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MOSPD2 sounds more tantalizing as an investor(implications in breast cancer migration and auto immune disease)that VB111 with what appears to be marginal efficacy. The more I think about it, the more dubious ovarian cancer sounds based on their phase II trial design. Dror could save a huge amount of money by shelving VB111 and getting rid of the recently hired corporate officers. But, can he change on a dime?
VBL Therapeutics Presents Data on MOSPD2, a Novel Immuno-Oncology Target
April 04, 2017
TEL AVIV, Israel, April 04, 2017 (GLOBE NEWSWIRE) -- VBL Therapeutics (NASDAQ:VBLT), announced today the presentation of new data on MOSPD2, a novel potential target in oncology. VBL's study, entitled "MOSPD2, a Newly Characterized Protein, Promotes Breast Cancer Metastasis" by Mendel et al., will be presented today at the American Association of Cancer research (AACR) conference in Washington, DC. The study observed from clinical biopsies that MOSPD2 is prevalent in invasive human breast cancer tissue and that levels of MOSPD2 correlate to breast cancer invasiveness. It was further observed that a knockdown of MOSPD2 in a human breast cancer cell line using CRISPR technology led to blockade of EGF signaling and significant reduction of breast cancer cell migration in vitro and metastasis in a mouse model.
"The current publication indicates involvement of MOSPD2 in motility and metastasis of cancer cells in a breast cancer model, with correlative clinical specimens expression pattern that is associated with breast tumor invasiveness," said Eyal Breitbart, PhD, VP for Research and Operations at VBL. "We believe that MOSPD2 may be involved in the regulation of cell motility in addition to breast cancer, as it is found in other tumor tissues as well. We recently reported its role in monocyte migration and are studying its expression and potential involvement in additional tumor types," added Dr. Breitbart.
The company believes that targeting of MOSPD2 may have several therapeutic applications, including inhibition of tumor cell metastases and targeting of MOSPD2-positive tumor cells, as well as inhibition of monocyte migration in chronic inflammatory conditions. VBL's "VB-600 series" of pipeline candidates is being developed towards these applications.
I think we will get more color on the GLOBES trial on March 15'nth. The company is at an inflection point. The question needs to be raised is VB111 strong enough to produce meaningful changes in survival; i.e.. were the phase II trials accurate? If you look at the ovarian cancer trial, there were only like 4 patients? in the lower dose cluster. My question is this: is that enough to justify POC? in light of the GLOBES failure. There is biomarker CA125 showing substantial reductions with VB111 as proxy for meaningful effect, but will that translate into/justify a phase III trial that may enroll very slowly.
One could make an argument for stopping VB111--or at least modifying the ovarian into a more robust phase II trial to establish meaningful POC. In light of the GLOBES(and my reading of the ovarian), I'm not sure it makes sense.
Alternatives? there are, I believe, backup compounds to VB111 which may be more potent--that's the real issue is strength of effect. In my exhaustive due diligence, one of the things that worried me was in the animal models, the potency/effect was not that dramatic. Another consideration is their preclinical program with MOSIP which looks to be very, very attractive, a true immune target. With their case, they could develop this technology, a true platform technology with autoimmune conditions such as MS.
Is there an argument to be made with stopping the ovarian trial until they can establish POC. All three of their phase II studies were flawed in this respect... low dose/high dose, changes in the trial structure in rGBM, a puny cohort for comparison in thyroid and ovarian. If I were CEO, I'd shelve future dollars on VB111 and move forward on their unique preclinical asset... MOSIP. I would buy back in on speculation would the CEO signal he's open minded on VB111. Look, Dror H. is a brilliant guy and an ethical guy, but sometimes you can be married to a particular asset and one can become blinded.... as an investor, as a doctor, or as a CEO.
$VBLT $150M mixed shelf prospectus filed https://t.co/EP1KKoOSkp
— Odi Bruckman (@odibro) December 18, 2017
BTW, on another point. At the last financing in late '15? weren't there warrants?? like 1.5 million or so in warrant with a strike price at like 7.50? So this is another source of monies for VBLT.
