Neuroscience News: Vertex's VX-993 fails, Praxis's vormatrigine succeeds

The neuroscience landscape is shifting fast and as we head into an exciting Q4 filled with neuroscience data readouts, it's valuable to look back: MS therapies still dominate, but psychiatry and Alzheimer’s are finally breaking into the commercial big leagues. Here’s how the top 10 rank so far in 2025 (revenues YTD): 1️⃣ Ocrevus (Roche, MS): ~$3.9B YTD. The MS powerhouse keeps growing, with new subcutaneous formulations boosting convenience and stickiness. 2️⃣ Kesimpta (Novartis, MS): ~$1.98B YTD. Strong momentum in B-cell therapy, showing patient demand for self-administered, lower-burden options. 3️⃣ Spravato (Johnson & Johnson, Depression): ~$734M YTD. Having crossed the blockbuster threshold in 2024, esketamine continues to prove psychiatry can support commercial-scale launches. 4️⃣ Interferons (Avonex/Plegridt) (Biogen, MS): ~$473M YTD. Another legacy therapy in decline, being eclipsed by newer biologics. 5️⃣ Tecfidera (Biogen, MS): ~$400M YTD. Declining legacy revenue as generics bite, but still material for Biogen. 6️⃣ Vumerity (Biogen, MS): ~$351M YTD. Picking up some Tecfidera patients; modest growth but unlikely to offset long-term declines. 7️⃣ Leqembi (Eisai US/Biogen, Alzheimer’s): ~$260M YTD. Uptake is rising but still constrained by safety, monitoring, and access hurdles. Execution in Alzheimer’s remains high-risk, high-reward. 8️⃣ Briumvi (TG Therapeutics, Inc., MS): ~$258M YTD. A rapid-growth entrant in MS, but still early. Watch for payer uptake and label expansion. 9️⃣ Aimovig (Amgen/Novartis, Migraine): ~$159M YTD. CGRP class is maturing; competition and pricing pressure are real, but demand remains steady. 🔟 Cobenfy (Bristol Myers Squibb, Schizophrenia): $62M. New launch, first-in-class muscarinic agonist. Early traction, but huge potential if label expansions succeed. Takeaways: 🧪 MS therapies dominate revenues, but innovation is shifting toward convenience and administration routes. 🧪Psychiatry is scaling: Johnson & Johnson’s Spravato just crossed $1B in 2024 sales, signalling that innovative psychiatric treatments can be commercially viable at scale - even with REMS and in-clinic administration. 🧪Alzheimer’s is the big swing - Leqembi’s early trajectory shows both promise and execution risk. 🧪New entrants matter - Cobenfy’s early sales show how fast new launches can muscle into the top 10. 👉 Question: Which CNS therapy (approved or pipeline) do you think has the best chance to disrupt the ranking by 2027 - and why? #neuroscience #biotech #pharma #psychiatry #drugdevelopment #cns #pharmaceuticals

A wave of multiomics clinical trials in neurology and psychiatry is taking shape. Here’s a look at the recent data 👇 After reshaping oncology and immunology, multi-omics is now reconfiguring the CNS space. But the culture is different, owing in part to the brain’s inaccessibility, long disease trajectories, and heterogeneous phenotypes. To explore this landscape, I’m developing an approach to query the clinicaltrials.gov API for interventional trials using two or more omics modalities (genomics, proteomics, etc.), then filtering for neurological, psychiatric, and neurodevelopmental disorders. Here’s what I find interesting: 🧫 While microbiome-based strategies dominate CNS multi-omics trials, most (>75%) are listed as “Phase: Not Applicable”, meaning they’re not under an FDA IND application. 🧬 In neurology IND trials, genomics + transcriptomics remains the leading combo. In psychiatry, it’s proteomics + metabolomics. This suggests the genotype-first mentality is evolving, with focus on layered views of circulating biomarkers (proteins, lipids, metabolites) for diagnosis, stratification, and pharmacodynamic readouts. 💊 Glioma studies are, in some ways, leading translational progress. One early phase trial, published last week, is taking longitudinal glioblastoma samples during viral immunotherapy treatment, thereby breaking a major barrier in CNS therapeutics: measuring target engagement in the brain (link in comments). 🧠 One development in psychiatry is at the intersection of homeostasis and behavior. Two Phase 4 trials are probing the effect of GLP-1 drugs on (i) the psychology of eating behavior and (ii) antipsychotic-induced metabolic disturbances in schizophrenia (NCT06132477 and NCT04892199). Intriguingly, another Phase 4 trial also examines GLP-1 drugs on weight during antipsychotic treatment using physiology (not multi-omic) readouts (NCT06754163).  👉 Multiomics is pushing momentum for breakthroughs in CNS therapies. Multi-scale integration of molecules, cells, behavior, etc. is uncovering causal human biology and taking us closer to disease modifying treatments.  See carousel for data overview and visuals. Let me know what you think. Which CNS areas are ripest for a true multi-omics breakthrough? #MultiOmics #CNS #TranslationalScience #Neuroscience #PrecisionMedicine #Biotech #DataScience #ClinicalTrials 

