|
|
Post by JHam on Dec 14, 2014 3:10:15 GMT
There is a poster at the ONCS Google Group that goes by the name JusticeandEquality, who is great at explaining the science at ONCS. Extremely knowledgable and makes it easy for everyone to understand. He has quickly become the "CDC" of that board, lol, minus the ego, unwillingness to listen to other perspectives, and calls for imminent JVs. He does however have a favorable view of ONCS and backs up what he says in his posts with facts. I am going to post a collection of his posts in this thread, as I think they are a very valuable resource. Some of the posts are answers to questions, but I think you are able to understand the question based on his answers.
|
|
|
|
Post by JHam on Dec 14, 2014 3:12:02 GMT
The presence of PD1/PDL1 expression in the tumor has been shown to be NOT a reliable indicator of efficacy (of the PD/L1 checkpoint blockade antibodies).
In the EARLY days of the trials, investigators *thought* it was potentially a reliable marker. Then, they started noticing patients were responding to the checkpoint blockade antibodies even though the biopsied tumors did NOT contain PD1/PDL1.
Basically, the immune system is highly complex. PD1/PDL1 expression can come and go. It depends when you one is actually measuring expression on the tumor.
The $1m question is whether or not combining Immunopulse + PD1 will result in significant synergies. My bet is yes.
I dug around Stanford University's research website and found the following
www.nejm.org/doi/full/10.1056/NEJMc1203984
As you can see, just introducing radiation therapy to a single tumor can make checkpoint blockade suddenly work (where it was not working before).
They got so excited that they even started a clinical trial combining the two:
clinicaltrials.gov/ct2/show/NCT01769222
Now, take this observation one step further. Go ask all the radiation oncologists how many times they have seen the "immunopulse effect" where zapping just one or two tumors can cause systemic antitumor effect. Very very few, if any will tell you they've seen it. The point here is that if simple radiation can cause dramatic response to checkpoint blockade, it is a reasonable, if not a strong bet, that combining Immunopulse with checkpoint blockade will result in this combination synergy, perhaps more apparent, at higher rates.
The scientific rationale is all there -- zapping a tumor with immunopulse causes immediate attraction of Tcells. Tcells attack the tumor, leading to an "in situ vaccine effect". These Tcells go on to attack other tumors throughout the body. However, tumors have highly immunosuppressive defensive mechanisms. That's where the PD1 checkpoint blockade comes in -- to remove these defenses.
My bet is we truly will see a shockingly high synergistic rate of responses to PD1 with Immunopulse. Furthermore, other alternatives such as radiation, vaccines may not be as good as Immunopulse because of the following:
1) Immunopulse DNA plasmids result in *constant* secretion of IL12 -- this creates a "constant vaccine" like effect. Imaging if you have to vaccinate a person (or irradiate) every minute. 24x7.
2) Electroporation causes transient intense inflammation. This is highly beneficial in generating the needed immune response. You can research something called cryo-ablation (or cryoablation). Many investigators have observed a transient systemic anti-cancer effect -- just like immunopulse -- from cryo-ablation. However, this effect is very temporary and nowhere as apparent as Immunopulse. The point is that the transient inflammation is very beneficial.
3) IL12 has been tried in the past (systemic infusions). However, it failed. Why? One reason posited was IL12 causes upregulation of "Bad stuff" like Tregs. You see, the immune system is highly complex will all sorts of checks & balances. These checks exist to prevent bad stuff from happening like auto-immune diseases (where your own Tcells attack your healthy tissue). IL12 has been shown to cause Tregs to initially decrease increase. This promotes the beneficial antitumor effects. However, after some time, Tregs may re-increase to prevent autoimmune type symptoms. This is one explanation for the countless "failed" immunotherapies from the 80s, 90s, and even today. This is where checkpoint blockade comes in. Checkpoint blockade (PD1) prevents Tregs from eventually stopping the anti-tumor effects of IL-12.
Anyway, no disrespect intended, but your friend in the biotech field is simply not informed enough. This is not a mere crap shoot. There are real and logical reasons why the combination trial can potentially lead to DRAMATIC increase in PD1 responses. When the interim results come out, ONCS market cap may instantly go up 5-10x.
|
|
|
|
Post by JHam on Dec 14, 2014 3:13:11 GMT
Oldcoot,
The immune system is not so easy to classify. There is a temporal/time effect.