I thought the same thing... didn't Dror previously guide towards the year end for initiation of phase III ovarian trial. It will be interesting to see how he powers the trial--how many patients... 100-200 isn. It will also be interesting to see what the SOC arm will be... since standard of care by definition would be Avastin failures for the most part; can they do a SOC arm which is only chemo??? or, could they allow these patients to get chemo--or some other treatment at the discretion of the clinician, but there would be a risk of then losing SOC patients to clinical trial. Maybe they will do one arm of VB111 plus chemo and compare that to a clinician choice which could be anything... chemo OR clinician's choice. I'm also interested in progress in their earlier preclinical asset addressing mete static disease.
Huge mistake to sell. I may still reenter(at 20 LOL!!!). I still think the Japanese company partnership is a very big deal. I think in their private discussions with AFMD they may have gotten non-public information with non-disclosure agreements. The Japanese company is fairly small; they wouldn't part with 15 million without a reasonable basis for success. I may have lost out on AFMD, but as a Neurologist, I pray that VB-111 hits the big time next year to expand options for rGBM patients. Look at SAGE, is a postpartum depression treatment worth 3-4 billion in market cap??? with an infusion of 60 hours? I sold based on my analysis of public threads on Inspire/Facebook/blogs of about 12 VB111 patients, or about 10 % of study patients. Another positive point, the company knows more than we can every know about how the trial is doing, would they really open a manufacturing center now? if the y knew the drug was questionable?
I think the stock could rise to 10-12 over the next few months awaiting unblinding early next year. What is the wrinkle in the near term? Only one. If I were VBLT, I would raise additional monies in a financing prior to unblinding to move forward with ovarian, move forward with POC in their other oncology target, and perhaps do more preclinical work on NASH. I am anticipating a financing in the near term. It would make sense to do so, UNLESS they were certain as to the signal they are seeing. In that case, you would wait until next year for a follow up financing.
I think it is a form of validation of concept... even a mid cap Japanese co... has more resources, can look at more data that's privately held... This is my point. The Japanese company has more resources for more detailed examination of VB111's chances. They don't want to blow 15 million. Doesn't mean they are right, but, to my eye, very good news for VB111 chances.
Good news today for old VBLT. I'm sure the Japanese company did their due diligence. Overall, good news.
Yea, it's weird their stock price tanked today after the release, but 6 CR's in a cluster of 56 patients is a 10 % level which is very good. On the other hand, I don't know if the inclusion criteria. For example, the stellar Duke Un. Polio viral therapy for rGBM had/has strict inclusion criteria regarding location and other rules that might skew the data towards great outcomes. CLDX also used strict inclusion criteria which is partially why the phase III trial tanked. VBLT's phase II trial design allowed a real world experience... i.e. the worst of the worse, which is strongly in their favor.
Slightly off-topic to VBLT, but this press release today had a stunning nugget buried deep in the copy. If I'm reading this right, the company had 6 CR in a cohort of 56 patients? with recurrent high grade glioma, even had some PR converting into CR's. https://finance.yahoo.com/news/tocagen-presents-updated-durable-complete-131500145.html
As noted and I can confirm, the enrollment escalated in the second half of '16... the overwhelming majority of patients were enrolled after June of '16... kind of an escalating level of enrollment up to the end of '16.
I believe the FDA wants to improve VB111. We know from numerous points of data in various conditions that VB111 is safe. We know there is virtually nothing useful against rGBM, so the field is wide open.
One of the things that gives me pause is where Dror, in various calls, notes that a formal meta analysis of multiple trials in over 600 patients gives about an 8 month overall survival for Avastin. That is true, but if you dig into the actual trials mentioned--you get a wide range of months for overall survival from 7 up to 10.5, so there is a range of numbers for these trials. If the Avastin group survives on average 7.5 months that is one thing--but 10.5 is quite another. Since there was no selection bias in the GLOBES trial, one would be surprised to see a large Avastin number--but my point is that the number jumps around quite a bit depending on the trial noted. So you can't put too much emphasis on 8 months for Avastin and that never deviates; it does.
