However i wish they wouldn't list the sponsor as "Enteron."

although the stock market seems to think of us that way.

Thanks, it's also here:

http://www.cancer.duke.edu/btc/modules/ClinicalTrials4/index.php?id=31

Guess if I'd a gone to Duke i wouldn't be so easily confused.

Second correction, that one is the breast cancer (Duke-Komen sponsor). So my original question remains.

Aha. correction it's still on there.

What has happened with the Duke GBM trial ?

here is a supposedly updated list of clinical trials at the Duke Cancer Center.

http://cancer.duke.edu/ClinicalTrials/AdultScientific_printable.asp

No sign of Panzem, 2 methoxyestradiol, on the brain cancer list or elsewhere. Trial over, terminated, not begun, what ?

Wonder if:
FDA had any news at all from the Duke study or took it into account before issuing this. While the PR indicates this was entirely based on pre-clinical data, you would think that FDA would have at least made some informal inquiry to see whether there were preliminary indications of a total failure of the study, in order to preclude totally unnecessary work.

BTW does ENMD have a new "Communications Specialist?" See bottom of PR.

That's great; thanks for posting.

Re CELG

Speaking of horizons, somebody sure likes what they can foresee for CELG.. When I looked at the Yahoo finance board for it a little while ago, the share price was an astounding 492 times trailing 12 months earnings. However, the "forward"
one-year PE was "only" 45 +.

Well, on a clear day....

Am not impressed by this BOD.

The price goes down to 1.56 and they give themselves options,
to make up for the higher exercise price for previously granted options. What have the non-employee directors done except change CEOs now and then ? It's not like we had a 50,000 employee company.

I'd like to see the scientist employees get the high number options.

re 20% ex-Asia ES/AS royalties.

That's 20% of what Childrens Hospital might receive as royalties, NOT 20% of gross sales , net sales, or anything else. A smart big pharma should negotiate with both Childrens and Medgenn to cover the bases; I expect a European copmpany would be more likely to do this. Anyway whether EMND would ever realize anything from these molecules would seem to depend entirely on what Childrens could negotiate.

RE 6/1 patent application , what exactly does it consist of ?

The purpose and achievement seems essentially seems to be "substantially continuous maintenance of the plasma level of the [angiogenesis-inhibiting]agent within the desired concentration range and so maximize the desired activity" --but what is stated to be new that accomplishes this ? In the patent terminology is there something coded in all those letters & numbers which would explain it but which can't be done in the published application for trade secret reasons ? ?

I don't read this as applying only to 2ME2 or Panzem. Is this wrong ?

Here are those stats:


http://www.abc2.org/statistics.shtml

A 2002 press release from a useful website on brain cancer:

http://www.abc2.org/news_04082002.shtml


I can't seem to link it here but this site can connect to some stats on (US) glioblastoma incidence.

European Federation Biotechnology ; Link to home page;


http://www.efb-central.org/index.php/Main/forasec.htm

Re: Endostar. This copied from site of European Congress on Biotechnology an interesting site which i will next link if i can. Q & A with Medgenn chief scientist. Note an addition of zinc binding site. ::

Dr. Yongzhang Luo, President and Chief Scientist of Medgenn and Head of Laboratory of Protein Chemistry at Tsinghua University


“The clinical trials showed that Endostar has promising therapeutic effects on non-small cell lung cancer"
March 2006 - The State Food and Drug Administration of China has recently approved a new type of anti-cancer drug named Endostar, which restrains tumors by cutting nutrition supply to them. Developed by Dr. Luo Yongzhang, President and Chief Scientist of the bio-pharmaceutical company Medgenn, the new drug has won a patent in China and applied for two more patents in the United States. Although Endostar has only been tested in China, Dr. Luo plans to seek US Food and Drug Administration (FDA) approval.

-Endostar has been specifically developed to combat non-small cell lung cancer. How would you describe the significance of this new drug?
“The target of Endostar is on endothelial cells, which are genetically stable. Endostar could inhibit tumour growth without inducing drug resistance. Unlike chemotherapy drugs, Endostar has virtually low toxicity, because it acts only on the endothelial cells of neoblood vessels, without harming other cells. According to the previous reports and our own discoveries, Endostar has very broad anti-cancer spectrum, and can be combined therapeutically with most of chemotherapy drugs.”

-Endostar is intended to be an improved version of Endostatin. What does this new anti-cancer drug offer that Endostatin did not?


“Endostatin was first reported as an endogenous tumor inhibitor by Dr. Judah Folkman in 1997. Endostar is a modified version of human Endostatin, and bears 9 extra amino acid at its N-terminal. Endostar was engineered to contain one more zinc binding site to make it more stable. The clinical trials showed that Endostar has promising therapeutic effects on non-small cell lung cancer.
Compared with Endostatin, Endostar has the following merits: higher expression level in E.coli expression system, more stable, more potent, conformationly homogeneous, more soluble."

-Endostar has already been approved by Chinese authorities after the drug showed promising results in human clinical trials between 2001 and 2004 on Chinese patients with cell lung cancer. What did the results show?

