Accelerator PipelineNEWS FROM WARF’S TECHNOLOGY COMMERCIALIZATION TEAM

MAY 2016 WISCONSIN ALUMNI RESEARCH FOUNDATION

The WARF Accelerator Program is one element of an evolving local ecosystem that helps to enable new or established companies to bring UW–Madison innovations to the marketplace for commercial products and services. WARF invests in other

programs and organizations in this ecosystem such as the UW–Madison Law and Business and Entrepreneurship Clinics, Discovery to Product (D2P), Entrepreneurons, UpStart, local venture firms, and most recently gBETA from gener8tor, the WI-based, nationally ranked accelerator for startups. One positive measure of the overall impact of WARF’s support is the extent to which our AP-supported investigators are utilizing these resources to help commercialize their technologies.

Several AP-supported investigators have participated in the D2P Igniter program and engaged with D2P’s team of mentors-in-residence. Among them are Nader Behdad, Mark Cook, Bill Murphy and Scott Reeder, all entrepreneurial innovators representing a very wide range of disciplines, from electrical and computer engineering to animal science.

A number of AP-supported investigators are now enrolled in gener8tor’s gBETA program, a pre-seed financing accelerator limited to teams that are connected to a Wisconsin college or university. The third gBETA class of five teams includes three entrepreneurial innovators with a link to the Accelerator Program. Two of the startups are currently focused on AP-supported technologies: Linectra is focused on metal 3-D printing technology developed by Rock Mackie and OpenNF is focused on network function control software based on technology developed by Aditya Akella. The third startup, SciArt, will be commercializing copyrighted design optimization software assigned to WARF by Krishnan Suresh and now licensed by WARF to his startup. Prof. Suresh received AP support for a different IP asset in this same space and we are excited to see all three of these AP alumni moving forward toward commercial success with the benefit of insight and expertise gained through their participation in gener8tor’s gBETA program.

— Leigh Cagan, lcagan@warf.org

The WARF Accelerator Program

speeds the development of

technologies with exceptional

potential for commercial success.

With targeted funding and expert

advice from seasoned business

mentors known as Catalysts, the

Accelerator Program helps inventors

develop their technologies and

advance to the marketplace.

The latest updates:

COMPUTER SCIENCE

DARK SILICON: The microprocessor industry is facing a critical juncture as demand pushes transistors to the max. But the much publicized

decline of Moore’s Law isn’t deterring Karu Sankaralingam. The professor of computer science is designing a real-time speech recognition chip that could provide massive energy savings and spawn new types of consumer devices. Speech recognition – in everything from phones to cars – is a $130 billion market.

Elements of this project have helped Sankaralingam land a Google Faculty award. Meanwhile, he and a collaborator in the business school have applied for special NSF funding to help build a prototype.

SOFTWARE SOLUTION: Computer scientist Aditya Akella and his team look to improve the management and scalability of next-generation computer

and 5G networks. Their technology, called OpenNF, enables network operators to replace dedicated hardware infrastructure (e.g., firewalls, load balancers, carrier grade NATs) with software, which will be critical in the rollout of new networks.

OpenNF was one of five teams admitted to the gener8tor gBETA program for spring 2016. They are currently tooling their business strategy and value proposition. In April they presented to more than 150 investors from across Wisconsin and Illinois.

TOMORROW’S ELECTRONICS: Michael Arnold and Padma Gopalan are pioneers in the field of materials science. The duo are refining a process to create field effect

transistors out of carbon nanotubes – super thin rolls of carbon that are among the best conductors known.

The team has increased performance by more than sevenfold and plans to publish their high profile results in the coming months. Meanwhile they continue to work closely with an electronics startup on the West Coast.

BIOPHARMACEUTICALS

INTRANASAL DELIVERY: Delivering drugs directly into the brain currently requires invasive surgery because a cellular layer called the blood-brain

barrier (BBB) blocks most therapeutic agents. This has confounded treatments for Alzheimer’s disease, brain cancer and other afflictions of the central nervous system.

