Ex-Merck research, biochem professor. Post for biochem literacy and use X as research notebook. Focus: ITK, STAT6, Treg, Th2, Th17, I&I Large $CRVS Shareholder
Joined September 2024
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Two collaborations I would love to see for $CRVS next generation #ITK inhibitors in oncology: cancer vaccine + solid tumour
1. $MRNA mRNA vaccine + ITKi may lead to deeper vaccine response due to special memory CD8+ Tcells
2. $MRK ICB anti-PD1 #Keytruda + next gen ITKi for solid tumour to reverse/prevent T-cell exhaustion
Series of posts on this potential imbedded here:
teapaw.org/HOThomasWPhelps/status…
$CRVS here are some prior posts with research showing ITK inhibition ability to make special memory CD8+ Tcells that would lead to cancer vaccine potential:
teapaw.org/HOThomasWPhelps/status…
$CRVS #Soquelitinib 3Q Call Takeaways:
• Ph3 PTCL/Ph2 SIERRA1 AD: Enrolling on schedule
• PTCL: 1Q27 futility guidance unchanged, EOY27 Topline data unchanged (note these are event driven)
• Angel AD: Part 1 fully enrolled, readout now March 2027; AD/psoriasis + IL-17 profiles reportedly resemble those of 8 Corvus patients
• HS: Interest/demand high; enrolment ahead of plan after 1-month, based on this 1H27 data; response durability a key focus
• Encouraging HS biomarkers and clinical activity could accelerate planning for a placebo-controlled Ph2b before Ph1b complete
• ALPS: Safety consistent with AD/PTCL despite substantial disease burden; findings could inform additional indications.
• ALPS/HS: B-cell depletion seen in ALPS, Miller comments on this on call and it is very important as may indicate strong potential in HS as SQL reduces Tfh cells required for B-cell formation in GC, see my prior post quoted below for this to be significant potential benefit for HS patients, especially in lesions
• Asthma: IND already accepted by FDA; likely January start reflects holiday shift from EOY26
Updated Nov 5 Corporate Presentation
corvuspharma.gcs-web.com/sta…
$CRVS ITK Inhibition Modulates B-Cells via #Tfh
In #hidradenitissuppurativa #HS #Soquelitinib benefit may be several fold w/ novel MOA and go beyond Th17 suppression:
1. SQL reduces #Th17 differentiation, lowers #IL17 + Increases #Tregs to restore Treg/Th17 balance
2. Reducing #Bcells present in lesions
ITKi suppresses B-cells, reducing total serum #IgG #IgG1 #IgG2a in arthritis model likely by preventing differentiation of #Tfh cells which provide critical help to B cells in germinal centres (GCs)
sciencedirect.com/science/ar…
$CRVS #soquelitinib: New JACI research adds mechanistic and more importantly metabolic support for planned Ph2 #asthma study, particularly in Th17-driven non-T2 disease:
• Mitochondrial #OXPHOS sustains steroid-resistant Th17 cells producing LIGHT and osteopontin, which drive airway remodelling
• Severe disease persisted without IL-4Rα signalling, pathology outside #dupilumab IL-4/IL-13 blockade
• Prior ITK research w/ CPI-818 (SQL) showed inhibition during T-cell differentiation favoured suppressive FOXP3+ Treg-like cells, w/ lower OXPHOS gene expression, reduced mTOR signalling and less BATF matching the metabolic changes in this new paper
Connection and mechanistic rationale for $CRVS upcoming asthma trial w/ non-T2 arm: SQL inhibiting ITK adjusts Signal 1 pathways including metabolic programme needed to sustain Th17-driven asthma, potential to broaden efficacy beyond type 2 blockade
The metabolic reprogramming of T cells controls airway remodeling in severe asthma
sciencedirect.com/science/ar…
@herro86957 @CincyImmunology @CincyResearch @jacionline Hope Steele
$CRVS Rare disease #ALPS abstract adds to confidence for safety and biomarker understanding of MOA of #ITK inhibitor #soquelitinib
Safety: Targeted Destruction of Double Negative Tcells w/ 20% to 75% reduction in Ki-67+ DNTs w/ SQL. SQL targets "bad" DNT T-cells, but left the "good" circulating CD4+ and CD8+ cells unchanged v traditional treatments that wipe out all immune cells
Biomarkers:
Patient 3 showed a profound systemic response w/ 75% reduction in DNTs + 50% reduction in mature B cells (which make autoantibodies) and a decrease in serum IL-10, FASL, soluble IL-2 receptor, and Vitamin B12. In ALPS, elevated Vit B12 and IL-10 are classic hallmarks of disease severity. Dropping these levels is concrete proof of disease reversal at a molecular level.
Patient Quality of Life:
100% Steroid & Immunosuppressant Discontinuation: All 3 patients successfully stopped all background medications (including steroids). Proves SQL isn't just an "add-on" therapy, but it is powerful enough to be a standalone, primary treatment.
