bioAffinity Technologies, Inc. ($BIAF)

Everyone, thank you for joining us tonight for our CyPath Lung in Practice webinar. My name is Julie Anne Overton, and I'm the Director of Communications here at bioAffinity Technologies. Before we begin the webinar, I have a few housekeeping items to go over. The session is being recorded and will be available for viewing on our website at www.cypathlung.com. Regarding tonight setup, all of the attendees are muted by default and your cameras will remain off throughout the session. Dr. Gordon Downie, who is our Chief Medical Officer here at bioAffinity Technologies, is going to moderate the conversation and he will introduce our panel of pulmonologists. You may submit a written question at any point during the webinar through the Q&A panel at the bottom of your screen. Dr. Downie will direct the questions to our panelists during our question-and-answer periods throughout the program. And if we don't get to all the questions, we're going to try to follow up with an e-mail after the fact. For our healthcare professionals who are joining us tonight, you will receive your DoorDash voucher on the same e-mail that you used to register for the webinar. With that, I'm going to hand things over to Dr. Downie and our panel of physicians. Thank you again for being here.

Thank you, Julie Anne. My name is Dr. Gordon Downie. I welcome you to the audience tonight for our CyPath Lung Testing, a simpler path forward. I'd like to thank bioAffinity Corporation for providing this platform for our audience and for our panelists. So I'm a first-generation interventional pulmonologist. I trained at UNC Chapel Hill. I've mostly published in photodynamic therapy, early lung cancer diagnosis and bronchoscopy education. I joined CyPath as their Chief Medical Officer about 12 months ago and have had a wonderful year working with them and talking about our product. Tonight, we're going to have an in-depth discussion about the clinical burden of processing early lung cancer and pulmonary nodules and high-risk individuals, either by screening or surveillance and survivorship or incidentally found pulmonary nodules. I'll be asking our expert panel to share their experiences with diagnosing lung cancer and assessing pulmonary nodules, and there will be two answer -- question-and-answer periods. We're fortunate tonight to have a wonderful expert panel who have significant experience in this arena and have added CyPath Lung to their clinical practice algorithms. We have Dr. Guda joining us from San Antonio. He's an interventional pulmonologist and specializing in robotic bronchoscopy, airway stenting and minimally invasive diagnostics in lung disease. We have Dr. Michael Nicholson joining us from New Jersey, Robert Wood Johnson, practice in New Jersey. He trained at Temple, and he does pulmonary and critical care. And lastly, we have Dr. Greg White, joining us from Texarkana, Texas at St. Michael Hospital. He specializes also in pulmonary and critical care. He assesses about 500 pulmonary nodules every year. So very expert panel. Tonight, our clinical problem is basically how we treat and how we assess patients who are involved with the pulmonary nodules. Every clinician who's joining us tonight is in a unique region that have different ways of defining the components of pulmonary nodules and the clinical challenges that assessing lung cancer, diagnosing the lung cancer and assessing pulmonary nodules. As an interventional pulmonologist at 1 time, the Vice Chair of the ACC Committee, on intervention. And now as a practicing pulmonologist and CMO, I have heard from clinicians all over the country about the challenges of dealing with pulmonary nodules. So I'd like to ask our panelists to talk about some of their challenges that they face in this interesting arena of assessing pulmonary nodules. Dr. Guda, perhaps you can start our discussion.

Thank you again, Dr. Downie for introducing me and bringing me in to talk about this. As an interventional pulmonologist and as somebody that does quite a bit of robotic bronchoscopy for diagnosis of these small nodules that we previously could not get to, it raised a very interesting question as to what we do with the smaller -- and if you're able to access smaller and smaller nodules or be able to go to those portions of the lung with a robot that we have never previously been able to get to, the question is, well, if you can do it for every single patient, should every single patient actually get that procedure that comes with a lot of risks associated with it. In our practice, we have a very robust practice and we do quite a few number of pulmonary nodules as well as advanced interventional procedures, including laser stenting, debulking, pleural biopsies. A lot of times the type of patients that we are seeing come in quite apprehensive because they either have a history of smoking or they know somebody that has had lung cancer or they have had family history of lung cancer and now they've got this abnormal spot that is there in their lung and they are unaware as to how they want to proceed with it. So when you -- one of the methods in estimating some of the grief that the patient may experience with that initial diagnosis, short diagnosis stuff, hey, there is something here on the CT scan that's concerning is to help risk stratify them. And that's essentially the biggest portion of why CyPath works. There are certain patient populations that do better with risk stratification and there are certain patient populations that just want to go forward and get a biopsy and be done with it. But either way, this piece of data informs us as to with what clinical confidence I can go in when I'm performing the biopsies to help answer those questions. So in most of our patients that are coming in, our practice is predominantly an oncology-driven practice, we have a lot of oncologists that refer to us. But we have a not insignificant number of patients that come to us through the ER, through primary care, through general pulmonary. And all of those nodules that we see can have a varying degree of risk. And so we do utilize it in those patients whose [ Mayo's ] calculator is insufficient in giving you the information or you have got a nodule that does not meet Lung-RADS 4B and then you were thinking, you know what, I need to do a biopsy of this, maybe, but there's risks associated with it. The patient may not be the best patient to take for anesthesia. Well, we definitely have a role for CyPath there to help risk-stratify. And then the patient gives us the -- patients, their own sputum gives us their information and then we proceed with the next steps, whether it's management with biopsy or management with imaging on at a reasonable cadence to all that is something that is informed because we have another tool to help us with risk stratification there.

