Robert Morris is helming a biotech-focused stock newsletter that’s called Biotech Supertrader (modesty has no place in the world of newsletter promotions, of course), and I’ve never covered this letter before so I thought I ought to have a look at the latest teaser we’ve been asked about.
Morris, incidentally, has been featured in our pages before — but that was back when he was editor of China Stock Insider at the same publisher. That letter, like almost all China-focused investment newsletters, seems to have disappeared quietly into that good night … which probably tells you that it’s time to invest in China again, since the newsletter publishers are ignoring the Middle Kingdom and rushing out their pitches about biotech and tech stocks. At the time, Morris was teasing NQ Mobile (NQ), which has turned out to be pretty good if you bought it down there in the $6-8 neighborhood (though it’s been a wild ride).
So now what’s he pitching for his Biotech Supertrader?
Well, the destruction of “Man’s deadliest disease”, of course. Here’s how the teaser gets our attention:
“This Tiny, Unknown Biotech is About to Unleash Its ‘Holy Grail’ Drug on Man’s Deadliest Disease
“Their ‘Guided Missile Approach’ Could Save Thousands of Lives Each Year
“It’s about to become the most talked about advancement in cancer treatment in our lifetimes and you can lock in a life-transforming fortune if you act quickly….
“I’m urging my subscribers to load up on this stock NOW….
“I’ve just uncovered a tiny, unknown biotechnology company with a new cancer drug in phase 3 clinical trials which is showing remarkable success at treating several types of cancer.
“Their scientists have found an innovative approach to cancer care which involves a breakthrough in treatment. It goes deep inside the inner workings of our cells.
“Plus, this medicine looks to be many times more effective and with fewer side effects than the chemo, radiation, and drug therapies currently available.”
If there’s one thing that investors know can make them rich and make them feel good about themselves and the world, it’s a cure for cancer — we’ve seen that effective cancer treatments can and do (occasionally) turn little biotech stocks into gigantic successes, so the dream lives on that you’re going to catch one of these lottery tickets and own the next Genentech. Will we be so lucky? Well, let’s see which one he’s pitching:
“When this drug wins FDA approval – which I believe it will – this small company’s $4.16 stock price will go straight to the moon.
“And the market for this drug is absolutely huge!
“You see, this small biotech is targeting its new drug, let’s call it ‘drug S’, at cancers of the blood and bone marrow. And it is already in very promising phase 3 trials for these two types of cancer.
“But here’s where it gets really interesting. It looks like the drug this company is developing will also work on other types of cancer!
“There are positive signs it works on Non-Small Cell Lung Cancer (NSCLC) too. There are 1.1 million people with this type of malignancy. Just in the United States alone there are over 300,000 patients with this disease according to The American Cancer Society. Each desperate for a cure.
“Plus it looks like ‘drug S’ may turn out to be an effective treatment for ovarian Cancer. There are more than 204,000 new cases of ovarian cancer diagnosed worldwide each year with 22,280 of these in the United States according to the National Cancer Institute estimates.”
So … who is it? Thinkolator sez this is Cyclacel Pharmaceuticals (CYCC)
Cyclacel is indeed a little biotech around $4 (it closed at $4.35 yesterday), with a market capitalization of only about $80 million — so be careful, we’re a big enough group here that if just a small percentage of Stock Gumshoe readers got enthused about this stock it could drive the shares up, less than a million dollars worth of shares trade each day (Biotech Supertrader says they limited their readership to 750 people — I don’t know if that’s still their cap or if they’ve hit it, but we’ll have more folks than that reading this free article).
And like many biotech stocks, it’s got some impressive scientists and it’s been losing money for a long time as they’ve been searching for a viable drug (their current lead drug also was a big focus of theirs back when it was in Phase 1 trials five or more years ago, so that’s a good reminder of the time these things take, it’s just starting Phase 3 trials now). It looks like they must have gone public in 2004, when they were about eight years old, and a quick scan of ten years of their financials over at Morningstar indicates that they’ve never generated more than a token amount of revenue (meaning, they’ve probably had some research collaboration payments or partnership funding, but never got a product to market), and have accumulated more than $250 million in losses to date. And had two reverse splits to keep the price from sinking far into penny territory.
So that’s not unusual, but it means that — as with all developmental-stage biotechs — it’s not about the financials or the fundamentals, it’s about what’s going to happen in their clinical trials and whether things are going well enough that they can continue to finance the trials … which get much more expensive as you progress through Phase 2 and Phase 3.
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All I know about them so far is that they say they’ve got enough cash to get through enrollment in their key Phase 3 study for “drug S” (which is sapacitabine) as of September when they last updated their investor presentation, but I know nothing about the science or the competing cancer drugs that are out there or how fabulous this particular one might be, so I asked our favorite medical writer, Doc Gumshoe (who, yes, is not a doctor) to check them out quickly and chime in. Here’s what he could share after looking into them for a few minutes (he’s just looking at the medical stuff, not so much the “investor presentations”):
- Cyclacel’s Prospects
Cyclacel has three drugs in development at this time, and is involved in eight clinical trials with these drugs, not including two clinical trials that have been terminated. Their top contender is sapacitabine which targets the division of cancer cells. If you can prevent cancer cells from dividing and reproducing, you have the cancer whipped, so targeting cancer cell division (or mitosis, which is the technical term) is a highly promising avenue for treating cancer. However, we need to take note of the fact that sapacitabine is one of a large number of drugs that propose to fight cancer by this method.
