Buh bye
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I am somewhat puzzled to all of the immediate internals at Advaxis right now. If I was divorced from my investment, and simply a casual observer, I would be hard pressed not to believe that aquistion talks have been in progress and are nearing closure. Why bring in Lombardo? Why the sudden removal of Doc? Why the unexplained exit from the conference? Why the intentional silence?
We know the tech is compelling. We know there is plenty of cash for the near term operations. Something is going on that can't be disclosed, at least to date.
I hope you're are right and BP doesn't figure this out before it's too late! However, I suspect there are a lot of smart folks looking at this, and they'd be wise to make a move sooner rather than later.
A bird in hand is worth two in the bush
You and I are making certain assumptions to draw a conclusion. In my case, I do not expect silence much longer from Advaxis. Furthermore, I believe Advaxis will have material news that will impact the pps positively. For the pps to languish in single digits the next four months, you have to be assuming that nothing material will transpire. I believe this is an overly "optimistic" expectation on your part. I like what Terry alluded to concerning "a trillion dollar" valuation for the company that cures cancer - now that's big-time vision.
I will say this: I do not see any viable or realistic scenario that keeps Advaxis from being acquired post EMA submission, other than failed results, which seems extremely remote at this juncture. Last thing, although I expect news in September, possibly this Wednesday, if the silence continues through September, this would leave me to switch my view that Advaxis had been and is in ongoing acquisition talks.
Either way, September looks to convey an interesting story.
Possible, but that seems a bit low at this stage. If you are correct though, then I believe that implies that process is happening right now, prior to EMA submission. If so, I sincerely hope they get other bidders, since 2 or so billion is basically stealing the tech.
Terry Hallinan,
Do you believe that Advaxis' current silence is due to acquisition proceedings?
I will be very, very surprised if Advaxis is acquired prior to EMA submission. If they sell prior to EMA submission, it would likely mean one of the following:
1. They get a price they can't refuse: 4.2 is the minimum IMO
2. They accept a very low price because they do not see viability and are looking to release now.
3. They accept a conditional price, based on licensing, partial ownership and other factors
I see none of the above transpiring. I expect to hear news in September, very possibly Wednesday (inferred by their pulling out of the Sept conference - something material is likely driving that). I do not expect the news is acquisition related, and probably more in line with some sort of licensing/partnership deal, followed by near-term road map, or possibly new leadership, and maybe a combination of the former. If what I believe is about the happen comes true this September, Advaxis will quickly move past the 6/8/2015 high before 2017 is over. From there, material events of EMA submission and AA EU and FDA approval will continue to drive the valuation beyond 4 billion. With all of this, an acquisition can still happen somewhere post EMA submission and post the first AA (~18-20 month timeframe). The acquisition price could range from FOUR to FIFTEEN, depending on a variety of factors.
And all of this will likely occur well before 2020, best case mid/latter 2018, worst case latter 2019. If Advaxis is not acquired before 2020, it's because of delayed events and or failed trials.
Everything has a price.
FOUR.TWO
You are correct sir!
A197 / Identification of an intratumoral immune gene signature
associated with tumor regression in an Axalimogene filolisbactreated
murine HPV+
tumor model
Kosoff R.E.1
, Ramos K.1
, Balli D.1
, Petit R.G.1
, Hayes S.M.1
1
Advaxis Immunotherapies, Princeton, United States
Axalimogene filolisbac (AXAL), a live attenuated Listeria
monocytogenes (Lm)-based immunotherapy that expresses
and secretes the E7 protein of human papillomavirus (HPV)
16, is currently being evaluated in clinical trials as a treatment
for patients with HPV-associated cancer. Advaxis´ Lm-based
immunotherapies act by stimulating innate immunity through
multiple mechanisms including the STING pathway, inducing the
generation of tumor antigen-specific T cells that infiltrate and
destroy the tumor and by reducing the numbers and functions of
immunosuppressive cells in the tumor microenvironment. To gain
a better understanding of the molecular mechanisms of action
of AXAL and to identify immune gene signatures that associate
with AXAL-mediated tumor regression, we performed immunerelated
gene expression profiling of tumors in an AXAL-treated
Abstracts / POSTER SESSION A
132 THIRD CRI-CIMT-EATI-AACR INTERNATIONAL CANCER IMMUNOTHERAPY CONFERENCE
murine HPV+
tumor model. Total RNA was extracted from intact
tumors harvested on day 19 post tumor implantation, at the first
appearance of tumor control, from HPV+
TC-1 tumor-bearing
mice treated with two doses of AXAL, XFL7 (parental strain of
AXAL that lacks HPV-E7), or PBS. Gene expression levels were
measured using the NanoString nCounter® PanCancer Immune
Profiling Panel and were analyzed using the nSolver™ Software.
