In a most remarkably accelerated process, the Psychedelics, which constitute a novel and heterogeneous class of therapeutic candidates, are soon to take their revolutionary leap from investigational to commercial, as Compass’ COMP360/psilocybin appears likely to receive FDA approval during 4Q, setting the stage for a nearterm first launch of a classical psychedelic, this for Treatment Resistant Depression. The stunning success of JNJ’s Spravato has demonstrated the market viability for innovative options for in-clinic interventional Psychiatry, and we expect several psychedelic compounds to reach the Market and be successful. This class is not a panacea, but represent a very useful, at times dramatically successful, alternatives for difficult-to-treat disorders. In addition to TRD,MDD, PTSD, GAD, and Addiction are areas that will benefit from these options. ibogaine (the least understood and most risk-laden psychedelic) has received particular and surprising attention in the Addiction space. Big Pharma has not yet embraced this class, but AbbVie and Otsuka have made significant investments in promising psychedelic assets. Over $1.2 billion has been raised by psychedelics companies thus far in 2026, led by the most advanced clinical-stage companies: Compass, Definium, AtaiBeckley, Gilgamesh, and Helus. The subgroup that seen its ascendancy at least temporarily slowed is the non-hallucinogenic psychoplastogen category, which has found funding hard to come by. This review assesses over fifty companies, including Compass, Definium, Atai Beckley, AbbVie, Otsuka/Transcend, Gilgamesh, Helus, Enveric, GH Research, Resilient, Reunion, Equulus, CaamTech, Delix, and Psilera. The Huntington’s area is going through a revolution of its own, as the mechanistic model increasingly shifts emphasis from mutant huntingtin to the somatic expansion process that leads to the generation of extended CAG repeats. LoQus23, Latus Bio, and Pfizer are among the companies pursuing MSH3 targeting. But huntingtin is still a major focus, Roche’s decision to go into another tominersen PhIII with early-stage patients struck us as an attempt to traverse an unbridgeable gap between efficacy and safety–the outcome will be known shortly. We are more optimistic about the Skyhawk PhII/III trial expected to finish a year from now, curious about Alnylam’s PhIb, and resigned to a long wait for Novartis/PTC’s PhIII, though we will see if they seek Accelerated Approval based on the trial already completed. uniQure’s regulatory journey has become a saga of its own, with an unfortunately politicized FDA reversing itself and giving uniQure the go-ahead for filing based on a tiny PhII cohort in comparison to a historical control group. If they are willing to do so for Huntington’s, the list of rare but not ultra-rare neurodegenerative disorders that could justify similar treatment includes ALS, FTD, and Spinocerebellar Ataxia, to name but three. Dispensing with placebo-controlled testing for these other disorders is a slippery slope the Agency did not fully consider. The third area is Migraine, the first time in eight years we have reviewed this area, one which went through its own revolution as the CGRP targeting programs achieved dominance. The triptans and CGRP drugs still leave a significant portion of the Migraine population undertreated, we suspect that PACAP targeting will be the next major advance, with Lundbeck in front, Slate, Mentari, and Vedana trailing. In the meantime, Axsome will target CGRP nonresponders with its recently approved Symbravo. The Summer issue also comments on clinical datasets from Praxis, Alto, Neumora, Definium, and acquisitions by Lilly (Centessa) and UCB (Neurona). Denmark’s Lophora is the subject of this issue’s Company Spotlight. A one-year (1-5 user) subscription to NeuroPerspective is $3500. A 6-10 user subscription is $5700. Other customized userbase and  startup pricing options are available. The Summer issue is being made available as a single-issue purchase, for $900, available for online purchase and download at https://www.niresearch.com/onlinestore.html.

