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I wondered the same thing earlier. Per the link that follows: "For each application for a new medicine, two committee members - known as rapporteur and co-rapporteur - from different countries are appointed to lead the assessment (for generics only one rapporteur is appointed). They are appointed according to objective criteria to make best use of the available expertise in the EU.
The role of the rapporteur and co-rapporteur is to conduct the scientific evaluation of the medicine independently from each other. They each form an assessment team with assessors from their national agency and sometimes from other national agencies.
In their assessment reports, each team summarises the data from the application, presents its judgments of the medicine’s effects and its views on any uncertainties and limitations of the data. They also identify questions that will have to be answered by the applicant. The two separate assessments take into account regulatory requirements, relevant scientific guidelines and experience in the evaluation of similar medicines.
In addition to the rapporteur and co-rapporteur, the CHMP also appoints one or more peer reviewers from amongst the CHMP members. Their role is to look at the way the two assessments are performed and ensure that the scientific argumentation is sound, clear and robust."
https://www.ema.europa.eu/en/about-us/what-we-do/authorisation-medicines/how-ema-evaluates-medicines-human-use
I liked this part also:
"Did you know..?
In some cases, for example when a medicine is intended to treat a life-threatening disease for which there is no satisfactory treatment or if the disease targeted is very rare, EMA can recommend marketing authorisation on the basis of less complete or limited evidence on the medicine, provided that further data are provided at a later stage.
As for all marketing authorisations, it must still be demonstrated that the benefits of the medicine outweigh the risks."
Is this our peer review or is it just a new article?
Anyone have access?
https://www.nature.com/articles/s41591-023-02709-6
It looks like MSQ provides a link to the Asian markets -
"Listen to our clients
“MSQ Ventures, with their expertise and broad connections in China healthcare industry, demonstrates great professionalism and outstanding performance during all the collaborations with us. MSQ team worked closely with us and completed high-quality deliverables on time with acute attention to our needs.”
— Mr. Yuval Gottenstein. Chief Executive Officer. Aposense
“MSQ provided key insights and informative interviews from KOLs in the research report, helping us to clarify our strategic goals in the Chinese market. MSQ team worked closely with us and completed high-quality deliverables on time with attention to our needs.”
— Dr. Masoud Tavazoie, Chief Executive Officer and Co-founder, Rgenix
“The Tier 1 strategic investors MSQ Ventures introduced were of the highest professional quality. The majority of the investors were knowledgeable and well-prepared. They understood our underlying technology and core competencies in short order, which differentiates MSQ Venture’s network in China from other firms.”
— Mr. Boo J. L. Nilsson, Chief Executive Officer, CBRITE Inc.
“MSQ Ventures’ insights into China’s healthcare industry was invaluable in enabling my team, and I, to evaluate, accurately, the enormous opportunities, within OBT’s therapeutic space, in China. MSQ’s custom-tailored research and meticulous approach helped my team and I achieve a deeper understanding of the Chinese biotech landscape, and effectively establish high-quality partnerships with active biotech investors and biopharma partners within a very short amount of time. ”
— Dr. Christian Rohlff, Founder and Chief Executive Officer, Oxford BioTherapeutics"
http://msqventures.com/
http://msqventures.com/client-testimonials
How statisticians have fun -
https://www.cinc.org/Proceedings/2009/pdf/0541.pdf
Kun Jin did tie for first place in the first exercise.
Very glad he's aboard.
A brief Rett testimonial appears to be recent - sorry if it has already been posted -
https://www.reddit.com/r/biotech_stocks/comments/zjr97v/anavex_life_sciences_avxl_rett_syndrome_trial/
Yep - Some of these operators may be looking for a new line of work but with their resumes what could they qualify for? Maybe get into politics?
or
https://themindcircle.com/terrifying-old-school-clown/
Michelle was a friend to Anavex back in the early days. I liked the work she did.
Hah! - I'll bet they were sweating it.
Thanks Bill - Good fortune to you and also all the other longs on here!
For the science buffs and anyone else including insomniacs here's a comprehensive article regarding the sigma-1. I highlighted the one sentence regarding 3-71.
