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New study for ENMD2076
http://clinicaltrials.gov/show/NCT02234986
Hey Ken
I know... but, like I said... someone has a sense of humor... lol...
I don't understand what the connection with Enmd 2076 is... DKK1 is a biomarker... is the Yahoo poster trying to say that this is an indication for 2076??? ...and I would be surprised if Enmd 2076 is now "CASI 2076..." I am becoming a bit of a cynic in my old age, especially about stuff posted on the Yahoo board...
...really... "Dickkopf???"... someone has a sense of humor... that translates to "Dick Head" from German...
And what is a "Peer Review Journal???"
Gotta love the... "National Key Sci-Tech Special Project of China" as well...
lol
...now... here's a guy with a unique investment strategy... "grab your huevos and hang on tight..." Right out of the Wall Street Journal...
...so Ken... Casi is transitioning into a service company for other pharmaceutical houses...
Here is the other abstract for sarcoma... Not sure why it was presented/accepted. It seems unremarkable. Only 10 patients participated.
Abstract:
Background: The use of angiogenic and Aurora kinase inhibitors has been shown to abrogate tumor growth in STS. ENMD-2076 is an oral Aurora A and angiogenic kinase inhibitor that has demonstrated single-agent activity in STS cell lines and inhibition of sarcoma growth for a patient in a phase 1 clinical trial setting.
Methods: This is a single-center, open-labeled phase II study of ENMD-2076 in advanced STS pts treated with =1 line of prior therapy in the advanced/metastatic setting. Pts were commenced on 275mg daily dose (on a 28-day cycle. Treatment-emergent adverse events were assessed by CTCAE (4.0). Radiographic or clinical tumor measurements occurred every 2 cycles (RECIST 1.1).
Results: 10 pts were enrolled from 2/2013 – 11/2013 and evaluable for efficacy. Median age is 58 yrs (41 – 72). Male: Female 1:9. Histology: Leiomyosarcoma / pleomorphic sarcoma / angiosarcoma: 7/2/1. Pts received the following prior systemic therapies: doxorubicin/gemcitabine/others: 2/3/5.
At time of abstract submission, median follow-up is at 7 months (2-12). 3 pts continue on study. Median number of cycles administered per pt = 2 (1-8). 2 pts had confirmed partial response (PR) and 1 pt with confirmed stable disease (SD) of > 6 months. Clinical benefit rate (PR+SD >6 months) was 30%. Median OS has not been reached. Median PFS at 1.8 months (95% CI: 1.2 – not reached).
ENMD-2076 has generally been well tolerated with primarily grade 1 and 2 adverse events (AEs). Specifically, drug-induced hypertension occurred in 6 pts (grade 1-2: 4 pts, grade 3: 2 pts). Proteinuria, all grade 1-2, occurred in 6 pts. Other drug related grade 3 or 4 AEs include (pts): elevated transaminases (1), leukopenia (1), and diarrhea (1). 1 pt developed Posterior Reversible Encephalopathy Syndrome (PRES) presenting as grade 4 loss of consciousness at Cycle 1 Day 15 required ICU admission. Full neurological recovery was attained after cessation of treatment.
Conclusions: ENMD-2076 has shown activity in patients with advanced STS, with meaningful clinical benefits and a side effects profile typical of this class of agent. PRES is a rare but fully reversible side effect of ENMD-2076. Clinical trial information: NCT01719744.
The abstracts are now available to the public at the ASCO website... here is the one you are inquiring about... TPS5260
The 58% refers to partial response or stable disease... I think this is is actually old data from an earlier trial... the current trial is to assess that and other data...
Background: Ovarian clear cell carcinoma (OCCC) represents nearly 15% of all epithelial ovarian carcinomas (EOC). This histology is associated with resistance to chemotherapy and a worse prognosis. VEGF has been found to be strongly expressed in OCCC. Somatic mutations in the ARID1A (the AT-rich interactive domain 1A gene that encodes BAF250a, a key component of the SWI/SNF chromatin remodeling complex) has also been demonstrated in 46-57% of OCCCs. Alteration of this chromatin remodeling complex may result in upregulation and overexpression of Aurora A.
ENMD-2076 is a multi-target kinase inhibitor, which has selective activity against Aurora A and multiple antiangiogenesis and lymphangiogenesis targets.