At present, all eight of Cyclacel’s clinical trials involve sapacitabine. Of these, at least one has been completed – a Phase 1 study of the safety and pharmacology of the drug. Four others are current, with no information about results. These are likely Phase 1 or small Phase 2 studies, to assess safety, determine what a correct dose might be, and evaluate whether the drug does what it’s supposed to do in human subjects with the target diseases, which in this case include acute myeloid leukemia (AML), cutaneous T-cell lymphoma, and some advanced solid tumors. Prior to the clinical trials, sapacitabine has demonstrated impressive results in delaying the spread of metastatic liver cancers in mice.
From what I can gather from public sources (i.e., the NIH Clinical Trials Registry), there is one Phase 3 trial, which started recruiting patients in February of 2013 and is expected to be completed in late 2015. The trial is in elderly patients with AML, and compares alternating cycles of sapacitabine and decitabine with decitabine alone. Decitabine (Dacogen) is FDA-approved for treating AML and also targets cancer cells’ replication by attacking their DNA.
It is possible that the Phase 3 trial by itself could lead to FDA approval for sapacitabine, depending on the strength of the results. However, that trial would not get the drug approved for use as monotherapy, since it is not being investigated as monotherapy. My guess is that Cyclacel is planning more trials of sapacitabine as monotherapy, perhaps in younger patients. And my further guess is that FDA approval is still quite a long way off.
Sapacitabine is also in a Phase 3 trial with cyclophosphamide and rituximab for the treatment of relapsed chronic lymphocytic leukemia. Cyclophosphamide (marketed under several trade names) is a well-established chemotherapy agent used in a number of cancers, and has led to remission in many cases; however, it is associated with truly harrowing adverse effects. Rituximab (Rituxan, Genentech) is used not only in cancers but in some autoimmune diseases. And sapacitabine is also being studied in patients with previously-treated non-small-cell lung cancers.
Although the piece from Biotech Supertrader said that the drug – identified as “drug S” –is also a promising treatment for ovarian cancer, I find no clue that it is being studied in such patients. [ed note: that’s because that “promise” is in the lab still, not in people — they had a press release about this in the Fall, “75% of Ovarian Cancer Patient Samples Highly Sensitive to Sapacitabine”, not studied in patients but on patient samples]
Cyclacel has two other drugs in development: selicilib and a drug designated as CYC116. One selicilib study has been terminated, and in a second Phase 1 study, selicilib is used with sapacitabine in patients with advanced solid tumors. Remember, however, that Phase 1 studies are many rungs of the ladder below what’s needed to gain FDA approval.
CYC116 is an aurora kinase inhibitor, meaning that it blocks the action of an intracellular enzyme that facilitates cancer cell mitosis. This is a promising avenue of cancer treatment, however, the traffic on this avenue is fairly heavy, and includes several other classes of drugs including tyrosine kinase inhibitors, and taxol based agents such as paclitaxel (Taxol, Bristol Myers Squibb); docetaxel (Taxotere, Sanofi-Aventis), Abraxane (a newer formulation of paclitaxel from Celgene) and others.
CYC116 supposedly also inhibits vascular endothelial growth factor (VEGF), which induces the growth of blood vessels that nourish cancer cells. Inhibiting VEGF is a well-established means of combating cancer, and CYC116 could hardly be characterized as a radically new departure in cancer treatment.
The one trial involving this agent has been terminated. That, of course, does not mean that development of CYC116 stops dead in its tracks – there are many reasons why a trial can be terminated, and ours is not to speculate without more information.
Beyond those three drugs, it’s hard to guess what Cyclacel may have up its corporate sleeve. It is certainly true that a successful cancer drug – even if only moderately successful– can be transformational for the biotech that develops the drug. But the drugs that Cyclacel has under development do not appear to this skeptical observer to be radically new departures in cancer treatment.
It’s important to remember, when trying to estimate the likelihood of a single drug demonstrating sufficient efficacy and safety to gain FDA approval and market share, that the competitive field is vast. As I mentioned earlier, Cyclacel has a total of 8 clinical trials in process at this time.
For the sake of perspective, it’s worth knowing that at present there are 41,445 cancer trials being conducted. So those are the odds.
So there you have it — it’s almost impossible to find a development-stage biotech whose financials look great or that makes your heart go pit-a-pat over their valuation, especially in a biotech bull market like we’ve seen over the past year or so, and Cyclacel doesn’t jump out as spectacular on that front either, not unless you’re a big believer in the promise of their specific drug. They’re a small stock and they don’t get much attention, other than from the analysts who probably helped them sell shares in secondary offerings in recent years, and there aren’t any major “skin in the game” insiders as far as I can tell (the CEO owns $1 million worth of shares, but he gets paid more than that every year), and there’s only one really focused owner on the institutional side that seems to have any kind of biotech focus (Eastern Capital owns about 7% of the shares, roughly $5 million worth … don’t know much about them).
