Best posts collection !

[Think2Succeed]

This is the thread for the best posts we've found online...all in one place for easier reference (you can either copy the entire message and post it here as a reply- make sure you give the original poster credit for it or you can just provide the link to the post). Also please number the post for easier reference to it. I will add more in the future as well...

1. Posted by dig_a_little_deeper_1 on Dec 2nd 2015

Can Arrowhead become the first trillion dollar market cap company?


This seems like a ludicrous question when Arrowhead is trading at MC of 360M.

This is early in the development of this company, so lots of things can go wrong. The point of the question is, are all the things that are necessary to break that trillion $ barrier present in this tiny company.

So the first question is what it will take?

CNBC refers to companies that are changing the world as disrupters.

Apple is a really good example of a disrupter company and really is still close to that lofty goal of a trillion $ MC. Apple technology changed the music industry (iPod) phone industry (iPhone) and the computer industry (iPad). This is an impressive list of accomplishments for 1 company.

Can Arrowhead technology change the Drug industry?

The biggest drug companies on the planet have spent Billions chasing RNAi. The way I understand RNAI is the DNA sits in the nucleus of the cell and gives orders (RNA) to the Ribosome to generate different proteins. What RNAi does is silences these messages so the proteins are never made. This is how ARC-520 For example can Knock Down s-AG, e-AG, Cr-AG and X in HBV. There are several reasons that these companies spent so much time and money pursing this technology.

1) No disease is undruggable, this is especially important in oncology, where many important targets have proven undruggable.

2) If you can prove you can do it (safely) once you should be able to do it over and over again.

The problem these companies ran into when developing RNAI was delivering to the target without causing Adverse Effects (AE). These programs were in the works for years without delivering results, so they were the first programs that got cut when companies downsized.

In 2011 Arrowhead acquired Roche assets and IP. Roche had spent nearly 800M on the RNAi program,
As it turns out the big prize in the deal was, Roche Madison Inc. (formerly Mirus Bio Corporation,), providing an advanced proprietary RNAi delivery platform known as Dynamic PolyCunjugates (DPCs)

With the DPCs Arrowhead got from Roche they are now destine to be the #1 RNAi Company

So far Arrowhead has dosed over 84 patients and has found No dose limiting toxicity. In fact they have not found even minor recurring AE. They have reported the Highest KD in Animals, Highest KD in Humans and the ability to move out side of the liver.

To top it off in 2015 Arrowhead acquired the RNAi assets of Novartis. Novartis spent a decade and nearly a Billion dollars on the research and IP they developed. They have already started to use this IP in drugs they are developing (ARC-F12) and (ARC-LPA).

Armed with nearly 2 Billion dollars in IP from big pharma and some impressive results in humans. It is very apparent that arrowhead has the technology to be a disrupter in the Drug industry.

The next question is do they have the talent to pull it off?

On November 17 presentation one of the chimps (Manetta) showed 98% reduction in s-AG 32 weeks after the last ARC-520 injection. The chart shows that the last labs were drawn on day 477 in the study

477 days prior to November 17 2015 is August 8, 2014

The chimp study started ARC-520 dosing around July 2014

The first doses of siHBV-I were given in the January 2015
In the span of 6 months the Arrowhead team

1) Determined the KD in the chimps was not what they expected.
2) Determined the s-AG was coming from the integrated DNA.
3) Found the Trigger they needed to use to turn off the s-AG coming from the integrated DNA.
4) Developed the drug.
5) Manufactured the drug
6) Tested the drug.

Around April the Arrowhead team had tested what will be ARC-521 in the chimps. 1 year for animal testing for a May IND for ARC-521. This removes any uncertainty that Arrowhead can be a disruptive force in the drug industry

2. Posted by hparch as a reply to the above post on Dec 2nd 2015

dig;

My thoughts, exactly, and I have posted as much over the past year, only, your post sums up the more recent AD data and information into the whole equation, making it that much more calculable.

In order for ARWR, or any company, to become a $1trillion+ market cap company, they must be able to generate at least 1/10 of that amount, $100b in yearly sales (market cap = 10X forward projected annual sales). Is this possible?

Well, considering that there are thousands of diseases that can be treated throughout the human body, and ARWR's DPC can deliver RNAi to any location in the body (theoretically), lets use 1,500 diseases for a modest possible potential target market for ARWR.

Now, figure ARWR can achieve RNAi efficacious drugs for only 1/100 of them. That's 150 drugs.

