ZIOP

[XMFfuma102]

So, since I’ve done ok with PAYC (thanks kids!), I have to get back on my soapbox to warn you folks about this wolf in sheep’s clothing called ZioPharm. You see, I post more because I want you all to do well, and it pains me to see you chasing such a dog, even if its only a small part of your portfolio. ZIOP is down a cool 22% while IBB is down 0.5%, NASDAQ up 2% and Dow up 1.5% since I posted the following below on the biotech board, just to get some thoughts on paper and documented… here goes:

Ad-RTS-hIL-12 and veledimex didnt work for recurrent / metastatic breast CA, with only one of 12 having a response. As an aside, if the clinical trials webpage has not been updated & the trial is completed, its likely a negative trial. This was considered a Phase 2 study with a whole twelve patients. Let me repeat that.

Phase two. For breast cancer. Twelve patients. (1,2)

There are 40,000 patients that die each year from breast CA (3), so there are (probably) about that many stage 4 breast CA patients out there. They can only get 12 patients? They have another 40 patient trial that is not actively recruiting, so I suspect they gave up. (4) This tends to be a common theme for them, since they did it with melanoma as well. (5)

ZIOP is losing 15m quarterly, with 81m cash on hand, leaving them essentially nothing by the time their GBM results come in - a whole 48 patient trial that is not due until 2019. (6) There are 74,000 people worldwide each year, and all they can come up with for a trial is 48 patients since 2015? And we keep clinging to a single center, single arm P1 study with an N of 7 ??? and with 17 overall patients?? (7) Though yes, they are doing a multi-center trial (at a while 4 sites) – its still a P1 trial (with a whopping 48 patients!) which by definition, is looking at safety profile and not ORR, OS, or PFS. (8) …. The N of 48 is about 25% that of other studies looking at GBM.

Now, lets move onto the excitement of a point-of-care system with 2 day turn around… Sleeping Beauty! … Sleeping beauty is still asleep, as it hasnt even been used clinically yet! “The Company expects to advance towards a Phase 1 study evaluating the point-of-care in 2017. “ (9) Basically, all of the money they have spent on the prior studies needs to be repeated with the Sleeping Beauty system.

Not to mention that this is delivered by intra-tumoral injection- can these brain tumors even be reached? - who’s going to inject them??? How the hell are you going to practice? will it be reimbursed? Will parents balk at the thought of having an unproven drug injected into their kids brain??? New drug, new delivery mechanism, unproven / low quality data… This is worse than Afrezza!

Then there’s this (10):

Intra-tumoral IL-12 RheoSwitch® programs:

• Updated clinical data from Phase 1 of Ad-RTS-hIL-12 + veledimex for recurrent GBM to be presented at ASCO
• Initiate pivotal clinical trial for recurrent GBM
• Initiate combination study of Ad-RTS-hIL-12 + veledimex with iCPI (anti-PD-1) for recurrent GBM during the first half
• Initiate Phase 1 study in the treatment of brain tumors in children during the first half

CAR+ T programs:

• Continue CD19-specific CAR+ T second-generation clinical study, enrolling patients under shortened manufacturing
• Advance CD19 third-generation mbIL15 towards a Phase 1 clinical study evaluating point-of-care
• Initiate a CD33-specific CAR+ T clinical study in adults and children for relapsed or refractory acute myeloid leukemia
• Advance CAR+ T-cell preclinical studies for at least one hematological malignancy under a shortened manufacturing process towards point-of-care

TCR programs

• Execute CRADA with NCI utilizing Sleeping Beauty to generate T cells targeting neoantigens for treatment of patients with solid tumor malignancies
• Advance development of process for delivering personalized gene-modified T-cell products against neoantigens
  NK cell programs
• Initiate a Phase 1 study of off-the-shelf (OTS) NK cells for elderly patients with acute myeloid leukemia not eligible for standard intensive chemotherapy
  GvHD (graft-versus-host disease) programs
• Advance preclinical studies

Then there is the dilutional issue with intrexon. (11,12)

Too many shots on goal, not enough money to go around. This shows a lack of focus, and is an attempt to put lipstick on a pig that has failed in 2 other arenas (breast CA & melanoma) already. Plus intrexon seems like a shady business partner…

ZIOP is a penny stock, it just doesnt realize it yet.

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I had previously posted here (links to references in post below)

http://discussion.fool.com/ziop-penny-stock-in-small-cap-clothin…

[BizKikr]

Evening Fuma,

That seemed like a lot of technical details to support a bearish case. Not sure it makes any sense unless you have several PhD’s in oncology to review and comment. As an investor in ZIOP, I tend to follow the money trail.