PD1 drugs work by taking the brakes off. In some cases, autoimmune effects happen. The treatment to abrogate those are standard steroid IV. HOWEVER, it is widely observed steroid IV does NOT remove the anti-tumor memory effect. One would think it should because steroids are immunosuppressive.
The running theory is that a time window during which a number of factors must happen within must occur. This includes priming the Tcells, taking the brakes off, etc etc.
Pharma is still used to the simplistic single drug , single pathway approach. This is where we have the opportunity to sieze the day.
|
|
|
|
Post by JHam on Dec 14, 2014 3:14:21 GMT
There is much more to it than Tregs too. There's MDSCs too. You know, there are even other types of immune suppressive weapons that tumors use such as exosome (think of "bullets" being secreted by tumor cells to suppress the immune system!) Seriously, these really exist.
It is 100% true that the immune system is so complex that investigators don't fully understand it. Take PD1 and CTLA4 itself, these 2 drugs aren't fully understood in the way they work.
Pharma has been trained over the decades to look at one pathway. This is simply because they need to patent a drug that explicitly addresses that one pathway.
Immunopulse probably works in multiple ways -- in situ generation of tumor-recognizing Tcells (TILs), physical puncture of the tumor (one way to get past the defenses !! ), acute inflammation, constant attraction 24x7 of immune system -- "come and get me" signal, and maybe even other mechanisms not well characterized yet.
The CAR-T space is all hot now. But I think a lot of investors could lose a lot of money eventually. CAR-T's achilles heel is the Tcells are engineered to attack only one antigen (tumor signature). With immunopulse or other intra-tumor approaches, you simply generate Tcells that recognize hundreds/thousands of the custom antigens found on the actual tumor in your body -- not some statistically researched antigen that's found in a majority of tumors of your type of cancer. The plethora of antigen approach makes it much, much harder for tumors to find away around the therapy.
BMY and MRK may yet win out against those betting on CAR-T (by combining their PD1 with intra-tumoral approaches)
best
|
|
|
|
Post by JHam on Dec 14, 2014 3:15:41 GMT
The general gist/impression I have on PVCT is that
1) it most likely does in fact cause an immune effect, similar to Immunopulse
2) it is based off a common dye, Rose Bengal. Could be this introduces problems with IP protection.
3) In comparison to Immunopulse, it is similar to many of the other existing vaccines out there (such as Tvec or other vaccines). Immunopulse still has advantages over it such as constant secretion of IL12, intense acute inflammation. The Rose Bengal dye is quite quickly metabolized (removed) from the tissue, thus does not have that "constant vaccine" effect.
Other than that, I don't really know much. I did read some "shady" stuff written about PVCT on SA.
|
|
|
|
Post by JHam on Dec 14, 2014 3:21:15 GMT
By the way, do not underestimate the importance of the 24x7 "come and get me" signal that Immunopulse creates.
You can already see that many things can cause the immune system to attack tumors systemically. Tvec, PVCTs rose bengal, radiation, cryotherapy. There are even reports of simple surgery or biopsy causing this!
The idea/theory is that damage of any sort to the tumor causes "danger signals" that attract the immune system, leading to Tcell recognition (TILs). I will actually be surprised if Tvec does NOT cause TILs. It should, in theory. Any of the above should.
To me, what may be the real advantage is the constant stream of IL12 cytokine excretion from Immunopulse. This advantage is likely why we see only transient short lasting systemic effects from radiation, or the occasional biopsy-induced systemic effect. Tvec is a live virus, engineered to secrete Gmcsf - another cytokine with similar "come get me" signal to IL12.
The beauty of Immunopulse is for as long as the tumor is alive, it will continue to secrete "come kill me" signals. I suspect this is one of the real advantage of ONCS, and the true way it creates "lots of TILs".
|
|
|
|
Post by JHam on Dec 14, 2014 3:23:05 GMT
This is a very important topic. It sounds almost too simple and obvious, but there is a school of thought that believes the path to a true durable "cure" is simply to have the body keep attacking immune cells over and over until you eliminate the very last one.
