Selected recent issues of NeuroPerspective are available for purchase on a single-purchase basis.
The Summer issue of NP has been released, evaluating the areas of Psychedelic Therapeutics, Epilepsy, and Rett Syndrome.
1) Psychedelic Therapeutics were the sole focus of the March/April 2021 edition of NP, but no area has been evolving more rapidly, or received more media coverage, the latter imbued with varying degrees of superheated hype. This return to the topic assesses the state of this nascent area as a brief flood of resources for these companies has been sharply diminished, even as the data continues to come in validating the value of these treatments for some patients, in some disorders. s. There are several tiers of companies, defined by both their science and fiscal resources. Atai stands out for its diverse plethora of psychedelic (and other) programs under its corporate umbrella (including Perception, DeMeRx), though there seems a risk of internal redundancy, with some three distinct subcomponents each pursuing novel psychedelic molecules. Compass Pathways stands out for its groundbreaking work on systematizing psilocybin therapy, including its core psychotherapeutic components. Whether it is blazing a path too easily followed by others is a separate but pertinent issue. MindMed‘s resources continue to outpace its corporate judgment, with an excessive reliance upon LSD programs that will never have wide applicability. Gilgamesh has a variety of intriguing programs, whereas GH Research has a singular focus on 5-MeO-DMT, and needs to use its resources to branch out. Cybin, Small Pharma, and Beckley Psytech also fall under the first tier category. The second tier includes smaller companies for the most part, with more limited resources: MindSet has achieved the first psychedelic partnership with a major company (Otsuka); Reunion is the new spin-out of Field Trip‘s research programs; CaaMTech, Eleusis, Terran Biosciences, and Diamond Therapeutics are just a few of the many others. There are companies determined to parse the therapeutic from the hallucinogenic, such as Delix. There are many micro-companies that are not going to survive, this Review considers 55+ of the more tangibly constituted. Some very basic questions remain to be answered in this new field, including the overriding lack of clarity regarding the hallucinogenic, euphoric, dissociative core experiences associated with classic, empathogen, and dissociative (e.g. ketamine) classes of drugs–are they a necessary route to therapeutic benefit, or are they side effects that can be avoided without sacrificing efficacy? Our bet is on the former, but this will be confirmed (or not) by the data as it emerges.
2) The Epilepsy review evaluates progress in the two major areas of contemporary work in the area; programs for rare genetically determined epilepsies, such as Dravet Syndrome and Lennox-Gastaut Syndrome, which is going to be the testing ground for gene therapy for disease modification, via programs from Stoke Therapeutics and Encoded Therapeutics. 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, with particular attention to multiple programs from Xenon, as well as the utilization of more selective GABAergic molecules (e.g. Cerevel, Engrail) and neurosteroids (Praxis,Marinus).
3) Rett Syndrome is the third therapeutic area covered in the Summer issue. Rett has shown the challenges of safely remediating even this kind of single gene target, for too much MeCP2 is as pathological as too little. This defeated the first gene therapy program from Novartis/Avexis, which had seemed promising. At this point, trofinetide from Acadia/Neuren is the most advanced treatment, the NDA should be filed soon, and should have no problem with approval.
Spotlight assessments are included for Engrail Therapeutics and Gilgamesh Pharma. The Summer issue also considers the continuing dilemma posed by Biogen even as it finally moves on from Aduhelm; the mixed record of neurosteroids (e.g. Sage, Praxis, Eliem, Marinus) Cassava‘s deterioration; Centrexion’s disingenuous lack of basic disclosure, and more. 70 pages.
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 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.
NI Research has released the November/December 2021 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, SOD1, and c9orf72. Neuroinflammation, GBA as a target, LRRK2, the gut-brain microbiome, autophagy, and other mechanisms of current interest are included.
The Parkinson’s review includes 130+ programs, including programs from AbbVie, Mission, AC Immune, Annovis, Bayer, Aspen Neuroscience, BIAL Bio, Biogen, Cantabio, Caraway, Casma, Denali, Roche/Genentech, Lundbeck, Neuropore, Prothena/Roche, Sage Therapeutics, UCB Pharma,Vanqua, Axial Biotherapeutics,Yumanity and Cerevel. The ALS review includes 85+ programs, including Amylyx, Biogen/Ionis, Sanofi/Denali, GSK/Alector, Neuropore, Libra, Locana, Neurimmune, Prilenia, QurAlis,and Verge Genomics.
QurAlis is the focus of the Company Spotlight. Sidebars include an overview of the burgeoning roster of CNS portfolio companies (e.g. Neumora, Neurvati, Cambrian, Atai); developments in Alzheimer's, including results from Cortexyme, AC Immune and Cassava. Our Psychedelic Update section assesses Pasithea's revenue-generation plan as well as developments at Atai/DeMeRx, Field Trip Health, and MindMed. 66 pages.
NI Research is the leading publisher of independent research on the neurotherapeutics industry, and has developed an unmatched information base regarding both publicly and privately held CNS companies. The November/December review of PD and ALS culminates a two-issue sequence on neurodegeneration, with the September/October 2021 issue having comprehensively covered Alzheimer’s and Huntington's.
NeuroPerspective is the authoritative, independent, bimonthly review of the neurotherapeutics area, providing critical analyses of therapeutics-in-development; A one-year (1-5 user) subscription NeuroPerspective is $2900. A 6-10 user subscription is $4950. Other customized userbase and startup pricing options are available. The Parkinson’s/ALS review issue of NeuroPerspective is available as a single-issue purchase for $700.
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 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.
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 2022 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 2022 provides a vital resource for licensing efforts on both sides of the transaction, both licensors and licensees.
103 pages. Released February 2022. Five-user (within one Company) subscription license:$4250.