NeuroPerspective has released its Spring 2026 issue, featuring our reviews of PTSD, an area with expanding therapeutic possibilities: Autism, a fast growing CNS disorder; and Epilepsy, where there have been several encouraging datasets in recent months. Our review of PTSD recognizes trauma as a human growth industry: In theory, many traumatizing factors could be under human control, and yet human folly continues to generate new cases by the millions. Treatment tends to be psychotherapy-based, with pharmacotherapies comprised primarily of psychiatric meds treating PTSD-related mood, anxiety, and sleep disorders, without dramatic effect. But a new treatment paradigm is emerging: The recall of trauma memories, both cognitive and somatoform, brings them to the point of awareness, so that they are accessible first to deconsolidation, and then reconsolidation in affectively-neutralized form. It is during this window of accessibility that pharmacotherapy can reduce the degree of somatic hyperactivation, and perhaps enhance the process of overwriting the old ‘engrams’, or default mode, with a less retraumatizing ‘edition’ of history–the goal is not to erase history, but to stop reliving it. Procognitive pharmacotherapy may help with ‘rewriting’ of traumatic memories, and there are novel approaches, psychedelic and empathogenic, which rebuild maladaptive interpersonal patterns and ‘neutralize’ trauma-related affect. Psychedelic and empathogenic treatment options have shown tantalizing efficacy in human trials, including Resilient/Lykos’ MDMA studies and Compass’ pilot study of psilocybin in PTSD. Promising indicators have been seen in programs from Transcend (recently acquired by Otsuka) and Emyria, and AbbVie has cited PTSD as an indication of priority for the bretisolicin program licensed from Gilgamesh. Autism also represents a burgeoning population, with prevalence estimates now reaching 3% of children. Autism has been turned into a battlefield in the current War on Science, with unfounded causal claims (e.g. vaccines) and unsubstantiated treatments being given undeserved credence, to the deteriment of the field and patients with autism. This is an enormous, heterogeneous disorder whose genetic underpinnings are complex and multifactorial, save for relatively rare gene-driven disorders that partially overlap with autism, including Fragile X, Rett Syndrome, and Phelan-McDermid Syndrome. The underlying biology appears to include malfunctioning neuronal network growth and subsequent ‘culling’. Specific treatments, including gene therapy, are in development for the rare subvariants, but for idiopathic autism, the search is on for improved symptomatic-treatments addressing irritability, social disengagement, and sleep disorders, even as work continues on identifying more homogenous subgroups who could have upstream pathway disruptions remediated. Trials of R-MDMA (Definium), muscarinic activation (Bristol Myers Squibb), epigenetic intervention (Oryzon), serotonergic upregulation (Maplight) are among those underway or approaching. Epilepsy decades ago was the reliquary of anachronistic drug treatments whose side effect profiles were daunting: Idiopathic epilepsy has seen improvement in the anti-seizure options, but there is still a substantial subgroup of patients whose epilepsy, usually focal in nature, is treatment-refractory. Considerable progress has been made in addressing genetically-driven, rare but devastating pediatric seizure disorders, such as Dravet Syndrome, Lennox-Gastaut, Tuberous Sclerosis, and the umbrella category of Developmental Epileptic Encephalopathies. Companies like Praxis and Xenon have had significant clinical successes, Phase III trials are underway for programs from Biohaven, Stoke, Encoded, Lundbeck, Harmony, Neurvati/GRIN Therapeutics, and Neurona, while earlier stage programs with promise are ongoing for Rapport Therapeutics and Jazz/Saniona. The Spring Issue also includes the Psychedelic Update, assessing datasets from Compass, AtaiBeckley, Gilgamesh, Helus/Cybin, and Johns Hopkins, which in aggregate continue to add substance to the explosion of interest in this area. Positive datasets outside of Psychedelics are reviewed, from Lundbeck, Xenon, and QurAlis. Prominent transactions are discussed, including Korsana’s reverse merger, Lilly’s acquisition of Centessa, Xenon’s mega-stock offering, and more.

