Argos Therapeutics

Quote
I'm an investor, not an employee, but will share my opinion about why I'm bullish on this stock.
The question has been asked here a few times - if you have 25 percent of events in June 2015,
and 50 percent of events as of June 2016, how do you get to 100 percent of events by 2017?

First of all, what are we talking about when we say an "event" has occurred? Since the primary
outcome is overall survival, an event is simply an answer to the question: is the patient alive
or dead? Viewed this way, an event is not a complicated question.

A negative outcome is easy to assess. According to clinicaltrials.gov, if 290 deaths have accured
on the study, that is one way for this to come to an end.

Argos said that it had completed enrollment of patients for the study on July 15, 2015. It was
noted that with existing treatments of these cancer patients overall survial is expected to
be about 15 months. 15 months from July 15, 2015 would be mid October, 2016. So, it would seem
that one could not claim success from this trial any earlier than this mid October date.

To be successful, I don't think Argos has to cure cancer. They just have to show that what they
are offering is better than the existing standard of care. It is noted in the trial that assessment
can take "up to" 42 months. If it took this long (from July 2015), now we're talking mid October 2018. Does have have to take 42 months? I think the simple answer is: no.

One comment that has been made consistently throughout this trial is that AGS-003 is not toxic. As
you know, a problem with other treatments for cancer is that they can cause other harmful side effects
to the patient. Whatever else AGS-003 is, it is not toxic.

I watched a company presentation, where they commented on the enrollment process. They said
that enrollment for the trial was slow in the beginning, but then it picked up at some point, and a lot
of patients enrolled. So, I don't think we can make the assumption that the dates are necessarily going
to follow a linear progression - certainly the enrollment process did not.

The real question is, at what point do you declare this is a success? Suppose that patients are alive
18 months after receiving treatment, and you know the drug is not toxic. That would be a 3 month benefit that you know of compared to the existing standard of care. 3 months may not seem a lot to you and me, but tell that to a cancer patient or his family who needs hope. Why would it be unreasonable to give the go-ahead for this drug then?

If there are specific factual errors I've made about what an event is, please let me know. Thanks.
 






SilentHunter said:
I'm an investor, not an employee, but will share my opinion about why I'm bullish on this stock.
The question has been asked here a few times - if you have 25 percent of events in June 2015,
and 50 percent of events as of June 2016, how do you get to 100 percent of events by 2017?

First of all, what are we talking about when we say an "event" has occurred? Since the primary
outcome is overall survival, an event is simply an answer to the question: is the patient alive
or dead? Viewed this way, an event is not a complicated question.

A negative outcome is easy to assess. According to clinicaltrials.gov, if 290 deaths have accured
on the study, that is one way for this to come to an end.

Argos said that it had completed enrollment of patients for the study on July 15, 2015. It was
noted that with existing treatments of these cancer patients overall survial is expected to
be about 15 months. 15 months from July 15, 2015 would be mid October, 2016. So, it would seem
that one could not claim success from this trial any earlier than this mid October date.

To be successful, I don't think Argos has to cure cancer. They just have to show that what they
are offering is better than the existing standard of care. It is noted in the trial that assessment
can take "up to" 42 months. If it took this long (from July 2015), now we're talking mid October 2018. Does have have to take 42 months? I think the simple answer is: no.

One comment that has been made consistently throughout this trial is that AGS-003 is not toxic. As
you know, a problem with other treatments for cancer is that they can cause other harmful side effects
to the patient. Whatever else AGS-003 is, it is not toxic.

I watched a company presentation, where they commented on the enrollment process. They said
that enrollment for the trial was slow in the beginning, but then it picked up at some point, and a lot
of patients enrolled. So, I don't think we can make the assumption that the dates are necessarily going
to follow a linear progression - certainly the enrollment process did not.

The real question is, at what point do you declare this is a success? Suppose that patients are alive
18 months after receiving treatment, and you know the drug is not toxic. That would be a 3 month benefit that you know of compared to the existing standard of care. 3 months may not seem a lot to you and me, but tell that to a cancer patient or his family who needs hope. Why would it be unreasonable to give the go-ahead for this drug then?

