Good morning, and welcome to the Aspira Women's Health Research and Development Day. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this call is being recorded, and a replay will be made available on the Aspira Women's Health website following the conclusion of the event. I'd now like to turn the call over to Nicole Sandford, President and Chief Executive Officer, Aspira Women's Health. Please go ahead, Nicole. Great, thank you. Anyone that's on the speaker line, if you could just mute your line until you're ready to go. We're getting a little bit of background noise there. So, thank you, Tara, so much for the introduction, and thank you, Life Sci, for helping us to put together today's presentation. I was really happy to see many of our long-term shareholders and supporters signed up to hear today's presentation, but I was equally thrilled to see so many new names, people that I haven't had a chance to talk to before and maybe aren't familiar with the Aspira story. So welcome. I know this is a really busy time of year, big, big things happening in San Francisco next week. Many of us are heading that way, so I know it was an important use of your time, and I thank you for being here. I personally believe that Aspira is positioned for great things, an extraordinary 2024. My goal is that by the end of today's program, you are all believers, too. So thanks for being here, and we can move to the next slide, and I'll talk about what we plan to cover with you. So, we're gonna give a brief background about Aspira for those of you who are new. We'll then talk about our proprietary technology. I think, you know, we have sometimes taken it for granted that people understand how advanced our technology is. So we thought it was important to actually take a little bit of a step back, talk about the progression of our technology before we dive into the portfolio reviews. So we'll talk about ovarian cancer and our test portfolio there, and then we will talk about the endometriosis test portfolio before I wrap up with an overview of the market opportunity and some of the near-term milestones that you all could be tracking for Aspira. You can go to the next slide, please. I'm gonna introduce our speakers. We have two fantastic and distinguished speakers, and I'm gonna start with Dr. Kevin Elias. Dr. Elias is an accomplished surgeon, researcher, and academic. As you can see here, he wears many different hats with respect to women's health. He's an associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, and director of the Gynecologic Oncology Laboratory and the Division of Gynecologic Oncology at Brigham and Women's Hospital. He's also a practicing gynecologic oncologist and a surgeon scientist at the Dana-Farber Cancer Institute. Dr. Elias' work is focused on the prevention, diagnosis, and treatment of women with gynecological cancer, and in particular, the early diagnosis of ovarian cancer and novel treatment approaches based on polymer chemistry. Dr. Elias, I wanna just thank you for entrusting Aspira with your life's work and the technology that you and your academic partners have worked so hard on. It's important for us, and we're really honored to have the opportunity to bring this great research to women and their doctors. Thank you for that. I was hoping, maybe you could share a little bit with our participants about, you know, why did you choose to partner with Aspira? What makes us special? Well, I think what really sets Aspira apart was your experience in this space, offering a clinical test already. When we were trying to decide who to partner with for our technology, one of the questions was: Who was most positioned to bring this to the clinic? It's one thing to work with a company that has never actually sold a product. It's very different to work with a company that has had a lab actually serving patients, specifically within the space of ovarian cancer, for a number of years. And so it was really that experience and the ability to reach patients in a short-term horizon that we were most interested in. Great, thank you so much, and thanks for being here with us today. It's always a pleasure to partner with you and your team, so appreciate your time. I'm now gonna introduce Jody Berry. This is the first opportunity many of you will have had to meet Jody. He just joined us this year from OraSure, where he served as Chief Scientific Officer, responsible for all innovation and product development. At OraSure, Jody led the breakthrough discovery of the first integrated swab-based test for COVID-19. And as an aside, if you're interested in hearing the story or reading about the story, you can read all about it in a book that was published by OraSure’s then-CEO, Stephen Tang, called A Test for Our Time, and Jody features quite prominently in that book. So, you know, I encourage you to go read more about that. But before that, he led immunochemistry research and development for Grifols Diagnostic Solutions, where he was responsible for the design of molecular and tissue culture laboratories and facilities for protein engineering, the development of a companion diagnostic for serous carcinoma using designer novel immune checkpoint inhibitor molecules. This is a lot to say, Jody. I should have made you do this. And immunoassays for blood-borne pathogens. He also served in senior scientific and executive leadership roles for BD Biosciences and Cangene Corporation. Prior to that, prior to beginning his prestigious corporate career, he served as head of monoclonal antibody and bioforensics response at the National Microbiology Laboratory of the Public Health Agency of Canada. Jody, I know you've had a long and impressive career, as everyone just heard it. I have no doubt you had many opportunities in front of you when you chose Aspira. Would you mind sharing what drew you here and what made you interested in joining the team? I think you're muted still, unfortunately. You can unmute. There we go. First, I made you mute, now I'm making you unmute. There we go. There we go. Absolutely, Nicole. Totally my pleasure to be here today. Since the beginning of my career, I've studied Chlamydia trachomatis, which is the causative agent of pelvic inflammatory disease and a really big concern for women's health. This has carried me through all the way till now, where 25 years later, I'm still developing diagnostics, and they still concerned women's health. You're right about OraSure. That was a fantastic experience. That little product called InteliSwab has brought them in over $800 million, and so we're hoping to hit another one out of the park here with Kevin. Thanks, thanks, Jody. I can't tell you how happy I am to have you as part of the team. I can't believe you've only been here a few months. I mean, you joined so seamlessly, and we're just thrilled to have you. And I also wanna mention that when we get to the Q&A session later on, the Vice President of R&D, Todd Pappas, will join us there. So, thanks, Todd, for making yourself available. I