In a Phase II study in platinum-resistant EOC, 58% of the patients treated with single agent ENMD-2076 showed partial response or stable disease, the PFS at 6 month was 22% with a median time to progression of 3.6 months. Two out of 3 patients with OCCC who were enrolled had a longer PFS than the median.
Methods: This is a multi-center, Phase II study, in patients with recurrent OCCC to assess response rate and progression free survival rate, as primary endpoints, and duration of overall response, as a secondary endpoint, of single agent ENMD-2076 275 mg/day. Exploratory endpoints include association of somatic mutations in PI3KCA, ARID1A and PTEN, and ARID1A and PTEN expression with outcome and response. Patients ECOG =2, with histologically documented diagnosis of recurrence OCCC, any number of prior treatment regimens (chemotherapy, biologics or other target therapies except for Aurora A targeted therapies), and measurable disease (RECIST criteria 1.1) are eligible.
Based on data from previous studies, a sample size of 36 patients will provide 95% power to detect an improvement in response rate from 10 to 30% and 90% power to detect an increase in 6 month PFS from 20 to 40%.
Since September 2013, 6 patien Clinical trial information: NCT01914510.
These types of conferences are targeting the researchers, providing information on ongoing research and new directions...the emphasis will be on what has been learned and what is to be learned... The patient populations in the 2076 trials have been small... it will take larger patient populations, usually in a P3 trial to validate the results that may be positive in the smaller trials...
I do believe that the presentation will be positive and will have some effect on the PPS... but again... I view this more as an update rather than a game changer... remember most of this data has already been reported/published.
The "blockbuster" news we are all looking for will come from the FDA in the form of approval...
Hey BW... the good news is that there will be two presentations at ASCO this year... one on May 31 and the other on June 5...
Hey BW... the good news is that there will be two presentations at ASCO this year... one on May 31 and the other on June 5...
Good news in preclinical tests of Enmd 1198 and MKC1...
"Raf Kinase Inhibitor Protein (RKIP) Blocks Signal Transducer and Activator of Transcription 3 (STAT3) Activation in Breast and Prostate Cancer
Saad Yousuf,#1 MeiLi Duan,#1,2 Erika L. Moen,1 Sam Cross-Knorr,1 Kate Brilliant,1 Benjamin Bonavida,3 Theresa LaValle,4 Kam C. Yeung,5 Fahd Al-Mulla,6 Eugene Chin,7 and Devasis Chatterjee1,*
Abstract.
Raf kinase inhibitor protein (RKIP) is a member of the phosphatidylethanolamine-binding-protein (PEBP) family that modulates the action of many kinases involved in cellular growth, apoptosis, epithelial to mesenchymal transition, motility, invasion and metastasis. Previously, we described an inverse association between RKIP and signal transducers and activators of transcription 3 (STAT3) expression in gastric adenocarcinoma patients. In this study, we elucidated the mechanism by which RKIP regulates STAT3 activity in breast and prostate cancer cell lines. RKIP over expression inhibited c-Src auto-phosphorylation and activation, as well as IL-6-, JAK1 and 2-, and activated Raf-mediated STAT3 tyrosine and serine phosphorylation and subsequent activation. In MDA-231 breast cancer cells that stably over express RKIP, IL-6 treatment blocked STAT3 phosphorylation and transcriptional activation. Conversely, in RKIP knockdown MDA-231 cells: STAT3 phosphorylation and activation increased in comparison to parental MDA-231 cells. RKIP over expression resulted in constitutive physical interaction with STAT3 and blocked c-Src and STAT3 association. The treatment of DU145 prostate, but not PC3 prostate or MDA-231 breast, cancer cell lines with ENMD-1198 or MKC-1[color=redcolor] dramatically increased expression of RKIP. Overexpression of RKIP sensitized PC3 and MDA-231 cells to MTI-induced apoptosis. Moreover, MTI treatment resulted in a decrease in Src-mediated STAT3 tyrosine phosphorylation and activation, an effect that was significantly enhanced by RKIP over expression. In stable RKIP over expressing MDA-231 cells, tumor xenograft growth induced by activated STAT3 is inhibited. RKIP synergizes with MTIs to induce apoptosis and inhibit STAT3 activation of breast and prostate cancer cells. RKIP plays a critical role in opposing the effects of pro-oncogenic STAT3 activation."
Thanks... Broadway... but I am no different than you when it comes to analyzing what is taking place with this company... its all speculation and to some extent, conspiracy theory...
