Neurizon Therapeutics (formerly PharmAust) is advancing monepantel, a repurposed veterinary drug, as a potential treatment for motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS). The company is preparing to evaluate monepantel within the Healey ALS platform trial, a collaborative effort spanning over 70 sites in the United States.
Monepantel, originally developed as a parasitic sheep drench and marketed by Elanco as Zolvix, has shown promise in inhibiting the mechanistic target of rapamycin (mTOR) signaling pathway, which plays a role in both cancer cell growth and neuronal degeneration. "Our mechanism of action is universal, in that it stimulates a cleaning mechanism in all cells – a process called autophagy," said Dr. Michael Thurn, CEO of Neurizon Therapeutics.
Mechanism of Action and Clinical Potential
Monepantel's mechanism of action involves stimulating autophagy, a cellular cleaning process, which may help slow the progression of MND. Preclinical and early clinical data suggest that monepantel can cross the blood-brain barrier and exert therapeutic effects at relevant doses. Preliminary data from a Phase I study indicated that monepantel, at a dose of 10 mg/kg, could potentially slow MND progression by up to 58% and increase life expectancy by as much as 56.5 months, compared to the current approved treatments that extend life expectancy by only two to six months.
Healey ALS Platform Trial
Neurizon's participation in the Healey ALS platform trial is expected to streamline the drug development process. This platform trial design allows for the simultaneous testing of multiple drugs, potentially reducing patient enrollment times, study costs, and overall completion timelines. "We know our arm of the platform will be designed to the best of their capability, with no stone left unturned," Dr. Thurn stated, emphasizing the rigor of the trial design.
The company anticipates enrolling approximately 120 patients on active treatment within the Healey trial, a reduction from the 200 patients initially planned for a stand-alone trial. This collaborative approach also allows for shared placebo groups, further optimizing resources.
Regulatory and Financial Considerations
In May, the FDA granted orphan drug designation to monepantel for MND. This designation provides several benefits, including tax credits, potential grants, waived clinical fees, and seven years of market exclusivity upon approval. Neurizon expects to have 24-week data from the Healey trial by the end of calendar 2025, which could be sufficient to approach the FDA for accelerated approval.
Neurizon has recently raised $10.66 million and an additional $7.8 million through a share purchase plan to support its clinical development programs. The company estimates that the current funding is close to what is needed to complete the Healey trial, but a top-up capital raising of $5 million to $8 million is likely.
Market Opportunity
The market for MND treatments is substantial, with a projected value of over US$23 billion by 2035. Currently, only a few drugs are approved for MND, and their impact on life expectancy is limited. This highlights the significant unmet need for more effective therapies.
"The bottom line is that MND is an indication with a high unmet need," Dr. Thurn concluded, underscoring the importance of developing new treatments for this devastating disease.
