London South East | The UK's favourite investor portal.

From ASCO

Newly Diagnosed Ovarian Cancer
Recommendation 2.1. Patients with newly diagnosed stage III-IV EOC who are in complete or partial response to first-line platinum-based chemotherapy should be offered PARPi maintenance therapy in high-grade serous or endometrioid ovarian cancer. For those with germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes, options should include olaparib (300 mg orally every 12 hours for 2 years), niraparib (200-300 mg orally daily for 3 years) or rucaparib (600 mg twice a day for 2 years). Longer duration could be considered in selected individuals after discussion of risks.

costs general perusal of
Lynparza (olaparib) is a member of the PARP inhibitors drug class and is commonly used for Breast Cancer, Breast Cancer - Metastatic, Ovarian Cancer, and others. The cost for Lynparza oral tablet 100 mg is around $7,845 for a supply of 60 tablets, depending on the pharmacy you visit.

Zejula (niraparib) is a member of the PARP inhibitors drug class and is commonly used for Fallopian Tube Cancer, Ovarian Cancer, and Peritoneal Cancer. The cost for Zejula oral capsule 100 mg is around $7,967 for a supply of 30 capsules, depending on the pharmacy you visit.

[0084] The compound of the invention can be administered as the sole therapeutic agent or it can be administered in combination therapy with one or more other compounds such as steroids or interferons.

Combination Therapy

[0085] It is envisaged that the compound of Embodiments 1.1 to 1.10 will be useful either as a sole chemotherapeutic agent or, more usually, in combination therapy with chemotherapeutic agents or radiation therapy in the prophylaxis or treatment of a range of proliferative disease states or conditions. Examples of such disease states and conditions are set out above.

[0086] Particular examples of chemotherapeutic agents that may be co-administered with the compound of Embodiments 1.1 to 1.10 include:
Topoisomerase I inhibitors
Antimetabolites: (e.g. Cytarabine)
Tubulin targeting agents
DNA binder and topoisomerase II inhibitors
EGFR inhibitors (e.g. Gefitinib - see Biochemical Pharmacology 78 2009 460-468 )
mTOR inhibitors (e.g. Everolimus)
PI3K pathway inhibitors (e.g. PI3K, PDK1)
Akt inhibitors
Alkylating Agents (e.g. temozolomide)
Monoclonal Antibodies.
Anti-Hormones
Signal Transduction inhibitors
Proteasome Inhibitors
DNA methyl transferase inhibitors
Cytokines and retinoids
Hypoxia triggered DNA damaging agents (e.g. Tirapazamine)
Aromatase inhibitors
Anti Her2 antibodies, (see for example http://www.wipo.int/pctdb/en/wo.jsp?wo=2007056118)
Anti cd20 antibodies
Inhibitors of angiogenesis
HDAC inhibitors
MEK inhibitors
B-Raf inhibitors
ERK inhibitors
HER2 small molecule inhibitors e.g. lapatinib
Bcr-Abl tyrosine-kinase inhibitors e.g. imatinib
CDK4/6 inhibitor e.g. Ibrance
Mps1/TTK inhibitors
Aurora B inhibitors
FLT3 kinase inhibitors
IDH1 or IDH2 inhibitors
BRD4 inhibitors
Inhibitors of immune checkpoint blockade signalling components including PD1, PDL-1 and CTLA4; and
steroidal compounds.

[0087] In one embodiment, the compound of Embodiments 1.1 to 1.10 may be administered in combination with an alkylating agent. Examples of alkylating agents include nitrogen mustards (e.g. cyclophosphamide, chlormethine and uramustine), nitrosoureas, alkyl sulfonates and platinum-based chemotherapeutics. In a particular embodiment, the alkylating agent is cyclophosphamide.

As far as I am aware the most important regulator of inteferon 1 and interferon 2 is Jak1. Jak1 crucial in both.

easier to take a peek at Wiki to explain easier than I can.