The options are a "right to buy" and the persons awarded the options have ten years to execute their purchase... like all options, if the stock goes up, they are in a good position to buy or sell and make a profit... if the stock goes down there is little reason to excercise their option...
However, there is one other consideration, i.e., the total number of shares is significant... and if the company is taken private... this plus what is already owned by the directors constitutes a pretty large voting block...
At the end of the day... who knows what evil (or good) lurks in the minds of the directors... only Mobery knows...
So the question is...
How difficult will it be to market shares of an unknown new company, now mostly Chinese with the exception of Capitelli, doing business globally with no track record of success???
...very funny... but you do know that Izzy lives in a basement apartment?
Chinese American Scientifics, Inc.
I really do not understand the name change... if there was postive information coming out of ANY of the on-going trials that would lead to FDA approval and a marketable drug... WHY would they feel a need to change the name of the company??? ...it doesn't make sense and it will be confusing...
And, importantly... it has been quite a while since the filing of applications for clinical trials in China and approval has still not been granted...
So... what's really happening??? I don't like the absence of light at the end of the road...
The worst case scenario is they let the stock drop to pennies... delisting will not be a consideration and then they execute a buy out for pennies on the dollar... this is all speculation at its worst... and hopefully not a consideration...
This is pretty old info... the suppositions are based upon preclinical trials... clinical trials have not yet begun and there was much criticism of the original press release last June... i.e.,
http://www.theglobeandmail.com/news/national/take-news-of-cancer-breakthrough-with-a-big-grain-of-salt/article12735079/
The China State FDA (SFDA) was renamed last year to the China FDA (CFDA). This is what their org chart looks like. http://eng.sfda.gov.cn/WS03/CL0763/
some more info...
...Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept) today announced that the FLINT trial of obeticholic acid (OCA) for the treatment of nonalcoholic steatohepatitis (NASH) has been stopped early for efficacy based on a planned interim analysis showing that the primary endpoint of the trial has been met. FLINT is a multi-center, double-blind, placebo-controlled clinical trial assessing the safety and efficacy of a 25 mg oral dose of OCA administered daily to biopsy-proven adult NASH patients over a 72-week treatment period. The trial has been sponsored and conducted by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), a part of the National Institutes of Health, at eight leading US academic hepatology centers comprising the NIDDK's NASH clinical research network (CRN).
The decision to stop FLINT has been based on the recommendation of the Data Safety Monitoring Board (DSMB) which reviewed liver biopsy data from before and at the end of the treatment period in approximately half of the 283 randomized patients, in accordance with a planned interim efficacy analysis. This analysis demonstrated that OCA treatment resulted in a highly statistically significant improvement (p=0.0024 on an intention-to-treat [ITT] basis) in the primary histological endpoint, defined as a decrease in the NAFLD Activity Score (NAS) of at least two points with no worsening of fibrosis, as compared to placebo. Those patients who had not yet completed the trial and therefore did not have a second biopsy were treated as non-responders in the ITT analysis. The pre-defined threshold of statistical significance for stopping FLINT was p < 0.0031.
Hey Broadway… Never an imposition… the on-going TNBC and Soft Tissue Sarcoma will provide an answer to your question… the primary data collection for the TNBC trial is to be completed this month… but we may not hear anything until??? …ASCO? The STS trial will be completed in January of next year.
I am cautiously optimistic… I do believe that Entremed is on the right track… they have gone from a shotgun approach to narrowing down on the science of cause and effect. If the trials successfully identify a biomarker to select patients who are responsive to Enmd 2076…one does not need to be a genius to understand the value… However, I think it is important to understand that the patient populations are low in these trials, and if there is a significant response, it will most likely have to be validated in larger patient populations…
I am impressed with the current trends and responses occurring in gene therapy… it is almost a “boutique” treatment… specific to the individual with hope for a cure rather than just disease management… it will be interesting to see where this leads…
P53 regulation...
Seasons Greetings to all with best wishes to Entremed for a prosperous New Year!
I tend to agree with you... I do believe that the group assembled by Tak and Mak are extremely capable and most importantly have a working knowledge of doing business in China... being fluent in the language as well as world class scientific credentials is a major asset...
The articles recently posted do make it clear that China is not going to be a quick and devious path to approval, but rather a progression through rigidly structured pre-clinical and clinical trials in which efficacy must be demonstrated.
The market potential in China cannot be overstated...but there is much work to be done...
