It is my understanding that the liver accounts for the production of only about 90% of the AATD protein, therefore the most that ARC-AAT can possibly KD is 90%, which is to say, it is aimed at the liver so it cannot KD more than the liver cells make.
If they are going to 5 mg doses, in a dose escalation study that means several things:
1. 4 mgs doses in patients have not consistently KD 90% of the AATD protein;
2. 4 mg doses in patients have not been toxic or showing signs of serious AEs;
3. ARWR believes that the KD is still ascending, hence 5 Mg/kg should be tested for higher KD,
4. They might even go to 6 mg/kg, or higher if they think that is more efficacious;
5. The KD they are seeing in the healthy volunteers is not the same as in the patients, thus they need to build a full comparison to understand what the differences are and why they occur so they are extending the single dose to healthy volunteers because the safety profile seems to be okay at higher levels.
Neither Powell or Rice are running for office, and if they were, their actions would come under review. Did any of them have 1340 top secret e-mails in their private email, or chains of emails that are so secret, that the authorities refuse to release them under FOI act? Clinton clearly took steps to evade the government servers because apparently because someone did not want her personal emails on those government servers, and in this idea, she allowed the nation's top secret emails to be compromised to meet her personal goals for privacy. How much she knew of this and participated in it is under review, but it is looking like she made some wrong decisions intentionally and willfully.
Add this to her string of commodity trades that miraculously got her a $100,000 profit, but look like a payoff for something; her lost billing records that showed up around the time that the third Amigo, Vince Foster supposedly jumped off a bridge and killed himself conveniently for Clinton to be unavailable when they reviewed her possible obstruction of justice, and her $27 Million in fees from speaking engagements for Wall Street donors, and I just don't trust this woman. She does have a life long history of public service, but the way she plays the game makes me nervous.
I am voting for Bernie, not Clinton, and I would never consider Trump who is just too crude and clueless.
Today, the republican party is for the extreme rich, religous fanatics that don't even believe in evolution, tea party extremists that will not work with anyone, rednecks that want to own guns, and dolts of all kinds that are tricked into voting against their own interests.
The republican candidates are a sorry lot today, and they lack the consensus building skills.
Trump is not remotely a statesman, and he does not have the temperament to hold the key to NUCs or to represent the needs of this society.
Perish the thought that Trump gets elected to anything beyond a TV show. He is no Regan.
The short covering is the best evidence that the current drop will not continue. The shorts are using the drop to cover, and the more some of them cover, the more likely the others will jump on the bandwagon and cover, barring bad news. ARWR is way oversold, but one of the adversaries, the short interest, is letting up. Next will be the return of the funds as soon as the storm against biotech stock clears and the weather is right for some buying. Hopefully as the clouds blow away, the Monarch results will stimulate a quick and decisive recovery for ARWR. That should finish off the remaining shorts and set the course for some new all time highs for ARWR. Good luck to you guys that have remained unflinchingly faithful to ARWR.
If anyone but Clinton gets the nod, that may take some pressure off the move to restrict drug company pricing for which Clinton is the leading spokesperson right now. If she drops out of the running, biotech could get a sigh of relief.
Whether Clinton did anything wrong or not, there is the "appearance of impropriety" and I think this is going to weigh heavily against her getting elected. And, with an FBI investigation of the emails still in full action, and more harmful information being released against her, she is definitely in potential trouble. When she was with the Rose firm in the 1980s and one of the "three amigos" one of her partners was convicted of embezzling $65 M and he was jailed over the Guarantee theft. Clinton worked on Guarantee but could never find her billings when they were subpoened by the justice department. Strangely those missing billings showed up in the White House in 1993. Somehow, with her husband being the President, she escaped being charged with obstruction of justice. Years later she signed papers acknowledging that she knew the rules for handling top secret papers and the penalties for mis-handling them, just like Petraias, yet she set up a separate email system that was used to violate those rules she promised to follow. Now the evidence is accumulating that she knew and even participated intentionally in the violations of the secrecy rules. Such violations are serious, if true, and the FBI is actively investigating her and her staffers. The latest release indicates there were 7 email chains that contained super top secret information found on her private servers, and there is no way that information could get there accidentally. Clinton is definitely in danger of being indicted for security breaches and that will abruptly end her presidential run, if that happens. But even if not indicted, this is a pall hanging over her.
