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Post by JHam on Dec 18, 2014 16:23:09 GMT
I went ahead and increased my position by about 50% this morning at .44 and .435 so I hope this price range is the new bottom and we go up from here after the holidays. Impressive lcd! I am not sure what to say other than, in my opinion we could see it continue to dip lower and be a bit volatile between now and P2b data. The good thing is that we may not have to wait too long for some kind of interim data, and that there aren't really any (if any) major concerns at this point. Other than how the data will turn out. I do not see them diluting for a while now, and as I have said prior, the way the company has guided (boasting their good cash position and having enough to last them throb 2016), I would be annoyed (putting it nicely) if they diluted any time between now and the fall. So in summary, I think there is a lot of upside for those who are buying or who have averages in the $.40's/.50's. Heck a lot of that Google Group seems to be averaged in the $.70's/.80's.
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Post by JHam on Dec 18, 2014 17:09:39 GMT
I just realized that auto-correct changed "through" to "throb". I would go back and edit it but it gave me a good laugh so I'll leave it as is
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Post by JHam on Dec 20, 2014 11:47:45 GMT
More posts from J&E on potential competitors. I did not know about this company that was also using IL-12: Somebody asked me my opinion about ZIOP. Since you asked, here it is:
I have been following it for a while and I have a very distinct view on it.
I participate in the ZIOP forum on investorvillage. Rather than rewriting everything, you can read my latest post here:
www.investorvillage.com/smbd.asp?mb=16353&mn=10162&pt=msg&mid=14488874
In summary, I'm betting that CAR-T will lose out to intra-tumoral + checkpoint blockers. However, there is a possibility that CAR-T players *could* find a way to achieve the complete antigen priming that is the distinct advantage of intratumoral. If there is any CAR-T player that stands the chance to do this, I believe it is ZIOP. ZIOP is NOT just an IL-12 intra-tumoral company. It is closely linked with XON, which is a first in class DNA engineering company. XON's CEO RJ Kirk has alluded to a CAR-T deal possibly in the making. Many ZIOP longs have been patiently waiting for a potential short squeeze, which looks like it may be starting.
Best I leave you to peruse my InvestorVillage writings.
Personally, I think it is a smart strategy to hedge both intra-tumoral and CAR-T by having positions in both ONCS and ZIOP.
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Post by JHam on Dec 20, 2014 11:49:06 GMT
cont'd...
I should add that I am not in any of the other big name CAR-T plays such as JUNO, KITE. The reader needs to be aware that in just the past YEAR, there have been at least 8 entrants into the CAR-T space. Right now, it's only proven for CD19+ blood cancers, which some quick research told me there are only about 80,000 cases across the various blood cancers. That's not a lot of patients for 8 (and counting) to fight for. Of course, the CAR-T (and TCR) players will be eyeing the much bigger solid tumor market. But it remains to be seen if they can safely treat patients there without the dreaded off-target toxicity. In short, my advice is to be VERY CAUTIOUS if you intend to get into the car-T recent IPO space. It is very hyped up right now with KITE, JUNO, BLCM all commanding huge market caps based on a lot of promise, and little else. ZIOP on the other hand is still relatively low market cap < $500m. Not just because of the IL12 potential but more so on the anticipation of a CAR-T deal that RJ kirk alluded to (see XON recent earnings transcript).
Buyer beware.
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Post by JHam on Dec 20, 2014 11:52:57 GMT
Incidentally the conversation about ZION started due to a thread about immunogen in which J&E posted the following:
ImmunoGen's is yet another "useless" targeted drug/antibody. Why won't the industry learn that a single antigen pathway attack (Her2) inevitably fails? You will simply select for the tumor cells that don't express that antigen, and the tumor will simply progress or grow back after a short delay.
The writing is on the wall. The only way we will beat cancer is if we have Tcells that recognize ALL tumor antigens, not just one. Furthermore, you need these Tcells to persist to maintain immunosurveillance.
JUNO/KITE and all these other single-antigen approach CAR/TCR companies are hyped up now. The industry always responds to the visual, the dramatic. Seeing tumors melt away rapidly is exciting. But if they don't figure a way to achieve epitope expansion, they will be just be a better, less toxic chemo because the cancer will come back. Also, the onus is on them to show they can surmount solid tumor related off-target toxicity.