“Since I am not a medical doctor, I can only quote part of the clinical trial summary from the medical doctors who performed the human clinical trials: “Trials between 2001 and 2004 on 493 Chinese patients with non-small cell lung cancer – the most common kind – revealed that 35.4% of patients who received Endostar along with chemotherapy showed substantial tumor shrinkage, compared with 19.5% for those who received just chemotherapy...”.
The median time for tumour progression (mTTP) for patients on Endostar along with chemotherapy and for those who got chemotherapy alone are also being monitored, and the exact data is not available to me at the present.”

-One of your goals is to bring this new drug to patients in the US. What are the chances of gaining the Food & Drug Administration’s approval?

“The Drug Manufacturing Certificate has just been issued by the State Food and Drug Administration of China (SFDA), so Endostar is going to be on the Chinese market anytime from now on. But our goal is to bring Endostar to the cancer patients in the world. Although the clinical trials follow the WHO standard, it has only been tested in China, and it’s not clear whether these trials have met the U.S. and European standards. Currently we are in talks with potential partners to work together to conduct additional clinical trails if required to seek US FDA approval.”

More articles about Endostar:


Wall Street Journal (December 22, 2005): “Once-Touted Drug For Cancer Finds New Life in China” (PDF document)
Nature Biotechnology (February 2006): “China offers alternative gateway for experimental drugs” (PDF document).
Dr. Yongzhang Luo (China, 1962) obtained his Ph.D. degree from the Department of Molecular and Cell Biology at the University of California at Berkeley in 1993. Dr. Luo was appointed as a professor at the Department of Biological Sciences and Biotechnology at Tsinghua University in 2000. He is currently head of the Laboratory of Protein Chemistry at Tsinghua University.

Medgenn Co. Ltd., located in Yantai city, Shandong Province, China, was established in June 1999. Medgenn is a bio-pharmaceutical company focusing on the research and development as well as commercialization of therapeutic drugs such as novel anti-cancer drugs. Inspired by bringing longer, happier, and healthier life to people, Medgenn is dedicated to the development of novel therapeutic drugs.


> 11th European Congress on Biotechnology

question re combo trials:

If approved as combo therapy, such as might be sought here if this trial achieves goal, can a new drug, orphan or otherwise, then be prescribed off label as a single therapy or as combo with some other (as other than Avastin) previously approved drug ?

Re 2ME2 and heart disease:

Since this linked article was published in 2001, have there been any further studies/observations re any protection afforded by 2ME2 vs. heart disease ?

http://hyper.ahajournals.org/cgi/content/full/37/2/658

Do ENMD patents cover heart disease ? Wonder if any of the patients taking Panzem for cancer will be followed for incidence of heart disease ?

OT: If this stock market doesn't stabilize in a few days i'm going to need some kind of cardiac medicine... or get some lessons from that VK guy and his dog about independent living on the street.

S-3/A statement filed with SEC 5/8:

http://www.sec.gov/Archives/edgar/data/895051/000095013306002333/w20887sv3za.htm

I guess is registering shares of the Miikana people or perhaps earlier private placement. Anyway, reading the "Risk Factors" portions of these things is always good as a check on "irrational exhuberance." Guess that's why they require it.

rubberchicken:
The pending (I guess but do not know) Senate bill referred to in my posts numbered 3665 and 3666 would I believe attempt to address in part the situation you speak of. If you can access it and think it would help you might want to write your senators about it urging passage.

Proxy statement worth reading:

http://www.sec.gov/Archives/edgar/data/895051/000095013306002185/w20537pre14a.htm

Updates summary of outstanding shares and CELG's voting power, stated to be 24.9 % when it is taken into account that CELG can vote the convertible preferred it holds on a "converted" basis.

Probably the proposal to increase number of authorized common shares by 50 million, potentiating further dilution, is part of the reason for the price decline of the past few days. It shouldn't make any difference if it is assumed that the company gets fair value when and if it issues the newly authorized stock (for other than as compensation or per employee stock options)but who can know what this is ? Also i'm not sure whether Celgene has preemptive rights to participate in any new issue. 24.9 % is less in proportion than it has been in the past, I believe. But I continue to think that its ability to accomplish a takeover--or stop one-- acts as sort of a lid on the potential "reward" factor of the risk-reward assessment in this stock.

Caution light? needs laymanizing:

http://clincancerres.aacrjournals.org/cgi/content/abstract/12/7/2038

One of your better finds, George. Thanks.

Encapsulated Panzem NCD sounds like a next logical step up. The fact they used 2ME nanocrystals for the experiment instead of encapsulating something else---serendipitous or intentionally selected as best possibility for impressive result..? ? ENMD needs to consult with these guys if they have not done so already. Does the article say in that regard ?

Docaaron: Thanks. could you
give an explanation of "sensitivity" and "specificity' as used in the following:

'Endostatin sensitivity for bladder cancer detection was 48% and specificity 81% and Midkine sensitivity was 44% and specificity 82%." Thanks again, in advance.

