Managed to host, Michael's coming on anyway, but Steven managed to crash his bike. Not his fault, and is not camera ready. I heard it was pretty rough, so we wish him well and a speedy recovery. But Michael, happy to have you here with us, and I actually think it's great for you to actually be on here, telling the story for Atossa. And it's a name for people who follow what me and my team do. They're in breast cancer. They are developing a drug called endoxifen, which is a metabolite of tamoxifen, the old breast cancer drug that's used everywhere, pretty much. It's not the hot, kind of sexy, sizzling CAR T. It's basic oncology. It's elegant in the way that it works, and I think it goes relatively unnoticed. Actually, no, it goes unnoticed because I look at the market cap sometimes, and I'm like, "I don't understand. Company continues to put out good data, yet it's not really responding." Company is very well capitalized, has been for quite some time. They have multiple trials ongoing. There's a number of data points that are coming up, and I think once this data starts to materialize in breast cancer, I think investors are going to start to notice Atossa, so I think it's a great time to have you here, Michael, and I think what would be helpful is first an introduction about yourself and maybe a high-level view of Atossa as a company. Absolutely. Jason, Chad, thank you for having me today and letting me pitch in for Steve. He does send his regards to everyone. So as Jason mentioned, I'm the Vice President of Investor and Public Relations at Atossa. I think I'm a little more than a month old here, and still getting my legs under me. But it's really, to Jason's point, an exciting time for the company. I'll give you a little bit of history. The company has been around for a while. It was founded back in 2009, but it was actually founded as a diagnostic company, but the focus has always been breast cancer. Back at that time, the company was looking at detection and prevention of the disease and had a product that essentially was kind of the equivalent to a Pap smear for breast cancer. It was able to bring that to market, ran into some regulatory challenges, and around 2020, changed its focus from the detection and prevention to more to the therapeutic side of things, so they went from being Atossa Genetics at the time to Atossa Therapeutics, so Atossa Therapeutics is still relatively young, but the sole focus of the company, as I said, is breast cancer, but also on (Z)-endoxifen, which is really our flagship product, and we're very excited about it for all the reasons that Jason mentioned, and I'll kind of walk through some of that. So (Z)-endoxifen is a very potent novel SERM, a selective estrogen receptor modulator. So as he mentioned, it's in the same class as tamoxifen, which has been around a while. But (Z)-endoxifen is actually the most active metabolite of tamoxifen. So you know, essentially what we're seeing with (Z)-endoxifen by itself is a very, very powerful SERM that we believe has a lot of potential. So not only have we isolated the (Z)-endoxifen, but we also have a proprietary way of delivering it. So the important thing with (Z)-endoxifen is our oral formulation, which does not require liver metabolism. It's encapsulated as such that it allows it to bypass the stomach so that there's no conversion of (Z)-endoxifen to (E)-endoxifen in that process. And the result has been a SERM that basically has been shown to be about a hundred times more potent than the activity that we're seeing with Tamoxifen. And fortunately, so far, we're also not seeing some of the issues that come along with Tamoxifen. So we're continuing to obviously do the required clinical trials, but the safety and tolerability seems to be very good at this point. At the end of the day, we really think that the (Z)-endoxifen represents a triple threat, and what I mean by that is that, you know, we know that it's a pure estrogen receptor antagonist. We know that it's an ER degrader, which is fantastic, but we've also shown that it has a strong PKC beta inhibition, so leading to apoptosis, so with those three key things combined, you know, we feel like (Z)-endoxifen can fit in pretty much any setting in the breast cancer care paradigms. What I mean by that is, we see that it can be applied in the prevention area when we're talking about breast density. We see that it can be applied in the neoadjuvant setting, so that's the period between diagnosis and treatment, whether that's chemotherapy, radiation, or surgery, but then also as a neoadjuvant on the other side, where we're trying to prevent a recurrence of the disease. I think we have a lot of opportunities for shots on goal here as it relates to (Z)-endoxifen. We currently have, I think, six total phase II trials underway. Two, maybe three of those are focused on the prevention side, and the rest are all focused on the neoadjuvant setting, as Jason mentioned. It seems very late in the year, but there's plenty of time. We have data readouts that we expect between now and December thirty-first. We'll definitely keep an eye out for announcements around that. I think one of the benefits that Atossa has had over the years. I know you're thirty days old, so I just won't take you back too far, but company during COVID or just after was able to raise a tremendous amount of capital. You know, how it did that is it's irrelevant, right? But it has remained well-capitalized. When you look at the stock over that time, it has literally tracked with the market. Even the COVID swing, you know, there are some interesting things that Atossa was thinking about at COVID. And then when the market for biotech at least last November started to recover, here comes Atossa's kind of stock is kind of tracking with it. And I think it's never really had a chance to work, and there's multiple reasons for that. I think, one, investors are... It's not