Anavex og CNS
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Anavex Is Likely To Report Positive Parkinson's Disease Trial Results!!!
TDT - en af de ganske få analytiker, der har forstået casen og kan argumenterer for, hvorfor hun tror at 2-73 sandsynligvis vil have en positiv effekt i Parkinson.
Så er det ikke kun os, der er hoppet på roller coasteren - håber den holder sig på skinnerne! -
Anavex - analytikeren bag Seeking Alpha analysen.
Hun forudså med faglig begrundelse bl.a. at Neutrope ville fejle i deres Alzheimer fase 2 forsøg - hvilket de så også gjorde i september 2019.
Håber hun med sin yderst faglige indsigt også får ret mht. et positivt udfald for Anavex i Parkinson og Alzheimer mm.
Enormt potentiale hvis det skulle lykkes:
The combined world market for an Alzheimer's disease ("AD") and Parkinson's disease ("PD") drug is estimated to be 21 billion by 2026 and has a compound annual growth rate of 10%.
Skulle Anavex opnå bare 10 % af dette marked og en PE på 10 - ville MC på Anavex skulle stige ca. 10.000 %!!!
HVIS SKIDTET ALTSÅ ViRKER!!!!Richelle Cutler-Strom
Long/short equity, Growth, growth at reasonable price, short-term horizon
Member Since 2019
Company: Battle biotechI am a research scientist and a registered patent agent, with a wide range of biotechnology expertise. I have high accuracy in predicting clinical success of compounds in development. My success is attributed to studying a compound's mechanism of action and possible side-effects using research publications and clinical trial data. In addition, I evaluate risk by identifying the competition, intellectual property status, and financial security. Altogether, my in-depth analysis provides a reliable appraisal of market potential to ensure investment success.
INVESTING IN SCIENCE ----87% return this year. 156% time weighted return.
Offering investment consultation for developing biotech companies at $51/hr.
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Noget tyder vel på, at de nu er nået frem til en anden konklusion. Deres pressemeddelelse antyder, at de mener at det ene af de 2 forsøg har vist sig at være positiv, se
https://investors.biogen.com/news-releases/news-release-details/biogen-completes-submission-biologics-license-application-fda -
Jeg tror de ikke magter at slåsse mere med det, og nu bruger FDA's ressourcer på at finde ud af om det kan svare sig eller ej at fortsætte.
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Biogen fejlede helt i både primære og sekundære i det ene af to komplette ens forsøg.
I det ene forsøg de nu bygger deres ansøgning på til FDA, har de pillet de dårligste patienter ud - nogle endte med svære skader på hjernen - frafaldet var ca. 50 %!
Herefter har de hyret eksterne matematikker for at presse noget brugbart ud af de sidste stakler.
FDA har nu 60 dage til at melde tilbage - spændende at se om dollars og pres kan få et efter min mening skadeligt stof på markedet. -
JPM's rundspørge viser at tvivlen om en godkendelse er ret udbredt blandt såvel læger som aktieanalytikere, men tyder også på en stor usikkerhed/ambivalens. De eneste som selv fortsat synes at tro fuldt og fast på casen er BIIB (og deres partner). Og det er de vel også nødt til
https://www.fiercepharma.com/pharma/docs-don-t-think-biogen-s-aducanumab-should-be-approved-but-they-would-still-use-it-analyst -
Anavex - omtale RETT Syndrome News.
Lidt sørgeligt, at selvom de fleste læger nok ikke mener, at Biogens middel burde godkendes, så føler de sig nødsaget til at udskrive det til Alzheimer patienter simpelthen fordi der ikke findes noget alternativ.
Samme læger ville jo også i mange tilfælde få en økonomisk gevinst ved at udskrive det til patienter - uanset virkning.
En ren pengemaskine - virkning eller ej.Skulle det lykkes for Biogen at overtale FDA til at godkende midlet, så skal 2-73 bare uanset vise sig at være mere effektiv for at blive godkendt - Biogen eller ej, er situationen uændret for Anavex og forhåbentlig de mange patienter, som ville få gavn af 2-73, forudsat at skidtet altså virker - ja ironisk nok gøre det nemmere for 2-73 at blive godkendt på baggrund af en evt. tvivlsom godkendelse af Biogen.
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Anavex - Patent for 2-73 i Alzheimer.
Læs de eksempler Anavex bl.a bygger ansøgningen på.
