Member Info for ajithoth

Iamhappy - good - glad I'm not on my own.
TYK2 will be massive if its half as good as they think it is and twice as toxic.
Many many indications, lupus, MS, weight loss, alopecia, psoriasis, cancer, RA. The list is incredible.
If we get just 5% of each indication we will be rolling in it.
if it all comes good I wont be begrudging Parker anything. We don't know what he is doing, and no news is good news.
Maybe its my fervent imagination but this could be like buying Microsoft shares in 1977......

I wonder if Parker prepared that annual report, correct me if I'm wrong but that seems a lot more substantial and glossy than any previous report. That looks like good PR to me, lots of previously withheld facts laid bare. A shop front if you like, for the wares on sale.
I'm optimistic - added another million or so over the last couple of months (or stupid, take your pick)
Maybe I should have bought some IMM today instead - the rise seemed to hold up well, wonder if it'll be the same tomorrow....

It'll never be too late for a amazing combo of drugs that work better than anything else. Not first in class but best remember.

nearly top of the risers board again

TYK2 promotes malignant peripheral nerve sheath tumor progression through inhibition of cell death
https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.2386
First published: 06 July 2019

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise most commonly in the setting of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome. Despite aggressive multimodality therapy, outcomes are dismal and most patients die within 5 years of diagnosis. Prior genomic studies in our laboratory identified tyrosine kinase 2 (TYK2) as a frequently mutated gene in MPNST. Herein, we explored the function of TYK2 in MPNST pathogenesis.

We have demonstrated that TYK2 was highly expressed in the majority of human MPNSTs examined. Additionally, we demonstrated that knockdown of Tyk2/TYK2 in murine and human MPNST cells significantly increased cell death in vitro. These effects were accompanied by a decrease in the levels of activated Stats and Bcl-2 as well as an increase in the levels of Cleaved Caspase-3. In addition, Tyk2-KD cells demonstrated impaired growth in subcutaneous and metastasis models in vivo.

Taken together, these data illustrate the importance of TYK2 in MPNST pathogenesis and suggest that the TYK2 pathway may be a potential therapeutic target for these deadly cancers.

Hi Utah - the TRK kinase inhibitor drug in that BBC report is part of the Tyrosine Kinase Inhibitor family.
I think they are more closely related to our FLT3 than TYK2 though.

I reckon these are the two most exciting paragraphs in the article:

"I think this is the way things are going and this is about better outcomes, curing more patients and producing kinder treatments with reduced side-effects."

"The benefits for patients - in particular children - of being able to treat many different types of cancers with one drug is potentially huge, helping them to lead longer, healthier lives"

More dots to join, but we still don't have the big picture.

why would B Klencke (SRRA director) buy over $100k worth of shares if its going down the pan?

good post Potnak.
After thinking about this for the last few weeks I'm now not so sure a mutiny is in our best interests.
Although the SP has taken a complete battering I still think Sar are sticking to their timescales. It would be great if they were singing from the rooftops too but they don't do that since the infamous speeding ticket.

Isn't that 0.1%?

btw followed you on twitter..

yes definitely......nothing negative in there at all, all positive, such as:

"Given that anti-PD-(L)1 drugs have recently been approved as monotherapy and in
combination with chemotherapy for the treatment of SCLC, and that the SRA737+LDG regimen
is well tolerated in clinical trials in SCLC (NCT02797977), our preclinical data provide a strong
rationale for combining this regimen with inhibitors of PD-(L)1 pathway in the clinic."

which to me means low dose chemo, our sra737 and either keytruda or imfinzi in a trial.

what's your email address Fadec?

this is an interesting read
https://www.theguardian.com/science/2019/sep/02/the-science-of-senolytics-how-a-new-pill-could-spell-the-end-of-ageing

it mentions a P1 trial in humans, the drug used was dasanitib, a leukemia drug. Its a tyrosine kinase inhibitor drug.
It doesnt sound as selective as ours though and has side effects.
http://www.bloodjournal.org/content/119/21/4817?sso-checked=true
imagine if we had all the Bezo's in the world after our wholly owned drug?
The secret to a healthier life and the delay of old age is one hell of a target to add to the ever growing list of illnesses a good tyk2 inhibitor could treat.

My sentiments entirely Potnak - I think I paid about 14k more for my 3M!
However its good to see a bit of positivity returning to the board, onwards and upwards, we will soon be out of the wilderness.
FWIW I think we are under NDA. There is no way our TYK2 candidates are flying under the radar with deals like Amgens transfer of Ortezla for £10B.
And when this rises it'll rise fast as so many of us won't be selling unless we get the mother of all baggers.

ah this is old news - but maybe we all need a reminder of what could potentially be going on in the background. I know I do....

Very interesting indeed. ly2606368 is Prexasertib which has been ditched by Eli Lilly.
I wonder how important this makes sra737 for the manufacturers of olaparip?
SRA737 is oral rather than iv and also an order of magnitude more selective against chk1 than Prexasertib
see slide 13 here
http://www.jefferies.com/CMSFiles/Jefferies.com/files/Sierra%20Oncology.pdf

3.7m for me.
Let me know if needed.

this is interesting
https://www.independent.co.uk/news/science/cancer-cells-immune-system-attack-study-research-a9029721.html

looks like the janus signalling pathway could block the protein cd24 too, a nice new target for tyk2.

https://dm5migu4zj3pb.cloudfront.net/manuscripts/44000/44745/cache/44745.2-20150223201327-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf

try this one:
http://www.sareum.com/download_file/view/171

Hi Searle - Isn't ours much more selective?
so a lower does is required, which also reduces the risk and severity of side effects?