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After all these years, it's kind of insulting that there's obviously a good rumor out there somewhere, and we're totally in the dark. It's not like we haven't had that sensation before, I guess.
Let's hope it has something to do with better drugs for cancer patients.
A positive spin on a negative result is a time honored tradition, but nobody but the shorts could be "pleased" about reaching the death of half the patients in a study. In fact, one could argue that this news release was deceptively trying to suggest success from a failed trial if that were the case.
I think we need to ask them to clarify this point!
While there's a certain satisfaction in watching Wall Street turn the short attack upon themselves their excess and malfeasance affect everyone, like always.
Wouldn't it be wonderful if the securities industry was set up like the rest of the civilized world, where it's called fraud when you try to sell something in the public marketplace that you don't actually own?
It would be so much more difficult to manipulate the public equity markets without short positions. Imagine how the public equity markets would function if they were controlled by conditions of supply and demand instead of traders playing games with each other?
My guess is Avastin. Watch for stories about lung ailments after a couple of good months.
I doubt that an I-Hub admin is able to read and understand georgejjl posts well enough to have a clue about what's relevant or not. After all, it's hard enough for those of us who've been carefully reading George's posts awhile to see the relevance of circumin, let alone some stock board geek who only expects to see stock weasels playing liars poker with each other all day long on these boards.
Maybe I-hub admins aren't old enough to know people with cancer.
The doctors in my family, when told of our GBM poster patient, agreed together "Are you sure he wasn't misdiagnosed in the first place?" (I answered that they try not to do that at Duke) (funny, when I first started posting on ENMD boards there were NO doctors in my family, and now I have 3). Jerry lived about 5 years post diagnosis, and might have lived longer IMO if he'd been able to stay with Panzem.
Let's hope ENMD 1198 gives us all the chance to have the active ingredients be managed well enough to help a lot more people.
I have believed for some time that ENMD 1198 was selected for development in order to provide Panzem's potential without it's bioavailability problems. This thought allows dropping future oncology development for Panzem without having to see any bad news.
The source of the company's confidence remains a critical curiousity in the face of future funding issues. Maybe we'll have some good news real soon now.
Regards to all.
Now you see why I've been wondering about my spelling!
I thought he was saying inter-species toxicity variability, that the toxicity levels are different between humans and the lab animals that were being studied, so the target dosages had to be adjusted (he didn't say whether it was man or mouse that has the greater toxicity experience).
He also kept saying "Thal-o-mid" instead of "Thal-id-o-mid" which has me wondering if I'm spelling it right.
One thing for sure: You don't do trials at top quality institutions unless you're after the straight, unvarnished truth.
Regards to all!
Avastin's successes are great for patients, but it's toxicities are not. There should be no question in anybody's mind that long term Avastin treatments can be dangerous and debilitating. So nobody's giving up on anything new because of Avastin.
A wonderful reason to move past Panzem would be success with ENMD 1198, the Panzem analog. But, the real reason for moving past Panzem is likely to be just what they said: they're not getting enough bang for the bucks they have left. Here's hoping there's still a rabbit in that hat somewhere.
I have always believed that Celgene is a White Knight contractural basis because of the way people talked about it at the time it was first announced as a "partnership" (the actual terms have never been released). Among ENMD's benefits in this scenario would be protection from hostile takeovers as well as protection from Celgene.
VK,
You and Fargo might want to run right over there to see if you can learn something by hanging out under the tablecloth:
http://www.antiangio2008.com/agenda/
Saturday, February 9, 2008
Session V: Clinical Trial Results - Part 2
8:00 am - 10:40 am
Moderator: Michael S. Gordon, MD
Co-Moderator: Kathy D. Miller, MD
The Lady Waits No More: Anti-Angiogenic Therapy for the Treatment of Breast Cancer
Kathy D. Miller, MD
Newsweek article on Dr. Folkman:
http://www.newsweek.com/id/106226/page/2
"All of these remarkable advances emerged from the vision, perseverance and determination of one man, Dr. Judah Folkman, whose keen powers of observation, ability to think beyond the accepted beliefs and ability to inspire others led him to leave one of the biggest footprints in modern medicine."
