Selected recent issues of NeuroPerspective are available for purchase on a single-purchase basis.
The September/October 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, led by Biogens Aduhelm. But Biogen, due partly to their gross misreading of the cost environment, may not be the major beneficiary of the FDA's abdication of its role in quality control: Lilly's donanemab may well be the next Accelerated Approval in the Alzheimer's space, its main role, other than being a slightly less mediocre aducanumab, will be to provide competition and drive down pricing in this nascent market.
Hopes for tau as a target for monoclonal antibodies have been largely dashed, a judgment unchanged by AC Immune's fluky finding on one cognitive endpoint on one out of two trials. The revival of the amyloid hypothesis will divert resources and patients from clinical trials for other therapeutic targets, the most promising of which tend 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 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. Cortexyme has done its correlational homework for the p.gingivalis hypothesis, in the next four months it will be clear whether there is a causal link to AD and an antibiotic solution. There are also a slew of small companies whose programmatic execution is sloppy and their hyperbole excessive, with Cassava and Annovis prominent in that group.
Among the 200+ programs assessed are those from: AbbVie/Alector, AC Immune, Anavex, Athira, Axon-Neuroscience, Biogen, Casma, Cognition Therapeutics, Cortexyme, Denali, Eisai, Lilly, Roche, Syndesi, TauRx. There is coverage assessing prospects for further Accelerated Approvals.
The issue also includes a full review of Huntington's, the landscape having been transformed by the failure of the first wave of ASO programs from Roche/Ionis and Wave/Takeda. UniQure, Triplet, Voyager, and Prilenia are among the other companies reviewed.
The September/October issue includes a focused review of ParosBio and their gene therapy program for autosomal dominant Alzheimer's. Our Psychedelics update section notes developments for Beckley Psytech and ATAI, and the implications of legislative movement in Oregon and California, which yields as much risk as opportunity.
The Alzheimer's/Huntington's issue is being made available for single-issue purchase: $700.
NeuroPerspective has released its March/April 2021 issue, featuring its first-ever, comprehensive review of the rapidly-expanding Psychedelic Therapeutics space, where substances formerly relegated to sacramental and/or illegal status are being formally tested as treatments for CNS disorders. Psilocybin, LSD, DMT, 5-MeO-DMT are some of the ‘classic’ psychedelic substances being explored, along with ‘empathogens’ like MDMA, dissociative drugs like ketamine, esketamine, arketamine, and a few substances less easily categorized, like ibogaine and its derivatives.
There is already substantial clinical support for their use in PTSD (where MAPS has had a successful PhIII trial), Treatment-Resistant Depression (Compass Pathways currently is running a PhIIb study), Cancer-related Pain/Anxiety, and Addictions. Other areas, like Eating Disorders, Phantom-Limb Pain, Cancer Pain and intractable migraines, and even cognitive disorders like ADHD and Alzheimer’s, are being assessed for the potential usefulness of psychedelics.
The Review assesses close to fifty companies involved in psychedelics research: Including MAPS, Compass Pathways, ATAI Life Sciences and its panoply of partnered programs (Viridia, Perception Neuroscience, DeMeRx, Entheogenix, EmpathBio); MindMed, Beckley Psytech, Field Trip Health, MindCure, MYND, Gilgamesh Pharma, Cybin, PsyBio, Small Pharma, Tactogen, Usona Institute, and many more. These companies cover the gamut of skillsets and viability, from well-founded to ephemeral pipedreams. The rationale for psychedelic mechanisms (5HT-2a binding, impact on default mode networks) are reviewed, factors governing the path forward for the class are examined in detail.
The issue also includes a Company Spotlight appraisal of MindMed; an assessment of the aducanumab PDUFA extension, and coverage of six Alzheimer’s programs and their clinical status, including Cassava Sciences, Cortexyme, Lilly, and Biohaven.
The Schizophrenia area has been relatively static, but there are novel mechanisms now maturing that may offer a viable alternative for positive symptoms, and some, singly or as adjuncts, that may finally chip away at cognitive/negative symptomatology. Still in relative infancy are efforts to remediate the underlying synaptic connectivity issues that epitomize the neurodevelopmental nature of schizophreniform illness.
Multiple Sclerosis is, in contrast, the CNS disorder where disease-modification options (for RRMS) have multiplied in type and profile, so that patients now have a range to choose from. The CD20-targeting drugs were the first category that did not require a trade-off between efficacy and safety. BTK-inhibitors may be the next major category to emerge
The issue also includes a Company Spotlight appraisal of Autobahn Therapeutics; an assessment of Acadia’s CRL for pimavanserin in dementia psychosis, and disappointing results for two high-profile Huntington’s programs, from Roche/Ionis and Wave Life Sciences.
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.
The May/June 2020 issue of NeuroPerspective features in-depth reviews of Depression and PTSD.
