Selected recent issues of NeuroPerspective are available for purchase on a single-purchase basis.
NeuroPerspective has released its Spring 2023 issue, featuring comprehensive reviews of neurotherapeutics programs addressing Schizophrenia, ALS, and Addiction.
The Schizophrenia area had been relatively moribund since the field became dominated by Second Generation (‘atypical’) antipsychotics, but that is now changing, as novel mechanisms aimed at the three domains of schizophreniform illness are maturing. The most tangible advance is in the slow-to-arrive début of muscarinic agonists, with Karuna‘s KarXT having performed strongly in two PhIII trials. While the second PhIII saw the readout for negative symptoms slip below statistical significance at one timepoints, Karuna is preparing to file the NDA midyear, and we have no doubt as to KarXT’s approvability. Negative symptom impact will not be part of the label, since the protocols used thus far could be at risk of pseudospecificity, but the negative sx data will be usable in marketing KarXT. Somewhat behind time wise are a flock of muscarinic agonists which hope to emulate KarXT by being highly selective for M4 or M1/M4 subtypes: Cerevel, Neurocrine/Sosei, and Maplight stand out in this group. New approaches to broad spectrum antipsychotic impact are also coming to fruition, with Otsuka/Sunovion‘s ulotaront finishing PhIII during 3Q:23. Cognitive impairment has been a challenging indication, one of the more intriguing programs is Neurocrine‘s DAAO inhibitor, licensed from Takeda, in PhII, while Boehringer Ingelheim has gone all in on iclepertin, in PhIII. Neurostructural interventions that might have a disease-modifying component are much more preliminary in their development, though Oryzon Genomics has their epigenetic modulator vafidemstat in PhII.
ALS has been the neurodegenerative disorder where FDA standards have traditionally been relatively lax, as was the case for Amylyx‘s Relyvrio, whose approval was largely attributable to coaching by the then-head of neuroscience for the FDA. The next example of Agency flexibility is like to be Biogen/Ionis‘ tofersen, for the rare SOD1 mutation form of ALS. Genetically defined subgroups have been more difficult targets than expected, and midstream disease-modifiers may be relatively more accessible: Programs from QurAlis, AbbVie/Calico, Denali, Sanofi/Denali, and Annexon are in the clinic, preclinical programs of interest include those from Libra Therapeutics, NRG Therapeutics, and Aclipse Therapeutics.
Addiction receives less pharma investment and attention than even stroke/TBI, and this has not really changed despite the onslaught of the opioid epidemic, exacerbated by the toxic potency of fentanyl. Orexin-1, GPR139, and mGluR5 inhibitors are three next-gen mechanisms of interest. Psychedelic compounds, particularly ibogaine and/or its analogs, are intriguing candidates for addiction disorders as well.
The issue also includes a Company Spotlight appraisal of Noema Pharma; a Company review sample from NeuroLicensing 2023, and a review of significant clinical, fiscal, partnering, and regulatory events from 1Q:23.
A one-year (1-5 user) subscription to NeuroPerspective is $3100. A 6-10 user subscription is $5250. Other customized userbase and startup pricing options are available. The Spring issue is being made available as a single-issue purchase, for $850.
The Fall 2022 issue of NeuroPerspective has been released. It features our comprehensive annual review of the Alzheimer's space, including an assessment of the current conceptual trends vis-a-vis pathophysiology and therapeutic targets. One major theme is the resuscitation of the amyloid antibody space by the FDA, initially led by Biogen's Aduhelm, which was derailed by discord around data and sticker-shock from the egregious pricing. Eisai/Biogen's lecanemab does not show superior efficacy, but the data is consistent, and it appears somewhat safer, though the risk of ARIA remains significant. With gantenerumab results coming at the end of November, and a donanemab readout next year, it is easy to foresee two or three amyloid antibodies approved. Whether they will be reimbursed by CMS Medicare will depend on whether any of these companies learned anything from the Aduhelm debacle.