Another thing that bothered me(a bit)when reviewing the Inspire threads it that I found a patient or two who had stable disease on MRI--but were feeling awful(i.e. doing poorly in a subjective sense)and contemplated quitting the trial because that had to fly to center x or y in order to receive VB111. In the phase II trial, I doubt patient had to fly anywhere. This is a small point to be sure, but I'm just throwing it out there.
I found about 11-12 patients who received VB111 from the various social threads when I was invested and my "feel" was that the overall survival was not 14-15 months in this cluster--but was much less. That is only 10 % of patients but I got a feel that the final results might be close compared to the historical Avastin controls. Then I found a few drop outs from the Avastin arms as was noted on the conference calls. So, I don't think this is a slam dunk, and I don't feel that the 8 months survivorship for Avastin is set in stone. I do think there will be a tail of longer surviving patients in the VB111 and this should be enough to approve the drug. As a neurologist and former shareholder, I'm cautiously optimistic about VB111 but have not bought back in to date. Good luck to all longs--and more important to the patients. If it were up to me, I'd approve the drug just based on a tail of long term survivors alone. That should be enough IMHO.
Dror Harats @VBLTherapeutic discusses $VBLT novel immunotherapy in late-stage testing for glioblastoma https://t.co/71R46exxW6
— Daniel S. Levine (@dslevine) September 14, 2017
VBLT manufactured VB111 and has a site where the drug was distributed for the trial. They don't know names, but they may that study number 15 was recruited on November 13 , 2016 and got VB111. Do they know that level of granularity. I think they do, but, of course, I cannot prove it. Open label trials like this tend to diffuse/bleed data out... not right away, but on the big picture, yes. I think by communicating with docs in the trial about their impressions, their knowledge of total study drug given in total over the GLOBE trial, with their knowledge of recruitment rates(they know the exact median/mean date of entrants, combined with their knowledge of death rates(at what time have 25, 50 % of deaths occurred), they can then backtrack and probably have a very good estimate about how the trial is doing. Not exact science, but pretty good.
The company is not really blinded IMHO. One thing I think they must know at this juncture is the following: how many patients are on VB111/Avastin versus Avastin only. That would be an interesting statistic no matter what the final overall survival number is. If you have say twice as many patients still on VB111 as on Avastin only--this would strongly imply a tail of long term survivors. In the stellar phase II results, the VB111 high dose cohort only got like 3-4 infusions of VB111. I have to check that but I think thats right. So, they probably know how many VB111 infusions have been given to date and with some fancy math can track how the average number of VB111 infusions compares to the phase II trial.
On second thought, it could be they now know they beat the pre-determined futility estimate. That would be a very big deal. I would bet they know--within a few days--the overall survival difference at this point in time. They could share this information with to cement some sort of non-US deal for market rights.
VBLT could run big here without news as well. Biotech is looking more than just fine lately. Take a look at AXON. Coming up on a big binary with a phase III for Alzheimer's which I think does not work, or works in the most tepid fashion. AXON bought there phase III drug from a big pharma for peanuts 5-10 million dollars. Why do I bring up this example? The market cap of AXON is well over 2 billion dollars... for smoke and mirrors. VBLT has ore interesting/innovative tech in a phase III program with a market cap of under 200 million or so. The only difference is the CEO of AXON is beloved on wall street; while Dror is an outsider. For a bet on technology, I would much rather play the biotech roulette table with VBLT than AXON. Sorry to get off topic. But I do get a big disgusted with all of the news reports on AXON; while ignoring the VBLT story; but that could change in a snap.
Congrats to VBLT longs! I wonder if there is some data leak out regarding the trial on the good side, but I wonder if the price jump today represents something completely different: maybe some rights for VB111 in Asia or some other territory, or a budding NASH deal? or some positive news on their earlier pipeline project? I would guess something is brewing in terms of a major deal for a non-US territory for VB111 or a NASH deal. Remember Dror mentioned he was in talks with a pharma regarding NASH.