Depression represents a glaringly incomplete success for psychopharmacology. The majority of patients do not find adequate relief from their first trial, and 25% do not find sufficient benefit from any of the antidepressants they try. Aversive side effects, including weight gain and sexual dysfunction, form a significant barrier to utilization, and the long delay to relief is counter-therapeutic. There have been advances and disappointments in the search for a Rapid-Acting-Antidepressant, the much-publicized utilization of off-label, IV ketamine echoed by JNJ’s success in developing intranasal esketamine, with the counterpoint of Allergan’s emphatic Phase III failure with rapastinel, which had seemed so promising. There are several programs that seem to have potential as RAADs, with positive efficacy findings from Axsome, Relmada, and Sage Therapeutics, though Sage’s zuranolone has not yet established the kind of durability that would make their intermittent dosing paradigm viable. Compass Pathways’ psilocybin program is now in PhII, offering what could be a rapid reset of a patient’s view of self and relationships. 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 glutamatergic drugs-in-development appearing to avoid this AE, and Fabre-Kramer’s Travivo demonstrating a beneficial impact on sexual functioning. Other antidepressant programs discussed in the review include those from Acadia Pharmaceuticals, ATAI/Perception, Blackthorn, Minerva Neuroscience, Navitor, and Novartis/Cadent.
PTSD (Post-Traumatic Stress Disorder) has once again risen in profile, this time as a result of the Covid-19 pandemic, another example of trauma born of both natural (tsunamis, firestorms) and human-made (combat, mass shootings, sexual/physical abuse) calamities. Therapeutic interventions can be focused upon attenuating the limbic system hyperactivation of PTSD and/or accentuating the cognitive rewriting of traumatic memory in a reconsolidation paradigm. 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, Azevan, and Nobilis. Tonix Pharma has emphasized PTSD in its persistently unsuccessful development programming.
The May/June issue also examines a flurry of recent data disclosures, with critical scrutiny of Axsome’s results in Alzheimer’s-agitation; Axon-Neurosciences’ long awaited Alzheimer’s data; and results from Roche, Lundbeck, and NoNO, the latter showing potential in ischemic stroke despite its trial failure. Supernus has finally broadened its portfolio, most importantly with its Navitor partnership. The impact of the Covid-19 pandemic on CNS drug development is considered, with data from AiCure, IQVia, and others regarding trial enrollment and compliance effects. The pandemic has thrown a major obstacle in the path of new drug launches, particularly disrupting Sage’s launch of Zulresso, threatening Intra-Cellular’s Caplyta introduction, and causing Neurocrine to postpone the launch of Ontgenys.
The Company Spotlight overviews ATAI Life Sciences and their creative portfolio of unorthodox therapies for depression, anxiety, and addiction, wherein their stewardship of Compass Pathways’ work stands out as relatively more conventional.
The July/August 2021 issue of NeuroPerspective begins with the Mid-Year Overview of the neurotherapeutics sector. It includes extensive coverage of and commentary about the FDA's dramatically negligent approval of Biogen's Aduhelm/aducanumab, negligent because of its disregard for its own ADCOM recommendations, omission of even basic limitations on labeling and REMS requirements. Other news coverage includes the mixed finds for Biogen/Sage's zuranolone, albeit with the bottom line that there may be a niche depression population for which zuranolone might be a preferred options; new partnerships for AbbVie; continued investor enthusiasm for the burgeoning area of Psychedelic therapies, made tangible by ATAI's highly successful IPO; Cerevel's PhIb success with its M4 agonist; and the tragic turn of events for the Huntington's community in the wake of tominersen's failure in PhIII. An update on the Psychedelics area is included, as are capsule summaries of progress at 150+ CNS companies, including AbbVie, Annovis, Athira, Axsome, ATAI, Biogen, Cassava, Cerevel, Lilly, MindMed, Minerva, Neurocrine, Novartis, Oryzon, Roche, Sage, Sosei Heptares, Tonix, UCB, and UniQure. The Company Review assesses Longboard Pharmaceuticals.
The second section of the issue features a comprehensive review of Addiction, NeuroPerspective's first since 2018. Addiction continues be a curious and disturbing contradiction, almost completely neglected by the pharma industry despite its worldwide prevalence and toll taken, and the extensive press coverage of such dire events as the American 'Opioid Epidemic'. There is a surfeit of hand-wringing and blame-placing, but little more than window-dressing when it comes to providing tangible resources . NIDA has done exemplary work in keeping the lights on for Addictions research, but hardly at the scale necessary given the scope of the disorder. This review details the neurophysiology and therapeutic approaches to opioid addiction, and its substance abuse siblings: Alcohol, Nicotine, and Stimulants (cocaine and methamphetamine). Promising novel target systems are appraised, including orexin, GPR139, HDAC2, and potential psychedelic approaches, including ibogaine and its derivatives. Therapeutic programs from AstraZeneca/Eolas, Cerevel, Delix, Embera, InterveXion, MindMed, Indivior, MediciNova, and Opiant are among those reviewed in the review.
NI Research has released the March/April 2020 issue of NeuroPerspective, which features comprehensive reviews for Huntington's and Epilepsy.