NeuroPerspective has released its Winter 2026 issue, featuring our annual look back at the preceding year, and our Preview of the year ahead. 2025 was a highly productive year for several subsectors of the neurotherapeutics space, including Psychedelics, Epilepsy, Narcolepsy, and muscarinics. The Psychedelic area has matured faster than we ever could have anticipated, both clinically and fiscally. Clinical successes were achieved by Compass, with its first PhIII in TRD; AtaiBeckley, who celebrated their 5-MeO-DMT PhII results by consummating their merger; Gilgamesh’s PhII results with bretisolicin were convincing enough to spur AbbVie into making a $900 million upfront payment to partner that program; and Reunion’s RE104 performed well in Post-Partum Depression. 2026 will see important datasets in anxiety (MindMed, Cybin/Helus, and AtaiBeckley) and depression (Compass, Atai/Beckley, Cybin/Helus, MindMed). The magnitude of reported treatment effects has been enough to galvanize institutional investment: in 2025,18.4% of all CNS investment went to psychedelics, which is remarkable. It is worth noting that, at least for now, this has taken away some of the momentum that had been building for ‘trip-free’ neuroplastogens. So far as non-psychedelic datasets in depression are concerned, we are looking forward to 2026 results from Autobahn, Alto, and Xenon. Epilepsy has emerged as a key area for clinical advancement, particularly in terms of rare, severe pediatric epilepsies, and treatment refractory focal seizures. 2026 will see PhIII results for Lundbeck/Longboard, Xenon, Praxis, and Biohaven, with key data coming next year for Biogen/Stoke and Neurvati. Narcolepsy treatment will see a basic paradigm shift as orexin-2 agonists come online, first in NT1 from Takeda, followed by Alkermes, Centessa, and eventually, Harmony. While BMS’ Cobenfy has been slow to ratchet up its sales pace, partly reflecting its failure in an adjunctive trial, Maplight was able to raise over $600 million to advance its M1/M4 agonist program, with topline CIAS results coming before year-end, Neurocrine is in PhIII with their M4 activator, Neumora and others are earlier on with their muscarinic candidates. Using a nonmuscarinic mechanism, Kynexis will have topline results from a well-constructed PhII in CIAS before the end of 2026. On the downside, the failure of GSK/Alector’s latozinemab in FTD-GRN was a sobering reminder that, even with the advantages of a genetically defined subgroup, a reasonable mechanistic rationale, and a relevant biomarker, disease modification in neurodegeneration is never guaranteed. This must have quickened the anxiety for other companies with progranulin-boosting programs, and PhII results will come this year for Takeda/Denali, Passage Bio, and Astellas. There was remarkably little progress made in Alzheimer’s, other than the incremental improvement in ease-of-use provided by subQ options for amyloid mAbs: Several companies, including Roche, Denali, AbbVie, Acumen, and Novartis, have invested in BBB-transit technologies, but to the extent to which these brain ‘shuttles’ are used to ferry amyloid antibodies, there is reason to doubt that removing plaque faster will make an appreciable difference in therapeutic effect. While another tau mAb failed in 2025 (JNJ), 2026 will see midyear data for Biogen/Ionis’ MAPT ASO PhII, and BMS will have AD-psychosis results for Cobenfy by year-end. But the failure of Novo Nordisk’s large studies of semaglutide in AD serve as a reminder that PhII should not be skipped on the way to running 3600 patients through PhIII. From a macro-financing perspective, while 2025 saw an 11% YTY reduction in fiscal resources provided to small-midsize CNS companies, it was still the fourth best year since 2009, and there was a healthy uptick in financings, including IPOs, during the last quarter of the year. And the acquisition of Intra-Cellular Therapies by JNJ was a reminder of the heady rewards that can result from taking developmental risks with an inhouse program. Among the 150+ companies with coverage in this issue are AbbVie, Acadia, Acumen, AC Immune, Alkermes, Actinogen, Alector, Alto, Alzamend, Anavex, Aspen, AtaiBeckley, Autobahn, Axsome, BioArctic, Biogen, Biohaven, BMS, Boehringer Ingelheim, Compass, Cybin/Helus, Eisai, Gilgamesh, GH Research, GSK, JNJ, Kynexis, Lilly, Lundbeck, Maplight, Merck,MindMed, Muna, Myrobalan, Neumora, Neurocrine, Neurvati, Novartis, Oryzon, Otsuka, Praxis, ProMIS, Prothena, Rapport, Resilient, Reunion, Roche, Sanofi, Seaport, Syndeio, Syremis, Takeda, Vesper, UniQure, and Xenon. The Psychedelics Update section appraises the impact of the AbbVie/Gilgamesh partnership upon Pharma ‘hallucinophobia’, the failure of microdosing, the dimming prospects for neuroplastogens, and notes the robust treatment effects achieved by multiple psychedelic assets. As always, there is coverage of significant clinical, fiscal, and partnering events. 40 pages. NeuroPerspective is the quarterly review of the neurotherapeutics area offering essential, unique, and comprehensive coverage of developments in the science and the business of the CNS sector. A one-year (1-5 user) subscription is $3400. A 6-10 user subscription is $5600. Other customized user base and startup pricing options are available. The Winter issue is available as a single issue purchase, US$900.