If each drug can reach, say, only 500,000 patients per year, at a cost of $10,000/year, the math is:

150 x 500,000 x $10,000 = $750b. Of course, building up to that will requires years of staffing and IP development, but, ultimately, it IS possible to pierce that $100b annual sales revenue number, as you can see.

RNAi is not a permanent cure for many diseases, but, like ARC-AAT, an ongoing successful treatment, so, for those diseases, much of the revenue is recurring.

I also believe that we need to be conservative in revenue modeling, because, as you can see from what is happening even now, scrutiny of big Pharma's predatory pricing models is only heating up. It is wisest to price drugs reasonably and reach more of the patient market to compile revenues and profits - this is good both for the patients and the economy: my modles, therefore, always uses that pricing logic.

The information in your post above and the economics I have just spelled out are apparent and will be recognized by market investors once they are convinced beyond a doubt that ARWR has the goods and is on its way to this buisness model. Then, paying up at current prices is nothing compared to where it will be.

[Think2Succeed]

3. Posted by hparch on Nov 7th 2015

Sharing something important from my talk with IR this week

Everyone;

I spoke with IR this week, and needed some time to digest everything I learned. I will not provide everything, as I'm still digesting and processing, but, I wanted to share at least one, really vital piece of information, which, when I shared with other investors privately, kind of blew them away:

ARWR has such confidence in DPC as a delivery system now - its SO derisked, that they now have the ability to bring a drug from concept to a physical drug injected into a lab rat in 7 - 10 days.

Yes, you read that right. 7 - 10 days. Feel free to confirm yourself. That's a rate of 50//year!

At that rate, once they are funded, they cam burn through Novartis's 30 targets within a year. Where will the rest come from?

The answer is "big pharma", I believe. Once the human genome was completed, how many pharma's invested in R&D for triggers to target major and minor diseases throughout the body (not just the liver)?? We don't know, but I would venture that many/most of them did, and likely patented their triggers, as well.

Due to the delivery issues with RNAi, though, much of this IP is likely locked away somewhere in some lab assistant's office, collecting dust.

THIS is where ARWR will be able to turn into a literal RNAi partnering factory for big pharma to help them monetize that IP.

7 - 10 days for proof of concept in a lab rat per drug.

If I showed you my projections for future earnings from this you'd call me insane. It's just not fathomable.

I believe that this is why the stock is so underappreciated and poorly represented in the media - even Cramer calls us a "nanotech company" WTF??? No one can be that stupid.

Investors needs to do some serious thinking here, and use only the known facts to finally understand what the real potential is, and then understand that the street takes NO prisoners, and will test every bit of patience possible. We are going to have to earn the rewards here, everyone, because the writing is clearly on the table now.

"DPC"

4. Posted by hparch on Sept 24th 2015 (after AD)

My thoughts on the data provided:

Seminal: First ever identification of integrated DNA as a production agent for s-AG! This is how/why e-AG (-) chimps are more difficult to treat than e-AG positive chimps. They then went on to PROVE this, by creating ARC-521 within months and tested it in 2 chimps and saw a 2 LOG reduction (99%) of s-AG in e-AG - chimps!

This, alone, puts them another year, easily, ahead of the compeittion, because no one - i repeat, NO ONE, even thought that integrated DNA was even related to s-AG production - so, if they want to find FC's in e-AG patients, they have to R&D their way to surpress its expression, or stop it from getting into circulation.

The e-AG+ data was exemplary. Once they honed in on e-AG+ vulnerability to RNAi in the chimps, it was like they knew, precisely, where they had to concentrate, and our prognostications here were true: NUCs did their job and ARC-520 did its job. I think that the 1 of 4 chimps that "saw an immune response" is likey FC'd, and they are saving it for AASLD - they were VERY careful to clearly indicate the immune response, but go no further and refer to AASLD for more.

That indicates that ARC-520 + NUCs for e-AG+ patients that have NOT been on NUCs before, (35%+ of the chronically infected) may be eligable for treatment, if FC is shown in Monarc. They will also add in PEG-IFN in Monarc for both e-AG + and - patients as well, likey to see if they can get FC's at a higher rate.

Finally, but most important: DPC is completely derisked now. Through the 80+ patients, and the chimps, an no signficant AE/tox issues, we can now safely say that Roche's $800m R&D should certainly be reflected into ARWR 's valuation, at the bare minimum.

