Thursday, July 31, 2014

What TKM-Ebola Could Achieve in the Current Outbreak

(please read financial conflict at the end)

We are in the midst of the largest recorded outbreak of Ebola hemorrhagic fever virus ever and there is little evidence that its spread is being contained.   Here, I will make the case how TKM-Ebola, the most advanced Ebola therapeutic in clinical development, could help in avoiding ever more damage from the deadly virus.

How TKM-Ebola could help

1.       Give suspected cases an incentive to go to the treatment centers.
2.       Provide medical personnel with a stand-by and therefore help in their recruitment.

The continued spread of Ebola can be partly attributed to a breakdown in confidence in the authorities and fear by medical personnel. 

I have been viciously attacking the World Health Organization (WHO) that by downplaying the significance of the outbreak it has been a key factor in re-igniting viral spread.  It is the WHO who have tried to minimize the true numbers of infected, possibly in cahoots with local authorities, and laughed off the suggestion that the virus could get on a plane in arguing against any kind of travel restrictions.  Of course, it recently did and I am still waiting to see top WHO officials send their families on a vacation to Western Africa.  But probably the most outrageous insult was in suggesting that the spread of the virus is explained by ‘funny’ cultural practices in these countries such as kissing the dead during burials.

The WHO, probably in the comfort of their headquarters in Geneva, even attacked on-the-ground Medecins Sans Frontieres as alarmist for calling the outbreak ‘unprecedented’ in late March.

This notion that the virus is very bad in spreading from person-to-person and can only do so with the help of obscure practices is obviously wrong given that more than 100 medical personnel have become infected. While I am still waiting for an explanation by the WHO of how this could happen, I refuse to believe that they kissed the dead in the treatment centers or licked any other of their body fluids for that matter.  Has the WHO (and others) maybe considered the unthinkable, namely that the reason why this is the biggest ever spread of the virus is because the virus has mutated and new routes of infections are possible, such as by aerosol?  The US military will have its reason to believe that this could happen, otherwise why would they be so concerned about it being weaponized and spending hundreds of million dollars on the development and stockpile of an Ebola therapeutic such as TKM-Ebola?

And if people that protect themselves with space-suits get infected, how would you feel as a suspected case of Ebola? 

I know I would do anything NOT to go to these treatment centers, because what is obviously for the good of the overall population would only exponentially increase my risk of contracting the infection in case I was one of those wrongly suspected to have Ebola.

In my opinion, providing individual isolation wards with the best medical equipment possible, a dignified environment, and a drug as an option for the patient could make the difference in whether suspected cases will turn themselves in or not.  The argument that ‘this is Africa’ and you cannot expect good medical care there should not count in this day and age when equipment can easily be shipped between continents.  It’s probably far cheaper to do it now than further risking for the virus to go global (obviously, the WHO thinks this is impossible).

And for medical personnel, the benefit of making TKM-Ebola available is obvious and most tangible: since the onset of flu-like symptoms in this population is highly likely to be due to Ebola and because they have ready access to the necessary equipment such as infusion apparatus, they could be treated immediately with the agent.  Treating as soon as possible is thought to be critical for TKM-Ebola to be efficacious.


What is TKM-Ebola?

TKM-Ebola is an intravenously infused RNAi Therapeutic that has been demonstrated to save the lives of monkeys infected with an otherwise fatal dose of Ebola.  It is being developed under the ‘Animal Rule’ in efforts funded by the US government which is afraid that this virus could be weaponized and used as a bioterror agent.  The ‘Animal Rule’ is a development pathway instituted by the US FDA for diseases such as Ebola for which it would either be impractical or unethical to conduct efficacy studies in humans. 

Because natural outbreaks are unpredictable and experimentally infecting volunteers with the virus out of the question, these monkey studies are as good as it gets regarding drug efficacy (so much for the mantra that there are ‘no drugs for Ebola’).

An important second element of the Animal Rule is that human volunteer studies demonstrate acceptable safety at the doses corresponding to the efficacious dose in monkeys.  For this reason, pivotal phase I safety studies have begun this year in healthy volunteers (so much for the notion that licensed Ebola drugs are far off- ‘phase I’ is misleading).

