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CVI in action
We shall be subjected to the yo-yo movements until we get very significant news. Few percents up, then few percents down ... Not a real roller coaster, but the frustration level here will be going up.
Job titles might be similar, but the actual job descriptions are not. Hard to infer, but I really doubt they have 13 brand new positions. LinkedIn is not a perfect platform, especially regarding the jobs/hiring. Moreover, they discriminate wmtgreeters with GEDs.
Now you are putting your words in my mouth...
That's a brilliant thinking!
Would TWO points be statistically significant? My GED background says no, but you know better.
Are you suggesting that the great CEOs are those who have run successfully a statically significant number of companies as CEOs? Vice versa, if a CEO did not bankrupt a company it's still considered a statistically insignificant to make a conclusion he would not bankrupt companies in the future?
As a @wmtgreeter and currently unemployed (nobody wants my worthless GED, sigh...), I've been constantly monitoring job listings at Advaxis. These new jobs have been posted recently, albeit some have been for a while. The number of open positions was as few as 2 this summer. The recent spike tells me one thing and it's the following:
We are about to get either huge cash influx or be bought out for few beeches.
Make your bet.
What a shocker! 13 Advaxis jobs posted on LinkedIn:
You too should be applying, it's a best place to work in the Orthogonal Universe.
@wmtgreeter and currently seeking an opportunity in media promotions (no pump&dump offers please!).
Senior Associate, ManufacturingPromoted
Company Name
Advaxis Inc.
Job LocationPrinceton, New Jersey, United States
Initial job responsibilities will include working with a group of manufacturing personnel responsible for a diverse range of manuf...
Be an early applicant
6 days ago
Advaxis Inc. logo
Job Title
Associate Director Clinical OperationsPromoted
Company Name
Advaxis Inc.
Job LocationPrinceton, New Jersey, United States
As applicable, this position is responsible for the coordination of all activities performed by Study Team Members assigned to her...
3 weeks ago
Easy Apply
Advaxis, Inc. logo
Job Title
Director, Human Resources Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
Design, select and implement training and development programs to meet business objectives, develop ... careers-advaxis.icims.com
2 months ago
Advaxis, Inc. logo
Job Title
Quality Control Analyst Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
The candidate should have sufficient background, technical skills and understanding to perform the c... careers-advaxis.icims.com
Be an early applicant
3 months ago
Advaxis, Inc. logo
Job Title
Senior QA Specialist Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
Experience working with third party contract research, development, manufacturing and/or testing org... careers-advaxis.icims.com
4 weeks ago
Advaxis, Inc. logo
Job Title
Associate Director of Clinical Operations Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
As applicable, this position is responsible for the coordination of all activities performed by Stud... careers-advaxis.icims.com
3 weeks ago
Advaxis, Inc. logo
Job Title
Sr. Scientist Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
Experience with developing and executing protocols and applying fundamental knowledge of micro- and ... careers-advaxis.icims.com
2 months ago
Advaxis, Inc. logo
Job Title
Director, Human Resources Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
Design, select and implement training and development programs to meet business objectives, develop ... www.startwire.com
Be an early applicant
2 months ago
Advaxis, Inc. logo
Job Title
Senior QA Specialist Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
A minimum of seven years pharmaceutical experience with at least five years of experience in Quality... www.startwire.com
Be an early applicant
4 weeks ago
Advaxis, Inc. logo
Job Title
Associate Director of Clinical Operations Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
As applicable, this position is responsible for the coordination of all activities performed by Stud... www.adzuna.com
Be an early applicant
2 weeks ago
Advaxis, Inc. logo
Job Title
Quality Control Analyst Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
The candidate should have sufficient background, technical skills and understanding to perform the c... www.startwire.com
Be an early applicant
2 months ago
Advaxis, Inc. logo
Job Title
Sr. Scientist Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
Experience with developing and executing protocols and applying fundamental knowledge of micro- and ... www.startwire.com
Be an early applicant
2 months ago
Advaxis, Inc. logo
Job Title
Senior Scientist Company Name
Advaxis, Inc.
