Argos Therapeutics

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Not obvious to me yet that your interpretation is correct. At issue is a sentence in your document which is admittedly unclear. I'm going to format the sentence below in a certain way, hopefully it makes my point. In other words, if AGS-003 has shrunk a bunch of tumors in 200 patients without toxicity, I don't see why they can't use that as the basis of accelerated approval.

FDA may grant marketing approval for a new drug product on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit

or

on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity.
 






SH - the Argos phase 3 study is a "single" endpoint, do or die study design. They either achieve a significant OS improvement (in the neighborhood of 6 months - recognize this depends on control OS and the delta between the 2 arms of the study, but the p value must be significant .. < 0.05).

There is NO surrogate endpoint, so you shouldn't waste your time, energy or dollars betting on an early trial readout. Argos has as much chance of an early trial readout in 1H 2017 (unless study is negative) as Bernie Sanders has a chance at becoming our next President.

Reality is reality, nothing more to debate. The weakness in the Argos approach with the FDA is that they have conducted a single pivotal study. The FDA prefers 2 to ensure the outcome isn't by chance nor impacted by any type of operational bias. At no point have you heard the company indicate an early readout based upon surrogate endpoint. There simply isn't one. Safety and response and PFS are nice to have secondary endpoints, but they clearly communicated the SPA is based upon an OS outcome alone.

In summary, high risk, low probably of high reward, good luck.
 






The trial has primary and secondary outcomes. The primary outcome measured is overall survival. Tumor response is listed as a secondary outcome to be meausured. So yes, they are measuring tumors all along the way.

https://clinicaltrials.gov/ct2/show/NCT01582672

Below is the FDA's discusson on Accelerated Approval. Watch the video, or read the transcript.

http://www.fda.gov/Drugs/ResourcesForYou/HealthProfessionals/ucm313768.htm

"Well for example, instead of having to wait to learn if a drug prolonged survival in cancer patients the FDA has approved drugs based on evidence that they shrink tumors. As a surrogate end point, tumor shrinkage is reasonably linked to real clinical benefit."

A bunch of folks out there think AGS-003 could be conditionally approved early. You don't feel this way. Is there anything you can point to, any documentation whatsoever, that says they have to wait all the way to the end, and are ineligible for the program that says they can get conditional approval today subject to Phase 4 confirmatory trials?
 






Simple - there is no precedent for early approval unless there is agreement with the FDA that a surrogate endpoint is acceptable. The only situation where this would apply would be cancers where there is no standard of care and/or there are limited, inferior treatment options.

In the case of kidney cancer, there are multiple targeted therapies and now immunotherapies approved for the 1st, 2nd, 3rd line of treatment and beyond that have all proven to be effective in randomized studies. No accelerated approvals in this indication have occurred except for the initial approval of Sunitinib and Sorafenib (eg., based upon tumor response rates in phase 2 trials).

You're continued posting and focus on accelerated approval is entirely off base. A phase 3 trial with an endpoint of OS means the only path forward with the FDA is to hit the primary endpoint. Argos has never indicated a surrogate endpoint would suffice.

Argos simply will not have data in early 2017 and if they do it will be negative as it would indicate too many deaths on the AGS-003 arm and not enough separation or difference versus the control arm. No surrogates will suffice, so you should either ride the stock out through topline data (late 2017 or 1H 2018 based upon my statistician's projections) or get out.

Of course, you may not be able to get out because it's highly likely you're an inside investor. Happy silent hunting.
 






Some people might think "effective" means something other than dying after 15 months, which is the current survival rate for the high risk patients. So, as you know, this is a 2:1 randomized study. So, you get to some point in the study, let's say, 18 months, and you notice that the tumors are gone in AGS-003 arm but are still there in the control arm in 200 patients. You think the FDA says "Nah, we need to wait another two years before giving approval" ? That's the
purpose of accelerated approval in an age where you have Joe Biden calling twice a day to see what they are doing about cancer?

"Argos has never indicated a surrogate endpoint would suffice."

Actually, they've said in those conference calls that you haven't listened to, that we don't even need to reach the end of the trial for this to be declared a success. It would be rather absurd to think the FDA would want to approve this, but Argos would object.
 






SH - forgot one additional critical piece of "real" data that should help you and others understand why a surrogate endpoint is not going to be sufficient nor is it even a remote possibility for Argos and their lone phase 3 trial.