Clinical Hold

Unfortunately, in the midst of the outbreak, the FDA instituted a Clinical Hold on the TKM-Ebola safety study because a case of dangerously high cytokine elevations was observed at the highest dose planned in this dose-escalating/dose-finding study (0.5mg/kg).  I agree that this is to be considered a serious adverse event in a volunteer that is not infected with the virus.

The reason for the cytokine stimulation is likely due to TLR-mediated, lipid-amplified innate immune stimulation, a known risk of liposomal RNAi delivery, especially at doses of 0.5mg/kg and higher.  It is also the reason why all other active development candidates by Tekmira and their licensee Alnylam are conducted in the presence of transient immune suppression with steroids and the like which in many cases is acceptable given the severe diseases these treatments go after.

As indicated, the adverse event at 0.5mg/kg should by no means spell the end of TKM-Ebola.  Firstly, the company argues that the pharmacologic corresponding dose to those curing the monkeys is lower than 0.5mg/kg.  Secondly, a side effect that is not tolerable in healthy volunteers (usually ~20-year old male students) could be well tolerated in subjects with a 70-90% likelihood of dying from a disease in a matter of days.  It is ethically more troubling to involve healthy volunteers in such drug development just as aggressive experimental cancer drugs are hardly ever tested in healthy volunteers.  Lastly, there may be ways to avoid the side effect altogether, such as by using transient immune suppression.  However, I do not know whether transient immune suppression is possible for Ebola, but I expect Tekmira will have the answer for this from their large-scale animal experience.

Next steps

For TKM-Ebola to have the best impact on the current epidemic, the first step would be to start manufacturing it at scales sufficient to treat at least ~1000-5000 patients.  This takes time and given the uncertainty around the future course of the epidemic, the investment needs to be made now instead of waiting until it is too late for a treatment center-focused approached involving an intravenously infused agent.

The next step depends on the feasibility of steroid pre-treatment during an Ebola infection.

In case that it is known that steroid pre-treatment was of little concern (e.g. based on infected monkey studies), start treating rather aggressively (e.g. start at doses of 0.25mg/kg).  In case it was not, go about more slowly by starting at sub-therapeutic doses as low as 0.025mg/kg and treat the initial experience like a dose-escalation study in actually infected patients.  Of course, everybody would need to provide informed consent.  In general, any semblance that the use of TKM-Ebola was imposed by the Western world and the local population used as guinea pigs is to be avoided which is probably a key reason why Tekmira to my mind has been almost in hiding during this whole episode almost to the point that they (and the FDA) are glad about the Clinical Hold.  

To support the accelerated development of Ebola therapeutics and vaccines, including TKM-EBOLA you can add your signature to the following change.org initiative: http://www.change.org/en-GB/petitions/food-and-drug-adminstration-fast-track-drug-and-vaccine-research-for-ebola-hemorrhagic-fever

Disclosure: Tekmira constitutes a meaningful part of my investment portfolio and I have to credit the WHO for greatly increasing its value.


27 comments:

Anonymous said...

I like the disclaimer..

Anonymous said...

Dirk, do you know the story about the elephant man at Northwick Park and how cytokine storms are worse than tropical ones for shutting down companies?

Keep up the good work, please!

Anonymous said...

looks like they may have started using some experimental drugs..

http://www.nbcnews.com/storyline/ebola-virus-outbreak/only-enough-one-experimental-ebola-serum-used-u-s-patient-n169626

Anonymous said...

It seems to me that Ebola infected patients should be given the choice of having Tekmira's experimental treatment, which has been shown to be effective in primates, or with treatments that have not shown any effectiveness at all. It is important that these two options are explained to the patients by trained professionals who are fluent in the patient's native language. it should also be explained that no treatment at all means a high probability that they will not survive the illness.

Given the grave danger this disease presents to the rest of the world, regulatory agencies have a duty to see that every means to stop its spread should be taken.

Subramanian Karur said...

Just for objective ness sake why not scale up a phase 2 drug for Ebola like bcrx, SRPT?I think the disclaimer explains it.Why ttekmira?

Anonymous said...

To your point of synthesizing large amount of siRNAs, just want to point out there is an alternative method of producing siRNAs in bacteria (pro-siRNA.com). Of course pro-siRNAs are very different from chemically modified siRNAs but this method can be easily scaled up and is potentially cost effective, which might be useful in a crisis like this in the future.

