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.
About statins, I am happy to weigh in again on them. They and vitamins and supplements have been the subject of quite animated debate elsewhere on Gumshoe. I’ll not recapitulate that debate except to make a few critical points. A critical one is that for the vitamin crowd, this is a belief system, and nothing more. Belief systems are impervious to data. In fact, the more adverse the data, the more entrenched the belief system adherents grow. When yet another study comes out (as did this week, showing that prenatal vitamins are associated with bad fetal outcomes) the refrain from the vitamin mongers is utterly predictable. Bogus trial! Rigged study! Doctors, big pharma and the FDA are all a bloc, all in cahoots, all working together to screw you and me! Those were SYNTHETIC vitamins, made in a LABORATORY! (This is nonsense. A substance is a substance. Its structure is the same regardless of the source.) Those vitamins were made from COAL TAR! All illnesses are a result of lifestyle! Diet! Bad choices! Try telling that to cancer patients, to patients with rheumatoid arthritis, to patients with type 1 diabetes, to patients with birth defects and congenital diseases. That line of reasoning is positively insulting and offensive. And If the Western diet (which no one can define) is so abhorrent, why is Western longevity at an all time high and climbing? The “natural” delusion has stalked and infected people all throughout western history. In Nietzsche’s day, he was berserk about this mindset, He wrote that at is very heart, it is nature that produces floods and fires and earthquakes, droughts, epidemics. Nature has no vested interest in seeing us live longer and thrive. Nature is about chaos and entropy. “To live,” wrote Nietzsche, ” is that not wanting to be anything OTHER than natural?”
In the early 90’s, I lived and worked in Taipei. At that time China and Taiwan considered themselves to be in a technical state of war. In southwestern Taiwan, where the Strait of Formosa is at its narrowest, there is a gun installation. At the time, China would lob one shell over at Taiwan on Monday, Wednesday and Friday. Taiwan would fire a cannon at China on Tuesday, Thursday and Saturday. I have a similar relationship with a close friend who is a nurse but also a vitaminmonger. Every day of the week, I send him a couple of new studies casting doubt on the claims of the vitamin crowd. And he replies, usually in the form of a column from Natural News. He is my friend, but the rebuttals are all the same. Conspiracy! Not natural! Synthetic! Deliberately screwy study design! No data will ever persuade the vitamin crowd because theirs is a belief system that floats oblivious to data. Meanwhile, I do not believe in belief. I follow only data. An analogy I have used here before: two religions are co-dominant in Japan, Shintoism and Buddhism. For the easy and happy things, the Japanese are Shinto. For the tough things, they are Buddhist. And so I say to the vitamin and supplement crowd, yes, go for it. Your wares and potions are fine until you get sick. When you get sick, which you will because that is nature’s way, serious medicine from doctors is always available. A very recent study shows that not only are vitamins not helpful, but that people are probably harming themselves. People who load up on antioxidants are clearly dying sooner of cancer and infectious disease. And the reason is simple: the body must have oxidative mechanisms in good working order as an immune defense. Quench all oxidation and you kill yourself.
The final word on what causes vascular disease is far from written. There are many many factors. Cholesterol is one. Low density lipoprotein cholesterol particle size and size distribution is another. Inflammation is another. Blood pressure, insulin resistance, and genes are huge others. There is not a physician alive who claims that cholesterol is the only factor. It isn’t. It is however a modifiable one. As I have said before, the reasons for taking statins are primary and secondary. Primary is prevention of a heart attack or stroke. Secondary is prevention of a second heart attack or stroke. Primary prevention is a work in progress. But to not take statins for secondary prevention is simply foolhardy. The data are overwhelming.
Does anyone remember the film distributor Rank from the 1950s? Watch TCM and you will see what I mean. All Rank films open with a clip of a native in a loincloth. He slams a baton into a gong. This bombast, this lack of nuance and subtlety, is what the anti-doctor crowd is all about. As other doctors here can attest, the idea that doctors, pharma and the FDA are part of a conspiracy is just belly bustingly hilarious! All of us can tell you awful things about both pharma and the FDA. These three factions are like a war in which there are three mutual enemies. Pharma fears the FDA and is often out to dupe doctors. The FDA? Gee, they’re like that Monty Python skit: “No one expects the Spanish Inquisition!” No one EVER knows what the FDA will do! They are imperious and capricious. They are like the SEC, underpaid, often out to enforce trivial matters to look astute while they ignore big problems. The FDA goes through pendulum swings. Oops, too many of us eating donuts and reading newspapers. Let’s come down like a ton of bricks on some drugs this quarter. Next quarter: let’s kick back. Last quarter was exhausting. Where are the donuts? WWII was about the Allies and the Soviet Union, two enemies, fighting the Axis. Three way enmity. So it is with doctors, pharma and the FDA.