Assistant prof. of pharmacy Robert Thorne wants to bypass the BBB altogether

BUILDING MOMENTUMTECHNOLOGY MONITOR

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Investing in tomorrow’s hardware, healthier herds, next-generation networks and more

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Accelerator Chronicle

CHEMIST “TUNING UP” POTENTIAL NEW THERAPEUTIC FOR WORLD’S DEADLIEST DISEASE

The 2003 discovery of PCSK9 – a protein with a clunky name and unknown function – would solve a genetic mystery on two continents.

In Paris, a group of researchers was tracking families suffering from abnormally high cholesterol. Around the same time in Dallas, scientists were astounded by a handful of cases registering extraordinarily low levels. In both instances, genetic sequencing quickly homed in on PCSK9.

The correlation sparked a gold rush in the pharmaceutical world.

Within nine years the first antibodies entered clinical trials. By 2015, two new drugs for treating cardiovascular disease were on the market.

It was translational medicine at warp speed, a discovery-to-product surge perhaps unmatched in the modern genomic era. And the story is far from over.

What makes Proprotein Convertase Subtilisin/Kexin type 9 the most exciting frontier in heart health since the invention of statins?

In his office in the pharmacy school, Weiping Tang gives a bold answer: target-ing PCSK9 is a game changer in how we think about and combat cardiovascular diseases, the number one cause of death globally.

Cardiovascular diseases, caused by LDL (“bad”) cholesterol building up as plaque and clogging arteries, kill more than 17 million people every year. And they’re a multibillion dollar scourge.

“Lowering cholesterol has the highest market share among all pharmaceuticals,” says Tang.

Sales of Lipitor alone topped $13 billion annually before it went off patent.

Statins (like Lipitor) are the blockbuster therapy of choice. However, approximately one in five patients cannot achieve the desired results due to side effects. For these patients, an alternative is needed.

That’s where PCSK9 comes in.

To understand how, Tang describes the process by which our bodies regulate cholesterol:

When LDL cholesterol travels through the bloodstream, receptors on the surface of liver cells catch the particles, haul them inside and degrade them. A job well done, the receptors then return to the surface of the cell to look for more interlopers.

The same cells secrete PCSK9 protein to bind to the receptors and act as a sort of referee. The problem is that PCSK9 can end up degrading the receptors themselves. The result is dead receptors, and cholesterol getting a free pass.

The process is a big red bullseye for pharmaceutical intervention.

But the drugs that sped to market so quickly following the 2003 discovery are antibodies, and antibodies have drawbacks.

“They require injection which is not ideal, and in some patients there are undesired immune effects because these are biological drugs,” says Tang.

His team of multidisciplinary collaborators (most notably, biochemist and lipids expert Alan Attie) are taking a different approach. Through their collective efforts, the team has been able to identify several small molecule secretion inhibitors that appear highly promising.

The inhibitors are inspired by a class of compounds called indoles that are naturally occurring (e.g., serotonin and tryptophan) and used widely in pharmaceuticals. Indoles and their derivatives are found in drugs for treating everything from cancer and schizophrenia to HIV and asthma.

With support from the WARF Accelerator Program, the team is fine-tuning the pharmacological properties of these small molecules for in vivo studies. Tang says this phenotype-based strategy is the most successful approach for developing first-in-class drugs.

He has reason for optimism. At this stage, the in vitro results are dramatic.

The project now faces a critical juncture. Tang, a Stanford- and Harvard-educated synthetic chemist, is currently “tuning up the soft spots” in the molecules, optimizing their structures to make them more potent, soluble and metabolically stable before proceeding in vivo.

He says support from the Accelerator Program has been essential to moving the project forward. Pharmaceutical development is a marathon not a sprint,

Cardiovascular diseases are the leading cause of death

globally, and statin therapy is not always effective.

Discovery to Promise

continued on page 4 >

Weiping Tang

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Venture capital has woken up to find agriculture is no longer grandpa’s farm. But to feed the future our vast and complex food system needs to get smarter. Today’s best tech won’t get us even halfway there.