Kan de omsætte dette i det igangværende forsøg, så bliver der langet meget 2-73 over disken i både flydende og fast form.A19-144 er den methaboliserede udgave af 2-73 - dvs. den form 2-73 omdannes til efter en tid i kroppen. A19-144 har mange af de samme egenskaber som 2-73.
Fra tidligere forskning er 2-73 omdannet efter ca. 10 1/2 t i kroppen. -
Avxl - lidt omtale mens vi venter på Parkinson.
Sidste PD patient færdig behandlet den 4. maj 2020.
Resultaterne fra PD fase 2 kan komme hvornår det skal være.
Er resultaterne dårlige har Anavex iflg SEC max 4-5 dage til at offentliggøre - er de gode må de trække den meget længere evt. for at fremvise flere detaljer.Midt 2020 er lige nu! ( CEO udtagelse om forventet tidspunkt for PD resultater )
Endnu et par skriv fra eksterne personer - igen har endnu ikke kunne finde nogen negative omtale af Anavex.
Anavex Life Sciences Corp (NASDAQ:AVXL) Commences Phase 1 Clinical Study Of ANAVEX3-71: Expects First Line Data In Neurodegenerative Diseases In H1 2021
News Alert: Citius Pharmaceuticals Receives FDA Approval For LYMPHIR™ (Denileukin Diftitox-Cxdl) Immunotherapy For The Treatment Of Adults With Relapsed Or Refractory Cutaneous T-Cell Lymphoma. Click to Read More.Anavex Life Sciences Corp (NASDAQ:AVXL) began phase 1 clinical study of innovative formulation ANAVEX3-71 by enrolling the first patient. The small molecule, which is indicated for the treatment […]
BioPharmaJournal (biopharmajournal.com)
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Takker igen Tasso1.
Jeg venter også med stor spænding på resultaterne.
Mine største bekymringer er:1: Deres patent er udløbet ifølge den dame på SeekingAlfa: Link i post 84982
2: De bliver opkøbt af en af de store spillere før aktien "modner". Det så jeg da mine Veloix aktier blev tvangs indløst. Vi kører stadig en sag imod de nye ejere da vi synes vi fik for lidt for dem.
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Avxl - Cogstate IDN - fælles endpoint AD og PD
Fra AD fase 2 forsøget så vi en meget markant forbedring af Cogstate IDN i forhold til standard behandling. ( Side 32-34 )
Efter få uger er der allerede en stor effekt, så med en behandlingstid på 14 uger i PD fase 2 forsøget, burde vi opnå meget signifikante resultater i det ene primære endpoint. - en af flere årsager til, at jeg tror på positive resultater i PD fase 2 forsøget.
AD og PD har mange fællesnævner - ca. 80 % af PD patienterne udvikler f.eks demens. -
Avxl - Endpoints.
Dvs hvis 1. Anavex og 2-73 i PD har samme virkning i PD patienter, som i AD patienter og 2. er uden bivirkninger, hvilket vi i flere omgange har fået bekræftet i andre forsøg - så skal overskriften på en pr. en af de næste dage hedde: Begge primære endpoints opnået i Parkinson. - forventer derudover, at de fleste af sekundære endpoints også opnås.
Bemærk at Eli Lilly anvender samme primære endpoint, så FDA må anse dette være fyldestgørende for at kunne anskueliggøre en tilstrækkelig virkning - hvis meget overbevisende, så måske nok til en hurtig godgendelse.
Se side 24.
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De kan trække den indtil data er analyseret ... https://www.sec.gov/rules/final/33-8400.htm#seciif
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Autophagy.
Så sent som i 2016 fik en Japansk forsker Nobel Prisen for opdagelsen af denne biokemiske mekanisme ved celledeling/ fornyelse.
En mekanisme han mener er nødvendig for at undgå især Alzheimer og Parkinson m.m.
I marts 2019 offentliggjorde forsker fra Mainz, at 2-73 evner at understøtte denne proces.
Har ikke kendskab til andre testede stoffer, der understøtter denne proces uden alvorlige bivirkninger.
Kun sult understøtter en bedre udrensning i denne Autophagy proces.
( Autophagy menes desuden til at være en meget vigtig mekanisme i forbindelse med den generelle ældningsproces.)
En overstimulering af processen kan dog betyde udvikling af kræft.Der er en hårfin balance mellem måske opdagelsen af den hellige gral og overstimulering i cellerne, der kan udvikle sig til kræft.
Derfor er de kommende resultater i Parkinson ekstrem vigtige, da de kan underbygge hele den grundlæggende teori for 2-73 og samtidig vise, at man ikke får uønskede bivirkninger.