The section regarding Anavex -
"Many pharmacological and genetic data have proven that activation of muscarinic M1 receptors (mAChRs) attenuates symptoms of neurodegenerative pathologies, as in the case of MTDLs able to bind both M1 and s1 receptors. The most investigated compound representative of this class is ANAVEX 2-73 (also known as Blarcamesine). This compound is in advanced clinical phases for several CNS diseases such as AD, Parkinson’s disease (PD), Rett, and Fragile X Syndromes (anavex.com/#!/pipeline, accessed Apr 3, 2021). In addition to binding M1 and s1 receptors, Blarcamesine also binds M2–M4 receptors (with micromolar affinity), Na+ channel site 2, and NMDA receptor (NMDAR). In this context, Fisher and co-workers, who previously developed orthosteric M1 receptors agonists (e.g., AF102B, AF267B, and AF292), extended their approach in order to target also s1 receptors. With this aim, compound AF710B (also known as ANAVEX 3-71, that can activate both M1 and s1 receptors with high potency and selectivity was identified. AF710B is a positive allosteric modulator (PAM) of M1 receptor, as it improves the efficacy of carbachol, and this activity, together with a comparable agonism at the s1 receptor can preserve synaptic elements in vitro. In vivo studies performed on trihexyphenidyl-treated rats and 3xTg-AD mice showed that AF710B can restore cognitive deficits and attenuate signs of AD phenotypes by the reduction of ß-secretase 1 (BACE1) levels, GSK3ß and CDK5/p25 activity (which contribute to the hyperphosphorylation of tau protein), neuroinflammation, soluble and insoluble Aß40 and Aß42 plaques, and tau pathology. In fact, AF710B reduces the expression of the putative BACE1, so that proteolytic fragments produced by ß-secretase were considerably lower in 3xTg-AD treated than in untreated mice. Moreover, tau kinases GSK3ß and CDK5 take part in the mechanism of hyperphosphorylation of tau protein. In particular, in AD patients, CDK5 activator p35 is cleaved to produce the protein p25, which binds with high affinity and activates GSK3ß. The activation of M1 receptors produces a reduction of GSK3ß expression, while the activation of s1 prevents the formation of CDK5/p25. Therefore, the inhibition of GSK3ß and CDK/p25 by AF710B, upon interaction with both M1 and s1 receptors, results as a promising approach in the treatment of tauopathies .
The effect of s1 receptors in inflammation through microglia modulation has been reported, and AF710B was shown to reduce reactive astrocytes and activated microglia in the animals, as detected by the low levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1). Notably, astrocytes and microglia are increased in number and size in AD patients.
Another study performed using AF710B on McGill-R-Thyl-APP transgenic (tg) rats revealed that this MTDL can reduce amyloid pathology and markers of neuroinflammation while increasing amyloid cerebrospinal fluid clearance and synaptic marker. The most important achievement is represented by the prolonged duration of these effects, which are maintained five weeks after the treatment is interrupted.
In addition to AF710B and ANAVEX 2-73, Anavex Life Sciences Corp portfolio comprehends an isomer of ANAVEX 2-73, named ANAVEX 1-41 (Figure 2) that next to the activity toward s1 and M1 receptors, also displays activity for a1, 5-HT2, and D3 receptors, with an indication for the treatment of depression, stroke, and neurodegenerative diseases (anavex.com/#!/pipeline)."
https://www.mdpi.com/1422-0067/22/12/6359/htm
Some detail on Tanya(adult Rett trial) by her father around the 1:09:20 mark.
A little FYI from Reverse Rett -
"Much excitement has been generated across the UK Rett community this week due to the announcement by the company, Acadia that they have submitted a New Drug Application to the American Food and Drug Administration (FDA), for their drug ‘Trofinetide’ for people with Rett Syndrome.
At Reverse Rett, we are receiving some questions about this announcement and wanted to share our perspectives.
The following points add to our reservations about this application:
There have been some anecdotal reports from families in America sharing positive experiences of the Trofinetide Lavender study. However, the data which have been shared by Acadia to date, only show very small differences between patients treated with Trofinetide over patients who received placebo. Also, a relatively high number of people (20%) left the trial; the most commonly cited side effect was diarrhoea. More evidence is needed before the community can arrive at a conclusion regarding Trofinetide and its potential for improving symptoms in people with Rett Syndrome.
