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Anyone with over 200,000 shares better freaking be walking on water!
I think that Lombardi may only have 25,000 vested shares? If I were him I would make the other free-loaders accountable for what they stole from us hard working investors!
I feel that the key to our technology is that we have a delivery mechanism (LM) that has been triggering immune responses since the stone age.
Others may develop the best antigens, peptides, etc.; but the challenge is finding a way to deliver these into the body in order to trigger the most robust immune response. That is why I feel the key to our future may be collaborating our LM delivery mechanism with the latest breakthroughs. This may also have applications in infectious disease; so you may have endless possibilities of combinations based on the latest scientific discoveries. This is just my humble layman's opinion of the science. Hopefully it does not get sold for cheap, but I feel that others can surely appreciate the value of this concept.
Agree that hiring has been out of control since nothing has materialized that warrants it up to this point. I would fire his arse for this alone based on my 31 plus years of manufacturing experience. Since I said this we will probably get approval in 2 weeks and start manufacturing like crazy so that I can look like a dumb arse.
I personally do not see a cheap buyout coming unless it is AMGEN. They have too much riding on NEO to let this sell cheap to anyone else.
FBG, did you join the monastery and take a vow of silence? Miss your input here!
If a buyout happens; will we command as much as Imclone?
Seeing some soft pumping of the peptides; well my drunk arse analysis is that if they are the answer, they may still need a vehicle baby. Here is the conclusion from the linked article in my previous post. Pretty sure we active both the CD8 and CD4?
The key issues will be how to direct the trafficking of tumor-reactive T cells to tumor sites and to enable their long-term persistence for tumor destruction. To achieve these goals,
1) we need to develop methods for in vivo(within the living) targeted delivery of peptides and RNAs into APCs such as DCs for inducing tumor-specific T cell responses;
Advaxis has granted SELLAS a license to develop a novel cancer immunotherapy agent using Advaxis’ proprietary Lm-based antigen delivery technology with SELLAS’ patented WT1 targeted heteroclitic peptide antigen mixture (galinpepimut-S).
1
Lm-LLO Immunotherapy Infusion
After infusion into the patient, the Lm-LLO system accesses dendritic cells and other antigen presenting cells (APCs) directly inside each patient. The Lm-LLO enters the APC, following the natural immune system pathway.
2
LLO Mediated Escape
Once inside the APC, as part of its unique natural life cycle, the Lmescapes destruction and enters the cytoplasm. Here, via Advaxis’s bioengineering process, it produces tumor associated antigen (TAA), fused to highly immunogenic bacterial protein (tLLO), collectively, the “fusion protein.” This fusion protein is secreted by the Lm-based antigen delivery system directly into the cytoplasm of APCs.
3
Immune System Activation
Once secreted, the fusion protein triggers the patient’s own immune system to cross-present the TAA as a bacteria associated antigen, to generate a powerful cytotoxic (CD8+) T-Cell response along the MHC I pathway. The fusion protein is also responsible for neutralizing regulatory T-Cells and myeloid derived suppresser cells (MDSCs) which are protecting the tumor, to allow the CD8+ T-Cells to be effective against the tumor.
NEO link; mentions many approaches:
http://www.nature.com/cr/journal/v27/n1/full/cr2016155a.html
Dew, if I remember correctly; Advaxis may not need to use a predictive algorithm.
WuXi: How does your approach compare to other immunotherapies?
Daniel O’Connor: What makes the Lm Technology so unique is its versatility. We have found that it has the potential to be paired with a wide variety of antigens. When it comes to ADXS-NEO, our preclinical personalized cancer immunotherapy, the technology has the ability to target potentially hundreds of neoantigens at a time, potentially eliminating the need for a predictive algorithm and ensuring that we are targeting all of the antigens may be causing the patient’s cancer.
The promise of targeting neoepitopes begins with improving the response of T cells. But because of the body’s central tolerance and deletion of self-reactive T-cell clones, naturally occurring T cells have low-affinity properties, meaning they are weak when it comes to binding to and killing off cancer cells. Some immunotherapy technologies that artificially create high-affinity T cells can be toxic.
With our approach, tumor-specific acquired mutations generate peptides that are changed from “normal” that serve as new antigenic targets (neoantigens or neoepitopes) that are not subject to central tolerance. Therefore, they are not toxic to normal sequence peptides in non-cancerous cells. Neoepitopesare the most ideal targets for T cell-based cancer immunotherapy wherever there are no viral or pathogen-associated targets that cause the malignancy.
