BioMed Valley Discoveries

Improving human health by combining a philanthropic mission with industrial capabilities

At first glance, BioMed Valley Discoveries (BVD) doesn’t have much in common with traditional biotech or pharmaceutical companies. There are no research laboratories, no manufacturing plants, and no gleaming headquarters. Instead, a handful of offices spread over Kansas City, Missouri, and Boston, Massachusetts, house a new kind of drug development company—one that goes about its business in a fundamentally different way.

From behind their desks, a handful of physicians and scientists direct a global network of almost nine hundred researchers, clinicians, regulatory experts, clinical trial coordinators, drug manufacturers, and consultants. “We are among the first to execute drug discovery and development on what could be called a virtual basis. This approach minimizes the bricks and mortar infrastructure and enables us to move much more quickly than we otherwise could,” explains BVD President Saurabh Saha, MD, PhD. “Most important, the virtual approach allows us to work with very talented and knowledgeable experts from around the world and create an all-star team for the duration of each project.”

But BioMed Valley Discoveries is unusual in more ways than one. When Jim and Virginia Stowers’ vision of an innovative medical research institute started to take shape, they knew that basic research was just the beginning. They wanted to make sure that the path from basic discovery to practical application was as smooth as possible.

Patients first

Typically, nonprofit research organizations rely on a central technology transfer office to protect and market their discoveries. The tech transfer office facilitates the patenting of potentially valuable discoveries and focuses on licensing the intellectual property to industry partners for further development. But without additional work to make a technology attractive for licensing by drug development companies, many promising potential treatments fail to generate interest and often linger for years on the shelves of universities and research institutes nationwide.

To speed discoveries from the lab to the clinic, Stowers decided to separate “discovery and development” from the institute’s basic research activities and create a for-profit company with its own distinct focus on bench-to-bedside translational research. They charged the organization they created, BioMed Valley Discoveries, with developing laboratory discoveries from the institute and elsewhere into new therapies and diagnostics. Although technically a for-profit company, BVD’s unique ownership structure means that all profits generated by BVD will be either reinvested in BVD or funneled back to the Stowers Institute to support additional basic research.

With a long-term perspective in mind, Stowers set up BVD with over $50 million in seed funding and a firm commitment to a steady stream of future funding. This exceptionally stable source of financing enables the nontraditional biotech to focus on long-term impact rather than short-term returns. “Our unique funding structure allows us to tackle projects that may be considered too early, too risky, or too challenging for traditional biotech or pharmaceutical companies,” explains Saha, who directed Novartis Pharmaceuticals’ new drug discovery incubator before he was recruited in 2008 to head BVD.

Combining clinical and research training with MD and PhD degrees from the Johns Hopkins School of Medicine and business training from McKinsey & Co. and Harvard Business School, Saha is intimately familiar with the forces that drive the science and business of drug development. “What sets BVD apart is our relationship with the Stowers Institute and our exceptional focus on helping patients. We are a for-profit company, but our first objective is to address unmet medical needs and, in whatever we pursue, our goal is to change medicine. Not incrementally, but substantially.”

Filling the pipeline

BVD was originally conceived as the Stowers Institute’s “translational arm,” a company with the capability to transform Stowers investigators’ research findings into new treatments. As BVD’s strategy evolved, it became clear that BVD could help patients both by advancing Stowers Institute discoveries as well as those made at other research institutions. Encouraged by Jim Stowers and the company’s board of directors, Saha cast the widest net possible to uncover developable technologies from organizations around the world.  

What followed was a very deliberate process of whittling down the list of candidates to the most promising projects. “In addition to the opportunity of addressing an unmet medical need and approaching a problem from a new operational or intellectual angle, we selected projects where we saw the potential of taking the technology not just to the next stage, but all the way to patients,” says Saha. Now, barely four years after starting work on the current slate of projects, BVD is advancing seven different drug candidates and diagnostic technologies, ranging from tumor-fighting bacteria to a new imaging tool that detects bacterial infections in artificial joints.

When patients are injected with FIAU molecules, bacteria in the body take up FIAU molecules and trap them inside. The accumulation of FIAU can then easily be tracked with high-resolution positron tomography (PET) scans to reveal an infection’s source. The new technology holds great promise for identifying notoriously hard to detect prosthetic joint infections and determining the extent of diabetic foot infections.

Illustration: Katie Vicari

Tracking down intruders

With Phase II clinical trials already in full swing, the imaging project is leading the way. Originally developed at Johns Hopkins, the new imaging technology exploits the difference in enzymatic activity between human cells and bacteria to track down hard-to-detect bacteria before they can cause life-threatening infections.

Many cells, including most species of bacteria, use the enzyme thymidine kinase to construct one of DNA’s building blocks. The enzyme’s bacterial version prefers a chemical known as FIAU, short for fialuridine, to its natural substrate. When patients are injected with chemically labeled FIAU, bacteria in the body take up the easily tracked molecule. FIAU accumulation can then be detected with high-resolution positron emission tomography (PET) scans to reveal the infection’s source.

BVD is currently testing the technology for two different disease indications: prosthetic joint infections and diabetic foot infections. “In the U.S., about one million joint replacement procedures are performed annually,” says Michelle Zhang, PhD, who oversees the FIAU project. “Anytime a foreign object, such as an artificial hip or knee joint, is introduced into the human body, patients are more likely to develop an infection in that joint.”