have to tell you, there's very few people in the diagnostic world that know as much about applying AI and machine learning to the development of novel diagnostic tests as Todd. So, we're thrilled to have you, Todd. Thanks for making yourself available. Finally, even though he's not a speaker today, I did want to mention and thank Dr. Ryan Phan, who continues to be a major contributor to the R&D at Aspira. He's been the driving force behind our OvaWatch product development, which Jody and I will talk about today. And he's also the company's CLIA lab director, so he's responsible for the launch of all of our lab-developed tests and therefore has been integral to the process. He's working closely with Jody and Todd on a daily basis, and we're really fortunate to have him on the team. So thanks, Ryan, if you're listening. So I'll come back to the two of you in just a minute. If we can go to the next slide, I'm gonna first give a little bit of an overview about Aspira and, you know, provide some backdrop as to why this is a unique investment opportunity. So we are a technology company with a very clear mission, a well-defined mission. Our focus is to improve health outcomes for women through the development and distribution of non-invasive diagnostic tools for gynecologic disease. While we're very proud of our R&D efforts, and you're gonna hear all about that today, it's important to note that we are a commercial-stage company. We have revenue-producing tests and a sophisticated sales team that has driven consistent growth in the post-pandemic era. As you'll also hear today, our blood tests are powered by AI and are processed in our own CLIA lab in Austin. So that's where we conduct much of our R&D as well, which shortens the time from development to product launch. Our commercially available tests are included on the CMS fee schedule at $897 per test. We continue to make great progress in reimbursement from Medicare Advantage, Medicaid, and a wide range of commercial payers as well. But as much as our success relies on our technology, it also relies on our experienced team. You know, over the past two years, I'll say I was absolutely shameless in taking advantage of the consolidation and disruption in the diagnostics industry and sector, snapping up a lot of truly experienced people in every part of the business, from finance to commercial, and again, to R&D, but also our back office. So, you know, we've built an extraordinary team that is really important to the future success of the company, and I'm super proud of what we've done so far. And I'm even more proud of how we've managed to do that with exercising a very healthy dose of fiscal prudence. So, you know, we're gonna get a little snapshot of some of those folks today on this call, but rest assured, there's a big team behind the company as well. So with that as backdrop, I'm gonna hand things over to Jody to start with an overview of our technology. So we can go to the next slide, please. Thanks, Nicole. So again, one of the other things that attracted me to Aspira Women’s Health is the fact that they’ve been working with artificial intelligence now for over 20 years. So they’ve been here since before working with AI was even cool, and now it’s really cool. And so that was a huge attraction for me. And the value there is 20 years of data that they have on all these different disease states for concerning women’s health. So we don’t really limit ourselves in the discovery phase to one particular approach. We will use decision trees, neural networks, support vectors, whatever it takes, initially to reduce the number of features that... If you see on the right in this little circle, those are all individual features, and some of them will be of great importance, and some of them will have no importance. And, you know, the neural network and the AI basically quickly get you to the ones that are important, and then it gets locked in. When I say locked in, it just becomes math at that point, because for a diagnostic test, you know, the FDA wants it locked. You can't have something that just keeps evolving as you go through the population. So, this is what's been used to develop Ova1, OvaWatch, Overa, and now for EndoCheck. So it's a great history of products that have been developed using this approach. Next slide, please. This is a build slide, so, you know, and Todd, feel free to jump in. We tried to capture our discussions here. The initial product of Ova1 and Overa, those, they were basically 100% designed upon protein expression and protein detection in the proteome of serum. Then on top of that, there was an algorithm that would calculate your score or likelihood of having ovarian cancer or not. Next slide, please. This is sort of our example of being nimble. On top of that, you know, we built in the metadata, things like age, menstrual stage, that kind of thing, weight. Patient features are also built in on top of that in OvaWatch and EndoCheck. These are an important addition because they're independent data points that build towards your score. The next slide, please. So what Kevin and Todd have done is gone out and found an entirely different independent source of indicators, your microRNAs, which are not overlapping with proteins or the patient features. When I say not overlapping, I mean, it's not like a particular protein that we measure. The microRNA that's specific to that is not linked to it. These are independent features, and this is what's building OvaMDx and EndoMDx, so very powerful technology. Next slide, please. I'm gonna tee this up for Kevin. Basically, you know, everything we've developed so far has been based on protein biomarkers, and now we're entering the realm of microRNAs, and this is a very exciting technology, and, well, I'll let Kevin reveal this to you. Thanks so much, Jody, and the reason that we're interested in microRNAs is how they complement sort of traditional non-invasive diagnostics. So, for those of you less familiar with microRNAs, we're talking about part of the non-coding genome. So we usually think of genes as being the part of the DNA that codes for proteins. microRNAs fall in the intergenic region, so the DNA between the genes. There's a number of regulatory forms of RNA, microRNAs being one constituent of that. The function of microRNAs is really to regulate gene expression. I have to think of these as the copy editors of the genome. So they will bind to messenger RNA as it comes out from the nucleus, and they'll help decide whether those messages should be degraded, and they'll modify protein output. The reasons why microRNA, in addition to being biologically very interesting, is particularly conducive for non-invasive diagnostics, is that we see microRNAs appearing in all body fluids. Unlike other RNA, microRNA is extremely stable at room temperature. You can have it sit out for several days or ship it at room temperature without any degradation of the analyte. But like other nucleic acids, it's amenable for PCR amplification, which