My estimate of current value is based on IP alone, still:

Roche assets: $800m
Novartis assets: $1b * 50% (the trigger enhancement IP allowing to operate outside of ALNY's IP is being incorporated into candidates now) = $500m
Cash: $100m

$1.4b / 60m = $23/share, min.

Today, we witnessed history.

5. Posted by bourbonisbest on Oct 29th 2015

10 points for a Thursday!

1). Someone or some organizations with a lot more money than me has an interest in ARWR.

2). All of the giant companies were small at one point in time.

3). One typically crawls before walking, and walks before running.

4). If the company had nothing to offer why would people be willing to run 70 + million shares traded in a single day in order to destroy the stock (October. 2014) and repeat similar activity on AD?

5). I understand the sell the news idea, but that typically is done on a company that has run up considerably above its intrinsic vslue and I have my own reasons in different scenarios as to when to sell on good news ( rebalancing portfolio,) but why sell on positive news when the value should be 20 X current stock price? (only answer I can come up with is see question 1)

6). If this technology, DPC works to its optimum potential, this could be the most valuable healthcare company of all time. If it works somewhat, then we have a company worth 100 billion plus, and all I've seen so far is activity and an excellent safety profile.

7). I believe algos are capping this company until they aren't. My confusion is to why? Currently the shorts are winning and it has been brutal, amplified by all of the incredibly positive news. Psychology says shake out the loose hands, show good data, bring in new blood, wash and repeat.

8). Currently, there cant be that many shares besides mine that they haven't already stolen, so with continued good news sooner or later this stock should be a portfolio maker.

9). Multiple products in development equals multiple shots on goal. All ARWR needs is one to peak someone's interest as most are blockbuster opportunities and in the case of some are life savers and dynasty makers.

10). Someone or some organization with a lot more money than me has an interest in ARWR and I thank them each time I purchase as they are giving me the greatest gift I've ever received from a stranger or strange computer.

As always IMO

6. posted by hparch as a response to the above post on Oct 29th 2015

bourbonisbest;

A great thursday morning post, thanks.

Finding a true (as in "real") diamond in the rough company is a rare event in today's market. Finding a biotech "diamond in the rough" is even rarer, because of the secrecy and delays in results and the cash/revenue deficits that often ruins some really good companies with just as good science.

Patience for long term value investors is the best advice one could give, along with continued due diligence, to assure that the company is continuing to stay on track.

When ARWR is trading in the triple digits/share sometime in the next few years, will it REALLY matter that it traded $5 - $10 for a year in 2014 - 2015?

Or, on the other hand, will we be asking ourselves why, in the face of ALL the positive scientific facts and progress, we weren't buying more "back then"?

I have been accused of not finding fault with ARWR. That's not true. I just don't find any in the science, and i do agree with everything that they have done, to date. That's kind of rare, but, it is proving out quite well; if they do something I don't think is in the best interest of the shareholders, I will certainly let them know; as a shareholder, it's my responsibility.



Just sayin...

Great post!

7. Posted by carrix_fool on Sept 24th 2015

A biotech powerhouse is born today!

I took today off and watched the entire webcast. Despite the lukewarm price action, what this AD did was profound and it truly is a inflection point in the history of ARWR.

I will not go over any specific about the ARC520 program and the various data. That, to me, is secondary. What's most important is they have demonstrated to me that they have the organizational structure, the deep scientific understanding and technical know-how to identify new issues, ask the right questions, propose a solution and implement a solution in an astoundingly timely fashion.

How did I come to that? Well, they noticed the difference between eAg+ and eAg- and the cccDNA and integrated DNA. They then came up with ARC521 and tested successfully in chimp already. Wow! This is powerful stuff. This is what makes ARWR in the same league as Amgen, Gilead and Regeneron.

This not only derisks their ARC520, AAT, and F12, this actually derisks the entire company.

At this time, Mr. Market is asleep. You can buy all you can at $8 and sock it away for the next 5 year and watch it grow 30-50 times. Short-term wise, selling front-month puts will get you a very nice return such as Oct $7 for 10% in 3 weeks.

I can honestly say that ARWR is a once in a lifetime wealth-building stock today.

GLTA

8. Posted by Think2Succeed on Nov 20th 2015

The value of ARC520/1 vs Entecavir even before a FC is achieved, is clear:

Some shorts are now trying to spread the idea that since a FC wasn't achieved then the KD of HBsAG is worthless. Well I got news for them:

"The oral antiviral drugs, initially approved in USA (lamivudine, adefovir and telbivudine) were well tolerated but efficacy of these agents is limited by emergence of antiviral resistance. However, newer agents (entecavir and tenofovir) are more potent, well tolerated, and have a high barrier to antiviral resistance. Long-term follow-up studies on newer agents has shown sustained viral suppression along with improvement in biochemical and histologic evidence of disease.

