Member Info for Rebster408

I'll have a look but I'm pretty much all in here and GGP which has been great for me this year and little sign of losing momentum. Now there's a bod who know how to communicate, and time it perfectly too...
have a good weekend mate.

No worried Dark, I just feel our time for further research is over. Tim is of an age where he should be looking at retirement not another ten years looking for something new to discover...
The win-win for me is on-licensing/sellout, so patients get a major working on taking the product through to release, and we as SH get a reward for supporting Sareum..
its all good...

Blackisleboy, Im sorry to hear about your father, I lost mine in similar circumstance, which lead to me investing here back in 2011.
Darkhorse, I'm sorry but you return to the topic of more funding again... I think we have been here before? :) Funding is not needed until next year following the recent raise so todays share price should not be associated with getting more/better funding to find a truly effective treatment... hopefully we already have 4!! Sareum should be fully focused on getting shareholder value, by on-licensing our products, not getting more funding for even more research...the time is now to maximise shareholder value by getting deals done, and increasing share price that way. Where I do agree with you is we need better comms from the BOD. IMO

Part 4 of 4... hopefully
Methods: Phase 1 dose escalation investigated cohorts of 3 to 6 subjects receiving escalating doses of SRA737 for 2 days after LDG administration on days 1, 8, 15 of 28-day cycles. Phase 2 expansion cohorts explored the hypothesis that LDG strongly synergizes with SRA737 in subjects with genetically-defined tumors hypothesized to be sensitive to Chk1 inhibition: urothelial, high grade serous ovarian, small cell lung, soft tissue sarcoma, and cervical or anogenital cancers. Results: A total of 55 subjects received SRA737 in 13 dose escalation cohorts at doses of 40 to 600 mg SRA737 combined
2
with LDG doses of 50 to 300 mg/m . No protocol-defined dose limiting toxicities (DLTs) have been
observed. The pharmacokinetic profile of SRA737 revealed an AUC0-24 and Cmax of 3550 ng·h/mL and 548 ng/mL at 150 mg SRA737. At this dose, the Cmin (52 ng/mL) exceeded that determined in preclinical models to be effective. Enrollment into expansion cohorts was initiated at 500 mg SRA737 plus 100 mg/ m2 LDG with intra-patient dose escalation permitted to 250 mg/m2 LDG. Approximately 80 subjects were planned and 82 have been treated. Median treatment duration was 51 days (range 1 to 358). The most common treatment-emergent adverse events were nausea (53%), vomiting (45%), fatigue (40%), diarrhea (38%), and anemia (28%); the majority were of mild to moderate severity. Proof-of-concept clinical activity has been seen in tumor types such as anal, cervical, and rectal. Conclusions: The combination of LDG and SRA737 has been well tolerated. This first-in-human clinical study provides proof-of-concept that sub-therapeutic LDG effectively potentiates SRA737. This novel replication stress- targeted therapy warrants further evaluation in genetically pre-defined solid tumors. Clinical trial information: NCT02797977.

Part 3 of 4
The Cmax and AUC0-24 at 1000 mg QD were 2391 ng/ mL and 26795 ng·h/mL respectively and the Cmin (411 ng/mL) exceeded that determined in preclinical models to be effective. Doses $ 300 mg QD also exceeded this level. Of 462 subjects prospectively screened for genetic alterations associated with Chk1 sensitivity, 93 were enrolled in expansion across all tumor types. Overall, the most commonly reported treatment-emergent adverse events were diarrhea (70%), nausea (64%), vomiting (51%), and fatigue (47%); the majority were of mild to moderate severity. Conclusions: In this first-in-human trial of SRA737 monotherapy, the MTD was 1000 mg/day and based on overall tolerability and PK, the recommended Phase 2 dose is 800 mg/day. The successful enrollment of prospectively-selected genetically-defined subjects will allow response data to be correlated with genomic profiles hypothesized to confer sensitivity to Chk1 inhibition. Clinical trial information: NCT02797964

The Cmax and AUC0-24 at 1000 mg QD were 2391 ng/ mL and 26795 ng·h/mL respectively and the Cmin (411 ng/mL) exceeded that determined in preclinical models to be effective. Doses $ 300 mg QD also exceeded this level. Of 462 subjects prospectively screened for genetic alterations associated with Chk1 sensitivity, 93 were enrolled in expansion across all tumor types. Overall, the most commonly reported treatment-emergent adverse events were diarrhea (70%), nausea (64%), vomiting (51%), and fatigue (47%); the majority were of mild to moderate severity. Conclusions: In this first-in-human trial of SRA737 monotherapy, the MTD was 1000 mg/day and based on overall tolerability and PK, the recommended Phase 2 dose is 800 mg/day. The successful enrollment of prospectively-selected genetically-defined subjects will allow response data to be correlated with genomic profiles hypothesized to confer sensitivity to Chk1 inhibition. Clinical trial information: NCT02797964

