Innovation Pharmaceuticals Inc (IPIX)

[F1ash]

I wonder if any of the docs here would mind offering an opinion. Could Kevetrin be classified as a checkpoint inhibitor? I ask because Keytruda seems to often be referred to as a checkpoint inhibitor.

"Many experts say that out of all of the therapies developed to harness the power of the immune system to fight cancer over the past several decades, PD-1/PD-L1 inhibitors look to be the most promising, even though it is still relatively early days in their development"

http://www.pharmaceutical-journal.com/news-and-analysis/features/immune-checkpoint-inhibitors-bring-new-hope-to-cancer-patients/20067127.article


" Importantly, inhibition of Chk1 in p53 deficient cells greatly sensitizes them to radiation, validating the hypothesis of targeting Chk1 in rational drug design and development for anti-cancer therapies. Oncogene (2001) 20, 7453-7463."

http://www.nature.com/onc/journal/v20/n51/full/1204942a.html

"From 2001-2010 he was a faculty member in the Dept. of Immunology, Mayo Clinic, Rochester, MN. Dr. Kumar commented, “The research began with trying to understand why Kevetrin™ was so effective against certain resistant cancers that other drugs can’t treat. After a period of extensive testing, the results showed that Kevetrin activates p53 which induces the expression of p21 and acts as inhibitor of cell cycle progression. Activated p53 induces expression of PUMA and initiates apoptosis. In addition to activation of p53, Kevetrin also induces G2 / M phase of the cell cycle arrest by decreasing CDK1 and cdc25 and increasing Wee1 regulatory proteins in the cell.” Dr. Kumar continued, “Kevetrin can become the ideal drug against many cancers.” - See more at: http://cellceutix.com/cellceutix-makes-breakthrough-in-cancer-research-by-activating-p53-the-guardian-angel-of-the-human-genome-2/#sthash.sTpjK1Tp.dpuf

Treatment of A549 cells with 400 µM of Kevetrin for 48 hours resulted in G2/M phase cell cycle arrest that was associated with a marked decline in levels of G2/M regulatory proteins, including CDK1 and cdc25B, and increased expression of Wee1.

http://cancerres.aacrjournals.org/content/71/8_Supplement/4470.short

I missed this when it was first posted but CMC seemed to be working along the same lines.

CallMeCrazy Sunday, 01/24/16 05:11:59 AM
Re: None
Post # of 139155

Immunotherapy To Propel Kevetrin’s Future Growth

In oncology, today, there is a consensus that immunotherapy is the future of cancer treatment. There is a major oncological offensive underway and it involves the rapid testing of novel immunotherapy combination protocols. I have made the presumptions that Kevetrin can replace the immunity-protecting role lost when p53 fails and that its path-to-market, by way of ODD, will be speedy and successful. Unencumbered by the present, these presumptions make it easier to see that this “rapid testing” trend could, in the future, lead to a thunderous- acceleration in Kevetrin’s sales growth by rapidly creating many “combos” for CTIX”s leading cancer drug.

“San Francisco – January 11, 2016 – Today, leaders from large pharma including Celgene and Amgen, biotech including NantWorks, NantKwest, Etubics, Altor Bioscience, and Precision Biologics, major academic cancer centers and community oncologists announced the launch of The National Immunotherapy Coalition (NIC), a historic alliance--in collaboration with Independence Blue Cross, one of the nation’s largest payers and Bank of America, one of the largest self-insured companies in the U.S.--with a singular focus: accelerating the potential of combination immunotherapies as the next generation standard of care in patients with cancer.
This unprecedented collaboration of multinational pharmaceutical, biotechnology companies, academic centers and community oncologists will make possible access to over 60 novel and approved agents under exploration in the war against cancer and will enable rapid testing of novel immunotherapy combination protocols, forming the basis of The Cancer MoonShot 2020 (http://www.CancerMoonShot2020.org). The NIC will design, initiate and complete randomized clinical trials in cancer patients with cancer at all stages of disease in up to 20 tumor types in as many as 20,000 patients by the year 2020.”

http://www.cancermoonshot2020.org/

You will note that the NIC will have “access to over 60 novel and approved agents,” so Kevetrin’s speedy path to FDA approval is highly relevant. My interpretation is that Kevetrin will not be eligible for “rapid-testing” until its FDA approved. But if immunotherapy is to propel Kevetrin’s future growth, why will Kevetrin be so attractive?

