Indiana University Distinguished Professor Dr. D. Wade Clapp is known internationally for his innovations in treating neurofibromatosis Type 1, or NF1, a rare genetic disease that causes tumors to grow in nerves throughout the body. Clapp's expertise and the past successes of his team at the IU School of Medicine make his lab an ideal partner for Healx, a British biotech company that uses artificial intelligence to develop novel treatments for rare diseases.
"If we didn't have the valid preclinical models and advice of Dr. Clapp and his team, we wouldn't have known which of our AI-driven drug predictions would have been a good one to bet on for clinical success," said Simone Manso, head of neurofibromatosis therapy development at Healx.
This collaboration that began in 2019 has progressed to clinical trials for HLX-1502, a new drug compound showing promise for shrinking tumors with minimal side effects.
Clapp leads in a new role as senior associate dean for entrepreneurial research and commercialization at the School of Medicine and serves as a scientific lead for the IU Launch Accelerator for Biosciences. Photo by Liz Kaye, Indiana University
"Given the comparatively small number of patients with any genetic disease and many of these patients being children, it is important to develop preclinical animal models that closely mirror the human condition," said Clapp, chair of the IU School of Medicine's Department of Pediatrics. "Our laboratory has worked to do that over the past 20 years for both the malignant and nonmalignant conditions of NF1 and a related genetic disease, NF2."
In his new role as senior associate dean for entrepreneurial research and commercialization at the School of Medicine, Clapp is also serving as a scientific lead for the recently launched IU Launch Accelerator for Biosciences. Known as IU LAB, this first-of-its-kind academic-industry initiative will position Indiana as a national leader in bioscience discovery.
Manso said IU is way ahead of most universities when it comes to supporting industry partnerships and speeding up the drug development process, making IU a good partner. Without public-private partnerships, he said, "There would simply be no cures for rare diseases."
Healx's formula for success: AI + IU
NF1 affects one in 2,500 people worldwide. Tumors can grow anywhere in the nervous system and may cause cognitive issues, heart conditions, vision loss and pain. In some cases, it may become cancerous.
Biotech companies traditionally like to put their dollars behind diseases affecting larger numbers of people, which offers potential for a higher return on investment. Research into rare disease mechanisms is most often left to universities, with funding from federal agencies and charitable foundations.
Healx uses AI technology to increase its odds of success. Its platform analyzes millions of drug and disease data points to find novel connections that could be turned into new treatment opportunities. While AI provides a jump start, experts like Clapp are needed to fine-tune the selection process and test the most promising therapies.
"We developed a lot of drug predictions using our AI platform, but we didn't know where to test them, how to test them and how to make sense of them with NF1 preclinical knowledge," Manso said. "Dr. Clapp and his entire team are what I would call the best in NF1 for their preclinical in vivo model, which has shown a very strong translation into human trials."
Healx isn't Clapp's first industry partnership. His lab has tested other neurofibromatosis drugs over the years, including one that is currently FDA approved for treating NF1. But Healx's drug is unique in its potential for effectively shrinking tumors without significant side effects including skin issues, nausea, mouth sores, fatigue, headaches, muscle weakness and more.
"We hope the NF1 community will not have to make this tradeoff between seeing their tumors shrinking versus having problems with their quality of life from the significant side effects of other drugs," said Manso, whose passion is fueled by a strong personal connection to the NF1 community. "Based on the data we have so far, the safety profile of our drug looks much, much better."
Collaborative science a win for patients
Manso and Clapp both serve on the Children's Tumor Foundation Board of Directors. In 2020, Clapp received the foundation's most prestigious award for his significant contributions to neurofibromatosis research and clinical care. He credits his team at IU.
"We've been fortunate to develop and retain a highly committed research team in our own laboratory and have had great support throughout the School of Medicine, but particularly in genomics, clinical pharmacology, the laboratory animal staff and the Wells Center," Clapp said.
The IU team tested Healx compounds in cell cultures and in genetically engineered mouse models that have a strong track record of faithfully forecasting therapeutic activity in humans. Now IU is a site for the INSPIRE-NF1 study, a Phase 2 trial for HLX-1502 enrolling 20 NF1 patients through the Neurofibromatosis Clinical Trials Consortium.
"The consortium and its 23 member sites provide the clinical trial infrastructure, patient access and expertise in running clinical trials," said Dr. Steven Rhodes, who leads consortium operations at IU and co-directs the IU Health Neurofibromatosis Multidisciplinary Program. The NF clinic at Riley Hospital for Children sees 300 to 400 patients a year from throughout the state and region.
"I think this partnership is an outstanding example of how we can fast-track the translation of therapies from the lab to the clinic in only a few short years, whereas historically, this used to take decades or perhaps even longer," Rhodes said.
It's likely the IU-Healx partnership will continue for years to come - a win for people living with neurofibromatosis.
"Dr. Clapp provides advice at the intersection between preclinical and clinical matters, and his perspective, knowledge and views are invaluable," Manso said. "Now we are doing the clinical trials with Indiana University, and we are continuing to do preclinical studies with Dr. Clapp and his team."