Mice from any treatment group whose tumors exhibited a
≥50% increase in size between days 15 and 19 were classified as
progressors (n=12), while mice whose tumors exhibited a ≥10%
decrease in size between days 15 and 19, all of whom were in
the AXAL treatment group, were classified as regressors (n=7).
Statistically significant differences in gene expression levels were
noted between regressors and progressors. First, high expression
of gene signatures indicative of CD4+
T cells, CD8+
T cells, cytotoxic
cells, and NK cells were observed in the regressors but not in the
progressors. The high expression of these effector cell-specific gene
signatures is consistent with our previous flow cytometric analyses
of tumor-infiltrating lymphocytes isolated from regressing tumors
in AXAL-treated mice. Next, significantly higher expression levels
of 59 genes were detected in regressors compared to progressors.
This 59-gene signature contains genes involved in T cell and NK
cell cytotoxicity, in antigen processing and presentation, and in
cytokine, chemokine, and interferon signaling. This study has
identified an intratumoral immune gene signature that highlights
the importance of effector lymphocytes, mature antigen presenting
cells, and cellular communication in AXAL-mediated tumor
regression. This intratumoral immune gene signature may serve as
a guide to identify molecular biomarkers associated with clinical
outcome in patients with HPV-associated cancer receiving AXAL
immunotherapy.
Keywords: Biomarkers, Immunotherapy, Gene signature
A189 / Gene expression profiles associated with stable disease in
metastatic castration-resistant prostate cancer patients treated
with ADXS-PSA immunotherapy
Hayes S.M.1
, Petit R.G.1
, Stein M.2
, Tutrone R.3
, Mega A.4
, Fong L.5
,
Agarwal M.6
, Naomi H.7
1
Advaxis Immunotherapies, Inc, Princeton, United States, 2
The
Cancer Institute of New Jersey CINJ Rutgers, Inc., New Brunswick,
United States, 3
Chesapeake Urology Research Associates, Towson,
United States, 4
Lifespan Oncology Clinical Research, Rhode Island
Hospital, Providence, United States, 5
UCSF University of California
San Francisco, San Francisco, United States, 6
Associates in Oncology /
Hematology PC, Rockville, United States, 7
University of Pennsylvania
Abramson Cancer Center, Philadelphia, United States
ADXS-PSA, a Listeria monocytogenes (Lm)-based immunotherapy
that expresses the tumor-associated antigen prostate-specific
antigen (PSA), is designed to stimulate an antitumor response by
directly targeting and engaging the immune system. However,
tumors, as well as chemotherapy and radiation therapy, are known
to suppress the immune system. For these reasons, we examined
the immune status of metastatic castration-resistant prostate
cancer (mCRPC) patients, pre-and post-treatment with ADXSPSA,
by profiling immune-related gene expression in peripheral
blood mononuclear cells (PBMCs). Total RNA was extracted from
PBMCs isolated at multiple time points from mCRPC patients
participating in the ADXS-PSA dose-determining stage of the
phase 1/2 trial evaluating the safety and tolerability of ADXSPSA
as a monotherapy and in combination with KeytrudaÒ
. The
NanoString nCounterÒ
PanCancer Immune Profiling Panel was
used to quantitate gene expression levels. Normalized NanoString
gene-level counts were compared against established immune
cell-specific gene signatures. Four of the 12 patients (33%) in the
ADXS-PSA monotherapy cohort had stable disease (SD) according
to RECIST criteria, thereby allowing us to compare the gene
expression profiles of SD and progressive disease (PD) patients.