The recent major statin guidelines were really not about statins at all. As I have discussed before, a major big pharma strategy is to succeed by making others fail. Those guidelines were about torpedoing gemfibrozil, niacin, ezetemibe, and other agents such as other fibric acid derivatives and fish oil. And in fact for all of those agents, there is no evidence based benefit at all. They improve lipid numbers, but neither survival nor event rate. The statin guidelines were also about the coming of the PCSK9 inhibitors. This is a new class of monoclonals that bind to PCSK9, which downregulates LDL receptor expression. When these drugs are given, LDL receptor expression surges, and LDL cholesterol really plummets. They are not approved yet but almost certainly will be. Pharma needs to sell statins now because those agents are coming. They will be expensive, require iv infusions, but for patients intolerant of statins, they will become drugs of choice.
In my early teens, I became entranced with an ideology called General Semantics. GS is a recognition that in processing information, the human brain is prone to certain reproducible cognitive distortions. GS is about avoiding those. One of its key tenets is: there is no such thing as allness. Any time someone comes at you and says all things are this way, all doctors are rotten, all drugs are evil, all supplements are good, well that is false because allness does not exist. We doctors, some of us, have led to this belief system by our own actions. Sometimes we do not listen as well as we should. Sometimes we have fixed patients in formulated phrases, as Eliot wrote in “Prufrock.” Sometimes we have done what is best for ourselves before we do what is best for our patients. We may recommend things for them from which we stand to benefit. But not all of us are that way! A great many of us are genuinely concerned about patient welfare and about treating our patients as we ourselves would want to be treated. Those are the doctors you need to find, stick with, and really take advice from. I am sure my physician colleagues will agree with that.
Dr. KSS: I have spent a lot of time (re)reading this thread and have to say that I have learned something new every time I have read it. This applies to what I have learned about health, biology, humanity, human nature as well as investing. First of all, kudos for the wisdom you have shown on this thread to say nothing of the patience you have shown to some of the other respondents . . especially towards the “doubters” on that other referenced thread regarding statins and Myron.
In my 30+ years of investing I have never really relied on others to steer my investments as it is difficult to peel away the onion as to whether there is an alternative motive involved. Like many others here, I have had my successes in investments (that have not been discussed here, i.e. CLDX, ISIS and INO and duds, i.e. DNDN. ) However I have taken your advise regarding BNIKF and RNN. For that I thank you.
Besides yourself, Siva, Allen and a host of others have indeed made this a “must read”. Thank you all and keep up the excellent work.
Hi KennyG,
Curious about your investment in Inovio Pharmaceuticals. I’ve had INO on my watch list for some time. I’m presently waiting on results of their Phase II synthetic DNA cervical dysplasia (HPV type 16/18) therapeutic vaccine data that are due in a few months. If the data is positive this would seem to me that their electroporation delivery system will then be proven which is necessary for the rest of their pipeline. Do you agree with that? I got burned badly with one of my investments (CLSN) last year when their delivery system failed miserably even though management exhibited much optimism throughout the Phase III cycle. So I’m a little cautious these days.
I agree with you that this is an extraordinary thread for biotech investors who do not have a medical background.
I absolutely don’t want to divert attention away from our major discussions surrounding investing, but I thought this post by KSS was well written and on the mark.
I am curious Dr. KSS, given your broad spectrum of knowledge and your reliance upon provable data, what would you say are the two, three, five, etc. things that people can and should do to maintain optimal energy and health as long as possible?
Sadly, I suspect that part of the reason so many fear drug companies, the FDA, etc. is that we live in a time in which we all know that money is so alluring to some that it will cause them to conduct business in ways that are not in the best interests of the general public.
The best example that comes to mind is the fast food industry, which spends millions of dollars on studying such concepts as “mouth feel,” and divising newer and more appealing ways of combining fat, sugar and salt specifically to intice us regardless of the lack of benefit in eating much of the resulting foods they design.
Anyway, would be curious to see your list of dos or don’ts for maintaining good health and longevity.
Don
Don, Great question you asked. I wanted to ask this question always but for some reason hesitant to ask here. Thanks for asking this question. I would like to know Dr KSS views on
1. Organic Vs non-organic food consumption – Eating non-organic good- Do they pose real health hazard?
2. GMO foods, labeling and FDA’s role (aka Michael Taylor).
3. Is Cholesterol/lipid profile management the right standard for managing heart disease?
4. Which method of cooking provides maximum health benefits – raw, steaming, boiling etc?
5. How do I manage inflammation ? Which foods to avoid(that causes inflammation) and which foods to eat that reduces inflammation?
6. Any other general habits that we should follow for healthy living.
Will really appreciate if you can provide some thoughts on these.
Good questions Siva; I too would love to hear the good Doctor’s thoughts on them, particularly, two, three, and five.
Karmaswimswami, GMO issues, the efficacy of the lipid hypothesis, and combating inflammation on a systemic level are all issues with the potential for profound impact upon all of our lives.
If you have any additional thoughts to share, we would welcome them.