*****Long-term therapy also led to decrease in fibrosis and regression of cirrhosis .****

HBsAg loss was achieved in only 8% of HBeAg-positive patients after 3 years of tenofovir therapy. Similarly, in another study, HBsAg loss rates for HBeAg positive patients treated with entecavir or lamivudine for 2 years were 5 and 3%, respectively."

"Current antiviral therapies are aimed towards inhibition of viral replication. Sustained viral suppression is associated with improved outcomes and it has been shown that elevated HBV DNA level is a strong predictor of increased risk of cirrhosis and HCC in CHB. None of the current therapies lead to HBsAg loss or seroconversion in the majority of patients. In addition, current antiviral therapies do not target defective immune response and persistence of covalently closed circular DNA (cccDNA) in the infected hepatocytes. Thus, the goal of current treatment is to achieve long-term virologic control since elimination or ‘cure’ is not possible."

"Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 2013:Provides evidence that long-term suppression of HBV can lead to significant regression of fibrosis and reversal of cirrhosis in a substantial proportion of treated patients." Source link

Now to put this into context: ARC 52x KD's HBsAG as well as all the other HBV antigens by at least 97% in ALL patients after just 1 dose in just 30-45 days !! Can you see the difference vs all the other antivirals that produced a weaker response after a much longer treatment time and in a fraction of patients (8%) ?

9. posted by hparch on Nov 20th 2015 as a response to the post above

t2succeed;

If I may, I'd like to point out something about the chimps that most probably have NOT taken into account:

ALL treatment stopped after the last ARC-520/ doses were given - NUCs, too, which is why the viral DNA went back up in the majority of the chimps.

In humans with immune systems that DO have the ability to clear the virus, it is VERY possible that just a periodic treatment of ARC-520 with continued NUC's can finish off the virus w/o PEG-IFN. This could be yet another arm of Monarch yet to come.

Remember, ARC-520 seems to be crippling the virus on all fronts, with it's immediate and deep KD of the entire genome. Dr. A's remarks yesterday all but confirmed that those e-AG - "delayed" KD were a result of just that: ARC-520 couldn't KD the s-AG because it wasn't cccDNA produced, but, after a few doses, it began to mysteriously decline anyway - how could that be?

There is only 1 answer: the virus is incapable of producing as much - it's being affected by something new - and the only thing that could be is ARC-520's KD of the entire genome.

This is how REAL scientists think and work: they look at the data - ALL of it, no matter how inconsequential, and try tot understand it to see how to improve what they are doing.

I recommend everyone go back to the AD presentation, again, and pay attention to Dr. Locarnini mentioning, for the first time, ever, the possibility of a "sterile" cure, after seeing this data that ARWR provided.

A world renown expert saying something like this is very, very telling.

The share price stinks, but the science and the company that is creating it, certainly doesn't in the slightest.

[Think2Succeed]

10. Posted by hparch on Dec 7th 2015

More confirmation

Well, I'm sure you have all seen the news this morning - immune reactivation in 7 of the 9 chimps as a result of ARC-520 + NUCs.

First, lets give kudos to DPC, shall we? None of this could be done if it wasn't THE ellite RNAi delivery system that it is.

Now, what does this mean for ARC-520 going forward?

Well, remember, chimp immune systems are much less evolved then human immune systems - if ARC-520 can KD enough of the genome in chips to get their immune system woken up, then this greatly increases the chances that it should work as well, or even faster and better in humans.

Prior to today, I was more optimistic for Monarch's ARC-520 + PEG-IFN arm than I was for the ARC-520+NUCs arm, because ARWR indicated signs of immune reaction in only 2 chimps. I guess the final bloodwork is now in, and that data has been updated, and this bodes VERY well for ARC-520+NUCs humans alone.

More importantly, 7 of the 9 includes the e-AG(-) chimps. This does imply that ARC-521, when in clinicals, may do even better than ARC-520 for that group.

Monarch is now looking EXTREMELY powerful for ARWR and he B sufferer's around the world - 350m - 400m chronic sufferers may finally be seeing a true treatment to help them lead a normal life again. How cool is that?

Yes, more validation of what we have all been seeing unfold over the past 14 months, right before our eyes.

