Ah, ok, wait. I was thinking about tumor size here but your original remark was that the patients would otherwise die in 3 months, which is not correct. The data shows the Mean OS at 8.5 and 11 mo for the chemo they were on. So, we would not expect them to all be dead by now if they did not receive Multi-TAA.

What is impressive is that of the five patients in Arm A who've been treated long enough to make it to the Median OS, four of the five are still alive. And only one patient died before the Median OS so far. Hopefully that trend continues.

Ok, thanks that makes sense. On slide 14 it said response to chemo usually occurs in the first 3 and plateaus or tapers off, and that after a tumor increases in size additional chemo is not likely to slow or reverse it. It makes the response for Arm B that much more impressive since they did not respond to chemo and still 3 of six became clinically stable.

"we can't take 1 CR out of 9 and say it means we'll have 11% CR rate in a much bigger sample size"

Man wouldn't that be something! But no, I think that would be expecting a bit too much.

Why do you say the patients would die in three months? The "7 of 9" alive refers to Arm A where the patients are getting chemo and the Median OS is 8.5mo and 11.1mo.

Because of the size of populations in those two studies I think 0.5%-2.9% would be pretty reasonable estimate for CR for the general population for Folfirinox treatment.

Re. Complete Remission (CR). Here's one larger study from last year looking at CR in what is called Locally Advanced Pancreatic Cancer (LAPC), which is Stage 3 cancer and metastatic pancreatic cancer (as opposed to our study looking at Stage 4, metastatic cancer).

They analyzed 11 studies with a total of 563 patients and found "The pooled complete response rate (CR) was 2.9%."

So CR is rare even when including Stage 3 pancreatic cancer patients which have significantly better survival rate than Stage 4 pancreatic cancer (see below).

https://www.nature.com/articles/s41598-018-26811-9

------------------

Here they discuss the criteria for the different stages and survival rates of cancer:

Localized: There is no sign that the cancer has spread outside of the pancreas. This includes stage 0, I, and IIA cancers.

Regional: The cancer has spread from the pancreas to nearby structures or lymph nodes. This includes mainly stage IIB and III cancers.

Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones. For pancreatic cancer, this includes stage IV cancers.

And the 5 year Survival Rates for each:
Localized 34%
Regional 12%
Distant 3%

https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html
------------------

Here is a link that defines criteria for Complete Response, Partial etc (p. 2):

https://www.cibmtr.org/DataManagement/TrainingReference/Manuals/DataManagement/Documents/appendix-n.pdf

The Arm A data does seem a bit confusing but if you look at slide 14 it appears to show the Arm A patient's data before and after chemo for the first three months (grey area). Specifically they appear to be measuring the size of a target tumor in the pancreas (Y-axis). With the info we have so far it's not clear if they measured lymph nodes or other metastases which can also be considered in the categorization of pancreatic cancer.

https://www.markertherapeutics.com/wp-content/uploads/2019/07/TACTOPS-Investor-Presentation-FINAL-7-21-19-PDF.pdf

Each seems to show what appears to me as stable disease or partial response between the start and end of the chemo-only period (grey). But to me it looks like Patient's 5 (medium blue), 8 (dark brown), and 9 ("too early to tell") all had slight progression of disease during chemo only so I wonder why they are not in Arm B.

But IIRC anything less than a ~20% change is considered stable disease.

Similarly for Arm B, to me it looks like Patient 2 (brown) had a stable response to chemo but is not in Arm A. . . ???

Hopefully it's all cleared up during the CC and before the market opens.

After a brief search what I posted is the best I could find. I did come across a few case studies with Complete Responses (CR) but they all just noted it was extremely rare and "antecdotic," I believe was the term used in one paper. In the ones I could view on line I did not find any references to large scale studies or data concerning CRs other than the 2011 NEJM study I posted.

Re. Complete Response in Pancreatic cancer. I'm posting this just to add to our perspective since Folfirinox and gemcitabine were the standard of care treatments used in our present study.


In this study comparing Folfirinox to gemcitabine there was 1 Complete Response (CR) out of 343 patients. The one CR was in the Folfirinox group of 171 patients. See Table 2:


FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer

https://www.nejm.org/doi/full/10.1056/NEJMoa1011923?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed

-----------------------

A 3-year disease free survival in a patient with metastatic pancreatic adenocarcinoma following folfirinox chemotherapy: A case report.

