Member Info for Fadec92

Latest research showing CHK1 and Aurora highly relevant in subtypes of SCLC and referring to a combinational approach is better with chemotherapy!

Triparna Sen tweeted this!

“MYC reprograms SCLC cells to various states highly relevant to tumor evolution and drug response, fascinating”

MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate

We find that individual human SCLC tumors are composed of multiple molecular subtypes. Given the reported unique therapeutic vulnerabilities of each subtype, we postulate that SCLC tumors represent a “moving therapeutic target” that may require more general, combinatorial, or plasticity-directed therapeutic approaches to combat this transcriptional flexibility.

“We find that many SCLC tumors are composed of cells representing multiple molecular subtypes at different frequencies, suggesting that bulk analysis methods may only identify the most abundant state in a given tumor. Studies are increasingly identifying unique therapeutic vulnerabilities for SCLC subtypes. For example, MYC-high tumors are preferentially sensitive to inhibition of AURKA/B, CHK1, IMPDH1/2, and arginine deprivation”

Reference

Sen et al., 2017
T. Sen, P. Tong, C.A. Stewart, S. Cristea, A. Valliani, D.S. Shames, A.B. Redwood, Y.H. Fan, L. Li, B.S. Glisson, et al.

CHK1 inhibition in small-cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib

https://www.sciencedirect.com/science/article/pii/S153561082030218X

Interview for sdc-1801 has been confirmed as initiated, so will look over next couple of days for the detail of interview!

Sorry Kellie not John!

Guys it’s a discussion between the examiner and John so he has ideas that will be put to Kara, and she will let him know what she thinks of that and maybe come to some agreement what can be proposed, it’s not a black or white answer so not nerve wracking as such it’s a positive step in Planning and putting forward a patent that is patentable!

ArticFox 15/351620 Patent SDC-1801 Autoimmune has been initiated from the start of 2019!

That’s fine RMM, it’s common patent motions here don’t see a problem, need to fail first to be able to identify the issues to work around them with the examiner and come too an agreement satisfying the patent process this is all usual!

Until we know the Pharmacological profile of SDC-1802 ie what IC 50’s the JAK’s and TYK2 are then you can’t compare we know the molecule is different, but need the profile we know the IC50’s of SDC-1801 but only then will you be able to see how selective each figures are, they should be different will look out for it on medichemexpress!

https://en.m.wikipedia.org/wiki/IC50

US Patent - 15/351620

Good news on patent, John has requested an interview too overcome the obviousness and double patent issue for SDC-1801 Autoimmune, interview either tomorrow morning or Wednesday morning!

https://imgur.com/a/ukSiyW5

Krone it could be a takeover target before before a license deal!

It was developed by Acerta Pharma. After promising results for CLL in initial clinical trials, Astra Zeneca purchased a 55% stake in Acerta Pharma for $4 billion in December 2015, with an option to acquire the remaining 45% stake for an additional $3 billion, conditional on approval in both the US and Europe and the establishment of commercial opportunity.

It’s critical for a solution Covid-19 to stop people dying from not just respiratory failure ARDS but also organ failure so will the research that the professionals already have and which is key here with the trials with other JAK inhibitors that would be an indicator whether Sareum’s preclinical autoimmune data can show that it can be a solution, we can see from the research in the public domain that there is a good chance for this!

On the new TYK2/COVID-19 page, they have the cash and the potential grant money, and are looking too progress with a partner or license out, it would be nice to know some of the details too!

“Whilst developing SDC-1801, we have produced compelling cellular and in-vivo data in models of autoimmune disease to demonstrate the beneficial effects of SDC-1801 in modulating the key cytokines involved in the cytokine storm phase of Covid-19. Details can be made available to potential funding, collaboration and/or licensing partners on request.“

Hi Stoney no your not going mad it’s me even though I meant it is in process of being found as Tim suggested in the other interview not this new “not reaching MTD was a good problem to have,” I’ve re-read my post and it sound as if I meant it has been found but not yet yes agreed sorry for the confusion! Lol...

MTD is found in safety studies only then a short trial in humans can happen, a clinical trial design for covid will happen, there will most probably be a second wave of infection as the scientists are saying or other variants of SARS-COV in the future, I suspect a bigger rise would be on the cards definitely when academics are stating:-

“targeting the JAK-STAT pathway may provide a new avenue toward the management of COVID-19 before a vaccine can be developed.”

It also mentions the well known adverse side effects of these first generation of JAK inhibitors and a good safety profile is a feature of Sareum’s SDC-1801/1802 being a second generation JAK inhibitor so the side effects should be reduced being a more specifically targeted JAK1/TYK2 related molecule so getting this in the clinic or news released about this would be exciting enough the raise the sp!