NeuroPerspective has released its Fall 2025 issue, featuring our annual comprehensive review of Alzheimer’s, as well as reviews of Depression and Narcolepsy. Our Alzheimer’s review appraises the impact of the commercial advents of Eisai/Biogen’s Leqembi/lecanemab and Lilly’s Kisunla/donanemab. They provide an imperceptible slowing of disease progression and a rare but not inconsequential risk of ARIA, that may prove to be deadly for .5-1% of patients, a seemingly small percentage that could translate into noticeable casualties given the size of the patient population. That risk could be reduced if genetic screening and exclusion of APOE4++ patients were mandated in the US, as is the case in the EU, but neither the companies nor regulators have taken that step, leaving the weighing of risk vs. benefit up to patients and their families. But the launch of two ostensible disease-modifiers has provided the medical/insurance system with the opportunity to develop treatment and payor infrastructure that will serve future, more effective options, and has reawakened the pharma industry to the commercial potential to be found here. Other amyloid mAbs, including Lilly’s remternetug, Roche’s trontinemab and programs from Acumen, AbbVie/Aliada, and ProMIS, hope to improve the risk/benefit profile, but they are years away from potential approval. The quest to improve BBB access has led to multiple partnerships for BBB-transit programs: During 2025 alone, Novartis has added two to its developmental repertoire via licensing/option deals with BioArctic and Sironax; GSK partnered with ABL Bio; Acumen licensed a JCR Pharma program; and Lilly licensed a Sangamo asset Hopes for tau as a target for monoclonal antibodies have been thus far dashed due to limited BBB access and even less, if any, intracellular access. There are active vaccine and antibody fragment programs that hope to improve on the original mAb legacy, including BMS/BioArctic, JNJ/AC Immune, and Nuravax. Beyond amyloid and tau, the most promising programs appear to be in the neuroinflammation and cellular waste disposal categories. We have been intrigued by TREM2 as a means of modulating microglial activity. But the unexpected demise of the Takeda/Denali lead mAb due to safety issues, in conjunction with evidence that TREM2 activation can itself lead to ARIA, complicates the picture. AbbVie/Alector’s AL002 failed, Novartis is in PhII. The small molecule TREM2 activator in development by Sanofi/Vigil may have an advantage in the TREM2 domain, at least until Muna Therapeutics advances its program. There are downstream mediators that may be alternative targets, including PLCG2 and SHIP1, and NLRP3 inflammasome inhibitors (Halia and Cerevance) . The wait for Novo Nordisk’s semaglutide PhIII trials should be approaching its end. The recent work on the link between AD and lithium depletion is considered. Symptomatic approaches could play a more important clinical role than the crop of very limited disease modifiers. But there has been complete silence regarding AbbVie/Syndesi’s ABBV-552 PhII data, which likely means bad news. Bristol Myers Squibb is assessing a number of KarXT dosing combinations for AD-psychosis, and first data should come soon. But tolerability issues in elderly patients leave the door ajar for other muscarinic candidates, including those from Neurocrine/Nxera, Neumora, and Maplight. Syndeio has developed a considerable body of evidence for its premise that there is an optimal level, and frequency, of NMDA upregulation for procognitive impact, and that historically it has often been exceeded, with negative results. A PhII in AD is being planned. Lighthouse Pharmaceuticals has obtained NIH funding for a definitive trial of its p.gingivalis infection hypothesis. AgeneBio continues to look for a partner to complete development of AGB101 as a treatment for non-APOE4 patients. There is also a slew of small companies whose programmatic execution has been as sloppy as their hyperbole, with Cassava, Anavex, Alzheon, Annovis prominent in that group. Among the 200+ programs assessed are those from: AbbVie/Aliada, Acumen, AC Immune, Actinogen, AgeneBio, Alnylam, Allyx, Alzamend, Anavex, BioArctic, Biogen, BMS, Eisai, GSK/Alector, JNJ, Klothea, Kynexis, Leal, Lexeo, Lighthouse, Lilly, Merck, Monument Biosciences, Muna, Myrobalan, Neumora, Nuravax, ProMIS, Prothena, Roche, Sironax, Syndeio, Takeda, TrimTECH, and Sanofi/Vigil. The second major review is of Depression, an area being transformed as Psychiatry adds new therapeutic tools, and begins to meaningfully parse patient populations based on phenotypic or biomarker differentiators. New mechanisms are in clinical stage, including novel approaches from Xenon, HMNC, Syndeio, Alto Neuro, Actinogen, Autobahn, Engrail, Evecxia, and many others. There have been disappointments, such as the kappa opioid antagonists from JNJ and Neumora. With the growing positive data for Psychedelic options (e.g. Compass, Atai/ Beckley, Cybin, MindMed, Reunion, GH Research), and AbbVie’s partnership with Gilgamesh on GM-2505, the psychoplastogen wing (e.g. Delix, Onsero) has lost some momentum. The third therapeutic area reviewed is Narcolepsy, the first time NP has reviewed that area since 2006. The timing is auspicious, as the highly successful oxybate franchises (Jazz, Avadel), which have shared the spotlight with H3 antagonist drugs (Harmony, Suven), now must contend with the prospect of orexinergic drugs that for the first time address the core deficit of narcolepsy. Major OX2-agonist programs come from Takeda, Alkermes, Centessa, Jazz, and Harmony Biosciences. The Fall issue includes an overview of Saniona, the inheritor of NeuroSearch’s ion channel expertise, which has signed epilepsy drug partnerships with Acadia and Jazz Pharmaceuticals. The Psychedelics Update section appraises Reunion’s successful PhII in Post-Partum Depression and the recently disclosed CRL previously issued by the FDA to Lykos (now rebranded as Resilient Therapeutics) regarding the use of MDMA in PTSD. There is nothing there that would not be solvable by a comprehensive REMS program, and with the FDA’s current receptivity to Psychedelics, that possibility could re-emerge. As always, there is coverage of significant clinical, fiscal, and partnering events. 125 pages.

