Scripps Research and Calibr-Skaggs awarded $4.5M from the Helmsley Charitable Trust

Michael Bollong, Howard Hang and additional researchers will lead projects to uncover new therapeutic options for Crohn’s disease, one of the most common forms of IBD.

January 29, 2024

LA JOLLA, CA—Inflammatory bowel diseases (IBD), which include Crohn’s disease, affect millions of people around the world and have a profound impact on a person’s quality of life. The Leona M. and Harry B. Helmsley Charitable Trust has granted awards totaling $4.5 million to Scripps Research for two projects that aim to better understand and develop new treatment options for these diseases. 

The Helmsley Charitable Trust is the largest private philanthropy focused on Crohn’s disease. Helmsley is committed to addressing the unmet needs of people living with the disease, as well as investing in research, technologies and treatments that could alleviate and potentially cure this condition.

“We know that current treatment options are simply insufficient for many people with Crohn’s disease,” said Jessica Langer, Program Officer in the Crohn’s Disease Program at Helmsley. “These new projects at Scripps Research hold great promise to advance drug discovery for IBD and will hopefully translate into treatments that will improve lives.”

Tailoring a precision solution

IBD is an immune-related disorder that causes chronic inflammation in the gastrointestinal (GI) tract. Along with ulcerative colitis, Crohn’s disease is one of the most common forms of IBD, and it is characterized by inflammation along any part of the digestive tract. This inflammatory environment, driven by an imbalance between harmful molecules and the immune system, can lead to oxidative stress and cause tissue damage. There are roughly 2 million people globally with Crohn’s disease—many under the age of 35—and that number is growing.

Michael Bollong, PhD, associate chemistry professor and Early Career Endowed Roon Chair for Cardiovascular Research at Scripps Research, is the principal investigator for a $4 million, two-year award to develop an oral small-molecule drug to specifically target the gut and improve IBD symptoms, including Crohn’s disease. Under the award, Bollong will collaborate closely with scientists at the Calibr-Skaggs Institute for Innovative Medicines, the drug discovery and development arm of Scripps Research.

“With this generous support from the Helmsley Charitable Trust, we are driven by a shared commitment to address the pressing needs within the IBD and Crohn’s disease communities,” says Bollong. “A precision medicine could transform the IBD treatment landscape, as patients don’t currently have safe and effective options that are tailored to the specific needs of their disease.”   

Bollong is uncovering IBD therapies that activate a key protein called nuclear factor-erythroid 2 related factor 2 (NRF2), which helps regulate oxidative stress and inflammation in the body. NRF2 activation has been shown to activate antioxidant pathways and suppress inflammatory pathways. So far, current drugs that target NRF2 have not advanced for IBD due to side effects — because they act on other targets besides NRF2, and they have systemic effects outside the gut.

Bollong, working with the Calibr-Skaggs team, aims to overcome these historical hurdles. They are developing oral drug compounds designed to precisely activate NRF2 in the gut, and then quickly clear from the body to avoid potential effects on other tissues. Their lead drug candidate and several backup compounds are selective in targeting NRF2 in the GI tract in IBD mouse models—even when administered at low doses. This tailored approach not only enhances the effectiveness of the drug, but it also minimizes the required dosage, thereby reducing the risk of adverse effects and promoting overall safety.

With the award, Bollong and his team will perform critical safety studies to select a lead compound that will undergo Investigational New Drug (IND)-enabling studies. If successful, the compound will then be investigated in a phase 1 clinical trial.

Translating microbiota mechanisms

Howard Hang, PhD, Scripps Research professor in the Department of Immunology and Microbiology, is the principal investigator for a $500,000, one-year award to uncover new approaches for treating Crohn’s disease.

In his lab, Hang has been studying NOD2: a receptor that plays an important role in maintaining a balanced digestive tract and detecting bacteria. NOD2 works by recognizing components within bacterial cell walls, called peptidoglycans. People with genetic variations of NOD2 are significantly more susceptible to Crohn’s disease because of defective intestinal barriers and aberrant immune responses.  

So far, Hang has shown that NOD2 activation in mice led to improved immunity in the intestine. He’s accomplished this several ways, including by using synthetic enzymes and small molecules to activate NOD2. With funds from the award, Hang and his colleagues will work toward identifying new therapeutic leads capable of activating NOD2, with the intent of improving the health of the intestinal barrier and overall immunity for people with Crohn’s disease. These efforts will include preclinical studies to better understand potential targets’ efficacy and safety. 

“Thanks to Helmsley, our research into the gut microbiota is taking a significant step forward, as it now has the potential to be translated into innovative treatments for Crohn’s disease,” says Hang. “By targeting the NOD2 receptor in these unique ways, there is promise in improving the overall health and disease outcomes in patients with this severe disease.”  

About The Leona M. and Harry B. Helmsley Charitable Trust

The Leona M. and Harry B. Helmsley Charitable Trust aspires to improve lives by supporting exceptional efforts in the U.S. and around the world in health and select place-based initiatives. Since beginning its active grantmaking in 2008, Helmsley has committed more than $4 billion for a wide range of charitable purposes. Helmsley's Crohn's Disease Program supports impactful ideas and mobilizes a global community committed to improving the lives of Crohn's disease patients while pursuing a cure. For more information on Helmsley and its programs, visit helmsleytrust.org. 

About the Calibr-Skaggs Institute for Innovative Medicines

The Calibr-Skaggs Institute for Innovative Medicines was founded on the principle that the creation of new medicines can be accelerated by pairing world-class biomedical research with state-of-the-art drug discovery and development capabilities. Leveraging the unique scientific framework of Scripps Research, Calibr has created a portfolio of drug candidates based on Scripps Research technologies and is shaping a new paradigm for advancing nonprofit biomedical research to impact patients. Learn more at calibr.scripps.edu. 

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked one of the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more at www.scripps.edu.

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