"Complete response is a rare outcome in patients with metastatic pancreatic cancer. . . In our patient, a complete response was achieved after 35 cycles of FOLFIRINOX over 16 months. . .

To our knowledge, we present the first case of a patient with metastatic non-resectable adenocarcinoma of the exocrine pancreas to achieve a complete response and continues to be on a 3-year disease free survival after monotherapy with FOLFIRINOX."

http://www.alliedacademies.org/articles/a-3year-disease-free-survival-in-a-patient-with-metastatic-pancreatic-adenocarcinoma-following-folfirinox-chemotherapy-a-case-repo-10396.html#3

Just for convenience sake and to see if I missed anything these are our sources of info from the past couple days. ? .


Marker PR with links to the AACR presentation and Monday's investor's presentaion:

https://www.markertherapeutics.com/2019/07/marker-therapeutics-reports-interim-results-of-its-multitaa-t-cell-therapy-in-patients-with-pancreatic-adenocarcinoma-at-aacr/



AACR article with abstract:
https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1324

https://www.aacr.org/Documents/Smaglo%20abstract.pdf



Article from Healio HemOnc Today:
https://www.healio.com/hematology-oncology/cell-therapy/news/online/%7B9f1dc18d-9a02-4b7c-8c17-dbb24f0a757a%7D/nonengineered-t-cells-may-be-clinically-meaningful-for-pancreatic-cancer?utm_medium=social&utm_source=twitter&utm_campaign=scheduledpost&page=2


Article from MedPage Today:
https://www.medpagetoday.com/meetingcoverage/additionalmeetings/81131

"How in the hell do you do a third phase pancreatic trial and give a patient who is surely dying a placebo and test that against an experimental treatment for a cancer that has a small success rate of omission. "

You can do a randomized, double blind, placebo controlled study where you essentially are comparing to standard of care. One group gets standard of care treatment plus experimental drug/treatment, and one group gets standard of care and a placebo in place of the experimental.

Here are a couple examples:

Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial.
https://www.ncbi.nlm.nih.gov/pubmed/26067687

Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer.
https://www.ncbi.nlm.nih.gov/pubmed/23642329

Thanks everyone for sharing data and opinions about the data. It's very helpful and it's greatly appreciated.

I bet we gap up on the open Monday when sane people hear the data before the market opens. No way did any institutions sell today on this news. A lot of retailers were expecting 100% radiographic complete responses and shit themselves today.

Looks like support at the 200day EMA at 6.46.

http://schrts.co/weNEDBPA

I don't have time to look at this more but I don't think "More than half of patients with pancreatic adenocarcinoma showed clinical responses" warrants a sell off like we're experiencing. The boat awaits. . . I'll be interested to see how the day ends.

I don't think safety data would warrant presenting at the plenary session that opens the conference.

Didn't they have a pretty low target price to begin with, around $8? Or maybe that was some other analyst. Yeah I'm not worried. I look forward to years of analyst underestimating the price.

Thanks makes much more sense. Thanks for the correction guys.

Pretty sure by "optimized" they are talking about the number of cells infused during therapy. In the PC study they're using 10 million cells per infusion. Most of our clinical trials use 5-20 million cells per infusion, with one using up to 100 million cells. I'm not sure what criteria were used to derive these cell counts, but IIRC Peter said it was about 1/10th the cell count used in CAR-T, so the idea might have been to aim low so to speak to avoid adverse reactions/toxicity. Also the primary endpoint for this study is safety, with efficacy as a secondary endpoint, and as discussed in the CC optimizing the cell count targeting efficacy would be the primary endpoint of a PII trial.

We must at or near Zack's price targets:

Zacks Investment Research, Inc. downgrades MARKER THERAPEUTICS INC from BUY to HOLD.

BY Investars Analyst Actions - private

— 10:12 AM ET 07/12/2019

On July 12, 2019 Zacks Investment Research, Inc. downgraded MARKER THERAPEUTICS INC (MRKR) from BUY to HOLD.

Switch to exponential moving averages and the 50 day crossed the 200 day EMA about a week ago: http://schrts.co/udspSrjG

And on the weekly the 20wk crossed over the 50wk about a week ago too: http://schrts.co/YVnkBhIA

Hopefully those moving averages don't catch up to us for a few weeks at least, lol.