Apologies if posted before!

JAK Inhibition as a New Treatment Strategy for Patients with COVID-19

“Further- more, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19.”

“Of note, Ang II mediates its actions through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, leading to vasoconstriction, hypertension, and chronic tissue injury.”

“The JAK-STAT pathway is involved in orchestrating the immune system to play a coordinated symphony. There are 4 mammalian proteins that belong to the nonreceptor JAK family, i.e., JAK1, JAK2, JAK3, and Tyk2. JAK1–2 and TYK2 are found ubiquitously, whereas JAK3 seems to act in hematopoietic lineage and exerts critical roles in lymphocyte function.”

“Accordingly, since not only AT1-R but also a lot of cytokine receptors use this pathway for signal transduction, targeting the JAK-STAT pathway may provide a new avenue toward the management of COVID-19 before a vaccine can be developed.”

“Eventually, in addition to antiviral therapy, ACE2 inhibitors, ARBs, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect JAK-STAT pathway in patients with COVID-19 to improve the treatment process and decease adverse effects because, although JAKi- nibs are highly effective, their high cost and adverse effects may limit their application. Therefore, low-cost al- ternative medications should be introduced to obviate the need for expensive and harmful treatments of COVID-19.”

https://www.karger.com/Article/Pdf/508247

Old stuff but makes you think with Keytruda and Gemcitabine gaining good ground in TNBC and referring to the pre-clinical research of T.Sen showing the in mouse trials of complete responses and total regression of Cancer in SCLC (small cell lung cancer) in mouses of Keytruda/Gemcitabine and SRA737 and T.Sen and Lauren Byers in the Academic paper suggests that is the same in other indications (Pancreatic/Colon) it does make you think when is this going to start it must at some point!

LDG (Low Dose Gemcitabine) strongly synergizes with SRA737, Conclusions and 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.

A trial of SRA737 with gemcitabine and cisplatin or gemcitabine alone for advanced cancer

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-sra737-with-gemcitabine-and-cisplatin-or-gemcitabine-alone-for-advanced-cancer#undefined

KEYNOTE - 355 (Keytruda with Gemcitabine/Carboplatin)

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-pembrolizumab-and-chemotherapy-for-triple-negative-breast-cancer-keynote-355#undefined

Combination Treatment of the Oral CHK1 Inhibitor, SRA737, and Low-Dose Gemcitabine Enhances the Effect of Programmed Death Ligand 1 Blockade by Modulating the Immune Microenvironment in SCLC

https://www.sciencedirect.com/science/article/abs/pii/S1556086419306926

I think there’s lot of info in the interview, Tim is always nervous and uncomfortable in his own skin, I have never seen an interview where he ticks the classic image on a front man or leader, that image will always lead a watcher to be negative, I think he’s just honest answering and I think will always battle in his own head what he can say or can’t say, so is an awkward affair but never any different to me, rather this than a bold ceo who are direct on timelines but can’t deliver!

So the clinical study’s they have is establishing safety of the compound and potential dosing limit in humans and that is ongoing and the focus is SDC-1801 Autoimmune which we now know, after this is completed then run a short human trial too show it has efficacy in humans.

Then they would compare the data to see where they would be best placed for an indication in the market at that time, so this is new too us imo!

Keytruda and Chemotherapy seams to be making new ground in TNBC (Triple Negative Breast Cancer), SRA 737 at the MD Anderson in Texas was with this combo!

http://www.pmlive.com/pharma_news/mercks_keytruda_hits_the_mark_in_triple_negative_breast_cancer_1340336?SQ_DESIGN_NAME=2&

Potnak focus too license is my point, the table/graph it is ahead of SDC-1802 but that’s because 1802 was put forward as an indication for cancer later than autoimmune as the RNS stated at first of all was a back up for 1801 but then a separate study indicated “don’t quote me” with a research grant found it had Cancer blocking quality’s, so the discussion here for a while was which one they would license out or both together or run a p1 trial, but now as said that the focus is completing preclinical so this is done because they will license it firstly!

Potnak it’s the first time it’s been mentioned that SDC-1801 in Autoimmune is the focus to get completed and the one to license out, and in all probably preclinical to get a deal, that’s what I gained from this, so for me it’s a clear sign of the objective for this too be licensed!

In the RNS it said:-

“The Company is targeting the completion of at least one of its TYK2/JAK1 inhibitor preclinical studies in Q4 2020, subject to successful progress. Clinical trial plans, including priority indications for both compounds, will also be developed in parallel.“