Don
http://www.benitec.com/documents/131113_MergerMarket.pdf
The company will update the TT-034 progress through out this year.
“The companyʼs lead drug candidate TT-034, for the treatment of the
Hepatitis C virus, is starting a 14-patient Phase I/IIa trial later this
year or in early 2014. Complete trial data will be available in about 18
months, French said, but noted this is an open-label study, so data
will be available throughout the trial. Viral load can be measured
initially in the first few days, and then again several weeks out, he
explained. The preclinical data showed a quick drop in viral load, he
added”
I have a couple of questions on the following about Benitec’s lung cancer program:
“About AUD 3m of the recent funding round was earmarked for
advancing Benitecʼs non-small cell lung cancer therapy program, a
disease with a high mortality rate because the cancer is very resistant
to treatment, French said. The therapy is currently in preclinical trials
in the University of New South Wales in Australia and Benitec is
gearing up to do a clinical trial in Europe late next year with the
Clinical Trial Group, a CRO. The focus of this therapeutic program is
not to cure the disease, but to make chemotherapy treatments more
effective, he explained, noting that in this case Benitecʼs therapy will
turn off a human gene that is hindering treatment.
”
1. Why is the therapeutic program not designed to cure the disease instead making the chemo treatment effective?
2. Also, they are doing the trials in Europe? Not sure what the rationale behind this, but will FDA accept trials done outside USA?
“The company is also pursuing an orphan indication related to liver
transplantation procedures for Hep C patients. The donor liver would
be pretreated with Benitecʼs DNA therapy before being transplanted,
French explained, noting this procedure could possibly prevent the
new liver from being infected with the virus. There are about 2,000
transplant procedures a year in the US, and because of the relatively
small size of this market, it is possible this procedure could receive
orphan status from the FDA which would speed the approval process”
Has anybody heard about Delcath’s chemosat treatment? I’m currently invested in DCTH (a bad investment for me). The FDA turned down Chemosat last year (their FDA filing was based on Gen 1 filters). Gen 2 is more efficient, claims the company. The liver is temporarily isolated from the body’s circulatory system, during which time a 30 minute infusion of the chemotherapeutic agent melphalan hydrochloride directly to the liver occurs. The blood is collected as it exits the liver for filtration by proprietary filters prior to returning it to the patient. Chemosat is approved in Europe and they seem to be getting some traction in UK, Germany and Italy. They are seeking reimbursements in Europe and have been successful in a few countries. There were a few touching stories that got benefitted with Chemosat. One story below:
http://www.dailymail.co.uk/health/article-2258625/Cancer-Mega-chemo-kill-cancer–effects-Treatment-transform-prospects-desperately-ill-patients.html
Will appreciate any insights on chemosat. The stock is floundering at 30cents. A R/S is coming.
Directed at Glenn, Karmaswimswami (what a name 😉 ), and all others interested in CTSO:
Check this out: http://www.linc-medical.co.uk/gallery/upload/file/beads%20that%20beat%20blood%20poisoning.pdf
Perhaps it gives You a bit more insight to their technology!
The company is well worth a bit of investigation, I might add!
Herbalix: Thanks for the links. I had come across those in researching CytoSorbents (CTSO). In my view, what those items report is very much why I do not advocate buying shares. Despite the notion of cytokine storm having been around for 20 years, and despite literally hundreds of thousands of studies, no one can agree on what it is. Certainly some cytokines, particularly the interleukins 1, IL-6, and TNF alpha, are deleterious. But beneficial cytokines conferring survival benefit, such as IL-10, are also released. Cytokine storm follows severe cases of flu, malaria, bacterial sepsis, fungal sepsis. It leads to leaky capillaries, endothelial dysfunction, and gradual failure of multiple organs. A huge array pf well-reasoned therapies have come and gone for it, including plasma exchange (plasmaphereis), charcoal hemoperfusion, even hemodialysis, as well as high-dose iv steroids, and use of a variety of monoclonals. Nothing works. Part of the reason nothing works may be that good cytokines are being removed just as well as bad ones. A huge number of drugs with theoretical reasons that might help, such as gemfibrozil, cyclooxygenase inhibitors, antioxidants and soluble TNF-alfa receptors have been deployed and they do nothing for it.
A concise review of cytokine storm, what is happening, and what has failed.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294426/
As you can see, I hope, it is not simple at all.
As this recent Nature paper suggests, TLR4 action is very promising. I am sure we will hear more about this:
http://www.ncbi.nlm.nih.gov/pubmed/23636320
Some company will acquire this agent.