If there are specific factual errors I've made about what an event is, please let me know. Thanks.
Click to expand...
 






Silent hunter raises some excellent points. Hopefully he is being honest and isn't simply an insider trying to persuade public opinion.

So, here's where Silent Hunter's assumptions are not necessarily on target.

1) End of recruitment to the ADAPT study occurred during summer of 2015. Based upon their accrual (slow in beginning then per quarterly calls, steady for rest of study .. meaning linear for the most part), this suggests they will need a good 24 months or so of follow up for the study to read out at 290 deaths per my reliable biostatistician consultants. This places trial readout in the mid to late 2017 time frame, not early 2017 as the company has recently suggested to support fund raising efforts.

2) The event rates for positive survival trials where you need to demonstrate a significant improvement, such as the 6 months or so Argos is trying to achieve, start to slow down as the trial matures and follow-up continues. This means that even if the company has observed about 25% of events at the mid-2015 time frame as the trial completed enrollment and then another 25% or so accrued by the mid-2016 time frame, you simply can't expect that 25% of events (eg., deaths on study for this type of study) will continue to accrue every 12 months. The rate should slow down if there is a positive impact being made with the addition of their product to standard treatment. This means, every investor should basically take the company's position on data timing with a huge grain of salt. There is simply no way possible the study reads out positively in early 2017.

If the data committee stops the trial early at 75-100% of events in the early 2017 time frame, the study will most likely be very negative, meaning it will not have demonstrated OR will not have any chance of achieving even a modest (eg., 3 month improvement) survival benefit.

3) Caution to Silent Hunter and other investors (I'm now out and saved my butt with the crazy run up earlier in 2016) - this is truly a one shot on goal opportunity. This company has and continues to plow money into their process, facility and has completely missed a window of opportunity to invest in other trials, combinations with PD-1 inhibitors and explore their approach in other tumor types. If they had simply invested in more R&D and expanded the number of shots on goal, a modest yet insignificant improvement in the survival for their ADAPT study would ensure longevity. If they fail to achieve a significant improvement in survival in this single phase 3 study (which the FDA always indicates may or may not be enough for approval), the company goes belly up and everyone who has invested at a price of $4 per share or above will simply write off the losses for years to come. That would spell doom and Argos would be a penny stock. The IP would get licensed by the lowest / highest bidder and perhaps this approach would see the light of day in 5-7 more years.

Silent Hunter made some valid points, but fellow investors ought to review the realistic, well informed points above prior to buying, holding or selling.

Good luck!! The seas are about to get rough for the Argos ship.
 






Thanks for writing. I'll think about what you said. Yes, I'm an investor, and if I had a crystal ball that said this stock would go to $10 by the fall, but that would be a good point to sell, I'd take the money and run.

There is one other angle to this that is worthwhile to think about. It's related to the point you made regarding the risk of the stock. As I understand it, the independent committee is due to make an announcement regarding the success or failure of this stock on or before February, 2017. It's quite right to say that if this announcement is anything other then success, there will be a huge loss on this stock.

Now, this risk cuts both ways. In the last few days, a 10 percent owner, Pharmstandard International, bought more of this stock. Correct me if I'm wrong, but this creates a legal obligation on their part to hold onto this stock for some 6 months, making the earliest they could sell the stock late March, 2017. In other words, if the independent committee announces bad news in February, these guys get to watch helplessly as the value of their insider buy approaches $0. Last I checked, they owned something like 17 million shares already.

Yet for some reason, they are buying more. I would think that if anybody knew what the story is, it would be these guys. Unless they have some desire to throw money out the window, they must be pretty confident of success.

It's a few minutes before closing today, and I note that the stock is up some seven percent today so far. It may be that folks out there figure that they guys wouldn't be buying unless they were very sure things were going to work out.
 