Dvs. fejler man i de 2 primære endpoints i PD fase 2 forsøget, vil man efter min mening skulle meddele dette til markedet meget hurtigt.
Omvendt når man disse 2 primære endpoints og sandsynligvis dele eller alle sekundære endpoints, ønsker Anavex nok at analyserer disse grundigt, for at kunne præsenterer dem samlet - hvilket alt andet lige må være mere tidskrævende.
Håber og tror derfor, at jo længere tid det går før vi får resultater, jo bedre er de - men det er bare mit bud!Autophagy is a method for breaking down and recycling large pieces of cellular "junk" - which could include clusters of damaged proteins or worn-out organelles. If a cell doesn't recycle enough, it can result in a buildup of cellular trash, which then leads to neurological diseases such as Alzheimer's and Parkinson's. Meanwhile, too much recycling has been linked to cancer, Science News reported.
What Is Cellular Recycling? Scientist Wins Nobel Prize For Discoveries on Autophagy
What is autophagy, and how will it impact the future of medicine?
Medical Daily (www.medicaldaily.com)
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Avxl - potential for 2-73 i COVID-19 !!!
Sigma-1 Receptor (S1R) Modulation with ANAVEX
2-73 as Potential Therapy for COVID-19https://hub.bio.org/system/files/2020-04/AV2-73 Sigma-1 Receptor COVID-19 April 2020.pdf
Dette har jeg ikke set tidligere!
Der er ingen dato på og dukkede pludselig op, men lyder lidt vildt, hvis 2-73 også potentielt kan anvendes i behandling af COVID-19.
Der sker godt nok meget bag kulisserne i Anavex - virkemåden/mekanismen synes underbygget af forskellige forskningsresultater, så der er lagt en del arbejde i dette.
Lidt af en bombe, hvis der er hold i casen!
Undre mig dog over, at Anavex ikke lige smider en pr. på, at man også kigger på 2-73 i COVID-19?
Alene dette ville sikkert fange en del interesse.Håber vi får en verificering af ovenstående fra Anavex.
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Anavex kopi af 2-73 for COVID-19
Linket er ustabilt og ville bare sikre mig indholdet.
Sigma-1 Receptor (S1R) Modulation with ANAVEX
2-73 as Potential Therapy for COVID-19
Confidential ' 2020Coronavirus Disease 2019 (COVID-19) Status and Therapeutic Potential of Modulators of Endoplasmic Reticulum (ER) Homeostasis
• The coronavirus disease 2019 (COVID-19), emerged in December 2019, has spread rapidly, with cases now confirmed in multiple countries. As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China. There have been 2,462 associated deaths worldwide (1)
• The impact of viral infection on cellular homeostasis is increasingly recognized as a major contributor to pathological manifestations and the mechanisms by which the virus promotes both viral replication and survival of the infected cell
• Targets and mechanisms of viral infection include the unfolded protein and oxidative stress responses, as well as auto- and mitophagy and ER homeostasis (2)
• Thus, in addition to identifying anti-viral agents and vaccines, it would be valuable to test modulators of ER homeostasis as inhibitors of cellular stress in infected cells
• Protection of infected cells by modulators of ER homeostasis could help the immune system to better deal with the viral infection, thereby improving the health status of infected individuals and decreasing mortality
(1) Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020 https://www.cdc.gov/mmwr/volumes/69/wr/ mm6908e1.htm; (2) Vasallo C., Gastaminza P., Virus Research 209 (2015) 100-117
2SARS-CoV-2 Nsp6 Protein Interacts with the Sigma Receptor
• Sigma-1 receptors modulate ER stress and the protein unfolding response
Sigma Receptor Identified as a Druggable Target for SARS-CoV-2
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing; David E. Gordon, et al.; March 2020 ; bioRxiv 2020.03.22.002386; doi: https://doi.org/10.1101/2020.03.22.002386
3Rationale for ANAVEX
2-73, a validated Sigma-1 Receptor ligand as Treatment candidate for Coronavirus Disease 2019 (COVID-19)
• Very recent proteomic/chemoinformatic analysis (1) identifying drug and clinical molecules that might perturb the viral-human COVID-19 interactome, it gives these potentially therapeutic perturbations a mechanistic context. Among those that may be infection relevant are the inhibition of lysosomal acidification and trafficking with Bafilomycin A1, via modulation of the ER stress and the protein unfolding response pathway by targeting the Sigma-1 receptor