the hot, hot space, right? It's endoxifen, tamoxifen, maybe. I had commented on that earlier. There was a switch in formulation coming out of that a breast density trial earlier. There was a cream, then it went to an oral, and I think there was a little bit of confusion there. And then also, waiting for the significant data sets, right? They have the good window of opportunity, and we could talk about that data in the neoadjuvant breast cancer setting. They've had good PK data that kinda shows the comparison, but not that big slug that people, I think on the street look towards, and I feel like now's the time, right? It's coming soon. We're gonna start this. Can you, so can you talk a little bit about that and kind of where the company is in terms from a catalyst perspective? And then we can go backwards to some of the nitty-gritty endoxifen stuff. No, I totally agree with you, Jason. I think, you know, one of the points about the stock, I mean, you know, it has been a tough market, but one thing that kind of drew me to Atossa is it's been very resilient, even in a tough market. So, but I think you're right. I mean, we, you know, we need to spread our wings a little bit, and I think the data is gonna help that. One area that really excites me is the breast density data, out of the KARISMA trial. We do expect to have that some data from that by the end of the year. And, you know, just to put that into perspective, and I don't think people always understand the importance of breast density as it relates to breast cancer. But any woman who is receiving a mammogram right now, 50% of them are gonna be identified as having dense breasts. To put that into perspective, if you go back to the old BI-RADS scale, right? You have basically four different categories that a woman can drop into. If they are on the lower end of that spectrum, a BI-RADS 1 or a BI-RADS 2, you basically have a 90% chance of identifying the cancer, potential cancer in that woman. However, if you're in the BI-RADS 3 or BI-RADS 4, that ability drops to about 40%-60%. I mean, almost a coin flip. So if you're able to influence that breast density and lower it down so we can, you know, have a clear view of any potential concern in that patient, that's a game changer. So, I think that data's gonna be very important coming out, and like I said, we'll have a readout on that before the end of the year. We also have the readouts coming up on the EVANGELINE trial. As you'll recall, that is a monotherapy trial in premenopausal women. And, you know, at the end of the day, so premenopausal women represent a challenge, right? From the standpoint that they still have intact ovaries. They're you know, you put a weak SERM into their system, and their body tells them to produce more estrogen, right? And that actually works against the grain of what you're doing, so that drug can be overpowered. It's a little bit different with the endoxifen because it is so powerful. So what happens if you put that drug into a premenopausal woman? How does that impact the need for or does it complement the ovarian function suppression? Which is something that would be great to avoid. So those are questions that we're hoping to answer in the EVANGELINE trial. You know, how does it impact OFS, does it impact OFS, and how can it be a complementary neoadjuvant to the overall program? So we will have EVANGELINE data on that, and we also expect to have I-SPY data. If you recall. I-SPY is, w e have two arms in the I-SPY trial, that's being conducted with Quantum Leap Healthcare. We will have a readout of the ten-milligram dose on that, the monotherapy, by the end of the year as well. So to your point, we have a lot of, I think of good things to come here, and this is still twenty twenty-four, and you know, we'll have additional readouts in twenty-five. Can you talk about what happens in, might as well start with the MBD, right? The breast density. First, what happens when somebody goes for a mammogram? I was, I had this experience with somebody near me who, like, they asked me to look at, like, I'm not a radiologist, but whatever, the report. But there was an extra step because it was dense tissue that they had to take. So it becomes not only problematic for seeing things, there's an extra step in treatment or preventative treatment for these women, which, and it's a lot of them. Yeah, so 50%, right? It's a good question, and it's actually a changing environment right now, so it's a very timely question. Traditionally, if a woman is diagnosed as having dense breasts, they're going to monitor that patient more closely. They're gonna probably have a more frequent mammogram. They may go to a more advanced technique, MRI, things such as that. But what's important here is that when you look at on a mammography, if you look at the image of a breast that is dense, it's very white. So that white is basically picking up the fibrous and glandular material within the breast. That fiber, and the fibrous and glandular material, is also where cancer starts. So the more of that you have in there, the higher probability you, you have of developing cancer. So what we wanna do is, I should also mention, it appears white on the mammography, so does cancer. So you're basically putting white on white, you know, and it's a very difficult thing to see. So if we can lower that density, get a clear view of the breast, and give it an opportunity to actually see where that tumor may be progressing, that's an optimal environment. A really important change just took place last month with the FDA. They updated the MQSA guidelines as it relates to reporting breast density data in women who are receiving a mammogram. It is now required that all women get a breast density score, which is phenomenal. That just helps in terms of raising awareness of the breast density issue. But now it's not just hit or miss, depending on where you're having your mammogram