Absolutely. Dr. White, you have a very busy practice in Northeast Texas. Maybe you could describe the challenges that you face in dealing with pulmonary nodule assessment.

Well, kind of echoing what Dr. Guda was saying, and kind of more -- in my simplistic way I think about it is not every patient needs a procedure and not every nodule needs a biopsy. It's just kind of an easy way to think about it. There's always risk anytime you put somebody under for a procedure. There's always a scary thing you're going to biopsy. That being said, risk stratification is always great. It's encouraged me to go after procedures, had patients get procedures, it encouraged me not to go after patients, [ procedures are actually ] -- I've even used sometimes with the patient with a high risk for a procedure and the PET scan was positive, and this was positive. I had radiation oncologists go ahead and start treating based off of that risk stratification. What I'm seeing with nodules is we've had a huge influx of low dose screening CTs for our hospital system. We're doing about 120 to 150 a month, now not counting what I'm already tracking, and I'm getting more and more nodules coming in, and you just can't spend all day bronching and finding a way where these things settle out at.

Mr. Nicholson, you are on the East Coast in New Jersey. Can you talk a little bit about your practice challenges with pulmonary nodule assessment?

Absolutely. I think 1 of the biggest things is I try to keep up to date on a lot of medical literature, podcasts, webinars and things and inundated with mediastinal cryobiopsy, [indiscernible], all of these new tools and tricks and everything is about how do we biopsy better but not who is the better person to biopsy. And I think that's a really important thing for us to focus on because the prevalence of lung nodules is increasing, and we need to utilize the resources correctly. So my fellowship was at Temple Lung Center, the bronchoscopy suite was 2 ORs that both had ions and cone-beam CTs, every 6, 7-centimeter nodule, someone -- millimeter nodule, someone wanted to take a poke at it. And now I'm in a community-based practice with an academic affiliation, several groups, high volume of nodules, smaller amount of ion time. And we have to find out who are those patients that are the best suited for it. Everything in medicine is about pretest probability. So before you go into a biopsy, who are the patients with the highest pretest probability to actually have a cancer, that's who you want to biopsy. And our current tools for that, are not great. We have multiple calculators in the Vumedi Talk. We showed how multiple calculators show different scores. And some say biopsy, some say don't. So what are you trusting? And so when you have a noninvasive diagnostic test like CyPath, it helps you to have a better pretest probability before you make a decision like that. Because this burden of nodules is only going to increase. Right now, most insurances in medicare will cover the USPSTF guidelines, which is a former smoker or current smoker or those who have quit within the last 15 years, but for several years, the American Cancer Society has been encouraging people to remove that quit within the last 15 years and just anyone who smoked for more than 20 pack years. And then if you've got a chance to review the new cholesterol guidelines from cardiology, they are really encouraging the use of Coronary Artery Calcium scoring, and I have a lot of incidental nodules in my practice found on Coronary Artery Calcium scoring. So there's just this real need to figure out who are the right people and optimize that pretest probability.

Absolutely. So for our audience, I know a lot of the clinicians that are listening tonight have similar problems and feelings that our panelists touched on. And just to review again very quickly, there's a rapidly evolving increased burden to all clinicians based on what you just heard from Dr. Nicholson, Dr. Guda, and Dr. White. So why is this burden exploding? Increasing screening. Finally, we're hardwiring a lot of family practice doctors, internal medicine doctors and hospital systems are hardwiring their screening for the high-risk individuals. Also, what the definition of high risk is it is expanding every year. We're finding out that non-smoking-related lung cancers are increasing in the population. We have now probably 10 to 20 carcinogens that most of the U.S. population is exposed to. So who's at high risk? That's an expanding population. And now with AI-driven mining of EMRs, there's more and more hospital systems that are finding every time a pulmonary nodule "as mentioned" in an EMR. And as pulmonologists and clinicians dealing in this area, we are getting the full burden of this. So Dr. Guda, I'd like you to talk a little bit about how you receive your referrals? Do you receive them from hospital systems, from internal medicine docs, family practice docs? How do you receive these referrals? And how are you told -- or how are you directed by those referring people about your next step in the process?

