A Philadelphia-area biotech is developing therapies for neurodegenerative diseases it says have the potential to perform better than others by targeting multiple proteins involved in the brain’s breakdown.
Now the company, Berwyn, PA-based Annovis Bio, has raised $12 million in an initial public offering to advance clinical development of its lead therapy in patients with Alzheimer’s disease, Parkinson’s disease, and people with Down syndrome who have developed Alzheimer’s.
The company, which listed on the NYSE American stock exchange under the stock symbol “ANVS,” sold about 4 million shares at $6 apiece, the low end of its projected range of $6 to $8. But it raised $2 million more than anticipated by increasing the number of shares it offered by 40 percent. Annovis was previously known as QR Pharma; it rebranded in June.
High levels of neurotoxic proteins impair communication between and within nerve cells, a process known as axonal transport, and Annovis says its lead drug—which it likens to a combination therapy available as a once-daily pill—targets three such proteins: amyloid precursor protein (APP), tau, and a-Synuclein (aSYN).
“The industry has encountered challenges in targeting specifically one or the other neurotoxic protein, be it APP, tau, or aSYN, indicating that targeting one neurotoxic protein alone does not change the course of neurodegeneration,” the company said in its prospectus. “Our goal is to develop a disease modifying drug (DMD) for patients with neurodegeneration by leveraging our clinical and animal evidence in inhibiting at least the three most relevant neurotoxic proteins.”
In preclinical studies the compound, ANVS-401, restored axonal transport, lowered inflammation, and prevented nerve cell death by reducing the levels of those proteins.
In the clinic, Annovis says it conducted safety studies in healthy volunteers and a proof-of-concept study, in collaboration with clinical research organization Parexel, in five patients with mild cognitive impairment. In that small patient population, Annovis said ANVS-401 was well tolerated and revealed “promising clinical signals,” including the reduction of protein levels and inflammation.
Although it aims to eventually treat all Alzheimer’s disease and Parkinson’s disease patients, Annovis’s strategy is to get the drug over the finish line for a smaller population first: Alzheimer’s disease in Down syndrome. People with Down syndrome often overexpress APP, which Annovis says contributes to the early-onset neurodegeneration that occurs in many adults with the genetic disorder.
“This will allow us to obtain human data for AD in an orphan subpopulation much faster than in the regular AD population,” the prospectus says.
The investigational compound was invented by Nigel Grieg at the National Institutes of Health’s National Institute on Aging. According to Annovis, he synthesized a number of molecules intended to improve upon donepezil (Aricept), which is used to treat confusion related to Alzheimer’s disease, and licensed the most promising compound to Axonyx. Later, he discovered an analog that inhibited APP, and licensed that to Axonyx as well. Following failures in Phase 3 studies of the initial molecule, Axonyx merged with TorreyPines Therapeutics, which subsequently combined with Raptor Pharmaceuticals. In 2016, Raptor was acquired by Horizon Therapeutics, from which Annovis licensed worldwide rights to the technology Grieg had patented.
Annovis says it will use the IPO cash to conduct a Phase 2a trial of its lead drug in Parkinson’s patients; to run chronic toxicology studies in rats and mice; cover costs associated with an ongoing Phase 2a trial in Alzheimer’s patients, currently run and funded by the Alzheimer’s Disease Cooperative Study; kick off planning for a Phase 3 trial in Alzheimer’s disease in Down syndrome; and more.
The company is also in clinical testing with an experimental drug that targets another protein, in patients with advanced Alzheimer’s, and has a preclinical program in which it is testing an injectable drug for traumatic brain injury and other acute indications.
The company roadmap projects the completion of pivotal studies of its lead drug in patients with Alzheimer’s disease in Down syndrome and in patients with Parkinson’s disease, and a request to the FDA to review the data, by the end of 2024, but it will need to raise additional funds to finance those Phase 3 tests.
Led by founder and CEO Maria Maccecchini, the company’s management team includes Jeffrey Cummings, formerly the director of neurology at the Cleveland Clinic, as chief medical officer. According to the prospectus, the majority of shares in the company are held by company executives and directors. Before the IPO, Ben Franklin Technology Partners—a nonprofit provider of seed capital in southeastern Pennsylvania—held 5.3 percent of the stock, the only outside investor listed as holding 5 percent or more of Annovis shares.