Great observations indeed. Pharmstandard International (PSI) was the largest private owner and is now the largest public owner of ARGS. Regardless of success or failure with AGS-003 and the phase 3 kidney cancer study, PSI owns the rights to develop, commercialize and profit from AGS-003 in Russia and its affiliated territories. Take a page from Antigenics (now Agenus), where the only approval and commercial sale for the HSPP96 vaccine (Oncophage) is Russia. My guess is that PSI is simply keeping the capital flowing into ARGS and in some ways is probably buying shares as a result of the private placement and the milestones whereby they agreed to purchase up to $30MM or so in shares (see press release and details from earlier this year).

I wouldn't view PSI's continued purchase as a sign they are bullish but yet a sign they are committed to seeing this company through data before making any final decisions on holding, buying more or selling their significant ownership.

Also, I wanted to highlight the fact that Argos will simply not have final data and readout in February 2017 from their independent data committee. Again, if you have access to a reputable biostatistician, they will inform you that based upon all of the "known" factors around accrual, timing of 25% and 50% of events and lack of any real news to date for the phase 3 study, there is simply no way the study reads out early 2017 if it's positive. If it reads out in early 2017 the probability of a failed outcome is 99% or greater, so we should all hope the data committee simply meets and recommends trial continuation (longer-term follow up for events to accrue and data to mature).

If you bought because you firmly believe what the company is saying about final data in early 2017, you should watch this stock like a hawk and be ready to bail. My statisticians have modeled the projected outcomes from this study and the bottom line is that a late 2017 or early 2018 readout is needed for a positive study.

Good luck!
 






Fellow investors - do not read into the acquisition of shares by the largest shareholder in Argos. Pharmstandard holds approximately 33% ownership in Argos based upon their current allotment of more than 13MM shares and the total outstanding number of shares being in the low 40MM range. They are systematically purchasing shares on a monthly basis and will most likely continue to do so based upon their agreement to purchase shares amounting to nearly $30MM in total, based upon the predominantly inside round earlier in 2016.

My statistician agrees with the former post, positive data will require longer term follow up. We are in a holding pattern and do not anticipate final data in early 2017, but Argos management is going to continue to stick by their story through early 2017. If topline results are not available, you can count on Argos management stating something like the following:

"Due to the reduce pace of events or deaths on study over the past 6-12 months and the likelihood the better prognosis study patients are living longer, we do not anticipate reaching 100% of required events or deaths on study to allow final readout until later this year or early 2018."

If the trial reads out in February, we can all write off our losses as the study will be negative.
 






I found this video helpful. The executive seems to be very straightforward with his discussion regarding enrollment and expected progression. It was their expectations as of March 2016.

https://www.youtube.com/watch?v=nCtb82J7Dk8

In the video, he says that Argos is expecting to hit 50 percent of events in June (which they did), 75 percent as of December 2016, and 100 percent as of mid 2017. (June, I guess).
 






It should be remembered that the FDA put this AGS-003 on the fast track program. Under this program, AGS-003 could be conditionally approved prior to having all the qualifying events met. The specific goal is to avoid the years of approval required by the traditional process. The clinical trials still proceed to dot all the i's and t's, but the drug is out there on the market. (In the unlikely event that it fails the later trials, the FDA would later remove the drug from the market). On the FDA site, cancer is specifically mentioned as one area where the FDA would like to see multiple treatment options and is looking to expedite treatment options. To get this approval, these are some of the conditions they are looking for:
  • Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
  • Avoiding serious side effects of an available therapy
  • Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
  • Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
  • Ability to address emerging or anticipated public health need
Remember that AGS-003 is not toxic. That was established early on. I really think that even a modest benefit (3 months) may be enough to get fast track approval, because the existing front line treatments do have some toxic side effects.
 






Good points, but I think you are missing the extensive risk associated with a single phase 3 study (SPA approval and fast track designations provide no guarantees that a modest benefit will do anything other than require at least 1 if not 2 additional phase 3 studies). This will very likely turn into another Dendreon situation, where their initial phase 3 study was not sufficient for approval and they ultimately conducted another large phase 3 study which delayed their approval for another 3-4 years.

