Taking Aim at Peripheral Neuropathy and Neurodegeneration Targets

Neuropathy, which encompasses various kinds of neuronal damage, has many causes but few fundamental remedies. It may result from infection, exposure to toxins, or traumatic brain injury. It may also occur as a consequence of diabetes or neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis.

Progress against neuropathy, which is also called peripheral neuropathy, has been frustratingly slow. Despite the availability of treatments to alleviate symptoms and address some of the conditions associated with peripheral neuropathy, there are no approved treatments to resolve the underlying mechanisms of peripheral neuropathy itself. Also, there are no cures for neurodegenerative conditions.

Regardless, neuropathy remains a subject of abiding interest. The 2015 movie Concussion shows that even Hollywood has brain trauma on its mind. More consequently, gifted researchers refuse to accept defeat. At Magnolia Neurosciences, scientific co-founder Philip Jones, PhD, recognizes that neuropathy is “an obvious area of unmet medical need.” The company aims to discover and develop therapies for the prevention of neuronal cell death, thereby providing novel treatment options for patients suffering from neurodegeneration and related conditions.

“Despite great attempts, the industry remains stymied in finding something efficacious in neurodegeneration,” elaborates Jones, who is also affiliated with Magnolia Tejas, a Magnolila Neurosciences subsidiary that is working to develop a novel targeted therapy for the treatment of neurological conditions caused by chemotherapy.

Chemotherapy-induced peripheral neuropathy affects 52.7% of patients receiving chemotherapy, according Mayo Clinic researchers select Shah et al., J. Neurol. Neurosurg. Psychiatry, 2018). In the absence of neuroprotective therapies, the condition can erode memory and seriously reduce quality of life.

At present, chemotherapy-induced peripheral neuropathy may be treated only by reducing chemotherapy dosages or creating breaks in the treatment. Either option, however, may reduce the likelihood of survival. Intent on providing a better option, Magnolia is, in Jones’ telling, “pushing ahead with novel neuroprotective compounds against a range of diseases.”

Details about Magnolia’s therapeutic platform remain closely guarded, but Jones refers to “a new biological mechanism of action” for neuroprotection. “Nothing like this has been previously explored,” he declares, “which is what makes this so exciting!”

The company indicates that its therapeutics are in the preclinical stage of development. Tests are in progress to assess safety and toxicity, determine the most efficacious concentrations of molecules, evaluate modulation of the protein target in the brain, and characterize the signaling changes that lead to neuroprotection.

“There will be a number of molecules in human trials in the near future,” Jones predicts. As vice president of therapeutic discovery at the University of Texas MD Anderson Cancer Center and head of drug discovery at the Institute for Applied Cancer Science select IACS union he’s in a good position to make such pronouncements. He’s also speaking as part of a powerful team. Jones has collaborated with Jim Ray, PhD, scientific co-founder of Magnolia and director of MD Anderson’s Neurodegeneration Consortium, on Magnolia’s foundational research at MD Anderson. Both scientists are overseeing the development of this research at Magnolia.

When their work came to the attention of Accelerator Life Science Partners, a venture capital fund, it didn’t take long for investors to be assembled and for Magnolia Neurosciences to be created.

Magnolia runs in near-stealth mode

Magnolia has flown largely under the media radar since its inception last August. “We’re not alone in developing this class of molecule, so we’re keeping everything close to the vest,” states David M. Schubert, president of Magnolia Tejas, chief operating officer at Magnolia Neurosciences, and chief operating partner at Accelerator Life Science Partners. Some of Magnolia’s competitors have drugs in the clinic already, he continues, but none have an approved drug on the market.

“The challenge,” Jones adds, “is prioritization.” Many neurodegenerative diseases need therapeutics, but Magnolia must focus on the program that promises to maximize benefits for patients and investors, and to demonstrate clinical utility relatively quickly.

Parent and subsidiary created simultaneously

Magnolia Neurosciences, which is headquartered in New York, NY, maintains its Magnolia Tejas subsidiary in Houson, TX. The two business entities were created at about the same time to leverage opportunities in their respective locations. Magnolia Tejas benefits from proximity to MD Anderson, the research home of its two scientific co-founders. Magnolia Neurosciences, meanwhile, focuses on the development of neurodegenerative therapies.

Both Magnolia Neurosciences and Magnolia Tejas will be led by experienced biotech managers from Accelerator Life Science Partners for the next several years. The venture capital firm acts as a catalyst and partner for young life science companies.

Established networks helped create Magnolia

Like other startups, Magnolia owes its formation to the networks cultivated by its principals. “I’ve had a long relationship with the MD Anderson Cancer Center,” Schubert points out. Living in Houston and working on company creation at Rice University, he got to know the people at MD Anderson as well as the IACS. When an IACS colleague told him about Jones and Ray’s work, it “clicked.” “Jim and Phil are smart, honest, and caring,” Schubert professes. “There’s a level of comfort in working with them.”

Magnolia also formed more readily because all of its strategic investors were familiar with the neurodegenerative space. Now AbbVie, Johnson & Johnson Innovation, Eli Lilly and Company, and Pfizer are strategically invested in Magnolia, along with WuXi PharmaTech and several venture capital funds, including ARCH Venture Partners. “MD Anderson has plenty of skin in the game, too,” Schubert emphasizes.

Magnolia Neurosciences launched in 2018 with $31 million in Series A funding to pursue neurodegenerative diseases. Last August, Magnolia Tejas received a $20 million grant from the Cancer Prevention and Research Institute of Texas to pursue treatment for neurological side effects of chemotherapy, including peripheral neuropathy and “chemobrain,” a cognitive dysfunction that can persist more than a year after the discontinuation of chemotherapy.

Jones expects the funding to take the potential treatment through Phase II trials. The next milestone, however, is to dose the first patient. That’s expected to happen in 2020 for chemotherapy-induced peripheral neuropathy, followed by a compound for neurodegenerative diseases in 2021.

Despite the interest in immuno-oncology, “chemotherapy has a definite role in the future,” Jones insists. Therefore, chemotherapy-induced peripheral neuropathy will continue to affect patients. He believes the compound being developed can moderate chemotherapy’s neurologic side effects, and that it will benefit patients even as immunotherapy enters the mainstream. Likewise, with an aging global population, chronic neurodegenerative diseases are likely to continue to rise.