• SARS-CoV-2 Nsp6 protein interacts with the Sigma-1 receptor, which is thought to regulate ER stress response
• Indeed, several of the human proteins in the interactome are targeted by drugs that have emerged phenotypically as candidate therapeutics for treating COVID-19, such as chloroquine, which targets the Sigma-1 receptors at mid-nM concentrations
(1) David E. Gordon et al., A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing; bioRxiv March 27th 2020; doi: https://doi.org/10.1101/2020.03.22.002386
4Coronavirus Triggers Endoplasmic Reticulum (ER) Stress
5ER Stress Implicated in Viral Infections
• InfectionwithSevereacuterespiratorysyndrome(SARS)coronavirus (SARS-CoV) induces ER stress
• SARS-CoVusestheERasasiteforsynthesisandprocessingofviral proteins
• SARS-CoVspike(S)proteinspecificallymodulatestheunfoldedprotein response (UPR) to facilitate viral replication
• ModulationoftheUPRbytheSARS-CoVSproteinalsorepresentsaviral strategy to combat the cellular protective response
Chan CP,et al. Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2006;80(18):9279-9287. doi:10.1128/JVI.00659-06
6Replication Cycle of Coronavirus and ER Stress Induction during Coronavirus Infection
To S. Fung and Ding X. Liu; Front. Microbiol., 17 June 2014 ' https://doi.org/10.3389/fmicb.2014.00296
7
The three stages that induce ER stress are highlighted with numbered star signs, namely:- Formation of double-
membrane vesicles (DMVs) - Massive production and
modification of structural
proteins - Depletion of ER membrane
during budding
Modulation of the UPR by Viruses
In virus-infected cells, three membrane transducers, PERK, ATF6, and IRE1, are differentially activated to enhance ER homeostasis. Arrows represent activation of UPR components by viral infection; lines indicate inhibition of UPR components by viral infection or inhibition between UPR components.
Shanshan Li, Lingbao Kong & Xilan Yu (2015) The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis,
Critical Reviews in Microbiology, 41:2, 150-164, DOI: 10.3109/1040841X.2013.813899 8The Sigma-1 Receptor (S1R) - An Overview
• S1Rsaredistributedinneurons,astrocytes,microglia,oligodendrocytes,andin non-neural tissues
• S1Risanendoplasmicreticulum(ER)proteinlocatedatthemitochondria- associated ER membrane (MAM), which links the ER with the mitochondria
• S1Rhasbeenproposedtoplayaprotectiveroleinstressedcells,asover- expression of S1R reduces ER and oxidative stress and mitigates the effect of pro-apoptotic signals (1)
• S1Rmaycontrolthestabilityofcertaincellularproteinstopreventstress- induced cell death
Modulation of S1R results in a wide range of cellular activities aiming at restoring homeostasis
(1) Hayashi, T., Su, T.-P., 2007. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell 131, 596-610;
9Sigma-1R Regulation of the Three Signal Pathways in ER-stress Activated UPR
Targeting Sigma-1R may regulate ER stress and UPR
ER chaperone BiP/GRP78 under normal conditions binds all the three ER-stress sensors (PERK: protein kinase RNA like ER-kinase; IRE1α: inositol requiring enzyme 1α; ATF6: activating transcription factor 6). Under ER-stress BiP dissociates from sensors. PERK and IRE1α are phosphorylated and oligomerized, ATF6 is translocated to the Golgi. (Abbreviations: eIF2α: eukaryotic translation initiation factor 2α; XBP1: X- box binding protein 1 (spliced form); TRAF2: TNF- associated factor-2; ATF4: transcriptional activator factor-4; MT: mitochondrion; CHOP: c/EBF homologous protein; Bcl-2: B-cell lymphoma 2; Bax: Bcl-2 like protein 2; Bak: Bcl-2 homologous antagonist killer; JNK: c-Jun terminal amino kinase; ASK1: apoptosis signal regulating kinase). Sig-1R activation increases cell survival by decreasing the activation of PERK, ATF6 and IRE1α as well as by lowering pro-apoptopic responses (CHOP, Bax, Bak) and increasing anti- apoptopic Bcl-2 activity.
Penke B, Fulop L, Szucs M, Frecska E. The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases. Current Neuropharmacology.