Meanwhile, CTSO’s method is so low tech as to be no-tech. Blood gets run through “magic” beads, and nonspecific adsorption of blood proteins occurs. It is not scientific. CTSO has not even definitely characterized what happens to the aggregate cytokine pool with their method. And definitive data showing that this helps patients live longer is totally lacking. What I was hoping for was something at least vaguely sophisticated, like perfusion of blood across a resin containing immobilized antibodies to IL-1 alpha, IL-1 beta, IL-6 and TNF alfa. But no such luck. CTSO hasn’t tried hard at all. Their method is approved in Europe as a Hail Mary intervention for dying patients. It has come, to little fanfare. I predict that soon it will be gone. Meanwhile, the best treatment for cytokine storm is treating the underlying cause. What we need are better antivirals. People really don’t realize it, but medicine lags profoundly in having a good arsenal of antivirals for influenza and other deadly viruses. It is 2014, and still, if you get very sick with influenza, there is no drug to kill that flu. Care is supportive only. We need better drugs to treat underlying causes. We need a better definition of what the true evil humor is in cytokine storm, and a way to go after that selectively while ignoring good cytokines.
I fear that biotech investors often do not have a long view of what has been tried before for a clinical problem, and also a lateral view, of what things compete or stand poised to grab share. CTSO has done almost nothing of note. They are advocating magic. Percolate sick blood through our magic beads and see if the patient gets better. How many times must we go down this road before we grasp that a lowtech approach does nothing for cytokine storm? CTSO is trying to fan the flames of unrealistic expectations and to lure medically naive investors. Don’t be one.
Heavens….I have no idea whether anyone will make money from this thread but I am absolutely certain that Swammi will have saved MANY from significant losses.Thanx again.
Congrats! on your use of “heavens” instead of the pejorative “JEZ” which is a symbollic curse using the name of Jesus that is extremely objectionable . I hop you have learned something from this besides how to invest your money.
Im glad you noticed……It was done with you in mind Bob. I know you to be a sensitive soul and you will doubtless get your reward in heaven.
Dr K Like many others before me thank you for your insight into the complexity of the biotech world of investing. The depth of your knowledge and resources is greater than most of us could probably obtain in a lifetime. The research you do and knowledge you share will save a lot of investors from many disappointment and lost money. Your right to say a lot of investors are led astray by these companies and their lofty perceptions of their own products. With that being said i have come across another company in the recent past that claims to have great prognosis for the treatment of various flu viruses.
My question to you is am I being led astray again or is there some legitimacy to there research and product. The company is Nano Viricides Inc (NNVC).
Thanks for your response also to an earlier post.
Don’t worry Randyman, I have already invented a cure for influenza (well man flu anyway). You swig a large glass of whiskey just before bed; load and extra duvet on top suffer one uncomfortable sweaty nights sleep, and your cured by next morning. NO no no don’t thank me……I’m expecting the Nobel invitation in the post as I type.
To Rodney Elmore re INO: I agree that a lot of INO’s success will depend on the success of their electroporation delivery system. But keep in mind that this here is the opinion (mine) as an investor and not someone in the medical field or whom possesses the depth of knowledge of our good Dr. KSS here.
Also, it appears that INO has cash on hand to support their activities till 1Q2016, so near term dilution should not be an immediate issue. And their recent collaboration agreement with Roche “will co-develop highly-optimized, multi-antigen DNA immunotherapies targeting prostate cancer and hepatitis B (the “Products” (per their 10Q) also shows promise both in their science and recurrent milestone payments to sustain their efforts.
So yes, INO’s ability to demonstrate good trial results (by 1H2014) and continued partnership payments from Roche will go a long way in determining their success. But as I stated earlier, this is a laymans opinion.
KennyG: I really appreciate your kind comments yesterday. To you and Rodney Elmore: when I first heard about the Inovio electroporation technique. I was quite doubtful. I have done quite a bit of electroporation work in vitro, and one key thing about it is that if you are zapping cells with enough of a jolt to introduce DNA into them, you will de facto be killing many of them. Despite that, Inovio and AGX seem to have finetuned their device, which works intramuscularly, so that there is evidence of transfection effect (albeit in a tiny, well circumscribed space), with thus far no significant problems with abscesses or sarcopenia (muscle loss).
But my next question was this: why give women with cervical dysplasia intramuscular electroporation? That makes little sense. You are transfecting muscle cells so that they express papillomavirus antigens, so that this stirs up T-cells, so that the T-cells go after the cervix. To me that is needlessly complicated. Why not just do intralesional intracervical electroporation with such a vaccine? So I dug, and in fact Johns Hopkins and NIH are doing this now in a multicenter US trial with no corporate tie-in.
http://clinicaltrials.gov/ct2/show/NCT00988559?term=cervical+dysplasia&rank=31
A second concern I have is whether once intraepithelial neoplasia is well underway, with all the cell regulatory changes that implies, whether fighting HPV will then do any good. I don’t know the answer. Seems no one else does either. Certainly most cases of HPV-induced cervical dysplasia do in fact abate, involute, spontaneously. Standard of care is to follow them for a time. As the clintrials site shows, however, quite a few drugs and vaccine approaches for this are in development. In women for whom HPV lesions regress, their immune system is fighting the HPV. In women with persistent lesions, the immune system has failed, and I am not yet convinced that jump-starting it will fix things. One thing I will say about this science: It has a huge market not yet anticipated. I have a small population of gay male patients with anal condylomata (from HPV) and prone to develop anal intra-epithelial neoplase, and for them there is no good therapy. Just last week, the American College of Ob/Gyn reversed itself and now allows such patients to be seen by gynecologists for anal pap smears. (That college had threatened to sanction any member treating males). I don’t know the numbers, but this is a huge contingent of patients, and a politically active one.