Job LocationPrinceton, NJ, US
Candidate should be prepared to develop and follow established protocols, identify and incorporate i... www.adzuna.com
Be an early applicant
3 weeks ago
Can you please stop badmouthing a Princeton graduate? Their IQ is quadruple of the average GED holders.
@wmtgreeter and a GED holder
Empirical observation and generalization based on three equities where CVI had a significant stake.
Disclaimer: I lost a memo sent out by CVI/Heights Capital Management with their plans about Advaxis.
Our "friendly" shareholder, CVI, has the following trading habits:
i) It thrives on stock volatility. The run up the equity 4-6% on a given day to then take it down about the same percentage points the very next day. The trading cycle can be as long as a single day, or few days. There's no real pattern, and it's done to confuse and frustrate retail who is trying to trade around a core position. However, the moving average (5-10 days) remains pretty much flat. Thousands and thousands of shares traded, CVI pockets the trading profits and likely reduces its position in doing so.
ii) They tend to create synthetic positions using a reverse conversion. This enhances volatility even more, and thus they pocket more profits.
iii) HFT trading is going to be on a full gear. Now, Iggy, we are talking about money-pullation.
Congrats to all for ending up in this mess!
No need to get creative to be complaining -- look no farther than the share price.
I do not believe they'll officially announce shelving Aim2Cerv/AXAL programs. Their MO is to do it quietly, as they've done it before. Why would it be any different now?
Besides, the markets assign ZERO value to AXAL programs anyway. If anything gets done, it'll be an upside surprise.
I'm concerned by the lack of conference call and a failure to update on the status of the program which Ken promised three months ago. I'll take this silence as a sign of shutting down the platform.
Look at the patents and patent applications with regards to NEO/HOT or even something that may not be related to the 1st and 2nd gen platform. There is Dr Patterson listed, just Dr Petit and co-authors from Advaxis. They're all assigned to Advaxis. Literally, Dr Patterson gets pushed out of the later generations of the platform.
That's a good question. I suspect that there might be some strained relationship between Advaxis and Dr. Yvonne Patterson. She might be really pissed at the company for winding down AXAL that uses her 1st gen Lm platform. It's her baby, and now she sees there might be a future for her. Sad.
Clearly, Advaxis is trying to distance from the 1st generation of Lm, by building a slew of patents that involve no Dr Patterson or UPenn. It's a basis for NEO and HOT. This Gen 2 platform will render G1-platform obsolete and push Patterson completely out of picture. Will she be trying to take her platform to some other company? How many years has she wasted with Advaxis?
New Patent
Listeria-based adjuvants
Document Type and Number:
United States Patent 10064898
Abstract:
This invention provides methods and compositions for using Listeria monocytogenes as an adjuvant for enhancing immune responses in a subject.
Inventors:
Rothman, John (Lebanon, NJ, US)
Wallecha, Anu (Yardley, PA, US)
Singh, Reshma (Brookline, MA, US)
Harn Jr., Donald A. (Athens, GA, US)
Paterson, Yvonne (Philadelphia, PA, US)
Application Number:
15/220641
Publication Date:
09/04/2018
Filing Date:
07/27/2016
Claims:
What is claimed is:
1. A method of reconstituting an immune response in a subject in an antigen-independent manner, the method comprising administering a live attenuated recombinant Listeria strain to said subject, wherein said Listeria strain comprises a mutation or a deletion of a genomic internalin C (inlC) gene and ActA gene, and wherein said administration reconstitutes said immune response in the subject in an antigen-independent manner.
2. The method of claim 1, wherein said Listeria strain comprises a nucleic acid molecule, wherein said nucleic acid molecule comprises a first open reading frame encoding a non-hemolytic LLO protein or immunogenic fragment thereof, an N-terminal ActA fragment or a truncated ActA, or a PEST amino acid sequence selected from the group consisting of SEQ ID NO: 8-19.
3. The method of claim 1, wherein said Listeria over expresses and secretes said non-hemolytic LLO protein or immunogenic fragment thereof, said N-terminal ActA fragment or a truncated ActA, or said PEST amino acid sequence selected from the group consisting of SEQ ID NO: 8-19.