Anonymous said...

@Anonymous, Ebola is a dangerous, but not a cancer-like terminal condition. No treatment means ~60% survival chance, with no *actual* way of telling which way it will go for each patient.

Regulatory agencies have the duty to retain their calm when media popularise scare stories for clickbaiting/viewer ratings/copy sales and opportunists try to make the most for their own benefit.

Anonymous said...

The disclaimer should read:

I, Dirk Haussecker, sold out of TKMR completely twice already in three or four months while pumping it.

First time after I sold, I, Dirk Haussecker, then blogged that it would be famine for these RNAi stocks for the next three years.

Once the price dropped enough, I, Dirk Haussecker, bought back and started pumping TKMR furiously again.

But after the FDA halted TKM-Ebola trial, I, Dirk Haussecker, sold and blogged that TKMR was not it anymore.

When TKMR dropped into the single digits, I, Dirk Haussecker, loaded back up and started pumping all over again.

Thanks to all my lemming followers helping me sensationalize Ebola this is making me rich even as the stock is going down!

- investron

Anonymous said...

In marketing terms, just how different is Ebola from SARS or Avian and Swine flu? Or even HIV in the eighties.

Looks like just another disease that's about to wipe out mankind to me.

But I guess if you can whip up enough of a frenzy about it through blogs and media then you can make a decent buck off it.

Anonymous said...

ARWR finally posted a date for Q2 CC. But here we are, Aug 1st and DNDN still has nothing on their website while Google Finance shows it to be approximately Aug. 4th!

Wonder where RNAi is re. prostate.

Anonymous said...

Ebola reston is the only strain known to travel via the air. THis is the only strand that is asymptomatic in humans, but affects pigs and non human primates.

-investron U are correct with your thesis

Anonymous said...

Lets not forget Dirk's bashing of TKMR & ARWR's patent protection. He rode that one hard driving down pps of both companies.

Anonymous said...


investron • 9 hours ago

.

The physician in question didn't know anything about the drug until told by a TKMR shareholder.

He just happened to have come to the US from West Africa.

He's hardly the expert.

Can you imagine what will happen if TKM-Ebola is injected and the patient immediately deteriorates and dies?

This stock will implode.

So don't think it all can only end well.

That's why modern medicines have to pass rigorous tests: First do no harm.


investron • 17 minutes ago

.

Dr. Thomas Geisbert of the University of Texas Medical Branch has done animal studies on the Tekmira drug and said there are few companies willing to develop Ebola treatments. There is "little financial incentive," given the small market potential for a drug that treats a rare disease afflicting developing countries, he said.

Geisbert said the drug "works great in monkeys in the lab," but that is largely because it is given relatively early in the course of infection.

"What if you start giving it to people who are almost dead and they die, but it's not the drug's fault? Then you blame the drug."

Geisbert said given the widespread mistrust of doctors in West Africa, which has driven dozens of victims to evade treatment, such an event could jeopardize the drug's prospects.

"It's a very delicate situation," he said.

Source: Reuters


Voila, what did I tell you?

So go ahead, the idiots on these boards starting with Dirk Haussecker should learn just how stupid they really are.

_____



I say go ahead also with the rush on TKM-HBV (whose IND has not even been filed today yet Dirk Haussecker started pumping early this year while talking down ARC-520, taking down both stocks as somebody here noted).

This is why I consider TKMR untouchable.

The risks are unacceptable all around and I said so months ago before the FDA halt.

I predicted that TKMR would go back to being a single-digit stock and it will again.

This company appears to have a collection of the most fanatical but stupid shareholders for a biotech company.

It was a Tekmira shareholder from these stock boards that contacted Ahmed Tejan-Sie, MD., and used him for the gains.

Sorry to sound strident, but I have lost all respect for these guys.

These are the very type that has caused the world much grief: stupid people who think they're smart and cause more harm than good.

- investron

Anonymous said...

The Russians are coming! The Russians are coming!

Quick. Dirk. Check for reds under your bed and make sure you are in an appropriate state of readiness.

http://www.reuters.com/article/2014/08/02/health-ebola-fda-idUSL2N0Q733H20140802

Anonymous said...