MD Anderson has been studying Kevetrin for more than 2.5 years and a research team member, James Welsh, M.D., had this to say in the Journal of the National Cancer Institute (Nov. 2015):

“Identifying this role for tumor-suppressing p53 provides both a potential biomarker for response to important new cancer immunotherapy drugs and a possible new therapeutic pathway for treatment.” According to Welsh, “The p53 gene is damaged, missing or under-expressed in 42 percent of common cancers and 70 percent of lung cancers. It is by far the most common mutation in cancer.” Additionally, “Welsh and colleagues found that p53 also blocks a protein called PDL1 that tumor cells can wield to halt immune attack. Like a key, PDL1 connects with and activates a checkpoint molecule called PD1 found on the surface of T cells that shuts down those killer white blood cells.”

http://www.news-medical.net/news/20151121/Crucial-tumor-suppressing-gene-protects-immune-attack-against-lung-cancer.aspx

From a global perspective, Professor Sir David Lane, the discoverer of the p53 tumor-suppressor protein, in a July 2013 interview, stated that:

“We think there are about 22 million people in the world today living with cancer and about half of those will have a mutation in the p53 gene – a genetic defect that can be determined from DNA sequencing. In the other half of people with cancers, we believe they have something wrong with the pathway. My feeling is that nearly every tumor has an affected or moderated p53 pathway.”

Logic suggest that lung, breast, prostate and colon cancers will be among NIC’s 20 targeted-tumor types because, annually, these 4 cancers, according to the American Cancer Society, account for approximately 50% of the estimated 1,658,370 new cancer cases (2015) in the U.S. The “rapid-testing” and identification of complimentary, synergistic-apoptotic compounds for these four indications should cause Kevetrin’s sales to skyrocket.

Kevetrin is a very valuable compound. In addition to its p53 restorative property, Welsh and his colleague’s at MD Anderson have found that Kevetrin also behaves like a checkpoint inhibitor. Two PD1-inhibiting drugs, Keytruda and Opdivo, were approved in 2015 for treatment of metastatic lung cancer and while they are effective approximately 20% of the time, they each cost about $150,000 annually.

MD Anderson and AbbVie have joined forces to advance immunotherapy and given what MD Anderson knows about Kevetrin, I fully expect that CTIX’s lead-cancer compound will be central to that joint endeavor.

http://www.prnewswire.com/news-releases/md-anderson-abbvie-connect-to-advance-cancer-immunotherapy-300207638.html

http://www.genengnews.com/keywordsandtools/print/3/38018/ (Sweet Sixteen of Immunotherapy)

http://www.nytimes.com/2016/01/12/business/drug-companies-to-try-a-unified-front-against-cancer.html?_r=2

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=120039872


I was impressed how many time Kumar was referenced in the following link

"At present, there are no approved therapies targeting TP53 alterations, despite their high
prevalence in cancer. Therapeutic approaches under investigation include gene therapy for TP53 and (dendritic cell-based)
TP53 vaccines (Schuler et al., 2014; 24583792, Vermeij et al., 2011; 21541192, Saito et al., 2014; 24982341). Inhibition of
components of the DNA damage checkpoint, including Checkpoint Kinase 1 (Chk1) and Wee1, has been reported to enhance
the activity of DNA-damaging agents in preclinical cancer models with deficiency of p53 function (Ma et al., 2011; 21087899,
Hirai et al., 2010; 20107315, Bridges et al., 2011; 21799033). Clinical trials of the Wee1 inhibitor MK-1775 are currently
underway for patients with solid tumors and hematologic malignancies. Kevetrin (thioureidobutyronitrile) is a novel molecule
currently under clinical investigation, and has been reported to have anti-tumorigenic effects in preclinical models; kevetrin
has been suggested to act upon several tumor-associated pathways, including activation of wild-type p53 and selective
destabilization of mutant p53 (cellceutix.com) (Kumar et al., 2012; AACR 2012, Abstract 2874



http://www.neogenomics.com/wp-content/uploads/2016/01/NeoTYPE-Gastric-Tumor-Profile-Sample-Report-01222016.pdf