As brief a summary as is possible I think...
A first-in-human phase I/II trial of SRA737 (a Chk1 Inhibitor) in subjects with advanced cancer.
Elizabeth Ruth Plummer, Rebecca Sophie Kristeleit, Elena Cojocaru, Noor Md Haris, Louise Carter, Robert Hugh Jones, Sarah Patricia Blagden, T.R. Jeffry Evans, Hendrik-Tobias Arkenau, Debashis Sarker, Sarah Danson, Stefan N. Symeonides, Harriet Walter, Joanita Ocen, Manreet Randhawa, Mark Marion Kowalski, Ines Verdon, Andrew Dye, Udai Banerji; Northern Centre for Cancer Care, Newcastle-upon-Tyne, United Kingdom; University College London Hospitals, London, United Kingdom; Gustave Roussy, Arcueil, France; Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, United Kingdom; The University of Manchester, Manchester, United Kingdom; Velindre Cancer Centre, Cardiff, United Kingdom; University of Oxford, Oxford, United Kingdom; University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; Sarah Cannon Research Institute, Cancer Institute, University College London, London, United Kingdom; King’s College Hospital, Institute of Liver Studies, London, United Kingdom; Sheffield Experimental Cancer Medicine Centre, Weston Park Hospital, Sheffield, United Kingdom; Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom; University of Leicester, Leicester, United Kingdom; South West Wales Cancer Centre, Swansea, United Kingdom; Sierra Oncology, Inc., Brisbane, CA; Sierra Oncology Inc., Vancouver, BC, Canada; Drug Development Unit-The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom
Background: SRA737 is a potent, highly selective and orally-bioavailable inhibitor of checkpoint kinase 1 (Chk1). SRA737-01 was designed to investigate the safety and tolerability of continuous, daily dosing with SRA737 and to evaluate preliminary efficacy in expansion cohorts of prospectively-selected genetically-defined subjects with advanced tumors. Methods: The escalation phase employed an accelerated titration design starting at 20 mg administered orally in 28-day cycles. Incremental 100% dose escalations in single-subject cohorts were followed by a rolling-6 design once SRA737- related $ Grade 2 toxicity was observed during Cycle 1. The expansion phase enrolled subjects prospectively selected by next-generation sequencing with: high grade serous ovarian, colorectal, metastatic castration-resistant prostate, non-small cell lung, and head and neck cancers. Results: In escalation, 18 subjects received SRA737 in 9 dose level cohorts, from 20 to 1300 mg QD; median treatment duration 62.5 days (range 1 to 226). Of these subjects, 3 experienced dose limiting toxicity (DLT; inability to receive 75% of the planned dose); 2 at 1300 mg QD due to gastrointestinal intolerability and 1 at 500 mg BID due to thrombocytopenia. The maximum tolerated dose (MTD) was established at 1000 mg QD or 500 mg BID. The Cmax and AUC0-24 at 1000

1. GGP
2. SAR
3. ZIOC

Any major who wants to buy Sareum outright, will know the future value of the products,(if they get to market) and will base their bid on future earnings potential, obviously with some risk factored in...
But... the future earning potential of our products has a fair number of zeros in, so I would hope, and expect if buy out came, it would be north of 20p.
Ideal scenario is 50p as that's me, and my kids sorted for life... here's hoping.

The news over the past few weeks is hopefully nothing compared to what’s coming over the next few months and the share price will re rate accordingly. Hopefully exceeding 28p by far...

Extrader
Blood river is indeed a fascinating read...
Very thought provoking

Not necessarily bad news for us though.
Will sharpen their minds and they may look in our direction...
Either way the clock is still ticking

And 6million from Sierra would give us a share price of ?

I’d say 3p... but knowing AIM we might just break 1p..
Either way hopefully this could be the start of good news flow... good luck all...

7p?
Sorry mate we would be a no from me... at that price its theft...

Krone
Would interesting to see how these definitions could be interpreted by Gileads ‘control’ over Sierra as no doubt the financial parameters ProNai were working under are nothing like Gileads? Interesting days indeed

Krone
So we could be in the hands of experts ? To decide the definition of reasonable.... great...no wonder lawyers earn a bloody fortune!!!
Who approves such loose terminology in contracts. I’ve been involved in lots over my time, predominately IT contracts and never agreed to the word reasonable unless it was caveated with a clear boundary such as time, money etc

Hopefully the contract spells it out clearly to Sierra...use it or lose it... and there is no leeway for the legal eagles to mess about and delay its return...or delay an on license deal which gives us our milestones.

28p party?
That’ll be the warm up to the £4 party... hopefully

I would be surprised given the size of NCM if they didn’t already have someone in this role...it might be nothing more than the incumbent has retired, decided to leave, been fired? so it could just be a replacement they are looking for.....
Or......WTFDIK

I’m Going with Thoths £4...
Well I can dream anyway!!! Haha
Serious prediction... 50p min