done, everybody is required to do that. And they're required to do so in very lay terms. So it has to be not communicated in medical lingo, it has to be you know conveyed in a way that a woman understands what that means in terms of her healthcare, and the appropriate follow-up that she needs to have with her physician. Could you just talk about the size and scope of the trial and, you know, when we could, you know, expect that data? Yeah. So, for the KARISMA trial, it's a total of 240 enrolled patients. You may have seen we dosed our last patient in May. So, that has allowed us enough time that we should have the data in hand, to present sometime before the end of the year. But so 240, it, it's a good size, good size study. And yeah, we're, I'm, this is one of the studies I'm really excited about and looking forward to, to seeing the outcome on. Just so it's a big market and a big opportunity for women. If you go back to the scoring for a second, how is that scored? 'Cause it takes the subjectivity out of it, right, for a physician or a patient's interpretation of what the outcome of the mammogram is. What is the score? How is it scored? In terms, like, is there a range? Is it what's good, what's bad, what's in the middle and needs monitoring? Yep. So you're on the outskirts of my learning curve, but the BI-RADS scale is probably the easier way to explain it. But modern mammography basically uses a scale between 1 and 100 now, and it's supported by software that will give it an actual reading, where it is not as subjective for the radiologist to make that determination. So they have ways of scoring it much better now, but in terms of the outcome, the percent of women who still are being scored as having dense breasts, it's still around 50%. The scoring won't be a part of the KARISMA trial, right? It's already, the protocol's already baked. Is that right? I believe so, yeah, yeah. But I think that I, I'll have to get back to you on that. Maybe as an exploratory just to see. Yeah. Okay. Maybe so going back to (Z)-endoxifen, just from a PK perspective, can you help everybody understand a little bit better the magnitude with how potent it is? Because you can get therapeutic levels within days, a week, you know, whatever, versus tamoxifen can take up to, you know, 100 to 200 days or so, if it even gets, it might take longer than that. No, absolutely. So we released data earlier this year at AACR regarding I guess it was the 40 mg ram cohort. I'm sorry, no, 40 mg cohort. But it was the PK run-in data, and it was quite impressive. So we had 100% response rate on (Z)-endoxifen as it relates to the Ki-67 reduction. And then what was more impressive is when you looked at the tumor size reduction, it was about 32% at 12 weeks and 37% overall average at 24 weeks. So to your point, it works fast, and we're seeing you know very significant reduction in tumor size, and as well as with the indicator, with the Ki-67 indicator. Yeah, and also just what about Ki-67 as a marker, and what was seen in the window of opportunity study? As I mentioned, the Ki-67 reduction was seen in all patients, some more extreme than others, but we had one complete response in the tumor reduction. But all patients showed some type of reduction as it related to their Ki-67 biomarkers in that study. So it was a small study. It was seven patients total, but still, you know, to get 100% response rate is pretty impressive. Can you, what is Ki-67? Just for everybody's benefit, just as a marker, like, what, what is it a marker of? Yeah, so it's a biomarker basically that measures tumor proliferation, right? So, if you have a reduction in that, the assumption is that you're having less proliferation of that particular tumor. So, it's a good biomarker just to kind of assess tumor activity, if you will. I'm sorry. In addition to understanding what took place in that window of opportunity study, can you just walk everybody through what a woman would experience from diagnosis through surgery? Like, what are your options, what. You know, kind of what are the timeline? You get diagnosed, then you go through X, get the surgery, then you go through Y. What, and what are what does that look like? Yeah, so typically when a woman is diagnosed, a lot of people think that it's immediately to surgery. But there's actually, to your point, that window of opportunity that you can actually shrink the size. You wanna do a couple of things. You want to stop the growth of the tumor, you wanna isolate it from metastasizing to other parts of the body, and to the extent that you can shrink the size of the tumor to make it more resectable. Those would be goals of a neoadjuvant therapy in that timeframe. Those are all things that we're seeing currently in the trials that we're conducting. And just need more data to kind of support its role in that particular setting. But you have. You can't do it with tamoxifen. It doesn't work. I'm sorry? You can't do it with tamoxifen. So yeah, that's the problem. So, you know, obviously, as we mentioned before, (Z)-endoxifen is a metabolite of tamoxifen, but tamoxifen has been known for a long time to have side effects that, you know, make it sometimes intolerable for the patient. So those are typically vasomotor type of side effects, so things such as hot flashes and very uncomfortable setting for the patient. So, as I mentioned earlier, you know, we're still seeing good data as it relates to safety and tolerability. So if we can overcome that hurdle, keep a patient on the treatment for a longer period of time, that would be great. Got it. Yeah. Could you just give us an overview of the I-SPY platform trial, and then the, you know, you guys have the monotherapy arm, and then the more recently added, combo arm with Lilly's CDK 4/6? Yep, absolutely. So on the monotherapy arm, as I mentioned before, these are ER positive, HER2 negative breast cancer patients. You