helps with sensitivity. Also, like other types of PCR, it's high throughput, so you can use the same pipeline for examining a lot of different microRNAs simultaneously. There are other laboratory-developed tests on the market for microRNAs, so we do know that microRNAs can be correlated with specific disease biology. For different disease states, we see microRNA profiles that correlate with unhealthy cells, both in cancer and other disease processes. We can go to the next slide. Next slide. So, yeah, but- Okay, great. Thanks, Kevin, and just to add to that point, there's over 2,300 different microRNAs that have been discovered in the human genome, and if you think about the timeline of microRNAs, they were first discovered in 1993. So it really hasn't been around a long time, but it's moved very quickly. So jumping over to ovarian cancer, I don't know, Nicole, did you want to talk- Yeah, I'll start here, but I... You know, of course, we have an expert here, so I'm gonna give the mic to Kevin pretty quickly. But, you know, just at a high level, when you think about ovarian cancer, I think one of the things that was a learning for me when I first joined the company, or actually, I invested in the company before I joined the company. And when I was doing research about ovarian cancer, I was surprised at how difficult it is to find. Because a lot of the things we typically think about as being useful in identifying cancer are really not particularly helpful for ovarian cancer. So, Kevin, why don't you take us through a little bit about the diagnostic dilemma? Sure. So, a woman presenting with an adnexal mass, by which we mean just a mass in the region of the ovary and fallopian tube, is one of the most common problems we see in general gynecology. And, unfortunately, we don't biopsy ovaries, and the reason for that is that these masses are typically cystic in structure, and by inserting a needle into them, you upstage the patient if there is a malignancy there. And so that can be the difference between a woman requiring chemotherapy and not requiring chemotherapy, and also can have a significant impact on prognosis. Without the ability to biopsy an ovary, we're really left to non-invasive diagnostic tools, principally ultrasound. And of course, ovarian cysts are very common. Ultrasound does a relatively poor job distinguishing ovarian cysts from normal ovaries. We also know that up to half of women with ovarian cancer will have a normal ovary on ultrasound. So just using ultrasound alone to decide ovarian cancer risk is really insufficient. That has led to a lot of off-label use of protein biomarkers like CA-125. Now, CA-125 is indicated for monitoring for recurrence for women who had ovarian cancer or for monitoring response to therapy for women with known ovarian cancer. But as a marker for diagnosing ovarian cancer, CA-125 is not approved, and leads to a lot of false positives, because CA-125 will be elevated really in any condition where there's peritoneal inflammation, whether that's diverticulitis, or ovulation, or pregnancy. Similarly, CA-125 will miss more than half of early-stage ovarian cancers- Mm-hmm. the ones that we really wanna diagnose when they're most curable. Mm-hmm. That's part of the reason why the majority of women, when they are diagnosed with ovarian cancer, present with advanced-stage disease, and that's really what I see in my clinical practice every day. Now, in order to avoid that, what ends up happening is that we do a lot of oophorectomies to try to diagnose a relatively small number of cancers. And as indicated on the slide here, we're doing more than 200,000 oophorectomies a year, but only 20,000 cases of ovarian cancer are diagnosed annually in the United States. The reason that might be seen as an extreme overreaction is that we're so bad at diagnosing the disease, that essentially anything that might be ovarian cancer, we tend to intervene on surgically. Although that's actually not improved our survival from the disease, because we're still not detecting the women who actually have ovarian cancer early. Yeah, this is a really personal topic for me. You know, I can, I can tell you that my own experience was, I'm a breast cancer survivor, so when I had and the granddaughter of someone who died of ovarian cancer, so, when I had a mass appear, anywhere near my ovary, the suggestion was, "You know, we should think about taking your ovaries." And, you know, frankly, I was really scared not to go forward with that, surgery. This was obviously before OvaWatch, and one of the major reasons why I'm so passionate about it. So you might say, "Well, what's the big deal? Go ahead and take them out." Well, not only did Kevin just point out that, you know, it doesn't seem to be really resulting in a great survival rate for women who have the disease, there are also some really important long-term impacts of having your ovaries removed premenopausally. Although, there is some research now that says that it, that is, they continue to be beneficial even into menopause for some period of time. You know, being pushed into surgical menopause, I can tell you from experience, was no fun from a lifestyle perspective. But also created risk, health, other health risks that I didn't know anything about until after, including, you know, higher risk of heart disease, a higher risk of Parkinson's disease, osteoporosis. I recently saw a study that showed that, you know, life expectancy for women who have had their ovaries removed premenopausal may actually be, you know, more than insignificantly shorter than women who haven't. So there's, you know, this is a mission for our company, not only to help find ovarian cancer earlier, which of course is, is central to everything, but also to get away from making important decisions about your health based on fear, and give people better data and actual information about the likelihood that the mass you have is cancer. Because the odds that it's cancer are very small, relative to the number of masses that we see every year. So, you know, that's what drove Aspira, in its early days to focus on ovarian cancer. You know, it's significant unmet need at that time. We currently have the only comprehensive portfolio of blood tests, of non-invasive tests, to find, or to measure the risk of ovarian cancer for an adnexal mass. With the launch of OvaWatch last year in 2022, we now have a test for all adnexal masses. So whether or not, the patient's physician has decided that surgery is the right intervention or not, we have a test, anytime a woman presents with an adnexal mass. And we've heard from our physician base that this has been incredibly helpful to them in making care decisions based on data and not based simply on fear. But, you know, there's still work to be done, and the first thing is that we need to focus on is OvaWatch and expanding that to a broader use or a broader indication. Currently, we launched OvaWatch as an LDT for a single use, meaning initial clinical assessment is when a