Cancer vaccine frequency is an important area of research. Initially, investigators thought the same thing - vaccinate over and over again to eliminate all cells.
Then, they found out that one can vaccinate "too much". At some point, "tolerance" was developed. Think about it - how do you get rid of allergies? One way is to vaccinate with small amounts of that allergy until you become "tolerant".
Tregs and other immune-suppressive aspects of our body are part of that process. They suppress the immune response and make us "tolerant" to that foreign substance. Likewise, cancer cells take advantage of this dynamic and become invisible to the immune system.
This is what PD1 and other checkpoint blockers seek to do -- to "take the brakes off" or remove tolerance.
It may very well be that investigators need to revisit years of thought conditioning and realize that the traditional danger of tolerance may be reduced/eliminated by adding PD1.
Consequently, increasing vaccine frequency (including to different tumors sequentially, as previously treated tumors "disappear") may have a role to play in achieving "complete kill".
One caveat -- more Tcells are not necessarily better. If you think about it - when you get a cold virus or infection - the immune system is often fully capable of generating enough Tcells to wipe it out. It may be that one only needs small number of TILs, but combined with the appropriate checkpoint blockers to reduce the various immunosuppressive defenses the cancer uses.
In time, we will understand these dynamics better.
|
|
|
|
Post by JHam on Dec 14, 2014 3:41:03 GMT
Tvec is the closest reference to Immunopulse. Oncosec has chaired intratumoral symposiums and invited Tvec scientist to give talks. Both products act in very similar fashion - using genetic engineering to modify cells to emit a continuous "come get me cytokine".
In the case of Tvec, the oncolytic virus is modified to secrete GmCSF.
In the case of Immunopulse, the cancer cells are directly modified to secrete IL-12.
Tvec phase 3 data virtually identical to Oncosec Phase 2 data.
Amgen combined Tvec with Yervoy. That took the ORR up from 26% -> 56%
wwwext.amgen.com/media/media_pr_detail.jsp?releaseID=1936196
Amgen got so excited that it decided to combine Tvec with PD1. Trial just started (October I believe).
Why? Obviously because PD1 monotherapy has ORR between 20-30% vs Yervoy monotherapy ORR of 10%.
So, Tvec + PD1 may take ORR up from 26% -> 76%.
76% ORR! That is quite revolutionary.
Doesn't take a rocket scientist to see that given
a) Mechanism of action very similar (continuous excretion of "come get me signal")
b) Virtually identical monotherapy data (Tvec vs Immunopulse)
Therefore probability of synergy with Immunopulse combined with PD1 is very very high. Tvec has virtually done the work for us.
Valuation:
Tvec was bought for $1B by Amgen in 2011.That was for monotherapy efficacy. That valuation does not include increased efficacy with combined with Yervoy (let alone PD1). What valuation should ONCS command then? How much will Merck or a competitor pay if we achieve 76% ORR? My bet is far, far more than $100m. If you assign the $1B valuation Amgen paid for Tvec, our market cap goes up 10x. Add to that dramatically increased efficacy when combined with PD1 and what do we get??
|
|
|
|
Post by jckrdu on Dec 14, 2014 14:19:16 GMT
The presence of PD1/PDL1 expression in the tumor has been shown to be NOT a reliable indicator of efficacy (of the PD/L1 checkpoint blockade antibodies).
In the EARLY days of the trials, investigators *thought* it was potentially a reliable marker. Then, they started noticing patients were responding to the checkpoint blockade antibodies even though the biopsied tumors did NOT contain PD1/PDL1.
Basically, the immune system is highly complex. PD1/PDL1 expression can come and go. It depends when you one is actually measuring expression on the tumor.
The $1m question is whether or not combining Immunopulse + PD1 will result in significant synergies. My bet is yes.
I dug around Stanford University's research website and found the following
www.nejm.org/doi/full/10.1056/NEJMc1203984
As you can see, just introducing radiation therapy to a single tumor can make checkpoint blockade suddenly work (where it was not working before).