Abstracts / POSTER SESSION A
128 THIRD CRI-CIMT-EATI-AACR INTERNATIONAL CANCER IMMUNOTHERAPY CONFERENCE
When the kinetics of expression of genes associated with T
cell activation were analyzed, SD patients were found to have
significantly higher levels of these genes post- ADXS-PSA-treatment
than PD patients. In addition, SD patients had significantly higher
levels of genes expressed by mature antigen-presenting cells
and by activated CD4+
T cell effectors than PD patients, which
is consistent with findings observed in mouse tumor models
treated with Lm-based immunotherapies. By contrast, PD
patients had significantly higher levels of genes associated with
immunosuppression than SD patients. Collectively, these analyses
not only provide insight into the mechanisms of action of ADXSPSA,
but also identify potential pharmacodynamic biomarkers
of clinical response in mCRPC patients treated with ADXS-PSA
monotherapy.
Keywords: PSA, biomarker, metastatic castration-resistant prostate
cancer
A188 / Persistence of expanded TCRß clonotypes is associated A
with clinical activity of ADXS-PSA immunotherapy in metastatic
castration-resistant prostate cancer
Hayes S.M.1
, Petit R.G.1
, Haas N.2
, Tutrone R.3
, Mega A.4
, Agarwal M.5
,
Fong L.6
, Stein M.7
1
Advaxis Immunotherapies, Inc., Princeton, United States, 2
University
of Pennsylvania Abramson Cancer Center, Philadelphia, United
States, 3
Chesapeake Urology Research Associates, Towson, United
States, 4
Lifespan Oncology Clinical Research, Rhode Island Hospital,
Providence, United States, 5
Associates in Oncology / Hematology PC,
Rockville, United States, 6
UCSF University of California San Francisco,
San Francisco, United States, 7
The Cancer Institute of New Jersey
CINJ Rutgers, Inc., New Brunswick, United States
Active immunotherapies, such as ADXS-PSA, are designed to
help a patient’s immune system recognize and respond to
tumor-associated antigens. ADXS-PSA is a bioengineered, highly
attenuated strain of Listeria monocytogenes that secretes a fusion
protein consisting of a truncated fragment of listeriolysin O, which
has adjuvant properties, and the tumor-associated target antigen,
prostate-specific antigen (PSA). Because aß T cell effectors are an
essential component of the antitumor immune response elicited
by active immunotherapies, we sequenced the complementaritydetermining
region 3 (CDR3) region of rearranged TCRß genes
to monitor and characterize the peripheral aß T cell responses
of patients with metastatic castration-resistant prostate cancer
(mCRPC) treated with ADXS-PSA. Sequencing was performed on
genomic DNA from peripheral blood isolated at multiple time
points from mCRPC patients participating in the ADXS-PSA dosedetermining
stage of the phase 1/2 trial evaluating the safety and
tolerability of ADXS-PSA as a monotherapy and in combination
with KeytrudaÒ
. Because 4 of the 12 patients in the dosing cohort
had stable disease (SD) as per RECIST criteria, the pre- and posttreatment
TCR repertoires of SD and progressive disease (PD)
patients were compared. All analyses were performed using
Adaptive Biotechnologies’ immunoSEQ Analyzer.
We first quantified the diversity of TCRß sequences in the
peripheral blood of mCRPC patients at baseline and after treatment
with ADXS-PSA. At baseline, a wide range of TCR diversity was
observed in both SD and PD patients. After ADXS-PSA treatment,
changes in TCR diversity were noted in all patients, but these
changes were not significantly different between SD and PD
patients. We next examined the dynamics of the peripheral aß
T cell response by tracking the abundance of the top 100 TCRß
rearrangements over a 9-week time course, which included 3
ADXS-PSA treatments. Expansions of new and pre-existing TCRß
clonotypes were observed in the peripheral blood of all patients
after ADXS-PSA treatment. In the SD patients, the clonal expansions
occurred primarily after the first ADXS-PSA treatment and were
stable over the entire time course, consistent with the report that
improved survival in YervoyÒ
-treated mCRPC patients is associated
with the maintenance of TCRß clonotypes. By contrast, the clonal
expansions in PD patients were asynchronous, occurring after
each of the 3 ADXS-PSA treatments, and were not sustained, as
evidenced by the subsequent loss of many of the newly expanded
TCRß clones. In summary, these results indicate that the stability
of clonal expansions during ADXS-PSA-treatment distinguishes SD
from PD and suggest that stable clonal expansions may be used to
identify clinical responders to ADXS-PSA treatment.