woman presents. But we've continued to follow patients from the original OvaWatch study, and are poised to now launch that with an expanded use. So Jody, I'll hand it back to you to talk about how OvaWatch will grow and change in 2024. I think you're muted again. We're really giving you a run for your money with that mute today, Jody. There you go. Yeah, OvaWatch has really changed the game in the sense that it's allowing for longitudinal testing and monitoring of the advancement of these masses, not just a single shot in the dark. So I think this is very important to women moving forward, in the sense that they'll be able to interact with their physician and basically have a running score, much the same as a chronic disease like diabetes. You know, "What's my A1C?" You know, "What, what's my OvaWatch score? I wanna see where I'm at." So that's an incredible advancement in the field. Aaron, could you just jump to the next slide for me, please? Sorry to interrupt, Jody. Great. Thank you. You're welcome. And I'll probably invite Todd to make a comment about the nice little report on the right, but essentially, Ryan Phan and Todd have put together two manuscripts. One for the longitudinal monitoring, which is under review, and one for the surgical impact in ovarian cancer on the score. And what happens is, basically, patients come in, and they'll get their score, as on the right, whether they're high risk or low risk or in between, and that will be carried out over time. I don't know, Todd, if you wanna add anything to that? ... Yeah, I don't, I don't have much more to add, and, and thanks, Jody, for pinging me on this one. I don't have much more to add to this. Generally, what we see in our research is that these scores are very stable, and so it's exciting to be able to provide that information in a longitudinal fashion. We have a publication that should come out that we've submitted, and that is undergoing review right now, so more to come on that. Great. Kevin, do you have something to add? Yeah, I just wanna emphasize what a difference this makes, having longitudinal assessment, because so much of our interactions in the past with patients have been static. What we often see when folks come in with what we consider to be a low-risk adnexal mass is that we're stuck in this loop of always advising women, "Well, I'm pretty sure it's not cancer, but the only way I know for sure is to remove it." You end up with this cycle every few months of continuing to observe these things. Really, with OvaWatch, we have the ability to continue to revisit that conversation and say, "Look, the odds that this is malignant are still exceptionally low. It's safe to continue to monitor it." That really changes the way that those interactions will be happening in the future. It's fantastic. We can go to the next slide. So, moving forward to OvaMDx, this is a new, additional layer that we talked about earlier, adding in the microRNAs on top of the protein and on top of the metadata. So what are our advantages on this? We already have the existing FDA-approved, protein-based tests. We have exclusive rights with, Dana-Farber and Kevin to use the microRNA in our assays. And we are experienced, as you heard earlier from Todd and from Kevin, in AI and the proprietary algorithms. So, this has led to brand recognition, repeat use by healthcare providers, and we also have access to a very large biobank of samples that will carry us through the verification and validation of this assay. So this is a non-invasive test. It's a blood-based test, which is what we're familiar with, and you do not need laparoscopy to go in and determine whether or not somebody has likely has ovarian cancer. So it combines some of the characteristics, and I'll pass this to Kevin, with his microRNA experience, protein experience, and also the metadata that he presented at AACR this year, earlier in October. Yeah, thanks, Jody. And I think the key here is, what were the gaps we were trying to fill by adding microRNAs into the existing Ova1Plus platform? And really, it was the fact that we needed something to improve specificity for all stages of cancer. And then also specifically looking at early-stage ovarian cancer, the ones where intervening is most likely to have the most impact on long-term survival for the patient. We've known for a long time that proteins alone are not as sensitive for early-stage disease, but as we'll show, adding in the microRNAs really helps fill that gap. So if we can go to the next slide. And the next one. Perfect. So we initially began looking at microRNAs back in 2017. We published our first report on this in eLife, and there, this is a very AI-heavy publication where we looked at ways that we could combine multiple microRNAs into neural network models for discriminating women with ovarian cancer from those without ovarian cancer. And in the figure here, just showing the receiver operating characteristic curves, comparing this neural network approach of microRNAs to a traditional protein biomarker like CA-125. You can see the CA-125 has fairly limited ability to actually distinguish women with ovarian cancer from those with other types of benign adnexal masses. Whereas with the neural network approaches in microRNAs, we really boost that performance. We followed this up with a second study involving 275 subjects, that was really focused on the Stage 1 and 2 disease. There we showed that, again, the sensitivity was preserved, with still a very good specificity, when we're only looking at Stage One and Two cancer, so women with disease confined to the ovary or the ovarian fallopian tube. You can go to the next slide. The question when we began collaborating with Aspira was really to say, based on the existing product in the marketplace, is there a role for combining what we had produced with microRNAs with what was already out there with proteins? So the first question was whether or not either test alone was superior, so to actually do a direct comparison, as well as to find a way to combine the two approaches. We set this up by using blinded internal and external validation sets. So we worked with Aspira to produce a training model and then actually exchanged samples back and forth in a blinded fashion, with protein analysis by Aspira, microRNA analysis our end, and then looked to see if a joint model would perform either similarly or better than each individual type of analyte alone. These are specifically women who were presenting with an ovarian mass, and really the idea was to see whether we could do a better job for early-stage cancers and specifically early-stage serous cancers, the cancers that cause the largest proportion of ovarian cancer deaths. Go to the next slide. Okay, so the training cohort of this really came from Aspira, and then we had a holdout group for validation. We then had an additional validation set, which came from Brigham and Women’s Hospital. And you can see this is not a small number of patients. So in total, we all had almost 700 