The lack of transparency from Argos regarding their p3 study outcomes should concern all investors. Again, biostatisticians who have modeled their study, indicate that based upon survival expectations, study design and event rates to date ... the events should be slowing down. While 50% of events / deaths occurred around mid-2016, meaning 25% of events had accrued since mid-2015. Perhaps 75% of events will accrue by mid-2017 and thus it is more likely that a slowing of events due to the better prognosis and longer survival of the good patients on their study (what they refer to as the intermediate risk factor patients) suggests that the final data will not be available until late 2017 or 1H 2018 at best.

Again, you make some great points and you're operating with the glass half full for this one product, one phase 3 trial, unproven biotech. I'm happy I sold when the stock peaked earlier this year and happy I didn't hold on for the downward spiral that appears imminent when they don't report anything other than trial continuation early in 2017. If they report topline data, the study is highly likely going to be negative per my statisticians review and projections.
 






Argos has actually addressed a lot of the concerns you've raised, and the way to get these answers is to go to their website and listen to the webcasts that they give to investors. There's no secret here, I think all you to do is give your name and an email address, and can listen to what they have to say.

For example, you feel that Argos has not been transparent with phase 3 outcomes. Listen to the June 16 webcast that they gave to investors. Argos says pretty directly that they can't give out this information. Fast forward to about 29 minutes into the webcast. Somebody asks a clever question what the margin is between the control arm of the study and the one where AGS-003 is being tested. That's really an indirect way of asking how compelling are the treatment outcomes.

Argos' reply is this: the independent monitoring committee (IDMC) will not permit Argos to share this information with the public. The IDMC is following the O'Brien-Fleming approach to analysis, and they don't want outside pressure being brought to bear until all the results come in. Think about it: if news gets out there there this may be a vaccine that more effective than the current standard of care, then tremendous outside pressure will be brought to bear on the IDMC to approve the vaccine sooner rather they later. By not releasing this information, this allows the IDMC to do more testing. It's a more scientific and objective approach.

By the way, it's the IDMC that keeps track of the number of events. For the reasons mentioned, they don't release any sort of "progress bar" with the public. During this webcast, Argos says that based upon their own unofficial tally, they have "more than half" (not half) of the number of required events already. Something to remember is that for every day that this trial continues, and the IDMC does not end it for futility (290 deaths), it makes it more likely that they will approve this. If the patient is not dead, he's alive, and the longer the survival benefit is extended, the more compelling the vaccine is.

During the June 16 webcast, Argos themselves makes the point that we don't need to go to the end of the trial in order for the product to come to market. You're missing this point every time you say we need to wait for full data read out. We may not have to wait until June 2017 or 2018. My own guess is it could be as early as October. In October, you reach the point were should could give conditional release for the vaccine, based upon it demonstrating that it extends overall survival at least as long (15 months) as the existing standard of care, yet is less toxic, which is no small detail. Were the FDA to give conditional approval, patients could start receiving the benefits of this vaccine in about a month. During these highly political days, I'm sure Joe Biden or the President would like to say that during their administration, progress was made with cancer treatments. Argos would still have to complete the trials, but the product is actually out there on the market and would only be withdrawn if bad news happens later. Take a look at what just happened with Sarepta Therapeutics getting their early approval. (Maybe the FDA rushed it too much, even.) The point is, lately the FDA seems to be erring on the side of approving drugs on the early side. Patients benefit. If there is only one treatment, the price is high, but when there is a second option, prices for patients come down.

By the way, Argos does have an HIV pipeline. I know they had a trial that had problem because it did not meet its primary endpoint. But, that trial actually showed AGS-004 has some clinical benefit, and the drug might be useful if used in a different way. That AGS-004 trial is progressing.

Finally, you raise a concern regarding risks. Sure, you can buy this stock, get bad news, and watch as you lose money. Is that the end of the story? Not exactly. "Play it safe", and put the money into cash instead, and await developments. Figure that you'll buy this stock if and only if good news comes out, and it is FDA approved. The only problem is, you won't be buying this stock for $5 a share - it will be considerably more expensive than that, to put it mildly. The other side to the risk/reward question is always the question of opportunity lost.
 






