Top Tweets for #TH1
ITK Inhibitor Selectivity Key to Viral AE Risks
$ACRS $CRVS #ITK #RLK #TXK #JAK
ITK inhibitor drug profiles will likely matter significantly and may be VERY different in virus risk to patients ⤵️
$CRVS ITK-selective inhibitor #soquelitinib - spares key #NK + #Th1 cell types and enhances #CD8+ for viral surveillance - likely low risk for viral AEs
$ACRS oral ITK inhibitors are more potent and less selective, their MOA shown to reduce CD8+, NK cells and Th1 cells which protect against viral infection and thus would expect viral infections (i.e, EBV, Zoster, etc) may emerge with these therapies:
- ATI-2138 #modzatinib tri-inhibitor inhibits ITK/RLK(TXK)/JAK3 and shown to reduce NK and CD8+ cells - likely high risk for viral AEs
- ATI-9494 is a dual ITK/RLK(TXK) inhibitor and reduces Th1, CD8+, NK cells - likely high risk for viral AEs
Understanding MOA differences between ITK inhibitors in development and what T-cell subtypes are being affected will be essential to understanding safety, AE profiles in this developing space.
Drug Profiles + T-cells Key for Viral Surveillance and AEs
$ABBV $CRVS $KYMR $LLY $PFE #JAK #STAT6 #ITK
CD8+ and NK cells are CRITICAL in protecting against viral infection/reactivation + Th1 plays supporting role
Drugs that spare or enhance these virus fighting T-cell subtypes will likely not have viral AEs
Below is data for JAKi used in dermatological I&I diseases for Epstein-Barr Virus EBV + Zoster virus ⤵️
JAK inhibitors all block CD8+, NK cells and Th1 at different levels, include virus risk on drug labels:
JAK1 - $ABBV #Upadacitinib
<0.4% cases of EBV, 2.5-5.2 Zoster/100 patient years
JAK1/2 - $LLY #Baricitinib
only 1 confirmed case of EBV in trials, 2.2-7.1 Zoster/100 patient years
JAK3/TEC - $PFE #Ritlecitinib
no known EBV in trials, 1.17 Zoster/100 patient years
New oral drugs in development for atopic dermatitis by comparison have ideal drug profiles that would predict significantly reduced risk of virus reactivation as MOAs leave the key viral surveillance T-cells (CD8+, NK, Th1) intact or even enhance them, see drug profiles:
STAT6 - $KYMR KT-621 MOA targets just Th2 cells and Th1, CD8+ and NK cells spared for viral protection
ITK - $CRVS #soquelitinib makes enhanced CD8+ memory cells, spares #NK + #Th1 cells all idea for viral surveillance/protection and drug's MOA reduces #Th2 and #Th17 activation while increasing #Treg cells
$CRVS New paper
Credible explanation why selective ITK inhibition (i.e., preserving #Th1/#IFNγ while increasing #Tregs) is biologically consistent and may be another component to why it is superior for Treg formation v indiscriminate suppression of BOTH ITK and RLK by less selective inhibitors
Paper shows sustained IFNγ signalling has supportive role in Treg expansion through endothelial IRF1, MHC II and PD-L1, rather than acting only as a pro-inflammatory cytokine.
Complements the proposed direct effect of $CRVS oral ITK inhibitor #soquelitinib on T-cell fates:
1. suppression of #Th2/#Th17 differentiation
2. sparing of #Th1 and IFNγ and
3. increased #iTregs
Corvus shows #soquelitinib spares RLK (>100:1 selectivity of ITK over RLK), it retains Th1/IFNγ activity (sparing) to preserve this tissue-level tolerogenic support while still suppressing pathogenic ITK-dependent responses (infection). Another piece of evidence and reason why a ITK-selective inhibitor can promote and sustain Tregs.
Endothelial IFNγ-IRF1 axis is dispensable for Th1 but required for Treg expansion and tissue tolerance to prevent GVHD in mouse allo-HCT @BloodPortfolio
https://t.co/sv2G7ZqYhh @OSUHematology @ParvathiRangan2
#ZGYO
• İlk 5 kurumun payı Hissenin dolaşımdaki paylarının neredeyse üçte ikisi sadece beş kurumun elinde. Bu, tahtanın "toplu" olduğunu ve dışarıda kalan (Diğer Kurumlar) ky/dağınık yatırımcı oranının %35,74 gibi makul bir seviyede kaldığını gösteriyor. Toplu tahtalar, teknik kırılımlarda çok daha sert ve kararlı trendler oluşturmaya müsaittir çünkü "malın sahibi" bellidir.