The only surrogate endpoints they could rely upon for any accelerated review and approval from their study would be response rate or PFS. If enrollment concluded mid-2015, both of these endpoints would have been fully mature on both arms by mid-2016. Interesting their independent data committee didn't stop the trial and only indicated "continue".

What does this mean? It means the results aren't overwhelming on the response rate or PFS fronts and the committee and the company and the investment community simply will need to wait for all events to accrue prior to topline data and unblinding. That's how pivotal phase 3 survival trials work in cancer.

Hopefully that helps you realize the reality that trial readout will not be early 2017 ... of course unless there are too many deaths on the AGS-003 and not enough separation / difference between the arms! Then early readout will equate to ARGS death and it will quickly convert to a penny stock.
 






Anonymous says:

"The only surrogate endpoints they could rely upon for any accelerated review and approval from their study would be response rate or PFS."


The FDA says:

"Well for example, instead of having to wait to learn if a drug prolonged survival in cancer patients the FDA has approved drugs based on evidence that they shrink tumors. As a surrogate end point, tumor shrinkage is reasonably linked to real clinical benefit."


Tumor response is one of the outcomes being specifically measured on an ongoing basis in the trial.

Time now to listen to more hand waving and opinions from anonymous, without links to documentation that back up what he's saying.
 






Baseless pontification by Silent Hunter a.k.a. Current Insider / Employee / Long-term Investor at Argos.

His/her argument regarding early trial readout are simply nonsensical. For those investors who aren't directly tied to Argos management and don't have a long-term stake in the company ... you should base your stock buying and dumping (suggested) for ARGS on the following reality:

1) Argos phase 3 study is a win or lose outcome only and the data will only be unblended and shared when they reach 100% of required events on their study (eg., deaths on study - which they have indicated in the past is 290 deaths).

2) Response rate and PFS for this study would already have been known (response - 2015; PFS by early 2016), meaning if there was any unexpected and thus significant difference between the arms, the study DMC would have recommended stopping the trial and the Company would have approached the FDA. Neither has happened. Ignore SH - he/she is an insider for certain based upon the postings.

3) Uncontrolled phase 2 data with a highly exploratory immunologic finding (T cell changes) will not necessarily predict the phase 3 outcomes. This is an extremely high risk company and study because of their inability to execute a broader development program and thus allow their chance for success to be based upon 1 shot on goal ... the phase 3 study in kidney cancer.

4) SH is a long-term investor in Argos and is simply pontificating and creating false perception because he/she has been hired / charged by inside mgmt. to dispel any truths or realities being suggested on Café Pharma.

Listen to your gut ... if Argos is going it alone and continues to overpromise regarding early trial readout ... and reality hits in February 2017 when the study simply continues and they wait for 100% of events to occur prior to unblinding results and analyzing outcomes - you will know that the Anonymous yet highly intelligent and informed investor on CP has provided you with excellent guidance in deciding how to manage your investment in ARGS.

As always, be careful, hold onto your seat and don't listen to the nonsensical unfounded perspectives from insiders or mgmt. that the Company will have a final readout on the phase 3 study by Feb 2017. If they do, it will be negative. If they don't, it's because my team and statisticians are still the best in the business at modeling outcomes based upon publicly available information.

Simply stated - we are correct. SH is dreaming and he/she will stop responding soon.
 






I guess it was time to change the subject. Anonymous didn't like how the early approval based upon tumor response discussion was going. As usual, we note that he can't provide links or other supporting documentation to counter the link provided that specifically says the FDA can give early approval based upon tumor shrinkage. He's right about one thing though. I'm not going to discuss this further until he can provide a link, documentation, etc. that backs up his claim that AGS-003 can't be approved early. I provide my links and documenation, he doesn't.
 






urgent news - Argos will not have the required number of events for any trial readout in Feb 2017.

Early readout for response and PFS would have occurred 6-12 months after enrollment concluded.

Silent Hunter has no facts and provides meaningless links.

Silent Hunter is an insider and is trying to fool the investment community just like Argos management.

The SEC is watching this company closely and will act accordingly when they have nothing to report early 2017 from their study other than "trial continues" due to insufficient OS events.