I would certainly hold INO shares at this point. It is a credible company doing interesting anti-malarial vaccine work, as well as anti-tumor work with DNA vaccines. The most interesting things with them are yet to come, as their really cool ideas are yet pre-clinical.
Doctor K I have been invested in a company AcelRx Pharmacuetical(ACRX) since early stages.Was
wondering if you had a opinion on their pain management drug pipeline.Zalviso could eventually take place or be a alternative to morphine in hospitals.Data suggest Zalvisio is
safer than morphine and just as efficient.ARX-04 looks promising also.I think this company has a bright future and the stock price has more room to run up with Zalvisio FDA approval which I think has a great chance in July.Also did you get a chance to read the forum on the Calimmune Safety Study that I mentioned yesterday?Thanks,Glenn
I happened to notice this comments on Benitec’s TT-034.
Dr KSS – Any thoughts on this poster’s comments on pleiotropic gene target and the longest safety/efficacy comments?
“I agree it will be really exciting to see the results from human trials, but right now I’m a bit concerned about possible side effects due to pleiotropic gene targets. Everything that I’ve seen so far doesn’t address these issues as much as focus on the “novelty” of the approach. In order for this type of medicine to be truly safe and effective I feel like you would have to couple it with personalized genetic sequencing using next-gen methods (which is not unrealistic down the line), but currently no cost effective or tractable. Also, what has been the longest safety and efficacy eval – in rodents or in primates? Humans are a whole diff ball game. I agree the science is very interesting an it definitely offers advantages over more traditional methods, but you should always be weary of new technologies, and while it sounds promising I’m not yet completely convinced. That said, from a long-term investment view, I also agree that this could be extremely profitable.”
THANK YOU FOR YOUR VERY INFORMATIVE THREAD…I am not a clinical researcher, but I think that the work being done here in California by Biotime might be useful in most of these trials, since they can manufacture any human cell from their fetal stem cell line…wouldn’t that speed things up?
To Robin Steel: Thanks. I like Biotime. I was long BTX shares years ago in the run-up to Hextend release and made money. The company has languished but with its new interest in stem cells has become quite interesting to me again. I have been thinking about going in long again, and have thought about reviewing the company here. In the stem cell space it is as of yet in stealth mode, but I have confidence in management. I had started studying up on them and then got waylaid mulling other companies for people (which I enjoy, by the way). If you have further thoughts or insights about BTX, pray tell. I am interested.
You may also like: Source BioScience plc SBS.L which provides diagnostics and genetic analysis services and products to healthcare and life science research markets primarily in the United Kingdom. The company operates through two segments, Healthcare and LifeSciences. The Healthcare segment offers cytology and diagnostics activities, including cervical cancer screening and diagnostic testing services for diseases, such as cancer. It also offers histopathology, cellular pathology, molecular diagnostics, and companion diagnostic testing services to NHS, public, and private healthcare providers. This segment also manufactures blood banking and serology products for the NHS and biobank providers. The LifeSciences segment provides DNA sequencing services and related products through a network of laboratories and distributors to academic research groups, biotechnology, and pharmaceutical companies. This segment also offers GenomeCube, a proprietary search engine and bioinformatics tool, which contains approximately 20 million DNA clones and 100,000 antibodies; Illumina MiSeq, a sequencing platform; and reSource range of own branded products, primarily focused on the life science research work flow requirements for the DNA extraction and preparation.
Ps this was a cut and paste quote from their website and Im long.
Still cogitating on Nanoviricides. This company’s nano agents are designed to act as a sump, to sequester or partition virus so that it does not infect cells. All well and good, but this does nothing for cells infected. The animal data are good. A virus gets into a cell, replicates, then lyses the cell to free its new virions which go to adjacent cells. NNVC’s drugs bind to virions so they do not perpetually reinfect. Their agents clearly can foreshorten the course of an bad illness in animals. Looking for human data.
Idera Pharmaceuticals… IDRA had a nice bump Friday, any further information or thoughts?
Siva: you raised great points as usual. Concern about pleiotropism of the gene silencing has crossed everyone’s mind, as has the question of persistence of effect. Just so we are all on the same page, strands of DNA and RNA do not prefer to be single. They prefer annealing or hybridization with complimentary strands. Adenine noncovalently associates with thymine (uracil in the case of RNA), cytosine pairs up with guanine.