Asıl Oyuncu: Yatırım Fonları
• %41,42'lik Devasa Pay: Takasın açık ara tek hakimi 35 milyon lot ile Yatırım Fonları. İş Yatırım (%7,63) veya Ziraat Yatırım (%5,77) gibi diğer büyük aracı kurumlar bile fonların yanında çok küçük kalıyor.
• Ne Anlama Geliyor? Hissede ciddi bir kurumsal yatırımcı (fon) pozisyonlanması var. Fonların bu kadar büyük bir paya sahip olması hisseye bir nevi "kalkan" sağlar; günlük piyasa volatilitesinden ziyade daha trend odaklı, orta-uzun vadeli bir oyun kurulduğunu gösterir.
• "Diğer" kısmının %35,74 olması, hissenin ky (küçük yatırımcı) elinde sürünmediğini gösteriyor. Ancak burada dikkat etmen gereken en büyük risk, Yatırım Fonlarının satışa geçme ihtimalidir. Eğer ilerleyen haftalarda "Yatırım Fonları"nın payı azalırken, "Diğer" kurumların payı artmaya başlarsa (mal dağıtımı), teknik grafikteki destekler bile çalışmayabilir.
Grafik şahane teknik kırılım gerçekleşti.
Takas tarafında ise #bulls fonların ana oyuncusu iş yatırım en güçlü ikinci oyuncu
BofA nında son hafta satıştan alışa dönmesi önümüzdeki günlerde hissenin hareketli geçeceğinin işareti
Bakalım önümüzdeki dönem yatırımcısının yüzünü güldürecek mi !
#svgyo #lxgyo
119回歯科医師国家試験
東京デンタルスクール無料講義動画
Th1・Th2・Th17の違い、もう迷わない。５分で学ぶ国試免疫119A84 https://t.co/BZo6Pd8zem
#Th1
#Th2
#Th17
#cbt
#119回歯科医師国家試験
#歯科医師国家試験
#東京デンタルスクール
$CRVS oral ITK inhibitior #soqueltinib has unique MOA profile for affecting different T-cell subtypes:
Increases #Th1, CD8+ to fight cancer and infection
Increases #Tregs to give duration benefit of inflammation control beyond treatment window
Decreases #Th2 + #Th17 for autoimmune across whole spectrum
No other drug has this profile and no pharma company has this target developed or in their portfolio
Updated Table of Different MOA Effects on T-cells/Innate Cell Types in Autoimmune Diseases
(incorporating new data)
Some of indications and companies affected:
i.e. Atopic Dermatitis, Asthma
$SNY $REGN $LLY $APGE $ABBV $PFE $BMY $NKTR $KYMR $NRIX $CRVS
🚨New paper highlights challenge of treating atopic dermatitis as disease follows pattern of immune aging!
Different T-cells contributors by age:
Pediatric: Low #Th2, IL-10 (Treg) immunotolerance
Adult: Enriched Th2, NF-κB, #Th1, #Th17
Geriatric: Reduced IL-4, High NF-κB
Immunological Differences in Atopic Dermatitis Across Age Groups: Insights from Single-Cell Multi-Omics https://t.co/b7qc1Cifc6 #biorxiv_immuno
Why $CRVS ITK inhibition w/ oral #soquelitinib is novel MOA:
1. Skews/increases #Th1 cells (prevents infections)
2. Makes memory #CD8+ cells w/ stemness that resist T-cell exhaustion in #TME
3. ⬆️ immunosuppressive #Tregs
4. Prevents #Th2 cells, ⬇️ cytokines IL-4, IL-5, IL-6, IL-13, IL-31
5. Prevents #Th17 cells, ⬇️ cytokines IL-6, IL-17, IL-21, IL-22
6. Reduces activity of #ILC2 cells dependent on ITK, IL-4, IL-5, IL-13 cytokines (major and early role in AD⤵️)
ITKi has ability to control inflammation across Th2/Th17 spectrum, from AD (Th2) to #psoriasis (TH17) in skin inflammation or #asthma (Th2) to #COPD (Th17) in airways.