If they do indict her, look for Biden to jump in against Sanders.
That 50 day average proved to be solid resistance and the shorts kept it down. When the biotech sell off began, ARWR was further clobbered along with the entire field. ALNY has dropped from $140 to $54, so we know this is not ARWR specific or any problem with ARWR. The market is in an "angry" mood, lead by developments about oil, slowing of growth in China, and weakness in confidence with the FED raising interest rates. The bios had a long run and they are in an inevitable correction, but when that correction ends, as they all do, then companies like ARWR have the potential to regain investment capital and their market caps will come back up. You can decide among many opportunities, so it is going to require some sharp analysis when you pick your low priced buys. If ARWR is gaining FCs I think a lot of buyers will flock here.
Put them on ignore, they are trying to get the PPS down for their bosses that are short seller funds. There is nothing to be learned by those that are spewing non-stop lies or FUD. Truth is, you should not listen to pumpers or any one on a MB other than to gain some insight and leads for your own research. Look at HPs posts which are all solid science and good leads about what is going on here. Read carefully the SEC filings, including the risks. You don't need a heckler to find out the risks, they are printed in the 10K.
Then figure out the risk/reward ratio and decide if ARWR is for you. Anyone that goes through a careful review of the opportunity here will end up buying and holding to see what develops. The opportunity is real, and risks remain, so that is why the PPS is so attractive.
How long will the investment rotation away from biotechs last? That is for you to factor into your analysis. I think the IBB is headed down and may hit 200, but it was recently at over 400, so a 50% retracement could be the level that stops this decline.
When money comes back into biotech, only those companies with promise will move back up. So ask yourself which ones are those, and is ARWR going to regain its footing.
Two possible types of "testing" testing collaborations coming. Either we will get someone that wants to license DPC for money paid to ARWR to be used for their own drug deliver system, something CA hinted at could happen, or we will find some in the field of cHBV drugs that wants to test their immune stimulant or booster drug with and without ARC-520 to compare the FC outcomes.
In both cases, it is my impression that this does not require first submitting the deal to ROFN. The first case because there is no way for Roche to offer a matching term sheet for the drug of another company, and in that case Roche will have to be content with license royalties. Exactly how the contractual terms and timing will follow are not clear, but there would be no chance of a competing offer from Roche because ARWR would not be granting the collaborator rights to ARC-520 for manufacturing marking or sale, just the combination. In that sort of deal, they would word it that ARWR remains the one that is manufacturing, marketing and distributing ARC-520 in combination with the X company that is doing the deal for its drug. To the buyer of the drug, they would be dealing with a combination therapy and two payees. Just a thought on how it could be done.
Both deals would help ARWR develop ARWR and see how it works in combination, and both deals should include that the collaborator is paying some or all the costs of ARWR being tested with the collaborator's drug.
Anyway, from CAs CC claims, we know they are talking to at least one collaborator now and it sounds like the deal is close, say by March time frame is my guess.
I believe that any collaboration deal that is aimed at testing would be followed by a marketing deal if the testing proves the drugs work together, or at least that is the potential. It is also possible for the testing deal to give some pharma partner all the impetus it needs to go after a full blown deal for ARC-520 with big up front money.
ARC520 just needs to perform!
It makes sense that lowering reserve requirements boosted business by reducing the cost of borrowing; and, raising requirements, even a little, changes that low cost of money environment, and it also weighs on the sentiment. So, much depends on the condition of the economy when you start the exercise.