On a broader level, we have spent the last 18 months learning as much as we can about the UK regulatory processes and Health Technology Assessments, so that we are prepared to work with regulators and payers when the time comes for new treatments for Rett to be assessed for funding. We know from this work, that it is going to be a complex and difficult task to get any treatment for Rett through in this economic climate, even though the patient population needs it so badly. Our early interactions with regulators have shown us that they much more strongly favour treatments which have clear cut positive effects, even if they are expensive. Especially here in the UK, where public funds are tight, and the NHS is under so much pressure. The regulators want to see they are getting value for money from new treatments. "
https://www.reverserett.org.uk/this-weeks-trofinetide-announcement/
It's Rare Disease Day - I'm hopeful we can improve the lives of these Rett girls and their families!
https://scontent.fagc1-1.fna.fbcdn.net/v/t39.30808-6/274595519_4743806345668253_7211835790364141334_n.jpg?_nc_cat=102&ccb=1-5&_nc_sid=730e14&_nc_ohc=JtXecQBIKJwAX9BA4Fk&_nc_ht=scontent.fagc1-1.fna&oh=00_AT8CjmNVYw15Vnt-rVgjckEZy75GmnA-LdFo5RgTjZ8tbw&oe=6222B7D4
Some new detail as to what may cause Rett - the role of TCF20
https://www.spectrumnews.org/news/protein-complex-points-to-new-route-to-rett-syndrome/
also
https://rettsyndromenews.com/2022/02/25/mecp2-forms-protein-complex-that-helps-regulate-brain-health/
Sounds pretty positive to me - highlight is mine
"Oral Anavex 2-73 Safely Eases Rett Symptoms, Severity in Phase 3 Trial"
“Anavex 2-73 was not only safe but it also demonstrated clinically meaningful improvements in multiple common areas of impairment, which are known to impair the quality of life of girls and women affected by the disorder,” Terence O’Brien, MD, a principal trial investigator, said in a press release.
O’Brien is also chair of medicine and head of Monash University’s Central Clinical School, and the deputy director of research at Alfred Health and program director of Alfred Brain, all in Australia."
https://rettsyndromenews.com/2022/02/02/oral-anavex-2-73-safely-eases-rett-symptoms-severity-phase-3-trial-finds/
I wonder if Anavex will be mentioned??
"Rett Syndrome Externally-Led Patient Focused Drug Development Meeting
March 11, 202210:00 am – 3:00 pm EDT"
https://rettpfdd.org/
Hmmm - Doctor M better watch it with that Model T. He was almost caught pestering Michel Vounatsos with it not long ago.
Nice! - Thanks Plex (and Guzzi).
Mayo - Here is a decent article regarding binding of a few Anavex compounds. Hope it's helpful.
In part -
"Many pharmacological and genetic data have proven that activation of muscarinic M1 receptors (mAChRs) attenuates symptoms of neurodegenerative pathologies, as in the case of MTDLs able to bind both M1 and s1 receptors. The most investigated compound representative of this class is ANAVEX 2-73 (also known as Blarcamesine). This compound is in advanced clinical phases for several CNS diseases such as AD, Parkinson’s disease (PD), Rett, and Fragile X Syndromes (anavex.com/#!/pipeline, accessed Apr 3, 2021).
In addition to binding M1 and s1 receptors, Blarcamesine also binds M2–M4 receptors (with micromolar affinity), Na+ channel site 2, and NMDA receptor (NMDAR).
In this context, Fisher and co-workers, who previously developed orthosteric M1 receptors agonists (e.g., AF102B, AF267B, and AF292), extended their approach in order to target also s1 receptors. With this aim, compound AF710B (also known as ANAVEX 3-71, Figure 2) that can activate both M1 and s1 receptors with high potency and selectivity was identified. AF710B is a positive allosteric modulator (PAM) of M1 receptor, as it improves the efficacy of carbachol, and this activity, together with a comparable agonism at the s1 receptor can preserve synaptic elements in vitro.