Yeah, but...
It looks like the "expert" isn't taking into account that the only patients in a cancer trial are going to be advanced cancer cases without other treatment options, patients who are already pretty well along with their "9 years."
This has been discussed many times before, and I have no new information, but the company line is that besides the orphan designations, 2ME is pretty well covered by patents, and Panzem is 2ME in a proprietary purified form, and Panzem NCD is uniquely Entremed's product.
Personally, I think ENMD1198 (a 2me derivative patented to ENMD) is going to steal the show anyway.
I've been here ten years already. I'd like to thank so many from whom I've learned so much. Some of the lessons have been more pleasant than others.
And, for Mobery, since you've held on so long with us in this marathon card game and you still don't want to fold, you may as well "call" and see the cards. Here's hoping you win the sailboat.
And for any who were wondering, "wheelbarrow-of-money-can't-tell-the-frau" is pseudo translated to: "Schubkarren des Gelds kann den frau nicht erzählen". This, in turn, is translated back to English as "Push cart of the money cannot tell the women".
So, sharing my ten years of Entremed insight, "As he contemplates near-term cartloads of cash, a wise ENMD investor is cautious about sharing his obsessions with those he loves."
Don't let Fargo know -- he might take your dog's ration cuts the wrong way and hold back on us.
Trial results
My understanding is that the company has very close communications with the trial docs, and knows all about how things are going. However, absent something newsworthy like the suspension of the trial, the company is probably obligated to wait for the trial docs to present the results at a proper conference.
But that wouldn't keep the company from acting on results as they develop. For example, they could use unpublished results to plan a future study or share them on a non-disclosure basis as part of a partnership negotiation.
RE: Partnership Announcements
Lots of things are possible, but the history has always been to make important announcements when the market is closed. So my prediction is that if you haven't seen it by 8am or so, you won't see it tomorrow.
Frankly, the departure of Corrado suggests to me that there won't be a partnership soon, unless its with Celgene. No one could willingly leave so near to his moment of triumph.
And on that subject, It really looks to me that the market has hugely overstated the the significance to Celgene of Velcade vs Revlimid. Thoughts?
Mobery,
I can't speak for Haod, except that his garden shed is available now for residence by any long term ENMD holders in need, and the last I heard he's become old waiting for his 200 ENMD shares to return their $2000 cost.
Meanwhile, the rest of us are wondering how PZ/Temodar is going to turn out at Duke.
Regards!
Entremed had a deal with Calbiochem to sell Endostatin, and they probably still have one for them to distribute 2ME2 as well. It's in a drug company's interest to provide a way for researchers to get consistent quality product so that they can do consistent quality research.
Tumor injections would need the same PI's as everything else, simply because you would need to know how the drug behaves, how often you have do do how much, how long it lasts, where it goes, what it does, and whether there are new toxicity issues before you go any further.
Otherwise, you risk another "Ready-Fire-Aim" exercise in the PII's. Considering that the Panzem capsules/NCD episode may ultimately prove to be the reason PZ isn't already a billion dollar drug like Revlimid by now, I think we want them to get things right before they spend a lot of money for human trials.
A partner for injections isn't a dumb idea, but I would speculate that the need for that depends on the serum concentrations they're currently getting and how close the company really is to significant good news from the current trials.
"Will ENMD capitalize on PR of Mayo clinic results AND lead article in the journal Cancer Research? These developments will drive herds of potential investors who don't know squat about ENMD to the website. The news IMO should be front and center at www.entremed.com"
The news is pleasantly good, but not new or surprising to those who have been following the company for awhile. In particular IMO, this is encouraging but not something for the company to stand up and shout about since the study was about Panzem's source molecule used in a way not currently in trials and not the product it is currently in development (PanzemNCD oral formulation is here and now, but an injectable version would have to go back 20 spaces and wait until the next turn before rolling the dice). My concern about overstating this study is that people will over react, blame the company for the hype, and not consider our team credible when something infinitely more important shows up in the human trials real soon now.