When they lowered, the economy needed the boost due to the housing crisis. Much of the decline of housing prices and the related impact on unemployment and other negatives that rippled through the economy from the events of 2007 through 2009 have been erased or vastly improved, and the banks are on a different footing due to increased reserve requirements, and a change in the rules regarding credit default swaps and other derivative games. But risk remains in the banking system and, IMO, it is because the bankers will allow the risk for the sake of profits.
The democratic attack on banks may finish what has been started to make them safer for the economy, which is IMO potentially a good things for markets and can further insulate markets and strengthen the dollar and the markets over time, if done right. We do need the banks to make a profit, but we don't need the concentration of banks that has occurred, IMO.
As to the regulation of wall street, it is so obviously a corrupt place in which the wall street bandits are working the markets. They really need to stop the way the markets are manipulated and achieve free markets that better allocate resources. It is a tough job and it starts with recognizing the problem. Eventually, action against short selling is needed, and if Sanders gets in, it is just possible they will start to replace SEC people that work for Goldman Sachs and find some that work for investors.
Nope, that is not what they said. CA is very high on monotherapy, fix your glasses.
You can guess about PPS all you want, but if you write down your guesses for tomorrow and the next 12 months on the 11th, you will have 12 wrong answers, LOL.
Given that none of us have the ultimate facts yet, I have to give you credit for the best histrionics on the MB as you make up your claims.
You clearly outclass ccribber, rookie, and that crooked person, none of which have the flare for really good exaggerations, and none of them know how to get a laugh.
"Paranoid schizophrenic. Watch it here and now folks. Won't get an opportunity to see the textbooks unfold before your eyes like this again. Next stop is a padded room and a lifetime supply of strained bananas and sweet potatoes."
That is just good argument, well researched, dead on, and clearly explains how you think about the problem. LOL.
When it comes to ARWR, I don't think you know the difference between your foot and your mother's sewing machine, so excuse me for mocking you.
I am going with the science which tells me sustained KD of sAG will be important. We will see who gets flushed where when we know if that achieves FCs during the upcoming data readouts.
Meantime, tell your short seller bosses to lay off the booze.
tene, I think the analysts just look at the recent drop in bios generally and lower their targets on all bios. In some ways, I don't blame them for reflecting what the markets are doing. ALNY hit $56.53 today, so that is down from $140 and still falling. I never thought we would see the spread between ARWR and ALNY drop in the way that it is. It is just completely unexpected to see how much money got taken out of biotech stocks, across the board. The one silver lining is that ARWR seems poised to bring out stellar Monarch trial results with humans getting multiple doses. I could be fooled but I cannot stop thinking that they will drop the virus antigens by more than 90% and hold them down for as long as they want. Sure, we need to see how it works in humans but it did a good job in multiple doses from 6 to 11 doses for the chimps. Ergo, I don't see it is too risky or in any way a stretch to expect humans to have sustained an high KD of all antigens, especially with eAG(+) patients.
If sAG "overwhelms" the immune system and that is the problem, then surely a 90%+ reduction in sAG will correct that and the immune system can finish the remaining sAG all the way to seroclearance.
If sAG "tricks" the immune system into leaving it alone, we can still hope that reduction of the amount of sAG can help the immune system "reconstitute" and attack sAG to seroclearance, or alternatively that hitting all the viral antigens will so disrupt the virus that the passage of time with viral antigen additions held at bay by ARC-520 and the impact of the immune system in removing some of the virus, or alternatively with a combination immune booster that turns the immune system back on or into higher gear, will lead, sooner or later to FCs with less side effects than IFN, and with a higher percentage of patients getting there.
There is no way, Jose, that a 96 to 99% KD of sAG could be anything but good; and an attack on all the virons is even better. How long before this is recognized?
On February 7, 2014, Jefferies set a price target of $30 for ARWR as reported below:
"Jefferies analyst Thomas Wei doubled his price target on Arrowhead Research (NASDAQ: ARWR) - from $15 to $30 - following a positive meeting with management.