In vivo studies performed on trihexyphenidyl-treated rats and 3xTg-AD mice showed that AF710B can restore cognitive deficits and attenuate signs of AD phenotypes by the reduction of ß-secretase 1 (BACE1) levels, GSK3ß and CDK5/p25 activity (which contribute to the hyperphosphorylation of tau protein), neuroinflammation, soluble and insoluble Aß40 and Aß42 plaques, and tau pathology [82]. In fact, AF710B reduces the expression of the putative BACE1, so that proteolytic fragments produced by ß-secretase were considerably lower in 3xTg-AD treated than in untreated mice.
Moreover, tau kinases GSK3ß and CDK5 take part in the mechanism of hyperphosphorylation of tau protein. In particular, in AD patients, CDK5 activator p35 is cleaved to produce the protein p25, which binds with high affinity and activates GSK3ß [83]. The activation of M1 receptors produces a reduction of GSK3ß expression, while the activation of s1 prevents the formation of CDK5/p25. Therefore, the inhibition of GSK3ß and CDK/p25 by AF710B, upon interaction with both M1 and s1 receptors, results as a promising approach in the treatment of tauopathies.
The effect of s1 receptors in inflammation through microglia modulation has been reported [54,86,87], and AF710B was shown to reduce reactive astrocytes and activated microglia in the animals, as detected by the low levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1). Notably, astrocytes and microglia are increased in number and size in AD patients.
Another study performed using AF710B on McGill-R-Thyl-APP transgenic (tg) rats revealed that this MTDL can reduce amyloid pathology and markers of neuroinflammation while increasing amyloid cerebrospinal fluid clearance and synaptic marker. The most important achievement is represented by the prolonged duration of these effects, which are maintained five weeks after the treatment is interrupted [88].
In addition to AF710B and ANAVEX 2-73, Anavex Life Sciences Corp portfolio comprehends an isomer of ANAVEX 2-73, named ANAVEX 1-41 (Figure 2) that next to the activity toward s1 and M1 receptors, also displays activity for a1, 5-HT2, and D3 receptors [81], with an indication for the treatment of depression, stroke, and neurodegenerative diseases (anavex.com/#!/pipeline)"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232171/#B88-ijms-22-06359
For anyone that's interested in some of the biology of Anavex compounds here's a pretty comprehensive article that describes the binding affinities and etc.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232171/#B88-ijms-22-06359
See the statement the author made regarding 3-71 -
"The most important achievement is represented by the prolonged duration of these effects, which are maintained five weeks after the treatment is interrupted."
Awesome pipeline imo.
Some sources say the Medicare increase is due in part to Aduhelm.
"CMS on Friday announced that monthly Medicare Part B premiums and deductibles will increase substantially in 2022, in part due to uncertainty around the Covid-19 pandemic and coverage for the Alzheimer's drug Aduhelm."
https://www.advisory.com/daily-briefing/2021/11/16/medicare-premiums#:~:text=In%20a%20notice%2C%20CMS%20said%20there%20are%20five,The%20expected%20relationship%20between%20incurred%20and%20cash%20expenditures
Just fyi
Good questions Tred - Some of the patents have quite a bit of back and forth messaging between Anavex and the patent office which can go on for months.
You should try looking at this link:
https://portal.uspto.gov/pair/PublicPair
enter the application number(or patent # etc)
The tab "transaction history" shows the back and forth dialog and the "image file wrapper" tab gives the details - it's pretty interesting(to me).
As to the inventors I'm guessing Anavex sometimes pays other parties to do the research and apply for the patents with Anavex being the owner. Probably someone else could provide a different view but that's just my thoughts. fwiw
Ref: "The comment on composition of matter patents is interesting. Isn't that the type AVXL was getting?"
Anavex was pretty busy on the patent front in 2021.
What a variety.
https://patents.justia.com/assignee/anavex-life-sciences-corp
Ref - "I doubt any medicine is the right way to address the stats of autism, Alzheimer's, Parkinson's, diabetes etc etc. all diseases of lifestyle, western culture and economics."