They got so excited that they even started a clinical trial combining the two:
clinicaltrials.gov/ct2/show/NCT01769222
Now, take this observation one step further. Go ask all the radiation oncologists how many times they have seen the "immunopulse effect" where zapping just one or two tumors can cause systemic antitumor effect. Very very few, if any will tell you they've seen it. The point here is that if simple radiation can cause dramatic response to checkpoint blockade, it is a reasonable, if not a strong bet, that combining Immunopulse with checkpoint blockade will result in this combination synergy, perhaps more apparent, at higher rates.
The scientific rationale is all there -- zapping a tumor with immunopulse causes immediate attraction of Tcells. Tcells attack the tumor, leading to an "in situ vaccine effect". These Tcells go on to attack other tumors throughout the body. However, tumors have highly immunosuppressive defensive mechanisms. That's where the PD1 checkpoint blockade comes in -- to remove these defenses.
My bet is we truly will see a shockingly high synergistic rate of responses to PD1 with Immunopulse. Furthermore, other alternatives such as radiation, vaccines may not be as good as Immunopulse because of the following:
1) Immunopulse DNA plasmids result in *constant* secretion of IL12 -- this creates a "constant vaccine" like effect. Imaging if you have to vaccinate a person (or irradiate) every minute. 24x7.
2) Electroporation causes transient intense inflammation. This is highly beneficial in generating the needed immune response. You can research something called cryo-ablation (or cryoablation). Many investigators have observed a transient systemic anti-cancer effect -- just like immunopulse -- from cryo-ablation. However, this effect is very temporary and nowhere as apparent as Immunopulse. The point is that the transient inflammation is very beneficial.
3) IL12 has been tried in the past (systemic infusions). However, it failed. Why? One reason posited was IL12 causes upregulation of "Bad stuff" like Tregs. You see, the immune system is highly complex will all sorts of checks & balances. These checks exist to prevent bad stuff from happening like auto-immune diseases (where your own Tcells attack your healthy tissue). IL12 has been shown to cause Tregs to initially decrease increase. This promotes the beneficial antitumor effects. However, after some time, Tregs may re-increase to prevent autoimmune type symptoms. This is one explanation for the countless "failed" immunotherapies from the 80s, 90s, and even today. This is where checkpoint blockade comes in. Checkpoint blockade (PD1) prevents Tregs from eventually stopping the anti-tumor effects of IL-12.
Anyway, no disrespect intended, but your friend in the biotech field is simply not informed enough. This is not a mere crap shoot. There are real and logical reasons why the combination trial can potentially lead to DRAMATIC increase in PD1 responses. When the interim results come out, ONCS market cap may instantly go up 5-10x. JHam - Thanks for posting. When are you expecting interim results from the combo trial with Merck's PD1 to be released? |
|
|
|
Post by JHam on Dec 15, 2014 1:11:53 GMT
Good question. It all depends on when they start treating patients of course. If they can start enrollment in early Q1 (late Jan/early Feb) as they have stated, then they may be able to have some data available by late summer/early fall. Some are hoping they have data available by the April ASCO conference. I think that is very wishful thinking. The company should be announcing their 2015 milestones in a few weeks, so hopefully they'll give us some guidance as to when they plan to release interim data.
|
|
|
|
Post by JHam on Dec 15, 2014 15:19:49 GMT
Someone asked if he could share his background. This was his response:
If you don't mind, I'd like to keep my background personal. What I can say is that I have spent a decade researching cancer immunotherapy to help a dear relative beat cancer. Cancer immunotherapy is not merely mental exercise nor interest. It is a matter of life or death for our family. We do not have the luxury of depending on hope nor imagination. We evaluate various cancer immunotherapy treatments based on close study of science and fact.
Consequently, every statement I make regarding the science or medical aspects are backed up by research findings and data. There are also many members of our family in academia. Furthermore, we have had the benefit of meeting leading researchers in the field, as well as executives in the "hot" biotech immunotherapy industry.
While it is impossible for the average investor to ramp up on years of medical knowledge, what you can definite do is use tools such as google scholar to get a gist of the various scientific topics. This will at least give you some level of assurance that what you're reading is not pulled out of thin air.