"We are becoming increasingly excited about the prospects for ARC520 in HBV and see the mid-year data in HBV patients as driving significant upside for ARWR," Wei said. "The company also plans on disclosing its liver orphan disease target and presenting preclinical animal data at an analyst meeting in late 2Q. ARWR is one of our top picks for 2014 based on the value of its RNAi platform and our increasingly positive stance on ARC520."
Now, after the best possible knock down record with humans and chimps, and a almost perfect safety record, with the company entering into multiple dose trials in 20 international sites, and with AAT attaining good phase 1 results with healthy patients, and Orphan Drug Designations, it has a price target of $4.
All this means is that ARWR has not hired Jefferies to do an underwriting, and we can probably trust CA that they are not going to do a dilutive financing, at least not with Jefferies or any other of the Analysts that have then on "hold".I guess we should start to worry if one of these "analysts" starts to upgrade them! LOL
Wall Street is way out of whack and it is corrupt as all get out, IMO.
Hecklers are desperately storming this board to block out any intelligent conversation. put them all on ignore and get free of the FUD.
Those who have studied zeroconversion know that it is a process. A switch does not flip in just one day. First the antigen disappears entirely from the bloodstream, not one log two logs or three logs, but the antigen becomes completely undetectable, or very close to that. As the process proceeds, at the point when the antigen becomes undetectable, there still is no surplus amount of antibodies that are detected in the blood. It is at this moment in the process that the conversion is occurring. The immune system is active in clearing the last of the antigen, but it takes time before the antigen is completely gone and extra antibodies guarding against the antigen are evident in the bloodstream. The amount of time for the immune system to remove the part of the antigen from the blood that ARC-520 does not knock down will vary between individuals and depend on their immune system fight with the antigen. I think this is the reason, or one of the reasons we use to hear from ARWR the words "with or without zeroconversion". I always thought they meant that the immune system could be active and clear the antigen that is left after the ARC-520 knock down, yet not yet showing the antibodies. From my review of literature some time ago, I concluded that the transition can take 1 to 3 months before antibodies appear in the blood system and the antigen is totally gone. So, while zeroconversion is a very important marker, and perhaps the most clear gatekeeper to FCs, I just want to point out that it will be very important if Monarch can show the predecessor to zeroconversion which is no detectable antigen.
The update also continued the claim that the safety profile of DPC is the best in the industry and without notable events. That means there are not any new troubling safety events. Every time they say that, it is after more time elapses. It does not sound new, but it is an important update.
The basic monthly cost of $3 M/month or $36 M per year was new to me. Maybe some of you financial types had figured that out. So they are saying that it will take about $40 M to run their key clinical programs for 1 year.
They do not need to get a lot of cash to extend the programs, so any collaboration deal does not really require huge money inflow for rights to gain a good runway. The kinds of deals that buy them $100 M in funding would be territorial in nature, for the most part. Rights to one or more countries or regions are potential deals.
It is a bit of a nail bitter whether the Monarch data will come in fast enough to get them what they want; but it seems that they already have the data they need to get money, and that is why they said, don't lose sleep over the funding. They will get the funding, and it simply is a question now over what they need to give and how much they will get in return. Those are functions of what Monarch shows and their AAT program.
Remember, they are now thinking about leveraging those programs to licence DPC for use by a drug company that wants to use it to deliver their own proprietary drug. This opens a lot of additional possibilities for collaborations and for raising capital, not to mention getting in to bed with important partners that could widen their activities where the program is sponsored by outside money, like AAT has support.
Those hecklers that just keep posting negative arguments are trying to keep sentiment down and promote selling . Some twist real facts, others are bald faced liars. Keep them on ignore.
All bios have risk, otherwise their would be little upside.We don't need short sellers to tell us they have risks. Read the 10K.
This investment is about taking the right risk, and everyone needs to make that decision for themselves, free of the emotional pressures.
Don't listen to hecklers.
He did clarify they seek testing collaboration to show what works, something allowed by the ROFN, as I have tried to point out to the board. This is a large new item from management discussing strategy.
And I understood them to say they are talking now to a potential collaborator they expect to sign, thus widening the chance for FCs.