So I mean -- I alluded to this earlier today, earlier in this meeting, where I said a lot of our clinical practice is kind of directed by the presence of oncology. So we have about [ 34 ] different oncologists that feed into our practice. And essentially, these oncologists, they are looking for answers. So our clinic is essentially a procedurally driven clinic because these patients have already been seen by oncology, either you're looking for metastatic disease or you're coming in with a higher clinical distal than you typically get from a primary care physician or a pulmonologist. So our clinic is pretty much directed by that kind of a burden. From the community also, we have -- we just reviewed some of our numbers, and we are seeing an increasing awareness in the community about screening. And it's a great point that Dr. Nicholson made is the 15-year mark -- benchmark, it's an arbitrary number. It is based on old data that doesn't really have the same kind of consensus as smoking history positive, smoking history negative. So there is an increased awareness in the community as well where we have a larger population of patients that do get sent to us from the primary care physicians. And those patients have a variable risk factors. There are also physicians that say, "Hey, I've got this 3-millimeter nodule. I do not know what to do about it. I am just going to go ahead and send this to the lung clinic for management and then the patient comes in quite worried." I have a 3-millimeter nodule, are you going to biopsy? Is this cancer or not, right? So that is where the patient population variance comes. Now with oncology, patients that have had breast cancer 5 years ago or cervical cancer 10 years ago, and they are being monitored for something or the other, they have had abdominal pain, they do a CT scan of the lung, they see a small nodule, get a dedicated CT scan, and then you get a small nodule on that. And then what do you do with a 6-millimeter nodule? How do you risk stratify somebody who has had a history of solid organ cancer and you have a 6-millimeter nodule that is there on their lung and now you have to choose, do you biopsy, do you not biopsy, right?

Absolutely. So the American Cancer Society -- I'm sorry to interrupt. The American Cancer Society is really wanting to focus on not just screening, but the survivorship and surveillance side, the off-ramping from treatment of lung cancer after lung cancer has been diagnosed and treated. Could you talk a little bit about CyPath Lung and your clinic and how you deal with survivorship and surveillance?

So we use it in moderate amount. I would say that a lot of our patients that do come in with nodules that are may not be amenable to a biopsy, but you still have enough of risk factors, which was the point I was about to make next is, those patients, we do have them get us CyPath samples, sputum samples to send for CyPath for us to be able to say, "Hey, this is the risk factors. This is what we see on the data coming out from them now, the nodules have not changed in a year, let's repeat it again and see how we can assess it." Now that volume is small. It is not the bulk of the patients that we have. For every 10 patients that for CyPath, one of them is going to be for the surveillance in our practice right now.

Dr. Nicholson, maybe you could comment about nodules, how they come into your practice and your practice algorithm and how you employ CyPath in your practice?

Absolutely. And I think Dr. Guda had touched on something important there when he said the anxious patient, right? And so we'll talk a lot tonight about data and about workflows and things. But at the end of the day, a lot of times, there's a patient with a 5-millimeter nodule sitting in front of you and you as clinician knows that this is probably nothing, but then as a patient with ChatGPT thinks that this is the end of their life. And so having CyPath as a way to bridge that gap between when is the repeat CAT scan if you're not going to go after this for any reason and relieve that anxiety for patients is a huge part of it that I wanted to bring up as well. For me, I'm in a practice with 10 other pulmonologists ranging in age from me who's at a fellowship recently and pulmonologists who finished med school in 1984. So we're all over the place and me and one other physician does most of our biopsies. So a lot of our referrals come from the community cardiologists who get CACs and primary care doctors who do a lot of screening, but we also have a very large patient panel who is doing LDCTs every year. And then I receive a lot of the referrals to do the biopsies. Basically, all of my colleagues who have patients who have a nodule, they will send and say, what do you want to do? Do you want biopsies? Do you want to do a PET, you want it?" And I would say, "Well, let's start off and let's get a CyPath. It will take us a few days to get the results. The patient just gives us sputum sample. And then we're going to know a better pretest probability of what the best next steps are." So it works in very early to my algorithm in a lot of these modules, especially the ones that are less than 1.2 centimeters and the ones where PET is more unreliable 7, 8, 6, things like that.

Dr. White, we're both from Northeast Texas, and we've been colleagues for a long time, and we talked about our individual clinics and I know we've discussed anxiety, patient stigma, patient nihilism and how anxiety and fear affects the process. Do you want to touch on that a little bit?

Absolutely. Our patients, imagine like most patients that live in the community. They're a little headstrong and stubborn. Most people hear smoke. I still have an ashtray outside of my front door in my office because I got tired of people throwing cigarette butts on my bushes. They know that. They smoke and there's a risk that goes associated with it. But they're like, yeah, I'm fine, it's not bothering me. But somehow they get a CAT scan, they can find a nodule that makes cough up some blood. It's okay the blood is stopped or it's still cough and no blood. Now this kind of kick the can down the line for a little bit. [Technical Difficulty] can be very scared. You know what Dr. Nicholson [indiscernible] 6 millimeter just threatful about it. Those people give you a piece of -- CyPath gives them kind of a piece of ease just like it's negative or if it's positive, we should probably do something sooner. So that's kind of upfront with CyPath. The other thing that was -- I kind of use CyPath a little bit downstream as neat -- I've seen Dr. Guda's bronchoscopy suite and Dr. Nicholson sounds like he's got a pretty good bronchoscopy suite. Ours still has not been updated yet. And so our comfortability for what we have for our navigation bronchs, I've always kind of on the fence on. So if I get a negative biopsy from a nodule and the lymph nodes are negative and the CyPath is positive, having more stronger clinical indication that especially if it's high risk to actually go into a resection or talk with radiation oncologist sooner than later. And it's just kind of an added -- for me is a downstream piece, so no 1 that -- well, was it truly negative? Or was it truly positive -- and is truly a true negative. And so there's some upstream value to it and some downstream value with respect to these nodules in terms of biopsies.