This is, indeed, yet more evidence of one of the most unique and incredibly adept biotechs in business today. The IP is incredible; the scientists are top notch, and management has, once again, proven to be WAY ahead of the markets.

Today is yet another day that reminds me of how proud I am to be an ARWR shareholder.

[Think2Succeed]

11. Posted by pietrzkiewicz on Nov 25th 2015

2b: the prevailing theory claims that when the level of antigen S, produced by infected cells and causing suppression of immune system of the host, is substantially lowered the immune system recovers and clears the liver of infected cells, bringing about functional cure. The chimp called Manetta had sustained viral response as it kept the level of HBsAg of 4% compared to the starting point before multidosing. What is the meaning of this? One has to remember that it has never been observed for chimp to clear HBV infection on its own, which is the case for most people infected with the disease. This bodes very well for the efforts of the company to achieve FC in humans with multi dosing and stimulation of immune system with Peg Interferon.

[Think2Succeed]

12. Posted by Bio Boy Scout on Dec 9th 2015

[qbeing1010]

13. Posted by TigerCapital on Dec 17 2015



Interesting bit from August 8, 2013 PR
.

This article primarily focuses on company shifting its research and development focus entirely onto RNAi drugs and discontinuing the Rondel platform, but one little snippet at the very end caught my attention:

"Going forward, he said, Arrowhead will only use the peptides to enhance DPCs for RNAi drugs, although he added that it would still consider partnering the delivery technology in non-RNAi areas through partnerships such as its ongoing alliance with Shire."

It may not be likely in the near term and two years is an eternity ago, but if a non-RNAi partnership such as what is alluded to above is announced that is an absolute game-changer for this company. I would go out on a limb to say that the majority of molecules currently on the market would likely benefit from elimination of non-specific uptake alone (not to mention the possibility of enhanced efficacy as well). If there is anything that could potentially jump the upside here any more than what the current potential looks like, I strongly believe it is in becoming a player in the non-RNAi space. A MC in the $T's doesn't become too far-fetched if such a scenario becomes a reality.

[Think2Succeed]

14. Posted by hparch on Dec 23rd 2015

mr_red;

I don't offer "koolaide". I offer discussion of the facts. I welcome contrarian opinions, based on facts. Most here want to find out as much as possible regarding their ARWR investment, long or short. This is one of our ways of doing it.

As for your questions:

1. I think ALNY is doing fairly well with some of their RNAi trials, despite their instability issues. They could get approval of an RNAi drug before ARWR, but, does that matter? Not to me. ARWR's DPC is the king of RNAi delivery. We are seeing groundbreaking science and medicine occur right before our eyes. Its starting with cHBV patients, and extends into ARC-AAT and should blossom out from there, throughout the body for many diseases that you, me, and our family members may have to deal with in our lifetimes. IF DPC proves out, genetically\ treating diseases is, at minimum, a life-saving treatment regimen for many, many human beings.

2. I think it fair to say that given appropriate pricing as I have set forth ($12,000/patient/year), FC's by any treatment will become extremely well received and covered by insurance and governments around the world, because of the huge savings to their medical systems such treatments will provide.

3. The stock market is all about finding bargains. Undervalued companies that the market hasn't discovered yet. ARWR is one such company, IMO. Based on IP alone, we should be trading at$25 - $30/share. More and more independent analysts and industry specialists appear to agree with that. Once FC's are achieved, then its a discounted revenue projection from their potential market size backwards to today. Why hasn't the market signed on yet? That's a good question. I would bet that there are many answers, but, my take is a more complicated one that I have explained many a time here: its part greed from the shorting manipulation, an angry IB that didn't get a merger it wanted, and, perhaps a significant competitor that has "Friends" in the market trying to keep ARWR down.

[Think2Succeed]

15. Posted by dig_a_little_deeper_1 on Dec 27th 2015

11 reasons to own Arrowhead

1) DPC safety:

The safety of DPC gets talked about allot on this Message Board. What does not get talked about is why this is a game changer for the RNAi field. The RNAi triggers that “interfere” with the RNA message are not the problem. The problem with toxicity is the delivery system. DPC has shown no major Adverse Effects. DPC has not even show any reoccurring Minor AE’s so far. AE’s is what has plagued the RNAi field for years. AE’s have cause major pharmaceutical companies such as Novartis to discontinue there RNAi programs.