If you follow this company because of stock ownership, sell when you are at break even, don't drink the Silent Koolaid and start to recognize Argos is a 2nd generation Dendreon. Only difference, they will nOT get approved unless
 






... Will not get approved unless they demonstrate a significant survival advantage which will only be determined when their ONE and only ONE shot on goal phase 3 study reads out in late 2017 or early 2018.

PS: Silent Hunter has lost millions and wants to recoup their company's investment. Hopefully Silent Hunter will take their losses and go invest in ...

Kite or Juno or BMS or Novartis


Those are "real" immunotherapy companies who actually know how to successfully develop and commercialize off the shelf immune therapies at scale.
 






anonymous said:
... Will not get approved unless they demonstrate a significant survival advantage which will only be determined when their ONE and only ONE shot on goal phase 3 study reads out in late 2017 or early 2018.

PS: Silent Hunter has lost millions and wants to recoup their company's investment. Hopefully Silent Hunter will take their losses and go invest in ...

Kite or Juno or BMS or Novartis


Those are "real" immunotherapy companies who actually know how to successfully develop and commercialize off the shelf immune therapies at scale.
Click to expand...
 






Well, there goes Pharmstandard once again buying more shares trying to pump up the stock price without any news and the long, long runway to data the Argos management team continues to mislead everyone about. At the current pace of buying 20-40k shares every few weeks, Pharmstandard will be the majority owner of Argos once their phase 3 study in kidney cancer reads out in late 2017 / early 2018.

As always, buyer (eg., investors) beware. You can't trust management and certainly can't look at insider buys (no selling) as an indicator of strength ... it's simply an indicator of what will soon be a wholly owned company based in Moscow in the next 2-3 years.
 












No - you shouldn't trust anything ARGS leadership issues in the form of a press release or call regarding expected outcomes. Long term follow up will be key to their success. Their leadership team will recant their position early 2017 that they expect an early trial readout. They will spin it to indicate the rate of events could only indicate that patients receiving AGS-003 are benefiting, but that's no guarantee. Definitely higher probability of success the longer it takes this study to readout, so an early 2018 readout might be "solid". Anything sooner could be disastrous.

Chuckie is not to be trusted. :)
 












Great outcomes for 2 patients, but hard to leap to phase 3 success based upon these results.

Just curious, why didn't they publish these results in NEJM or JCO? Would have been more impactful.

In any event, the rest of the investors out here already know that SH's comments and links are inherently informed and biased due to their insider status with Argos.

Good luck with that Feb 2017 readout of "nothing" and then management's request for more funding to get to the final data and real outcome of the phase 3 study about 9-12 months or so later. :)
 






Hey SH - just read that link you provided to the astute investors out here. Quite intriguing that Patient Case #1 had such a remarkable response that based upon imagery, the following occurred:

1) His lungs turned into his liver
2) His liver turned into his lungs

Why did his immune response decline? Hmmmm ... lots of other errors and omissions in this write up, so highlights why it wasn't submitted to NEJM or JCO and that the editorial review was limited at best.

Conclusions:

1) Anything SH posts our here is filled with insider bias and intent to deceive other investors.
2) The SEC continues to monitor this company and their practice of provided misinformation.
3) Argos study simply can't read out in early 2017 or it will be negative. They need at least 50-60 of these types of responses in their phase 3 study to have a chance of delivering an overwhelming survival benefit.
4) Wait for that "vanilla" press release in early 2017 when the study data committee says nothing but "continue"
 












Not sure anyone else out here believes you are not an insider based upon yours posts and peculiar timing of becoming an active board participant.

But nonetheless, if you are an independent investor, you are one of many who will suffer great losses over time with this stock unless the phase 3 study is positive. One or two patient successes in a disease such as advanced kidney cancer do not predict outcomes for the entire population, especially when the 2 cases you referred to in the recent Kidney Cancer Journal issue represent relatively young patients. They have much greater potential to recapture the innate immune response than the average 60-70 year old patient with kidney or other cancers.

Keep that in mind SH and as always ... good luck with your position in ARGS and belief that an early outcome will occur. If we could place a bet, I'd ask you to go all in as would I and unfortunately you would be the loser at the end of the day when Feb 2017 rolls around and readout is simply "trial must continue" or "negative" due to lack of benefit.

Go Chuckie and team Go!
 






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