NeuroPerspective has released its Spring 2025 issue, featuring comprehensive reviews of neurotherapeutics programs addressing Schizophrenia, ALS, and Addiction. The Schizophrenia area is on the verge of its most significant transformation in decades, as the pharma industry is seeing a heated competition between companies attempting to ride the new wave of novel and refined mechanisms aimed at the trifecta of schizophreniform symptoms. Once dismissed as a backwater of generic antipsychotic me-too options, pharma companies have begun to invest heavily, with Bristol Myers Squibb's acquisition of Karuna, and JNJ's purchase of Intra-Cellular Therapies, each with a $14 billion pricetag. From a commercial perspective, the clash of Cobenfy and Caplyta, with two massive marketing efforts behind them, will be one of the fascinating stories of 2025. The degree to which the return justifies the outlay will be a major factor in modulating the return of Big Pharma to Psychiatry, already underway. Caplyta falls under the overly broad category of second-generation antipsychotics, its tolerability profile and effect on both positive and negative symptoms having set the stage for Intra-Cellular to have achieved an impressive launch on its own. Cobenfy is KarXT, the first muscarinic agonist to make it to the Market, with impact upon both positive and negative symptoms as well. KarXT has a flock of muscarinic hopefuls coming up behind it, with Neurocrine/Nxera having shown a signal in PhII. The challenge of this area was epitomized by the shocking failure of AbbVie/Cerevel's emraclidine, which had hoped to achieve through selectivity what KarXT had managed by using a peripheral blocker. One potentially crucial differentiator is the orthosteric vs. allosteric activation, both Cobenfy, the Neurocrine/Nxera program, and an earlier-stage entrant from Maplight, fall into the former category. Emraclidine was an allosteric modulator, as are programs owned by Neumora and Neurosterix, which could signal trouble ahead for them. CIAS, the cognitive impairment seen with schizophrenia, has been a difficult area to treat, but there are a number of intriguing novel mechanisms in clinical testing, from Kynexis, Atai/Recognify, Neurocrine/Nxera, Oryzon, Cerevance, and Alto Neuroscience. ALS has been a neurodegenerative disorder where FDA standards have traditionally been relatively lax, as was the case for Amylyx's Relyvrio, whose accelerated approval was largely attributable to coaching by the then-head of neuroscience for the FDA. With that miscarriage of regulatory oversight eventually corrected, and Relyvrio pulled from the Market (after $400 million in futile sales), we are back to two mediocre therapies for ALS in the US. The hope that ATXN or EIF2b might be workable access points has been dashed, the most widespread question in the field is whether targeting TDP-43 dysfunction can be directly or indirectly workable. UNC13A has been attracting attention, with programs in progress by QurAlis/Lilly and Trace Neuroscience; SARM1 inhibitors are in development by Lilly, Nura Bio, and Asha; TRPML1 is targeted by Libra Therapeutics, Samsara, and Denali spin-out Tenvie. We do not take seriously generic workarounds like NeuroSense, or failed neurotrophic cell therapy (Brain Storm). Addiction receives less pharma investment and attention than even stroke/TBI, and with NIH/NIDA now being subjected to experiments in institutional vivesection, that deficit will only worsen. Orexin-1 inhibitors and the mega-enterprise of GLP-1 agonism are two next-gen mechanisms of interest. Psychedelic compounds, including ibogaine and/or its analogs, are intriguing candidates for addiction disorders as well, and the early data in Opioid and Alcohol Abuse are promising. The issue also includes a Company Spotlight appraisal of Neumora, which has entered a new era of existential risk following the failure of the first navacaprant PhIII; a review of significant clinical, fiscal, partnering, and regulatory events from 1Q:25, with particular attention to some unusual positive developments in the Pain space, and the damage done to the kappa-opoid thesis in depression.