Chardan biotech analyst Rudy Li, PhD expanded his CNS coverage with three initiations. He initiated coverage of 1) Immunic Therapeutics (IMUX) with a Buy rating and a $3 PT on the potential of its lead asset IMU-838 (vidofludimus calcium) for the treatment of multiple sclerosis (MS). IMU-838 is in Phase 3 development for the treatment of multiple sclerosis (MS). It has a dual MoA targeting both Nurr1 (neuroprotective effect) and DHODH (anti-inflammatory effects), potentially leveraging the success of Aubagio (teriflunomide, DHODH). The company has completed Phase 2 studies in RMS, PMS and UC, demonstrated promising efficacy and clean safety for all tested doses (10mg, 30mg, 45mg). 2) Alto Neuroscience (ANRO) with a Buy rating and a $15 PT as a diversified play in the depression space. The company’s drug development strategy is based on brain-based biomarkers derived from its Precision Psychiatry Platform, with data from neurocognitive assessments, electroencephalography (EEG), wearable devices, as well as genetic and genomic samples. 3) Reviva Pharmaceuticals (RVPH) with a Buy rating and a $2 PT on the potential of its lead asset brilaroxazine as a next-gen antipsychotic product. Brilaroxazine is a serotonin/dopamine modulator in late-stage studies for the treatment of schizophrenia, and the MoA has been validated with multiple products approved. Brilaroxazine has completed 1 Phase 2 and 1 Phase 3 studies in schizophrenia, and 50mg dose has demonstrated consistent treatment effect in 2 studies despite some caveats. Clients can view the full notes here: https://lnkd.in/ejzamzkS (Immunic), https://lnkd.in/e4HTqf9Q (Alto Neuroscience), https://lnkd.in/ee3TccUw (Reviva Pharmaceuticals). To learn more about Chardan research or request access at info@chardan.com.  #ChardanResearch

A quiet but potentially pivotal moment for anxiety therapeutics. Synendos Therapeutics AG has completed Phase 1 testing of SYT-510, the first selective endocannabinoid reuptake inhibitor to enter humans. Across 60 healthy volunteers, the molecule showed no drug-related safety issues, demonstrated CNS penetration at expected pharmacologic levels, and produced EEG changes aligned with established anxiolytics — early but meaningful signs of target engagement. This program represents a new approach to the endocannabinoid system: enhancing endogenous signaling rather than directly activating or blocking receptors. If the translational EEG signal seen in healthy volunteers predicts clinical benefit, SYT-510 could offer a next-generation alternative to SSRIs and benzodiazepines — one with potentially better tolerability and functional outcomes. But the path forward hinges on whether biomarker effects convert into symptom change in patients, a challenge that has historically derailed ECS-modulating efforts. Phase 2 design will be critical: indication scope, functional endpoints, and placebo-control strategy will shape the read-through for regulators and partners. For operators, EEG standardization, central reads, and hybrid visit models are emerging as defining logistics in CNS drug development. Could endocannabinoid modulation finally deliver on its therapeutic promise — or will it remain an elegant mechanism in search of clinical traction? 𝐑𝐞𝐚𝐝 𝐌𝐨𝐫𝐞: https://lnkd.in/d-bG8VMz #Neuroscience #AnxietyDisorders #ClinicalTrials #CNSDrugDevelopment #BiotechInnovation Andrea Chicca Simon Russell

A first-in-class endocannabinoid reuptake inhibitor just cleared Phase 1 with clean safety and CNS engagement—could this be the next paradigm in anxiety treatment? Synendos Therapeutics AG SYT-510 showed no drug-related safety concerns in 60 healthy volunteers across single- and multiple-ascending doses, achieving both plasma and CNS exposure at expected pharmacologic levels. EEG readouts suggested a central effect consistent with anxiolytic activity, supporting a mechanism that gently boosts endogenous endocannabinoids rather than relying on receptor agonism or enzyme inhibition. The company plans to advance into Phase 2, targeting meaningful symptom reduction and functional improvement, positioning SYT-510 as a potentially non-sedating, low-risk alternative to benzodiazepines and legacy antidepressants. Strategically, this illustrates a broader opportunity in mechanistically novel neuropsychiatry, where biomarker-backed proof of concept and functional outcomes could define early value for payers and prescribers. The challenge will be translating tolerable pharmacology into clinically meaningful symptom relief, adoption in primary care, and a differentiated patient experience amid a generics-dominated landscape. Do you think gentle modulation of the endocannabinoid system can deliver reliable, real-world functional improvements in anxiety—or will mechanistic novelty alone be insufficient without robust symptom-scale validation? 𝐑𝐞𝐚𝐝 𝐌𝐨𝐫𝐞: https://lnkd.in/dEAw8k6D #anxiety #neuroscience #psychiatry #biotech #clinicaltrials Andrea Chicca Simon Russell

