one doctor in 1924, and that caught on for decades. Only in the latter half of the century was celiac’s autoimmune nature uncovered and with it the prescription for most patients: Stay away from gluten, the chemical behind bread’s chewiness.
But researchers didn’t stop looking for something that could better assuage and prevent the dysfunction that all but killed Arataeus’s patient zero. And now Takeda thinks they have a candidate. Impressed with a partner’s new Phase IIa data, the pharma giant is putting nearly half a billion behind the idea.
Takeda will license CNP-101/TAK-101 from COUR Pharmaceuticals for $420 million in milestones, plus royalties. Takeda exercised their option from a 2015 deal on the same day COUR unveiled Phase IIa data showing celiac patients receiving the drug saw an indicator for autoimmune response fall dramatically.
“It’s tough to always say cure but, you know, disease-modifying,” COUR CEO John Puisis told Endpoints News. “I can’t make the [cure] claim from a regulatory standpoint but I think there’s something really here.”
Puisis has grand plans for his company’s nanoparticle platform and views today’s results as confirmation for a technology he hopes to bring to other autoimmune disorders. For Takeda, the results are an important win as the company continues to streamline R&D in the wake of the Shire deal, focusing on key areas such as gastroenterology.
The Japanese giant will be entering a crowded space, as just in the past three months multiple large players have signed deals to address celiac’s root causes. Most notably in September, Anokion bought out Kanyos Bio and its antigen-specific treatment, while GlaxoSmithKline purchased a biotech with a different approach.
Essentially, COUR used their nanoparticle platform to trick the body into believing that gliadin, the gluten component that triggers the autoimmune response, is a natural bodily antigen: friend, not foe. They encased gliadin in a biodegradable polymer smaller than a micron and sent it whirling Alice in Wonderland style through the body – ushered by monocyte “sentinels” down into the spleen and livers, where antigen-presenting T cells encoded it as non-harmful.
“Somewhere along the line — whether it’s genetics or virus or a combination – the immune system went haywire and started attacking these people’s small intestine when they digested gluten,” Puisis said. “And what we had to do is reprogram that.”
COUR gave two small groups CNP-101 or a control on days 1 and 8 and then administered gluten for two weeks days. Six days after the gluten doses, COUR tested patients for interferon-gamma spot forming units – a biomarker measuring the autoimmune response – and found 17.57 in the control group and 2.10 in the treatment group. A secondary endpoint measuring the anatomical autoimmune response, duodenal villus height to crypt depth ratio, also showed “expected, significant reduction.”
Puisis told Endpoints they also asked patients about symptoms, but the survey data were not announced.
After 6 dropouts for gluten-related symptoms, there were 28 patients in total.
Puisis, who early on rejected investor pressure to focus the company on one indication, spoke of the results with loftier ambition than treating one disease. He and the promotional materials touted the Phase IIa as the first trial to “demonstrate induction of antigen-specific immune tolerance in any autoimmune disease.” In other words, the first case of a company convincing the autoimmune patient’s body not to attack itself, at least using this method.
The main non-diet treatment for celiac is immune suppressants that can have significant side effects, and more broadly the management for autoimmune diseases has been whole-body approaches that treat symptoms without addressing the root cause, such as insulin for diabetes. But faced with diminishing returns on those therapies, researchers have recently turned toward ways of snubbing out or preventing the underlying issue.
Last year, for instance, Vienna University of Technology researchers displayed an antibody technology that would latch onto and neutralize incoming gliadin antigens.
“The problem is that classical immune intervention has relied almost exclusively on broad acting agents, which, although they have shown therapeutic benefits, are not specific for the disease and often increase the risk of infections and malignancies,” Novartis’s José Carballido and Parvus Therapeutics’ Pere Santamaria wrote in an issue of the Journal of Experimental Medicine in January, before running through some new developments, including eliminating mature hematopoietic cells to start a complete immune reset. “A far less aggressive and more amenable choice to promote immune tolerance involves targeting the existing peripheral effector and/or memory autoreactive T cell compartments using antigen-based approaches.”
Takeda will next initiate a dose-ranging study, while COUR looks to develop their multiple sclerosis and peanut allergy drugs. Puisis said they began with celiac because the disease itself was relatively well-understood – but that’s all the more reasons why the next applications may be that much harder to produce.