Suppose I make a piece of inhibitory RNA:
AAGCCUAGCGGCUUA
If I get this inside a cell, 100 bucks says that within 5 minutes in that cell, this strand of RNAi is going to have bound to it a strand that goes UUCGGAUCGCCGAAU (IF such a strand is to be found). How can I be so sure? Certainly bits of RNA may float by that are complimentary to a few of the residues. But the piece I have inserted will sniff out and find a complimentary fit because thermodynamics says it will. The lowest potential energy state results when two perfectly complimentary strands anneal, and any other partial strand will be displaced because the overall binding energy state is lower with the full strands. This phenomenon, and the possibility of errors (which is real but slight) is discussed here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879521/#!po=3.57143
This is why cloners exuberate about how easy their work is. You can purify a batch of DNA from cells, and place with it one long DNA probe encoding a particular sequence, and it will seek out and find only sequences complimentary to the full strand. It works. Any off-signal targeting is minimal. And so it will be, I feel, with the Benitec agent. In fact off target pleiotropism is possible with ANY RNAi intervetion. SIva’s point is that with Benitec, once it’s given it’s in. No withdrawing it.
Which leads to the second point. I just don’t see evidence the transfection is permanent. Basically I think that is a function of the virus chosen. Adenoviruses such as they are using just do not tend to set up permanent residence. If they find evidence that is happening, the AAV can be modified to make cells with it more susceptible to eventual immune action. But right now, based on primate data, there is no reason to think that IF the infection were permanent it would be harmful. The cells in liver would just keep making anti-HCV RNA in perpetuity. If there is evidence of extrahepatic sanctuary going on, that might even be redeeming. I just cannot envision the treatment causing mutant people whose livers are subverted. The DNA advisory committee that went over this broodingly before approving it for use in the US considered that possibility and agreed (as I do) that based on their pages and pages of animal studies, a harmful or perennial infection is extremely unlikely to happen. And if it did, my guess is that you could administer interferon-alfa to the recipients and drive out the AAV vector.
Greatly appreciate the insights here, Dr. KSS. The science of RNAi is mind boggling but exhilarating to say the least.
Alan: Source Bioscience is certainly a diversified and integrated behemoth. I am sure it is an excellent play defensively, but admit I do not necessarily understand healthcare in the UK. I think they would do well to grow themselves as a contract research organization for clinical trials. I have noticed for years: I hear of big multicenter international trials going on. Sites in Germany. Sites in France. SItes in Italy and Austria. Lot of sites in Spain. Never, it seems, sites in the UK. Why is that? I could be wrong but I don’t think it is just perception. I cannot thing of a single major virus hepatitis trial of the last 15 years for which the UK has been a major participant.
About two weeks ago, there was a Guardian article about the NHS’s plan to sell patient information to big pharma, which is disturbing to me and no doubt to many there. I am sure this will fluff the coffers of NHS. The given reason is that it will provide those companies facts and figures about what diseases are being seen, in what prevalence, so as to guide drug development and marketing, and so it will be in the national interest. I do not know about what degree of medical confidentiality is presupposed there, but since our culture is a spin-off of yours, I cannot believe that the British are indifferent to medical privacy. I fear that could turn into a real mess of specific patients being targeted for drug adverts.
Its all in the weasle definition of words. Once upon a time we ‘all’ knew the meaning of the word ‘private’. In fact, like the western diet, there are a >million different definitions. I think there would be outrage if people’s identitifiable personal info was sold/devulged…..see USA tapping phone calls/texts/emails. However, if they just devulged that 32% of un-named people suffer from hangovers, that might help focus research into our (over) drinking habits. In fact I think anything that aids research (without naming names) is probably good. Look at how Microsoft et al issue a beta version of software to get the worlds geeks to find their bugs for free…….far more efficient (and cheaper) than sitting 100 paid researchers down. Equally, phone tapping can help keep us safer (I believe O’Bummer when he says this)…..but no one should imagine that the gov has enough civil servants or budget to sit down listening in intently to my mother in law blathering on about the price of eggs and her lumbago.
As for UK research, simply I dunno….Im just a Dr KSS on plumbing and 1970’s bands. I did see an article today talking about the lack of research (worldwide) into virus’. They mentioned that the study etc for temodal and later temozolomide for cancer treatment, was done in UK and became the first-line therepy for brain tumours, finally being approved after 3 decades in 2007 (dont blame me if this isnt accurate, Im just quoting the article) . I think the problem is that the UK had the National Health Service (NHS) behemoth ie free treatment, since the 1920’s, so we dont have so many small private clinics, just humongus hospitals for the treatment of the masses. So the research moved to other ‘foreign’ clinics. But one of the beauties of frontier research is that, like art, it knows only cerebral boundaries, not national boundaries. I’m darn certain that the UK has its fair share of clever, inquisitive people gagging to save the world and get a Nobel to hang in their loo. But as the US pays better wages and OZ has better weather, they sensibly follow the money and the sun.
