The global burden of neurological disorders is increasing, driven by aging populations, environmental factors, and an overall rise in life expectancy.1 Conditions such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and psychiatric disorders continue to present significant challenges for healthcare systems worldwide. Despite decades of research, central nervous system (CNS) disorders remain some of the most difficult to treat. However, the field of CNS drug development is undergoing a transformation, with biotech innovators, pharmaceutical companies, and investors collaborating to forge breakthrough therapies that address these challenges.
Overcoming Barriers to CNS Drug Development
The brain's natural defense mechanisms, while crucial for protecting against toxins, also make it difficult for therapeutic molecules to reach their targets. Moreover, the heterogeneity of CNS disorders, in which symptoms and disease progression vary widely among patients, complicates the development of one-size-fits-all treatments. CNS therapeutics have long faced significant high-risk hurdles, including limited drug efficacy, difficulty in penetrating the blood-brain barrier, high clinical trial failure rates, and a historical lack of investment compared to other therapeutic areas. Recent scientific advancements are overcoming these barriers.Biotech Companies Leading the Charge
As the landscape of neurological and neuropsychiatric drug development evolves several biotech companies are spearheading efforts to bring groundbreaking therapies to market. These companies are advancing novel mechanisms of action and strategic partnerships to address significant unmet medical needs.Headquartered in Bresso, Italy, Newron Pharmaceuticals focuses on developing innovative treatments for central and peripheral nervous system disorders. Newron’s lead compound, Evenamide, is a unique modulator of the excessive release of glutamate in treatment resistant schizophrenia (TRS) and poorly responding patients with schizophrenia, currently in Phase III development. This is the first new chemical entity to show significant benefits as add-on therapy in this difficult-to-treat patient population. Clinical trial results to date demonstrate the benefits of this drug candidate in the TRS patient population, with significant improvements across key efficacy measures increasing over time, as well as a favorable safety profile, which is uncommon for available first- and second-generation antipsychotic medications. The treatment was tested as an add-on to second-generation antipsychotics, including clozapine, currently considered the most effective antipsychotic for reducing symptoms. To enhance Evenamide’s clinical development, Newron has entered into strategic partnerships. In December 2024, the company signed a licensing agreement with EA Pharma, a subsidiary of Eisai, for the development and commercialization of the drug candidate in Japan and select Asian territories. This was followed by a collaboration with Myung In Pharm in January 2025, covering the South Korean market. These partnerships will support an upcoming pivotal Phase III trial, set to commence in the first half of 2025, evaluating Evenamide as an adjunct therapy for TRS patients.
Oryzon Genomics, a clinical-stage biopharmaceutical company, is pioneering epigenetic-based therapies for CNS disorders and for cancer. The company’s lead CNS asset, vafidemstat, is a potent and selective LSD1 inhibitor optimized for CNS indications. It has been studied in more than 400 subjects to date and has proven to be safe and well tolerated. In several clinical trials, the drug has demonstrated the ability to reduce agitation and aggression, symptoms common in many psychiatric disorders and neurodegenerative diseases such as Borderline Personality Disorder (BPD), Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder.
Currently, vafidemstat is under investigation for multiple neuropsychiatric conditions. Among its most promising applications, it has shown potential in treating BPD, a condition for which there are no approved drugs yet. Oryzon recently completed the Phase IIb PORTICO trial and following constructive discussions with the FDA, is preparing to launch the Phase III PORTICO-2 trial to further evaluate its efficacy in BPD.
Beyond BPD, vafidemstat is being assessed in the ongoing Phase IIb EVOLUTION trial for schizophrenia, specifically targeting negative symptoms and cognition—an area with few effective treatments. Additionally, Oryzon is exploring vafidemstat’s potential in genetically defined subpopulations, such as patients with Kabuki Syndrome, reinforcing the company’s commitment to precision medicine.
Galimedix Therapeutics is taking a novel approach to CNS drug development by targeting misfolded amyloid beta (Aβ) to combat neurodegenerative diseases. The company’s lead candidate, GAL-101, is a small molecule designed to prevent the formation of toxic Aβ oligomers, a key driver of neurodegenerative diseases of the eye and brain, including Alzheimer’s as well as glaucoma and dry age-related macular degeneration (dry AMD). Compelling pre-clinical data support the potential of Galimedix’s approach to slow or stop neurodegeneration and even, at least partly, to restore lost neuronal function, with excellent safety and tolerability data from a first-in-humans trial. With its patient-friendly administration via oral capsules or eye drops, GAL-101 represents a potential breakthrough in neuroprotection and disease modification.
In collaboration with the renowned eye disease company Thea, Galimedix has initiated the Phase 2 eDREAM study with GAL-101 eye drops in geographic atrophy, an advanced form of dry AMD, with results expected in 2026. Most recently, Galimedix has initiated a Phase 1 study with GAL-101 to evaluate the safety, tolerability, and pharmacokinetics of the orally administered compound. This milestone underscores the company’s ambition to address CNS-related conditions through innovative therapeutic strategies. Galimedix’s product candidates offer clear potential advantages to positively impact millions of patients and their families by providing treatments that not only slow down but could also stop the advancement of their disease.
Through their pioneering research, strategic collaborations and commitment to addressing unmet medical needs, these biotech companies are shaping the future of CNS and neurodegenerative disease treatment.
The Future of CNS Therapeutics
As the scientific community deepens its understanding of the brain’s complexities, the future of CNS therapeutics looks increasingly promising, regardless challenges remain: the high cost of CNS drug development, regulatory hurdles and the need for more precise diagnostic tools continue to slow down progress. Investors play a critical role in addressing these challenges by providing both financial backing and strategic expertise to early-stage biotech companies.
Firms like TVM Capital Life Science are instrumental in advancing CNS innovations. This firm’s investments include Colucid Pharmaceuticals, acquired by Eli Lilly in 2017 to strengthen its pain management portfolio and expand its presence in neurological indications. After the acquisition of TVM’s portfolio company Acer Therapeutics by Zevra Therapeutics, Zevra received FDA approval in September 2024 for MIPLYFFA™ (arimoclomol), a treatment for neurological symptoms associated with Niemann-Pick Disease Type C.
Similarly, Andera Partners is actively investing in CNS-focused companies at the forefront of neurological and psychiatric treatment development. Andera’s portfolio includes Exciva GmbH, a German biotech developing therapies to address behavioral and psychological symptoms associated with Alzheimer's disease. In February 2025, Andera Partners co-led a €27 million Series B financing round for EG 427, a biotechnology firm advancing genetic medicines for chronic neurological disorders.
A Paradigm Shift in Neurology
The integration of cutting-edge research with financial support is accelerating the development of more effective and accessible treatments, providing new hope for millions of patients worldwide. With continued investment, scientific breakthroughs and cross-disciplinary collaboration, the future of CNS therapeutics is developing rapidly, offering a new era of possibilities for neurological care.