Member Info for Krone

The AACR Panel Discussion on 9th April chaired by AZ (https://www.abstractsonline.com/pp8/#!/9325/session/49) - 'DNA Damage Response (DDR) Treatment: Evolving Diagnostic Approaches, Understanding of Replication Stress, and Resistance Mechanisms to DDR Targeting Therapies' notes : This session will cover the current preclinical and clinical data on different diagnostic approaches to identify patients with tumors sensitive to therapies targeting the DNA damage response (DDR), in particular PARP inhibitors. This includes tests for loss of function mutations in genes involved in homologous recombination repair, genomic scar tests for homologous repair deficiency (HRD), and the prospects for functional tests for HRD. The replication stress response (RSR) as a component of DDR and therapeutic approaches to targeting the RSR will be discussed. CURRENT PRECLINICAL AND CLINICAL DATA ON RESISTANCE MECHANISMS TO PARP INHIBITION AND COMBINATORIAL APPROACHES TO OVERCOMING RESISTANCE WILL ALSO BE SHARED.
Note that Vall d'Hebron Institute of Oncology, one of the partners in the SRA737 combination study will be presenting. Must be a reasonably safe bet that a Sierra announcement re further trials/fast track of 737/tie up with AZ, will be timed to coincide.....so 9th April could be the timeframe??? GLA

New compound can reduce overactivation without impairing the body's immunity response.
...The team has established an integrated platform spanning the design, synthesis, and cellular testing of RNA therapeutics. TYK2 stands among a range of therapeutic targets for immunology and cancer therapy, which is the primary focus of the team.
The NTU researchers plan to partner several academic collaborators to test ASO-1 in animal models and are open to industrial collaboration on the development of the ASO-1 compound towards clinical use.
https://www.news-medical.net/news/20210310/New-compound-can-reduce-overactivation-without-impairing-the-bodys-immunity-response.aspx

I didn't previously registered that the research team cited in the paper are all ICR employees led by Udaj Banerji AND
travel expenses to the meeting are to be reimbursed by none other than Sierra Oncology.
Disclosures
A. Stewart: ; SRA737 was discovered in collaboration with the Institute of Cancer Research. AS is employee of ICR; The Institute of Cancer Research. L. Pickard: ; SRA737 was discovered in collaboration with the Institute of Cancer Research. LP is employee of ICR; The Institute of Cancer Research. A.E. Hallsworth: ; SRA737 was discovered in collaboration with the Institute of Cancer Research. AH is employee of ICR; The Institute of Cancer Research. S. Sauvaigo: ; LXRepair. G. Muggiolu: ; LX Repair. F. Raynaud: ; SRA737 was discovered in collaboration with the Institute of Cancer Research. FR is employee of ICR; The Institute of Cancer Research. U. Banerji: ; SRA737 was discovered in collaboration with the Institute of Cancer Research. UB is employee of ICR; The Institute of Cancer Research. ; Have received funding for investigator initiated clinical trials of an unrelated compound (Vistusertib); Astra Zeneca. ; Travel to scientific meeting reimbursed by Sierra Oncology.; Sierra Oncology.
https://www.abstractsonline.com/pp8/#!/9325/presentation/2082

Hi Thoth,
AZ sponsored paper to be presented at AACR 9th April:
Resistance mechanisms to DDR targeted therapies and potential for combination approaches to address resistance.
Presenter/Authors
Fiona Simpkins. University of Pennsylvania School of Medicine, Philadelphia, PA
Disclosures
F. Simpkins,
AstraZeneca Grants/Research Support Recipient.
AstraZeneca Advisor/Board Member.

A study of combinatorial growth inhibition, cell death and DNA damage repair caused by CHK1 inhibitor SRA737 and WEE1 inhibitor adavosertib in TP53 mutated cell lines Conclusions: The combination of SRA737 and adavosertib caused cell death in TP53 mutated cell lines. There were differences in the DNA damage repair mechanisms in across cell lines and the combination showed significant activity in the xenograft models studied. The combination of SRA737 and adavosertib warrants further evaluation for the treatment of selected TP53 mutated cancers.
https://www.abstractsonline.com/pp8/#!/9325/presentation/2082

10-K page 11 Intellectual Property - December 31, 2020, Patent Cooperation Treaty with MD Anderson...suggests development ongoing.
As of December 31, 2020, these rights also included one pending Patent Cooperation Treaty application filed by the Company and The University of Texas M.D. Anderson Cancer Center comprising claims directed to methods of using SRA737 to treat cancer indications. Additionally, as of December 31, 2020, these rights also included one pending Patent Cooperation Treaty application comprising claims directed to methods of using SRA737 in the treatment of cancer associated with an intermediate mutational burden (TMB), or genetic abnormality in one or more particular genes associated with replicative stress. We have filed and will continue to file patent applications directed to the composition of matter and methods of use related to various aspects of SRA737 as they develop.
http://investor.sierraoncology.com/financialreporting?cat=&year=2021

"Amendment to CRT Pioneer Fund agreement for SRA737 allowing for potential future development of the compound"
Well that inspires confidence!
http://investor.sierraoncology.com/2021-03-11-Sierra-Oncology-Reports-2020-Year-End-Results

Dilly confirms 'maniacal' focus on Momly.....no mention whatsoever of 737.