Confirmed - Silent Hunter is not being transparent and is NOT an investor. This individual is an employee of Argos and either resides on the commercial or investor relations team.

Note to other investors who browse this area - Silent Hunter is a newly created profile by Argos. I've informed the SEC and hope they will continue to evaluate and investigate this company and their rogue employees and leadership who continue to make false promises and statements regarding timing of their phase 3 study readout in kidney cancer.

This company is spending millions on facilities and a never before created or validated automated manufacturing process. They have tons of risk and continue to be less than forthcoming with the investment community.

Silent Hunter needs to retire his blog here and go back to focusing on business at hand.

Per a reputable individual with strong connections to the study and the company, the phase 3 study readout is looking like late 2017 to early 2018 at best. As one other post on here has mentioned many times, the rate of deaths on their study has slowed and it appears as though the better prognosis patients are surviving longer. That's a good thing. Don't buy the hype (if you did a month or so ago, then sell when this stock is above your strike price) that final data will be by early 2017.

Garbage in Garbage out. Let's hope the product actually works ... time will tell that as well. Time meaning late 2017 or early 2018 at best.
 






Read previous post about Silent Hunter - aka insider / employee in the commercial or investor relations realm at Argos. Ignore all posts from SH and realize this is an employee trying to pump up their stock for investors like us who read the postings here and elsewhere to gather insights.

One other key point that Silent Hunter disregarded. This company doesn't have a facility to produce their product and is in the process of building and outfitting and validating (usually takes 18-24 months from start to finish) a new commercial manufacturing facility in Durham NC. This facility would not be ready for any early approval for their product and the reality is - Silent Hunter is blowing smoke out of his butt and ears when he remarks that FDA will approve a non-toxic product early based upon similar efficacy and better safety than standard treatments in kidney cancer. Their SPA agreement requires Argos to achieve at least a 6 month improvement in Overall Survival for the FDA to consider the product for review and approval. They also consistently highlight in their SPA reviews that 1 phase 3 trial may be inadequate. Thus, if the survival isn't robust, despite the safety, the product will not be approved when the trial matures and they reach 100% of events, let alone even fathoming the product would be approved mid-stream prior to trial completion because it's safe.

Guess what, placebo is quite safe and non-toxic, but has never been approved.

Silent Hunter - please crawl back into your cube or office at Argos and stop posting here.
 






As I mentioned, I'm an investor, not an employee. Ad hominem attacks aside, you wrote
one thing that is interesting. You say that the SPA agreement requires Argos to achieve at least a 6 month improvement in Overall Survival for the FDA to consider the product for review and approval. Do you know of a link to this agreement? I'd like to read it for myself. Thanks.
 






Ad hominem is appropriate if you are portraying yourself as an investor. You sound like an insider / employee trying to justify your position. Whatever the case may be, you can simply plow through the early quarterly call transcripts and IPO documents. Leadership has been asked and has routinely indicated that success on the phase 3 trial, according to the statistical plan and design, which is part of their approved SPA with the FDA, indicates they are targeting an approximate 6 month improvement in survival when AGS-003 is added to standard treatment.

Happy reading "Silent Hunter".
 






I went back and read the original prospectus. Interesting reading:

http://ir.argostherapeutics.com/secfiling.cfm?filingID=1193125-14-40941&CIK=1105533

Here are some points that interest me and are worthy of further thought:

1) The above document actually says that as of December 31, 2013, they had enrolled approximately 100 patients in the phase 3 clinical trial. (Other documents indicated they had completed their enrollment of 462 patients on July 15, 2015). This means that the IDMC would have had a 30 month look at these 100 patients in June, 2016, when they recommended continuation of the trial. As you know, in the phase 2 trial, a 30 month survival was observed in 21 patients when Phase 2 was concluded.

2) The original goal, approved by the FDA, was completion of enrollment by December 2014 and data by the first half of 2016. In other words, 1.5 years from trial beginning to data being available. So, 1.5 years from July 15, 2015 would be Jan 15, 2017. We note that a review is currently scheduled for Feb. 2017 which would be entirely consistent with the original timeline.