2) DPC effectiveness:

DPC has shown the Highest KD in animal models. DPC has shown the Highest KD in Humans ever recorded in a single dose. What this really means is DPC is delivering the triggers to the target very well. DPC is the Safest and most Effective of the RNAi delivery methods. Arrowhead has solved the RNAi delivery problem. This alone will forever change the RNAi field but, there is more much more.

3) ARC-520: ARC-520 has already proven to be effective with the KD Of the entire HBV genome. Arrowhead can move forward with a NDA without ever getting 1 Functional cure. I don’t believe that this will be necessary but, it is an option in the worst case scenario for the effectiveness of ARC-520

Arrowhead seems to be convinced that it will take more than just HBsAg KD to “awaken” the immune system. This could set any competition in HBV back several years. HBV is a DNA virus that the pharmaceutical industry has been unable to conquer for decades. No one has been able to KD HBsAg directly, let alone HBsAg and All the other HBV antigens. My point is, ARC-520 very well may be the only way to get consistent Functional Cures for the foreseeable future. 7 of 9 chimps showing an immune response makes it very likely that ARC-520-521 will achieve FC’s in humans as a mono therapy.

4) The Arrowhead team:
The chimp study started ARC-520 dosing around July 2014

The first doses of siHBV-I were given in the January 2015
In the span of 6 months the Arrowhead team

1) Determined the KD in humans was not what they expected.
2) Determined the s-AG was coming from the integrated DNA.
3) Found the Trigger they needed to use to turn off the HBsAg coming from the integrated DNA.
4) Developed the drug.
5) Manufactured the drug
6) Tested the drug.
Around April the Arrowhead team had tested what will be ARC-521 in the chimps.
Arrowhead went from the observation that they needed a drug that would KD HBsAg in the integrated DNA, to running the necessary Animal safety trials For ARC-521 in an incredibly short time frame. This removes any uncertainty that the Arrowhead team can deliver.

5) In the goals for 2015 Arrowhead revealed they would announce the first subcutaneous administration or extra-hepatic delivery preclinical programs. Arrowhead delivered both. First they announced: ARC-HIF2 that is designed to reduce the production of hypoxia-inducible factor 2 alpha, or HIF-2 alpha, to treat clear cell renal cell carcinoma. It is the first drug candidate using a new DPC™ delivery vehicle designed to target tissues outside of the liver.

Not only is it the first extra-hepatic delivery but, it is shows how effective arrowheads cancer drug’s can be by actually reducing the tumor size.” Treated mice exhibited statistically significant reductions in size and weight” One of the major advantages of RNAi is it effective against any Dieses. Many cancers are considered un-drugable but, all that is about to change with extra-hepatic DPC.

ARC-LPA that is designed to reduce production of apolipoprotein A, or apo(a), a key component of lipoprotein(a), or Lp little a, which has been genetically linked with increased risk of cardiovascular diseases. ARC-LPA employs Arrowhead’s new hepatic delivery format being developed for subcutaneous administration.

6) Nearly 2 billion $ in Research and IP.

Arrowhead acquired the RNAi Assets of Roche the 3rd biggest pharmaceutical company on the planet. Roche spent nearly a billion dollars developing the program and generated many patents to protect the technology. All this and the Madison facility with all its equipment and personal were assigned to Arrowhead in October 2011. In 2015 all the RNAi Assets of Novartis, the biggest pharmaceutical company on the planet were acquired by Arrowhead.

“We anticipate this acquisition will provide us with expanded freedom to operate, proprietary technology that appears to enhance the activity of RNAi triggers”
It would be interesting to find out if they used this technology in ARC-521.

“We now have additional flexibility to optimize each new candidate using the most effective RNAi-trigger design and modifications”. ARC-f12 and ARC-LPA use Novartis Intellectual property for the triggers they chose, effectively leaving ALNY irrelevant to Arrowhead.

7) Big pharma has a vested interest in Arrowheads success.
Out of the top 25 pharmaceutical companies in the world Novartis ranks #1 and Roche Ranks #3
Both of these companies have a vested interest in ARWR success. Novartis owns millions of shares of Arrowhead and will receive single digit royalties on any drugs that use IP acquired from Novartis.

Roche will receive single digit royalties on sales of ARC-520 and ARC-521. if Roche receives as little as 3% of sales, that would = billions over a 10 year period. It would defy logic for these companies to let Arrowhead fail over what would be chump change to either of these companies.

8) Often overlooked is ARC-AAT, which is a rare genetic disorder that can lead to lung damage and liver disease. During the Phase 1 study a predetermined level of knockdown was met in healthy volunteers and transitioned the study to enroll patients with AATD. ARC-AAT was also granted orphan drug designation by the FDA this year.