To date, the best clinical responses have been seen in treatment with PD-1 (PD-L1) and CTLA4 checkpoint inhibitors and from TIL (Tumor Infiltrating Lymphocyte) cellular immunotherapy.
Data shows that patients who have good clinical responses to PD-1 and CTLA4 treatment all were found to have a low level of T cells targeting neoantigens that were pre-existing before treatment. The expansion of these neoepitope-specific T cells under checkpoint inhibition allows the patient to generate enough of these cells to cause the tumors to shrink.
TIL clones with the most anti-tumor power translates to complete responses. TILS always target a tumor neoantigen or neoepitope resulting from a mutation and never target a natural sequence epitope.
That’s why we believe our immunotherapies – which generate new T cell responses against neoepitopes – are uniquely positioned to work without excess toxicity from artificial technology.
WuXi: What have you learned about immunotherapy from your research?
Daniel O’Connor: Our preclinical and clinical research has shown our Lm Technology to be tremendously versatile, scalable and compatible. We’ve always known that cancer is caused by mutations, and we know immunotherapies are most effective when T cells are directed against the very mutations that cause cells to become cancerous in the first place. At Advaxis, our research has shown us the power of the Lm vector to direct the full attention of the immune system against these mutations just like if it was responding to a bacterial infection.
We’ve also learned a great deal about immune tolerance and the multiple mechanisms that protects cancer cells, but we do not know them all. Two elements that protect cancer in the tumor microenvironment that we do know well are regulatory T cells and MDSCs that have the ability to shut down a T-cell response. Lm Technology has shown to reduce the ability of regulatory T cells and MDSCs to ward off a T-cell response in a mechanism that is distinct from and synergistic with checkpoint inhibition.
We continue to get excited about how the bioengineered and attenuated Listeria monocytogenes vector both brings a response based on whichever antigen we are presenting, as well as the way it simultaneously reduces these tumor protection mechanisms.
Yes I remember Tex leading me to slide in fall presentation that mentioned that LM could be loaded with something like 100 neo-antigens.
I bought pre-market; trying to start a stampede of the lemmings towards the edge of the cliff. Let's get the Holiday started with a Bang!
Well spoken. I would be worried if we were still stuck with only the original construct model; the ability to adapt and change is what will keep our technology on the forefront.
It will all come down to efficacy and cost of treatment. Hard to say, but HOT could be the winner; but way to early to know for sure. If I were Amgen, I would go after HOT ASAP.
Agree. I speculate that DUAL will make AXAL obsolete, and HOT if applicable should do the same thing. Cost of treatment will be the driving factor across the world. Just need to get one approved, and the rest should follow quickly. Sucks to have to constantly be changing; but on the bright side, at least our platform is adaptable, which is the real value play in my opinion.
The older you get, eventually time becomes worth more than money. Seems to fit NEO perfectly. In my interpretation of the poet Vachel Lindsay, eventually your future becomes memories of your past!
Hot is definitely intriguing! I think that Amgen knows what we have; so more suitors are definitely welcome from my perspective. I speculate that Amgen will not let us get sold for cheap. In my opinion we should be worth minimum 10 billion, and that is cheap when you consider infectious disease and the ability to adapt your platform on short notice.
Trading Cyclist, you are spot on with your analysis. However, I feel that the NEO platform is probably the end game for all of this, as cancer is being shown to be highly personalized. AMGEN owns NEO, thus I struggle understanding why anyone else would want to buy the company; with the exception of possibly the infectious disease platform which could be equally huge. My uneducated hypothesis is that Advaxis remains an independent company.
Interesting article about infectious disease:
https://www.sciencedaily.com/releases/2017/06/170608124548.htm
Yes, even after a 12 pack, here is the definition of several: more than two but not many.
Do not underestimate the power and intuition of dreams! You have been a believer for a long time, remember when it was just a handful of posters back on the old Yahoo MB? Back when FBG was cool?
Thanks for posting that was awesome. I really like the Marine Corps Leadership motto of "To Lead Is To Serve". I came across that motto once while reading about stories of USMC Leadership during the Battle of Iwo Jima. To me that is the Key Element for any Success in Business Management; and is unfortunetly often overlooked.
Had a dream last night that Yvonne Paterson was on the cover of Time Magazine with the caption "The Cure". I ran around with the magazine telling my friends about the biotech that I first invested in back in 2009/2010. Just logging this; in case it comes to fruition. AKA Nostradamus.
There is a good chance of that happening in my opinion. This opened the door for HOT in my opinion. Smart money should gobble this up quick:
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm
For what it's worth from a guy who drinks cheap beer. I also bought after hours at $8.27 this morning, and possibly drove the price up? Of course I probably drink a hell of a lot more cheap beer that the guys that drink expensive beer; so in the long run I probably end up spending more dollars!