Very interesting article on China Operations recently received...
http://ebdgroup.com/partneringnews/2013/12/entremed-leverages-best-of-china-and-the-west-and-seeks-to-expand-pipeline/
Your last sentence says it all... there were no choices...costly suit and no money...
Revlamid/lenalidomide is attracting a lot of attention at the ASH symposium...
http://www.myelomabeacon.com/tag/ash-2013-lenalidomide/
There have been quite a few anecdotal successes using this type of therapy reported recently. This year's ASH symposium currently underway has established a separate category for gene therapy and transfer.
This new paradigm of research and treatment just makes sense... going to the core of the disease to determine the treatment/correction... The unique feature of this personal approach is that it is specific to the individual... and, most importantly, presents an opportunity for a cure rather than treatment as a manageable disease.
The results have been remarkable in clinical trials, some of which will be reported out at the current ASH meeting.
The Drug Registration Process in China... James Yan...
http://www.healthinlink.com/down/An%20Overview_New%20Drug%20Registration%20System%20and%20Approval%20Process%20in%20China.pdf
The future of cancer treatment...
http://www.huffingtonpost.com/2013/12/01/patrick-soon-shiong_n_4351344.html?ref=topbar
Hi Aaron
That is interesting if true... the confusing thing is that the reference notes that the patent was issued in 2006 and the next 7.5 year payment was not due until 2014... does that mean the original mainteance fee was never paid...
Further, the maintenance fee is just $3600... would CHB's confidence factor be that bad that they would not risk $3600 to protect their proprietary interests?
I think 1198 may be covered by the patent for Panzem/2ME2 as an analogue.
You might find this interesting, if not amusing...
Dr. Wright reports that compounding pharmacists, even those who compound bio-identical hormones, find it virtually impossible to acquire 2-methoxyestradiol. "One compounding pharmacist," he writes, "told me that chemical supply sources advertising 2-methoxyestradiol for sale online refused to sell to compounding pharmacies .... Another compounding pharmacist ...was able to purchase a very small amount, which arrived in a package emblazoned with a skull and crossbones..."
http://www.thefreelibrary.com/Panzem%5BR%5D+(2-methoxyestradiol).-a0184141379
Sort of... Enmd was issued a patent for methods of treatment and formulations, but the licensing of 2-methoxy estradiol is still controlled by CHB:
"...EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, announced the issuance of a U.S. patent covering methods of treatment and formulations for its lead clinical-stage compound, 2-methoxyestradiol (2ME2). Panzem® NCD, an oral formulation of 2ME2, is currently in Phase 2 clinical trials for cancer. Panzem® is also in preclinical development for rheumatoid arthritis.
Patent No. 7,081,477, entitled "Estrogenic Compounds as Anti-Mitotic Agents," contains claims granted by the U.S. Patent Office covering methods of using 2ME2 to treat diseases that are characterized by abnormal cell division (mitosis), including cancer and non-oncology diseases. The claims are independent of mechanism and cover various cancers, tumor metastases, vascular abnormalities, inflammatory and immune disorders, and abnormal angiogenesis that accompanies diseases such as rheumatoid arthritis. The patent also covers multiple formulations for 2ME2. The inventors are Drs. Robert D'Amato and Judah Folkman from Children's Hospital Boston. Children's Hospital has licensed 2ME2 exclusively to EntreMed..."
There were only 10 patients enrolled in the trial and any results would have to be validated in a larger patient population.
It appears that the next step was to find a biomarker to determine those patients most likely to respond to Panzem. "...Dr. Sidor further commented, “Breast cancer remains a significant health problem, killing over 40,000 American women annually, despite the introduction of new therapies. A primary resistance mechanism to chemotherapeutic agents is thought to be the upregulation of HIF-1a and Panzem® is a potent inhibitor of HIF-1a. We hope that this study will also begin to identify biomarkers that we can use to further identify patients who would most benefit from treatment with Panzem® NCD...”
My guess is that this was back-burnered after the decision was made to focus on 2076 in December 2008.
In that press release Panzem was mentioned as a potential treatment for RA not TNBC...
"...While the Company’s other product candidates, including MKC-1, ENMD-1198 and Panzem® in rheumatoid arthritis, continue to be promising, the Company will consider further clinical development only if additional financial resources are available. As a result, the Company expects to reduce all research activities to the minimal level necessary to continue its efforts to realize their potential value through arrangements with third parties. The Company’s plan for these programs is not expected to affect ongoing trials and current patients..."