9) The platform: CA says it best in the 2015 q4 CC “We have always said that a key benefit of developing a suite of RNAi therapeutics is that data and experience from each program can be leveraged to inform the development of new drugs. Each of these new drugs can potentially have progressively lower risk and a faster path from discovery to human trials if they are built on an underlying delivery platform that is validated in humans. Once this validation is achieved in one candidate, it may provide better certainty in future candidates. We believe that recent data on the ARC-520 drug candidate against chronic hepatitis infection validate our DPCTM delivery system”

10) Lots of things will be happening in 2016: Fiscal 2015 Year End Conference Call – Prepared Remarks December 14, 2015

1. Fully enroll the currently planned 6 MONARCH cohorts
2. Add new MONARCH cohorts
3. Enter into one corporate collaboration in MONARCH with a new compound for combination therapy 4. Complete enrollment of Heparc-2002
5. Complete enrollment of Heparc-2003
6. Complete enrollment of Heparc-2004
7. Complete enrollment of Heparc-2001 open label extension
8. File IND or equivalent for ARC-521
9. File IND or equivalent for ARC-F12
10. Complete Phase 1 study of ARC-AAT in healthy volunteers and patients
11. Initiate longer-term multi-dose study of ARC-AAT
12. Report additional preclinical data for ARC-LPA and ARC-HIF2

11) ARWR is the clear leader in HBV (a multi-$billion opportunity) and RNAi technology a (much larger than HBV opportunity) ARWR trading at $6.20 may be the most ridiculous thing on any exchange anywhere in the world. The multi-million dollar question (at least for ARWR investors) is, when will the ARWR MC accurately reflect the opportunity?

[Think2Succeed]

16. Posted by harcerz4 on December 30th 2015

Theory on how this plays out over the next year or two

The theory is that ARC-520 will be sold to the highest bidder (probably Gilead for around $20B - $30B) once a clear path to a functional cure for HBV is shown.

How do we get to this theory?

1. Pharmasset was acquired by Gilead for $11B for one drug only that targeted HCV.
2. We know that Gilead is profiting greatly from this acquisition.
3. The HBV market is much larger than HCV.
4. Arrowhead's ARC-520 has a significant lead on the competition in developing a FC for HBV.
5. Gilead is already uniquely positioned world-wide to sell and administer HBV drugs into the marketplace.
6. Time is of the essence to achieve maximum profitability for ARC-520, and Gilead can do it much quicker than Arrowhead can.
7. Arrowhead has a larger pipeline that addresses much more than HBV. Its DPCs can be applied to numerous other targets. They own IP rights to 30 select targets from Novartis, giving them full freedom to operate. Sales potential for drugs not targeting HBV is easily in the hundreds of billions of dollars, but will take time and money to get there.
8. Selling the company would limit, if not entirely stop, development of drugs beyond HBV.
9. ARC-520/521 are equivalent to Pharmasset as far as the drug offering, and ARC-520/521 are worth much more than Pharmasset, clearly making ARC-520/521 worth at least $11B if a FC is shown.
10. Arrowhead will need more cash in about 1.5 - 2 years.

So the ultimate decisions that need to be made by year's end literally boil down to the following two questions:

1) Do you dilute your shares and raise more money for a few more years?
or
2) Do you sell off one of your drug lines for $11B+ giving you the freedom to develop, test, and bring to market dozens and dozens of drugs where you have the full freedom to operate, will NOT dilute your shares, and will give you at least 10-20 years of drug development (with the pedal to the ground)?

Valid theory? I think so - to me, this is a no-brainer.

[qbeing1010]

17. Posted by hparch on 1/8/16

Great Day to Consider the Market Thread:

No, management hasnt disclosed the 2001 follow-up dosing regimen. The only thing we have is the text from the last QC:

"(4) A 2001-extension study is open to patients that were treated in our single dose 2001 study. We will be testing ARC-520 + NUCS in e-negative and epositive patients who are both NUC-experienced and NUC-naïve. Unlike 2002/3/and 4, this is open label so we have flexibility as to when we disclose data."

Here are my thoughts - take them as hypthetical, because of the limited information we have at this point:

Just 1 dose of 4mg ARC-520 lead to a 1.2 mean peak KD in e-those 6 AG+ patients. How much damage did that do to the virus in those patients. We KNOW that they have not released all relevant information, as those studies are now in extension mode.

