We asked industry leaders from neuroscience-focused biotech and biopharma companies which therapies in development or clinical trials they are watching closely this year.

Which brain-targeting drugs currently in development are you most excited about?

Klaus Dugi, Chief Executive Officer of Vandria Therapeutics:

I’m most excited about clinical development programs focused on exploring broader anti-neuroinflammatory drugs, such as those targeting TREM2, ERK signaling, and 11ß-HSD1, all of which play a key role in neuroinflammation. Many forms of neuroinflammation are still treated with steroids, which are not suitable for long-term use due to their side effect profiles. At Vandria Therapeutics, we are developing VNA-318, an oral, brain-penetrant drug that activates a metabolic master switch to reduce neuroinflammation and improve mitochondrial function. This approach has the potential to be broadly applicable to central nervous system (CNS) diseases, including inflammatory and neurodegenerative disorders. 

Neil Miller, Cofounder and Chief Executive Officer of NRG Therapeutics:

There is a resurgence in innovation aimed at developing new ways to treat neurological diseases. It is an area of great unmet need, with the incidence of CNS disorders growing in the aging population. Despite this, there are still very few disease-modifying treatments for chronic neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), which severely impact patients’ lives and shorten their lifespans. However, there is hope, and I am particularly excited about Mission Therapeutics’ USP30 deubiquitinating enzyme (DUB) inhibitor, and Nodthera’s NLRP3 inhibitor, both in clinical trials for Parkinson’s disease; as well as Dewpoint Therapeutics’ TDP-43 condensate modulator, currently in preclinical development for ALS. At NRG Therapeutics, we have also made advances as we move closer to clinical development for our lead drug candidate, NRG5051. This brain-penetrant small molecule inhibits the mitochondrial permeability transition pore, offering strong neuroprotective effects in preclinical models. I believe it has potential as a disease-modifying treatment for neurodegenerative diseases like ALS and Parkinson’s disease. 

Neils Plath, Chief Scientific Officer at Muna Therapeutics:

I'm still convinced that small molecules are the preferred modality to target brain disorders as they can most effectively reach the right disease targets in the brain. Recently, there’s been significant progress in developing antibody-based drugs for neurological diseases, and these therapies are showing promising results. At Muna Therapeutics, we’re focused on finding treatments for diseases like Alzheimer's disease and Parkinson's disease, both of which are currently dominated by antibody-based treatments. While these therapies are promising, we believe there is room for improvement. I’m hopeful that we will soon see small molecules that can complement these therapies by targeting amyloid-beta formation or tau phosphorylation in Alzheimer's disease, and alpha-synuclein misfolding and clearance in Parkinson’s disease. I believe this will be a key part of the next wave of treatments, building on the success of anti-amyloid, anti-alpha-synuclein, and anti-tau antibodies. 

Kasper Roet, Founder and Chief Executive Officer of QurAlis:

With recent advances in our understanding of disease genetics, I’m excited about the potential of RNA therapeutics. These therapies have already shown success in treating conditions like spinal muscular atrophy and SOD1-linked ALS, and they’re showing promise in treating epilepsy. This is why QurAlis has developed its next-generation FlexASO technology, which has the potential to change gene expression by modifying how RNAs are spliced. Currently, we are developing RNA therapeutics to restore STMN2 expression in ALS and frontotemporal dementia, as well as RNA-based treatments for rare neurological diseases like Fragile-X syndrome and progressive supranuclear palsy. 

Craig Hopkinson, Chief Medical Officer and Executive Vice President of R&D at Alkermes:

There is a lot of excitement around the orexin pathway for sleep disorders, because of its role as the master regulator of wakefulness. Orexin is also involved in regulating energy balance, reward systems, cognition, mood, and attention. At Alkermes, we are focused on investigating the potential of targeting orexin to address significant unmet needs in neurological and psychiatric conditions that involve one or more of these symptom domains. Our lead investigational drug, ALKS 2680, is an orexin 2 receptor agonist, and we are evaluating it as a potential therapy for narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH). Despite currently available therapies, people living with narcolepsy and IH still have high unmet needs for new treatment options. As we work to develop potential new treatments for these conditions, we have gained a deeper understanding of the brain and are fortunate to have a strong foundation of existing research to build on.  

Some responses have been edited for length and clarity.