So I don’t see a lot to make them stand out other than Robert Morris’ apparent enthusiasm for the shares (which certainly goes over the top, he calls his special report “The End of Cancer Worries Forever“), and I don’t know enough about the science to be a believer (though, to be fair, I almost never speculate on developmental biotechs because they’re so hit-driven and I’m not smart enough to be a hit-picker in the sector). It is at least encouraging that they are enrolling patients for Phase 3, and that they probably won’t have to raise more money before they have some indication of how the trial is going, but sometime in the next year or two they’re probably going to have to either get good results from this trial that let them raise cash at a good price, or have promising enough results that some big pharma company wants to jump in and help fund development of “drug S” (or just buy up the whole company, as happens with some regularity when a little biotech gets promising results).
Oh, and they are presenting at an investor conference next week, so maybe they’ll have something interesting to share then. As you can tell, this one doesn’t jump into my cup of tea … but these kinds of stocks almost never do. Sound interesting to you? Interested in the science or the lottery-ticket possibilities of $80-million developmental biotechs? Have any experience with Robert Morris or know whether or not we should consider him a biotech savant? Let us know with a comment below.
Greetings Dr. KSS. Thank you so much for all your thoughtful, patient and easy to understand insights into these various biotech companies. I am now long in Benitec. I came across — GOVX — which on 1/13/14 just completed a tiny (9 patients) Phase 1 HIV vaccination study. (I have always wondered how to clinically measure the effectiveness of a vaccination in humans, since one obviously cannot expose trial subjects to the disease.)
http://finance.yahoo.com/news/geovax-announces-preliminary-top-line-130000998.html
With warmest regards.
Dr. Karma, an add on to the questions posed above…
Does GFT-505’s activation of PPAR-Beta/delta which switches fuel preference from glucose to fatty acids give it an additional advantage over ICPT’s FXR agonist?
Activation of PPAR-delta in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids.
http://www.ncbi.nlm.nih.gov/pubmed/16960684
Activation of Peroxisome Proliferator–Activated Receptor (PPAR)d Promotes Reversal of Multiple Metabolic Abnormalities, Reduces Oxidative Stress, and Increases Fatty Acid Oxidation in Moderately Obese Men
http://diabetes.diabetesjournals.org/content/57/2/332.full?sid=02429956-fe60-4a50-aeca-2f108658d3a6
To William Koesters: Fabulous and robust discussion, which I appreciate. It puts me in intellectual nirdvandva because we are embracing the entire range of considerations all the way from molecules to macro clinical effect. Yes, there is clearly crosstalk between PPAR-gamma and the farnesoid X receptor. Bile salts, certain of them, which are agonists of FXR, boost expression of the former because the PPAR-gamma gene has an FXR response element in its promoter. Keep in mind that in the “natural” case, just boosting levels of a receptor does not increase downstream consequences of stimulating that receptor. But it starts to matter in a huge way when excess exogenous receptor ligand becomes available.
I was interested in the obverse question: does provoking a PPAR-gamma-mediated effect require a working FXR? Indeed it does:
http://www.jbc.org/content/285/47/36759
In a homologous FXR knockout mouse, rosiglitazone exerts no effect. I am quite interested to know what would be the case in a heterozygote ie FXR +/- mouse, as one often finds that effects are very much different from 50 per cent in these cases.
So yes, Genfit’s agent may prove to be a strong anti NASH effector. Just keep in mind that the somewhat similar glitazones do not seem to reverse NASH. And the big bugaboo for the glitazones is edema/weight gain, which drives many people to stop them as it can be considerable. I am not sure if that effect has been excluded for Genfit’s drug. Perhaps that was examined in phase I. But since the Genfit compound will certainly not perturb LDL and HDL, yes, it could prove to be quite an agent. Just bear in mind that the similarly acting drugs available did seem to be very anti-NASH in early studies, but less so in longer term looks. Although PPAR-acting agents need an FXR to mediate their effects, intrinsic agonism of FXR is fairly low because the endogenous bile salts that bind to it do not abound and have a hard time getting there (from the bile canaliculus to the hepatocyte nucleus). A functioning FXR is necessary for a PPAR-gamma agonist to work, but is not sufficient to mediate all of its effects, I suspect. What this could mean is that small doses of each agent result in astounding synergy for NASH, though I do not mean that to sound like a “more drugs are better stance.” One of the downsides to Intercept’s obeticholic acid no one is mentioning yet is that when FXR is stimulated, bile salt synthesis gets shut down, via negative feedback, in a big way. A diminished bile salt pool is probably why LDL cholesterol accumulates, because biliary elimination of solubilized cholesterol is a key way it is gotten rid of. We may also find that obeticholic acid leads to cholesterol gallstones, for the same reason. So the future for Genfit’s drug is quite bright.