Keywords: TCRß, PSA, metastatic castration-resistant prostate
cancer
This is nothing, just teasing. When this thing busts out, it will blow past $10, on the way to $16+ before you can blink.
"What is really, really, really, terribly bad right now is the determined silence and obvious lying of new management imposed by directors."
By design. I do not think they are lying. They are simply not answering the questions. I was told as much in a question I had. The answer, "We will not disclose", which infers there is something to disclose that is probably not ready for disclosure.
I suspect September will be a month we look back on as the month things [changed].
you forgot one,
(4) they just ain't that smart
Hey Meishairwin, news flash for you in case you didn't know:
The science just works. You know, like the Nike slogan "Just Do It"?
"Advaxis, it just works"
All your other rhetoric is best suited for vanilla ice cream. We're talking about tiramisu or creme brulee here...
Yah, but it's still about 2 years of bake time, give or take...
I find it "interesting" that the pps has started to move up, just a few days before the PSA trials results are announced.
Could it be? Nah, it couldn't, could it? Nah. Maybe?
Just maybe there is a BP that has started to take notice.
Just maybe the silence has been due to behind-the-scenes licensing deals.
Just maybe shite is going to hit the fan, come September.
Just maybe pulling out of the conference has to do with licensing deals and material info.
So, suppose the data is great and some entity already has enough "early" info to have been forming a licensing deal, with big-time up front cash.
The pps will respond, significantly.
Then throw in EMA submission
Then throw in an EU partner
Then throw in AA EU
Then throw in AA FDA
And you'll have $100+ pps easily...
And, finally, add acquisition at 100% premium from there, and there's your 8-10 billion valuation
So, throw out the early acquisition talks, throw out the EMA submission discussion, throw out the EU partnership supposition, and hypothetically assume that near-term results are SUPER compelling and result in licensing deals.
The effect on the pps could/would be:
a. Inconsequential - market yawn and 5% gain
b. Moderate - market takes notice and a 10% gain
c. Significant - market says, "oh oh" and a 30% gain
d. Insanely good - market says, "holy shite", and the stock runs and runs and runs and runs and closes in the land beyond $30
Interesting times right now for certain...
Blue, I'm with you. I just hope Advaxis holds firm and avoids early acquisition. The potential is too great.
BTW, have you heard the news? DOC is no longer CEO.
Up 10% in just 7 trading days; keep that going.
See I can spin it anyway too.
"At least you know now why the presentation was canceled."
Terry, please correct me if I've misunderstood, but I believe you are implying that Advaxis is in process of being acquired or actively looking to be sold, given your other comment "Tony Lombardo standing by silently without a single thought to share"
If you believe that Advaxis will avoid an acquisition post an EU or FDA approval, you are very, very naive. Once that EMA submission happens, the sharks will start circling...
Ah, so you believe it's going to be sold early, as in within months? What I meant by not having to wait much longer is more like 2018/2019, when we'll see an approval or two, maybe? I, like you, would much rather see the maturation of Advaxis, which implies many, many good things for folks suffering with cancer.
Hopefully, the acquirer (if true), carries things forward.
No worries Terry. Relatively speaking, you won't be waiting much longer...
Bezos is on the West Coast...??
I'm not sure if you know, but here is some info that may help clear things up a bit.
https://www.cnbc.com/2017/07/06/reuters-america-advaxis-ceo-daniel-oconnor-resigns.html
Sure, I can see the conversation now,
"Hey guys let's dump this thing right now for 600 million. Yes, I know we are on the verge of EMA submission and, very likely, AA in both EU and FDA, but I don't think we should wait anymore. I mean look around - the immunotherapy market is starting to gain traction, so let's take advantage and sell early. Yes, I get that KITE has added more exposure, but it's time to cut our losses and move on.
