Member Info for Krone

We need clarification of Parker’s role in the current situation. He’s supposed to be the chap with the big finance and deal making experience but on the face of it he has done sweet sod all since his appointment. He will be in for a very bumpy ride at the AGM that is if he doesn’t bail out beforehand.

Does the payment of milestones constitute general corporate purposes?
Sierra Oncology intends to use the net proceeds from the public offering to fund MOMENTUM, its planned Phase 3 clinical trial of momelotinib, as well as for general corporate purposes.

Lutonnews - thanks that’s reassuring. Would you expect Tim/John to have any influence on the approach taken by CRT to Sierra’s game playing?

http://investor.sierraoncology.com/2019-11-06-Sierra-Oncology-to-Report-New-Analyses-Supporting-Momelotinibs-Anemia-Benefits-at-ASH-2019
"Sierra Oncology retains the global commercialization rights to momelotinib, SRA737..." Not for much longer one hopes!!!

https://sitc.planion.com/Web.User/AbstractDet?ACCOUNT=SITC&ABSID=12497&CONF=SITC19&ssoOverride=OFF&CKEY=

Abstract below. Full article published by JITC - does anyone have access?

ID: P250
Combination treatment of the oral CHK1 inhibitor, SRA737 and low dose gemcitabine, enhances the effect of PD-L1 blockade by modulating the immune microenvironment in small cell lung cancer.

Triparna Sen, PhD, Memorial Sloan Kettering Cancer Center, Triparna Sen, PhD, Triparna Sen, PhD

Background
Small cell lung cancer (SCLC), the most aggressive form of lung cancer, shows poor response rates to immunotherapy targeting the programmed
cell death protein 1 pathway (PD-(L)1). Our group previously discovered that SCLC exhibits high expression of checkpoint kinase 1 (CHK1) and that the CHK1
inhibitor SRA737 activates the innate immune STING pathway, demonstrating robust anti-tumor activity and synergy in combination with anti-PD-L1 in an SCLC
model.

Methods
As SRA737 is being tested in SCLC patients in combination with low dose gemcitabine (LDG), we evaluated the efficacy and immune correlates (including
macrophages associated with resistance to immune checkpoint blockade) of the SRA737+LDG regimen in combination with anti-PD-L1 in an SCLC model.

Results
Trp53, Rb1 and p130 (RPP) triple knockout SCLC cells were implanted into the flank of B6129F1 immunocompetent mice. After the mice developed
tumors, they were treated with single agents or various drug combinations. Anti-PD-L1 and LDG demonstrated minimal effect on tumor growth as single agents
and only a modest effect as a combination. Moderate to strong anti-tumor activity was however observed with SRA737 monotherapy which directly correlated
with dosing intensity. The most profound and synergistic anti-tumor activity was observed when anti-PD-L1 was combined with the SRA737+LDG regimen, with
all animals showing durable regressions. Analysis of tumor infiltrating immune cells at the end of this treatment regimen showed a dramatic induction of
cytotoxic T-cells and a reduction of exhausted and regulatory T cells. Similarly, pro-inflammatory M1 type macrophages and dendritic cells were increased while
immunosuppressive M2 type macrophages and MDSC cells were dramatically decreased. As monotherapy, the more dose intensive SRA737 schedule resulted in
similar effects on lymphocytes when combined with anti-PD-L1. These effects are consistent with our previous data showing that SRA737 treatment leads to an
induction of STING and type I interferon signaling in tumors, which is associated with the establishment of an anti-tumor immune microenvironment.

Conclusions
Our findings suggest that the combination of anti-PD-L1 with the SRA737+LDG regimen may represent the optimal implementation of these
agents, leading to a dramatic anti-tumor activity accompanied by the establishment of a strong anti-tumor immune microenvironment. Given that anti-PD-(L)1
drugs are approved but show limited efficacy in SCLC, our preclinical data provide a strong rationale for combining these agents with the SRA73

Not even a hint of positivity in the RNS.....wondering whether Tim still thinks Sierra has 'every chance' of finding a suitable funding solution.
In August Tim said "We continue to believe, based on the very promising clinical data that has been generated to-date, that Sierra should have every chance of finding a suitable solution to progress the development of SRA737, which in due course would lead to Sareum receiving the milestones set out in the CPF/Sierra licensing agreement."