Q: How did you get involved with the Accelerator Program? A: It starts with the reputation of UW–Madison and WARF. I should tell you that my full time job these days is looking for new technologies in the food and ag sector since I’m running a venture capital fund that invests strictly in those areas. This was a natural.

Q: Venture capitalists invested $1.4 billion in ag tech in 2015, a 17x increase in just four years. What’s driving the boom? A: One driver is thematic investors who are looking at global trends – a near shortage of commodities back in 2008-09, a growing global middle class that wants to eat more meat and less grain – and concluding that this will be a profitable area. The other big driver is that agriculture and food have finally become recognized by the venture community. Venture capital was invented around computers and software back in the 1970s and 80s and then it moved into health care. But it has largely overlooked agriculture until recently. In 2006 I was unable to find a single specialized food and ag fund in North America, even though there were over 800 private venture funds.

Q: Can the Midwest keep up with the coasts?

A: It’s true that we don’t have the same history of venture capital here. That’s been a challenge. But we set ourselves up [in Chicago and Indianapolis] because the biggest concentration on the planet of food and ag R&D is in the Midwest and around our land grant universities.

Q: The U.N. has called for doubling annual food production by 2050. Possible? A: The food system is in need of constant innovation; today’s best technologies will only get us 30 percent of the way there. If we fail to keep up we pay a stiff penalty as we saw in the recent commodity price spike. When the price of corn went from $2.25 a bushel to $7.80 there were food riots in Mexico. The Arab Spring was in large measure driven by the spike in food prices. Everyone was caught off guard. We don’t have to fall too far behind the curve to have dire consequences.

But I wouldn’t bet against the American farmer or the global farmer or the food system. It does require continued innova-tion and continued investment. That seems to be happening.

Q: It seems like someone who wants to feed the world cares deeply about people. Is this as much a calling for you as a job? A: Everyone involved in feeding the world is engaged in what I consider to be a fairly noble undertaking. Someone once said to me that the U.S. has a six month supply of oil that’s officially known as our national strategic reserve. And then he went on to say that the U.S. has a 45-day supply of food that is officially known in Washington as our “surplus problem.”

Most people don’t realize that the human race lives on the edge. And while we’re very good, and the American farmers in particular are astounding at their ability to year after year meet the needs of society, we’re only one or two bad seasons away from some serious challenges. So yes. I see this as a calling to buttress this system, to help support all these wonderful people who are keeping us fed and secure.

Q: What new technologies are needed in this sector? A: The short answer is: across the board. Food safety is one area – everything from diagnostics to natural ways to pasteurize, decontaminate and guarantee quality. A second area is labor. Increasingly the supply of seasonal labor in the developed world is being strained. Automation,

robotics and artificial intelligence are very profitable areas to invest in because the world no longer has the luxury of hundreds of thousands of people on demand at low prices.

Also, waste reduction and recycling. The amount of food we produce on this planet that ends up being wasted is currently between 30 and 40 percent. Finally, health. We’re seeing everything from apps that can be used to tell how fresh a head of lettuce is, to indoor farming that grows produce more uniformly and with less waste and no insects or need for crop control chemicals.

It’s an amazing range. It should probably be considered a half dozen sectors and not one.

Q: Where does university research fit in? A: It’s foundational. We need to understand everything from genetics to

The Leading EdgeThe Constant Innovator

NAME:Ron Meeusen

TITLE:Managing director of Cultivian Sandbox

EXPERIENCE:Meeusen cofounded Cultivian Ventures, the first pure-play venture capital fund dedicated to food and ag technology. He has led R&D for major corporations in agricultural chemicals, plant genetics and breeding, animal health, novel foods and industrial materials. His projects include the world’s first field trial of a genetically engineered crop trait in 1986, launch of one of the first insect- and herbicide-resistant corn hybrids, introduction of a trans fat-free canola oil, and development of dozens of new crop varieties on three continents.