Best,
Justice
|
|
|
|
Post by JHam on Dec 15, 2014 15:23:49 GMT
Shortly after he posted this. This obviously took some time to write up but is absolutely worth the read. While he is obviously Pro-ONCS he is also very supportive and respectful of the competition. He definitely backs up his statements with links and facts and for that I am very appreciative: Hi all,
I wrote up a valuation case for Oncosec. It may be useful as a starting point to debate the worth of the company:
tinyurl.com/o4zztqf
Feedback is welcome.
Best,
Justice
|
|
|
|
Post by JHam on Dec 16, 2014 5:14:32 GMT
Another good one posted in response to some negative remarks to the valuation piece he wrote (linked above) by someone at iHub. Actually, that someone is now a moderator at iHub and has been banning everyone left and right who posts positive things about ONCS. It is actually a big controversy right now that could get pretty ugly, but is what led to the creation of the ONCS GG. Anyway, here is the post, and like before the questions asked are addressed in the post:
I took a quick look at his comments. He misrepresented my writing regarding the $1B valuation. My article specifically stated that Amgen purchased Biovex at a valuation of $1B. I didn't not say that Amgen actually paid $1B up front. This is simply the nature of biotech deals. A portion is paid up front, then when certain miletones are hit the rest follows. To omit the milestone promises from the valuation total would be deficient and misleading. Even this Wall Street Journal article put the $1B number it their title. His misrepresentation of my writing, and focus on this trivial aspect up front demonstrates lack of real substance in building a counter argument.
As to his concerns about extrapolating between P3 and P2, he is perhaps not aware of a very important difference between immunotherapy trials and older chemo/targeted agent trials:
In immunotherapy trials, investigators are seeing very consistent results between Phase 1, 2 and 3. You can go compare Yervoy and PD1 phase 2/3 results with earlier Phase 1. You will see for yourself that the ORRs and CRs are basically the same (providing for rounding error due to sample size). This pattern is also clearly seen in ONCS Phase 1 and Phase 2 trial results. This consistency was not commonly reproducible with the older targeted agents and chemo drugs. Why? Most likely because of the PATHETIC efficacy of older drugs. Weak efficacy led to investigators trying to game the system. They would try to select only the "healthier" patients - those who weren't about to die. They could game this in Phase 1 and 2, but in Phase 3 the true efficacy would come out.
A second very important difference is that these older cytotoxic and pathway inhibitors attacked the cancer directly. The problem is this quickly selects for cancer cells that are not affected by that drug. So, a common observation was that patients might experience initial shrinkage of their tumors, but the OS (overall survival) was NOT improved. Tumors would shrink, and patients experience maybe 1 or 2 months of improved PFS (progression free survival). Meaning their cancers stopped growing for a few weeks/months. But when the cancer returned, it grew even faster and the patients, on average, died within the same amount of time.
For immunotherapy, things are very different. In many of these trials, patients had failed multiple prior chemo regimens. More importantly, it is very difficult to game the immune system. You either succeed in getting the immune system to work, or you don't. If it works, it tends to work in predictable fashion. Furthermore, responses tend to be far more durable than many of the older cytotoxics. The fundamental difference is that the older failed extrapolations involved drugs that attacked the cancer directly. In contrast, immunotherapy empowers the immune system to attack the cancer. The immune system is adaptive and it is much harder for the cancer to "escape". This is how you get patients with years-long durable complete regressions with only a few PD1 infusions performed years ago.
Also, his comment about CTLA4 being different from PD1 is appreciated and noted. He is correct that the mechanisms of action are different. However, his fear that the comparison is "risky" is either misguided - or he is trying to scare readers. The indisputable fact is that the pharmaceutical industry and medical community has voted with BILLIONS of dollars and resources to focus on PD1 instead of Yervoy. This is not just because of superior toxicity, but significantly superior efficacy. The fact that he did not mention this infers he is either uninformed, or is intentionally trying to scare.