2018 ;16(1):97-116. DOI: 10.2174/1570159X15666170529104323 10Evaluation S1R as a Potential Target for Antiviral Therapy: Lessons from Hepatitis C Virus (HCV) Infection
• Multiple viruses induce ER stress by dysregulating UPR, intrinsic mitochondrial apoptosis and other related cellular processes, in order to ensure survival, replication and pathogenesis
• In the case of HCV infection, the ER-mitochondria MAM coordinates the antiviral innate response and is the primary site for HCV replication
• S1R, located at the MAM, has been proposed to play a protective role in stressed cells, as overexpression of S1R reduces ER and oxidative stress and mitigates the effect of pro- apoptotic signals. Conversely, silencing of S1R leads to ER stress, induction of UPR, oxidative stress, alterations of Ca2+ homeostasis (ER Ca2+ influx into the mitochondria), induction of dysfunctional autophagosomes, as well as increased susceptibility to pro-apoptotic signals
Given the tight links between ER stress, UPR, mitochondrial apoptosis, MAM and viral replication of HCV and other viruses, it is possible that the S1R could play a role in modulating the cellular response to viral infection and ameliorate pathogenesis
Li S, Kong L, Yu X; Crit Rev Microbiol. 2015 2015 Jun;41(2):150-64. doi: 10.3109/1040841X.2013.813899. Epub 2013 Sep 9. Review. Vasallo C, Gastaminza P; Virus Res. 2015 Nov 2;209:100-17. doi: 10.1016/j.virusres.2015.03.013. Epub 2015 Mar 30.
11CANDIDATE
PRECLINICAL
ALZHEIMER'S DISEASE PARKINSON'S DISEASE DEMENTIA
*RETT SYNDROME *RETT SYNDROME *INFANTILE SPASMS
FRAGILE X ANGELMAN'S
*FRONT. DEMENTIA (FTD) ALZHEIMER'S DISEASE PARKINSON'S DISEASE
DEPRESSION
STROKE
PARKINSON'S DISEASE ALZHEIMER'S DISEASE
VISCERAL PAIN
ACUTE & NEUROPATHIC PAIN
PHASE 1
PHASE 2 PHASE 3
AD ANAVEX2-73-AD-004 ANAVEX2-73-PDD-001
Pipeline of Sigma-1 Receptor (S1R) Modulators
ANAVEX2-73 (Blarcamesine)
U.S. ANAVEX2-73-RS-001 AVATAR ANAVEX2-73-RS-002
Fast Track, Rare Pediatric, Orphan Drug (U.S./EU)
ANAVEX3-71 (AF710B)
ANAVEX1-41
ANAVEX1066- = Orphan Drug Designation by FDA
12
S1R Target Occupancy of ANAVEX
2-73 both in vivo and clinically Established
2D [18F]FTC-146-PET imaging of ANAVEX2-73: Dose- dependent ANAVEX2-73 Target Engagement with S1R
ANAVEX2-73 positive response in functional (ADCS-ADL*) outcome in Alzheimer's disease patients correlate with SIGMAR1 mRNA levels
0 mg /kg 1 mg/kg 10 mg/kg 30 mg/kg
100
80
60
40
20
0
0 5 10 15 20 25 30 mg/kg of ANAVEX2-73
p=0.015
p-value of Mann-Whitney U test
All n=20 patients in study. Slope of ADCS-ADL* from baseline to week 57 with available genomic data
Decrease (Negative) Increase (Positive)
Source: Reyes S et al, AAIC 2018; H Hampel et al., AAIC 2018; *Alzheimer's Disease Cooperative Study Activities of Daily Living 23-item scale (ADCS-ADL) 13
Percent Sigma-1 Receptor Occupancy
SIGMAR1 RNA expression (TPM) - Formation of double-
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Avxl - 18 nye sites i fase 2/3 Alzheimer.
Opdatering den 28. juli 2020
Heraf hele 16 i UK og 2 i Holland!
Igen - hvordan lykkes det Anavex at overbevise så mange læger/ forsker at give 2-73 chancen i Alzheimer - især i denne COVID-19 tid, hvor man skulle tro at fokus lå et andet sted.Primary Completion Date siger stadig 30. sep. 2021, så med en behandlingstid på 48 uger, må Anavex forvente fuld indrulning af de 450 patienter omkring okt. 2020.
Anavex har travlt og afventer ikke endelige resultater i PD.
De må dog have kendskab til tilstanden af rigtig mange af de patienter i både AD, PD og RETT, der er forsat i de åbne ekstension forsøg - min. 300 patienter.RETT US med 21 + min. 50% patienter må være færdigbehandlet ( 7 uger fra den 16. juni ) omkring 3 aug. 2020 - resultater nok omkring sep./ okt 2020.
Q3 afholdes normalt 7.-9. aug - så mon ikke vi får lidt nyt inden da.
Resultater fra Parkinson fase 2 kan komme hvornår det skal være.
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