Karnofsky score:

George thanks for the heads up on at least the start of recruiting for the Duke GBM trial. I notced that a "Karnofsky Score" of 70% or better is required. For anyone as uninformed as I here is Wikipedia definition:

http://en.wikipedia.org/wiki/Performance_status#Karnofsky_scoring

"Marginally effective in slowing tumor growth "
does not sound like stable disease to me. I expect that the poster relating to this report/abstract would clarify things but I don't know how to access them . Agree that stable disease for brain cancer would be great.

Comments re AACR PR ??

"Treatment with either 2ME2 or Temodar(R) alone was only marginally effective in slowing tumor growth."

This PR does not refer to Panzem NCD, I therefore assume it was not used. Is this correct ? The Duke Phase II trial to treat for advanced GBM seems to me to be with NCD as a single agent. From the quote above, it seems more likely than not that the Duke trial will not be particularly impressive, but if it looks better than the single agent trial reported here,and without additional toxicity, then the company can reason that the NCD version in combination with chemo can still be successful with brain cancer.. Of course yet another phase II clinical trial would in that case seem required. On the other hand, if the Duke NCD trial is impressive, then it's off to the races. Comments ?

Where is physician leadership ? :

http://www.medscape.com/viewarticle/523650?src=mp

Agree or not, something to think about.

Text for bill:
To get the text of the bill i referenced, S. 1956, go to:

http://thomas.loc.gov/

and then for the search box select "bill number" and type in S.1956. (Section 2, the proposed "findings" will have meaning to many here. Sorry i can't post a direct link. Must be a way.)

Re accelerated approvals for drugs for life-threatening conditions;

RRGY2K, I read a letter to editor in Wall Street Journal I think maybe last Tuesday which I forgot to save from a guy whose cancer-patient wife had recently died but who he felt had achieved significant life extending benefit from Iressa, regarding a pending U.S. Senate bill to hasten (compassionate use ?)approval for these drugs without the extensive statistical analysis presently required. He urged readers to write their senators to urge enactment. I believe he must have been talking about a proposed "Access Act" or S. 1956 which is referenced here:

http://thomas.loc.gov/cgi-bin/bdquery/z?d109:SN01956:@@@P

There is another bill S. 470 "Fast Access to Clinical Trials" (FACT) with a corresponding version in the House, H.R. 3196.

These would entail more accessible reporting of clinical trials. The pharmaceutical industry might have some problems with these latter ones. All of these bills seem to be languishing in committees at this time.

Couple of questions:

1. In today's company pr re the impressive preclinical results for 2ME2 for rheumatoid arthritis, neither the trade name "Panzem" or "Panzem NCD" was used in describing the experiment. Would there be an explanation for that ?

2. My guess is that preclinical success with an arthritis treatment has probably been more predictive of clinical success than with various cancer drugs, but that's all it is-- a (definitely uneducated) guess. Anybody know what the facts are on this?

Thanks George and Kaddy27.

The abstract 2135 ? re combination Panzem w/ Temodar, which was an ENMD abststract, for GBM brain tumors is interesting in view of the upcoming/ongoing (?) Duke single agent trial.

Re several other abstracts, these repeated UK (Leeds, Bath) experiments with "sulphamoylation" of 2-ME which have been seen here some time ago, and which in pre-clinical seem to make 2 ME 2 so much more effective, leaves me wondering why ENMD dsoesn't at least try it out..

Thanks George, interesting. EOM.

Docaaron, thanks. Doesn't seem fair to have the patent life depend in part on how long the patent office takes to process the application; I guess the answer is if you have it ready when you first file, you can go ahead and market it... but in the case of a drug which takes so long to get FDA approval, kind of puts the inventor between a rock and a hard place, it seems to me.. It's not like it was a new kind of wiper blade or something.

Re new patent for 1188

Great, but I wonder why per pr it just goes to 2020 ?

Found the web site under "Domain Associates" Nice to know they like us.. Is that anybody here ??

Domain Public Equity Partners
filed an SEC form today to report acquisition of shares
to make it more than 5 % oswner.. Who Dat ??

Re Patent; Re placement

1. In terms of familiarity with 2ME, it would make sense to use the same law firm to put the application together; but if the purifying method were thought to be competitive with ENMD I would think that there would be conflict of interest questions. The applicants are shown to be located in or near Rockville. Are they ENMD employees? If so I expect we could anticipate an assignment.

2. Re placement,Is the price comparable to the per share price used in the Miikana deal ? If so, this would probably be consistent with Celgene's pre-emptive rights arising from previous years deal.The fact they didn't pass up the option to maintain their large % position would be a good sign.

In the annpuncement reference was made to development of "Panzem(T)" for arthritis... not "Panzem(NCD)(T)"
Why would they not want to use the Elan "NCD" stuff for RA ?

Correction-- <no one anti-angiogenic agent> ...

Any GB in any phase 1's ?

Any indicated responses (including stable disease) ?

I don't remember seeing any. Nevertheless,this seems good strategy. If you get a hit with this fast growing cancer, with these advanced patients, it would be huge. Moreover, if you can just get stable disease, you will know it soon because of the nature of the cancer's pace. No waiting a year. At the same time, if you miss, sad as that will be for the patients in the trial, it's not going to be a complete train wreck for the therapy. I've come to accept that no one angiogenic agent is going to control all cancers by itself.