Some truth in what you say at least in regards to Alz(and I suspect diabetes as well) -
"Globally, the lowest validated rates of Alzheimer’s in the world are rural India, where they eat low meat, high grain, high bean, high carb diets. It’s possible that the apparent protective association between rice and Alzheimer’s is due to the fact that the drop of rice consumption was accompanied by a rise in meat consumption, but other population studies have found that dietary grains appear strongly protective in relation to Alzheimer’s disease. In other words, perhaps, don’t pass on the grain, but “pass the grain to spare the brain.”
"This is consistent with data showing those who eat vegetarian appear two to three times less likely to become demented, and the longer one eats meat-free, the lower the associated risk of dementia."
https://nutritionfacts.org/2015/11/12/where-are-the-lowest-rates-of-alzheimers-in-the-world/
Ok true enough - I was thinking he'd be listed if he is a vice president but I understand.
If Edward does work at Anavex the addition of an Epidemiologist makes you wonder why-
"Epidemiology is a field where trained epidemiologists study patterns of frequency and the causes and effects of diseases in human populations. Epidemiology provides the scientific footings for evidence-based medicine and allows placement of strategies for improvement in public health. Epidemiology is often referred to as the cornerstone of modern public health research and practice and it relies on a variety of relevant public health areas, including biology, biostatistics, social sciences, and assessing risk of exposure to a threat.
What does an epidemiologist do? Epidemiologists design, implement, and manage studies of various types regarding pathogens. Their work could pertain to pandemics, such as the present COVID-19 pandemic, or to isolated outbreaks of wholly unrelated diseases. Even in relatively mundane situations, such as a minor salmonella outbreak, it is up to epidemiologists to contain the outbreak, investigate the cause, and determine if any other factors are in play. They will collect data, analyze the data, and make sure that all of the proper authorities in every instance get the information they need."
https://www.healthcare-management-degree.net/faq/what-is-epidemiology-and-what-does-an-epidemiologist-do/
Good find - I'm not sure why he doesn't show up on the company directory
https://www.anavex.com/about-us
But his Linked in profile says that he's a vice president at Anavex
"Experience
Anavex Life Sciences
Vice President, Clinical Development
Company Name Anavex Life Sciences
Dates Employed Jul 2021 – Present
Employment Duration6 mos
Horizon
Director, Clinical Development
Company Name Horizon
Dates Employed Mar 2021 – Jul 2021
Employment Duration 5 mos
Viela Bio
Director, Clinical Development
Company Name Viela Bio
Dates Employed Jul 2020 – Mar 2021
Employment Duration9 mos
AstraZeneca
Company Name AstraZeneca
Total Duration 5 yrs 1 mo
Title Life Cycle Management, Medical and Payer Evidence, BioPharma
Medical Respiratory & Immunology
Dates Employed Aug 2019 – Jul 2020
Employment Duration 1 yr
Title Head, Epidemiology, Infection, Neuroscience and Autoimmunity & Center of Excellence
Dates Employed Sep 2018 – Aug 2019
Employment Duration1 yr
Title Director, Epidemiology, Infection, Neuroscience and Autoimmunity
Dates Employed Apr 2017 – Sep 2018
Employment Duration1 yr 6 mos
Title Director, Epidemiology, Inflammation and Autoimmunity, Medical Evidence and Observational Research
Dates Employed Jul 2015 – Apr 2017
Employment Duration1 yr 10 mos
Thank you for clarifying - now I understand what you mean by doubling the market(as in twice the number of Anavex drugs taken).
I was not in a quiet place so I thought he was referring to a combo pill.
Happy Holidays
A combination of 2-73 and 3-71. I'm still not sure they'd actually go that route - but - let 2-73 run until it's almost time to go generic and then patent a combination. Rule the market until something better comes along.
I'm glad Missling has a group of experienced directors to help with the decision making. Figure it out and then see what Big Tom thinks.
https://www.anavex.com/about-us/
I do like the animated graphic at the top of that Anavex page.