know, essentially, we're looking at that neoadjuvant window again, looking to see if we can get the tumor under control, but also find out what that impact is on ovarian function suppression treatment. So, is there an impact, you know, one way or the other, in coordination with OFS or without OFS? On the combination therapy, again, neoadjuvant setting, as you mentioned, this is being studied with abemaciclib, Eli Lilly's drug. And so if you really think about abemaciclib, it's typically, say, reserved for those hard-to-treat patients later down the downstream in the treatment regimen. We're essentially moving that up a little bit. So, it's an 80 mg dose of (Z)-endoxifen and about a 150 mg dose of the abemaciclib. And we're basically seeing what impact we can have in that window of opportunity. Can we achieve the things that I mentioned before in terms of stopping the growth of the tumor, improve resectability with tumor shrinkage, and achieving those goals prior to surgery or some other treatment, radiotherapy or chemotherapy? Have they used the CDK 4/6s for neoadjuvant in the neoadjuvant setting often? Is that standard? I don't know that, Jason. Yeah, I'd have to look that up. Here's something else you might not know, but I'm gonna ask it anyway. Just, so, Ibrance, Pfizer's, CDK, same category in breast cancer, has a patent expiry 2027 or 2028, and then this one, Verzenio, Lilly's drug, you're right, is like a year after, right? So the CDKs seem like they're at a crossroads, right? Where they might need to add on something or do something to extend their patent life. Is that something that you guys are talking about internally, as going for this type of combination, maybe working with one of these larger groups to see if there's something there? I mean, I think always a partnering opportunity would be great, right? That's something we're always, constantly thinking about. To the extent we've had that conversation, I think we're gonna wait and see kind of how the data play out in this particular trial. But yeah, I mean, it's, it's interesting because one thing I do hear from investors are those, patent expiration dates, that are fastly approaching, and, and is that helpful, is that hurtful? But that, just in the short time that I've been here, have not been, you know, engaged in that discussion. I'd say it's helpful because they're gonna be looking for partnering. They're not gonna be like: "Leave us alone, we have, like, fifteen years of exclusivity here. That's right. Maybe we could back up to the EVANGELINE study, kind of the size and scope of that study. It's a big study for breast cancer, right? It's not like you're doing, you know, 10 or 20 people in this trial, which is another aspect of why is this going unnoticed? 'Cause can you give us an update on that? Yeah, absolutely. So, as you recall, we started off with two treatment arms there, a 40 mg arm and an eighty milligram. We were not seeing some of the the serum concentration levels that that we wanted in the 40 mg, so we switched over and focused on the 80 mg arm. What's interesting there is we also, during that time frame, started looking at tissue concentrations of the drug. And I don't have a a readout on the data from that, but you know, we're we're really making sure that we're getting the drug in the right area, achieving the concentrations that are necessary to get the therapeutic effect. To your point, the drug has been, the trial has been going on for a while. We do expect to have some 80 mg PK data this year, before the end of this year, and look forward to seeing the data and see how it plays out. Okay. Any other, w hat, when is that data due? Sorry, I might have just missed it. Before the end of the year, the 80 mg. For EVANGELINE will be before the end of the year? Yep. The full data, all 175, so a full data set coming? For the PK run-in. Oh, PK run-in, not the full- Yep. F ull trial. No. What do you think the timeline is for the full trial? I believe that it should be in 2025. In 2025. And also, maybe, do you want to just touch on the runway? 'Cause I mentioned it in the beginning. You know the company is very, very, very well capitalized for a small biotech, and I think it's something people should pay attention to, where there's a lot of companies who seemingly can't rub two nickels together and raise money. You know, this company is in very good shape. No, you're absolutely right. I mean, we're sitting right now with about $79 million and change in the bank. That gives us about a two and a half year runway with the current burn rate. So to your point, yeah, we are very comfortable in that situation. You know, obviously, with the data readout, it will kind of dictate where we go from here. But yeah, we're very comfortable with the runway, and that was one of the things that drew me to the company. It's very efficiently run and, you know, planning ahead and to make sure that we can achieve the goals that we're set out to do. We're getting an investor question related to insider ownership. Have insiders participated in prior rounds? It seems like the percentage of insider ownership is lower than one might expect, given all of the phase II studies that are ongoing and potential here. Yeah, I've seen that as well. It's a discussion I haven't had yet, internally. I don't like to make crystal ball projections or anything, so, but, you know, I think the ownership has been somewhat stable, insider ownership, over the last, what, 24 months. But yeah, that's about as far as I can comment on that. It's only been 30 days. Sounds like you're running the company. I think you're in pretty good shape, Michael. No, t hat's as quick as that's as much time as we have. No, I appreciate you coming on. Again, our best to Steven. Hope he has a speedy recovery, and we will catch up with Atossa again soon, hopefully. Thank you, Jason. Thank you, Chad. Thanks for having us. Thanks, Michael. Thanks.