Meeusen holds a Ph.D. from UC-Berkeley in plant cell biology.

continued on page 4 >

“We’re only one or two bad seasons away from some

serious challenges.”

and deliver drugs intranasally. Thorne’s group continues to study a natural enzyme called matrix metalloproteinase-9 (MMP-9) that makes the nasal lining more permeable to drugs. Toxicology studies in animals have been completed, with results indicating that MMP-9 nasal spray does not negatively affect sense of smell or build up in cerebrospinal fluid. Immunochemistry studies are now underway to better understand the mechanism of action.

FOOD SCIENCE

EARLY DETECTION: Johne’s disease affects more than half of the dairy herds in the U.S. alone and costs the industry more than $200 million every year.

The disease is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Current diagnostic tests are not sensitive enough to detect infection at an early and more treatable stage.

Initially, microbiology prof. Adel Talaat set out to develop a faster solution based on biomarkers. His group has now validated several key genes, and in the next phase of the project they will work on incorporating the identified biomarkers into their diagnostic test.

LIVESTOCK HEALTH: A team of researchers might have found an alternative to antibiotic treatment of respiratory disease in beef cattle. Mitch Schaefer, Mark

Cook and Dan Schaefer of the animal sciences department are investigating whether interleukin-10 (IL-10) antibodies administered in feed can promote healthy growth in beef animals and cut antibiotic usage at the same time. Early trial results show promise. A company has expressed interest in the work, and conversations are ongoing.

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For more information about available WARF technologies, please contact the technology commercialization team at licensing@warf.org.

The WARF Accelerator Pipeline is published by WARF Communications, 614 Walnut Street, 13th Floor | Madison, Wisconsin, 53726.

TECHNOLOGY MONITOR …continued from page 1

WARF supports a pipeline of promising projects in an effort to accelerate the public benefits of technologies developed in university laboratories.

Visit warf.org/pipeline to see a list highlighting the Accelerator Program’s projects in medical devices, biopharmaceuticals, computer-related sciences and other fields.

and he knows that he’ll need years more data before broaching industry.

“The more work you put in at the beginning,” he says, “the higher chance that the pharmaceutical company will take the licensed compound into clinic.”

He also values the technical insights provided by Brad Henke, who recently joined the Accelerator Program as a biopharma Catalyst. Henke directed chemistry at GlaxoSmithKline for years and led research teams that produced 10 clinical drug candidates.

Tang says they “share a common language.”

Approaching his tenth year at UW–Madison, Tang is uniquely qualified to lead the project. He is co-director of the new UW Medicinal Chemistry Center, launched last summer. The center’s mission is to design and synthesize the drugs of tomorrow by collaborating with UW–Madison biomedical researchers.

Current projects include new therapeutics for treating diabetes, breast cancer, metabolic disorders and autoimmune diseases.

With a cool and confident demeanor, Tang carries the heavy mantle of his work in stride. But a stunning quote on the bottom of his slide deck seems to reveal his inner thoughts. It comes from science writer Stephen Hall, writing in the journal Nature:

“Of all the intriguing DNA sequences spat out by the Human Genome Project and its ancillary studies, perhaps none is a more promising candidate to have a rapid, large-scale impact on human health than PCSK9.”

thermodynamics to economics if we are to run this system on which we all depend effectively and efficiently.

But it’s also changing dramatically. More and more the universities are being called upon by society to be economic engines. They are an indispensable weapon in international competition. If the U.S. economy is going to compete we can’t have our universities standing on the sidelines. They are juggernauts of knowledge and technology that the nation needs engaged.

Q: Is that an asset of the Accelerator Program? Engaging inventors and building networks? A: Absolutely. One thing that should never be lost is how big, complex and sophisticated our food systems are. None of us are experts on even a significant portion of it. It’s an old cliché but it gets driven home in this line of work – we are all smarter than each of us individually.

The Leading Edge …continued from page 3

Accelerator Chronicle…continued from page 2

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