Intra-tumoral therapy (ONCS, Tvec etc) has the advantage over these, especially when combined with checkpoint blockers. We shall see in due time....
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Post by JHam on Jan 20, 2015 23:38:10 GMT
I haven't been good about copying his posts here lately, but to sum up most of his recent posts...he has been very bullish on ADXS recently (after I brought it to his attention ironically), and rightfully so. He thinks ADXS' platform is inferior to ONCS, but that they are taking ONCS to school on th business side. Obviously hard to disagree with that. He is also very bullish on ZIOP, which had s big run-up recently. Here is a post from today which I think summarizes his current feeling on things:
I watched some of the videos night. 3 in total. One by Khort. One by Pierce. And the final panel Q&A.
My summary:
All the science they discussed was as I would expect. Primarily were educating others on the intratumoral effect of achieving anti tumor immunity. Khort started off with Coley Toxin, which is apt because that is the first strongest collection of evidence that the immune system can cure cancer. It's insane that the medical industry has ignored that evidence.
I did not hear any part where anybody said that one should not kill tumor too quickly. Maybe that's in a different video.
With regards to CAR-T. My interpretation of what Khort said:
a) CAR-T has dramatic initial responses, but after 6 months, tumor comes back. This is likely due either to immune escape or else accumulation of immunosuppressive factors such as PD1)
b) CAR-T cells cannot penetrate the solid tumor stroma (defenses around solid tumors). He further goes on to say that direct intra-tumoral injection of CAR-T cells into tumor "works".
Basically I did not really hear anything new in the 3 videos I watched. The one thing that was of interest to me was during the Q&A, the moderator brought up a point of where is the best spot to focus intra-tumoral therapy - the periphery of the tumor vs into the "core".
As for IL12 replacing CAR-T, I don't know. The evidence is as follows:
a) CAR-T and TCR adoptive therapies *can* work for solid tumors, the but primarily problem is off-target toxicity (I've explained this in previous posts, highlighting where ERBB2 CAR-T ended up killing a patient by attacking healthy lung). I personally know a solid tumor patient who had dramatic shrinkage of bulky disease with Adoptive T cell therapy. So, to say that it doesn't work for solid tumors....err.....I think is a bit of a stretch.
b) The issue of cancer *coming back* despite initial success -- well, that is a the real key to focus on. Does intra-tumoral have a real advantage over adoptive T cell procedures? I believe so. However, there is just not enough evidence to conclusively make that statement at this point. There have indeed been adoptive Tcell procedures where the patient experienced long lasting regression.
One big variable that has not been explored yet is the combination of adoptive T cell procedures + checkpoint. I suspect this is due to the dangerous toxicity of T cell procedures thus far. However, with methods to finely control toxicity such as ZIOP's Rheoswitch (I know of no other), I believe we will soon see the combination of checkpoint + CAR-T/TCR. What will the results be then? How will they compare with Immunopulse + checkpoint?
Anyway, as you can see, there are many open ended questions. My personal position is I have hedged 3 way ONCS ADXS ZIOP.
ONCS - Advantage = intratumoral & constant IL12 "come kill me". Disadvantage = intravenous
ADXS - Advantage = bacteria (like Coley Toxin) + In-situ dendritic + intravenous. Disadvantage = single antigen
ZIOP - Advantage = intravenous + ability to engineer anything they want (IL12 & PD1 directly on the Tcell). Also access to the largest body of patients in the world at MD Anderson (can push through trials very rapidly, also with the quick turnaround of their transposon based gene editing). Disadvantage = currently single antigen (though in most recent conference they talk about some method of creating a patient specific customized multi-antigen CAR with quick turnaround.
Best J
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Post by RLC on Jan 21, 2015 0:25:01 GMT
I haven't been good about copying his posts here lately, but to sum up most of his recent posts...he has been very bullish on ADXS recently (after I brought it to his attention ironically), and rightfully so. He thinks ADXS' platform is inferior to ONCS, but that they are taking ONCS to school on th business side. Obviously hard to disagree with that. He is also very bullish on ZIOP, which had s big run-up recently. Here is a post from today which I think summarizes his current feeling on things: I watched some of the videos night. 3 in total. One by Khort. One by Pierce. And the final panel Q&A.
