Woolsey secures additional funding to advance ALS therapy Bravyl
Study showed therapy lowered nerve cell damage biomarker after 6 months
Woolsey Pharmaceuticals has extended its Series B preferred financing round, securing additional funds to continue advancing its ROCK inhibitor Bravyl (oral fasudil) for amyotrophic lateral sclerosis (ALS).
The extension was completed with participation from existing investors. Series B financing is an early round of funding that usually takes place after a company meets certain milestones and has moved past the initial startup stage.
Bravyl is an oral medication that’s intended to reduce inflammation and nerve cell death. Data from a Phase 2a clinical trial (NCT05218668) has shown that a low dose of it can reduce markers of nerve damage and slow disease progression when compared with an external control group. This has prompted Woolsey to reopen the trial and investigate a higher dose to help determine the optimal one for an upcoming Phase 2b trial. The additional funds from the financing round will help the company advance these plans.
“We are immensely grateful for the continued support of our investors and remain steadfast and confident in our mission to advance Bravyl for the treatment of ALS,” Sven Jacobson, Woolsey’s CEO, said in a company press release. “With these funds, we are well positioned to complete critical milestones.”
The ROCK, or Rho Kinase, enzyme is found at higher levels in people with ALS. It promotes inflammation and cell death and also disrupts nerve cell regeneration and growth, so it’s believed that inhibiting it may have therapeutic benefits.
Bravyl’s active ingredient fasudil is already approved in Japan for certain types of stroke and research in ALS animal models has indicated it may slow the progression of ALS, leading to better motor function and survival.
The REAL test
To see if these benefits are observed in people with ALS, Woolsey launched a Phase 2a clinical trial called REAL that tested a 180 mg daily dose of Bravyl in 31 people with ALS. After six months, levels of neurofilament light chain (NfL), a biomarker of nerve cell damage, were significantly decreased by 15.5% compared with before treatment.
While the study lacked a control group, NfL levels typically increase by 11% over a similar period when the disease runs its natural course, so the results suggest Bravyl may reduce NfL by up to 26% over a placebo in a clinical trial.
Greater reductions in NfL were significantly associated with a slower decline in being able to perform daily activities, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Comparisons with untreated patients from an ALS database indicated Bravyl slowed the decline in ALSFRS-R by 17%, while lung function and muscle strength declines were reduced by 37% and 56%.
Encouraged by these results, Woolsey reopened the REAL study to evaluate a higher dose (300 mg/day) in 31 more participants. Enrollment was completed in November and the first results are expected in the coming months.
Last year, Woolsey shared results from additional experiments that may shed light on Bravyl’s mechanism of action in ALS. In particular, the therapy was found to significantly reduce the spread of toxic TDP-43 protein clumps, which form in the nerve cells of most ALS patients. The clumps can spread from one cell to another, with normal TDP-43 in healthy cells becoming abnormal when they come into contact with faulty TDP-43.
The researchers found that when mouse nerve cells were grown in the lab with vesicles collected from ALS patients before Bravyl treatment, the toxic TDP-43 in the vesicles disrupted the TDP-43 in the nerve cells. However, TDP-43 aggregation and misplacement in nerve cells was reduced by more than 60% when cells were grown with vesicles collected from patients after six months of Bravyl.
The therapy has won orphan drug status in the U.S. and in Europe. This is a designation that’s intended to speed up the development and approval of drugs for rare diseases and offers a range of incentives, including fee exemptions and a period of market exclusivity if it’s approved.
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