"Panzem's first killer indication in cancer could be as an injectable breast ca anti-metastatic for osteolysis. Who woulda thunk it?"
While it will be great if one day Panzem is found to provide the benefits suggested by the Mayo/Oregon State study, Panzem's first rocking success will hopefully happen soon as orally delivered PanzemNCD as a combo therapy in the human trials. And, please don't use the word "killer" to mean something positive in the context of a cancer med. Avastin has actually done this to patients in trials, ya know, but our team will hopefully never have to deal with this problem!
Assuming that the NCD formulation solves the bioavailability problem (by all accounts we think it does), there's no need for an injectable version. But it's great to see another study that points the way to great success.
Over the years, we've learned more on these boards about the differences among rodent digestive systems than we ever expected to. The great thing about an injection study is that you know the dose for sure in this one.
Approval: It's really hard to know, and of course, the company has to be very cautious about speculating (clue: look at published business plans for future revenue projections).
First we need solid trial results in a sample big enough to be statistically significant. Smaller & slower efficacy results require larger samples, elapsed time from now: Between Zero (they already have it) and never, most likely to me to be about 12 months out, assuming the thread is already well in hand that's going to take us there (which I believe to be the case from the company taking the loan).
Then, the NDA needs to be filed with the FDA (Elapsed time: between zero (it's already been filed) and never. While this is man-years of work for the company, the elapsed time can be significantly compressed by working in anticipation of the trial result. Then there's the FDA approval cycle that can take 6 months to never. With a low toxicity drug for a fatal disease, hopefully they'll move quickly (for the FDA).
With slam dunk results, Gleevec was approved about 6 months after the trial announcement. This could happen for GBM at Duke, for example, if Panzem was shown to significantly increase the number of GBM patients who respond to Temodar or add to the expected length of their response. But slam dunk results are neither likely nor necessary for the drug approval process.
Right now, the company isn't given much for odds by the market. Every step along the way should improve the odds and reduce the risks, which should improve the market cap as expectations build. This process doesn't really end for a successful company either -- look at Celgene, or Pfizer, for that matter.
So the long answer is it's between 6 months and never, most likely in 18 months to 3 years if one of the current trials leads us to approvable statistics (all IMO, of course).
I think ENMD-1198 is just one piece in a bigger puzzle. The Dr. Bair hire was because of PZ/2ME2/MKC-1 success prospects (maybe PZ/Temodar at Duke, for instance), not because of impending interim results from a PI study with longer term benefits.
Of today's announcements, the Celgene revenue announcement is of greater near term impact IMO, because it means that Thalidomide royalties will be carying the company further on higher sales, and the suggestion of a slower than expected rate of displacement by Revlimid.
ENMD-1198 PI interim report
1) The hope for ENMD-1198 was that it would offer all of Panzem's benefits, without its administration issues. The poster (link below) and the press release confirm that the bells and whistles are all there. ENMD-1198 as the "New, Improved Panzem" will be the ENMD drug that really takes us to the market, IMO. In addition, with no NCD, there will be no NCD royalties.
2) The focus of the study was about pharmacokinetics in humans, dogs, and mice: How much of the drug was administered, how much got to the blood stream, how long did it stay there, etc. Why do we care about dogs and mice? Because this study will tell the team how to build better ENMD-1198 animal studies that model human cancer patients better. I'm very happy that the team figured out how to FIRST make sure the drug is getting absorbed and how long it's available in the bloodstream before starting PII trials.
3) From the poster on the ENMD web site:
"ENMD-1198's Phase 1 study continues in refractory solid tumor patients with the current dose level approaching the MTD in rats without any ENMD-1198 related toxicity."
Significance, NO ENMD-1198 RELATED TOXICITY: The importance in combo therapies and long term use situations is priceless. The number of approved cancer drugs with no drug related toxicities: Zero.
http://www.entremed.com/files/0716_lavallee_poster_final.pdf
EntreMed Presents Results for Panzem(R) NCD Phase 2 Ovarian Cancer Study
Wednesday October 24, 7:00 am ET
Results Demonstrate Activity in Advanced Disease
ROCKVILLE, Md., Oct. 24 /PRNewswire-FirstCall/ -- EntreMed, Inc. (Nasdaq: ENMD - News), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced the presentation of results for its Phase 2, open-label study for Panzem® NCD (2ME2 or 2-methoxyestradiol) in patients with ovarian cancer. The results were presented by Dr. Daniela Matei, principal investigator for the study representing the Hoosier Oncology Group, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics being held this week in San Francisco, California.