The HD review includes an appraisal of the current thinking around pathophysiology and therapeutic targets, including the varying approaches to modifying the production of mutant huntington, considered the core pathology of this monogenic neurodegenerative disorder. Isoform selective and nonselective gene therapy approaches are considered in detail, given the preliminary indications of promise from the Roche/Ionis program. Neuroinflammation and other mechanisms of current interest are included. The Huntington’s review includes 40+ programs, including programs from Takeda with Wave Life Sciences, Voyager, Triplet Therapeutics; Affiris, Celgene, Locana, Prilenia, UniQure, Vaccinex, and Vybion.
The Epilepsy review considers the two major areas of contemporary work in the area; programs for rare genetically determined epilepsies, such as Dravet Syndrome and Lennox-Gastaut Syndrome, including the first attempt to utilize gene therapy for disease modification rather than settling for seizure-suppression . The second area addresses novel approaches to sporadic epilepsy, with an eye towards the treatment-refractory patient population for whom current anti seizure medications have not provided sufficient control. The review includes 35+ programs, including those from Stoke Therapeutics, Encoded Therapeutics, Marinus Pharmaceuticals, Xenon, UCB Pharma, Zogenix, GW Pharma, and AskBio.
Xenon Pharmaceuticals is the focus of the Company Spotlight. Sidebars include what has become a perennial, rolling appraisal of Biogen's complicated relationship with aducanumab and the early trends in CNS investment activity.
NI Research has released the November/December issue of NeuroPerspective, which features comprehensive reviews for two major neurodegenerative disorders: Parkinson’s and ALS. These reviews include a consideration of the current thinking around pathophysiology and therapeutic targets, including the protein aggregates considered to be associated with these disorders: Alpha-synuclein, TDP-43, and c9orf72. Neuroinflammation, GBA as a target, the gut-brain microbiome, and other mechanisms of current interest are included. Progress in the delineation of biomarkers and models is discussed.
The Parkinson’s review includes 160+ programs, including programs from AbbVie with Mission, Voyager, and BioArctic; AC Immune, Affiris, Lysosomal, Biogen, Cantabio, Caraway, Denali, Roche/Genentech, ImStar, Inflazome, Intra-Cellular, JNJ, Lundbeck, Neuropore, Prothena/Roche, Sage Therapeutics, UCB Pharma, Axial Biotherapeutics, Yumanity, Cerevel, and Neurocrine/Voyager. The ALS review includes 85+ programs, including those from AC Immune, Aquinnah Pharma, Brainstorm Cell Therapeutics, Astellas/Cytokinetics, Biogen/Ionis, Sanofi/Denali, Neuropore, Gladstone Institute, MediciNova, ImStar, Locana, Neurimmune, Voyager Therapeutics, and Wave Life Sciences.
Merck is the focus of the sample Company Review from NeuroLicensing 2020. Sidebars include a more detailed look at Biogen‘s decision to revive aducanumab and the end of the Ehlers era at Biogen, events that are likely more than just temporally correlated. 66 pages.
The November/December issue of NeuroPerspective features a comprehensive review of the Pain space, divided into two major sub-sections, Nociceptive (including Inflammatory) Pain and Neuropathic Pain. Even as attention has necessarily been focused upon the Opioid Epidemic that had its roots in an overreliance upon prescription opioid analgesics, the Pain field has yet to develop non-opioid alternatives that provide sufficient analgesia for severe pain. Some companies have focused upon developing modestly-less-abuse-prone opioid reformulations, these have failed to impress regulators or prescribers. Trevena's 'biased agonists' represented an unacceptable trade-off of efficacy for safety, while NGF antibodies have had a torturous path through clinical and regulatory challenges, and are burdened by their own safety risks. Extending the range of short-acting anesthetics in order to circumvent the need for post-operative opioids is a strategy that has shown some promise. Neuropathic pain is in some ways even more ephemeral and frustrating, there has yet to be a 'gold standard' for neuropathic pain, which comes in several major sub-varieties, and for which current treatments tend to offer only partial relief to a minority of patients.
Among the 60+ programs are assessed are those from: Centrexion, Lilly/AstraZeneca, Teva/Regeneron, Trevena, Vertex, Cara Therapeutics, Wex Pharmaceuticals, Mesoblast, Adynnx, Recro, Novartis/Spinifex, Xenon, Astraea, Coda Therapeutics, Aptinyx, and Amgen. The Boehringer Ingelheim licensing agenda is excerpted from NeuroLicensing 2018-19. Sidebars include coverage of JNJ esketamine program in depression; competition rapidly pursuing Biogen's Spinraza, the ambiguity of Eisai/Biogen's BAN2401 data in Alzheimer's, and the ADCOM rebuff of Alkermes' highly flawed NDA submission for ALKS 5461. 53 pages.
NeuroLicensing 2021 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 2021 provides a vital resource for licensing efforts on both sides of the transaction, both licensors and licensees.
104 pages. Released February 2021. Five-user (within one Company) subscription license:$4200.