To SS: The premise of the company you have mentioned, Foundation Medicine (FMI), is that the way forward for cancer therapy is genomics. To that I say, well, that may be right, but proof is certainly lacking. It is a theme I have touched on in other forums: genes tell only part of the story. If Travis is interested, sometime I will post a long discussion of what went wrong with deCODE Genetics, the Reykjavik company that bankrupted itself by spending a billion dollars chasing a gene found in early CAD patients….they cloned it, expressed it, made an inhibitor for it, developed that as a drug, and gave it and found it made not a whit of difference. They screwed up because they had too much faith in genes. What matter is not genes. What matters is gene expression. What matters is the proteome. What matters is epigenetics, the regulation of gene expression, which we are several Nobels away from grasping fully. Cancer therapy based on gene profiles is great in theory but has little to back it up. My former fiance is an academic oncologist who did a major randomized study of patients with advanced tumors. They were randomized either to get the best most definitive chemotherapy for their tumor type and stage and degree of responsiveness to prior regimens, or to get a chemo cocktail based on the tumor gene profile. There was no statistically significant survival difference. The field was set way back by the Anil Potti scandal of 2012…..so much data seeming to suggest that personalized chemo made a huge difference. Potti was a scoundrel: for every patient that did well, he went to their gene data and falsified presence of genes that conferred drug responsiveness. For patients that didn’t do well, he confabulated data that their profiles were wrong for the drugs they got. Anyway, I cannot see a reason at all to be in FMI. From FMI’s literature, they do not understand epigenetics and proteomics and so unwittingly or not, I feel they are misleading investors.
Thank You for taking the time.
Not that it matters but Google Ventures and the late Steve Jobs backed this company. Not sure misleading is the right term.
Dr. Karma, thanks again for your generosity and contributing your time educating us non-scientists.
Since GFT-505 is a PPAR-a and PPAR Beta/delta agonist…wouldn’t GFT-505 be less likely to exhibit side effects such as weight gain, fluid retention, heart attacks, and bone mineral loss that has been demonstrated by activation of PPAR-gamma by the Glitazones/TZDs such as Rosiglitazone?
Dr. Karma, Re: Genfit, GFT505… I just noticed this statement in the abstract published in the May 2013 issue of Diabetes care…http://care.diabetesjournals.org/content/early/2013/05/23/dc12-2012
>>There was no safety concern or any indication of PPARγ activation with GFT505.<
Ameritrade came back with the following for my query about trouble trading BNIKF
Thank you for contacting TD Ameritrade. We truly appreciate this opportunity to assist you.One common misconception regarding OTC equity securities is assuming they trade just like listed stocks (i.e. NYSE, NASDAQ, etc.). Dealers for OTC equity securities don’t use the same trading and communication technology dealers for listed securities use. The more manual systems used by OTC equity dealers can lead to significant lag times in quotes and executions. This is especially true in the first several minutes after market open, and when a security begins trading higher than average volumes. During these times an order entered at the quote might not fill due to a queue of orders entered before that order, and/or orders entered at more aggressive prices.
Regulations do prohibit OTC security dealers from trading ahead of orders in their own book. However, this does not prevent a different dealer from trading at, or even through an order at another dealer. Therefore, at times you may see trades above and below your limit price while your order remains open. Factors leading to a trade printing through your price may include, but are not limited to, volatility, pressure on inter-dealer communications, the size and type of the transaction, and the accessibility of markets and quotation sources.
With grey market securities the market maker working your order will validate the indication on his book with 3 other market makers if it is found that your order can be filled at another destination your order will be completed, however if it is found that your order cannot be matched up at another destination then the order will go back on to the books of the market maker working your order. Since this is a segmented and manual market this does not prevent other market destinations from executing orders off their own books at or through your price. Please reply if we can further assist.
If you have any questions or concerns, please contact a Client Services representative at 800-669-3900. We are available 24 hours a day, seven days a week.
Thanks for posting. So its manual……That goes a long way to explain why the spreads are so wide and the price can be so volatile. Machines are quicker and dispassionate. Its basically an old fashion bookie and if he/she cant lay the bet off, it doesnt get filled.
BNIKF trial starts
http://www.clinicaltrials.gov/ct2/show/record/NCT01899092?term=shrna&rank=5
Below is a link to Biotech Showcase presentation of Benitec:
http://www.asx.com.au/asxpdf/20140113/pdf/42m2yzjg68fxjm.pdf
In here, it is stated ‘Once administered, no ability to withdraw therapy’.
Is this a big downside to this single shot therapy as it operates on DNA ? I don’t know why there would be a need to reverse the therapy. Any expert comments will be appreciated.
This is a safety concern with the FDA (and EMEA) as there is no off switch. This is one reason why therapeutic vaccines (outside of cancer) are so slow to develop. “If something bad happens, how do we stop it?” Here, you can’t outside of some antiviral therapy (a-AAV vaccine; not going to exist) or built in kill switch (ex doxycyline suppressor in the promoter to stop transcription when dox is given). Remember, a perceived potential safety issue can be as bad or worse than a real one as it is much harder to prove that it is not a significant issue: it is often impossible to refute this with anything other than ‘handwaving’ arguments.
Hi,
I’ve been following this thread avidly for the last few days and its by far the most informative thing I’ve read in a long time !
Just a couple of quick comments from my side :
– does Travis or someone else have a public url for all the stocks and tickers mentioned here so we can track whats going up/down sideways etc ?
– has anyone seen (and would care to comment on) this article about how someone seemed to beat / curtail prostate cancer ? http://globaleconomicanalysis.blogspot.de/2013/12/cancer-free-i-beat-prostate-cancer-mish.html
Thanks.