Organ Shrinkage: 2 out of 3 patients saw physical reductions in spleen size, and 1 saw a reduction in lymphadenopathy (swollen lymph nodes). This directly reduces the risk of splenic rupture and the uncomfortable "fullness" ALPS patients live with.
Strong Safety Profile: Achieving zero Grade 3 or 4 adverse events and zero therapy interruptions over a full 360-day period is very rare for a systemic immunomodulator. This indicates excellent long-term tolerability matching data from PTCL trial
Conclusion:
One year of treatment with SQL was well tolerated and controlled disease with discontinuation of background therapies in 3 of 3 pts
ASH Abstract:
eppro02.ativ.me/web/page.php…
$CRVS sees success for #ITK inhibitor #soquelitinib in #ALPS "patients were able to discontinue background medications," data presentation on Dec 14 at #ASH26
Opens door based on MOA for much larger cytopenias/indications (see quoted post below) and CEO Miller has discussed them, expect to hear more about this tomorrow on earnings call.
Quote from PR want to extend to pediatric, younger patients. This is another de-risk event and many ALPS patients have fibrotic disease, this will be very interesting to hear how that
"All three patients were able to discontinue background medications including steroids and reported improvement in ALPS related systemic symptoms. Corvus believes the data supports continued enrollment in the trial and based on the results to-date, we plan to explore longer treatment durations and enroll younger pediatric patients."
corvuspharma.gcs-web.com/new…
This data set should be enough for $CRVS to apply for Breakthrough Therapy Designation (BTD) for #soquelitinib for ALPS which currently has no FDA approved treatments specific for disease.
$CRVS success for its #ITK inhibitor in #ALPS was not completely a surprise based on prior posts showing similarities w/ rapamycin downstream effects and that drugs strong benefit, but #soquelitinib offers much safer targeted approach. This adds to the data supporting SQL overall immune regulation and control, more safety data and further shows potential across autoimmune diseases.
Further, "Treatment with [rapamycin] results in complete responses in patients with autoimmunie lymphoproliferative syndrome ALPS"
3 of 4 patients RAPID COMPLETE RESPONSE
$CRVS Ph2 ALPS study just looking for 25% reduction in size of spleen and lymph nodes, probability of achieving this goal seem very high, when considering $CRVS #soquelitinib ITK inhibitor => same effect on mTOR as mTOR inhibitor rapamycin which induces cell death and apoptosis in abnormal lymphocytes => COMPLETE RESPONSES.
pmc.ncbi.nlm.nih.gov/article…
$CRVS sees success for #ITK inhibitor #soquelitinib in #ALPS "patients were able to discontinue background medications," data presentation on Dec 14 at #ASH26
Opens door based on MOA for much larger cytopenias/indications (see quoted post below) and CEO Miller has discussed them, expect to hear more about this tomorrow on earnings call.
Quote from PR want to extend to pediatric, younger patients. This is another de-risk event and many ALPS patients have fibrotic disease, this will be very interesting to hear how that
"All three patients were able to discontinue background medications including steroids and reported improvement in ALPS related systemic symptoms. Corvus believes the data supports continued enrollment in the trial and based on the results to-date, we plan to explore longer treatment durations and enroll younger pediatric patients."
corvuspharma.gcs-web.com/new…
Success for $CRVS #soquelitinib in #ALPS sets up other autoimmune cytopenias worth $24B, including:
- immune thrombocytopenia purpura (ITP) - $4B
- autoimmune hemolytic anemia (AIHA) - $750M
- autoimmune neutropenia - $15B
- lupus - $3B
- Evans syndrome - $1B
#Rapamycin led to patients in ALPS seeing CRs, soquelitinib has same MOA effect on mTOR in T-cells for cytopenia diseases, and Ph2 study opens up similar diseases worth $24B.
pmc.ncbi.nlm.nih.gov/article…
$CRVS #Soquelitinib: Positive mechanistic read-through from new IL-2 paper, also could apply paper to $NKTR #Rezpeg a PEG-IL-2 agonist
• More Tregs alone did not guarantee better control Higher doses of one PEG-IL-2 worsened mouse colitis; but adding mTOR inhibitor improved outcomes.
• SQL similar two-pronged approach, increasing Tregs and reducing effector inflamatory T-cells: SQL targets immune balance as MOA of ITK inhibitor reduces #Th2/#Th17 + increases #iTregs. AD biomarkers support switching for iTregs over Th17 differentiation
Engineered receptor-biased IL-2–drug immunoconjugates selectively expand Tregs and suppress effector cells for autoimmune therapy @CellRepMed
cell.com/cell-reports-medici…
$NKTX Another job posted, now 5 new jobs in 2 months - Senior Director/Executive Director, Biostatistics
Potential Interpretation: Nkarta appears to be strengthening biostatistics and clinical data management for potential later-stage development
job-boards.greenhouse.io/nka…
$NKTX New Job Posted Today - Senior Director/Executive Director, Clinical Data Management
Prepare NKX019’s DM infrastructure for potential pivotal trials and a BLA, establish readiness before pivotal studies begin, and recruit/manage staff.