ADVERTISEMENT
(Logo: http://www.newscom.com/cgi-bin/prnh/20010620/ENMDLOGO )
Data from the Phase 2 study demonstrate that Panzem® NCD, administered as a single agent in patients with platinum refractory epithelial ovarian cancer, resulted in one patient with a confirmed partial response of their CA- 125. Five patients, out of the 18 patients enrolled, achieved stable disease lasting greater than three months. Panzem® NCD was well tolerated and no significant neuropathy, myelosuppression or thromboembolic side effects were reported. Three patients remained on study for more than 6 months and two of these patients are still on study.
Data from in vitro studies demonstrated that 2ME2 has activity against a variety of ovarian carcinoma cell lines including those resistant to other chemotherapeutic agents. In preclinical models of ovarian cancer, 2ME2 has shown a significant survival advantage compared to animals that did not receive treatment. Furthermore, in a Phase 1 clinical study conducted by the National Cancer Institute with Panzem® Capsules, an ovarian cancer patient with the clear cell subtype experienced a durable partial response to 2ME2 lasting over three years after failing three prior chemotherapy regimens.
Carolyn F. Sidor, M.D., EntreMed Vice President and Chief Medical Officer commented on the study, "Results from this study continue to demonstrate that Panzem® NCD has modest activity and an excellent safety profile as a single agent in heavily pretreated and refractory ovarian cancer patients. The stage is now set for us to consider additional trials where Panzem® NCD can be combined with approved agents in an attempt to provide clinical benefit to patients with advanced cancers."
To view the poster presentation, visit the Company's web site at www.entremed.com.
About Ovarian Cancer
Ovarian cancer accounts for 4% of all cancers among women in the United States, and ranks fifth as the cause of cancer deaths. The American Cancer Society estimates that there will be approximately 22,000 newly diagnosed cases of ovarian cancer in the U.S. in 2007 resulting in approximately 15,000 deaths. About half of all ovarian cancers occur in post-menopausal women. Ovarian cancer is frequently asymptomatic in the early stages. As a result, ovarian cancer is often not diagnosed until stage III or IV, where 5-year survival rates decline to 10-20%. Current drug therapy involves paclitaxel and carboplatin/cisplatin regimens. Many patients develop resistance to these drugs, so there is substantial need for innovative therapies that can overcome resistance, either as a single agent or in combination with cytotoxic agents.
About EntreMed
EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem® NCD (2-methoxyestradiol or 2ME2) is currently in multiple Phase 2 clinical trials for cancer. MKC-1, an oral cell-cycle regulator, is in multiple Phase 1 and 2 studies for cancer. ENMD-1198, a novel tubulin-binding agent, is in Phase 1 studies in advanced cancers. Panzem® is also in preclinical development for rheumatoid arthritis, and ENMD-2076, a dual-acting Aurora-angiogenesis inhibitor, is in preclinical development for cancer. EntreMed's goal is to develop and commercialize new compounds based on the Company's expertise in angiogenesis, cell-cycle regulation and inflammation -- processes vital to the treatment of cancer and other diseases, such as rheumatoid arthritis. Additional information about EntreMed is available on the Company's web site at www.entremed.com and in various filings with the Securities and Exchange Commission.
Forward Looking Statements
This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act with respect to the outlook for expectations for future financial or business performance (including the timing of royalty revenues and future R&D expenditures), strategies, expectations and goals. Forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Forward-looking statements speak only as of the date they are made, and no duty to update forward-looking statements is assumed. Actual results could differ materially from those currently anticipated due to a number of factors, including those set forth in Securities and Exchange Commission filings under "Risk Factors," including risks relating to the need for additional capital and the uncertainty of additional funding; variations in actual sales of Thalomid®, risks associated with the Company's product candidates; the early-stage products under development; results in preclinical models are not necessarily indicative of clinical results, uncertainties relating to preclinical and clinical trials; success in the clinical development of any products; dependence on third parties; future capital needs; and risks relating to the commercialization, if any, of the Company's proposed products (such as marketing, safety, regulatory, patent, product liability, supply, competition and other risks).