Unfortunately, the symptoms of infection—localized swelling, redness, and pain—resemble inflammatory symptoms caused by normal wear and tear or the mechanical failure of an implant. Conventional imaging techniques and other tests often fail to distinguish between the two since they don’t directly detect bacteria. As a result, many patients with misdiagnosed prosthetic joint infections undergo replacement surgeries followed by weeks of rehabilitation when the cause of the problem could have been treated with a simple course of antibiotics. “Often, these revision surgeries are performed without appropriate debridement and antibiotic treatment, which puts patients at risk,” says Zhang.

Diabetic foot infections, one of the most common and serious complications of diabetes mellitus, present a different challenge. As many as two thirds of infections will spread to the bone and require amputation if not treated aggressively. MRI scans, the current diagnostic procedure, can only identify a fraction of bone infections. Plus, many diabetic patients have poor kidney function and cannot tolerate the contrast dye required for MRI imaging. “We hope that FIAU will help physicians decide how aggressively they need to treat diabetic foot infections and spare some patients from major surgeries,” says Zhang.

The genetically modified bacterium C. novyi-NT can only multiply within large tumors whose center is no longer adequately supplied with oxygen. The bacteria hone in on these “dead zones” and destroy the tumor from the inside with minimal damage to healthy tissue. When C. novyi-NT runs out of cancer cells to consume, the bacteria stop growing and are subsequently cleared by the body. Certain bacteria produce spores—hardy dormant versions of themselves that can be easily stored.

Illustration: Katie Vicari

Busting tumors

Despite huge inroads into cancer treatment during the last few decades, it is still a leading cause of death in the developed world, and scientists are constantly looking for new ways to eradicate tumor cells. BVD has recently been advancing a novel approach developed by renowned cancer researcher Bert Vogelstein, MD, at the Johns Hopkins School of Medicine. In sharp contrast to conventional chemo- or radiation therapy or even personalized cancer treatments, the new treatment relies on bacteria to destroy tumors from within.

As solid tumors increase in size, they outstrip available oxygen and nutrient supplies. This leads to hypoxic areas inside the tumor that are resistant to conventional radiation and chemotherapy, but still have the potential to harbor cancer cells capable of metastasizing. The bacterium C. novyi-NT, however, thrives under these conditions. It homes in on the “dead zone” and destroys tumors from the inside with minimal damage to healthy tissue. When C. novyi-NT runs out of cancer tissue to consume, the bacteria stop growing and become inactivated. Subsequently, they are cleared naturally by the body.

Even with its potential as a novel cancer therapy, many pharmaceutical companies consider bacteriolytic therapy, such as C. novyi-NT, too unconventional and risky. “Because BVD has a unique source of funding and mission, we have the freedom to pursue promising but unprecedented strategies that require a long-term investment and commitment,” says Saha. BVD licensed C. novyi-NT from Johns Hopkins, and Linping Zhang, PhD, the project team director, assembled a worldwide group of medical oncologists, FDA regulatory experts, physician investigators, clinical trial leaders, pharmacologists and toxicologists, drug manufacturers, and veterinarian oncologists, among others.

In an unusual complement to traditional preclinical studies, BVD is treating dogs that have developed cancers to assess the safety and effectiveness of C. novyi-NT. “Pet dogs naturally develop a variety of cancers for the same reasons that humans do,” explains Linping Zhang. With limited treatment options available for canine cancers, most dogs suffering from malignant tumors face euthanasia or amputation. Owners who choose to participate in the C. novyi-NT canine clinical study give their dogs a chance to avoid these fates and also help generate valuable data to identify a better therapy for humans. “The opportunity to study our drug in dogs with spontaneously occurring tumors will likely provide valuable perspectives for optimizing therapy in human cancer patients. Even though we are still generating more data, we believe that a drug that works in dogs is much more likely to succeed in human patients than a drug that has only been tested in mice,” she says.

Early results from the studies in pet dogs have been encouraging. Human Phase I clinical trials designed to assess the safety of the C. novyi-NT therapy and uncover potential side effects have begun in earnest. “The available data has shown great promise, but, as with any novel therapy at this stage, we still have a long way to go to realize that promise,” says Zhang.

Dean Welsch, PhD

Improving human health

In addition to new tools that track down infections and bacteria that attack tumors from the inside out, BVD has several other cancer therapeutics and a pain treatment under development. One of these, a more traditional cancer drug therapy, illustrates the strength of BVD’s virtual approach. This drug targets a specific genetic vulnerability frequently found in melanoma, pancreatic cancer, and a subset of colon and lung cancers. About a year after licensing that compound—currently referred to as BVD-523—the company has started Phase I clinical trials in patients with metastatic melanoma and other solid tumors.

In an unexpectedly short time, BVD’s global network of partners generated more than thirteen thousand pages of preclinical data on the experimental drug. BVD used this data for the successful submission of an Investigational Drug Application to the FDA, the prerequisite to start clinical trials in human patients. Dean Welsch, PhD, who leads a team of more than a hundred experts, consultants, and fee-for-service partners, says that, “assembling a team of talented people with years of experience in the area you need takes extra effort and coordination, but can make the process very efficient.”

In the end, it all comes back to Jim and Virginia Stowers’ guiding values—a commitment to excellence and teamwork, a long-term perspective, and an unwavering dedication to improving the lives of others. Those principles drive each entity of the intertwined triad of organizations founded by the Stowerses. Founded in 1957, American Century Investments helps its clients achieve their financial goals while its “profits-with-a-purpose” philosophy provides the funding for work at the Stowers Institute and BVD. Opened in 2000, the institute seeks an understanding of life’s basic mechanisms to lay the foundation for the development of novel treatments and diagnostics. BVD, the youngest of the three, has the mission of improving human health through medical innovation. Together, the three organizations aspire to fulfill Jim and Virginia Stowers’ grand vision of giving people around the world “Hope for Life®.”