Absolutely. As far as -- in my practice, patient stigma was a big deal, COPDers blaming themselves and not really want to pursue it. So the fact that CyPath could be mailed to them privately in their home, and they didn't have to travel. It could be done at their own time and their own pace. That was a big deal. And you touched on something very important. All 3 of you did that it's a data point that each clinician can add to their armamentarium when talking to patients to relieve anxiety and relief fear because there are mixed messages. Dr. Google is alive and well. And a lot of patients will come in having consulted Dr. Google. And so having an additional data point with a high sensitivity, 92% negative predictive value, 99% for nodules under 20 millimeters really helps in these discussions. And [ quells ] anxiety and fear. So I think at this point, before we break for questions, I would love to hear from Dr. Guda maybe with the case that you've had. And then Dr. White maybe you could follow that with one of your cases.

Absolutely. Do we want to break for questions or do you want to put the -- do the case first?

Well, so far, there are no questions. There are no questions yet. So I think we can go straight to the -- your case. I do invite the audience absolutely to please submit your questions.

Okay. So this is actually 1 of the first cases where -- it was like the first use case for CyPath for me because I'm a skeptic at heart. I like a very healthy dose of skepticism with my morning coffee. So whenever there's something -- any new piece of technology that comes through, I like testing it and making sure that it actually works. So from what I see -- so this is actually a very interesting patient. She is a 66 year-old female who has -- who's known former history of smoking, quit about 5 years ago. And she developed abdominal pain, some discomfort. She has got some vasculopathy in the abdomen. So they thought there was some sort of an obstruction taking place or essentially ischemia. They did a CT scan of the abdomen and pelvis, and they noticed some ground-glass changes in the base. So the next thing they did after that was, hey, we're not sure what this is, but let's get a CT angio also because we think that our CTA of the aorta just to make sure that there is no evidence of vasculopathy. And they caught what's highlighted here in the red circle is the schmutz as the best way of some of the radiologist describing it. It's essentially some ground glass nodules for us -- who are more technical as ground glass nodularity in the right upper lobe with other ground glass nodularity throughout the entire lung. Now based on our history, it is not a very solid nodule. It is at the most -- in the greatest dimension about 13 millimeters. There is no -- it's not very suspicious, but it is a little bit suspicious, where you are considering and based on the history and the surrounding emphysema in a patient that had quit smoking just recently that maybe there's something more to this. But how do you risk stratify based on all the other modalities that Dr. Nicholson was touching on. Every single modality that you put in for risk stratification, it gives you a different number. It gives you -- the benchmark keep -- the goalpost keeps changing, right? So in those situations, we thought maybe we should do a PET scan because the patient got sent over to us from the ED for this nodule. The patient was quite nervous about it, obviously. She had some family members and some not immediate relatives, but friends have lung cancer, [ deadly ] lung cancer issues. She was worried. PET scan wouldn't be very informative because a solid component is less than 6 millimeters. So we looked at what the follow-up options were available to us, which was both like a 6-month CT scan watchful waiting for 3 to 5 years. But the patient was given that she has family members who developed cancer, and now we are worried about something that's going on in the lung. So she is aware of what that means and what that looks like. And so we decided to go forward with CyPath. This was, I think, our third or maybe fourth patient that we had set up for CyPath, the prescreening risk was low. And the CyPath results came back at 0.8, which -- sorry, not 0.8, at 0.7. So we, at that point, we're quite surprised. We proceeded with discussing risks and benefits of a biopsy. We did a robotic bronchoscopy and performed a cryobiopsy, which is where you freeze the tissue and you pull it and you get a larger chunk of tissue. And low and behold, it was positive for adenocarcinoma. She was then sent for Tumor Board review. We reviewed her case, and it was early invasive adenocarcinoma. She had a PET scan done, the full gambit. And because the ground glass nodules were only isolated to the right upper lobe, they elected to go forward with doing a full right upper lobectomy on her because of all the other -- and this patient, I think this was about 1.5 years ago, and she has had follow-up CT scans that have been cleared thus far. She did not need any further testing. And sure enough it was early invasive adenocarcinoma in this patient. So this was 1 of those first patients that maybe believe -- may be a believer, I would say that there is a modality out there that can be reliable in comparison to some of the other modalities that are there, where -- this patient profile doesn't fit under those models that other risk stratification profiles are available, right? So this profile of this patient fit just with this or biopsy of -- wait for -- watchful waiting, sorry. And so when we are nervous about following through and just doing 1 for somebody who has risk factors. And the biopsy is maybe -- seems too aggressive because of surrounding emphysema, risk of pneumothorax, all those things. This really is helpful. This -- CyPath really was helpful to push us into the direction of doing a biopsy. Where I, at the time of evaluating this patient in the clinic was not convinced 1 way or the other that we should be doing a biopsy. And I'm glad we did because now she is potentially lung cancer free.