NEW PAPER: Baseline Mismatch Negativity Amplitude Predicts Direction & Magnitude of Ketamine Effect in Healthy Volunteers - A “Disordinal” Effect This research study from our team at Cognision was conducted in collaboration with EEG/ERP Biomarker Qualification Consortium. PREPRINT: https://lnkd.in/gwmdrnhF BACKGROUND: Mismatch negativity (MMN) is a component of the auditory event-related potential (ERP) that is elicited during a passive oddball paradigm where task-irrelevant infrequent deviants are presented in a stream of more frequent standard stimuli. MMN is believed to index a pre-attentive stage of auditory information processing closely linked to N-methyl-D-aspartate receptors (NMDAR). Ketamine is thought to act primarily as an NMDAR antagonist, has been used in clinical trials to model the symptoms of schizophrenia and is increasingly used in the clinic to treat depression. Various studies have reported that ketamine reduces MMN amplitude which, in turn, might reflect reduced function of NMDAR-mediated neurotransmission. Nonetheless, there is growing evidence showing MMN amplitude either having high variability or, paradoxically, moving in the opposite direction after ketamine in different individuals. METHODS: We analyzed results from three independent ERP studies to test the hypothesis of a cross-over interaction (“disordinal” drug effect) between the duration-deviant MMN at baseline (without ketamine) and the direction and magnitude of the ketamine effect. To rule out regression to the mean (RTM), a statistical phenomenon that may also partially explain this cross-over interaction, we separately estimated RTM using a drug-free test-retest study. RESULTS: Our results are the first to statistically demonstrate the existence of a disordinal drug response to ketamine, where the direction and magnitude of ketamine-induced changes in MMN amplitude can be predicted by baseline MMN amplitude. CONCLUSIONS: These new insights may contribute to novel precision medicine approaches to treatment of CNS disorders. ⭐️ Contact our team to learn more about implementing EEG/ERP biomarkers in clinical trials. #neuroscience #mentalhealth #pharmaceuticals #clinicaltrials #biomarkers #precisionmedicine

🚨🧠 Neuroscience News – 7 day recap: 24/10 ––– 𝘪𝘯 𝘱𝘢𝘳𝘵𝘯𝘦𝘳𝘴𝘩𝘪𝘱 𝘸𝘪𝘵𝘩 World CNS Series 🥼 Clinical News Alto Neuroscience announced plans to accelerate the development of ALTO-207 which is a fixed dose combination of pramipexole and ondansetron targeting Treatment Resistant Depression. The decision comes off the back of a positive FDA meeting atai Life Sciences received Breakthrough Therapy Designation from the FDA for BPL-003 (5-MeO-DMT) AnnJi Pharmaceutical Co., Ltd. have been granted Fast Track Designation from the FDA for AJ201 targeting the mutant androgen receptor for the treatment of Kennedy’s disease SciSparc collaboration with Clearmind Medicine has led to the publication of a US patent application relating to a combination therapy of 5-methoxy-2-aminoindane and N-Acylethanolamines such as PEA to address binge behaviour disorders Basking Biosciences Inc dosed their first patients in their Phase 2b evaluating BB-031 targeting ischemic stroke PLL Therapeutics have completed their Phase 1 evaluating PLL001 targeting ALS Neuphoria Therapeutics Inc didn’t meet their primary endpoint in their Phase 3 evaluating BNC210 targeting social anxiety disorder Alector found no clinical benefit when evaluating latozinemab targeting frontotemporal dementia in a Phase 3 and will now end the program 💰 Financial News Minerva Neurosciences have secured financing up to $200M to advance Roluperidone for the treatment of negative symptoms associated with schizophrenia through a Phase 3, plus enabling the resubmission of their NDA and prep for US commercial launch atai Life Sciences and Beckley Psytech raised approx. $150M in equity financing off the back of the news detailed above. This capital enables a runway through into 2029 which includes getting to topline readout of the first Phase 3 trial of BPL-003 Alto Neuroscience announced a $50M private placement which will support development of ALTO-207 as referenced above Basking Biosciences Inc unlocked a $27.5M tranche following progression into 2b as detailed above CND Life Sciences received an NIH grant for $3M to fund to study the risk of Parkinson’s in patients with essential tremors Pangea Bio received a $1M grant from The Michael J. Fox Foundation for Parkinson's Research to support development of their TrkB activators AbbVie’s acquisition of Bretisilocin developed by Gilgamesh Pharma has been completed 🤝 Collaborations Ventus Therapeutics entered a collab and license agreement with Genentech to utilise Ventus’ drug discovery platform targeting “major disease areas”. Ventus will be entitled to up to $460M plus royalties Lundbeck and Contera Pharma entered a research collaboration with the aim of accelerating discovery and development of oligonucleotides targeting neurological conditions

