Welcome to the Winter Wrap-Up Microcap Rodeo Virtual Conference. The first presenting company is Atossa Therapeutics. I'd now like to turn the floor over to today's host, Mr. Stephen Quay. Stephen, over to you.
Thank you, Jenny. I appreciate this opportunity. We are a public company, and as such, all of the comments I will be saying today are forward-looking statements within the meaning of the U.S. Federal Securities Law. So actual results could differ, and you should check with our filings before making any investment decisions. Okay. I'm waiting for the next slide. The leadership team includes myself, Dr. Stephen Quay, Heather Rees, Tessra Mohseni, Dale Beighle, and Eric Van Zanten. I am an MD/PhD from the University of Michigan and taught at Stanford for about 10 years and have invented seven drugs that have helped about 80 million people. In addition, we have a number of R&D collaborators, including Dr. Per Hall from the Karolinska Institutet, where the Nobel Prize is issued each year. He has over 40 years' experience in researching breast cancer prevention.
Dr. Laura Esserman, a nationally known breast surgeon, directs the UCSF Breast Cancer Center. She is a Harvard undergrad and medical student at Stanford University. Full disclosure, she was a student when I was teaching at Stanford in the medical school. She also has an MBA from Stanford, and she was Time Magazine's 100 Most Influential People in the year 2016. She developed what's called the I-SPY Trial Program, which is a groundbreaking national public-private collaboration among 40 cancer centers around the country. It's a multi-center neoadjuvant clinical trial design to reduce the time and cost for drug development. And we're partnering with I-SPY on two of our trials. Dr. Matthew Goetz is the director of translational research for the Mayo Clinic Comprehensive Cancer Center and co-leader of the cancer center's Woman Cancer Program. He has extensive experience with endocrinology, both in the laboratory and in the clinic.
He leads our Evangeline study. Dr. David Lyden, a professor at Weill Cornell Medicine, is a foremost expert on exosomes, which are collectively responsible for some of the systemic effects of cancer and metastasis. He is leading our preclinical work on using the potential of changing the way triple-negative breast cancer is treated. And finally, Dr. Caitlin Andriano, who is a PhD from Duke University, focused on ER-positive breast cancer. This slide shows the investor highlights, and I'll touch on each point specifically. Our lead compound is called (Z)-endoxifen. It's being investigated in multiple ongoing and completed phase II trials for both breast cancer prevention and treatment. It has an advantageous safety profile compared to existing treatment options. And we have a deep intellectual property portfolio. I have 90 issued patents, and I've won 5 litigations around those patents. It is addressing large underserved market opportunities.
We also have $94 million in cash as of September 30th. This gives us approximately three years of operating runway. There are going to be significant data catalysts expected this year. This slide is a reminder of the breast cancer problem. Probably everyone listening has at least one person that they are aware of in their family or their friend circle who has breast cancer. It arises primarily in women with dense breasts, and half of all women have dense breasts. One out of every eight women will experience breast cancer during their life. In the United States, approximately 300,000 women each year are diagnosed with breast cancer. 80% of the cancers, 80% of those 300,000, are what are called ER-positive, which is the kind of cancer that (Z)-endoxifen addresses. This slide shows the clinical positioning in breast cancer.
We are covering both prevention, as shown on the left, the neoadjuvant or window of opportunity space, and the adjuvant space. Let me talk about each of those specifically. In the prevention setting, we are identifying women with high mammographic breast density. That is, they have a very white mammogram. We know two things about those. Number one is it's very hard to see cancers in a highly dense breast with a highly dense mammogram, so the sensitivity of mammography is lower. And there's about a 5- to 7-fold increased risk of breast cancer in these patients. The next area where we're operating is in what's called the neoadjuvant window. This is the time between the diagnosis of breast cancer and the definitive treatment, whether it's surgery or radiation.
And finally, the adjuvant setting is when you're trying to prevent a local recurrence in the breast or preventing a new cancer in the other breast. And so again, (Z)-endoxifen is operating in clinical trials in all of these spaces. So as indicated, (Z)-endoxifen, the little molecule in the top right, is a selective estrogen receptor modifier or SERM. It's very de-risked because we have a strong IP portfolio. I'll go through some of the science around it, but it is extremely powerful both in estrogen receptor cancers and also in cancers that express what's called Protein Kinase C beta. So it has two activities, which is rather distinct for a breast cancer drug. It's been de-risked by multiple clinical trials, both by Atossa and by the National Cancer Institute. It may have an improved safety profile.
In our studies to date, we're seeing a reduced effect of side effects compared to other kinds of cancer drugs, which is very gratifying. Finally, we have a very strong IP portfolio. This long pause is because these slides that I'm advancing take significantly long to advance. It's a technical problem, and we'll work through it, but I just want to point out why you have these long pauses between slides. As shown here on our intellectual property slide, we have 20 patent applications. 3 have been granted. 17 are in the process of being reviewed by the U.S. Patent Office. Our patent protection includes methods of use, that is, treating cancers, indications such as oncology, compositions of matter, formulations, and also, of course, an international portfolio around the world.