...and we all know that there were no "third parties" stepping forward...
Equally interesting is the Mayo Clinic pre-clinical study...
http://www.news-medical.net/news/2007/11/02/32073.aspx?page=2
...in which the following comment was made: "...Although clinical trials of 2ME2 for breast cancer patients have not taken place, other clinical studies of 2ME2 have been conducted. These trials are based on an oral version of 2ME2 to treat primary tumors, but this method has its limitations, as the oral version of 2ME2 is poorly suited to getting into the blood system and reaching tumors. The new Mayo Clinic study resolves this by delivering 2ME2 by injection and in a lower dose -- eight times lower than the comparable oral version used in mouse models..."
...and this...
http://www.lef.org/magazine/mag2009/nov2009_The-Unimportant-Molecule-That-May-Help-Cure-Cancer_01.htm
Clearly, Panzem was left to founder after the decision was made to abandon/shelve the ENMD pipeline in favor of Enmd 2076... Sidor's departure has had further negative implications on future Panzem research...
Having said that, I do believe we will soon see a resurgence in the interest in methoxy-estradiol. Unfortunately, because CHP controls the licensing rights, it may end up with a more aggressive pharma.
Hey Broadway
Selleck is one of many biochemical supply houses. They provide a variety of products to the research community. It is doubful that an individual would be able to purchase from them.
http://www.selleckchem.com/aboutus.html
...I think he may be in treatement for EEOD... Excessively Exurbiant Optimism Disorder...
Enmd 2076 in combo with Kevetrin for treatment of esophageal cancer???
"[Aurora kinases and cancer].
[Article in Japanese]
Kimura M, Okano Y.
SourceDept. of Molecular Pathobiochemistry, Division of Disease Control, Gifu University Graduate School of Medicine, Japan.
Abstract
Aurora kinases are highly conserved in eukaryotes and involved in many processes during cell division. Three Aurora kinases have been identified in humans and designated as Aurora-A, -B, and -C. Aurora A regulates centrosome function during M phase through its interactions with various cell cycle regulators including TACC, chTOG, Ajuba, BRCA1, LATS2, and p53. Aurora-B localizes at the kinetochore from G2 to metaphase, and relocates to the midbody after anaphase. Aurora-B plays roles in spindle dynamics, chromosome condensation, and cytokinesis by interacting with many proteins such as INCENP, Survivin, CENP-A, MgcRacGAP, and intermediate filaments. Overexpression of both Aurora-A and -B proteins is frequently observed in various human cancer tissues, and a common coding region polymorphism in aurora-Aaffects the risk of breast or esophageal cancer. Ectopic overexpression of Aurora-A or -B protein leads to aneuploid cells. The cells overexpressing active Aurora A or wildtype Aurora-B are tumorigenic in nude mice.
http://www.ncbi.nlm.nih.gov/pubmed/15675572
http://www.biomedcentral.com/content/pdf/1471-2121-12-13.pdf"
...an excellent reveiew of the biomarker development process underway in the TNBC trials presented by Jennifer Diamond...
http://www.entremed.com/files/Diamond022113.pdf
Tak Mak and UCLA colleague announce new drug discovery...
http://www.ascopost.com/issues/july-10,-2013/investigational-new-drug-application-filed-for-cfi-400945.aspx
...more...
"AUGUST 7, 2013 · 9:43 AMGate 10 Leads to Year 11 – Field of Dreams
http://getpassioncapital.files.wordpress.com/2013/08/toronto-20130807-00177.jpg
This is Gate 10 at the southwest corner of the Rogers Centre and this is also the entry way for all participants in the Shoppers Drug Mart Weekend to End Women’s Cancers to be held September 7th and 8th. Early Saturday morning all the thousands of walkers and volunteers will make their way through Gate 10 and down to the field of the Rogers Centre for opening ceremonies. The support of the Toronto Blue Jays and the Rogers family has been incredible and we will call the Rogers Centre home Saturday night to sleep over and celebrate. Dr. Tak Mak has huge news on his new drug that has been approved by Health Canada, and Saturday night will be special as we all gather to hear performances by Burton Cummings and Johnny Reid. I’ll be sleeping out on the field in a tent with a couple thousand of my walking buddies. This is going to be the 11th year of the Walk and it will be the best route ever both days. With the Rogers Centre, we will truly be celebrating on a “Field of Dreams”. Here’s the web site because plenty of time to register and donate. Go to www.endcancer.ca."