Can we abbreviate this discussion and just say its just another drug company using west Africa for its own experimental purposes with the hope of a payday at the end. All that's required is for the patient to put their thumb print on the dotted line after the physician has explained all the potential risks.

Anonymous said...

Having Been Used For Your Gains,

Ahmed Tejan-Sie is asking you to donate your TKMR blood profit to victims and relief of Ebola

Ahmed Tejan-Sie @AhmedTejanSie · 12h

Could #TKMR shareholders donate profits to victims & relief of #Ebola? Tekmira shares skyrocket as Ebola intensifies bit.ly/1kqXtwr

_______

Earlier in the outbreak Dirk Haussecker was leading TKMR shareholders in what one would get the distinct impression of rooting for mass hysteria and for Ebola to spread viciously in hope making a killing on TKMR.

That was the proverbial last straw on the camel's back for me with regard to Dirk's unscrupulousness.

It was one thing to be openly boosting one's laggard stock (TKMR) and trashing another (ARWR) so blatantly when the former had not so much as filed IND (HBV)and the latter was undergoing Ph 2, but when that failed, to latch on to hoping for the suffering of many for the benefit of a few, why, it was simply beyond words.

As I described in one of my earlier posts on ARWR, although I grew up in science I've lived long enough to discover that it is not the be all and end all, and here's a curse that these people will take with them and to their children.

In a very real way, they are already cursed. These people are stuck at a certain level while others have progressed to a higher state of being and understanding. And like other things their children will inherit.


The Character Of A Man - Posted On Dirk Haussecker's Blog

by investron • Mar 28, 2014 5:43 PM
.

The character of a man is invariably revealed when his money is at stake.

I am beyond disgusted to see the depth Dirk Haussecker will stoop, to pump up his investment in TKMR.

The tweets and blog desperately try to sensationalize Ebola, latest equating it to Avian Flu as TKMR pps continues to deflate from his hot air.

Flu affects millions, Ebola hundreds, if that, some years, NIL.

Reading the tweets and re-tweets reveal the misguided hope that TKMR stock will double overnight if panic and fear could be incited.

One can not avoid this eerie feeling that if he could get the virus to spread he would do it to profit.

I have amused myself parodying Dirk Haussecker and his blog else where, but there is nothing to be funny about anymore.

This man is dangerously missing the sense of right and wrong.

- investron

jennenth said...



my name is jennenth from Liberia, i was having a very dangerous disease which normally kill people called Ebola, i was having this disease for the past 11 days and no one was able to help me out, i went to different places cause i did not want to die young but no way, i travel to different states in my country to look for solution no way out, i went online to contacted some spell caster no one was been able to help ma out until i get to know of a man called dr.zack balo, he is a great man that help me to cure my Ebola disease all my thanks goes to dr.zack balo, when he commence a spell cast on me ofter three day later i went back to the hospital for Ebola test and the doctor confirm that the Ebola disease was no longer there again, all thanks goes to dr.zack balo again please this man can as well help you cure all type of sickness and diseases, you need to contact him now, his email is: wiseindividualspell@gmail.com or contact him on his phone number +2348078927387.




Anonymous said...

Survivors' Sera - Effective Treatment For Ebola
by investron • 39 minutes ago

The most hopeful experience to date involves blood donors who were recovering from Ebola, back in Congo in 1995. Their blood was transfused into eight patients who were ill with Ebola. Normally 80 percent of people with Ebola die, but in this case, seven of the eight survived, according to a report by scientists from Congo and Belgium. - NPR 2 Aug 2014


Serum Of Survivor Worked!
by investron • 6 hours ago

Dr. Brantly who was given a unit of serum or blood from a 14 year old boy survivor of the Ebola infection apparently recovered to the point that he could shower by himself before boarding the plane and walked off the ambulance into the ward at Emory U Hospital.

As I pointed out earlier, this would likely be the source of treatment in this outbreak, plasma of survivors.

We have hundreds of those at this point as 44% of the patients survived. (CNN: 56% fatality)

Anonymous said...
This comment has been removed by a blog administrator.
Anonymous said...

Reply to To All The MENSA Rejects Pumping TKMR by investron •3 hours ago
.

investron • 41 minutes ago

.

"The word serum can be used to describe any drug that comes from a serous fluid." - symptoms88

So what do you think a serous fluid is?

