Member Info for Krone

Thanks Stoney - so how does this work in terms of licensing? Could a licence restrict the application of the drug to a distinct pathway? Obviously what I’m getting at is whether we can licence the same drug for different applications?

Hi Stoney - but have the formulations/patents not been tweaked so that the molecules whilst similar are sufficiently different to in effect be two distinct drugs?

TYK2/JAK1 - Covid-19 vaccine is not the only way out of this, the whole world needs to work together on effective treatment, tyk2 inhibitor might provide a breakthrough:
http://www.sareum.com/discovery/tyk2jak1-covid19/

Linkedin post by Marshal Ma of Link China Pharma Solutions https://www.linkedin.com/feed/update/urn:li:activity:6790983323935211520?commentUrn=urn%3Ali%3Acomment%3A%28activity%3A6790983323935211520%2C6791323526419898368%29
http://www.chinapharma.co.uk/about.asp

Working - well spotted!! https://www.sixthelementcapital.com/index.php/chk1

Hi Stoney - thanks, and this would surely warrant a tweet form Tim at the very least and you’d expect Hybridan to be on the case!

https://endpts.com/eli-lilly-plots-nda-as-second-jak-study-backs-baricitinib-for-alopecia-areata-alnylam-heads-to-fda-after-full-vutrisiran-data-pans-out/

Wondering whether Sierra will use the high profile opportunity provided by ASCO to declare their intentions re 737?
Also the x2 outstanding phase 1/2 trials data could be published to coincide with the conference.
Abstract titles published on 28th April.

As previously posted, it is becoming increasingly difficult to see how CRUK are abiding by their own principles for commercial collaboration (as below). There is clear potential for reputational damage/adverse publicity if SRA737 isn’t either progressed in the very near future or CRUK/ICR provide details of the development plan.

OUR GUIDING PRINCIPLES FOR COMMERCIAL COLLABORATION AND LICENSING26 Feb 2021 14:40
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

Hi RMM - another great post, thank you.
According to the UKRI website, the timeline for the Covid study was December ' 20 - May 2021, so there are just over 6 weeks to go. Tim and John will by now have a very good idea of whether the data are indicating positive PoC, unless that it there has been any slippage. Your expectation therefore that June/July could be pivotal appears to be entirely realistic.

Ooops, hit send too quickly.
Not sure what, if any, of the relevance of the patent update 'PCT data prior to European publication' ?

https://register.epo.org/application?number=EP19794095&tab=main

TYK2 KINASE INHIBITORS
Appl./Publ. No. Appl. No. Reference Date of change Event
EP19794095 19794095 2021-04-12 PCT data prior to European publication

1) What is the Patent Cooperation Treaty (PCT)?
The PCT is an international treaty with more than 150 Contracting States.1 The PCT makes it possible to seek patent protection for an invention simultaneously in a large number of countries by filing a single “international” patent application instead of filing several separate national or regional patent applications. The granting of patents remains under the control of the national or regional patent Offices in what is called the “national phase”.

You’d expect Pascal Soriot to be breathing very heavily down Dilly’s neck to get a bloody move on with 737.
https://www.youtube.com/watch?linkId=115758925&v=IhrkZbVlocg&feature=youtu.be

Thanks Citizen - so we can expect an RNS from Tim/John in the morning however the bigger question is when will Dilly show his hand.

#AACR21 The combination of SRA737 and adavosertib may be a future alternative for the treatment of selected tumors with the TP53 mutation. Learn more about the study presented at @AACR :bit.ly/3t8GtQo

https://twitter.com/brasiloncologia/status/1380981162269622274?s=21
CHK1 and WEE1 are critical determinants of the G2 / M phase of the cell cycle, allowing DNA repair caused by endogenous and exogenous stress

During the first week of the American Association for Cancer Research (AACR) Annual Meeting 2021, a study in mice was presented that evaluated the effect of simultaneous inhibition of CHK1 and WEE1, leading to the death of cell lines with TP53 mutation by replication stress in G1 / S phase stop.

The work investigated the combination of SRA737 (a potent, highly selective CHK1 inhibitor) and adavosertib (small molecule inhibitor of tyrosine kinase WEE1) in OVCAR3 cell lines with TP53 mutation and in MDA-MB-436 cell lines with TP53 mutation and BRCA1.

In the OVCAR3 xenograft model, the combination of SRA737 and adavosertib caused tumor regressions, in which tumor volumes were significantly smaller than controls (p <0001). The combination generated a lesser, but significant, degree of tumor volume reduction in the MDA-MB-436 xenograft model, compared to the control (p = 0.003).

Functional analysis of DNA damage repair showed that the combination of SRA737 and adavosertib led to a reduction in the repair of base excision related to oxidative stress, as well as in the repair of double DNA strand breakage via alternative end junction in OVCAR3 cells compared to MDA-MB-436 (p = 0.009; p = 0.014; p = 0.005 respectively).

The authors conclude that the combination of SRA737 and adavosertib caused death in mutated TP53 cell lines. There were differences in the mechanisms of DNA damage repair in all cell lines and the combination showed significant activity in the studied xenograft models. The combination of SRA737 and adavosertib therefore requires further evaluation for the treatment of selected cancers with the TP53 mutation.

Hi RMM - another great post, thank you.
Coincidentally Lily have just published details of their Baracitinib trial and conclude: "There remains a driving unmet need for treatments with the potential to further decrease mortality for COVID-19 patients," said co-primary investigator E. Wesley Ely, M.D., MPH, professor of medicine and co-director of the Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center at Vanderbilt University Medical Center. "While COV-BARRIER did not hit the primary endpoint based on stages of disease progression, the data show that baricitinib meaningfully reduced the risk of mortality above and beyond the recommended standard of care, without additional safety risks. These important findings advance our pursuit of treatment options to save lives in hospitalized COVID-19 patients."https://investor.lilly.com/news-releases/news-release-details/lilly-and-incyte-announce-results-phase-3-cov-barrier-study

Hi Potnak - given Dilly’s “maniacal focus on momly” and the total radio silence for nearly 2 years, I’m not holding my breath for imminent news, but hope I’m wrong!

"Immune-regulating JAK inhibitors are among the most promising strategies, although this new class of drugs was developed for myeloproliferative and autoimmune diseases and not for combating viral diseases [37].
https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202149173

“Major collaboration efforts among industry and academia are exploring synthetic lethality, to develop small molecules against novel gene pairs. “This opens up new opportunities to realize the full potential of precision cancer treatments,” says Hoos. “I expect the field of synthetic lethality will explode.”
https://www.nature.com/articles/d42473-020-00234-5?twclid=11379090099821027330&utm_source=twitter&utm_medium=social&utm_campaign=bcon-gsk_article_3

Hi Basser, yup and it ain’t Momly.... 737 news imminent!