Hopes for tau as a target for monoclonal antibodies have been largely dashed. The most promising programs appear to be in the neuroinflammation and cellular waste disposal categories. The neuroimmunological space has just started to mature, with clinical stage programs underway from Denali/Sanofi, Alector/GSK, and Alector/AbbVie. This type of midstream focus offers the prospect of disease modification without having to precisely identify the upstream molecular culprit that initiates the disease process. There are also a slew of small companies whose programmatic execution has been sloppy and their hyperbole excessive, with Cassava and Annovis prominent in that group, the former well on its way to oblivion.
Among the 200+ programs assessed are those from: AbbVie/Alector, AC Immune, Alex, Anavex, Athira, Biogen, Casma, Cognition Therapeutics, Cyclerion, Denali, Eisai, Karuna, Lexeo, Lilly, NervGen, ProMIS, Roche, and Vigil.
The issue also includes a full review of Anxiety, where the pervasive prevalence of the disorder has far eclipsed the paltry resources devoted to bettering the limited generic options currently available. But more selective GABAergic programs are underway at Cerevel, Engrail, and GABA Therapeutics, with other novel mechanisms being explored by Bionomics, JNJ, and Idorsia.
The third therapeutic area reviewed is TBI, another high-prevalence disorder with little available therapeutically. There are programs well into clinical development by SanBio and Biogen, with TBI a possible expansion target for NoNO Therapeutics if nerinetide is successful in its stroke trial.
The Fall issue includes a focused review of Gate Neurosciences and their promising approach to neuroplasticity. The approval of Amylyx's ALS drug is examined. Our Psychedelics Update section notes updated information questioning the erstwhile benefits of 'microdosing'; notes MindMed’s attempt to correct course before it is too late; questions the premise of psychedelics as a direct route to neuroplasticity in neurodegeneration; as well as incipient signs of a backlash to the rapid growth of the sector.
The Winter issue of NeuroPerspective has been released. This is the Overview Issue, which assesses the past year, with a particular eye to how the Alzheimer’s landscape has (and hasn’t evolved), and looks ahead to forecast key developments that can be expected in 2023. 2023 begins a two to three year sequence of trial completions that will transform the CNS space. The issue includes:
1) Highlights and Lowlights from 2022, with due consideration of Leqembi/lecanemab, Amylyx, Biogen’s new CEO, and much more.
2) Key questions and anticipated data reveals for 2023.
3) Fiscal parameters from 2022, trends in fundraising via both institutional investors and pharma partnering, the latter down 75% compared with 2021.
4) Corporate capsule summaries covering 180+ CNS companies, some in considerable depth.
5) Psychedelic Update: The status of this highly hyped subsector is reviewed, with particular attention to key questions facing the Psychedelics field, and how they are being handled by Compass Pathways, Atai, MindMed, Small Pharma, Delix, Onsero, and their peers, including an assessment of which companies appear to have the necessary fiscal resources to achieve POC, and which ones do not.
6) The impact of Karuna’s PhIII success on the general perception of the Psychiatry field and the prospects for novel therapeutics. Promising new programs are in development by larger companies ranging from Merck to Sunovion to Neurocrine, as well as a host of small companies, including Cerevel, Neumora, Engrail, and Gate Neurosciences.
The Spring 2022 issue of NeuroPerspective has been released, featuring in-depth reviews of Depression, PTSD and Stroke.
Depression continues to be a frustratingly incomplete success for psychopharmacology. . There have been advances in the search for a Rapid-Acting-Antidepressant, an increased commercial deployment of off-label, IV ketamine, the commercially unrewarding advent of JNJ’s intranasal esketamine. There are several programs that claim to have potential as RAADs, with generally mixed efficacy findings from Axsome, Relmada, and Sage Therapeutics. Sage’s zuranolone features anxiolysis, somnolence, and an intermittent dosing paradigm. Compass Pathways’ psilocybin program is getting ready for PhIII, at the head of a burgeoning array of psychedelic and dissociative candidates, for which an optimal protocol is far from having been defined. These include programs from Atai/Perception, Delix, Field Trip Health,MindMed, Mindset/Otsuka, Beckley Psytech, and Small Pharma.