My summary:
All the science they discussed was as I would expect. Primarily were educating others on the intratumoral effect of achieving anti tumor immunity. Khort started off with Coley Toxin, which is apt because that is the first strongest collection of evidence that the immune system can cure cancer. It's insane that the medical industry has ignored that evidence.
I did not hear any part where anybody said that one should not kill tumor too quickly. Maybe that's in a different video.
With regards to CAR-T. My interpretation of what Khort said:
a) CAR-T has dramatic initial responses, but after 6 months, tumor comes back. This is likely due either to immune escape or else accumulation of immunosuppressive factors such as PD1)
b) CAR-T cells cannot penetrate the solid tumor stroma (defenses around solid tumors). He further goes on to say that direct intra-tumoral injection of CAR-T cells into tumor "works".
Basically I did not really hear anything new in the 3 videos I watched. The one thing that was of interest to me was during the Q&A, the moderator brought up a point of where is the best spot to focus intra-tumoral therapy - the periphery of the tumor vs into the "core".
As for IL12 replacing CAR-T, I don't know. The evidence is as follows:
a) CAR-T and TCR adoptive therapies *can* work for solid tumors, the but primarily problem is off-target toxicity (I've explained this in previous posts, highlighting where ERBB2 CAR-T ended up killing a patient by attacking healthy lung). I personally know a solid tumor patient who had dramatic shrinkage of bulky disease with Adoptive T cell therapy. So, to say that it doesn't work for solid tumors....err.....I think is a bit of a stretch.
b) The issue of cancer *coming back* despite initial success -- well, that is a the real key to focus on. Does intra-tumoral have a real advantage over adoptive T cell procedures? I believe so. However, there is just not enough evidence to conclusively make that statement at this point. There have indeed been adoptive Tcell procedures where the patient experienced long lasting regression.
One big variable that has not been explored yet is the combination of adoptive T cell procedures + checkpoint. I suspect this is due to the dangerous toxicity of T cell procedures thus far. However, with methods to finely control toxicity such as ZIOP's Rheoswitch (I know of no other), I believe we will soon see the combination of checkpoint + CAR-T/TCR. What will the results be then? How will they compare with Immunopulse + checkpoint?
Anyway, as you can see, there are many open ended questions. My personal position is I have hedged 3 way ONCS ADXS ZIOP.
ONCS - Advantage = intratumoral & constant IL12 "come kill me". Disadvantage = intravenous
ADXS - Advantage = bacteria (like Coley Toxin) + In-situ dendritic + intravenous. Disadvantage = single antigen
ZIOP - Advantage = intravenous + ability to engineer anything they want (IL12 & PD1 directly on the Tcell). Also access to the largest body of patients in the world at MD Anderson (can push through trials very rapidly, also with the quick turnaround of their transposon based gene editing). Disadvantage = currently single antigen (though in most recent conference they talk about some method of creating a patient specific customized multi-antigen CAR with quick turnaround.
Best JThanks for sharing this JHam! I need to go over to that board more often. What are your expectations for ADXS in the near term? I'm not inclined to put money into a company that's up around 300% in less than 3 months, but it does seem like they've been on a roll lately (from a business perspective). I hate knowing that I owned shares of ADXS under $3 and sold to put it into the ACTC interim data run!
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Post by JHam on Jan 21, 2015 0:40:09 GMT
I haven't been good about copying his posts here lately, but to sum up most of his recent posts...he has been very bullish on ADXS recently (after I brought it to his attention ironically), and rightfully so. He thinks ADXS' platform is inferior to ONCS, but that they are taking ONCS to school on th business side. Obviously hard to disagree with that. He is also very bullish on ZIOP, which had s big run-up recently. Here is a post from today which I think summarizes his current feeling on things: I watched some of the videos night. 3 in total. One by Khort. One by Pierce. And the final panel Q&A.
My summary:
All the science they discussed was as I would expect. Primarily were educating others on the intratumoral effect of achieving anti tumor immunity. Khort started off with Coley Toxin, which is apt because that is the first strongest collection of evidence that the immune system can cure cancer. It's insane that the medical industry has ignored that evidence.
I did not hear any part where anybody said that one should not kill tumor too quickly. Maybe that's in a different video.
With regards to CAR-T. My interpretation of what Khort said:
a) CAR-T has dramatic initial responses, but after 6 months, tumor comes back. This is likely due either to immune escape or else accumulation of immunosuppressive factors such as PD1)
b) CAR-T cells cannot penetrate the solid tumor stroma (defenses around solid tumors). He further goes on to say that direct intra-tumoral injection of CAR-T cells into tumor "works".