Oren, I've often wondered about the feverish issue as well-does it make sense to treat it or not. In my due diligence on VBLT, in the phase II trial for rGBM, those with fever were treated with Tylenol, ect... So, treating the febrile response should not impact the trial.
I think you're right. At the end of the day, if VB111/Avastin shows a 30 day benefit in prolonging life in patients with no options, it will be approved(especially under current FDA stewardship). If VB111 also shows a tail of longer term survivors... i.e. over 18 months, this will strengthen their case. If the survival benefit is less than a month, probably not. The central issue is if the trial shows a survival benefit for patients who received VB111. Fingers crossed for VB111.
Listening to the call, there will be no futility analysis, so that's not an issue--only the final survival data. I wonder why this is no longer needed? Maybe because they are so close to the conclusion of the trial and if they have a subset of long term survivors, a futility analysis isn't needed? In other words, the company, monitoring board and FDA do want to give every chance to see a survival benefit.
My fear is that the response will be lackluster given the nature of RBM and failure of so many treatments... hence it is possible VB111 might not pass futility. Unlikely, but a real binary-event possibility. On the other hand, I would love to be proven wrong. NOTHING, as a neurologist, would make me happier. I catalogued about 10 -11 patients(in aggregate) on Inspire/Facebook that made me doubt VB111 in rGBM. I suspect the company has a strong hunch on how VB111 is doing and are making much more educated hunches than I. They probably have better number based on their analysis than I.
Still the drug could be approved even if the overall survival isn't stellar. Let's say there is only 30 day's of overall survival benefit... say 9 months with Avastin only, but 10 months with VB111 plus avastin, but if there is a minority of long term survivors--say like 10-20 patients are doing well after 18 months but only 5 percent with Avastin only are living for 18 months or more, I could easily imagine a scenario where VB111 would be approved.
I also expect the stock price to move up in anticipation of the interim in September, perhaps to the plus 6 price per share. But, upward movement moving into September(or even downward)is not evidence of success or failure.
The company has a lot going for it outside of VB111 as well. We're moving into a hard binary event with the interim.
This was my fear as well during my due diligence phase in investing in VBLT. I've read that Avastin can create an hypoxic environment in glioblastoma(already a hypoxic environment to begin with). In theory, this could dampen immune therapies such as VB-111. There is actually a paper suggesting the order of Avastin plus immune therapies may be important--ie immune therapies first, then Avastin. However, I've read other papers suggesting Avastin may potentiate immune therapies and this is what the second cohort suggests in the phase II trial, so we will only know when the final results come out.
In looking again at VB-111, I'm more convinced than ever that it works, i.e. it has a biological effect. I'm less convinced that rGBM was/is the right initial target. I do recognize the companies mindset, an untapped, fairly large indication to gain a foothold with zero treatment options. Should they succeed, they can expand to newly diagnosed and other cancer indications. Should they fail, will they proceed with ovarian? moving to Modin? or will they retrench and move onward to the VB600 series and wait to proceed with ovarian after they finalize a NASH partnership.
It doesn't work that way. I believe dror misspoke and/or is wrong. I followed this process closely with CLDX and other companies. I believe the company knows when the period of twelve months has occurred in half the patients--lets call this date D-Day. When D-Day occurs-the data review board will meet--but not right away--there is a period of one month--to even six weeks until this actual date. The data review board will then issue a specific go/no go recommendation. They will recommend a no-go rec if the company has not met futility, or a go if futility is met. I highly doubt this will leak out in even the slightest manner... it could happen, but highly doubtful. So you can discount both a price rise/or price decline in the days before such a decision.
So, you can discount a price decline or rise has having any meaning, at least in terms of the outcome of the interim analysis. A partnership for NASH, on the other hand, might start to leak out in the days before a final inking of the deal, but I doubt it. Will have to simply wait and suffer until the interim comes out =)
Good analysis. I think it is very good news overall.. seeming vote of confidence.
To paraphrase an old pray, he that watcheth over VBLT shall neither sleep nor slumber.
