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Here you go:
Intralesional DNA Immunotherapy: Converting Anti-PD-1 Non-Responders to Responders
SPEAKER
Dr. Robert Pierce
Chief Medical Officer, OncoSec
ABSTRACT
Monoclonal antibodies (mAbs) inhibiting the T cell immune-inhibitory PD-1 pathway are demonstrating unprecedented durable responses in a variety of solid tumor types, including melanoma, NSCLC, squamous H&N and bladder (ASCO, 2014). In melanoma, the most extensively studied indication for anti-PD-1 mAbs, PD-1 responders appear to be those patients, whose tumors harbor significant numbers of pre-treatment CD8+PD1+ TILs. Conversely, patients who fail to respond to PD-1 mAbs are characterized by low numbers of pre-treatment TILs. These patients constitute the majority (approximately 60-70%) of patients with Stage IV melanoma and represent a tremendous unmet medical need. Data will be presented supporting the TIL-dependent responder hypothesis and the potential of intratumoral therapies to enhance immunogenicity. The future role of intratumoral therapies in driving a de novo TIL response and potentially converting PD-1 mAb non-responders into responders will be discussed.
Loving the buying action.
I re-read the shareholder letter and noticed something that hasn't been commented on that I'm aware of. This is the quote:
"Correlative data were also presented for a subset of eight patients that supported the hypothesis that IL-12 electroporation leads to the induction of interferon-gamma and downstream interferon-gamma-inducible genes, including key modulators of antigen presentation and processing machinery and chemokines."
You scientists, in plain English, what is he referring to?
Is the lack of bashers the last two days indicative that the powers at be are going to let this run?
Yes. Enjoy your family!!!!
If Pierce/ONCS presents data tomorrow to support ONCS' theory of turning non-responders into responders than I don't care if he presents wearing a dress on his head. Just saying.
Thanks. Very interesting. This will only get more intense in immunotherapy. Big market than Hep C.
Dr. Ferrone's presentation:
Chondroitin Sulphate Proteoglycan 4 (CSPG4), an Attractive Target of Antibody-based Immunotherapy in Various Types of Solid Tumors
SPEAKER
Dr. Soldano Ferrone
Professor, Massachusetts General Hospital, Harvard Medical School
ABSTRACT
Like CD44 (CSPG8), the tumor cell membrane-bound CSPG4, also known as high molecular weight-melanoma associated antigen (HMW-MAA), or neuron-glial antigen 2 (NG2), is a member of the CSPG family. CSPGs are key bioactive molecules that play a major role in tumor growth, migration and neo angiogenesis. CSPG4 is a unique glycoprotein-proteoglycan complex consisting of a 250 kDa N-linked glycoprotein and a 450 kDa proteoglycan component. It is composed of three major structural components: the extracellular domain (consisting of 3 subdomains), the transmembrane region, and the cytoplasmic C-terminal domain (CTD).
Flow cytometry analysis of established cancer cell lines stained with mAbs and immunohistochemical staining of surgically excised tumors from patients have shown that CSPG4 is expressed on glioma, squamous cell carcinoma of the head and neck (SCCHN), esophageal squamous cell carcinoma, triple negative breast cancer (TNBC), melanoma, mesothelioma, renal cell carcinoma, chordoma, chondrosarcoma, osteosarcoma, and soft tissue sarcomas. On most malignant cells CSPG4 has a high expression with limited intra- and inter-lesional heterogeneity. It is noteworthy that CSPG4 is expressed not only on differentiated malignant cells, but also on cancer initiating cells (CICs). Therefore targeting CSPG4 may eliminate not only differentiated cancer cells, but also CICs. In contrast CSPG4 has a restricted distribution in normal tissues. It is expressed on activated pericytes in the tumor microenvironment. As a result neo angiogenesis and growth of tumor cells, even those which do not express CSPG4 are inhibited.
The structural and functional properties of CSPG4 are highly conserved through phylogenetic evolution. The high degree of homology, but not complete identity among CSPG4s in various animal species accounts for their ability to overcome unresponsiveness to self-CSPG4 in xenogeneic hosts. This mechanism accounts for the ability of DNA encoding human CSPG4 in combination with electroporation to elicit humoral immunity to self-CSPG4 in dogs with melanoma. In agreement with results obtained in patients with melanoma immunized with CSPG4 mimics, this immunity appears to have clinical significance, since it is associated with a favorable clinical course of the disease.