I could see us moving up to $10-$13, in the range of last year's highs, leading up to the 22nd. And then assuming reasonably good news maybe $17ish to hit the high from 2015. Or, maybe we hit the 200 week EMA at $51?

http://schrts.co/evIjVCvS

Re. Plenary presentation


Saturday, July 20, 2019

Breakfast
7-8 a.m.

Plenary Session 1: Cellular Therapy Clinical Updates (I)
Session Chair: Christine E. Brown, City of Hope National Medical Center, Duarte, California
8-10 a.m.

Chimeric antigen receptor T cell therapy for chronic lymphocytic leukemia
Saar Gill, University of Pennsylvania, Philadelphia, Pennsylvania

CAR-T antigen evasion: The emerging role for multi-targeted CAR therapy
David Miklos, Stanford University, Stanford, California

Advancing CAR T cell therapy for treatment of brain tumors
Christine E. Brown

Targeting pancreatic cancer using nonengineered, multiantigen-specific T cells (TACTOPS)*
Brandon G. Smaglo, Baylor College of Medicine, Houston, Texas

Cellular immunomonitoring for the first personalized adoptive cellular therapy trial using defined multiple targets (ACTolog® IMA101-101)*
Anna Nowak, Immatics Biotechnologies GmbH, Tübingen, Germany

Break
10-10:30 a.m.

https://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=178&DetailItemID=1011#Plenary%20Session%201

Apply your reasoning to going long. Which of your two purposes of the stock market does your short term trading fall under?

Should short term long-only trading be allowed? Is that an "artificial means to manipulate and (increase) a stock price?" Is that "artificially created demand?"

When you make trades are you doing it to help the company? Are you trying to influence the share price? Are those the reasons institutions buy, or go short?

Shorting is not "artificial pressure." It is one of the tools the market uses to gauge a fair price. Everyone knows about it so there is nothing unfair about it. The short shorts because they genuinely believe the security is overpriced. The short is not Snidely Whiplash, and the long is not Dudely DoRight.

Edit: Just a FYI, I don't think you're a pain in the arse talking about the short position. I like hearing about it.

"If and when they cover it will all happen again at a different price albeit at a higher price. "


It's funny because I had the same thought earlier today. How the total shares short might not change because as a lot of shorts will get burned, at some point others will start to pile on to replace them. But the key is, like you said, it will be at a "higher price." That's fine with me. The shorts can play hot potato all the way up for the next few years.

I don't think there is anything wrong with shorting, it has it's place in the market. They can help prevent a stock from getting grossly overvalued and as a result longs might not lose as much if the company disappoints and the price drops. Also, shorts do help put the breaks on when they start covering if a stock takes a tumble.

I would not be surprised if a lot of shorts placed the last few months were whiplashed in and out a number of times already just like traders going long can experience.

One thing about your analogy that is not accurate is the "setting fire to the house" part. If the company doesn't perform, they're the ones setting the fire. If the company delivers, the shorts are the ones set on fire.

If I had confidence in the company and I were hoping to get in on the private placement sometime later this year or next, I'd start soaking up shares at this level while I waited. After the last round, I would not want to end up empty handed because was over subscribed again. And besides, the placement price will likely be significantly higher than the current price.

Yeah, based on the cc it sounded like one of the analyst, I forget which one, was pretty surprised at how quickly they maxed out enrollment. And iirc Peter said cancer patients and their physicians tend to be very knowledgeable and aware of what's going on in terms of clinical trials, and the rapid fill would suggest there was a hint of success in our trial. I don't think he actually said that second part, but someone can confirm or deny in the morning.

The 200 day EMA is at $6.06. So we got that going for us.

With our addition to the Russel 2000, even if we do not see a substantial change in share price we at least know some of the float is being absorbed by more institutions.

Can you provide a link to the twitter . . . "announcement"???

I see nothing on MRKR's Twitter page. I see nothing at the link you provide to aacr and the only thing I see on slide 48 is the reference to the pancreatic clincial study.

Well that was The Good, The Bad and The Ugly. If you are a fan of It's Always Sunny in Philadelphia you might think Dee and Charlie have produced the Sach's video today.

I don't think this is Peter's fault. The two notes on the youtube page for the video seem to make it clear it was Sach's fault:
"SachsTV" ?Dear Viewers, presentation will start approximately 10 minutes later than planned.

"SachsTV"
?Please accept our apology for interuptions....We are experiencing technical difficulties.... (sic, cubed)

Way too many "Technical difficulties."

