Uplizna Launch Is a Testament to NC’s Prowess in Drug R&D
When singer songwriter Joni Mitchell wrote “...you don’t know what you’ve got ‘til it’s gone,” she didn’t know Thomas F. Tedder, Ph.D.
Tedder, the Alter Geller Professor for Research in Immunology at Duke University Medical School, knew.
Close to four decades ago he and his team, and a handful of other scientists from around the world, began the search for cell-surface switches that would turn the body’s B-cells on and off. B-cells are important in regulating the immune system. But they’re overactive in many autoimmune disorders and can help cause tissue inflammation and organ system dysfunction.
When Tedder developed unique monoclonal antibodies to target the CD19, CD20 and CD22 B-cell proteins, he knew he was on to something. These antibodies were designed to block the underlying causes of autoimmune disease without getting in the way of the body’s normal response to infections.
Tedder founded Cellective Therapeutics in 2005 to move that research into clinical trials. The company focused on B-cell technologies licensed from the Dana-Farber Cancer Institute – where he began this work – and Duke, where he kicked it into a higher gear.
Biotech company MedImmune thought Tedder was on to something, too. It invested in, and then acquired Cellective just a year after its founding. The drug candidates were still in preclinical development. But, with Tedder’s international reputation as a leader in B-cell biology, it was a solid bet.
The acquisition marked a missed opportunity for North Carolina. Had these molecules been propelled from preclinical platform to final approval, it could have strengthened the state’s reputation as an incubator for new drug research and development. Maryland-based MedImmune bought Cellective first, though, and the B-cell therapies were gone.
They weren’t forgotten.
One year after it acquired Cellective, MedImmune was bought by AstraZeneca. And Tedder’s CD-19 therapy (inebilizumab) —the most promising of the three molecules – became the lead drug candidate of Viela Bio. This AstraZeneca biotech spinout specializes in new treatments for autoimmune and severe inflammatory disease.
Viela finally closed the loop on inebilizumab. In June, the U.S. Food and Drug Administration approved the therapy – brand named Uplizna – to intravenously treat neuromyelitis optica spectrum disorder (NMOSD) in patients who are anti-AQP4 antibody positive. It’s only the second approved drug for the illness.
NMOSD is a rare and severe autoimmune disease of the central nervous system. It most often affects the optic nerves and spinal cord.
The immune system mistakenly attacks proteins and healthy cells in the body, which can cause a variety of serious symptoms. They include eye pain, vision loss, numbness, weakness or paralysis of the arms and legs, loss of bladder and bowel control, and even death. Somewhere between 4,000 and 8,000 people in the U.S. suffer from the disease.
Tedder said Viela also is investigating the drug for several other indications, transplant rejection and oncology among them.
Gratitude to NCBiotech for early support
Tedder reached out to Kathy Meserve, senior director of investments with the North Carolina Biotechnology Center's Emerging Company Development team, when he learned of the recent FDA approval. “You were very helpful when I founded my first company, Cellective Therapeutics with Intersouth Partners in 2005,” he said. “We were the CED spinout of the year.”
Meserve and other NCBiotech specialists help coach scientists as they establish a foothold as an entrepreneur, helping them network and introducing them to investors
“I do consider this a tremendous N.C. success story, as it is a great drug and will make a huge change in NMOSD patients’ lives as well as oncology and other autoimmune disease patients’ lives,” said Tedder of the drug approval.
“You guys [at NCBiotech] played a big part in this early on, for which I will always be grateful. Thank you!”
Then he added, "I should have mentioned that NCBiotech also paid for my entire recruitment to N.C. from Harvard in 1993. Hopefully, you all still think it was a good investment and I’ve paid part of that debt back."
North Carolina quietly advancing drug R&D
The North Carolina connection to Uplizna is just one recent example of how the state’s scientists, universities and biotech companies are advancing the research and development of new, and often revolutionary, therapies. It’s an often-unappreciated area that’s positively impacting the biopharmaceutical industry.
Here are a few more examples:
- Ralph Baric and his team from the UNC Gillings School of Global Public Health were instrumental in developing Remdesivir, one of the most promising potential treatments for COVID-19.
- Martin Rodbell, a Nobel Prize-winning Chapel Hill biochemist, made groundbreaking discoveries that shed light on the earliest stages of human disease.
- Duke University’s Irwin Fridovich found that the body naturally produces toxic molecules called free radicals, the key to aging. His discovery helped spawn new drugs, a new branch of biochemistry and a different way of looking at disease.
- Duke neurologist Allen Roses and his team were the first to find a genetic link to Alzheimer’s disease.
- Researchers at UNC-CH created a mouse with cystic fibrosis, a dramatic advance that provided science with the first animal model to test therapies for one of the world’s leading genetic killers.
- Research Triangle Park-based Burroughs Wellcome (now GlaxoSmithKline) developed AZT (Azidothymidine), the first drug to substantially improve the quality of life for HIV/AIDS patients.
- Y.T. Chen, Priya Kishnani and their teams at Duke University created Myozyme, an enzyme replacement therapy to treat a rare metabolic disorder called Pompe Disease.
- Scientists at Research Triangle Institute discovered Taxol, which was approved to treat both ovarian and breast cancer.
And the list goes on.
Even some of the most well-known over-the-counter headache powders – BC, Stanback, and Goody’s – were developed by North Carolina pharmacists many years ago.
The numbers of new drugs with a North Carolina imprint continue to grow as new biotech companies set up shop in the state, and as the pharmaceutical industry makes major investments to expand its footprint here.
You may even hear from Thomas Tedder again. In 2015 he formed another company, Cellective BioTherapy, that develops regulatory B-cell-based immunotherapies to treat cancers, autoimmunity, and immunodeficiency.