Logic - take a loss now, just prior to the beginning of starting the engine.
Makes ZERO sense to sell now UNLESS some entity is looking down the road at the potential and is willing to place an insane bet to get in early at the "right price".
It's not "required" but it's needed for Advaxis. They would be neutered without an EU partner and they know it, and so do you - obviously.
As for my conversation with IR, my question was binary and had nothing to do with a partner. The response was not boiler plate and definitely implied something else. Take it for what it's worth. I still think your response was disingenuous because you know full well what folks here are trying to wrap their heads around with respect to an EU partnership.
It's fine, continue to play your game. I'm not playing though.
Let me phrase it another way, so you can stop dancing around the core issue:
Does the company Advaxis have the "facilities" and current "infrastructure" necessary to successfully achieve approval from the EMA?
I'll give you a hint: When I asked IR about EMA submission and a distribution partner, their response was "We will not disclose this information."
Your diligence is due.
First, fbg, by Hovacre's view you're actually bloating the numbers and wrong, so you need to be consistent. Jump on that support and sell for 500 -750 million and take your loss. Go for it.
Sure, the safe, conservative view is to follow the thought process:
"What does the market say Advaxis is worth right now? A: about 6 and change
"Okay, now what is a typical multiple in BIO acquisition these days?" A: 50% to 150% premium
So, you get anywhere from $9-$15 pps. Vanilla ice cream. Yummy.
What you fail to account for are intangibles. That is something nobody can predict, thus we speculate.
So, you're basically assessing valuation on the current market value by some multiple, which is the absolute most conservative (although valid) thought IF, IF, IF you are coming from the position of "What does the market say Advaxis is currently worth?"
However, I sincerely doubt the BOD has that conviction, and I would imagine that companies like Fidelity would be very much opposed to a sale of $12 or $15 per share.
Nevertheless, we shall see.
Completely disingenuous response. Explain how Advaxis will market and distribute their product line without an EU partner?
Yes, explicitly the EMA process does not require a partnership, but there must be demonstrable support for distribution. Advaxis, in it's current form, is not remotely capable of that support. They need a partner OR some radical change to make that happen.
So, yes, literally "There is no such requirement to submit an MAA to the EMA.", but you know better what that implies.
Per Hovacre, there just isn't any logical reason for Advaxis to be acquired right now. Of course, there are a lot of illogical reasons, in addition to very high-risk reasons!
"Irrational Exuberance"
Chatter growing around immunotherapy and Advaxis has, potentially, the most versatile, cost-effective platform? Ironically, the timing could be just perfect as I believe we will see a bubble in the immunotherapy market eventually. We are just at the beginning of somebody putting the needle into the balloon...
4.2 billion - it's just a number with no rational support I keep revisiting
I draw a few different conclusions from the KITE acquisition:
Pros:
1. If we believe the Advaxis platform has greater potential and impact than KITE's immunotherapy platform, and KITE was just acquired for 12 billion, than what does that mean for Advaxis' potential?
2. It's awfully quiet at Advaxis - too quiet. I believe it may infer imminent material news - BUT being "acquired" is not something I believe is a possible near-term event.
Cons:
1. What is Advaxis missing that is preventing them from being acquired for significant valuation? Does it come down to just having an approved drug and it's game over?
2. Lombardo is an interim CEO. We need more permanent leadership, unless the company is up for imminent sale.
If you have to sell your position "right now" yes, that would suk. However, there is a lot in the queue that may unfold for the next several weeks/months, so we'll either continue to suk OR change dramatically.
I believe it's the latter.
What leads you to believe that something is wrong with the platform? Sure there has been a change in leadership, but beyond that what has really changed?
It makes absolutely no logical sense to sell the company right now, significantly under potential value, UNLESS something is seriously wrong with projections and viability.
There have been no indications that Advaxis has stopped moving forward with POR.