The almost ubiquitous prevalence of sexual dysfunction as a consequence of depression and SSRI/SNRI has been a significant deterrent to treatment and compliance, with several new-generation entrants appearing to avoid this AE, and Fabre-Kramer’s Exxua demonstrating a beneficial impact on sexual functioning in depression. Other antidepressant programs discussed in the review include those from Atai/Perception, Supernus/Navitor, Novartis/Cadent, multiple candidates from Janssen/JNJ, and more than seventy others. At least eight novel mechanisms will report POC results in the next two years.
PTSD (Post-Traumatic Stress Disorder) has risen in profile, as a result of the Covid-19 pandemic, and most recently the war in Ukraine. The pharma industry has generally taken a passive approach to PTSD, leaving the funding of research to the DoD and VA in the US, but small companies are working in this undertreated and very large-scale domain, including Aptinyx, Alto, and Bionomics. PTSD is also the arena where MAPS’ MDMA program showed impressively solid PhIII results, and other ‘psychedelics/empathogens’ companies are working as well, including Atai, Gilgamesh, and MindMed.
The third therapeutic sector review covers Stroke.With almost 800,000 stroke cases annually in the US alone, this neglect became untenable in the long run. Biogen is the first of the major pharma companies to make a return to ischemic stroke, via its partnering of TMS’ promising new thrombolytic. There is progress on solving the seemingly intractable puzzle of neuroprotection (NoNO, Avilex, ZZ Biotech), with NoNO wrapping up PhIII with nerinetide.
Spotlight assessments are included for NoNO and the NeuroLicensing 2022 review of Lilly.
The Spring issue also considers the grim fiscal start to 2022; a second ASO failure in neurodegeneration; partnering/acquisitions by AbbVie, Biohaven, Sanofi, and Acadia.
It is being made available as a single-issue purchase for $750.
The November/December 2020 issue of NeuroPerspective reviews Autism Spectrum Disorder. The nomenclature itself is a confession of conceptual sloppiness; ASD is a vaguely defined umbrella category, under which huddles a highly heterogeneous assortment of phenotypic presentations, divergent in their type, intensity, and prognosis.
ASD is always impactful, and it can be devastating on several levels, though that depends on where it falls on the range of developmental disruption. At the micro-familial level, few events are likely to be more painful for parents than to slowly learn that the kind of intense attachment they feel for a child may never be fully felt or expressed in return. At the macro-societal level, the prevalence of autism in its multiple manifestations has exploded, with the latest estimate, in 2018, reaching one of every 59 children in the United States, up from one in 68 just four years ago, up twenty-fold over the past three decades. No other disorder has displayed anything near this kind of dramatic growth in sheer numbers. Approaches range from nonspecific efforts to reduce hyperstimulation or boost cognition to thus-far frustrating attempts to access the oxytocin-vasopressin axis, modulate the gut-brain microbiome, or find gene regulators that may impact gene networks that might permit broadband interventions. Gene therapies are more directly applicable to the second group of neurodevelopment disorders covered in the issue; Rett Syndrome, Fragile X, Angelman Syndrome, where monogenic targets are apparent, though each appears to involve a narrow therapeutic window, its viability as yet unproven.
Companies whose programs are included in the review include Janssen, Roche, Novartis, Acadia, Neuren, Ovid Therapeutics, Taysha Gene Therapies, Axial Biotherapeutics, Kaerus Biosciences, Sangamo, Biogen/Ionis, Ultragenyx/HealX, and Servier/Neurochlore.
Other clinical topics covered in the issue include the failure of the first tau antibody in Alzheimer’s (Genentech/AC Immune), ambiguous Parkinson’s results from Roche/Prothena‘s alpha-synuclein antibody, clinical successes for Aptinyx and Intra-Cellular Therapies, and overhyped data for Cassava and Amylyx. Corporate developments assessed include BIAL’s acquisition of Lysosomal Therapeutics, four more small neuro companies going public, and a continuing flow of fiscal resources into the sector.
NeuroLicensing 2023 is completely revised and updated, analyzing current trends in CNS deal parameters, providing candid assessments of the major and midsize companies involved in CNS inlicensing. Licensing agendas and performance are reviewed and appraised. NL 2023 provides a vital resource for teams on both sides of the transaction, both licensors and licensees.
107 pages. Released February 2023. Five-user (within one Company) subscription license:$4500.