Siva: Now set up to track insider movements in BLT is Australia. This month is key I think. For now these are still the biggest owners:
Christopher Bremner 8,013,201 9.540 %
Irwin Biotech Nominees Pty 4,769,091 5.680 %
MJGD Nominees Pty Ltd 4,769,091 5.680 %
Dalit Pty Ltd 4,545,455 5.410 %
Great idea Dr. KSS. I will track these as well plus the phone calls from Duke 🙂
Important stuff….thanx Siva
Here is the document that lists top 20 owners of benitec per july 2013 filing.
Dr- KSS – where did you pull the below information?
Christopher Bremner 8,013,201 9.540 %
Irwin Biotech Nominees Pty 4,769,091 5.680 %
MJGD Nominees Pty Ltd 4,769,091 5.680 %
Dalit Pty Ltd 4,545,455 5.410 %
The one item that doesn’t match with benitec’s filing is Christopher Bremner. I see it as ‘National Nominees Limited’.
Don: One thing I meant to mention, and it slipped my mind, was about CoQ10, Yes, definitely and unequivocally, all patients on statins need to take CoQ10, preferably in the morning as it can interfere with sleep if taken later. Statins are probably best taken at night on the hope of sleeping through myalgias. Mitochondria are the energy making organelles inside all cells. Statins deplete CoQ10, and this compromises mitochondrial function. We are only now beginning to understand mitochondria. but it is fair to say that by age 30, they are down to about 25 per cent of the efficacy they had at birth. Optimizing them with CoQ10 is vital.
As to overall hea(lth, thanks for asking. Aside from obvious things like not smoking and like wearing seatbelts. these are key:
(1) if you were born between 1945 and 1965 inclusive, you need to be screened for hepatitis C. You may have had a perfectly G-rated existence and still be at risk. HCV is there in that birth cohort. We do not fully understand how all those people got it…..?dental instuments before we knew to sterilize them, ?pneumatic vaccine guns.
(2) everybody needs to be aware of their status as regards diabetes and insulin resistance. It is a large-scale problem, Age does play a role because as one ages, the gut secretes less GLP-1, and that favors diabetes. By age 70, a third of people are diabetic. By age 84, half are. I genuinely think that most MDs do not know how to monitor people for it. In my view, the disease itself is insulin resistance, which begins perhaps 20 years before onset of diabetes. If you wait til your glucose is elevated, you have waited too long. The horse is out of the barn. I honestly think people over 50 who have any risks for type II diabetes should ask their doctors to please run on them a fasting glucose and fasting insulin level. Your doctor may not have heard of doing this. Fast overnight, go to the doctor in the am, get blood drawn, for glucose and insulin levels simultaneously. The relationship of the numbers tells you whether you are in insulin resistance already. If the product of the 2 numbers is greater than or equal to 700, you are insulin resistant. The long trundle to diabetes has begun and you need to get serious about weight loss and aerobic exercise. Actual diabetes is not upon you til the product gets to about 3000. But increasingly, smart doctors are picking up on insulin resistance early, before diabetes onset, and giving those patients agents like metformin to prevent diabetes. And that is good practice.
(3) exercise. It does not take much to accrue the benefits. I tell patients to try to get to 60-80 per cent of their target heart rate (which is 220-age) for 20 minutes three times per week. This increases insulin sensitivity, helps keep basal metabolic rate up, and clearly really does help prevent certain kinds of cancer (pancreatic, for example).
(4) caloric restriction is associated with longevity, as is slenderness. This is not always easy to achieve, but it is clear that a lifestyle of frequent small meals rather than fewer big ones, is beneficial. It keeps BMR up. It leads to less insulin release. (Insulin is necessary but also toxic). Calorie restriction highly activates the sirtuins, longevity proteins.
(5) The data seem now inescapable. Vitamin D deficiency is hyperendemic in this country, and people need supplements. I suggest D3 as 2000 IU taken each am. This regimen clearly has deterrent effects on certain cancers (particularly colorectal), autoimmune disease (it slashes risk of MS), infections, and depression (people with vit D blood levels above 35 ng/mL essentially never experience clinical depression). We were discussing cytokine storm earlier. For want of anything better to do, some centers are pumping sick ICU patients full of vitamin D to help tame cytokine storm, and it appears to work.
Exactly what I was hoping for. Thank you!!
Don
Your karma of generosity is beyond belief. Your help to others with knowledge and wisdom is the best giving of all. I am blessed for being a reader of this thread. Thanks Dr.
I have a quick question re: #316. Dr. KSS, you suggest that anyone born between 1945 and 1965 be screened for HCV. I fall into that cohort and have read that it is possible to be infected and not know it, but I was a regular blood donor for many years and I believe that HCV is one of the things they screen for. I would guess that the donor organizations would inform a blood donor if their blood was found to be infected and tell them they must not donate blood, but I don’t know that for sure. Does anyone here know if that is true?
There has been some news as of late, that the bisphosphonates also deplete COQ10.