On 05/12/17 Ziopharm announced a public offering of ZIOP common shares worth $50 Million to a single institutional investor. So, I would assume a 50 million dollar investment was well vetted by a team of PhD advisors with a price of $5.15 a share. Else this would be fraud right? Or a whale sucker bet right?

Here’s the article:
http://ir.ziopharm.com/releasedetail.cfm?ReleaseID=1026244

So, if you really feel this company is a penny stock, please explain how an institutional investor would bet $50 million on Ziopharm?

Do that, and you’ll have a very convincing argument.

~Scott

[HeartMD]

Scott,

Fuma makes some good points. However, I do wish he wouldn’t be so dismissive because I appreciate a lot of what he says. He makes me think and that is a good thing. What he has posted above should make you think as well. I realize to the non-medical it is complicated. Even to us medical folks it can be pretty intimidating, especially the world of oncology. Let me see if I can break it down some as I know a few on this board are invested in ZIOP.

First, let me inform everyone about clinical data presentations at medical conferences. This can be a real sh!t show to be honest. But there are 3 basic levels of clinical trial outcomes at a traditional conference. There are “late breaking clinical trials”, clinical trials presented orally with visual power point presentation and then there are poster presentations. The coolest kids at the conference are late breakers and will get most of the press, either good or bad. The poster presentations are all in one room usually (sometimes more if it a huge international conference) with the presenter either absent or standing nearby (there are usually times posted when they will be present) to answer questions. The middle ground are the run of the mill trials that aren’t good enough to hang with the cool kids but more revealing/important than a poster. Hope that helps.

Next, lets review trial phases 1-4. I’m not going to review preclinical or Phase 0 trials as they are animal testing or bioavailability or pharmacokinetic in nature and irrelevant for this discussion. Phase 1 trials are small hypothesis testing and generating trials often on healthy volunteers to assure safety. However, with these drugs being studied, that sort of Phase 1 trial is irrelevant and not useful as these Ziopharma meds are for patients with no other alternative in general. Phase 1 trials often have only 5-50 patients. That is very common. So a phase 1 trial for Ziopharma is really a smaller Phase 2 trial and I wish Fuma would have informed you of that fact. Especially if he’s going to rehash that is a Phase 1 trial over and over. Phase 2 trials assess for efficacy and safety in the target patients and often dose ranges are involved to get a “goldilocks” dose to achieve the perfect balance of efficacy and safety. They generally involve 100 patients or so but often significantly more or less. Phase 3 trials are generally larger Phase 2 trials involving many more patients (usually thousands but sometimes hundreds) looking to confirm and shore up the Phase 2 data. Phase 4 are post marketing trials often voluntary but sometimes required by the FDA in order to continually assess for safety in therapies that show a lot of concern from a safety perspective. Hope that helps too.

So lets move on to Fuma’s post (This is getting long already). Let’s start with the Glioblastoma POSTER presentation. Again, this is a POSTER. It is a Phase 1 trial. So you can gather by what I stated above that this is not intended to be an earth shattering moment for them. This is a safety and efficacy and dose ranging trial to see if it works and what dose is the best. Fuma asks who is going to inject this medication into the tumors but neglected to say or read that the patients were undergoing resection of some tumor so it was injected at the time of resection. The results were encouraging and they have settled on the 20mg dose. Remember, these are very ill patients with an incurable cancer that gives a median lifespan of 6 months. Survival in the studied patients was extended to around 12 months. Pretty good and the side effect profile was encouraging as well. Now as Fuma points out, this has not been effective in breast CA or melanoma but I’m not up on those trials to be honest.

They are starting a lot of Phase 1 trials this year. Fuma states that all of the money will have to be re-spent to look at “sleeping beauty.” I’m not sure that is true but be sure the FDA will have a say. However, if they can unequivocally show their ability to turn it on and off in several patients I’m not sure they will have to redo it all but it will definitely burn some cash.

His points about cash burn shouldn’t be taken lightly. They are burning cash but almost any startup biopharma is so I’m not sure they are out of the norm in that regard. As for the 50 million dollar investor… I’m not sure that is a confidence booster or should be construed as one. Do they have advisors with more letters after their names than me? Yep. Have they done their due diligence? Yep. Are they privy to info that we aren’t? Yep. Will they be the first to invest 50 million in biopharma and lose it all? Nope, and I would suggest that the number of times that has occurred would boggle our minds.

I hope that was useful. I have no position in ZIOP and don’t intend to at this juncture. I still consider ZIOP pretty speculative. Their entire company is built on hypotheses with just a little bit of data and I’m not too comfortable with that. I do have a small KITE position that I’m not increasing or selling.

MC