CureLab Oncology's Elenagen: DNA Vaccine Shows Promise in Immuno-Oncology and Beyond

I'll show you in the next 30 minutes or so the journey of my serendipitous work, which we started, believing that we are developing a classic anti-cancer DNA vaccine. And I'm convinced now that we just lucked out and what we have is not a vaccine.

Legally, I have to start with reminding you don't buy or sell anything based on what I any stock based on what you hear from me now. I'm sure my mother in law would tell me, don't worry, Alex, nobody takes you seriously anyways

I think of a DNA vaccine or plasmid-based therapy is like a letter in the envelope. A backbone plasmid is like an envelope. And what you can insert there is a letter. And the letter could be a love letter, hate letter, pink slip, or job offer. And we inserted there a letter called P62.

Actually, a lot of confusion comes from this short, truncated name because there are multiple proteins that have 62,000 kilodaltons in molecular weight. So, the full name would be P62/SQSTM1. If you go to PubMed, you will see thousands and thousands of papers talking about different functions of this protein in our cells.

Virtually every cell has this protein. For autophagy purpose, for signal transduction, for control of chronic inflammation. And for the sake of time, I will not tell you why I believe that all these thousands of papers are irrelevant to what we do. But if you ask me a question after my presentation, I will try to justify this argument.

We have a plasmid encoding P62, and it is called after my wife. My wife is Elena, so the product is called Elenagen. Okay? We recently published a clinical trial, phase two, ex-US clinical trial with the deadliest form of ovarian cancer, platinum-resistant ovarian cancer. We were suggested to focus on this particular form of ovarian cancer by Gynecologic Oncology Group Foundation.

In my opinion, they are the experts in gynecologic oncology. So, they told me, listen, sooner or later every woman who responded to platinum drugs stop responding. Yes, there is a minor subset. of patients who don't respond to platinum drugs from the very beginning and their disease progresses after the very first course of platinum, but most of them respond pretty well.

Sometimes for years. And then, sooner or later, the cancer becomes platinum-resistant, and there are no good options for treatment. Yes, there are a few chemotherapeutic agents like gemcitabine or paclitaxel or doxyl. But in average they provide progression-free survival of three months or less.

So, here you see two groups of patients.

The blue line is a group of patients who received standard treatment: gencitabine chemotherapy. And, similarly to what is published in the literature, we observed that 50 percent of patients had their disease progressed within 2.7 months.

However, the red line represents a randomized group of patients who received the same gencitabine treatment. Plus, once a week, intramuscular, a two-and-a- half milligram dose of Elenagen. And 50 percent of patients had their disease progressed not within 2. 7 months, but 7. 2 months. So… two-and-a-half times longer.

Importantly, almost 40 percent of patients, or roughly 40 percent of patients, did not progress at all during the entire time of the study, with the longest observation being 30 months.

We had to abruptly stop this study due to macro-political reasons, but even the time we had gave us a highly statistically significant result, with p value being less than 0.03.

Actually, let's smile together. We say a patient progressed. Actually, it's not a patient progressed; it's a disease in patient which is progressed. A patient did regress. But, we are so trapped in our professional slang.

As Orwell said, all animals are equal, but some are more equal than others. So, all patients are equal, but some are of a more of a poorer prognosis group than others.

For example, patients which had their disease progressed within less than three months after the first course of platinum treatment, they are the worst prognosis patients, because their disease is so severe that platinum cannot work on them.

Honestly, I was hesitant even to include these patients into our study, but as Bill Gates said, "We don't take the best people to tell them what to do, but take the best people so they would tell us what to do."

And our oncology experts told us to include them. To the greatest of my surprise, a response to a combination treatment of gemcitabine plus Elenagen was stronger, much, this red line, much stronger response in the worst prognosis group comparing to a best prognosis group .

Quite a counterintuitive serendipitous contrarian observation!

Another factor of a poor prognosis is the level of a molecular marker called CA 125. The higher CA 125 is, the worse is the prognosis for the patient. Once again, contrary to our anticipations, we saw that patients with high level of CA 125 responded better.