I had not seen that article. I am keeping a copy just in case I or someone I know needs to know about it. Thank you!!!
This is an amazing thread. Dr Karma and other intellectuals on this site have provided more information than can be found on any other 10,20, 50, more ? WEB sites, discussion groups, etc, combined. Thanks to all contributors and to Travis for allowing this thread to continue to educate (from both a financial and medical perspective).
Im sorry this isnt ‘expert opinion’, but one assumes that its a one way street treatment. Once the gene is modified, there no way to put the genie back in the bottle. As it’s never been tested on humans, no one can be sure how/whether other dominoes will be affected. Truly frontier stuff. Those who apply must have reached a stage where they have no other choices. They should be in all our prayers. Im not to sure how I feel about my trivial financial involvement any more.
Actually, ddRNAi has been used in clinical trials before. The City of Hope/Benitec conducted a PI trial for HIV several years ago. It produced no adverse side effects and the ddRNAi was still active, and in one case expanding, after 3 years. It was not a therapeutic dose however. The City of Hope are looking at ways to improve the transduction. and have said this is just a technical challenge. Also, Gradalis has treated over 150 patients with their bi-shRNA FANG vaccine (which uses a ddRNAi), with no adverse side effects and are showing very good results in PI for various advanced cancers, and PII for ovarian cancer. I too truely appreciate the patients that potentially put their health on the line in clincial trials to advance these treatment. Of course, there are always risks, and I guess they will be looking very closely and hoping for no off-target effects. I really don’t see this trial as any more risky than any other vaccine trial.
I forgot to also mention that Calimmune have dosed cohort 1 using ddRNAi for HIV as well. This is a therapeutic dose (all cohorts get the same therapeutic dose, the first without chemo, the second low level chemo, and the third a medium level chemo to speed up the therapeutic. Results pending but obviously they would have stopped dosing after the first patient if there were any safety issues. Just as a reminder, Calimmune have taken a non-exclusive licence from Benitec to use ddRNAi as a treatment for HIV.
Hi All,
Just want to add – I’ve also been following this thread for the last few days and its been a riveting read !
Also – has anyone seen this article about a prominent fund manager and his experiences with overcoming prostate cancer ?
http://globaleconomicanalysis.blogspot.de/2013/12/cancer-free-i-beat-prostate-cancer-mish.html
I read Mish’s story and I disagree with some of it. I have survived my prostate cancer for several years, but Mish failed to mention the treatment that worked fine for me and many others (including a famous ex-mayor of New Yori, I believe), i.e., brachytherapy. Mish’s PSA testing also was unnecessarily frequent. I believe the surgery that he seems to favor (but disdains) may be OK, but being invasive, I believe surgery is more risky and costly than brachytherapy .
Aided by a urologist, the oncologist shoots a number of tiny radioactive palladium “seeds” (like pieces of pencil lead) through the skin below the prostate and into it, using a small frame that holds about 100 seeds so they are evenly distributed for radiation treatment within the prostate. Prior to treatment, a biopsy from my prostate showed a Gleason score of 7, quite high on a scale of 10.
So I had this treatment 6 years ago, and my PSA immediately went from over 5 down to a minimal measurable level of 0.1 and has remained there since, as evidenced by my yearly PSA tests. The procedure took about an hour in the hospital and my wife drove me home just three hours later. No pain to speak of, but I bought a lead blanket and placed it in bed between me and my wife to shield her from radiation for about three weeks until it decayed to a minimal level registered on my Geiger Counter.
There may have been improvements since my treatment, and brachytherapy may have become obsolete, but I wouldn’t hesitate to recommend it based on my personal experience. My previously minor problem with incontinence may have been slightly exacerbated, but this may be largely age-related, as I will be 90 in March, but in good health considering my years.
To respond to those concerned about the fact that there is no way to undo, “undose,” the Benitec therapy for HCV, I might offer this analogy for HCV. HCV is like having a horse barn with a mice problem. The mice burrow. They harbor leptospirosis, which is deadly. They eat the grain. They attract snakes. They leave droppings everywhere. You’ve GOT to get rid of them. They are not acutely deadly, but they pose serious long term hazards that will damage the barn, possibly kill you, and harm the horses. They mostly live under the barn’s tack room where you cannot get to them.
How would you get rid of the mice? You could place mousetraps. This is like thymosan-alfa and silymarin. A cosmetic fix that doesn’t root out the problem. You could back your pick-up truck up to the barn, and place a hose on the exhaust and pump that exhaust under the tack room. And you could get your friendly neighborhood herpetologist to come and place three dozen snakes in the barn. Creepy right? You wouldn’t want to be in that barn. This is the interferon/ribavirin approach. Can be effective but with awful downsides.
You could put out warfarin, but your dog might eat it. So might the horses. And what it does is leave mice corpses around that have come out from under the tack room seeking air as they get anemic from the blood loss caused by the warfarin. They stink up the place. To me this is like transplantation. Gory, gross, disgusting, not perfect.
