Member Info for Krone

Hi Ahfam - interesting summary of the toxicity issues around Pfizer’s JAKs below. Given that thus far we have no such reported issues we must be in a good position. The question presumably therefore is would Pfizer include 1801/2 in their developmental pipeline to bring on in future.
https://endpts.com/pfizers-jak1-challenger-to-dupixent-shines-in-another-phiii-but-safety-issues-still-cast-a-shadow/

Hi Fadec - interesting papers!
There is clearly a growing mountain of empirical evidence which supports the key roles of both CHK1 and TYK2/JAK1 in the cancer and autoimmune spaces. The big question remains as to whether Sareum has the commercial nous to capitalise on the apparent massive potential in SRA737 and SDC1801/2.
I am a relative newbie having only been invested in Sareum for 8 years. In that time I have seen no evidence to doubt the professional integrity of Tim and John who appear to be tightly focussed on moving the science forwards for the benefit of patients. I would echo the increasing frustration of others on this board in respect of the approach to PR/communications. The BoD appear to adopt a teflon approach to any comments in this regard and I guess that simply adds to the frustration. Not sure they have the capacity or will to divert from their existing head down strategy. I guess when this all comes good the frustrations will dissipate in an instant. All that said if we don't get some substantive news in the short term the EGM option is likely to become necessary if we are to learn what's going on behind closed doors!

“ We predict that combination therapy with JAK inhibitors and other agents with the potential to normalize NF-kB-signaling, such as anti-viral agents, may serve as an effective clinical strategy.”
https://www.researchsquare.com/article/rs-33390/v1

Thoth - excellent, thank you.

Does anyone have the link to the contract between Pronai/Sierra and ICR....specifically the wording around consequences of non progression.

I received a response below to the question: Could you please confirm when you intend to provide a substantive update on progress with SRA737.

Thank you for your question.
As we noted in our recent quarterly update, we have suspended the continued development of SRA737, however we maintain collaborative relationships with the other key asset stakeholders in SRA737 and are working to explore potential non-dilutive strategic options to support its future continued development. Should we have material developments on this front, we will disclose them.
Regards,
James

James Smith
VICE PRESIDENT, CORPORATE AFFAIRS

AbbVie beefs up the immunology pipeline, betting up to $865M on a PhII-ready drug — and fueling a biotech stock frenzy
https://endpts.com/abbvie-beefs-up-the-immunology-pipeline-betting-up-to-865m-on-a-phii-ready-drug-and-fueling-a-biotech-stock-frenzy/

Reviewing the Sierra presentation in respect of SRA737 from June 3 2019 by Regius Professor De Bono and Dr Kristelheit, it just seems absolutely astonishing that Sierra have been allowed to get away with prevarication and obfuscation which will ultimately cost lives. It will also be astonishing if ICR don't take robust action to secure the further development!
http://investor.sierraoncology.com/events-and-webcasts?item=35

Hi Fadec - absolutely, as flagged yesterday and followed up by Thoth. This must increase the urgency regarding what's happening with 737. Inconceivable that ICR aren't banging on Nick Glover's old office door to rummage through his waste basket to establish what's happening. Interesting to note also that Michael Owen was formerly SVP and Head of Research for Biopharmaceuticals R&D at GSK.

https://endpts.com/billions-on-the-table-gsks-hal-barron-antes-120m-cash-to-partner-with-a-specialist-in-synthetic-lethality

Hi RMM - thanks.
FWIW in the absence of substantive progress we surely need to be ready to get things moving by September. The situation could be remedied quite simply with regular and effective PR/communications.

Correction - an optimist could regard the GSK deal as evidence of the potential deal size for SRA737. If GSK are willing to pay big money for a pre-clinical candidate so will others......

http://investor.sierraoncology.com/2017-04-03-Sierra-Oncology-Collaborator-ICR-Reports-Preclinical-Synthetic-Lethality-Data-for-Chk1-Inhibitor-SRA737-at-AACR

Billions on the table, GSK’s Hal Barron antes $120M cash to partner with a specialist in synthetic lethalityGSK R&D chief Hal Barron has turned to another Bay Area biotech for his latest oncology drug development pact, which could total billions for a preclinical deal that starts with $120 million in cash. And this one speaks directly to one of his favorite topics: synthetic lethality.
Barron is partnering with Ideaya Biosciences $IDYA for this new alliance. GSK is handing over $100 million in upfront cash, plus another $20 million for a chunk of stock.

Then there’s around $940 million to $960 million in combined development and regulatory milestones for each product to successfully emerge onto the market, according to the biotech’s SEC filing.

Ideaya started the day with a $182 million market cap — not big in this market. And their shares soared 70% on the news.

At the front of the queue is Ideaya’s MAT2A program, which comes with a $50 million buy-in if GSK picks up its option. Before that payout, though, GSK has rights to trigger a combination study with their Type I PRMT inhibitor GSK3368715 to check out its potential. That is followed by other programs targeting Pol Theta and Werner helicase.

