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Breaking down gluten
SAN DIEGO, SEATTLE & OSAKA, Japan—Celiac disease affects one in 100 people worldwide. It causes significant health problems, including acute gastrointestinal symptoms, malnutrition, weakness and failure to thrive. Celiac disease can develop at any age and, if left untreated, can lead to additional serious health problems.
Takeda Pharmaceutical Co. Ltd., a global research and development-driven pharmaceutical company, and PvP Biologics Inc., which is developing an oral enzyme for the treatment of celiac disease, have entered a global agreement for the development of KumaMax. The enzyme is designed to break down the immune-reactive parts of gluten in the stomach, thereby avoiding the painful symptoms and damage done in the small intestine from accidental gluten ingestion.
“Celiac disease is a disorder in which the ingestion of even a trace amount of gluten can damage the small intestine,” said Dr. Tadataka “Tachi” Yamada, chairman of PvP Biologics. “In preclinical experiments, KumaMax has shown the ability to degrade gluten with sufficient efficiency and effectiveness to indicate its exciting potential as an oral therapy for a disease that impairs the lives of millions.”
A preclinical, uniquely engineered, recombinant enzyme, KumaMax is active under acidic stomach conditions and has high specificity for the parts of gluten that cause the autoimmune reaction leading to celiac disease. Currently, the only treatment available for celiac disease patients is a strict gluten-free diet, which is challenging to maintain. For celiac patients attempting to maintain a gluten-free diet but who may accidentally ingest gluten, KumaMax has the potential to degrade the immune-reactive parts of gluten before they exit the stomach in order to decrease an immune response and reduce the symptoms and intestinal damage associated with celiac disease.
Under the terms of the development agreement, PvP will conduct all research and development through Phase 1 proof-of-principle studies according to a predefined development plan. Takeda will fund $35 million for PvP’s expenses related to the plan in exchange for an exclusive option to acquire PvP following receipt of a predefined data package. Upon PvP’s successful completion of the development plan, Takeda may exercise its option to acquire PvP by paying an undisclosed fee as well as development and regulatory milestones.
The KumaMax project began in 2011 when students in Dr. David Baker’s laboratory at the University of Washington (UW) were designing, building and testing a biological molecule or system as part of a project at MIT, according to Ingrid Swanson Pultz, senior research fellow at the UW Institute for Protein Design and co-founder of PvP, as well as the company’s chief scientific officer. “Some of the students had friends with celiac disease, and they decided to work with the Rosetta Molecular Modeling Suite to take the amino acid sequence and use software tools to design new proteins. They applied the tools of protein design to address the problems of celiac disease.”
Celiac disease, she explained, is an inappropriate intestinal response to gluten, which is only partially digested, causing an inflammatory immune response. By designing an enzyme similar to the one in the GI tract—but one that could break down gluten—the students reasoned that they could stop the disease before it started. They produced the enzyme over three months, tested it in the lab and developed a prototype. A paper was published in 2012; Swanson Pultz took on the program as a postgraduate project and then as a faculty member.
Using the technology invented at the Institute for Protein Design at University of Washington, PvP was founded in 2012 with grant funding. By 2015, PvP had developed a strong team and was ready to go into human studies, Swanson Pultz said. Today, PvP Biologics has corporate offices in San Diego and research laboratories in Seattle.
According to Adam Simpson, president and CEO of PvP Biologics, “The transaction is unique and very progressive. Takeda’s GI experience and capabilities are a great fit with our goal of developing a novel oral enzyme therapy to make a meaningful impact on the lives of people with celiac disease. In addition, the significant non-dilutive financing provided by Takeda will accelerate therapeutic development of KumaMax. It’s a wonderful opportunity with a high probability of success.”
In more recently breaking news related to Takeda—with a much more substantial pricetag—see the article “Takeda begins tender offer for ARIAD shares” on page 39.