Before we hand over to Dr. White's case, I did receive a question just now to go over some of the statistics of our clinical trials. So our clinical trial for CyPath Lung was published -- peer review published and we reported a 92% sensitivity, 87% specificity. We provide data as a binary, either likely or unlikely. And this is based on our negative predictive value, which for nodules, less than 20 millimeters is 99% positive predictive value. Dr. Guda's case, based on the specificity and positive predictive value of 61% benefited -- obviously, the patient Helen benefited from that positive predictive value. So we have a very robust clinical trial demonstrating I think, best in industry sensitivity area under the curve of 89% and specificity as well as the positive and negative predictive values. And as you know, everybody's prevalence in regional United States is slightly different. And that's why the negative and positive predictive values are so important. So I hope that answers the question from the audience. Dr. White, would you like to talk about your case of Samuel?

Not yet. I actually want to talk about the statistics real quick because you raised a good point that I always think is important for me. As the statistics, the positive predictive value is actually the weakest statistics there at 60%. But the negative predictive value is really high. And so going back to my statement that not everybody needs a procedure, not everybody needs a nodule, if I can give somebody peace of mind that this is truly not likely cancer, there are no reason to put them through a procedure. That being said, it's also [ all comers ]. When they cough up their [ flu ] they're identifying cancer cells. It's not saying it's a squamous cell or an adeno or a prostate, whatever the lung -- breast cancer, it's all common cancers that is coming out when they cough up. And you're saying, yes, it's going to be a cancer or it's not with the final results, with the biopsy. But the positive predictive value is about 60%. So you still ultimately have to get a biopsy if it's positive. And even then, it's not always going to be a cancer, but it kind of gives you a risk stratification on who needs to watch closer, who do you need to kind of pursue quicker. But if it's truly negative, I feel much more comfortable to let things ride. And that's what it's kind of nice about it. Again, now you can talk about my patient.

Now in the meantime we've gotten several more questions. So before we go to your case, I'm going to answer some of these questions. So the next question is, what is are the biochemical markers of the CyPath test? Can you please elaborate a bit more on what it looks like and how it detects medical -- malignant cells, excuse me? So the reason I became interested in CyPath lung testing was my background in photodynamic therapy, which uses porphyrin biochemistry as its core technology. So we're a diagnostic test, a supplement diagnostic test that uses sputum, which goes through flow cytometry which is AI machine driven for amplifying those results. There are basically 4 main data points that go into our algorithm. We incubate the sputum and porphyrin which stains the malignant cells. We identify pulmonary macrophages with receptor stains. So we know we're getting a good lung sample. We filter every sputum sample that comes in that gets rid of debris. We identify apoptotic cells, which we found extremely important for the flow cytometry. And we also special stain immune active inflammatory cells within the lungs. So it isn't just the cancer cells we're looking at to give us our likely or unlikely diagnosis or probability. We are also looking at the micro environment within the lung. And you can imagine that the small tumors are producing a unique immune response that we'll be able to see in the sputum. And so these 4 data points, the macrophages, the immune cells, the tumor cells, and the apoptotic cells are assessed in flow cytometry and gives us our results. So I hope that answers that question. The next question is what patient populations have you found that CyPath may be more likely to give false positive results in or in what situations would you not recommend using it? That is an excellent question. We have a huge study that we've started with 2,000 patients, and I think we'll better answer that when that study is at completion. But clearly, what we see in for the negative predictive value is we had an interesting case where someone had floored thrush and that sample turned out to be unlikely. And then we realized in our lab that all of the patients, when there is a heavy population of yeast, we were getting negative values. And we realized that the yeast was blocking the gating in the flow cytometry. So now that is one of our exclusion criteria, active thrush. And so I think we're going to find more and more about what we need to exclude and include as we go through our bigger study. The positive predictive value of 61% is very competitive. It's comparable to the Cologuard test for colon cancer and certainly stands up to imaging mammography for breast cancer. So even though that sounds like a weak number is actually very predictive. And I do think, again, the bigger study will show some of the reasons for positive predictive value being at 61%. All right. Dr. White, Go ahead, your case Samuel is up.

Okay. Well, this guy is kind of a classic patient. He's a 68 years old, still smoking. He was referred by a primary care doctor for coughing up blood. Primary care doctor treated him with some antibiotics and some steroids. He was such an active smoker. He was smoking in the parking lot when I walked in to see him coming from the hospital. Smoker, coughing up blood, but between when he saw the primary care doctor and saw me, his bleeding is stopped. He is kind of this -- kind of -- still kind of a guy just leave me -- I'm just -- I don't want to be a problem to anybody. So I'm happy to be in who I am and just leave me alone, kind of attitude. Wife was there. She was kind of worried -- [Technical Difficulty]. He did a little biopsy and he's listed in our CAT scan in 3 months. Well, the CAT scan image screened cancer. He looked like he had cancer, still smoking on top of cancer. They like -- let's, we can do that, but let's do a CyPath and if it's positive, then we can kind of talk about biopsy. And if it's negative, we'll watch. And so he's okay doing that. Sitting out, came back, it was positive on the CyPath. We biopsied him, Stage I cancer. He's gone under resection at this point. He's doing well. He's still smoking, but we're just watching for new things to grow at some point. But he's done well with this, but this encouraged a reluctant patient to actually get something done that needed something done.

Perfect. So Nicholson, I don't believe we have a slide for you, but I think you have an interesting case also that you'd like to discuss.