There is a new substance out, The Compound. Everybody’s using it. It works 97 per cent of the time. You do not leave it out for the mice. No, you take it, and you feed it to the horses and the dog. It makes you and the critters give off anti-mouse juju that drives the mice away. It will get rid of the mice, yes, but it costs you more than a year’s salary, and your farm/homeowners insurance just doesn’t want to pay for it. And The Compound causes headaches, malaise, diarrhea for you and the dog and the horses.
One day a salesman shows up at your barn. He has a new nanobot. You cannot see it, but he has photomicrographs that show it exists. It eats nothing. You will never hear it or sense it. It’s got a battery that will last for 6-12 months. The nanobot does not kill mice. But it has a chip that allows it to sniff out any place and situation where mice are breeding. It zips to those sites, and interrupts mouse copulation. So no baby mice will be born, and the mice will thus fade away as they die off. The nanobot isn’t cheap, but it costs less than the other approaches because one nanobot rids you of mice.
I’d want the nanobot. If I had HCV, I’d so be in San Diego right now.
Dr. KSS, do you know when results of Benetic HCV P1 trials to be known? Also, what are your thoughts on the results from a recent paper by Lisowski et al. from Stanford (Kay lab) which appeared in Nature relating to AAV8’s transduction in human hepatocytes? Thanks
Hi Kenneth: I saw that paper. It is hard to know what it means. It is referring to xenografts of human liver-derived cell lines in mice. I am not sure that is a fair model system in which to assess AAV8 because so many factors are different, including, for one main consideration, that there a mouse immune system in play. AAV8 has been shown to be a very efficacious and efficient transducer of hepatocytes in primate and human models already.
The full set of Benitec data is months away. It will include liver biopsies that will be assessed by immunohistochemistry and by in situ hybridization for antiHCV shRNA and HCV RNA. But basically all HCV patients have what I sometimes call a “cruising altitude” burden of HCV RNA in serum. They get infected, and that burden stays there over the years, integrating the effects of genotype, quasispecies divergence, and innate immune function. Any movement in that burden is material. Patients getting TT-034 will get their first HCV RNA quantification by RT-PCR at 4 weeks (if memory serves, they may also be getting it at 2 weeks post-dose, but I need to review the study protocol). Patients should be getting first doses now. So I think some data are going to be known quite soon. The first doses will be deliberately subtherapeutic, to be sure this isn’t Gelsinger Redux. It won’t be. Those subtherapeutic dose recipients should in fact manifest a ding in their virus burden, I feel, and so that is meaningful. I do not know when the company will begin first reporting data. My guess is that they might like to have an abstract at European Association for the Study of Liver meeting this spring. But I also think that if buying starts to pick up in mid-February, or if any insider buys, that will be, you know, mene mene tekel upharsin.
SS: I most definitely did not state that Benitec’s TT-034 trial is binary. It is not. I said that there are many possible outcomes: no HCV RNA decrement, complete rapid eradication of HCV RNA, and all points in between. If the outcome is anything other than a null response, which all heretofore data suggest will be the case, then suddenly this almost unknown company becomes very sought after.
As to FMI being backed by Google and Steve Jobs, are you suggesting that that should be awe-inspiring and humbling, that that should be a reason for investing in it? In phrenological terms, my bump of veneration, for people and for institutions, is a dent. I never follow crowds. I follow data. Meanwhile, FMI is a $30 stock in a company losing $11 per share per year.
Sorry I misread this. You get a little ” boiler roomesque” at the end of this.
http://www.youtube.com/watch?v=TbIRedOqDwE
My feeling is that at this point with Benitec, I genuinely do not care what is on any message board. To everyone posting in those sites, I say: all that matters is the trial now underway. All the intellectual handwringing about RNAi no longer matters. The key trial has started. You are either in or not. The outcome will not be a binary success or fail. There is total failure, there is quick eradication of HCV, and there are all points in between, If the outcome is anything other than total failure, people are going to wish they were in Benitec. Analysts are going to initiate coverage. Institutions are going to want in. The sand is now trundling through the hourglass. If there is any form of effect at all, and all data argue there is going to be, then this goes into the clinic to treat cancer, HIV, HBV, HCV, pain, diabetes and any disease that owes to expression of any undesirable gene. I do not want to keep sounding off on this because each person should honor his/her comfort zone. But with the first doses now being given, you are either in Benitec or you are sitting it out. You are either fishing or you are cutting bait. From now until the end of February, what the boards and forums have to say about Benitec has become a sound and fury signifying nothing.
I agree…….if you in its sh1t or bust, if your out its bust and possibly, OH SH…..!
The wheels are turning and all further comment is hot air.
s s; Why did you copy and paste from message #156, one of karmaswimswami’s posts without referencing that you were quoting him? If I were karmaswimswami, I would not bother responding to your comments.