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (?c) of type I cytokine receptors, to elicit signals from the IL-2 receptor family (e.g. IL-2R, IL-7R, IL-9R and IL-15R), the IL-4 receptor family (e.g. IL-4R and IL-13R), the gp130 receptor family (e.g. IL-6R, IL-11R, LIF-R, OSM-R, cardiotrophin-1 receptor (CT-1R), ciliary neurotrophic factor receptor (CNTF-R), neurotrophin-1 receptor (NNT-1R) and Leptin-R). It is also important for transducing a signal by type I (IFN-a/ß) and type II (IFN-?) interferons, and members of the IL-10 family via type II cytokine receptors.[5] Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. [6] Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.[7]

It is interesting to note that while other pharmas have made new innovative compounds that tend to avoid Jaks completely ( most likely due to adverse effects) amd concentrate on ways to over come Jak related problems, Sareum have stuck heavily with Jak1 with Tyk2. Jaks work best in pairs. Jak 2 and especially Jak3 can have severe side effects. All down to dose dependancy and whilst Tyk is far more selective than the other Jaks I am of the opinion it is far too selective.
Is a miniscule amount of Jak2 or Jak3 likely to cause problems? Very doubtful. Yet in high doses they do create adverse side effects. A very fine balance indeed hence why some inhibitors work better in some indications whilst others do not.

737 which we were heavily involved in the development of has yet to reach its potential. By its very design it would not have a vast significant effect in treating cancers on its own. it is not designed to kill cancer cells as such but to stop the replication of, hence why 737 had such encouraging results when combined with gemcitabine.
Gemecitabine as we know is a chemo. Chemo actively destroys cancer cells, There are limits to how much chemo we can tolerate. Gemcitabine has in high doses severe side effects and toxicities. Chk 1 does have severe ( no where as severe as some) effects. However, a far greater efficacy can be achieved with lesser doses of chk1 and gemcitabine combined. Indeed adverse effect will drop considerably. Even greater efficacy can be achieved in combo with a PD-1 inhibitor. This proved, and I will use the stated term ' remarkable results'. This of course relates to Lung cancer. HGSOC and Breast Cancer are proving to be much tougher to overcome.

Michelle Garrett an ardent supporter of CHK1 has carried out phenomenal work to overcome this obstacle.

Regards

Updates from GSK’s efforts in synthetic lethality

GSK will share data from combined analysis of three phase III studies in patients with BRCA mutated ovarian cancer, examining the efficacy of niraparib, as well as its safety profile (ASCO abstract #5518). This research adds to the understanding of the use of this poly (ADP-ribose) polymerase (PARP) inhibitor for maintenance treatment in ovarian cancer. GSK remains committed to fully exploring the potential of niraparib, with clinical trials underway evaluating it in ovarian cancer in combination with other therapies and in other solid tumours.

CHK1 has proven excellent results in in vivo and in vitro with both PARP and PD-1 as proven by the likes of Sierra oncology and Michelle Garrett, especially with low dose gemcitabine. I cannot for one see GSK ignoring this fact. Their prime objective to promote and protect Niraparib.

full link below. They also are in process of managing adverse side effects with Belantamab mafodotin (monoclonal antibody)

https://www.gsk.com/en-gb/media/press-releases/gsk-to-showcase-scientific-advances-and-progress-in-oncology-at-asco-and-eha/#:~:text=GSK%E2%80%99s%20latest%20research%20in%20oncology%20cell%20therapy%20Lete-cel%2C,including%20synovial%20sarcoma%20and%20myxoid%2Fround%20cell%20liposarcoma.%20

Question arises. Had GSK made any attempt, prior to takeover for SO, for ownership in any shape or form for SRA737, taking into consideration of in combo investigations and pre clinical trial work with PD-1 and PARP inhibitors.

GSK are buying 16th August 22
Under the terms of the agreement, GSK has acquired 100% of the outstanding shares of Affinivax. The acquisition comprised an upfront payment of $2.1 billion paid upon closing and two potential milestone payments of $0.6 billion to be paid upon the achievement of certain paediatric clinical development milestones. The transaction was subject to customary closing conditions, including the expiration or early termination of the waiting period under the Hart-Scott- Rodino Anti-Trust Improvements Act of 1976. GSK will account for the transaction as a business combination.

Full link below.
https://www.gsk.com/en-gb/media/press-releases/#:~:text=GSK%20Board%20changes%20Elizabeth%20%28Liz%29%20McKee%20Anderson%20to,for%20GSK%E2%80%99s%20momelotinib%20for%20the%20treatment%20of%20myelofibrosis

SDC1801 and especially SDC1802 which has in its patent desrition the desirable characteristic of combo/ compatibility with many other treatments to overcome cancer resistance must surely put our compounds at the very top of the GSK lookout for list.

Time will tell.

Regards

Latest Share Chat

Member Info for sadoldgit

Followers

Following

Posts (Last 30 Days)

Posts (All Time)

Last Post

Member Since

Share Chat Post Distribution (Last 30 Days)

Activity Log (Last 30 Days)