Definitely. And I know Dr. Downie and I have discussed many different cases and utilizations of CyPath. And actually, a couple of days ago, not a case I was planning on coming here to talk about, but something that struck me is so interesting. And I was so happy that I had the ability to use CyPath now when before I would have not known what to do in this situation. And it's actually a patient who is currently being worked up for a heart transplant with obviously, severe heart disease, not someone you want to put under general anesthesia and throughout the workup, former smoker, had a CAT scan done, showed a 6-millimeter nodule, plot right in the middle of the right upper lobe, IR can't touch it with a TTNA, it doesn't look like you're great at how we're going for a navigational with someone with my experience. And obviously, someone you don't want to put in a general anesthesia and heart failure is saying like, we need to know about this nodule before we pursue doing a heart transplant on this patient. And I was like, "Well, what if I told you, I can send the sputum kit to the patient's house and they could do a noninvasive diagnostic test with the 99% negative predictive value." And it was just such a unique situation. Obviously, most of us are not going to encounter something like this really frequently. But Dr. Guda, Dr. White, and myself can go over tons of cases like the ones they just presented. I want to kind of add that unique perspective of something that came up and also about how simple it is to do. There are so many things in healthcare now. When you tell the patient you have to get this test, you have to get this product. They have to make phone calls, their insurance, they have to schedule appointments, it's difficult. And CyPath, I tell them, the company is going to contact you. I'm going to fill out the paperwork. They're going to send it to you. They're going to call you and instruct you on how to do it and then they're going to come pick it up from you and bring it back to their lab and send me the results. And the patient is like, so what do I have to do? You have to answer the phone and you have to give us some sputum. And they're really relieved to see something so simple that they can do and especially a patient like this who has all the anxiety going on of doing a heart transplant evaluation to have something that's so easily accessible and valuable is really phenomenal.

I had 2 questions, almost identical, asking about the low percentage of screening that we see in the United States. And we touched on the fact that patient nihilism has a lot to do with that patient stigma, ablating themselves has a lot to do with them wanting to pursue that. And then as a corollary in these questions, they said, well, do you think CyPath Lung can help with the screening process, making it improving those screening numbers? So I'd like each of the panelists to maybe comment. Do you think CyPath as an adjuvant supplemental test will allow us to do better with screening?

I mean -- so I have a very interesting take on this because -- or at least, I think it's interesting. Patients, when you tell them you have got to go and get screened to find out if you have cancer, immediately go, well, I don't want to know or I don't think I have cancer, I don't feel bad. I don't want to go through with the testing because you're unsure. At the end of the day, I like a colonoscopy where you go in there and you do -- you see a polyp, you dissect the polyp, you've essentially taken out the precancerous space, the lesion and you've also screened them at the same time, an imaging study like this, it's different, right? So in patients that -- when they are going to go get a CT scan done, shell so much of money out, most of them living like very much under their means, giving them a test that says, "Hey, listen, you meet several risk criteria. Doing a screening for you is going to tell us something, whether it's really bad emphysema or really bad or you've got pulmonary nodules that need to be evaluated." Maybe doing this sputum testing may help them understand the importance of it because you're doing more than just screening them for the nodule that they have, but you're also going to risk stratify them not at the same time, but in sequence. And sometimes patients may seem a little bit more willing to go forward and get a CT scan done. If they have a known higher risk, not just by numbers by saying you're a smoker or you had quit smoking 15 years ago or like 12 years ago, you still may be at risk for developing this. So while you want to have a nodule when you're performing this, I wonder, it's a question, I wonder if those patients that get screened with a sputum test first, you define whether or not they are having increased risk based on their sputum analysis and then they do the CT scan. Will that increase the number of patients that we actually collect for biopsy that are going to be positive down the line just because you've had the risk stratification test done first. So it's an interesting take. It's not imaging and then you do the risk stratification, but it's like putting maybe the card in front of the horse kind of a method. But I wonder if that is something that might help improve the screening of patients that are already at risk at all.

Dr. Guda, I've heard similar questions along that line. So it's an excellent point. Dr. Nicholson, what are your thoughts on this?

Yes. And I think like even our scopes we steal from our GI colleagues. But -- so now I think the -- on the Vumedi Talk, I talked about the similarities between fit testing and this. And so finding the ways to identify those patients who otherwise would not be screened and use some kind of screening for them in terms of this testing. And there's a lot of concern in my area and my practice from patients with radiation. And then it's a true concern from them. They don't want to be getting CTs every year. A nodule pops up, you have to file it again in 3 months there. So I had 1 gentleman who said, if I didn't have cancer before I have it now from all the CAT scans people are ordering for me. So to have a radiation free way to try to risk stratify somebody. I think that's the future of all early detection in all -- across all medical specialties is to do it in the most effective and least invasive way possible for the patient safety, for healthcare utilization and costs, and to figure out how to increase that pretest probability, like I mentioned, to find the patients who really do need a CAT scan and really do need a biopsy.

Dr. White?