JAKi can block Th2 and Th17, but they also reduce Th1 and Tregs so patients get infections more often, lower safety and benefit does not last off treatment⤵️
Current drugs can't treat across #Th2 <––> #Th17 spectrum effectively in either skin or respiratory diseases requiring different treatments, combination therapies, and large patient populations with unmet need.
A single new drug candidate being developed by #Corvus Pharmaceutical $CRVS may for the first time bridge this gap in both skin and respiratory diseases:
🔹#atopicdermatitis (Th2) to #psoriasis (Th17)
🔹#asthma (Th2) to #COPD (Th17), and #ACO (mixed)
$CRVS oral #ITK inhibitor #soquelitinib novel MOA reduces both Th2 AND Th17 cell subtypes and downstream inflammatory cytokines. Additionally, recent work by both Corvus and #Janssen $JNJ showed selective inhibition of ITK over RLK results in increase in anti-inflammatory #Treg cells.
Soquelitinib shows 115-fold selectivity for ITK over RLK and has shown a strong increase in Treg cells and reduction in Th17⤵️
1. https://t.co/OZhbW2Bgc1
2. https://t.co/OPTelXmBYD
Soquelitinib unique MOA allows drug to address dysregulated Th17/Treg diseases by restoring the balance between the two cell types addressing the underlying immunological cause of the disease.
#Elevated #Th1 and #Terminally_differentiated #cytotoxic_T_cells with #suppressed #Tc17_lymphocytes in #lung_tissue of #advanced #COPD and #IPF #patients undergoing #lung_transplantation
👇
https://t.co/LB5T1v1I7B
#copd @GOLD_COPD @ATSBlueEditor
@atscommunity @ATS_Assemblies
@copd_inet @exosome @Tim_G_Dixon
@RespirologyAPSR @RespiratoryBMC
@BMJOpen_Resp @EMJRespiratory
@SPLF_SocPneumo @BTSrespiratory
@NIH @CResnews @exosome @AnnalsATS @DrLBoominathan
@EuroRespSoc @EuropeanLung @copd_inet @ERSpublications @WHO @UKPleura @RespirEffect @COPDdoc @UPTURN_COPD @COPDCanada @copdnewstoday_ @COPDaction @COPDFoundation @ThoraxBMJ @AJPLung @SMSbiotech @DrTedros @HelmholtzMunich @PulmPEEPs @ATS_AII @ATS_RCMB @ATS_RCMB @ATSCPAssembly @KulikovUNIATF @FDA @Hananianick @ATS_PC @EU_Commission @Nicole_european @apepoc_es @cpgale3 @eu_eeas
#ITK inhibitors prevent pancreatic islet infiltration by T cells in #T1D
New: #BCL6 #Tfh cells key role in T1D
ITK inhibitors block #Tfh by suppressing the key Bcl-6 and promoting #Th1 factor #Tbet, skewing for Th1
Would love a study of $CRVS ITK inhibitor #soquelitinib in T1D:
- ⬆️ #Treg
- ⬇️ #Tfh (potential benefit reducing autoreactive B-cells in pancreas)
https://t.co/VU7fxHrKIf
BCL6 in T cells promotes type 1 diabetes by redirecting fates of insulin-autoreactive B lymphocytes https://t.co/5ERIysM2tP #biorxiv_immuno
Paper suggests repurposing metabolic GLP-1RA for use in inflammatory diseases⤵️
- #semaglutide + #tirzepatide increase insulin sensitivity, have #cardio + #hepatic protective properties
- #liraglutide improves renal #CKD disease and decreases #Th1 + #Th17 cells
Invert: Consider potential for safe, oral anti-inflammatory drugs to address metabolic diseases + inflammation.
- ITK inhibition reduces #Th17 cells+ increases #Tregs, lowers #inflammation of adipo-, hepatocytes, and skeletal muscle cells and lowers #macrophages, which can increase insulin sensitivity and restoring Treg/Th17 balance also shows benefit in renal kidney disease
AE safety profile of oral ITKi #soquelitinib reducing inflammatory T-cells much better than GLP-1RAs.