While it obviously remains to be seen of Tvec+PD1 would be superior to Tvec+CTLA4, the risk is more to the upside (that PD1 will work better than Yervoy). If Amgen KNEW for sure that PD1 is better than Yervoy, there would be no risk, and ONCS would not be $100m, but far closer to the $1B today. Hence the time to "place your bets" is obviously right now. Amgen has done so. Otherwise, with the superb Phase 1/2 Tvec+Yervoy results, why didn't they move on to Phase 3?? Why would they instead choose to switch to Tvec+PD1? The answer is obvious.
Finally, his assertion that the case for ONCS was "not made strongly" is his personal opinion. But everyone is entitled to their own.
best,
Justice.
|
|
|
|
Post by JHam on Dec 16, 2014 20:08:03 GMT
Response to me after I asked him if he thought it was unrealistic to hope to see a 90%+ ORR from the Phase 2b:
That 90% number is not an impossibility.
Just think about it -- simply taking the brakes off with PD1 has yielded ORRs in the 30% range. Take a step back and think about what this means.
These are patients who have not had any explicit Tcell generating treatment performed. Yet, a whopping 30% respond. This means there was a small amount of "natural" Tcell generation -- maybe from previous surgery, maybe from previous radiation, or maybe just the natural immune system trying to recognize the cancer, but being suppressed by the the cancer.
I cannot understate how significant that 30% number is. These are patients who traditionally would have no other option but death.
Now, there is general consensus in the cancer immunotherapy community that you absolutely require those Tcells to be in place before PD1 can work. Previous attempts at generating these Tcells primarily centered around cancer vaccines. Yet, cancer vaccine monotherapy efficacy was nowhere near as obvious as Tvec & Immunopulse. Complete responses were non existing. Any sort of benefit was typically equivocal and murky, typically measured in slightly extended overall survival. But generally speaking, there were no "obvious shrinkage of tumors" with cancer vaccines.
With Tvec & Immunopulse, the overwhelming generation of Tcells results in obvious visible tumor regression. This is the first time I know of where an in vivo intramural therapy has achieved this. The visible tumor regression is undoubtedly a huge reason why Amgen was willing to assign $1B valuation for Tvec. The only other therapy that can achieve obvious tumor shrinkage reliably is adoptive T cell procedures (CAR-T and TCR). For those, Tcells are extracted from the patient, engineered, multiplied to billions in number, then rein fused. In other words, one is using brute force to shove in a huge number of "ready to go" Tcells.
The fact that Tvec / Immunopulse monotherapy can result in obvious shrinkage without any sort of "removing the brakes" implies that a large number of Tcells are generated by the constant secretion of "come get me" cytokines. The number of Tcells is probably not as high as in CAR-T/TCR procedures. However, it's high enough to result in shrinkage. More importantly, these Tcells probably recognize all tumor antigen, not just the single engineered antigen that CAR-T/TCRs are programmed to go after.
So, if you have in place a large number of Tcells ready to go, and then you add the checkpoint antibodies, you should see a much higher ORR. This is in fact what Amgen saw when they added Yervoy to Tvec.
Yervoy is rather weak (compared to PD1). By itself, you see only about 10% ORRs. With this "weak" removal of the brakes, those Tcells were still able to push up ORRs from 26% to 56%.
So the question now is with the significantly stronger brake removal of PD1 (30% monotherapy ORRs), what do you think the ORR improvement is going to be? By no means is the 90% wishful thinking. I really do think it can be anywhere from 70%-90%.
I see the end-game scenario in cancer immunotherapy being Immunopulse or Tvec combined with multiple checkpoint blockers (PD1, Yervoy, OX40, TIM3). The rare patient who fails this simple, non-toxic, outpatient therapy will have to go for the much more involved/expensive/dangerous CAR-T or TCR procedures (requires in-patient or ICU monitoring in case of cytokine release syndrome or off-target toxicity).
In contrast, the extremely low toxicity of Immunopulse/Tvec + PD1 (and other checkpoint blockers coming soon) will be the first line treatment for all cancers. Like I wrote in the thesis, you go in to clinic, oncologist wheels in the cart, zaps one tumor, send you to outpatient infusion lab for PD1. Maybe you do this every month. If you have a deeper tumor that cannot be reached with longer probes, you get sent to the interventional radiologist or surgeon to get the probe into your tumor. Then you go for PD1.