This recent Alzheimer's Clinical Trials Report has listed drugs in various phases of development. Anavex 2-73 has been put in the "synaptic activity" category of effect.
https://issuu.com/alzdiscovery/docs/addf-ctr-2021-06-singles
Perhaps I missed something but I did not see Simufilam listed?
fwiw
The best of luck to you IHID - To stay informed of the latest info from a patient perspective I can recommend this site -
https://healthunlocked.com/
A recent post from Reverse Rett - I did not listen to the entire presentation but I do know that the discussion gets more specific to Anavex around the 52:30 mark. Other parts explain why delays have happened(yes covid) and more trial location specifics. fwiw
Rett and anxiety - can 2-73 help? We may soon find out -
"Anxiety is a common yet often under-estimated problem for children and adults with Rett Syndrome, which can impact other symptoms and be detrimental to their quality of life.
In this session, Consultant Clinical Psychologist at the CIPPRD and CIPP Rett Centre, Dr Ruksana Ahmed, will discuss these issues, drawing on her wealth of experience and particularly the work of the CIPP Rett Centre in managing the symptoms of over 250 people with Rett Syndrome.
Dr Ahmed will discuss the CIPP Rett Centre's findings around diagnosis, presentation and possible treatment pathways, as well as considering the impact of anxiety on both the individual and the family.
Following the presentation Dr Ahmed will take questions."
https://www.eventbrite.co.uk/e/dr-ruksana-ahmed-anxiety-in-rett-syndrome-tickets-186271341597
The CIPP center is a clinical trial site for 2-73 -
https://m.facebook.com/reverserett/photos/a.118893834826217/4064057623643132/?type=3
For example -
This is Tanya, who is taking part in the Anavex trial at the Clinical Trial Facility at St Mary's Hospital.
— Reverse Rett (@ReverseRett) September 18, 2021
If you're interested in future clinical trials for #RettSyndrome for your child, please register him/her on the Reverse Rett Patient Registry👇https://t.co/PxplcquPel pic.twitter.com/XjLOTIufM3
Yes that is a grim reminder of some future day. In the meantime I suggest you find yourself a bottle of Don Julio 1942 and enjoy today. It really is one of the best I've tried.
Just fyi
That sounds like a great experience Red - thanks for contributing to that projects success. I'm sure it was interesting and exciting.
When I was around 10 or so my older sisters boyfriend brought me a box with 2 dozen or so sci fi books in it (EE "Doc" Smith type stuff). He told me,"My parents won't let me keep these books so you might as well have them."
I have read quite a few since then.
I'm still not sure why Marco Cecchi was ever listed as an inventor on Anavex patent #11,103,478 but I noticed in the patent document detail(image file wrapper) Marco conveyed his interest to Anavex on 6/14/19.
Sorry but I never had any luck copying images from that database to IHUB.
Just FYI
https://portal.uspto.gov/pair/PublicPair
Also have to throw in the fact that 2-73 metabolizes into Anavex 19-144 which continues to stimulate the Sigma-1 but differently in some way?
" ANAVEX2-73 is metabolized into the pharmacologically active metabolite, ANAVEX19-144
Metabolite also acts as sigma-1 receptor agonist with neuroprotective action like ANAVEX2-73, restoring homeostasis and neuroplasticity
The apparent elimination half-life of the metabolite (21.45 hr) is approximately twice that of ANAVEX2-73 (10.71 hr) hence the active metabolite result in extended activation of the sigma-1 receptor"
https://anavex.com/wp-content/uploads/ANAVEX2-73-PKPD-Phase-2a-2017.pdf
Bringing a drug to market is serious stuff - peoples health and maybe lives are at stake and caregivers too. Dr Missling gets to build up a company while he plans for what is to come.
Really it reminds me of the thought and planning that must go into military campaigns.
"Perhaps the single greatest logistical triumph in military history, Hannibal almost destroyed the armies of Rome by ingeniously marching an army of elephants from Africa, through Spain and over the Alps into Italy. His envelopment and destruction of a much larger Roman army at Cannae was the worst defeat ever suffered by Rome in its history. Credited with stating, “We will either find a way, or make one,” Hannibal’s march over the Alps was not only a military success, but also an exceptional feat of engineering science."