Doc, thank you for your reply to my post. I will discuss further with my physician. I appreciate the time and thoughful response to my personal question. I don’t know if I need them or not and want to simplify what I am putting into my body after 45 years of laisse-faire. If they are going to prevent me from having a heart attack then obviously I know the choice, I just didn’t know if the benefits outweigh the side effects etc. and will continue to educate myself as we all have to be our own best advocate.
I love TCM and enjoyed the analogy. As for this thread, I can’t thank you enough for your input.
BTX was touted in several puff pieces for “newsletters”,
They have several new companies via acquisition, and one of them just signed a lease on 100k sq ft facility in Silicon Valley (which I define as anything south of SF)…so sinceI don’t know enough science to ask the right questions..
you can probably do a better write up if you talk to Dr.Michael West….
My main concern is the almost daily financial filings for the benefit of “insiders”…
“Seeking Alpha” was negative on it too, but that could be in it’s own interest…
my questions are more like
Who are the major stock holders outside of the company?
And
What are they going to do with all that space, after the $4.5M renovation?
BTX is looking interesting, especially with all that insider buying 4th quarter 2013.
Dr. KSS: re post #313: You took the words right out of my mouth. Say what?? Impressive.
Folks – many of us have acknowledged the good work and words of wisdom of the good Doc here, but I think Travis also deserves a shout-out for this thread. Thanks Travis for allowing this to continue, And those of us that are benefiting from it (knowledge as well as investment wise) need to consider stepping up and consider becoming what Travis calls an Irregular. Really Travis….Irregular? Is that the best name you can think of? 😉
Re post 319, I’ve been a free subscriber for many years, but this thread did indeed inspire me to pony up and join the Irregulars (and I agree with your comment on the name 😉 )
I think I understand why Travis chose the name. The regulars are those who expect something for nothing. The irregulars are those that are intelligent enough to know when they are getting something of value and will happily pay for it. Ive followed this thread and Ive followed Myron. So far Ive made enough to pay for a lifetime subsciption 10 times over….Heaven ( Howdy Bob) knows how much Ive saved by not buying into pumped up crud. I nearly gave up with stocks. I was being skinned by tipsters, spreads, brokers and multi bagger losses. More importantly, I had lost all belief in my own abilities. GS (thats Gumshoe not General Semantics) is simply the BEST ! Travis we owe you……..big time !
If I am remembering, the ‘Irregulars’ title comes from Sherlock Holmes, the Baker Street Irregulars being the street boys who helped Sherlock Holmes ferret out information when he needed it quickly.
Elementary my dear watson….and in that light, perfectly apt. Good spotting Keith.
Thanks Siva for inviting me here. lots of great comments here. At this point i am long RNN, RXII, BPTH & CLTX. I am looking at Benitec based on whatever discussions are going on here. Meanwhile please take a look at BPTH. This stock has gone from mere 30 cents to $4.40 as of last Friday. Yes without a R/S. This company is part of MD Andersons Moonshot program and they have a very unique neutral lipid drug delivery platform technology to treat cancers. At this point they are focusing on all forms of blood cancers and finishing up phase 1 trials and will be initiating 3 phase 2 trials by mid of this year. They have reported 0% toxicity in their phase 1 trials so far. They just completed a direct placement of shares entirely bought by Sabby Management for $3. So they have $ until end of next year. here is one link for for the latest report by Grant Zeng of Zacks. http://nt4.zacks.com/ZResearch/PublSnapshotPdf/BPTH_SCIR.PDF
Also BPTH has totally gone up unnoticed by the investment community. The current outstanding shares is close to 89m after the direct offering and the MC is about 360m now. They also plan to outsource their delivery technology and also planning to initiate trials for Triple Negative(TNBC) and Inflammatory Breast Cancers (IBC). The blood cancers they are currently targeting is r Chronic Myelogenous Leukemia (CML), Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), and Myelodysplastic Syndrome (MDS).
And here is a short overview for those who are interested.Bio-Path Holdings is a biotechnology company focused on developing therapeutic products utilizing its proprietary liposomal delivery technology designed to systemically distribute nucleic acid drugs throughout the human body with a simple intravenous infusion. Bio-Path’s lead product candidate, Liposomal Grb-2, is in a Phase I study for blood cancers and in pre-clinical studies for triple negative and inflammatory breast cancers. Bio-Path’s second drug candidate, also a liposomal antisense drug, is ready for the clinic where it will be evaluated in lymphoma and solid tumors. These product candidates have been licensed from MD Anderson Cancer Center. Bio-Path’s drug delivery technology involves microscopic-sized liposome particles that distribute nucleic acid drugs systemically and safely throughout the human body, via simple intravenous infusion. The delivery technology can be applied both to single stranded (antisense) and double stranded (siRNA) nucleic acid compounds with the potential to revolutionize the treatment of cancer and other diseases where drugable targets of disease are well characterized. The Company’s current focus is on developing liposomal antisense drug candidates
Dr. KSS Any thoughts on BPTH would be appreciated! Your input will be very valuable!
Thanks!