Basically I did not really hear anything new in the 3 videos I watched. The one thing that was of interest to me was during the Q&A, the moderator brought up a point of where is the best spot to focus intra-tumoral therapy - the periphery of the tumor vs into the "core".
As for IL12 replacing CAR-T, I don't know. The evidence is as follows:
a) CAR-T and TCR adoptive therapies *can* work for solid tumors, the but primarily problem is off-target toxicity (I've explained this in previous posts, highlighting where ERBB2 CAR-T ended up killing a patient by attacking healthy lung). I personally know a solid tumor patient who had dramatic shrinkage of bulky disease with Adoptive T cell therapy. So, to say that it doesn't work for solid tumors....err.....I think is a bit of a stretch.
b) The issue of cancer *coming back* despite initial success -- well, that is a the real key to focus on. Does intra-tumoral have a real advantage over adoptive T cell procedures? I believe so. However, there is just not enough evidence to conclusively make that statement at this point. There have indeed been adoptive Tcell procedures where the patient experienced long lasting regression.
One big variable that has not been explored yet is the combination of adoptive T cell procedures + checkpoint. I suspect this is due to the dangerous toxicity of T cell procedures thus far. However, with methods to finely control toxicity such as ZIOP's Rheoswitch (I know of no other), I believe we will soon see the combination of checkpoint + CAR-T/TCR. What will the results be then? How will they compare with Immunopulse + checkpoint?
Anyway, as you can see, there are many open ended questions. My personal position is I have hedged 3 way ONCS ADXS ZIOP.
ONCS - Advantage = intratumoral & constant IL12 "come kill me". Disadvantage = intravenous
ADXS - Advantage = bacteria (like Coley Toxin) + In-situ dendritic + intravenous. Disadvantage = single antigen
ZIOP - Advantage = intravenous + ability to engineer anything they want (IL12 & PD1 directly on the Tcell). Also access to the largest body of patients in the world at MD Anderson (can push through trials very rapidly, also with the quick turnaround of their transposon based gene editing). Disadvantage = currently single antigen (though in most recent conference they talk about some method of creating a patient specific customized multi-antigen CAR with quick turnaround.
Best JThanks for sharing this JHam! I need to go over to that board more often. What are your expectations for ADXS in the near term? I'm not inclined to put money into a company that's up around 300% in less than 3 months, but it does seem like they've been on a roll lately (from a business perspective). I hate knowing that I owned shares of ADXS under $3 and sold to put it into the ACTC interim data run! Yeah that is unfortunately how it goes sometimes. I am still frustrated that I didn't take some ONCS profits back in December. I am not sure about what happens with ADXS in the near term. It has been on such a tear recently that I am inclined to stay away. It could continue to go up, but the current valuation seems about right for where they are in clinical development. Like ONCS, if they show promising results in their combination trial then the sky is the limit, imo.
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Post by RLC on Jan 21, 2015 15:26:24 GMT
I guess it's no surprise to see ADXS down significantly two days in a row after a surge like the one they had. I know I likely would have exited my entire position by now if I still owned my <$3 shares...
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Post by happyjawa on Jan 22, 2015 17:08:34 GMT
Thanks for sharing this JHam! I need to go over to that board more often. What are your expectations for ADXS in the near term? I'm not inclined to put money into a company that's up around 300% in less than 3 months, but it does seem like they've been on a roll lately (from a business perspective). I hate knowing that I owned shares of ADXS under $3 and sold to put it into the ACTC interim data run! Yeah that is unfortunately how it goes sometimes. I am still frustrated that I didn't take some ONCS profits back in December. I am not sure about what happens with ADXS in the near term. It has been on such a tear recently that I am inclined to stay away. It could continue to go up, but the current valuation seems about right for where they are in clinical development. Like ONCS, if they show promising results in their combination trial then the sky is the limit, imo. You'll get your chance eventually JHam. If investing in these speculative companies has taught me anything, it's that they go up and down at a whim. I've seen OCAT go up and down so much without taking any profits, and I've done the same with ONCS. While I doubt it will bounce back up to the .90s, I'm confident it will jump up to the .60s sometime in the next few weeks.
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