CONTACT:
Ginny Dunn
Associate Director, Corporate Communications & Investor Relations
EntreMed, Inc.
240.864.2643
--------------------------------------------------------------------------------
Source: EntreMed, Inc.
Carolyn Sidor is the chief medical officer, and runs the clinical trial program. It's likely that she now reports to the new guy. Among the problems you have in the tiny company aspiring to be the big company are the personel issues that go with one guy doing many jobs which then get split off and given to newly hired specialists (another is the problem of all the chiefs working long hours because there aren't any Indians). Hopefully Carolyn is on board with this move, and that this will need to happen to the company in hundreds of other ways real soon now in the wake of clinical success.
Carolyn F. Sidor, MD, MBA, Vice President & Chief Medical Officer
Dr. Sidor joined the Company in 2001 as Vice President, Clinical & Regulatory Affairs and was appointed Chief Medical Officer in September 2004. Dr. Sidor is a board-certified hematologist/medical oncologist.
Prior to joining EntreMed, Dr. Sidor held various leadership positions at Cato Research Ltd., a prominent Clinical Research Organization (CRO), including Vice President, Scientific and Medical Development; Medical Director; Senior Clinical Research Physician; and Project Director. She also holds a clinical staff appointment in the Department of Medicine at the University of North Carolina at Chapel Hill. From 1985 to 1993, Dr. Sidor was Associate Professor and Physician at Philadelphia’s Lankenau Hospital, Department of Medicine.
Dr. Sidor earned her M.D. degree from Thomas Jefferson University School of Medicine and her M.B.A. degree from the University of Delaware.
Resveratrol...
I've been in that study for some time (red wine and peanut butter). No unpleasant side effects so far.
Regards!
"...FDA would be thinking in terms of years rather than months of testing for quality of life..."
Actually, I think the reverse would be true. RA shows up on the xray (look at the rat slide in the ENMD presentation), and the patients can tell you all about how they're feeling, so improvement in man like the improvement shown in the rat could establish efficacy very quickly. Safety is already pretty well accepted, although it will continue to be monitored in every trial, of course. I would expect that there are some open questions about method of administration, dosing, and schedules (so don't be surprised if they still call the first trial a PI). Cialis was approved on a study of less than 500 patients, so PZ for RA could conceivably be very easy (or not, depending on how much tweaking of the protocol it takes to find some reliable patient benefit).
The "when" part is curious, in that they've been saying "Real Soon Now" for awhile, but they're still saying we'll see the IND in 2007. The first we'll probably hear of it is when the IND's been approved by the FDA (as opposed to announcing when the IND is submitted).
The company's announcement offered more detail, but I'm sure the AP people just lost the rest when they cut it down. After all, you can't expect the news people had to understand everything they write. But real stories about PZ and RA will hopefully be coming soon.
The study they are talking about affirms useful activity without worse than expected side effects, but there's not a lot of detail. If Dr. Sidor says she's got data that support single agent activity, I'm inclined to accept that.
A 17% success rate for breast cancer patients without other treatment options could be a blockbuster, even if it only worked for 4 months. But, these results would have to be sustained in further studies in order to know it for sure.
So these results are encouraging, but not conclusive, IMO. It's exactly what one would expect to see in a successful Phase II study.
Update on Jerry (I just posted this on Yahoo)
Jerry has been moved to another trial (Avastin + VP16) because his tumors have begun to grow again. For Jerry, this means facing his cancer all over, and he remains heavily within our thoughts and prayers. We pray that his new meds will produce spectacular results for him.
For us in the ENMD camp, it is a perfect example of why one case has to be viewed in a larger context:
- Panzem offered Jerry many months of extended relief from his disease.
