Denali Shares Pop After Positive Parkinson’s Trial Data
Published: Aug 02, 2018 By Mark Terry
Denali announced positive results from its dose-ranging Phase I clinical trial of DNL201 in Parkinson’s disease. It was a randomized, double-blind, placebo-controlled, oral dose trial in healthy patients. It met all safety, pharmacokinetic, and pharmacodynamic goals. The drug was generally well tolerated with no serious side effects.
The drug is a small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2). LRRK2 gene mutations are the most observed genetic cause of Parkinson’s disease and a major cause of lysosomal dysfunction. This adds to the formation of Lewy body protein aggregates and neurodegeneration seen in the disease.
LRRK2 regulates lysosomal genesis and function, which doesn’t function properly in Parkinson’s. It may be fixed by inhibiting LRRK2.
In the trial, more than 100 healthy patients received either single or multiple ascending doses or a placebo. Based on the results, the company plans to advance the drug into a Phase Ib clinical trial in Parkinson’s disease patients with or without a genetic LRRK2 mutation. Denali expects to start the trial by the end of the year.
“We conclude from this clinical trial that DNL201 was able to achieve the targeted level of LRRK2 inhibition at doses that were safe and well tolerated,” said Carole Ho, Denali’s chief medical officer, in a statement. “We are pleased that the trial was a success in all these key measures. The trial data give us confidence to proceed with further clinical testing in Parkinson’s patients and provide a solid basis for selection of the optimal dose for future clinical trials in patients.”
The company also has a Phase I dose escalation trial ongoing in the Netherlands with another small molecule LRRK2 inhibitor, dubbed DNL151.
“We are leading the way in testing LRRK2 inhibitors in humans with the goal of bringing a disease-modifying therapeutic to patients suffering from Parkinson’s disease,” said Ryan Watts, Denali’s chief executive officer, in a statement. “We are also encouraging to see mounting evidence supporting a role of LRRK2 inhibition in the broader sporadic Parkinson’s disease population, in addition to Parkinson’s disease genetically associated with a LRRK2 mutation.”
On May 30, the company exercised its option to buy all outstanding shares in F-star Gamma. This was based on an Option Agreement it signed on August 24, 2016, that expanded its collaboration with F-star on Denali’s biologics Transport Vehicle blood-brain barrier platform technology.
Denali decided to go ahead and acquire the company based on preclinical proof-of-concept data for the TV platform technology and the progress Denali’s lead program has made using the technology.
“Our decision to exercise the option to buy F-star Gamma reflects the progress in our collaboration with F-star and the generation of preclinical data showing that our proprietary TV platform technology may enable us to deliver biologics across the BBB and into the brain,” said Watts, in a statement at the time. “Specifically, recent data demonstrated robust and sustained peripheral and brain activity for our ETV:IDS program for Hunter Syndrome and hence preclinical proof of concept. Furthermore, the expanded collaboration allows us to deepen and broaden our research efforts supporting our TV platform technology.”