Most, if not all the available CSPG4-specific mAb are not effective in mediating complement- and cell-dependent lysis of tumor cells. On the other hand, the few CSPG4-specific mAb used have been very useful to generate chimeric antigen receptors to redirect T cells to tumors expressing this tumor antigen. Furthermore CSPG4-specific mAbs are very effective in inhibiting both in vitro and in vivo signal transduction pathways associated with tumor cell proliferation, survival and migration. These results provide a mechanism(s) for the ability of CSPG4-specific mAbs to inhibit tumor growth, and more importantly disease recurrence and metastatic spread in immunodeficient mice grafted with human melanoma, TNBC or mesothelioma cells.
I think this will be a really relevant presentation as well:
Combination Immunotherapy - Augmenting Anti-tumor Immunity Elicited by DNA Vaccines
SPEAKER
Dr. Wei Xu
Senior Scientist, Roche Innovation Center
ABSTRACT
The field of Onco-Immunology includes the development of therapies that harness the immune system to provide durable and adaptable cancer control. DNA vaccine platforms for the treatment of cancers are highly appealing owing to their favorable safety profiles, and inexpensive, simple and stable nature. However, immunization with a DNA vaccine is often accompanied by a lack of strong and durable immunogenicity, potentially resulting from the inefficient antigen processing and presentation, limited T cell priming, and the negative regulation of effector T cells in the tumor microenvironment. Thus there is ample room to improve the efficacy of DNA vaccination by combing different immunotherapy modalities, including checkpoint inhibitors, adjuvants for antigen presenting cell activation, and/or cytokine modulators. I will discuss the rationale and data supporting the selected use of immunotherapeutic combinations in preclinical models of cancer.
Can you copy and paste the article?
The answer is "yes" Kristen.
I don't think this deal is comparable at all IMO. The financial responsibility is all on advaxis. We are a lot further along with way better numbers. However, it does illustrate an example of a non-exclusive deal.
That is awesome. Another piece of the puzzle.
IMO, this is perfectly analogous to the PEGS conference for systemic response rates. At PEGS, ONCS presented data through a mouse trial specifically demonstrating what was ALREADY observed in the human trials, namely that systemic response was observed in untreated tumors.
I believe it is the same here. After ASCO, there is an easy comparison between the intratumoral environment observed between responding tumors and non-responding tumors which is then compared to the intratumoral environment that is created through Immunopulse. However, these were unexpected/awesome observations from human trials, not the intention of them. Therefore, a mouse trial isolating the specific effect of immonupulse upon tumors known to be non-responding to PD-1 would confirm the observations in the human trials--namely that Immunopulse creates the appropriate playground for PD-1s to do their intended job.
Below is the quote from Dr. Pierce in the April Blog Post:
"We are working on trying to understand why it is that IL-12 is driving the immune response strongly enough to push through the PD-1 checkpoint. By that, I mean – you would expect that if IL-12 is driving the generation of tumor-infiltrating lymphocytes (TIL’s), and the TIL’s come into the tumor, you should see an up-regulation of PD-L1. This would then turn off the PD-1 checkpoint on the T-cells and turn off the immune response. In a significant number of patients, we are blowing right through the PD-1 checkpoint and we don’t quite understand how that is happening with IL-12.
But like I said, that is a great problem to have."
http://oncosec.com/dr-pierce-combination-therapies/
I think this is mouse trial data at least partially answering this problem.
I'm thinking it is a mouse trial(s) proving the hypothesis of turning non-responders into responders. As i mentioned in a post a few days ago, this is the last and logical step for the foundation of the P2b trial IMO.
I agree that the pps might not appreciate much but I do think this conference is fundamentally different than the closed door meetings with professionals. Here, there is an abstract already in the public domain that says data will be presented. If the data is new (which I think it is), I've never seen oncs not also submit that data to the public. Maybe this will be the first time, but that would inconsistent with their prior practices.
True, but that was discussing data already presented, wasn't it? If they discuss new data, wouldn't it give those scientists the opportunity to buy oncs on the open market with an advantage over the rest of the public?
Understand. However, I still don't see any disadvantage to oncs for data to be released this week at the conference. In fact, it would see the exact opposite, especially for partnership terms. A high pps would always be advantageous just like have a surplus of cash.