Whatever they do (or have been doing) for additional dosing to those patients will be an "additive" effect, whether its 1mg, 2mg, 3mg or 4mg dosing after that. They could be experimenting with 1mg/kg every 2 weeks for all we know for them. We just don't know.

What we do know is that those chimps 80% immune responses are screaming with megaphones that genetically attacking the virus is weakening it so much that even their less evolved immune systems have taken advantage of it.

You are right, IMO, to be excited about this extension. By definition, it is currently ongoing, and all 12 patients in cohort 7 are in a terrific position to really show what ARC-520 can do, near term.

Remember, it KD's the genome in all patient types, just not so much s-AG in e-AG- NUC treated patients, BUT, they are extending at least one of those studies, as well, because of the "delayed" s-AG reduction they saw, suggesting that crippling the virus alone is enough to be theraputically beneficial.

IMO, of course.

[Think2Succeed]

18. Posted by wyattkap on January 7th 2016

This is why they do the science trials. YEARS of refining ideas-theories, slow but steady work in the lab, hundreds of million invested, have now lead us to these two fantastic open label trials in humans. A 300 Million Market Cap company on the cusp of making a massive penetration in a $700 Billion Dollar market that can touch 1 in 3 or 4 humans in the world and we argue about daily share price and how to best leverage yourself for each of our futures. Amazing we can buy today at $5 and a few pennies/sh, but the market once saw us 5 times this value with just that one single chimp multi-dosed optimistic KD data with no clear side effects showing. So glad many here see the opportunity to constantly add to your position as WE KNOW SO MUCH MORE of not only ARC 520 that has remarkably lead us to create 521, but the vast diversification we are just starting to tap into our DPC platform. Wall Street at times makes zero logical sense and thus the need to do your DD and make the best decisions for yourself and your family. Investing is emotional for many and thus the turmoil. Relax and enjoy the path to new science that could easily change the healthcare industry & qualities of life forever!

[qbeing1010]

19. New patent covering delivery uses (spoiler: covers coronavirus!)

Posted by tigercapital51387 on 1/13/16:

Interfering RNA delivery system and uses thereof
Patent number: 9233170
Abstract: The invention provides a delivery system comprising a cell penetrating peptide, a polyarginine peptide, and an interfering RNA molecule. The system can be used for delivering interfering RNA molecules into a cell in vivo or in vitro. Therapeutic uses for the delivery system are also provided.
Type: Grant
Filed: January 17, 2014
Date of Patent: January 12, 2016
Assignee: Arrowhead Research Corporation
Inventor: Jon E. Chatterton

A patent covering delivery of a molecule to inhibit upper respiratory/sinus infections?! Can you hear that sound? If you are a shareholder that is the sound of a cash register ringing to the tune of tens of billions of dollars once again. How much do people spend each year on the common cold? I'll let you figure that one out for yourselves.

***

I'd love to see some discussion of this.

[qbeing1010]

20. Posted by hparch January 15, 2016

So, lets talk about the short position, practically speaking.

A normal healthy short position for a stock would be about 3- 5%, or, say 3m shares. That leaves us about 10m nefariious short shares to contend with.

10m shares to get to $0 from $5 = $50m. That's the maximum short "upside" at this point. Of course, they can cycle shorting and make more, but, ultimately, this is the ballpark.

The shorts are already sitting on about $100m or so in shorting profits, if you do the math, excluding, of course, the cycled shorting that has been done.

Any material event that shows ARWR has realistic revenue earning potential will outweigh the potential downside reward, theoretically, unless.. UNLESS...

There is "more' going on behind the scenes, which I, and others believe may have been happening - if this is the case, then the short position has been nothing more than a smoke screen to mask the true intention of keeping the market cap low for a company that has $2b worth of IP, a lead in HBV, and the ONLY safe extra-hepatic RNAi delivery system in the market today.

The media''s deliberate dismissal of anything good for ARWR is suspect: there is tons of money to be made to the upside to tout that IP, as was done with many other companies with much, much less.

This is, IMO, a "land grab". RNAi is the future of medicine, and ARWR has the goods. The forces in control don't want this company to succeed on its own, and cannot buy it or force it to sell to one of their holdings, so, the downward pressure has ensued.

BUT, the rules cannot change, and won't. At some point, the profitability potential will be so great that the investing public will take over, and no one wants to get in the way of that train.

Till then, we have tremendous buying opportunities.

As holden has so characteristically said many a time here: "the egg timer has been turned over".

I'm not selling a single share. Not one. They are too valuable.