This scenario could become first line treatment for all cancers. CAR-T/TCRs may become second line. Radiation and chemo may be relegated to third line. The cost dynamics, toxicity profile, strategic management of cancer all point to this. The writing is on the wall if you know where to look....
|
|
|
|
Post by JHam on Dec 16, 2014 20:14:23 GMT
HIs response/breakdown after I asked him how he compared Advaxis and their new combo trial with ONCS: 1) They use gene modified live bacteria. Bacteria is rendered "harmless". However, it still wakes up the immune system (our innate system is coded to get revved up when it sees bacteria)
2) Bacteria is also embedded with DNA plasmid that encodes single target antigen. This antigen is a "well known" antigen for a specific cancer. They can target different antigens for different cancers.
3) Results from Advaxis HPV trial:
- 11% ORR
- additionally about 30% had "stable disease".
As I wrote prior, this is the characteristic pattern of responses from vaccines where very little actual visible shrinkage. But more so "stable or slowing of disease". The 11% ORR is at least better than nothing.
4) Toxicity - relatively mild. Fever, chills and cytokine release syndromes from live bacteria infusion. Seems more so than Tvec virus. But overall manageable. Requires antibiotic to eliminate the live bacteria after.
5) It is CLEAR the company sees no future in monotherapy (with the less than so so results above). Therefore, they have immediately changed strategy, hired a reputable new CMO and pushing hard for combination PD1 trials. They are starting 2 combo trials. One with Merck. One with MedImmune. Like Tvec and ONCS, they are hoping for big increase in responses from combination.
This brings me to the crux. I repeat - very very few vaccines lead to obvious, visible, regression of tumors. Traditionally, vaccines have led to slowing of disease, or making cancer come back slower after surgery (cutting it out). But very few actually cause tumors to disappear. Tvec & ONCS have very clear shrinkage of tumors. Actual shrinkage has only been reliably seen with CAR-T and PD1.
As to whether combo Advaxis+PD1 will be as good or better than Tvec/Immunopulse + PD1, since they have no human data, the only clue we can use is their mouse data.
Mouse data:
(a) We know ONCS mouse data shows 100% complete regression with Immunopulse + PD1
(b) Advaxis' PR page links to the following medical publication. That publication states Advaxis+PD1 yields 20% complete regression (compare that to Immunopulse 100% regression).
The 20% vs 100% in mice should give you an idea as to comparative efficacy. Which would you put your money on? |
|
|
|
Post by lcd on Dec 17, 2014 13:08:47 GMT
JHam, thanks for sharing the JusticeAndEquality posts. They make me feel better about holding my shares after the post-milestones price drop. I am curious if you and others on this board who bought shares for the run up are still holding? I kept all my shares and am considering adding to them once I feel the price stabilizes.
|
|
madamemagoo
Junior Member
don't shoot mandy magoo!
Posts: 70 
|
Post by madamemagoo on Dec 17, 2014 13:16:26 GMT
I'm holding. Too much potential.  |
|
|
|
Post by JHam on Dec 17, 2014 14:37:28 GMT
JHam, thanks for sharing the JusticeAndEquality posts. They make me feel better about holding my shares after the post-milestones price drop. I am curious if you and others on this board who bought shares for the run up are still holding? I kept all my shares and am considering adding to them once I feel the price stabilizes. I am not in love with this guy or anything, but I think he is able to articulate the pros vs cons extremely well and I like it that he always backs up his opinions with facts, and leaves it up to the reader to decide. He also always insists on people to do their own DD and not take his word for it, which is refreshing. For me, it has been easy to see how ONCS feels about what they have based on all of their recents moves and hirings, but he adds a more detailed perspective. I have not sold a share since I started buying. My cost average is $.46 and it is my largest holding. I had planned on selling 20% once the stock hit $.65, which it did. But I got greedy and am now content with holding and adding up until P2b interim data, which I agree with J&E, should be very promising. |
|
|
|
Post by RLC on Dec 18, 2014 13:51:45 GMT
Thanks for posting these JHam. I'm still happily holding my shares and wish I had some more cash to pick more up at these prices!!
|
|
|
|
Post by lcd on Dec 18, 2014 16:00:40 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.
|
|