study subjects in this particular study. And if you look at the receiver operating characteristic curves on the right, I've sort of put the arrows to highlight where we're making our discrimination. And you can see that we—we—of course, we see that proteins do perform well. If we add microRNA, if we use microRNAs alone, they also perform very well, but really, it's the combination of proteins plus microRNAs plus metadata, and Jody alluded to some of this, so the age and the menstrual status of the patient that we get the highest performance. And so now, when you combine those three different categories of data points, proteins, microRNA, and metadata, we have an AUC that's really the highest that we've seen in this space of at 0.95. In particular, what was exciting to us is the improved sensitivity for early-stage ovarian cancer. So whereas protein biomarkers alone, you might get two-thirds of early-stage ovarian cancers, now we're getting 90% of ovarian cancers. And when you really laser that in on the early-stage serous ovarian cancers, again, the ones that have the highest proportion of ovarian cancer deaths, we're bringing that up again from two-thirds to almost 90% of those early-stage serous ovarian cancers. If you look across all cancer types, the overall sensitivity is about 97% for serous cancers and 94% for non-serous cancers, which again, is a radical improvement over most protein biomarkers because we know things like CA-125 are not elevated necessarily in all histologies. You can go to the next slide. This has led to an opportunity for us to actually continue to collaborate with Aspira, and the NIH put out a call for academic-industrial partnerships, and since we were already working in this form of collaboration, this was a great opportunity. So this is an application that's going in later this month, that is focused on translation of technologies for diagnosis and treatment. I think this describes OvaMDx perfectly. We've realized that to make a commercially viable version of OvaMDx, the best technology platform is digital PCR because it allows us to get absolute quantification of microRNAs. It allows us to provide reference ranges to laboratories that are easy to interpret, which is an important advance over relative expression, which is oftentimes how things are done on the research side. And so we've laid out the aims here. I'm not going to go into them in detail right now, but just for actually putting this really into the commercial space. This is an NIH initiative to push new technologies into the market, and so we're excited to work with Aspira to make that happen. Absolutely. Thank you, Kevin. We can go to the next slide. I'm going to have Jody talk through the development pathway for OvaMDx. I will mention that when we get to the end of today's session, we'll go through the major milestones, which will primarily be pulled from these development pathway slides that we're going to share. That will give all of you as investors a roadmap to follow for things that we will achieve that will keep you give you insights that we're well on our way. So, Jody, why don't you give an overview of where we are on the development pathway for OvaMDx? Thank you, Nicole. Absolutely, Kevin teed it up very well. He's already determined the microRNA signature using NGS and also quantitative PCR. And so obviously, we're a publicly traded company, and we have to verify this on our own, and we're going to transfer that. It's underway to put it onto a Bio-Rad FDA-approved digital droplet PCR platform, which will make all of our lives easier and make our regulatory approval much smoother down the road. So, the box on the left and the box on the right are either complete or underway. We're verifying the signature with an external CRO at this point, and Kevin is going to summarize in a publication very shortly the initial findings that he used with his protein set and his microRNA analysis. Really, our work at this point is down selecting. So we're trying to, you know, take it from the observational discovery to an actual practical test that we can use in the lab on a routine basis. So that's underway right now. And then after that, it's standard transactional verification and validation, and then, of course, regulatory launch to the right. We're going to go for a 510(k) submission. Next slide, please. Thanks, Jody. And that kind of brings us into our endometriosis test portfolio. I just want to remind you, I do see a few questions coming in. If you have questions, you can put them into the Q&A, and we're going to read through those and try to cover as many as we can at the end. So if you have questions about ovarian cancer portfolio, please drop those in there. We're gonna move ahead here and now start talking about our endometriosis test portfolio. And, you know, again, I'll ask Dr. Elias to talk about his experience, but, you know, just to kind of give, I think one of the more interesting parts of my role as the CEO of the only gynecologic disease diagnostic company that I'm aware of is I often am in a position where I'm explaining female anatomy to people who don't possess female anatomy. So I really sometimes feel like I'm explaining the great mysteries of the world. But endometriosis is something that is really a not just a diagnostic dilemma, it's really an overall clinical dilemma. It's one of the most difficult diseases to find. It's the most difficult disease to treat, but it affects a staggering number of women and girls. Young girls in their teens are often, you know, for... They will develop endometriosis as early as their first cycle. It's really tough, but, you know, it's a debilitating condition where a tissue that's similar to the lining of the uterus grows somewhere where it doesn't belong outside of the uterus. And maybe that sounds benign, but it continues to behave in the same way that it does while it's in the uterus, and that causes all kinds of problems, because it plays an important role during menstruation. But it's not so great to have it play that role when it's attached to your colon or your bladder or somewhere else in your pelvic cavity. You know, Kevin, this is obviously another area where you have been at the forefront of research. I don't know if you'd like to comment a little bit on endometriosis. ... Well, exactly, Nicole. So, from the research side, this came as sort of a natural extension for us, because a lot of the women that were enrolled in our ovarian cancer studies as the controls, a lot of them were going to the operating room because they, in fact, had endometriosis. So, it became, after having, you know, enough women in our studies, an interesting question to say, "Well, is there something that distinguishes the women with endometriosis from women with other types of benign pathologies?" Whether those are functional cysts or women just coming in for, you know, fertility evaluations or other benign indications. And we found that using a lot of the same tools that we had used in ovarian cancer, we could also start to see signatures for endometriosis as well. And much like with the problem with ovarian cancer, it's a similar clinical issue, that other than sort of going to the operating room and actually visualizing a lesion, there really is no circulating biomarker or radiographic test that is gonna tell you that someone has endometriosis. And as you point out, we're often dealing with very young women, and it's not a benign thing, so to speak, to take them to the operating room for a surgical intervention. Yeah. And you can see here that, you know, only about half of the women who do have a laparoscopic procedure receive a diagnosis of endometriosis. Now, that doesn't necessarily mean they don't have endometriosis, because if you haven't visualized it, then you can't diagnose it. You can't take a biopsy of it if you can't see it, and it's pretty tricky. It can be, you know, really good at hiding behind other organs. And so, you know, not only is laparoscopy invasive and not an ideal first step for any diagnosis, but it is not perfect even on its own. One of the other interesting things that we found is, you know, this has been a really hard test to develop, very hard. You know, we're the first to make progress and to have a blood test for the identification of endometriosis. That is a huge deal. So I want to make sure that I don't underplay how important and difficult that was. Partially because some people I know that have been invested in the stock for some time have been, you know, had a hard time understanding why it's been so hard to get samples. And part of that is because we insisted on using histologically confirmed endometriosis, histologically confirmed for both our controls and our positive cases. That's important because, as I said, if you're only relying on visualization, it doesn't mean that endometriosis isn't present. It just means you didn't see it. So, you know, that's been a really important characteristic of the test development, both for proteins and microRNA. So we can go to the next slide, and we'll just dive right in on EndoCheck. Oh, actually, I did want to mention, too, you know, that I think you can get there on your own about the significant unmet need for patients. 6.5 million women, by some accounts, in the United States alone, 10% of women around the world, the World Health Organization has estimated 10% of women around the world, suffer from endometriosis. It costs an extraordinary amount of, in terms of the U.S. economy, with these women are typically out of work if they have a severe case. With high levels of pain, they could be out of work for as much as three or four days a month. And the expense of the surgery and the medications that are available currently are quite expensive. So the patient cost, direct and indirect, can be very, very high, $12,000-$16,000 annually, not to mention all of the cost to the payer, the payers that are covering these procedures. What's exciting, though, as you can see on the chart below, this is some research that we secured that talked about, you know, new tests that are in development- or new therapies, sorry, that are in development for endometriosis. Which is important for us for two reasons. First, in order to get these products to market, pharma companies are gonna need to be able to find patients for clinical studies before they have their endometriosis surgically removed. And so the only way you can do that is with a non-invasive diagnostic like we have developed, number one. And number two, to drive physicians to prescribe medication, including ones that are already on the market. A diagnostic that doesn't involve taking a patient to surgery is going to be very helpful, especially if you're going to target the pediatric, which I am talking adolescent, market, right? So, it's an exciting opportunity right now with all these new therapies in development. I think we're talking to potential partners all the time. And you can see that by twenty... I think that's so tiny, but I think it's by 2032, most of the market will be with therapies that aren't even completed today. So we can go to the next slide and talk about EndoCheck. And again, you know, I just wanna, I just wanna stress again, this is a huge, huge accomplishment. To have a test that works for the non-invasive identification of endometriosis is a big deal, especially for endometrioma, which is the most common form. So, Jody, go ahead. Thanks, Nicole. No, this is the headliner right here. We have a test that can actually detect almost half of endometriosis. Endometrioma is a major form of endometriosis, and it also is the one that probably most significantly impacts fertility and the ability to have children. And again, we've built this based on our FDA-approved platform for ovarian cancer. It's very similar biomarkers, but slightly different, and this will be validated in our CLIA lab. And again, using our experience with AI, with Kevin and Todd, we will get down to the minimum factors that we need. And initially, this was done with a set of samples that came from University of Oxford, and that's what gave us our training model. We've already had an independent verification of that, and then we have the last verification underway this month. So we're very excited. This will be non-invasive, a blood-based test, utilizing our proprietary algorithms at Aspira that are protected through patents. So, a very exciting time. And there are other biomarkers also that keep coming up in the literature that we're examining also just for, you know, an orthogonal means of testing for additional specificity. So that's underway also, and I can't really say much more than that. Next slide, please. So this is probably Todd's most exciting slide he's put together this year, and I'll let him make a comment about it. It's a probability plot, and we intentionally did not put on the Y-axis just because we're combining this data with other cohorts to produce a publication. But we wanted to share this with you in terms of what our algorithm will generate in terms of endometrioma versus no endometriosis, and it's night and day and very black and white. So this is the first of a kind blood-based test with about 85% accuracy for endometriomas. And there's a quote at the bottom there I'll pass to Kevin that really came from him in terms of what this might mean in terms of a physician-patient relationship. Well, exactly right, Jody, because when, again, when I'm seeing a patient in the office for evaluation of some sort of adnexal pathology, you really have two components to the question. The first is, well, is it cancer or not? And if you're saying it's not cancer, then being able to follow that up and saying what you think it is, adds a lot more confidence to your diagnosis. Because, again, if you've got one test which says, "Well, it's very unlikely to be ovarian cancer," and another test which says, "It's overwhelmingly likely to be endometriosis," it really simplifies the clinical conversation and makes you feel a