Sierra Oncology Reports Third Quarter 2019 Results

- MOMENTUM Phase 3 myelofibrosis clinical trial anticipated to launch in Q4 2019 -
VANCOUVER, Nov. 4, 2019 /CNW/ - Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, today reported its financial and operational results for the third quarter ended September 30, 2019.
"During the third quarter, we continued to prepare for the launch of the MOMENTUM Phase 3 clinical trial, which is expected to occur in the fourth quarter of 2019. Data that will be generated from this trial, along with data from more than 800 myelofibrosis patients previously treated with momelotinib, many of them durably benefiting for several years of treatment, will form the basis of our planned regulatory submissions for this drug," said Dr. Nick Glover, President and CEO of Sierra Oncology. "If ultimately approved, momelotinib could represent a significant addition to the limited number of therapeutics available to patients with myelofibrosis, and potentially become the first therapeutic capable of improving anemia in these patients rather than exacerbating it, while also providing meaningful and long-lasting symptom and spleen benefits."
Sierra's pipeline also includes a portfolio of DNA Damage Response (DDR) assets, SRA737 (Chk1 inhibitor) and SRA141 (Cdc7 inhibitor). Sierra has previously announced plans to prioritize its resources on the development of momelotinib and has launched a campaign exploring non-dilutive strategic options to support the future continued development of these other drug candidates.
About the MOMENTUM Phase 3 Clinical Trial for Patients with Myelofibrosis:
Sierra plans to launch the MOMENTUM Phase 3 clinical trial in the fourth quarter of 2019. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic and anemic, and who have been treated previously with a JAK inhibitor. Patients will be randomized 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.
The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; p-value < 0.05).
Secondary and exploratory endpoints include:
Transfusion Independence (TI) rate at Week 24 (key secondary: >90% powered; p-value < 0.05),
Splenic response rate (SRR) at Week 24 (>90% powered; p-value < 0.05),
Duration of TSS response to Week 48,
Other measures of anemia benefit, including Transfusion Dependence response rate and various measures of cumulative transfusion burden,
Patient Reported Outcome measures of fatigue and physical

https://twitter.com/ByJoFagg/status/1191332454398939136
https://www.evaluate.com/vantage/articles/analysis/spotlight/success-still-eludes-pancreatic-cancer-pipeline
Surely an opportunity to bang the Sareum drum i.r.o the AACR poster presentation Sar -20351

Belhus - the purchases are more likely to be in respect of Sierra’s main target Momelotinib.....

SAR....best in the world!

Thoth2 - do the charts on the SAR website accurately reflect the current respective stages of development? is it accurate to say that 1801 is late stage pre-clinical and 1802 is less advanced but fast approaching late stage pre-clinical?

RMM - thank you and very well said, I totally agree.

RMM - yes of course and I’ll be delighted to honour my bet before the end of the year.

Good news for Sar....
https://www.fiercebiotech.com/biotech/glaxosmithkline-s-rip1k-inhibitor-dead-arrival?

RMM- phew, that’s a relief! Good to Parker on the case and banging the drum....not!!

RMM - yes, Parker will/should be hung out to dry if he doesn't pull his bloody finger out sharpish!
The rather blase comment in the Q&A to the effect that SRI will publish the lupus data within the next few months doesn't wash. An organisation such as SRI will be working to a finely tuned project plan with detailed timelines. Tim and John know exactly when the data are to be published.

Here’s hoping Tim is on absolute top form and really socks it to them at AACR!!

Thoth2 - Is the patent to which you refer the same as that noted in the Disclosures section of the Sen paper? https://www.sciencedirect.com/science/article/abs/pii/S1556086419306926

RMM - If Parker gets an institution on board by the end of the calendar year I’ll donate £1,000 to a charity of your choosing.