4. The method of claim 1, wherein said recombinant Listeria further comprises a mutation or a deletion of a genomic PlcA gene, PrfA gene or a PlcB gene.
5. The method of claim 2, wherein said nucleic acid molecule further comprises a second open reading frame encoding a metabolic enzyme, wherein said metabolic enzyme complements an endogenous gene that is lacking in the chromosome of said recombinant Listeria strain.
6. The method of claim 5, wherein said metabolic enzyme encoded by said second open reading frame is an alanine racemase enzyme or a D-amino acid transferase enzyme.
7. The method of claim 2, wherein said nucleic acid molecule is integrated into the Listeria genome.
8. The method of claim 2, wherein said nucleic acid molecule is in a plasmid that is stably maintained in said recombinant Listeria strain in the absence of antibiotic selection.
9. The method of claim 1, wherein said subject is an adult human, a child or a non-human mammal.
10. The method of claim 1, wherein the Listeria strain is used alone or is combined with an additional adjuvant.
11. The method of claim 10, wherein said additional adjuvant is a non-nucleic acid adjuvant including aluminum adjuvant, Freund's adjuvant, MPL, emulsion, GM-CSF, QS21, SBAS2, CpG-containing oligonucleotide, a nucleotide molecule encoding an immune-stimulating cytokine, comprises a bacterial mitogen, or a bacterial toxin.
12. The method of claim 1, wherein said method allows the treatment of said disease.
13. The method of claim 12, wherein said disease is a tumor or a cancer, or an infectious disease.
14. The method of claim 13, wherein said method increases the ratio of CD8+/T regulatory cells in said tumor.
Description:
FIELD OF INVENTION
This invention provides methods and compositions for using Listeria monocytogenes as an adjuvant for enhancing immune responses in a subject.
BACKGROUND OF THE INVENTION
Adjuvants have extensive use in immunotherapy. The majority of cellular based immunotherapies administer adjuvants prior to giving antigen specific treatment. Typically these antigens include GM-CSF, IL-1, QP-100, Keyhole Limpet Cynanin, and others. These adjuvants are typically administered systemically via IV, IM, ID or similar routes.
Listeria monocytogenes (Lm) is an intracellular pathogen that primarily infects antigen presenting cells and has adapted for life in the cytoplasm of these cells. Listeria monocytogenes and a protein it produces named listeriolysin O (LLO) have strong adjuvant properties, that unlike the majority of adjuvants used for cellular based immunotherapies, can be administered after providing an antigen specific treatment.
A method of rapidly elevating a subject's immune response to any antigen is needed in order to decrease disease frequency in the subject and mortality resulting thereof. The present invention provides methods of elevating an immune response in subjects such as human adults and children by taking advantage of the adjuvant properties provided by live Lm vaccines that secrete non-hemolytic LLO or a truncated ActA.
Further, the same method is provided to reconstitute the immune response or facilitate the recovery of an immune response to normal or approximately normal levels in subjects that have undergone cytotoxic treatment as a result of cancer.
SUMMARY OF THE INVENTION
In one embodiment the invention relates to a method of reconstituting an immune response in a subject, the method comprising the step of administering a live attenuated Listeria vaccine strain to the subject.
In one embodiment the invention relates to a method of reconstituting an immune response in a subject, the method comprising the step of administering a live attenuated Listeria vaccine strain to the subject, the Listeria strain comprising a nucleic acid molecule, wherein the nucleic acid molecule comprises a first open reading frame encoding a PEST-containing polypeptide.
In one embodiment, the invention relates to a method of facilitating recovery of immune responses after cytotoxic treatments in a subject, the method comprising administering a live attenuated Listeria vaccine strain to the subject.
In one embodiment, the invention relates to a method of facilitating recovery of immune responses after cytotoxic treatments in a subject, the method comprising administering a live attenuated Listeria vaccine strain to the subject. In another embodiment the Listeria strain comprising a nucleic acid molecule, wherein the nucleic acid molecule comprises a first open reading frame encoding a PEST-containing polypeptide.