And Sachs didn't organize the event very well by the sound of it. You could clearly see Peter lose his concentration a couple times when you could overhear what sounded like another talk in the background.

But after about the 19 minute mark I think Peter hit's his stride and does an excellent presentation. Unfortunately we didn't get to see some of it due to the video cuts/skipping, but at least those in attendance did get to hear the rest.

I really liked the more in-depth explanation on the cell culture methodology at 19:08-20:35. It's frustrating it got cut off.

The discussion of the Lymphoma trial was outstanding and I now understand it much better.

I think he did a better job at explaining the data than he did in the past. It seems like he has refined the presentation based on questions audiences have had in the past. I think he defined some of what most of us would call jargon, and what most of us laypersons were not likely to understand.

So missing out on some of the talk really sucks, but most of what was presented, if you can tolerate the Technical difficulties, was excellent IMHO. I think institutions, unlike retailers, are much more likely to overlook the noise and get excited about the actual data.

Nope. Long story, but nope.

rwwest, from:

http://www.virginia.edu/vpr/irb/HSR_docs/CLINICAL_TRIALS_Phases.pdf

"Phase IIb: Well controlled trials to evaluate efficacy ( and safety) in patients with the disease or condition to be treated, diagnosed, or prevented. These clinical trials usually represent the most rigorous demonstration of a medicine's efficacy.
Sometimes referred to as pivotal trials.


Phase IIIa: Trials conducted after efficacy of the medicine is demonstrated, but prior to regulatory submission of a New Drug Application (NDA) or other dossier. . . "

Micro, I remember being in a biotech years ago and the stock mysteriously started moving up without any catalyst. And then within the same week the company announced a private placement and jeez whatdayaknow, the stock just happens to be a few nickels over the newly announced share offering price. I don't know how that works or how it is legal.

As for MRKR doing nothing, the stock did run from $3 to $12+ on the merger announcement last year. So of course it only makes sense we float back down here . . . /s

Yeah microcapI, I wish there was more buying too, lol!

I was a little surprised and impressed with our activity Wednesday, going through a million shares while steadily working our way up all day off the lows at the open. It looked like capitulation to me. Lots of traders and disappointed longs cashed out and yet we kept creeping back up after every volley of selling. And of course some shorts probably piled on (and took one in the knuts as we climbed all day), but smart shorts covered.

I would expect that kind of volume would be more likely to attract a large buyer or two and they could be patient while lemmings exited. That sort of applies to the whole month so far. With people losing patience and the increased volume we had, I guess I kept expecting us to fall further and faster than we did.

It will be interesting to see the changes in shares short and institutional holdings after this mostly nonevent.

The delay until we hear about the pancreatic cancer trial gives institutions more time to buy shares from weak and impatient hands. Judging by yesterday's volume and price activity I'd say I agree with those who said the other day they thought we were under accumulation.

Just a reminder:

April 17, 2019
Abstract titles released online via ASCO iPlanner

This is timely.

Overcoming the Limitations of CAR-T Therapy: Burnout
https://oncobites.blog/2019/03/19/overcoming-the-limitations-of-car-t-therapy-burnout/


This one is a year old but new to me. The ending about Provenge using prostate cancer-associated antigen is very interesting. I don't know how their therapy works but the fact that they have success with one antigen, where as we use multiple antigens, is sort of proof-of-concept independent of MRKR labs.

Cancer Vaccines: Educating Your Immune System Since the 1800s
https://oncobites.blog/2018/05/16/cancer-vaccines-educating-your-immune-system-since-the-1800s/

Hi erg61, I'm not really sure I understand what you are asking so let me know if I don't answer your question. Anyone else with thoughts on erg's question please feel free to chime in.

If you mean how does our therapy compare to the Applied Science's CAR T cell therapy in terms of the biology, the big difference is we don't genetically engineer the T Cells. We recruit T cells already present in the patient's blood, or from Donor stem cells.

The CAR T people are producing an army of T cell clones that seek out the tumor using the exact same tool to identify tumor cells. We produce an army of individual T cells, each with their own unique tool to identify the tumor cells. Check out this page on MRKR's web site. It has good graphic and synopsis describing our MultiTAA tech.:

https://www.markertherapeutics.com/multitaa-technology/

If you were asking more in terms of how the CAR T therapy compares to our therapy clinically, Peter explains that pretty well here: