Bold, new approach focuses on developing innovation through next generation clinical trials

The Weiner lab has an ambitious goal: to develop a nasal vaccine to prevent – and reverse – the progression of Alzheimer’s disease (AD). Their work in preclinical models of AD had yielded promising results, preventing the accumulation of amyloid-beta plaques – the hallmark of AD – and dramatically reducing the burden of these plaques in older mice, among other promising measures.

“We felt it was time to translate this work into people,” Howard Weiner, MD, of the Ann Romney Center for Neurologic Diseases, recalls. “In our lab, we like to borrow the phrase from hockey of ‘shots on goal.’ Doing a clinical trial and getting a treatment into people that works, that’s how you score. Of course, not every shot works – most don’t. But to paraphrase Wayne Gretzky, you miss 100 percent of the shots you don’t take. We wanted to take this shot.”

It was at that time that Weiner connected with Lina Williamson, DVM, PhD, director of Entrepreneurship & Innovation for the Translational Accelerator (TA). The TA is a resource and team at the Brigham designed to help researchers take those shots on goal. Weiner’s team had the data and the scientific knowledge to drive things forward. The TA could provide the infrastructure, support and advisement to give them the best chance of making their shot count.

Building Bridges, Making Connections

Among the services the TA offers are access to large cadre of internal and external business and scientific advisors, project management, access to visiting entrepreneurs, and connections with external investors. The TA encompasses two teams that help investigators: an Entrepreneurship and Innovation (E&I) team and a Clinical Operations team. E&I provides strategic planning, business development, project management and market research. Clinical Operations manages BWH’s clinical research facilities and provides expertise in clinical study strategy, design and execution.

The TA also has the expertise and connections to optimally leverage the vast array of scientific and clinical resources already in existence, including scientific cores, IT infrastructure and data from more than 9 million patients. Knowing how and when to leverage specific resources can provide significant efficiencies. For example, new systems which integrate genomic and biobank data with information from medical records and other data warehouses provide query tools which can identify a specific, validated patient population most appropriate for a potential therapy.

To that end, one of the key goals of the newly established TA is to revolutionize translational medicine by advancing next-generation clinical trials. Next-generation clinical trials are those that can match patients with the treatments and tests that may be most effective for them, given their particular genetic and physical make up. Investigators can leverage big data to stratify and select patients most likely to respond to a particular class of drugs. This potentially allows a trial to be conducted with many fewer patients and a higher likelihood of success. Similarly, when a trial is designed appropriately, data mining can allow for iterative adjustments to a trial’s design as the trial is underway, allowing for rapid innovation and optimization of the intervention.

According to Allison Moriarty, a member of the TA’s advisory committee, the TA leverages three components that differentiate BWH from any other place in the world: talented faculty, access to cutting-edge technology and resources and a unique and vast patient population.

“Marrying those three components is something that very few other institutions are capable of doing,” said Moriarty who is also the vice president of Research Administration and Compliance. “We believe the TA will be a critical resource for our entire faculty – both early career investigators who may be conducting a clinical trial for the first time as well as seasoned experts who have plenty of personal experience, but who can benefit from having an infrastructure of support for launching innovative trials.

Our community has tremendous breadth and depth of knowledge on all aspects of getting a clinical trial off the ground, but unless you are incredibly savvy, it’s very hard for an individual to leverage these effectively,” said Moriarty. “The TA is designed to build bridges and help investigators navigate these resources.”

The TA team began working with Weiner six months ago, just as his lab was beginning to design the clinical trial phase of their project. Together, they thought through the manufacturing process to make sure that the drug would be ready in time; tracked the different components needed for FDA approval; developed a business plan; and helped usher the project through all necessary steps for Institutional Review Board approval.

“Dr. Weiner was on the cusp of formalizing all of these pieces when we connected – the TA was able to provide project management support to ensure that all of these components moved forward successfully,” said Moriarty.

A Team of Builders

In addition to a core team of leaders from the Brigham, the TA team includes more than 18 highly skilled, internal advisors who offer rigorous scientific and strategic advisement on projects, particularly those with commercial potential (read more about entrepreneur-in-residence and TA advisor Eamonn Hobbs in a CRN profile here).

Lindsey Baden, MMSc, MD, serves as the TA’s medical director. He says that the TA is re-envisioning how to do clinical translational research.

“Over the last 40 years, we’ve built the human research lab: we have the knowledge and facilities to take careful measurements and do studies in humans safely,” said Baden, director of clinical research in the Division of Infectious Diseases. “We have the ability to do careful, evidence-based clinical trials and to offer the most cutting-edge treatments to patients with diseases like multiple sclerosis, cancer and more. When nobody else can treat you, we can.”

Weiner anticipates that if all goes smoothly, clinical trials for the nasal vaccine for AD could begin as early as 2018.

“I’ve been involved in translating basic research into the clinic for the last three decades,” said Weiner, whose work has led to the development of new therapies for multiple sclerosis and who successfully launched a therapeutics company, Tilos, last year to develop a cancer immunotherapy. “I have a lot of translational research experience, but I can’t do this alone. I needed the TA’s structure and support – that team has been crucial for this project, and we’re now working on other projects with them as well.”

BWH investigators and potential partners who are interested in engaging with the TA can contact the TA administration to learn more about opportunities and offerings.