In one embodiment, the invention relates to a method of improving the immunogenicity of a vaccine, said method comprising the step of co-administering the vaccine and a Listeria-based adjuvant to a subject, wherein the Listeria-based adjuvant enhances the immunogenicity of said vaccine, thereby improving the immunogenicity of the vaccine.
In one embodiment, the invention relates to a method of enhancing an immune response against a disease in an antigen-independent manner in a subject, said method comprising administering a Listeria-based adjuvant to the subject.
Other features and advantages of the present invention will become apparent from the following detailed description examples and figures. It should be understood, however, that the detailed description and the specific examples while indicating preferred embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
It's interesting that there are absolutely NO defenders of the stock price by those who participated in the recent offering. The stock is down by 1/3 from their "purchase" price of $1.20 and a complete exhaustion of any trading. The same thing happened after the last secondary. Why this happens? The answer is clear -- the entities who participated in the secondary are vicious predators and vultures. Not a single decent health care fund participated, just traders. Possible that the Advaxis management had no other options, but it also possible they have no clue or don't care.
The current market cap is a measly $55M which is just $25M above a complete collapse threshold. This company has a standalone future only and if only they could increase a market cap to over $100M by non-dilutive option, i.e. a monetary deal or partnership. Otherwise, the vultures eat flesh when the company is still taking its last breath. Time lines are now got really tight -- the direction has to be changed by this December, or, the gravitational forces finish us.
It's one of the shareholders friendly hedge funds that will take this share price to over $55.83 in 294 trading days. Then, they'll sell this company for 5.637 beeches.
Can you provide a link? I do not see any changes in the price targets. Benzinga shows the following PTs this year:
Date Research Firm Action Current PT
6/13/18 Jefferies Downgrades Hold 2.0
3/14/18 H.C. Wainwright Maintains Buy 6.0
3/13/18 Cantor Fitzgerald Maintains Overweight 5.0
Alliance Global is a Phillipines based company that is not in biotech or healthcare. Elaborate why would they start coverage or put a buy rating on this company?
From Wikipedia:
Alliance Global Group, Inc., styled on its logo as AllianceGlobal and also known as Alliance Global, Inc. (AGI), is a large holding company with business activities spanning the food and beverage industry (including both production and restaurant operations), gambling, and real estate development.
It is one of the largest companies based in the Philippines, and is controlled by the family of its chairman and CEO Andrew L. Tan.[1] The company headquarters is in the Bagumbayan area of Quezon City in the Manila metropolitan area (the national capital region of the Philippines) on the island of Luzon.
Are you saying Advaxis has NO cash spending on NEO now? Why then ADXS said several times that they shift focus on NEO and HOT programs to conserve cash? We all know that "Amgen will be fully responsible for funding clinical and commercial activities."
We are flush with cash, hardly any trials going on to pay for
How so? The cash runway was extended by 4 more months, at best, does it qualify as "flush"?
The company may have plans to run Phase 1 for HOT alone, and they are paying for NEO. They need cash even though AXAL is not going to consume as much as it used to.
Short interest has been declining, and it was reported at 2.278M as of 8/31 before the offering. We could assume some shorted right after and then covered, but we did not see a huge selling pressure except for a day or two, and it's hard to believe the rest of the offering (12.5M) went to the short to cover. I'm still concerned with the lack of new 13G/F forms.
Regarding the aftermath of the dilution, the management gets a light fever and they're okay next day, while we get pneumonia and we're taken to the ICUs...
KB was also granted 250,000 RSUs in addition to 3/4M options at $1.62. It ain't no nothing...
Tin,
Who do you think could be exempt from filing Form 4s (or, 13G/F previously) if you suggest a creeping takeover is underway? I find no exemptions from the SEC rules, however, could it be some stealth foreign-based entity is trying to swallow Advaxis?
Is anyone concerned that there have not any 13-F/G filings besides the CVI's? Where are other filers for the remaining 12.5M shares? I could hardly believe they were split among the multiple buyers (must be at least 5 not to exceed 5% threshold. No large legacy shareholders participated in the offering? Likely, Adage did not as they are no longer insiders.
We also had about 7M unaccounted shares from the last secondary. The "official" short numbers were under 2.5M, thus I do not buy into a theory the shorts used the newly issued shares to cover.