- Panzem was a useful drug for Jerry, and would be a useful drug for any cancer patient if it did for them what it did for Jerry.
- All currently approved cancer drugs have issues with drug resistance, where tumors grow back resistant to the therapy that knocked them down at first.
- In Jerry's case Panzem either hit limiting effectiveness from drug resistance, or as Cpeptide postulated on this board the other day, it's possible that there are adaptive digestion factors that get in the way of drug absorption in the long term.
- The side effects were minimal, and Jerry felt great both mentally and physically.
- The trials do not offer the kinds of flexibility that patient care offers in the real world for adjusting doses or altering other medications. In the trial, if the tumor grows, you're out, that's it.
- The purpose of drug trials is to learn how a drug should be used, and our team is learning pretty fast these days.
- It's not fair to expect Panzem to leap from PII trials to a magic bullet panacea that kills all cancers forever.
- The Temodar+Panzem trial offers great hope for effects amplified by synergy. Synergies with other drugs is going to be the key to this game.
- There are many new tricks still to be learned about dosing tumors with Panzem.
Since somebody will ask, "Doesn't this mean Panzem doesn't work?" The answer is "No, it did work for Jerry. But it might mean that Panzem may not keep working the same way forever unless it's used in some other ways or in combo with other agents."
Doc Aaron,
Please send me your Email address at
RRGY2K@yahoo.com
Thanks!
Paranoid postings...
Dr. Folkman has no personal financial interest in Panzem. He freely shares credit with other researchers. He's about as honest and sincere as it's possible for a Harvard doctor to be. There's no friggin way he's telling anybody anything he doesn't believe to be absolutely true.
The most important reason to test with currently approved therapies: It's unethical to offer a dying person a placebo, so you don't do traditional control group studies. Instead, you test a new drug in combo with with the current standard of care, and try to get approval by showing that your drug makes the current drug better. Then later you can do studies that show your drug has other or better ways to be used.
Sure, it takes a long time, but the FDA would much rather have 10000 dead Americans every week than have them out experimenting on their own with drugs the FDA is still ignorant about.
"EntreMed investors should realize that the company may be more about keeping itself in business by being a research company than in actually bringing products to market. Is this an unreasonalbe thought or fear on my part?"
The thoughts and fears you express are pretty unreasonable.
Hey, what exactly would you expect a clinical stage biopharmaceutical company to look like? Ten years ago, Celgene was a company holding nothing better than an orphan drug approval for Thalidomide to treat leprosy. Not to demean leprosy patients, but there just aren't enough of them to make that business very interesting to anybody.
A "research" company... is that like when there's some key guy with a big ego telling you how smart he is and how great his discoveries are going to be for all mankind (please point out a press release that suggests ENMD has anybody like that on the payroll)? Only an idiot could look at a list of 14 active ongoing trials and conclude that the company is not actively trying to bring drugs to market. See, research is in a lab somewhere, not out there in the clinic with real patients, and real patients have real doctors who will publish real results for all the world to read. All that would be a huge risk for a "research company."
Celgene is a stockholder and a partner. Entremed success is to their benefit. Thanks in part to Celgene's investments in Entremed, Panzem research continues to proceed. There's no evidence of Celgene or anyone else stalling anything.
Helpwanted, it's possible that you're an intelligent fellow, but your Fears, Uncertainties, and Doubts are in conflict with that hypothesis unless you're here with a disingenuous agenda.
Maltby,
It has been the practice in all the cancer trials I've heard about for many years now that in trials that offer a new standalone medication, everyone gets the drug. This is for exactly the the ethical reasons you mention. We do have trials where there is one group that recieves a currently approved medication and another group that receives the current med plus the new one.
Regards to all.
I gotta say, they are not spending a lot of effort translating the company's press announcements into English! Did you see the look on that Duh-street.com interviewer's face when our man Burns said "antiproliferative?" (It's almost as if he was expecting a biotech commentator who knows something about cancer... don't hold your breath)
Hopefully, the words "survival" and "feeling better" and "living with their cancer instead of dying from it" will very soon be in ENMD press releases.