lot more confidence in moving ahead with the treatment plan. Great. Thanks, Kevin. We can go to the next slide. So where are we in the EndoCheck development pathway? The two left boxes are complete. We have the protein signature, we've down selected the biomarkers, and we're running through the final V&V for the next cohort to take it forward. And this is coming from Kevin's lab at Dana-Farber, the final external verification set. And the plan is to potentially launch it as an LDT, which is a quick way to get it to market, and then later as a 510(k). And these pathways are well entrenched and very familiar with us at Aspira. So we have an abstract that's with Oxford, and we plan on submitting based on their data to a fertility conference next month. We have additional biomarkers, again, being analyzed to see whether or not it adds anything to expand the types of endometriosis that we can pick up. Then, of course, as Kevin mentioned, we have an NIH grant submission in process. Move to the next slide, please. So Jody, we have about a little over just around 15 minutes left in the session. So we'll talk about EndoMDx, which is also extremely exciting. And then give me just a couple of minutes to wrap up before we try to answer some questions, so. Okay. Thanks, Nicole. So EndoMDx is basically a molecular diagnostic form of the EndoCheck, which we believe will, based on Kevin's data that was carried out under a research agreement, he's shown that you can pick up a lot more of endometriosis when you combine, again, the microRNA data with the metadata, with the protein data. So this is very exciting, and, you know, this actually has an opportunity of overtaking the EndoCheck test if it, you know, bears out the way we think it might. So it leverages what we've done with the Ova molecular test in terms of similar microRNAs, but not exactly the same, but a similar approach using digital droplet PCR. We have a large number of samples already in our biobank to complete the verification and the AI expertise also to carry this out. So very exciting. On the biobank, Jody, if you don't mind. One of the things that's in the biobank is, you know, a very large number of samples that we acquired from Myovant several years ago. These were whole blood samples, so we couldn't use them for the EndoCheck development, but they are usable for the OvaMDx validation process. There's about over 1,000 samples that were acquired through that acquisition, and the ones we have already that we have accumulated from our own clinical study and samples that we will have access to through our sponsor research agreement with Kevin and his academic partners. So, you know, I'm feeling very good about our access to samples for EndoMDx, much better than EndoCheck, which was a real struggle. So, if we can go to the next slide, I think, Kevin will talk. I think it's also important to note that we own the technology. So this was developed through a sponsored research agreement, you know, so this is Aspira's IP. Right. So with EndoMDx, we really took the same approach that we've been using for OvaMDx and said: Are there similar ways that we can optimize this for endometriosis? And what we're showing here is now expanding beyond just endometrioma and talking about endometriosis generally, including peritoneal endometriosis, deep infiltrating endometriosis, really trying to capture the full spectrum of the disease. And we found that similar to with ovarian cancer, when you add metadata, microRNA, and protein, they each add independent data to the model such that the combined model has the highest sensitivity and accuracy for diagnosing endometriosis. So this is not—it's not a huge model. It's 10 microRNAs and four proteins. It's not. So I'll make it clear, this is not some sort of giant fishing thing. We've really got the number of variables relatively narrowed down now. It's, I think, because of our experience working together at the OvaMDx space, we've really been able to move at a much quicker pace with EndoMDx. Very true. And that kind of carries through on the development pathway on the next slide as well, which essentially, you know, one of the important components of this, you could see, you know, the signature is the discovery is completed, the design's in process. Sorry, Jody, I'm gonna go through this kind of quickly. But importantly, we will be leveraging the same commercial platform, FDA-approved commercial platform, the Bio-Rad system, as we are currently validating for OvaMDx, which is why we chose to do it in that order. We're very close to being able to launch that OvaMDx product. It fits perfectly into our existing product portfolio for ovarian cancer. And if we are able to get that platform migration completed for OvaMDx, there's a high degree of certainty that it'll also work when we go to do the technology transfer for platform migration for EndoMDx. So, there's a method to the madness there, so to speak. So thank you, Jody and Kevin. I'm gonna spend a few minutes on the... You can go to the slide with the pipeline. Just go a couple forward. Right here. So, you know, this is where, as an investor, I think, you can get very excited. Yes, it's great that we're helping women and that we're gonna make a huge impact in women's lives. But we are also looking at a very significant market opportunity, given the challenges and the diagnostic dilemma we described. We believe that, with the addition of the longitudinal monitoring test and OvaMDx, we're confident that the market is in the $600 million-$700 million range. You know, these, again, are domestic, these are domestic opportunities. Of course, ovarian cancer doesn't discriminate. It's so there's a global component to our future as well, but we're focused right now on the large opportunity right in front of us in the domestic market. And again, with endometriosis, you can see, you know, what's critical here is EndoCheck, which is been designed for endometrioma, has a 2-2.5 million potential patient population. So, you know, this is a really big opportunity, even for the protein test that's ready to go. And then as we shift to EndoMDx, which will be effective in identifying endometriosis, regardless of where it resides, then you're looking at, you know, a $6+ million patient population. So, you know, a very significant opportunity across the board for our in-development and in-the-market tests. On the next slide, I've laid out, and this will be posted to the website, so I'm not gonna read these off, but what we did is pulled out some of the near-term milestones. It says 2024 milestones, but I wanna be clear that these are not all of the milestones for 2024. These are sort of the near-term milestones that we have identified throughout this presentation as sort of in process, that completion will validate where we are in the development and launch. So, you can kind of use this as a report card for us going forward. We're committed to keeping our investors up to date and abreast of our progress on milestones. So that's