Well, I'm glad both of the guys mentioned gastroenterology. The way I look at this is actually more kind of my vision of where I see pulmonary going. I think we're in an amazing time for pulmonary. We're actually finally doing some stuff. We've done -- historically, pulmonary is just kind of like the closet and the end of the hall that people are doing bronchoscopies in for pneumonias maybe a cancer. We're in the age of robotics, where we're going after lesions that are less than 1 centimeter, which is phenomenal and amazing if you think about it. We're going to go to the age of therapeutics, just starting that. Going back to the GI doctors, they've done an incredible job marketing themselves. So it used to be 50 years old, you blow out your candles, you got yourself a colonoscopy. Now it's moved up to 45. We're starting to do low-dose screening CTs. Those are going to be start finding more and more nodules and polyps or more nodules. Going with the GIs after colonoscopy, my brother had his done, he had 3 polyps. We didn't [indiscernible]. My thoughts in the next 5 to 10 years, pulmonologists won't be treating lung cancer anymore. We're going to be treating nodular lung disease. We're going to have tools that will say high-risk lesion, it's a biopsy demand, real-time pathology reads in the room, then we can go and treat it with whatever the therapeutic was going to be out there. We're getting really close to that. CyPath is kind of going to be -- in my mind, will be kind of the starting line to get this whole process started going from where we're treating lung cancers and start paying attention to more nodular lung disease.

Yes. So 1 of the questions that I have not answered asked about, and we're reading as clinicians and healthcare providers were reading about potential screening tests for lung cancer, blood test for lung cancer, you name it. And there's certainly a lot of data out there and a lot of newsworthy data out there. The question was specifically why sputum? Why not blood or some other mode of or direct biopsy? So the great thing about the CyPath Lung test is that it's a real-time cancer test. It is looking at the microenvironment of the lung at that time that the sputum has produced. And so when we say that something is unlikely or likely in our binary result, we are talking about real-time changes that are occurring in the lung. So you can use this in patients that have had previous cancers, anywhere in the body, previous lung cancer. Unlike blood tests, which have echoes of the cancer floating around as proteins in the blood. And usually, these tests restrict cannot be used whenever there's been a cancer within 5 years, including lung cancer. The real-time exam of the sputum, I think, is a huge benefit that favors sputum analysis over the blood and obviously not compared to going in and biopsying. But as all of our 3 panelists have mentioned, the risk and a bad lunger of a percutaneous needle biopsy or even a robotic biopsy is tremendous. And we haven't really talked about the finances yet of these high-end robotic procedures. But it is a very expensive test, and we're in an era of financial crisis and trying to figure out the best use of our money. And so having a cost-effective test like CyPath as compared to going after low probability, as Dr. White just said, low probability nodule with a very expensive test, just I don't think makes sense to me. I also wanted to mention that early on, when I was introducing Dr. Guda, I was looking cross side, and I said he was from San Antonio. He's actually practicing at Fort Worth. So I apologize Dr. Guda about that, and he can be contacted through his office. And at the end of our talk, all the attendees will be receiving an e-mail from us with contact information of Dr. Guda, Dr. Nicholson, Dr. White and also our reps around the country, our contact with Dallas Coleman, who is the Head of our Marketing Department because I also got several questions about the logistics of how to order the test and how to go through the test. I think at this point, we've caught up on questions. I would like each of the panelists to kind of summarize their thoughts. We'll go in reverse order. Dr. White, you actually gave a really good insight into the future of where pulmonary is going. So the future and CyPath you mentioned it, but just kind of restate that in a sentence or 2?

Well, I'll just state what I like about CyPath. It's an easy test. It's pathology agnostic. It doesn't matter, it's a squamous cell adeno, breast cancer or prostate cancer, it's whatever malignancies in the lung gives lots of peace of mind to the patients if it's negative. It encourages me that we should probably biopsy or watch it more aggressively if the CyPath is positive. I've had patients get procedures that they didn't want it. I've had patients not get procedures that they wanted it because the CyPath was a negative. It's a good clinical decision tool to use downstream. Also, again, I think there's a huge place for it, too. If you do a biopsy, and it's negative. Is it truly a true negative? Or do you -- do we need do something different? Do we need to go to a surgical approach? I've had patients get treated for lung -- or treated for cancer. That was a lesion that was positive on CyPath weekly added on PET. And there's a high-risk patient for any procedure. So just go ahead and do some SBRT. It's a nice easy test that gives you a lot of clinical data and...

Dr. Nicholson?

Yes. I would close by saying that when I was a fellow and a new attending, nodules were probably 1 of my least favorite patients to see in clinic. I was constantly stressed about whether or not I was making the right decision and overwhelmed by the amount of risk stratification tools that I didn't feel like actually helped me make a better decision and didn't help me to communicate with the patient. So I think having a tool that, a, helps me to make the right clinical decision, and b, makes the conversation with the patient more on their level and able to tell them like kind of pull back the cart and say, "Hey, this is the data that I'm going on, and this is why we're doing this test." It's made me so much more confident in my ability to deal with these nodules in the office. And every pulmonologist that I've talked to or worked with, like I said, I have 10 who work out of my practice, I was the first to start utilizing CyPath and every single one of them who used it once after 1 use now, like incorporates it into their practice because they see how useful it is both to them as the clinician and also on the patient end of things when you get that. While you're waiting for the next CAT scan in 3 months, you get that sigh of relief from the patient when you call them and say, "Hey, the CyPath sputum was negative. And they say, "Oh, thank God, now I won't be thinking about this CAT scan every day for the next 3 months.

Guda?