Further, I don't see any risk for discussions with the FDA either. This is just the next piece of the puzzle that would be helpful on their discussions with the FDA like their ASCO data, pegs data, etc. maybe I'm missing something.
We will see though.
Why would that matter? PEGS was closer to the public, they issued two PR's for that one with the data release the day of the conference. What would discussions with the FDA have anything to do with whether or not oncs releases data showing the effect immunopulse had on pd-1? I'm not being sarcastic just trying to understand the rationale behind your post.
Ya, saw that. I have this suspicion that punit has this very dry sense of humor and the quotes just mess with shareholders because we read into all of them--me included.
I would agree with that. I'm excited about the % increase that it gives to pd-1. Over 50% watch out. Even 20% increase would be very valuable to the big boys.
I think weds data is going to tell a great story.
I don't know about the partnership deal but around that time is when I believe they will start the combo trial whether, maybe later. So, it does coincide doesn't it.
Thanks. That link worked great.
I can't open the link. When was the application?
It was listed. Invented by dr. Heller but oncs owns the patents. Whatever, it doesn't matter.
Thanks for posting oncs' patents. It's important for oncs investors to know what we own.
It is also helpful before you make a claim to actually read past the first line.
Your find this morning was good. Ihub investors can see that there is quite a few patents in the same field as oncs which shows interest in the fuels of electro proration.
However, to claim that oncs' is not in that list is just simply a false claim. By the way, dr heller is affiliated with oncs if you didn't know that already. That's why their patents are pretty easy to find. Then you can check the patent numbers with oncs' list.
Good luck to you.
No, oncs' is like 5 down on that list. Dr heller. Patented 2011.
I see at .50. Where are the others?
I'm not a huge technical guy but I'm learning. Looks similar though. As you say, the rest of the day will tell the story.
Is it just me or does it look like the mm's are starting to let this one go?
I don't see the constant lower bid price that I've been seeing for it seems like forever.
Really jj?
Isn't it just the best felling in the world to see the bid price higher than the current one.
I believe it was T cell that was relaunched, not MCC.
Finally, big pharma and oncs need this data anyways because one the FDA will want it but more importantly it will be important for the structure of the trial itself.
A while back I posted Merck's presentation at Goldman Sachs. Their cmo said over and over the importance of these factors when they are looking to partner.
This data I believe has the possibility to drive a major bidding war. Also, I will be particularly interested to find out which pd-1 it is. I believe that will be our partner or at least thesjor pharma who offered the drug for oncs to use for the mouse trial with the right of first offer. If they lowball, let the bidding war begin.
IMO, the data next week will be new. The next logical step is a mouse trial that has tumors that are non-responders to pd-1 drugs when treated with immunopulse will respond.
So far, we have the following proven in mouse trials:
1. Immunopulse by itself on one tumor.
2. Immunopulse by itself with treatment of one tumor resulting in a systemic response on the other tumor. (Pegs)
3. Immunopulse + pd-1=100% response rate on one tumor. (Dr heller last fall)
4. Next Wednesday=immunopulse triggering responsiveness to non-responding tumors.
Remember, these mouse trials are really important because they are specifically testing a hypothesis. If the answer is positive, it will confirm the observations in both oncs' trials and pd-1 trials as presented at ASCO that the same factors for responsiveness are present. Can't wait.
Maybe, but next wed is a potential data release. It's their conference with all their scientists focusing on their type of technology.
Generally, I agree with you but I think the number of catalysts/data releases is the wild card.
Hold on tight friends. I really think this is going break hard the other way really soon. Not only has there been mm's galore, bashers everywhere, but the amount of catalysts are stacking up.
Follow the big money: direct placement for institutions plus mm tactics at the height of there powers which by their own admission work for the big boys too. ASCO data is not lost on them and they want in. The only way to get in at a low price is to scare the pants off weak retail investors.
It's time to stop being mad at the rules this "game" is played and embrace them to your advantage. Just play the game with the big boys and you will win big.
Lol. I was just poking you a little. I'm glad he's is confirming what we all know. External forces, not fundamentals. Also, did you notice that they look forward to meeting all 2014 goals. Go read the 2014 strategic update again. I really believe they are going to blow the roof off this one. "Stay tuned."