3) It does say: "Based on the design of the trial, the data from the trial will need to demonstrate an increase of approximately six months in median overall survival for the AGS-003 plus sunitinib arm as compared to the sunitinib monotherapy control arm in order to show statistical significance and achieve the primary endpoint of the trial."
 






Happy reading again - glad you were able to locate the goals of the study from the details shared a few years back.

The reality is the study will not conclude early and unfortunately the assumptions you outline regarding trial completion in 1.5 years from conclusion of enrollment is not only unrealistic but impossible based upon what the company has reported.

As my biostatistician has shared based upon modeling, the "actual" enrollment pace between early 2013 and mid-2015 will have an impact on expected deaths and the accrual of 25% of events as of June 2015 coupled with 50% of events / deaths being reported as of June 2016 also impacts expected timing for data readout from this study. In essence, if the 25% of events continues to take about 9-12 months, this means we are waiting to reach the 75% mark in 1H 2017 and most likely will not see final data and 100% of the required events until late 2017 or early 2018.

Glad you are now "clear" on the realistic timing of things. This is where ARGS management continues to mislead the investment community. If there were a striking difference between the 2 arms to date, I'd be hearing anecdotes from the key cancer centers who have been participating, but the reality is nobody is saying anything positive or negative. This is an indicator the study will proceed to 100% of events prior to unblinding, as you and every investor ought to expect for a single phase 3 trial under SPA with the FDA.

Happy silent hunting today in the market!!
 






One final comment and reply to SH regarding prior comments about Argos' HIV program. As you might expect, analysts and the majority of the investment community has dismissed this program as anything other than a pure science experiment. Their failed study reported in early 2015 highlighted one of many challenges in this population when they failed to meet their primary endpoint. Although their CSO always seems hyped about this program, it's clear he has a vested personal interest and bias in this program. Other investors agree that you must completely discount this program and focus on Argos being a 1 product, 1 study opportunity. That's why this company represents the very highest risk with the potential for tremendous returns, should the phase 3 study prove to be highly successful. However, just like Dendreon, this company is going to have to figure out how to mass produce and distribute their fully personalized product to be successful and deliver the returns on everyone's investment. In my humble opinion, they are 3-5 years from proving this .. which means one can only hope the phase 3 study is positive and that the FDA believes in their capabilities to consistently produce and deliver a high quality product.
 












Great question - read the details below. Not a chance the AGS-003 study qualifies for any type of accelerated approval. If you have invested in this stock / company based upon that expectation, I'm sorry to inform you that you have not been properly informed on the subpart H approval process.

http://www.accessdata.fda.gov/scrip...RPart=314&showFR=1&subpartNode=21:5.0.1.1.4.8

The single AGS-003 phase 3 study under SPA is an agreement with the FDA based upon one "hard" and only one "hard" endpoint ... not a surrogate endpoint. The primary endpoint per every document and the study synopsis on Clintrials.gov is "overall survival" or OS. They either achieve the benefit and become eligible for review or they don't and they go back to the drawing board and determine if they should and can execute another pivotal study.

If the product were being utilized 4th line and demonstrated a respectable response rate, then it might qualify for accelerated approval, but Argos would have had to reach agreement with the FDA under SPA, that their study design would permit a surrogate endpoint for early assessment and review. Simply not the case for Argos. They live and/or die by their primary endpoint and that's why it is nearly impossible for any early readout from their phase 3 study. Their data committee and the FDA do not want any un-blinding to occur prior to 100% of events to ensure the highest quality study and prevent any bias from impacting outcomes and treatment decisions in a single phase 3 study.

Happy silent hunting in the markets today. ARGS is up big time (eg., a nickel or so) as you can see. They must be reading our banter and pouring dollars into this stock. Haha!!!!

All investors should continue to be very, very cautious with this high risk company. It would be different if Dendreon had been successful with their vaccine. But they failed miserably, beyond generating an approval for a product soon to be obsolete due to other treatment advances. The PD-1 and checkpoint inhibitor approaches could spell doom for AGS-003 and other personalized approaches in the kidney cancer space.
 












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