Parkinson’s disease research has revealed insights into a specific protein that is now a hot target, attracting hundreds of millions of dollars for drug research aimed at stopping it. Scientists at Neuron23 believe their drug candidate may be the best of its kind, and the startup has raised $100 million, some of which will be used to bring the compound to human trials this year.
SoftBank leads the way Series C financing Announced Wednesday, investing from its Vision Fund 2.
The Parkinson’s disease target Neuron23 is called leucine-rich repeat kinase 2 (LRRK2). This protein is found in various tissues and cell types throughout the body, including neurons. Research Mutated LRRK2 has been found to be toxic to neurons, and mutations in this protein have been linked to inherited forms of Parkinson’s disease. There is also emerging evidence that the activity of the mutated protein may also play a role in a subset of people with non-inherited Parkinson’s disease, said Neuron23, which is based south of San Francisco.
Neuron23 is designed to treat Parkinson’s disease by blocking LRRK2. The lead drug candidate, NEU-723, is a small molecule designed to penetrate the brain and block the activity of the mutant protein. Neuron23 has some work to do to show how its LRRK2 inhibitor matches up with a larger competitor’s candidate and has the potential to be the best candidate.
An LRRK2-targeting drug is one of the lead programs for South San Francisco-based biotech company Denali Therapeutics, which has a pipeline of multiple brain-penetrating drugs for a range of neurological disorders. For Parkinson’s disease, the company’s most advanced program is BIIB122/DNL151, a small molecule developed in partnership with Biogen, starting in 2020. Biogen paid $400 million upfront to start with Denali’s brain-penetrating LRRK2 inhibitors and those that don’t penetrate the protective blood-brain barrier. Denali has said that BIIB122/DNL151 was selected for further development because of its properties that provide additional dose flexibility. The company expects to begin a Phase 3 study of BIIB122/DNL151 in patients with LRRK2 mutations later this year.
Cerevel Therapeutics is also pursuing LRRK2 with Pfizer-licensed drug candidatesThe Cambridge, Massachusetts-based biotech aims to treat a specific LRRK2 variant called G2019S, the most common risk mutation for Parkinson’s, the company said in its 2021 annual report. The company’s LRRK2 inhibitor is in the discovery phase. Cerevel’s state-of-the-art Parkinson’s program targets a different target, the D1/D5 receptor.
Neuron23 acknowledges that it faces LRRK2 competition. In an email, CEO Nancy Stagliano wrote that her company’s drug has two characteristics that differentiate its drug as possibly the best in the class of LRRK2 inhibitors. First, she said, not only is the drug highly efficient and able to penetrate the brain, but the Neuron23 molecule is more selective in how it hits its target than its competitors. Second, she said the drug is taking a precision medicine approach to Parkinson’s by using companion diagnostics to select patients most likely to respond to this treatment. In addition to treating patients with LRRK2 mutations, Stagliano said Neuron23 will identify and treat a subset of patients with sporadic Parkinson’s disease, whose disease is also driven by LRRK2.
“This should increase our chances of late clinical success,” she wrote.
Neuron23 expects to begin clinical trials of NEU-723 by the end of 2022. There is more research in this biotechnology. The new funding will also support the development of a drug designed to block immune signaling protein tyrosine kinase 2 (TYK2), part of the JAK protein family. These proteins have been the target of drugs to treat a range of autoimmune diseases. Blockbuster JAK inhibitors from companies like PfizerIncyte and AbbVie are approved to treat conditions including rheumatoid arthritis, atopic dermatitis, psoriatic arthritis and ulcerative colitis.
Unlike other JAK-blocking drugs, Neuron23 says its preclinical drug can penetrate the blood-brain barrier, allowing it to potentially address diseases characterized by neuroinflammation, such as multiple sclerosis. Entire class of JAK-blocking drugs subject to FDA’s stricter cancer and cardiovascular risk warningsIf Neuron23 can demonstrate that its drug can block JAK while offering better side effects, the molecule will be able to further differentiate itself from the field.
Neuron 23 Launched in late 2020 Backed by $113.5 million, it’s a combination of Series A and B rounds. The company’s medicines are licensed by the German company Origenis. Investors in Neuron23’s early-stage financing include Westlake Village BioPartners, Kleiner Perkins, Redmile Group, Cowen Healthcare Investments, Acorn Bioventures, HBM Partners, Perceptive Advisors and Surveyor Capital. These investors also participated in the Series C round.
Image: Dr. Microbiology, Getty Images