Require someone with previous pivotal-study and marketing-application experience
Upcoming presentations are Nov 8: myositis; Nov 9: #Ssc; Nov 11: overall safety
job-boards.greenhouse.io/nka…
Success of $AZN PACIFIC-9 #oleclumab could make CD73 next immune checkpoint target. 2nd delay in 2026 may represent fewer PFS events could be positive
If oleclumab matches/exceeds Ph2 COAST PFS HR 0.59-0.69, $CRVS could add +$300-$400m MC similar to 2021 for its anti-CD73 #mupadolimab as a second oncology asset. Would offer any pharma interested in Corvus #soquelitinib a second ICB asset that synergises w/ anti-PD1, CTLA4 therapies.
Interest to pharmas w/ dominant ICB franchises: $MRK $BMY $RHHBY
or
Interest to pharmas looking for inroad into oncology: $SNY $AMGN $GSK
$AZN PACIFIC-9 readout that includes arm w/ anti-CD73 #oleclumab pushed to 1H27 from 4Q26, this is mild positive as it is event driven and could be supportive of positive data
Relevant to $CRVS #mupadolimab
Hidradenitis Suppurativa #HS
$ABBV $AVTX $CRVS $IFRX $INCY $MLTX $NVS $ORKA $PFE $SYRE $UCBJY $ZURA
HS est cases (1.7M) in US similar to UC, heavily undiagnosed + undertreated in need of new approaches
Based on market size for indications w/ similar patient populations, HS set to grow 15%/yr to $7.8B by 2034
pharmaceutical-technology.co…
Hidradenitis Suppurativa 2 short episodes
- 1% prevalence globally
- 2/3 in US female
- 2/3 in Asia/ME male
- US Black patient may have more severe disease
- Early onset (teenage girls/early 20s men) variety of types/severity (mild to severe)
- 2nd late onset (40s) mostly severe cases
managedhealthcareexecutive.c…
Hidradenitis Suppurativa 2 short episodes
- 1% prevalence globally
- 2/3 in US female
- 2/3 in Asia/ME male
- US Black patient may have more severe disease
- Early onset (teenage girls/early 20s men) variety of types/severity (mild to severe)
- 2nd late onset (40s) mostly severe cases
managedhealthcareexecutive.c…
$NKTX New Job Posted Today - Senior Director/Executive Director, Clinical Data Management
Prepare NKX019’s DM infrastructure for potential pivotal trials and a BLA, establish readiness before pivotal studies begin, and recruit/manage staff.
Require someone with previous pivotal-study and marketing-application experience
Upcoming presentations are Nov 8: myositis; Nov 9: #Ssc; Nov 11: overall safety
job-boards.greenhouse.io/nka…
$NKTX New job posted - Associate General Counsel
“Advise... including license, collaboration, and strategic vendor agreements”
“Support capital markets, financing, and strategic transactions, including due diligence and transaction documents”
job-boards.greenhouse.io/nka…
Tough article in FT today on $SNY challenges to replace #Dupixent
"Belén Garijo took over as chief executive of French drugmaker Sanofi with one overriding task: to secure a blockbuster to succeed anti-inflammatory drug Dupixent"
Graph shows how reliant Sanofi is on Dupi
$SNY New CEO showing more urgency than prior management. Continues theme of LOE and patent cliff pressure that should continue to support bios w/ novel MOA, large TAM, pipeline potential, etc for the next several years. Bio investors overall should benefit
Atopic Dermatitis Review
1. #STAT6 GOF drives type 2 disease
2. #JAK1 affects broader cytokine network
3. IL-9/IL-18/IL-22 biology explains why IL-4/13 blockade may leave residual inflammation + barrier damage
"disease onset, tissue inflammation, barrier impairment, pruritus, and therapeutic response are governed by partially overlapping but nonidentical pathways"
Novel MOA and/or combinations may be necessary to address the various AtD pathways to provide increased patient benefit and deeper control of this heterogeneous disease
sciencedirect.com/science/ar…
$ACRS Tallying 2026 ATMs + Capital Raises
ATM total shares in 2026 => 29.2M
12.7M @ $3.13 - Mar 2-9
5.7M @ $3.5 - Mar 10
7.3M @ $5.54 - Jul - Aug 6
3.6M est @ $5.60 - Aug 6 - Oct 27
Oct $50M offering
7.8M sh + 6.5M warrants @ $3.50
Prior complaint regarding raises stands
$ACRS $50.0 Million Offering of Common Stock (7.8M sh) + Pre-Funded Warrants (6.5M wrnts) @ $3.50
Participation from TCGX, RA Capital Management, Invus and a large mutual fund
investor.aclaristx.com/news-…