Barely two months ago, synbio company PvP Biologics, spun out of Washington University. Last week, the company closed a $35 million deal with medical company Takeda to cover phase 1 clinical trials of KumaMax, a new engineered protein capable of breaking down the immune-reactive parts of gluten in the stomach, potentially bettering the life of around 74 million people worldwide estimated to suffer from gluten intolerance.

From iGEM to Company

The work behind the development, however, began five years ago. In 2011, a group of University of Washington undergraduates presented a computer-generated protein design to combat the symptoms of celiac disease as their entry for that year’s iGEM competition. The logic behind their idea was that instead of focusing on substrate specificity when choosing their base candidate enzyme, they would first identify an enzyme that was already capable of working properly in the necessary conditions – that is, in the highly acidic pH level of the human stomach. Once said that base enzyme was selected, the team worked to reengineer its substrate specificity through in silico tools, making it now gluten-specific. They went on to become the first US team to win iGEM's global prize.The project could have ended there, with a nice gold medal and a new BioBrick to UW’s name in the Registry of Standard Biological Parts. Instead, recent pHD graduate Ingrid Swanson Pultz decided to take up the further development of KumaMax as their post-doctoral project in 2012 in David Baker’s Institute for Protein Design. “The enzyme that the students had generated was still a prototype at that point,” says Swanson, “so my goal was to further engineer it and then use more sophisticated methods to test it.”Swanson’s interest in engineering life from its base translated nicely from her childhood to her pHD and eventually to the company she founded. “Having been obsessed with Legos as a child, I’ve always loved the idea of building something that becomes more than the sum of its parts “I liked the idea of studying life on its most basic level, as a simple closed system.” When she applied to graduate school, her goal was to learn as much as she could about how bacteria work on a molecular level, since the better she knew their inner working, the better she could reengineer them. “This was in 2005,” notes Swanson, “and I had never heard of the term “synthetic biology”, but that’s what I was interested in”.After reading about iGEM in Nature and finding out the University of Washington, where Swanson was getting her pHD, did not have a team for the competition, she decided to take matters into her own hands and fund the first team at the University in 2007. Years later, the 2011 team was advised by David Baker, Justin Siegel and Swanson herself. After the competition, the students performed a few more experiments, published a paper and later left for graduate schools. Justin, David and Ingrid founded PvP the following year.

The tech

KumaMax now arises as perhaps the only near-future available treatment for celiac disease. True to the initial concept conceived in 2011, the enzyme will be consumed orally and break down the immune-reactive parts of gluten, thereby avoiding damage to the patient’s small intestine and any other painful symptoms that accompany accidental gluten ingestion. Just like lactase pills for the lactose intolerant, KumaMax is probably not going to allow a patient to blow through pizza and beers like it’s nothing, but it quite certainly defeats having to avoid gluten at all costs with near to religious fervor.

The impact

It is estimated that celiac disease affects around 1% of the population worldwide, with distributions varying according to ethnicity and closely related to the prevailing regional diet. This autoimmune syndrome affects mainly the small intestine, where exposure to gluten causes an abnormal inflammatory reaction that irritates the intestinal mucosa. The health problems caused by this intolerance include gastrointestinal symptoms, malnutrition, weakness, anemia, growth problems, among others.Misdiagnosis is so common that close to 80% of the celiac population might not be aware of their condition. The symptoms can look like lactose intolerance, like cystic fibrosis, or just like a picky kid throwing a temper tantrum. These happen to be the conditions my brother was mistakenly diagnosed with fifteen years ago, when celiac disease was still a novelty.Up until now, a strict gluten-free diet and hoping for the recovery of the intestinal mucosa was the only option. Now, KumaMax may give celiac patients much needed freedom and peace of mind. “In pre-clinical experiments,” said Tadataka "Tachi" Yamada, MD, chairman of PvP Biologics, to BusinessWire, “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.”

The deal

Keeping in mind that the average drug development process was recently pegged by Tufts CSDD at $2.558 billion, with over 10 years needed to finalize the cycle, it’s hard not to feel awed with PvP Biologics’ seemingly out of nowhere deal with Medical Innovation company Takeda barely two months into the company’s official spin-off from Washington University. More impressive still, is to have managed to cover Phase I without having to raise a traditional round from a venture group. Upon the terms of the development agreement with Takeda, PvP Biologics will conduct all research and development through phase 1 proof-of-principle studies, funded by Takeda with $35 million to cover expenses related to their development plan. And now for the silver lining: the funding comes in exchange for an exclusive option to acquire PvP Biologics (for an undisclosed fee) upon successful completion of the plan and corresponding regulatory milestones. Talk about an exit strategy.This impressively non-traditional funding strategy has left the industry reeling. “Tachi is really the one who had the idea to go directly to pharma and avoid the traditional financing,” Adam Simpson, CEO of PvP Biologics said in an interview with Medcity news, “In terms of what it means for us, and celiac patients, we think there is an improved probability of technical success because we have access to a world leader in GI.”But notably enough, the Takeda deal was not the company’s first plunge into non-traditional financing. “We were planning on spinning off much sooner,” says Swanson, “but a fortuitous thing happened: David Baker’s Institute for Protein Design got off the ground, and started a Translational Investigator program. This program is for individual scientists who are working on something that is on version 1 but could ultimately become commercially viable given sufficient development. The program is meant to bridge the “Valley of Death”, and Translational Investigators are expected to leave within a few years after the start of their position with a company based on their technology. The Institute hired me on as their first Translational Investigator, and I was awarded a faculty position in the Department of Biochemistry. My research scientist, Clancey Wolf, and I then further developed the enzyme at the Institute supported by outside grant funding from the WA State Life Sciences Discovery Fund, which supports early-stage commercialization projects. We were able to perform this non-traditional mode of funding because we had such strong internal support, and because the Translational Investigator program was available to us through the Institute, we were able to incubate at the Institute and have access to all the wonderful UW resources in order to perform our work. Then in late 2015 - early 2016, we began looking for a partner that could help to take this out of the University once the enzyme was fully developed.”The Takeda deal is just the tip of the iceberg that’s been PvP Biologics’s story: an impressive collection of non-traditional development, which will hopefully pave the road for more ways of developing faster, more impactful solutions based on what synthetic biology now enables us to do.