Tanglewood, I was apologizing as I misread his post per his binary reference hence I reposted it. Relax, who made you sheriff. I am trying to extract info to help me make my decision. Its called due diligence and I thanked DR. KSS for helping me with this process as well as educating me further in the Biotech space. The market is littered with biotechs. Were you trading in 2000 the day GERN ” cured cancer”
PVCT is down on some random article. Her is point and counter point.
http://www.thestreet.com/story/12261242/1/the-obsolescence-of-provectus-skin-cancer-drug-means-current-speculative-run-ends-badly.html?puc=yahoo&cm_ven=YAHOO
http://seekingalpha.com/article/1732082-provectus-pharmaceuticals-up-17-percent-in-a-month-potential-still-huge
PVCT has hemorrhaged down 60 per cent on 8 times usual volume today. I hope people had gotten out earlier. I expressed doubts about this agent back at the beginning of this thread. They are studying Rose Bengal, a dye, as an agent to treat melanoma by injecting it into lesions. Bad science, no reason it should work, and the photos of what it does to patients are pure horrorshow: blisters, sloughing and cellulitis. Something awful has happened. Not sure what, but I cannot help but wonder if either there has been a report of widely metastatic melanoma in patients treated, or else the FDA has refused to authorize its phase III trial. The theory was nil, the science and data weak, and frankly there are better agents for melanoma.
On PVCT;
http://www.thestreet.com/story/12261242/1/the-obsolescence-of-provectus-skin-cancer-drug-means-current-speculative-run-ends-badly.html?puc=msn&cm_ven=msn
To S S: The so called “counter-point” is from Oct 7, 2013, three months ago, and is obsolete ancient history, in view of today’s utter debunking of PVCT, as opposed to what you dismiss as just “some random article” by The Street.
Dr KSS – It is really baffling to see the eminent scientists, FDA etc let companies get into trials that has just Rose Bengal Dye? I look at the Advisory board of Provectus and it looks spectacular.
I’m pasting one of the credential here
“Dr. Orlow is Professor of Dermatology, Cell Biology and Pediatrics and Chairman of New York University (NYU) School of Medicine’s Ronald O. Perelman Department of Dermatology, known worldwide for its innovative leadership in patient care, education and research. A graduate of Harvard College and the Albert Einstein College of Medicine”
You can see the rest here:
http://www.pvct.com/advisory.html?index=6
Why would these folks be involved in such trials if they are not seeing progress with the trials? Or is it just the ‘evidence based medicine’ in progress?
I just think this dump today is all orchestrated by Cramer with his peer AF. PVCT could fail eventually and AF may be vindicated.
PVCT responds.
http://www.otcmarkets.com/edgar/GetFilingHtml?FilingID=9723393
Seems reasonable? or Am i gullible?
For all the companies that have been discussed, I am surprised I havent seen HALO tossed around. It has steadily been trending up, has a broad portfolio based on its tech and is being discussed as a prime M&A target. Even if the only future sales are generated from its use as a cosmetic agent (injection to get rid of cellulite), it will have meaningful revenues (as a cosmetic agent, more than botox). Its not a microcap, but take a look. Many of these pancreatic cancer companies should also be looking to partner with them to allow drug exposure in the pancreas (pancreatic cancer is notorious for choking off the blood vessels to minimize entry of small and large molecule drugs into the tumor mass).
There was a kindly oncologist who posted some questions above that I meant to answer yesterday and then got busy.
One, about estrogen and prostate cancer: here is a good fulltext recent review of the matter.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134227/#!po=1.28205
There have been some small pilot studies of agents like anastrozole for prostate cancer therapy and prevention with promising results. If would be interesting to take a group of men with defined BRCA1 or BRCA2 mutations who are at risk for the disease try Arimidex as a preventive.
For a long time I have wished I had the resources to study prostate cancer incidence in what I consider an interesting model system of at-risk patients: men with cirrhosis. Cirrhotic males get significant levels of estrogen because of failure to catabolize by an ailing liver. They often come in with gynecomastia and mastalgia, which Arimidex fixes beautifully. I often supplement these men with testosterone because they are all quite deficient as one of the protean manifestations of cirrhosis, and it helps them feel better, maintain bone mass (which cirrhosis robs them of) as well as muscle mass. I usually monitor both testosterone and estrogen levels in them and have a low threshold for Arimidex. Tamoxifen is a no-go in cirrhotic men, as it causes bad microvesicular steatosis. The natural history of the prostate in liver disease isn’t known, of course, because the death rate is high in the absence of transplant. But it is striking how often they get enlarged, bulky prostates even in their low-testosterone states, and how often their PSA’s go up.
As regards Gardasil (an anagram of Gradalis, “Holy Grail”….bit of PR there), you are right. HPV induced cancers are on the rise, and the vaccine may have a role in preventing those. I have a large population of gay patients that I encourage to take it because most of them are at very high risk for anal cancer from condylomata. And I thought of getting it myself because I often do ablative endoscopic therapy for those lesions, and fear aerosolizing virions.
The main case against Gardasil has been made by Diane M. Harper, MD, a department chairman at a Kentucky medical school. She was lead investigator for its pivotal studies. Unfortunately her remarks have been co-opted by the natural/supplement/anti-vaccine crowd, which she is not a part of (and neither am I). She has yet to write a good review or editorial, but some comments on her comments:
http://www.pop.org/content/merck-researcher-admits-gardasil-guards-against-almost-nothing-985
http://scienceblogs.com/insolence/2013/08/16/yet-another-antivaccine-meme-rises-from-the-grave-again-no-diane-harper-doesnt-hate-gardasil/
Her argument is an evidence based one: if you take the falling incidence of cervical cancer into account, the low antibody titers after 5 years, the fact that about 90 per cent of cervical HPV infections abate after 2 years, and the fact that there are growing reports of complications in females getting the vaccine, she argues that you are likelier, if female, to have an adverse effect from the shots than you are to prevent cervical cancer.