Take a pick:

Biology[edit]
Serum (blood), plasma from which the clotting proteins have been removed
Antiserum, blood serum with specific antibodies for passive immunity
Serous fluid, any clear bodily fluid
Any drug derived from an animal's blood or serous fluid
Truth serum, a general term for sedative drug or unspecified drug that is likely to make people tell truth or divulge information
A buzzword for lotion in the cosmetics market

Source: Wikipedia (Wiki is used as a source of convenient reference, you may pick your own)

TKM-Ebola is not based on a serous fluid. Get it already.

And Tekmira has plenty of TKM-Ebola because testing has been halted.

All sources indicate that there was just enough of the experimental serum for one person.

This lends credence to the story that the serum came from the NIH and was extracted from the blood of previous survivor(s).

Even if ALL the reporters were as ignorant as you and didn't know what serum meant, there surely would be enough of any other experimental drugs for more than just one person.

But the most important point that TKMR MENSA rejects just can't understand is that THE ONLY THING THAT HAS BEEN SHOWN TO BE SAFE AND EFFECTIVE IN HUMAN EBOLA PATIENTS IS BLOOD SERUM FROM SURVIVORS.

ALL OTHER DRUGS UNDER DEVELOPMENT INCLUDING ONES FURTHER ALONG THAN TKMR-EBOLA HAVE NOT BEEN SHOWN TO BE SAFE OR EFFECTIVE IN HUMANS.

THEY CAN NOT BE LEGALLY INJECTED INTO EBOLA PATIENTS AT THIS TIME.

Get it already, people.

Besides, Kent Brantly did not take it, he in stead took the blood of the recent Ebola survivor from the same outbreak which I predicted would be better (see previous post).

Nancy Whitebol took the experimental serum and is doing worse. (CNN - 2 Aug 14)

Anonymous said...

investron • 20 minutes ago


Told You, Not TKM-Ebola
.

The government plans to fast-track development of a vaccine shown to protect macaque monkeys, aiming to test it in humans as early as next month.

If the vaccine proves effective, it may be given to health care workers and others at high risk for infection sometime in 2015, said Dr. Anthony S. Fauci, the head of the National Institute of Allergy and Infectious Diseases.
...
Assuming the necessary Food and Drug Administration approvals are obtained, Dr. Fauci said, about 20 volunteers will receive the experimental vaccine beginning in mid-September.
...
Researchers have been studying the Ebola virus for decades, and vaccine efforts have begun to bear fruit with the development of several new strategies for priming the immune system to recognize and attack the virus after exposure.
...
Development of an Ebola vaccine should not be as challenging as developing an H.I.V. vaccine, scientists say. Yet the unpredictable and sporadic nature of this infection has made an Ebola vaccine an unattractive goal for drug makers.

“It’s not really a good target for a pharmaceutical company,” said Kartik Chandran, an associate professor of microbiology and immunology at Albert Einstein College of Medicine in New York who researches Ebola. “It’s not clear you could even earn back your investment.”
...
The vaccine to be tested in humans relies on a benign virus that carries two proteins from the surface of the Ebola virus. The proteins help the virus penetrate human cells.
...
The initial human trial is intended to evaluate the safety of the vaccine and to see whether it induces an immune response similar to the one produced in the monkeys.

The immunized animals were deliberately exposed to the Ebola virus and survived. But human volunteers will not be exposed to the virus under any circumstances, Dr. Fauci said.

Source: NYTimes



Reply to Told You, Not TKM-Ebola by investron •21 minutes ago
.

investron • 7 minutes ago
.

TKM-Ebola has been halted in Ph 1 due to eliciting potentially life threatening cytokine storm in even a healthy person.

Cytokine storm in an already ill person can lead to sudden death, it is how many diseases kill.

TKM-Ebola is untouchable as it's been halted in Ph 1 (safety) due to the above.

The company has yet to respond to the FDA.

Their best hope according to their own words is to restart the trial at the end of the year after explaining to the FDA's satisfaction what the hell happened and why it won't happen again.

And if it happens again...

TKMR MENSA rejects can't/refuse to comprehend what the management has come out and stated explicitly many, Many, MANY times that "there is no framework that would allow the use of TKM-Ebola at this time."

Hello?

TKMR MENSA rejects can't/refuse to comprehend that THERE IS NO MONEY IN IT, MOOOOORRRROOOOONNNNSSSS!