This is actually a great conversation because we're not just talking about lung screening. We're not just talking about biopsies, but we're talking about risk stratification. So where do you start? What type of -- what size of nodule do you take? For CyPath I found it reliable to be from 6 millimeters or greater, right? For those patients that have already had a previous history of lung cancer, other risk stratification modalities may not be useful because they have already had previous history of other cancers or organ tumors. In -- the future is very, very wide. It's very bright. It's -- you can develop an in vitro way you need to, but a lot of this to -- to piggyback on what Dr. Nicholson said, when I was in IP training, we were the goers. We were the -- we're walking around with a scalpel, a figurative scalpel in our pocket, right? We're trying to go ahead and do the biopsies and do the biopsies and do the biopsies. This tells us when to not, which is great because when you can tell to -- tell a patient like Dr. White said, your chance of you having a negative test from a biopsy is very high based on this other tests that we have done based on the sputum that you have given us, not some arbitrary number based on age or your height and your weight and how many -- what the nodule looks like. It's a much more reliable tool, in my opinion, that -- when you're having a conversation with people. So I -- we use it. I mean, I ordered it a couple of times just today on patients that have a 6 and 6.5, 7-millimeter nodules, and they have a history of other cancers. It's not really looking like a full nodule like a ground glass nodule, and I'm expecting it to help me make a decision whether I go after that and do perform a biopsy or not. Can we do the biopsy? Sure. Should we? It answers that should we?

Absolutely. Julie Anne or [ Alexi ], if we could put up the algorithm. So I have 2 more questions. Okay. I hope that comes up pretty clear. So this is the algorithm that CyPath Lung has developed, and I'm going to walk through it as I answer the 2 questions, which 1 was about the Ohio River Valley, Indiana and Cincinnati and histoplasmosis and the fact that probably 90% to 95% of CT scans of patients over 60 will have pulmonary nodules. All 3 of our panelists mentioned the impact of the negative predictive value for nodules under 20 millimeters being 99% in our clinical trial. That is a huge positive. When you want to talk to your patient that has these small sub 2 centimeter nodules, probably sub 1 centimeter nodules in these high endemic areas of fungi, you can go by society recommended CT scans. If you do a CyPath, then it's unlikely because the negative predictive value is 99%. That is a very powerful test.

Dr. Downie, well, I have a bunch of histo out where I'm at as well. And I haven't seen any problems in terms of the CyPath having bad results in the histo. We just don't see a lot of histo out here.

Yes. The Red River Valley also is an endemic area, absolutely. And then there was a question about what is the smallest size. Well, I'm going to go and talk about surveillance. I think we have utility and we've shown utility in radio-occult disease, having a negative predictive value and a positive predictive value even in radio-occult disease. But clearly, there is utility in the sub 10-millimeter all the way down to 6 millimeters. I have personally used it in 5 millimeters and 4 millimeters with success and maybe the panelists that you used it as small as 4 millimeters?

Absolutely.

Yes. So I think 4 millimeters is probably a pretty good cut off for its utility. If you go below 4 millimeters, all of the pulmonary nodule calculators don't even bother with a probability. And I think you can follow society guidelines for follow-up CTs at that point. But you have the algorithm of that that we're suggesting. And I'm going to start by giving the disclaimer, which is the little clear box at the very bottom that says the provider, the patient conversation and the clinical experience outweighs any data point. I mean, in the end, as a clinician, you will have a gestalt. You'll have a feeling about that nodule based on your clinical experience and your clinical wisdom. And that trumps so many -- any data point that we can come up with. But that being said, I particularly find and or -- if you have a patient that's at high risk and they have the low-dose CT scan, and you're sub-15 millimeters. So the right-hand side of our algorithm, you get a CyPath test. If the CyPath test is likely, then even though this is a small nodule, the positive predictive value is 61%. We're going to recommend in our algorithm of biopsy. But again, clinical gestalt might say, well, positive predictive value of 61%. That means that 39x out of 100, that will be a false positive. So if you have the nodule -- and even with the likely result, if you want to maybe do a closer follow-up with CT scan that is certainly reasonable. And maybe our panelists -- 1 of the panelists can comment on that.

Could you clarify the question again, Dr. Downie?

Yes. And you know what, I'm just seeing that we're approaching -- I was very verbose with all that, and we're approaching the 7:00 time limit. We're definitely getting near the wrap-up time. So I'll restate the question and then I think we'll call it after somebody answers that question. If you have a likely result and it is in a smaller lesion that -- can you wait and do a follow-up CT scan or should you go with the biopsy?

So we -- our practice is to biopsy. So the smallest lesion I have ever biopsied was 4 millimeters for metastatic cancer, and that patient did receive a CyPath and it was positive. That's why we biopsied. So 4 millimeters is pretty small, but we have done a biopsy of it with successful results. So in our practice, we can get after those. And so we perform a biopsy on those patients.

So again, we're at the top of the hour. I'd like to thank the audience for joining us and the excellent questions. I'd like to thank our panelists who really have given insight. I will mention that Dr. Nicholson has done a wonderful Vumedi Talk on the CyPath test, which, if any of you are -- if you can follow the Vumedi, it is very informative and very complete. So thank you panelists and thank you audience for being involved tonight.

Thank you.