The more receptive to our treatment than patients with lower level of CA 125. Surprisingly, Elanagen, in combination with gemcitabine, was more effective in the worst prognosis of patients.

Okay are we only about ovarian cancer? No, we're not. Oh, here I want to show you a case study. Some other case study was published and this was not. The deadliest form of breast cancer, triple-negative breast cancer, a patient was 38 years old and Elenagen was combined with, I would say the oldest form of chemotherapy for triple-negative breast cancer: CMF.

It is so old that it is already out of fashion in America for oncologists, although specifically for triple-negative breast cancer patients, it's not any worse than other more modern and more expensive chemotherapeutic treatments. But it's out of fashion already.

If you take CMF and combine it with Elenagen, in this particular case, that after six months, both primary tumor and metastatic lesions were gone. Obviously, not every patient would be as responsive as this particular one. But I just wanted to show this case study, case report, just to exemplify that we will not be focused only on ovarian cancers, but on other cancers as well.

The blue line shows how a tumor grows in a group of wild mice. And the red line shows that if you give the same mice the same number of cancer cells plus Elenagen, tumor growth is greatly inhibited.

Okay, but what if we give it to SCID mice, which do not have lymphocytes? We'll see that Elenagen does not inhibit tumor growth and the same number of cells given with or without Elenagen roughly gives the same tumor progression. It does work through immune response.

Now, there are many ways how it can work through immune response. One of the ways is to increase the number of tumor-infiltrating lymphocytes, TILs. Here, let's remember that Homo Sapiens is a great model for a dog as comparative medicine experts teach. So, we had a group of 11 dogs with breast cancer, mammary tumors, and that when we had a group of 11 dogs and we saved 10 out of 11, which is a pretty good statistic.

Now, there are many ways how it can work through immune response. One of the ways is to increase the number of tumor-infiltrating lymphocytes, TILs. Here, let's remember that Homo Sapiens is a great model for a dog as comparative medicine experts teach. So, we had a group of 11 dogs with breast cancer, mammary tumors, and that when we had a group of 11 dogs and we saved 10 out of 11, which is a pretty good statistic.

What does the previous picture mean? It could mean either that we gave a tumor-specific antigen, P62, because yes, P62 is selectively increased in cancer cells, comparing to normal cells.

Or, and by the way, the first option was my original hypothesis. Or, it can change a tumor microenvironment... tumor infrastructure... in such a way that now it is easier for lymphocytes and NK cells to penetrate a tumor.

And this is very important because one of the biggest bottlenecks of modern oncology is so called cold tumors. Cold tumors means that lymphocytes cannot penetrate them and cannot become TILs: tumor-infiltrating lymphocytes.

And we published the data when we demonstrated that extracellular matrix in those tumors is changed in such a way, for example, collagen 1 to collagen 3, which is favorable for lymphocyte infiltration and not favorable for metastatic cells exiting the tumor.

The last is also important because, for example, in our experiment, which we didn't publish yet, with oral melanoma in dogs, we don't see that much of a dramatic effect on a primary tumor, but we do see a dramatic inhibition of metastatic process in oral melanoma dogs.

And we also published an experiment when we show in mice that now we can use our p62 encoding plasmid, our product, as an adjuvant for immune therapies because now, whatever immune therapy you will be using it would be more effective because now lymphocytes can penetrate the tumor and be more effective against the cancer.

Also, we observed quite serendipitously that the entire tumor structure in dogs is changed and islands of cancer cells are getting arrested in newly formed surrounding of connective tissue. And that could not be explained as much as changing of tumor microenvironment could not be explained with my original hypothesis of a classic DNA vaccine.

Okay, so how does it work? Here, the answer, or a hint, came from another line of research we were conducting, when we were studying an anti-aging and anti-osteoporosis effect of our plasmid. It was more or less a serendipitous experiment, when we found that in animals, which were ovariectomized. And ovariectomy is what? It's an artificial expedited aging, yes? And when you remove ovaries, anti-inflammatory cytokines go down, and pro-inflammatory cytokines go up. And this is a textbook fact.