That's why the work has to be subsidized by the government.

Please do not breed.

_____


The above from the Yahoo! TKMR board so pardon yahoo speak.

- investron

Anonymous said...



Not TKM-Ebola, Back To Single Digit

by investron • 2 minutes 53 seconds ago
.

The Canadian company that is developing an experimental Ebola drug says its product was not given to one of two American aid workers infected with the virus.

Tekmira Pharmaceuticals said in an email that no one infected in the ongoing outbreak in West Africa has been treated with its drug, called TKM-Ebola.

The Christian relief group Service in Mission or SIM said late last week that one of its missionaries, Nancy Writebol, had been given an experimental drug flown into Liberia, where she contracted the disease while working in an Ebola treatment facility.

Liberia, Guinea and Sierra Leone are battling a months-long outbreak that has infected at least 1,440 people and killed at least 826.

Another American, Dr. Kent Brantly, was also infected at the same centre in Liberia. Brantly works with the international relief agency Samaritan's Purse.

Its president, Franklin Graham, said in a statement last week that limited supplies of an unnamed experimental drug arrived at the facility. There was only enough to treat one person, and Brantly asked that the drug be given to Writebol, Graham said.

Speculation boosts stock price

Although there are a number of Ebola therapies in development, Tekmira's is thought to be the furthest along in the regulatory process. And there has been some speculation among scientists that it was the one given to Writebol.

Meanwhile, the price of the company's stock has soared as media coverage of the Ebola outbreak has intensified.

But Tekmira said Writebol did not receive their drug.

Tekmira Pharmaceuticals
Based in Burnaby, B.C., Tekmira Pharmaceuticals has been developing an anti-Ebola therapeutic called TKM-Ebola. Its Phase I clinical trial was recently put on hold by the U.S. Food and Drug Administration.

Source: cbcnews

___

What did I tell you?

And the "scientists" who speculated that it was TKM-Ebola, why, they're obviously second-rate.

If they could not deduce something this straightforward they need to find another job.

Anonymous said...

>>The argument that ‘this is Africa’ and you cannot expect good medical care there should not count in this day and age when equipment can easily be shipped between continents.>>
So, what would you propose for the host of other diseases and scourges that besiege these people. Rabies still kills 23k a year, and the solution for that is cheaper and more proven than for Ebola. Forget you are invested in TKM a moment (I know that's hard) and consider the most bang for the donated buck and limited manpower. Is it necessarily Ebola?
(So now we type in an advertiser name to prove we're not a robot? That's rich. Are you willing to donate those proceeds to the Ebola effort?)

Anonymous said...

Hello Dirk,
the drug by Tekmira was tested against Zaire strain Ebola. The current outbreak is a different strain. What is the difference between the strains? Is the site of action for the drug effected? Is the drug likely to work for non Zaire strain too?

Jacob said...
This comment has been removed by a blog administrator.
Anonymous said...

Investron-

Why don't you return to your Mom's basement and resume the day-long jacking off you practiced before discovering this blog.

Clearly you weren't paid sufficient attention during your pre-adolescent years.

Anonymous said...

And I bet that basement has is littered with empty coke cans, packets of doritos, and questionable porn.

Investron, go get some sunshine. You seriously need the vitamin D.

By Dirk Haussecker. All rights reserved.

Disclaimer: This blog is not intended for distribution to or use by any person or entity who is a citizen or resident of, or located in any locality, state, country or other jurisdiction where such distribution, publication, availability or use would be contrary to law or regulation or which would subject the author or any of his collaborators and contributors to any registration or licensing requirement within such jurisdiction. This blog expresses only my opinions, they may be flawed and are for entertainment purposes only. Opinions expressed are a direct result of information which may or may not be accurate, and I do not assume any responsibility for material errors or to provide updates should circumstances change. Opinions expressed in this blog may have been disseminated before to others. This blog should not be taken as investment, legal or tax advice. The investments referred to herein may not be suitable for you. Investments particularly in the field of RNAi Therapeutics and biotechnology carry a high risk of total loss. You, the reader must make your own investment decisions in consultation with your professional advisors in light of your specific circumstances. I reserve the right to buy, sell, or short any security including those that may or may not be discussed on my blog.