$CRVS ITKi T-cell control future in metabolic diseases?
Honest post-topline assessment for $ACRS Ph 2a AD:
Expected + confirmed:
- Prior work showed ATI-2138 ⬇️ Tregs, confirmed by no durable/long-lasting response beyond treatment
https://t.co/u0Gw1doV93
- Non-selectivity blocks all #Th1 #Th2 #Th17 #Treg
Surprises:
- ATI-2138 seems active, but no PBO control
- good EASI reduction, 50% black and/or dupi resistant
- itch response encouraging, but n=5/8 patients (63%)
- Hints of immunesuppression, not definitive, n=12
(1 case of #Lymphopenia at one blood draw, 1 case #myalgia w/o elevated #CPK, but not a requirement for immunosuppression)
@lifesciencerpt $ACRS ATI-2138 blocks JAK3 + ITK + TXK may be counterproductive reducing all T-cells (#Th1, #Th2, #Th17 and #Treg cells). Hard to predict if clinical benefit in atopic dermatitis.
$CRVS only selective ITK inhibitor #soquelitinib, increases Tregs
https://t.co/gw2n6MnI03
Corvus $CRVS highly selective #ITK inhibitor #soquelitinib reduces #TCR signal strength, moderates #mTOR activity.
These cell signal adjustments select for #Th1 and memory CD8+ cells to fight cancer and #Treg to rebalance immune system, while blocking #Th2 and #Th17 that cause autoimmune diseases across spectrum from #AtD #asthma #COPD to #psoriasis #IBD etc
$CRVS continues to strengthen patent moat for ITK inhibition platform. New patent published July 3, 2025 for #soquelitinib CPI-818 and other ITK inhibitors:
- Increasing #Th1 activity
- Treat cancer (including relapsed/refractory #lymphoma, solid tumor, lung cancer, colorectal cancer, pancreatic cancer, prostate cancer, breast cancer, gastric cancer, head and neck cancer, leukemia (pg 32)
- Treat autoimmune (very extensive list, see below + pg 33)
- Treat allergies (pg 33-35)
- Reverse T-cell exhaustion (decreasing #LAG3 #TIGIT #PD1, pg 30-31)
- Dose and Dosing Regiments well discussed including numerous ways of intermittent dosing methods (pg 40-42)
- ITK selectivity over RLK is key and discussed and identified as key differentiator of CPI-818
- Examples in patent discussed: PTCL, #Lupus #Psoriasis #PulmonaryFibrosis (pg 62)
https://t.co/Zs2fk1TxbV
🚨 TNF-α signaling requires ITK for metabolic reprogramming in dysregulated #Th1 + #Th17 cells in rheumatoid arthritis.
Potential opportunity for $CRVS in RA, w/ only clinical selective oral ITK inhibitor #soquelitinib blocks Th17 + ⬆️ Tregs, ITKi prevents metabolic change
T cells release TNF-α that stimulates changes to their metabolism via ITK-Akt-mTOR during differentiation, a pathways dysregulated in rheumatoid arthritis @scisignal @SarahDimeloeLab @EmLBishop
https://t.co/TqdsaGhJfX
Cystatin A promotes the antitumor activity of T helper type 1 cells and dendritic cells in murine models of pancreatic cancer
👉 https://t.co/mgG26AV1L6
#Th1 #PDAC #DendriticCells #Tcells
View #BTC update ... !
Sẽ có 2 trường hợp sẽ xảy ra ✍️✍️✍️
#TH1 : Từ đây #BTC sẽ phá đỉnh rút râu sau đó điều chỉnh về 95k-100k sau đó #AltcoinSeason
#TH2 : Từ đây #BTC sẽ điều chỉnh về 95k-100k sau đó là #AltcoinSeason
Anh em thích trường hợp nào hơn ?
Chúc ae buổi chiều vui vẻ .
GÀ EXCEL VBA
#Th1 khai báo from thì viết code đơn giản còn người sử dụng phức tạp hóa vẫn đề.
#Th2 thì phải viết code khó hơn vì phải trả kết quả ngay lập tức.
👉Chỉ cần bạn biết gõ số việc còn lại chương trình tự xử lý.
#Ketoannguyentuan
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