As regards the flu shot, again I am not anti-vaccine. You might just have a look at the 2010 Cochrane flu shot meta-analysis. If you take into account flu incidence, likelihood that this year’s prevalent flu strains are going to be covered by the shot, and so forth, 1 case of flu is prevented for every 100 shots. (Which does not mean that 99 people get the flu). For the elderly who may get really ill from the virus, shots are a good idea. Ditto for the immune compromised, and ditto perhaps for health workers who both get expose and also expose others. People need to decide case by case and on advice of a personal physician.
And though I am definitely not in the alternative camp, the data about vitamin D and prevention of all infectious disease is really now growing exponentially. We know therapy with it definitely helps prevent falls in the elderly by increasing strength. But there really i now good evidence that therapy with it both turns on antiviral, antibacterial and antitumor defenses, and also curbs autoimmune responses. This is a good review of it:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855046/
There are still questions as to whether vitamin D interventions fix things. It may be that low vitamin D is a marker for poor health, that adequate vit D is a marker for good self-care and better nutrition, and that it isn’t the crux and cause. But in view of the clear lack of harm from supplementation and the emerging evidence of benefit, this is one practical flu prevention strategy, I feel. Leo S., you might consider trying 2000 IU/day of D3 for your concern about chronic Lyme.
Dr. Karma, thanks for thinking of me, I really do appreciate your comments about vit D. About two years ago I told my primary doctor that I wanted my vit D checked. It took his office a year to put it on the lab report which came back level 24, quite low. He said to take 2000 IU/day. Since the only bottle Costco had was 5000 D3 units, and you know how some patients are , if 2000 is good, 5000 can’t hurt. Yes, I know D can. I took them for a year with absolutely no increase above 24 ml. In looking into it further I became aware of two things; 1. it is difficult for older people ( I’m 80) to absorb vit D3, and 2. vit K2 is highly attendant to vitamin D3 absorption. I just now started taking 2000 units vit D3 with 45mcg K2. I am also laying in the sun for an hour each day. What is rather amazing to me is that I always eat a handful of fried spinach with one fried egg every morning. You would think that there would have been plenty of K2 in that spinach to enhance the D3 absorption. I am still trying to be part of the team but it is difficult. The only LLD or even ID doctors are 120 miles away. Thank you for your concern.
Sorry for the typo. I believe 24 ml should have been 24ng/ml.
Sorry, meant to post link for the Cochrane flu study:
http://www.ncbi.nlm.nih.gov/pubmed/20614424
A juicy quote from that article:
” The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies.”
Kudos to Dr. Karma for warning all of us away from PVCT back on Jan 8, 2014, in his “blistering” [ha ha] post #2, above, i.e., before PVCT lost 2/3 of its value on January 23, 2014. In the face of a soaring stock price, mass investor fervor and “news” of an imminent meeting with the FDA, it is no small feat to keep a cool scientific head. Thank you again for your analyses which makes the science approachable for the rest of us.
If you were warned away from $PVCT because of one man’s self-admittedly cursory review of the company and its lead candidate PV-10, then, unfortunately, you have missed a great opportunity. I will not and perhaps for many here need not recap the drama that unfurled over the past couple of weeks with the stock. Suffice to say the detractors are scampering, tails between their legs; in particular one Alan Feuernstein of thestreet.com, who, I have on reliable source is being investigated by the SEC and a lawsuit being developed against him. The recent BTD given by the FDA to Provectus is a significant milestone. The FDA and Provectus are quite naturally proceeding cautiously but expeditiously as this IS truly a game-changing treatment with VERY SIGNIFICANT implications for a variety of cancers. Check the science and scientists thoroughly. “…data show that if a tumor is accessible to PV-10 injection, the drug is likely to destroy that tumor. If approved, PV-10 would be the first tissue-sparing local therapy for recurrent melanoma.” …”Furthermore, we believe our clinical and immunologic mechanism data show that it may be possible to delay or prevent melanoma metastasis to distant sites.”
“While the rapid ablative effect immediately evident in patients treated with PV-10 highlights our path to initial approval, the bystander effect continues to be of scientific interest and studies to quantify systemic tumor-specific immune response in cancer patients are ongoing. This emerging understanding of the secondary effect of tumor ablation with PV-10 is an important foundation for future studies to assess the long-term impact of PV-10 on distant metastasis and possible combination strategies for use of PV-10 in the treatment of cancer patients with more advanced disease.” Chief Executive Officer Craig Dees, Ph.D.
From the quote: “destroy that tumor” not shrink it.
Big pharma, particulary Pfizer, is acutely aware of these implications and have been in talks with Provectus for some time now. Bottom line, the number of patients that can benefit from this novel treatment and the billions of dollars to be made make this company one of the best investments, financially and morally, one can make this year.
SEC & lawsuits are not new to Adam F. It is his way of living. I will not be surprised if he comes out with another Bearish article on PVCT.