Roche announced that the FDA has cleared its Elecsys pTau181 blood test, designed to identify individuals aged 55 and older with early signs of cognitive decline who do not exhibit Alzheimer's-related amyloid #pathology. https://lnkd.in/dzktQTku #Alzheimers #dementia #diagnostics #FDA #neurology #pharmaceuticals #productapprovals #regulatoryaffairs

Alzheimer’s Breakthroughs: What Lecanemab Means for Human Performance, Brain Health, and Trauma Care A New Era in Alzheimer’s Therapy In 2025, the approval and first real-world use of Lecanemab (Leqembi) marks a turning point in Alzheimer’s disease management. Unlike earlier drugs that primarily addressed symptoms, Lecanemab directly targets the underlying pathological process—by binding to amyloid-beta protein and prompting its clearance from the brain. Recent hospital-based evidence shows most early-stage patients tolerate it well, benefiting from a slowed cognitive decline, though comprehensive screening and regular monitoring are essential. Beyond Dementia: Implications for Human Performance Optimisation These advances resonate well beyond memory clinics. In high-stakes professions—military, elite sports, emergency services—cognitive health is a core pillar of human performance optimisation. Sustained attention, memory, and decision-making under stress directly impact mission success and long-term well-being. Thus, the ability to preserve and even enhance brain health is of profound interest to anyone working with high-performing populations. Head Trauma, Amyloid, and Lessons from Alzheimer’s The fields of Alzheimer’s research and head trauma—ranging from concussion to chronic traumatic encephalopathy (CTE)—are now converging. Both involve amyloid and tau accumulation, neuroinflammation, and progressive cognitive deficits. Therapies like Lecanemab provide valuable insight: what if similar mechanisms could be harnessed for those exposed to repeated brain injuries? Advanced imaging, genetic risk stratification, and early biomarkers used in Alzheimer’s studies could help develop proactive brain health strategies for at-risk personnel and athletes. Opportunities and Challenges Ahead - Could rigorous cognitive screening and biomarker monitoring become routine for soldiers or athletes? - How might protocols from strict Alzheimer’s trials improve early detection and care after head injury? - Are immunotherapies just the beginning of a comprehensive toolkit for brain health optimisation? Call for Collaboration Optimising human performance isn’t only about speed, strength, or endurance—it’s also about sustaining cognitive clarity and brain resilience throughout a career and lifetime. As new Alzheimer’s therapies emerge, now is the time for deeper cross-talk between neuroscientists, trainers, military health experts, and clinicians. What practical steps should we take to integrate these insights? How do you see the next wave of research and protocols evolving for brain health in high-performance and trauma-exposed populations? Let’s drive the conversation forward. #Alzheimers #BrainHealth #HumanPerformance #HeadTrauma #Innovation #Neurology #MilitaryMedicine

Recent Advances in Neurological Research 🔬 Stay updated with the latest developments in neurology: 1. **Advancements in Alzheimer's Treatment** - Donanemab (Kisunla) has been approved in Australia for early symptomatic Alzheimer's, targeting amyloid to slow disease progression in specific patient groups. - Lecanemab (Leqembi), another antibody therapy, has also received approval for early Alzheimer's patients with mild symptoms. - Roche's BrainShuttle™ program is making strides with Trontinemab, demonstrating significant amyloid plaque clearance in Phase IB/IIA trials, with Phase III trials planned for early symptomatic and preclinical AD individuals. 2. **Enhanced Diagnostics and Biomarkers** - The investigation of the promising blood-based biomarker pTau217 as a standalone test for amyloid pathology is underway. - In Parkinson's, a spinal fluid biomarker utilizing immuno-infrared sensor technology has shown remarkable accuracy in early-stage detection of misfolded alpha-synuclein. - Multimodal approaches combining MRI imaging, cognitive tests, biomarkers, and deep learning are being explored for early Alzheimer's detection. 3. **Neuroprotection Strategies** - A small molecule targeting the BAX protein, involved in apoptotic mitochondrial damage, shows promise in preventing neuron loss in diseases like Parkinson's and Alzheimer's. - Research on specific calcium channel inhibitors (Cav1.3) in Parkinson's aims to decelerate disease progression. 4. **Innovative Therapeutic Delivery** - Development of long-acting injections for Parkinson's (levodopa + carbidopa) is underway to provide sustained medication release over a week, improving patient adherence and stabilizing plasma levels. 5. **Expanding Clinical Trials and Drug Pipeline** - The Alzheimer's drug development pipeline boasts around 138 drugs in various testing phases, offering hope for potential