Emma Walmsley
Each MAT2A program is tied to $465 million in potential regulatory and development milestones, with another $475 million for commercial goals. The other 2 programs are linked to regulatory and development milestones of $485 million with $475 million in commercial milestone money.

GSK CEO Emma Walmsley made it clear early on in her tenure at GSK that oncology would return to the front of the pipeline. She sealed that deal by recruiting Genentech vet Barron to run R&D. Since then, the company has carefully focused on a range of preclinical deals through commercial acquisitions to build up its work in cancer. And synthetic lethality is one of Barron’s special focuses.

Barron remained in the Bay Area after being selected for the top research job at London-based GSK. And he’s been tapping a wide network of scientists and execs in San Francisco to beef up his pipeline.
https://endpts.com/billions-on-the-table-gsks-hal-barron-antes-120m-cash-to-partner-with-a-specialist-in-synthetic-lethality

Hi RMM - Can you please remind us of the rationale for waiting until September for an EGM given that the AGM will be in December. Agenda items could include the sacking of current advisors responsible for PR strategy along with the other items flagged by Thoth around 12-18 months ago. Updating of the database of PI's with significant holdings may also be helpful.

https://twitter.com/sareumplc/status/1272811643785838593?s=21
Eli Lilly launches PhIII JAK study, aiming for the first drug to lower mortality in Covid-19 - endpts.com/eli-lilly-laun…
Sareum $SAR.L #TYK2 #COVID19 #AIM #biotech

Hi Basil, excellent post. Suggest you forward to Hybridan/ Citigate for action.

So who is responsible for the PR strategy, Hybridan or Citigate? The consistent and recurring theme that runs through this board is poor and ineffective PR. If Tim et al are being poorly advised then it’s the advisors that need changing.

.... JAK inhibitors, a treatment for patients with myeloproliferative neoplasms (MPN), may help reduce the severity of COVID-19, the respiratory disease caused by the coronavirus.

In fact, JAK inhibitors are in Phase III trials for COVID-19, said Dr. Raajit Rampal, a hematologic oncologist from Memorial Sloan Kettering Cancer Center in New York City. Dr. Rampal participated in a Patient Power webinar last month about MPN patients and COVID-19.

“That's owing to the idea that there is a massive cytokine storm that seems to occur during the course of the (COVID-19) infection that we think, at least, is contributing to what happens in the lungs,” he told Patient Power Co-Founder Andrew Schorr. “And so, of course, the JAK inhibitors are wonderful drugs to inhibit cytokines.”

https://patientpower.info/myeloproliferative-neoplasms/ask-the-expert/could-jak-inhibitors-be-used-to-treat-covid-19

Sierra Oncology Reports Favorable Long-Term Safety and Dose Intensity Data for Momelotinib

- Data presented at the 25th European Hematology Association (EHA) Virtual Congress further demonstrate the potential anemia benefits and favorable hematological safety profile of momelotinib -
- Long-term tolerability facilitates sustained dose intensity and prolonged clinical activity; longest ongoing treatment now extends to 10 years -
VANCOUVER, BC, June 12, 2020 /CNW/ - Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage drug development company focused on the registration and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, announced that Long-Term Safety and Dose Intensity data for momelotinib are being presented today in two posters at the 25th European Hematology Association (EHA) Virtual Congress.
More than 820 patients with myelofibrosis have received momelotinib during its development, including a number of patients who remain on treatment since the start of the original Phase 2 studies initiated a decade ago. One of these patients will reach a major milestone this week, having received momelotinib therapy for 10 years, highlighting the relevance of the long-term dosing and safety data for momelotinib being presented this week at EHA. The data presented at EHA draw from more than 550 patients across the two previously conducted SIMPLIFY Phase 3 studies and their subsequent ongoing extended treatment periods. More than 90 SIMPLIFY-1 and SIMPLIFY-2 patients continued to receive momelotinib for 3.5 years or longer.
"Consistent with prior data, and reflecting momelotinib's differentiated pharmacological profile, our new long-term safety analyses continue to show a rapid and sustained increase in hemoglobin levels during momelotinib therapy, in contrast to the significant decrease in hemoglobin for patients receiving ruxolitinib. Patients treated with momelotinib also experienced significantly higher mean platelet counts compared to those receiving ruxolitinib. Importantly, patients who switched from ruxolitinib to momelotinib also achieved a sustained improvement in both hemoglobin and platelets," said Prof. Claire Harrison, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom. "In addition to an absence of significant rates of high-grade hematological toxicities, long-term tolerability was favorable with no new safety signals or evidence of cumulative toxicity. Notably, this was achieved with most patients receiving full-dose momelotinib."
"Momelotinib's safety profile and durable anemia benefits facilitated sustained dose intensity across the continuum of JAK inhibitor naïve and previously JAK inhibitor treated myelofibrosis patients. While the starting doses for ruxolitinib were often attenuated due to low platelets, further reductions in dose intensity were also commonly required for ruxolitinib. In contrast, momelotin