Thanks got the update, I have a younger friend who I introduced to Advaxis years ago, and he made a substantial investment. My friends father has been diagnosed with Myeloma; related to being exposed to Agent Orange during his service time in Nam. So please let me know if you hear anything about the beginnings of this trial with Sellas. Thanks
Okay, got it. Future milestones from Sellas for 358 Million, plus Amgen 475 million = 833 million. Then add in upfront payment to Advaxis of $40 million and purchase $25 million of Advaxis common stock. Thanks, I forgot about Sellas deal. With BP help these trials hopefully get moving quickly so that the milestone payments start coming in soon.
Hi Bill, where did you find the information about the 900 million in current/future revenue stream? Thanks for your help!
For a cure for cancer; I would speculate on 50 Billion at least. If the treatment works, I would guess that folks would be willing to pay more than existing treatments. Worldwide cancer market is predicted to hit somewhere between 150 to 225 Billion in 2017/2018.
Given our worldwide contract with say 10% royalties; I would speculate on company value somewhere around 10 Billion market cap, since we are also the manufacturer. This does not take into account the infectious disease market which is also quite large. Being able to possibly create a vaccine for new diseases in a month or possibly antibiotic resistant bacteria should also be a lucrative venture in my estimation. Also animal market could be equally huge.
Also I am making the assumption that NEO is possibly the cure; so I did not factor in the other constructs.
https://www.forbes.com/sites/matthewherper/2015/05/05/cancer-drug-sales-approach-100-billion-and-could-increase-50-by-2018/#97282082dc69
http://www.prweb.com/releases/cancer_therapies/chemotherapy/prweb8973379.htm
Dude I can totally relate. All through college I very seldom consumed alcohol; and for most of my adult life I have played chess as a hobby and for the most part avoided alcohol until about 10 years ago. When I was sober I could be a mean SOB; but give me a couple of beers and I will give you the shirt off of my back. I love beer; and hopefully ADXS will allow me to retire so that I can further pursue my love for beer.
Interesting article about research at MSK:
https://www.cancer.gov/news-events/cancer-currents-blog/2017/mutations-metastatic-cancer?cid=eb_govdel
FBG, just looking at this from 10,000 feet. DO has probably purchased as many shares as you on the open market with his own money? Which he did not have to do. I know that you feel that this doesn't matter because probably another 2/3 or more eventually of his shares were somewhat gifted; and he will be able to theoretically make-up for SP erosion. But I would be curious to know how many CEO's acquired that many shares (% of total holdings) with their own money? I know you have been here since the early days, and this does get frustrating at times; but I am personally excited that our platform is able to evolve and improve.
I feel that MINE and HOT may possibly benefit from FDA news on May 23rd; which I think was possibly the first time ever FDA gave accelerated approval for treating solid tumors with a specific genetic feature:
The U.S. Food and Drug Administration today granted accelerated approval to a treatment for patients whose cancers have a specific genetic feature (biomarker). This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.
I just think that this possibly opens the door for targeting solid tumor genetic features.
FDA Guidance for Industry document, explains fast track, break through and accelerated approval:
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM358301.pdf
Perhaps this will possibly open the door for NEO to gain accelerated approval? Glad that we have AMGEN with us; as I personally feel that NEO will probably possibly gain approval within a year of AXAL? Helps to have BP on our side.
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm
I am very excited that our constructs continue to develop and evolve, however somewhat frustrated about always being back at the start of another study without any significant cash upfront. Hopefully a mega deal is in the works instead of more dilution. The good news is that our platform continues to evolve; and that is what I believe someday possibly may ultimately lead to a cure.
AXAL also has the same designation. Not sure if there is any significance to this; although I would have guessed that AXAL was a new molecular entity? Not sure of any other existing LM vaccine, excluding our potential copycat competitor?????
http://adisinsight.springer.com/drugs/800025081
http://medical-dictionary.thefreedictionary.com/New+molecular+entity
https://en.wikipedia.org/wiki/Biosimilar
Not sure if I am interpreting this correctly, but the first attachment under New Molecular Entity states NO ..... so does this possibly mean that MINE will be considered bio-similar to our other vaccines? I am guessing that this will ultimately speed the approval process after AXAL is hopefully approved.
http://adisinsight.springer.com/drugs/800043642
Also forgot about the synthetic DNA agreement for 5 years.
http://ir.advaxis.com/press-releases/detail/1206/advaxis-truly-personalized-cancer-immunotherapy-moves