Our granted patent protection will cover through at least year 2038, giving us a very strong patent life. There are patent pending claims around a number of related areas, including other kinds of cancers. This slide shows some of the advantages of (Z)-endoxifen. First off, it is the most active metabolite of tamoxifen, which is a well-known cancer drug. In fact, tamoxifen itself is a prodrug. It is a pro-drug. And (Z)-endoxifen consists of two isomers, an E and a Z form, and it's the Z form that is active. It's about 100-fold more potent as an ER-targeted therapy when compared to the parent drug, tamoxifen. It also degrades the receptor, which is a unique activity which is important for preventing activity on the receptor. And again, finally, it has PKCβ activity at high concentrations.
This slide shows the growth inhibition of cancer cells as a function of concentration, where the green curve, the farthest to the left, inhibits at the lowest activity, and that's (Z)-endoxifen. And then other metabolites, including 4-hydroxytamoxifen and N-desmethyltamoxifen and tamoxifen itself, are shown to the right. So this demonstrates its superior activity among all of these SERMs. I truly apologize for the delay in the slide advancing here. This is a technical problem that's outside my control. The next slide shows (Z)-endoxifen's receptor degradation. As you can see on the right, under panels A and B, you can see that the ER-alpha signal is getting lighter as you increase the concentration of (Z)-endoxifen. This means that the receptor is actually disappearing. It's being degraded inside the cell in the 24 hours after (Z)-endoxifen is being treated with it.
This is the hallmark of a receptor degrader, which is, again, a special activity that (Z)-endoxifen has, and most other SERMs do not. Next slide. This shows estrogen on the left binding to the estrogen receptor with the green molecules being estrogen. On the right, you can see (Z)-endoxifen binding at a slightly different angle, and that's probably responsible for its very high activity on the receptor. Next slide. One of the important aspects that (Z)-endoxifen has that we wanted to focus on is its effect on mutations in the receptor. Like an infection that becomes resistant to a particular drug after long treatment, the estrogen receptor develops mutations that prevent most activity from going forward. For a lot of drugs, it will work for a period of time, maybe a few years, and then the tumors will become resistant.
The three characteristic mutations that occur in the estrogen receptor, a particular amino acid 536, 537, or 538, very specific positions in the receptor itself, account for about 68% of the treatment-emergent mutations that occur. Next slide. So this shows from in the individual boxes, the effect of (Z)-endoxifen on the wild-type receptor, which is in the first top left panel. So as you go up in (Z)-endoxifen concentration, you see the columns getting smaller and smaller. That is (Z)-endoxifen inhibiting the wild-type receptor. And then as you go across the top panel, you see various mutations in the 536 position, 537 position, 538 position. Each of those shows that (Z)-endoxifen continues to operate even in the presence of these mutations.
This is a powerful capability of (Z)-endoxifen, which, again, is not shared by most SERMs and allows (Z)-endoxifen to continue to inhibit cancers even as they try to escape by mutating. Next slide. Because of its strong activity on ER-positive breast cancers and because these are found not only in ER-positive HER2-negative cancers but in a percentage of HER2-positive cancers, (Z)-endoxifen should be able to treat 83% of all of the subtypes of breast cancer. A very powerful statement. Next slide. So this, in fact, shows the inhibition of a cancer that is both ER-positive and HER2-positive, which, again, is a subtype that most SERMs cannot reach alone. And often, a second drug is required to inhibit these. But in the case of (Z)-endoxifen, it will inhibit both HER2-positive, HER2-negative, ER-positive, HER2-negative, and ER-positive, HER2-positive cancers. Next slide. It's a remarkable delay in this system. I apologize.
The activity of (Z)-endoxifen is its inhibition of a protein called PKCβ1, which is a breast cancer target that is important in the sense that when it's inhibited, it actually induces the cells to commit suicide effectively, a process called apoptosis. So what you're seeing in the left experiment is the PKCβ going down in concentration as you increase the (Z)-endoxifen levels. And on the right, you see proliferation changing in the same fashion. This demonstrates that higher concentrations will reach this PKCβ breast cancer target. Next slide. This, in fact, shows the molecular modeling in the pocket of (Z)-endoxifen where it's into the PKCβ kinase activity. And in the right-hand panel, you can see it inhibiting the cancer growth. We're waiting for the next slide again. At the end of December 2023, an important paper from Dr. Goetz's laboratory at the Mayo Clinic came out.
This is the title page from it. It's entitled, "(Z)-Endoxifen Downregulates AKT Phosphorylation through PKCβ Inhibition in ER-Positive Breast Cancers." And this is really the definitive work that allows us to have confidence that we'll be able to reach this additional target for breast cancer. Next slide. This shows our development pipeline.
I do apologize, ladies and gentlemen. Dr. Quay's line has just dropped for a second. Well, just please a moment while we try to get him back connected. Again, apologies, everyone. We are waiting for Dr. Quay to join us. Okay, ladies and gentlemen, we have Dr. Quay back with us.
Thank you again. I apologize. I just close again with thanking you for your time to hear about Atossa Therapeutics, ATOS on the NASDAQ. We have three years of runway with respect to our balance sheet and clinical readouts coming in 2024. So, again, appreciate your time today.
Thank you very much, Dr. Quay. Thank you, everybody. This does conclude Atossa Therapeutics' presentation. You may now disconnect your lines.