Any other theories?
“I don’t recall seeing any companies making such predictions.”
—————————————————-
Since I recall you follow Ziopharm you should know that the company came out with a PR back in February (?) that the internet rumors about Ziop secondary were not true and the company has no plans to raise money via secondary in the near future. They also reiterated that stance during the most recent conference call.
To your point, those statements are always made as the safe harbor statements to cover their ass if they need to do a raise.
Rumors are that Apple was misspelled.
You were hypnotized by Mr Zhang, correct?
#byebyebye
I think you were a part of cohort who said Ken had a brilliant plan to play the big pharmas when he announced a plan to shelve AXAL in a specific period of time if no takers. Now that the “plan” did not work out as advertised here Ken is suddenly has some ulterior motives to destroy the share price and then resurrect AXAL. Because a Princeton graduate cannot be that stupid. I have seen many Ivy League graduates walking into my store and let me tell you that not all off them are that smart and intelligent. Besides being smart or stupid, more important qualification to run this biotech company is being qualified and have smarts to run it right.
It’s likely that Ken tried to bluff and possible partner called his bluff. And here we are, three months later Ken had no other options than to raise money via a secondary. Bottom line is no one can push in the rope. Remember? I said back then Ken is either too smart or too inept to telegraph shelving AXAL that way.
It’s a 3D chess game that Ken has been playing all along: where multiple big pharmaceutical companies are pawns, and Advaxis is a bishop. Of course, we all know who Ken is - a King. It’s a game where BPs attack each other and fight for the right of the first night with the company. Did you not know that?
Dew,
Bear with me here as I just had five Sapporo beers and seven sashimi at Weehoo. Are you saying the legal way to circumvent the SEC Insider trading restrictions is to setup a shell company that insider owns and buy shares in the secondary from the company you sit on the board even if you are in a possession of the material information. If so, isn’t that beautiful? Do other insiders do that kind of sheet?
Sorry, but you are wrong. Beside the Bloomberg link you supplied, do some digging. Even the 13G says this:
"** Heights Capital Management, Inc. is the investment manager to CVI Investments, Inc. and as such may exercise voting and dispositive power over these shares."
Wrong what?
The commonality among the companies where CVI filed their recent 13F/G is the chart. If you look at stock chart where CVI has "invested", almost each chart looks ugly. The company crashes and then CVI shows up...
Recent CVI 13/F/G filings:
STOCK: Date filed : Stock price change since then, %
FCSC 5/29 -21%
RKDA 6/12 -45%
NVIV 6/21 -2%
VBLT 6/25 -36%
CHFS 6/29 -42%
AMPE 8/ flat to slight up
PITE 8/15 -25%
AMPE had multiple trial failures, stock crashed few times, from $9 to $0.55.
This is the company that chooses to "invest" in previously failed companies. Are they that "unlucky" to see negative returns on all of their purchases? Think again, they play games with warrants, options, and trade around to make money. Is this time going to be different with Advaxis? I do not have that feeling...
Yes, unfortunately I've seen them to keep killing small biotechs that are poorly managed financially. One of the recent ones is Ziopharm. Just look it up. Their 13F/G filing made me sick...
think CVI, a trading arm of Susquehanna.
I'm afraid my worst expectations are coming true. These bastards bought 4.166M shares...
We are in so much trouble.
I hope you are not an insider for some other public company. The assumption you made is wrong and you could end up in a trouble with the SEC if you follow your "advice".
PS. Are you a lawyer?
I did not say "negotiations", but said "material". Most of the companies are always in a state of negotiations, but only small fraction of them lead to something material. Insiders are prohibited from trading based on the "material" information.
You are deliberately twisting my statement.
I don't think the insider buys or sells are that important to be considered as the critical indicator of the company's health.
If they want to send a signal to the shareholders and the markets they are serious about turning this company around, there other ways to do so:
1) Ken publicly states that he foregoes his 150K bonus, or, better, puts that money into the company stock;
2) Top management announces they reduce their compensations by, say, 20% until the company is financially healthy.
Is that too much to ask?