NICE approval of JAK bodes well for Sareum.
https://pharmaphorum.com/news/lillys-olumiant-is-first-jak-drug-backed-by-nice-for-eczema/

It will be interesting to see what, if any, reference is made to SRA737 in Sierra's 10-Q given Dilly's recent somewhat blasé comment: "We have quite an interesting pipeline agent in our back pocket in SRA737 which is a DNA damage repair agent, a CHK1 and we are thinking deep thoughts about how to take that forward".
On 12th November 2020 Tim said "...While the aggregate level of these milestone payments is reduced, we are confident that this amendment will expedite the advancement of the SRA737 programme in a timely manner...."
I suppose it depends on how one is defining timely manner.

Galapagos: New patent related to TYK2 (= GLPG3667).

The present invention discloses compounds according to Formula (I) wherein R1, R2, and Cy are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of allergic diseases, inflammatory diseases, metabolic diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IFNa, IL12 and/or IL23 by administering the compound of the invention. https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021032582&_cid=P10-KLOWXI-71159-1

Not sure to what extent CRUK are adhering to their Guiding Principles in their dealings with Sierra.
Patient benefit is a paramount goal so we need to ensure that innovations arising from CRUK-funded research are continually developed and introduced to market in a timely and efficient manner. To this end, we need our partners to commit to:
• Diligence provisions which address product development in oncology applications and pursuit of marketing approval of such products in major markets, specifically the UK.
• Generation of a development plan (and provision of annual updates) covering significant activities, associated timelines and key decision points.
• A diligence monitoring mechanism focused on constructive two-way dialogue and a commitment to regular face-to-face interactions to review development.
• A right for us to regain rights to a project (including partner’s IP to the extent required for onward commercialisation) should our partner no longer be developing it (in exchange for a revenue share reflecting the contributions of the parties).
• Provision for biomarker IP of generic value to patients/ projects to be used freely (including by 3rd parties).
http://commercial.cancerresearchuk.org/sites/default/files/Guiding_Principles_Handout_October_2019.pdf

https://endpts.com/japans-softbank-plots-billions-in-biotech-investments-in-move-that-could-keep-the-valuation-flood-rising-report/

From 2015-2017 half year results were published in Feb.
2018 - 13th March
2019 - 4th March
2020 - 26th March
2021 - ?
It will certainly be an interesting and potentially very exciting IMC meeting.

Good question, I don't know.

Assuming no slippage we can expect confirmation of CTA within the next 5 weeks.
"For SDC-1801, which is our near-term focus, we conducted and completed initial toxicology studies in rodents demonstrating excellent tolerability and established its manufacturing process. In recent months, we developed a new formulation, specifically designed to deliver higher exposure levels of the molecule, which we are now testing in additional toxicology studies, with a targeted completion date EARLY IN THE NEW YEAR.
Data from these studies will form part of the planned Clinical Trial Application (“CTA”), which we aim to submit in the FIRST QUARTER of 2021, and if approved would allow the start of clinical studies with SDC-1801. This would clearly be an important milestone for the Company.

Five genes that could explain why healthy young people die of Covid mol.im/a/9281575 via @MailOnline - and Cambridge-based @Sareumplc is developing a drug against TYK2 to help here. Grateful for a grant from @UKRI_News to help with this.
https://twitter.com/sparksinsurrey/status/1363419970022092800?s=21

Hi RMM - all this is in the context of Dilly being at the helm since June 2019and being privy to the emerging data, which by all accounts is very positive. Any negotiations with interested partners will have been ongoing for some time and the renegotiated contract with CPF/SixthElement will likely be based on the requirements of the prospective partners. Lift off very soon hopefully.

Dilly refers to SRA737 at 53.28 - https://wsw.com/webcast/lifesci2/srra/2150296
"We have quite an interesting pipeline agent in our back pocket in SRA737 which is a DNA damage repair agent, a CHK1 and we are thinking deep thoughts about how to take that forward"

The Sareum tab on the Lifesci Partners page does refer to SRA737 although probably a *ock-up.
https://www.meetmax.com/sched/event_71143/conference_companies.html?bank_access=0&event_id=71143