Although I'm out of VBLT, I watch it closely. I internally predicted this stock movement a month ago. I expected a move--on low volume--down into the 4's, but I believe it may rise back to the low 6's before the interim. This will be the make/break moment for VBLT. If it passes muster, it will break much higher. If not, I'm skeptical the company will commit 20 million for ovarian--but I predict a possible NASH deal and full steam ahead with the 6 series IMHO.
BTW, the ASCO data for VB111 was very interesting to me--as it the potential for combination therapy with checkpoints.
I believe there were/are two fears.... One is a fear of VB111 not passing futility. Ii believe this chance is low-but would estimate the chance at 20 %. That figure was too high for me--hence my sale. The second fear was/is would the company try to do a financing prior to the interim. VB600 seems like an excellent drug-but will take $'s to develop further.
The interim is more important/relevant here because the trial is so close to being concluded. Basically, had the interim occurred under the original mechanism after 91 events, it was too early, but here... you have more events but a 12 month potential drug follow up for 50 % of patients, so if the drug passes futility, IMHO that is a VERY big deal. My risk tolerance for stocks(and life)has simply changed in the past year. So, I do think VB111 will pass futility, but the risks are definitely there given how brutal rGBM has been to crack with so many failures.
So, I can see big swings--perhaps up to 6.5 or higher and/or down to 4.5 before the interim in a few months. I don't think you can read anything into positive(or negative)price swings.
As to a potential financing. I feared that, but I don't really see that now. The volume/price move after ASCO has been lacking. Had the price spiked to 6.5 like last year, maybe, but I highly doubt another financing now.
Even though I'm out, I still am highly interested in how this plays out... so I hope you guys don't mind me occasionally posting.
Positive upside prior to the interim . In the KOL event on NASH, Dror mentioned in the q and a that they are in discussions with a pharma regarding NASH. An upside prior to the interim could be a NASH partnership. Why now? If Dror is unsure of VB111 in rGBM, he may be pushing hard for a NASH partnership. The early phase II data was intriguing with VB201 and they have a backup which is more potent. Such a move would give them the cash to develop VB600 series compounds. Such a deal would really de-risk the entire interim analysis event. VB600 looks very good, it's very interesting, but early.
I did not bet on such an event, but it is a real possibility. From Dror's position, it makes sense. I would not be shocked by a NASH partnership or option to a partnership in the next few months.
That was my hunch. If you were given a tip on some bad news coming down the pike in say four months... you would have to remain calm and hope that nobody else has--or will have--that news and dribble out of your position 10-15 thousand share per day, or such a person might panic which might lead to irrational selling urgently.
I'm not sure it was a leak from the blinded data, but rather someone was jinxed at the cut off date in March being hit(triggered by an event number being hit). That would be someone in the know. Obviously not anybody in the company as that would constitute insider selling--but.... friends or other relations. Let's say the cutoff for this safety review was 92 events(my hunch), this might indicate that the Avastin and VB111 events are occurring very closely to one another.
There was some pre specified number for the second safety analysis... Yes. the PR effectively said that. Something to the tune, based on the timing of the interim, we can now predict mid year for the interim analysis. In fact, the actual wording was something that the cutoff for the safety analysis was a date some time in March. That was the other thing I forgot to mention in my last post--probably not a factor--but in late March there was a huge fire sale in VBLT for an hour or two, when someone exited a position in a fury--droping the stock price well under 5 for a few minutes. That kine of freaked me out--there were various hunches such as margin calls ect...then she the safety analysis mentioned the wording based on a date in June--I drew a possible connection--maybe a false one. But this was my least important rationale for selling.
I sold my position Monday. I believed holding through the interim was too risky. Having said that, I do believe VB-111 "works" but rGBM may have been the wrong initial target... a literal and metaphorical graveyard for so many cancer targets. I do fear they won't past futility in the interim. I think there is a chance I'm wrong, but too risky at this juncture based on Dror'r cryptic comments on the last KOL about worrying about powering trials adequately, my own unscientific review of public posting regarding VB-111 on Inspire/Facebook/Blogs, and, most important, my review of how anti-angiogenics and immune based targets have performed(in the negative)in rGBM.