the full extent of the prepared presentation, which leaves us just a couple of minutes for questions. So any last thoughts from Jody or Kevin before I go to some questions? I have quite a few, so I'm gonna try to whip through a bunch of these quickly. Great. So I'm gonna start with a question about the response from physicians to EndoCheck. And I'll say, and I'm... You know, Kevin gave his input a little bit earlier about the power of combining it with other with our OvaWatch tool. You know, everyone's eye is on the big opportunity to identify endometriosis, regardless of its location. However, all of the physicians that we talk to recognize the significance of having a non-invasive tool for endometrioma. So, you know, it's a little bit narrower, but it's an important stepping stone towards OvaMDx because it builds the basis for the protein piece of the test that will include both proteins and microRNA. So it's a very significant achievement, and that's been very positively received, although everyone's really excited about the test on the other side of that. There's a question about, hypothetically speaking, how many more women are willing to get properly tested, knowing it's non-invasive? This is an important question. I think we tend to sometimes oversimplify the care pathway here to say, "Well, if I think it's this, I'll just go ahead and do the surgery." But that doesn't recognize the fact that a lot of women in this country don't have health insurance to pay for that surgery, whether it's a prophylactic removal of their ovaries or a laparoscopic exploratory surgery for endometriosis. They don't have the coverage for it, and therefore, they won't go ahead and have that test done, you know, if it's invasive. Also, there are good reasons not to mess around with your ovaries if you don't have to, even if it doesn't result in removing the ovary. There's been some recent studies that Jody and I have been looking at, about the impact on ovarian reserve. Any time that there's a surgery done to an ovary, you know, you can disrupt the ovarian reserve and make it more difficult for a woman to become pregnant. So younger women are extremely hesitant, and rightfully so, about going for an invasive procedure. So I think hypothetically speaking, you know, we'll see a big uptick in people who do the follow-through and the compliance, which is an issue. There's a question here about: does any of the microRNA originate from environmental sources, such as biofilms, and are the identification of these factors proprietary? I don't know, Kevin, is there anything in terms of, you know, the microRNA and the question about the environmental sources or? So, the microRNAs are tissue-derived. So in the original Elias publication, we actually did in situ hybridization to show the microRNAs in the ovarian cancer cells themselves. So while it's possible that some of them might also be in circulation from other sources, the ones that we're focused on are actually, we're able to identify them within tissue. Great. There's a few questions that I would wrap together around standard of care and guidelines. There's one that says: what will it take for OvaWatch? But it's, I think it's a broader question about non-invasive ovarian cancer diagnostics to replace CA-125 as a standard of care. I would say to replace CA-125 in prophylactic surgery as the standard of care, seems like neither the doctors nor insurance companies want this to happen. You know, I would say that, you know, we have strong adoption of our current portfolio with the doctors that that use it, right? What we need to do a better job at, and I'll put this on our commercial team, and one of the main reasons why I've changed the commercial team, quite a bit since taking over as CEO, we have to get in front of more of the large physician groups and the health systems that are really driving a lot of decision-making around the standard of care within those systems. So medical guidelines are important. They're always gonna be important, but they're... I think it's even more important to make sure that, medical policy within the physician groups and health systems, recognize the power of a non-invasive tool for both ovarian cancer and endometriosis. So that is a pivot that we have made as part of our commercial refresh that I've talked about many times in the past. But we are continuing to work with medical policy, with the insurance companies, and then, of course, the professional guidelines. So, we're refocusing on that, and that'll be a big part of our new product launches going forward as well. There's a whole bunch of questions here that I would group together as: what other kinds of biomarkers might we then... You know, if we have our three-circle chart at the beginning, you know, is there a fourth circle that we're looking at to add there? And as Jody mentioned earlier, there is additional discovery with other biomarkers, but frankly, we're not really in a position to talk much about that, because we haven't completed the discovery, and we haven't protected the IP yet. But yes, there's additional discovery happening that we think could even add to the accuracy of the test. We're actually out of time. I think I've covered a lot of these. One question, yeah, a lot of these are sort of commercial, and I see who asked them. If we're able to get back to you individually, we'll certainly do that. But I think that's probably the majority of them here. Actually, there's a question here from Ben Hayner. Hi, Ben, from AGP. With Ova, OvaMDx and EndoMDx planned to pursue 510(k) clearances, how do they ultimately get commercialized alongside OvaWatch and EndoCheck, given the benefits? So now, that's the beauty of a portfolio approach. It's important to remember that each of our tests has a different intended use, so they're complementary, but they're not identical. And so, you know, having a mix of lab-developed tests that are quick to market, and are protein-based, that we can do the R&D and the commercialization in the lab we already have, and combined with some in-development tests, that we will take the FDA-cleared route, that those will be extremely important for global expansion. Also important when we're looking to bring on board large physician groups and health systems who do not prefer to run their tests internally versus send outs. So having an FDA-cleared test helps with that as well. I t's a portfolio approach, and that we think is gonna work very well. So, okay. So I think that's probably all the time we have, and I tried to answer as many as possible. But, you know, to the extent that we have contact information for people who asked a question we didn't get to, we'll try to get back to you individually. So, I just wanna thank all of you for being here, and especially thank Dr. Elias, who has a lot of things he could be doing with his time today. So not only for your partnership, and for entrusting us with your life's work, but also for taking the time to join us today. So thank you all so much.