I'm still bullish on the VB600 series, NASH prospects, but it's early(and very interesting) and other potential indications for VB111.
That was one of a few weird parts of the conference call... declining an SPA from the FDA???
I thought the whole process involves a company petitioning the FDA to allow a SPA, then there is negotiations, and an SPA is agreed to. Weird. Perhaps there was something the FDA demanded to be part of the SPA... related to biomarker--CA125, or efficacy analysis, or maybe VBLT wanted two arms.... VB-111 versus standard of care to avoid some of the problems involving the GLOBES trial where patients at first dropped out after being assigned to the Avastin arm.
To be perfectly candid, I'm a bit more uneasy after this call regarding VBLT regarding the interim based on how the manufacturing facility for VB-111 will open in the second half, the ovarian trial(results were known from the phase II a year ago) will start late in second half with the checkpoint plus VB-111 trial will begin end of year and after next year.
My point... it looks like a lot of VB-111 activity will commence after VB-111 passes the interim analysis. There could be a real fear of passing the futility hurdle in the interim analysis. If VB-111 fails to pass futility one can readily envision dropping the manufacturing facility, canceling the ovarian cancer trial(the whole SPA issue is weird beyond almost any rationale).
I can see, should VB-111 not pass futility, you will see the company focusing all available monies on the VB600 series and trying to partner for NASH.
I would agree. A positive distinction. I think it is possible VB-111 will be on the market by year-end '18.
The preclinical support of combining VB-111 with checkpoints is also highly encouraging since the future of oncology and immune oncology will be combination therapies.
Either neutral--non related to the phase III rGBM trial, or positive. You're not going to have bad news in a planned company presentation at ASCO. My point is the company is emphasizing this presentation with an audio component. Could this mean some sort of significant announcement?
Interesting the company has all three upcoming presentations on their website... The one this Friday on VB-111/checkpoints, the earnings call next week, and ASCO '17 presentation.
I don't recall the company having an aural presentation at this past year's ASCO? And some big things were discussed such as ovarian ca results. Yet, this one is a company presentation? about phase II results.
http://ir.vblrx.com/phoenix.zhtml?c=253311&p=irol-EventDetails&EventId=5256665
Hmmm.
gr, just sent an email ur way. david
The DMSC will meet when there are 105 events and 50 % of patient in the trial have had 12 potential months of treatment. The will meet and determine of the futility criteria is met... does the drug pass futility. Then they will give the decision back to the company. In my experiences I remember with similar situations--ie CLDX, the stock is typically halted in the timeframe of the meeting/immediate aftermath, the company gets the news, issues a PR, then the stock reopens(hopefully higher =)
I got a kick out of your edit. No worries Value, my grammar sucks. I second gr... no grammar police here, bro.
While Oren could be right, the phase II data argue otherwise.
In the limited exposure cohort, progress ors on VB-111 went onto Avastin... total overall overall survival was 8 months, average time to progression on VB-111 was 2 months, so patients might have averaged something less than 6 months on Avastin--probably just 3-4.
In the continuos exposure cohort, progressors on VB-111 went onto combination therapy with avastin.... time to progression on VB-111 was 2 months, overall survival was 14 months... that means several more months of Avastin exposure.... since the average number of VB-111 dosages was like 4.4, so by definition the continuous cohort received much more avastin than the limited exposure group.
Oren's argument appears to be Avastin is harming patients. There is no data that shows the placebo outperforms avastin in rGBM. There is also no data showing the converse.
But if you examine the phase II data, looking at the swim lanes of both cohorts, the continuous cohort received twice as much VB-111, lived twice as long as the limited cohort, AND received twice as much Avastin than the limited disease cohort. How do we know, the continuous cohort received Avastin and VB--111 on progression, lived twice as long as the limited cohort.
If you look at the phase II data carefully, if anything there appears to be some synergy b/w Avastin and VB-111. That's not to say that Oren's is wrong, but the phase II data suggests he is.