Immunovia AB (publ) (IMMNOV) Earnings Call Transcript & Summary

Good afternoon, and good morning, everyone. Welcome to Immunovia's Key Opinion Leader Event. My name is Patrik Dahlen. I'm the CEO of Immunovia, and it's a pleasure to welcome you all today, both our audience on the webinar and the imminent experts that we will listen to in the panel discussion. We, Immunovia, are standing on a threshold of launching our first product, IMMray PanCan-d, a blood test for early detection of pancreatic cancer as a laboratory developed test, or LDT, in the U.S. by Immunovia, Inc. This means that clinicians soon will be able to use the test, and the purpose of this event is to provide a better understanding of how our test will be used. It will also be an opportunity for you to ask questions to the invited key opinion leaders, who are all seeing patients in different parts of the health care system. The aim of this event is that they will share their perspectives on why this test is important for different high-risk groups. The analysts are Dr. Stephen Pereira; Dr. James Farrell; and Dr. Geoffrey Burns. Thank you, all 3, for joining us today and for sharing your views with us. The moderator for the panel discussion will be Dr. Thomas King, our Medical Director from Immunovia, Inc. We will be taking questions from participants throughout the event, so please submit your questions to the panelists at any time you like. The moderator, Dr. King, will indicate when he opens to questions from the audience. [Operator Instructions] We urge you to focus your questions on clinical and scientific matters, and the panelists will answer all questions. If there are Immunovia business-related questions, we, that is Tom and myself, will address those at the end of the seminar. I really look forward to a very productive and informative webinar for all of us. And again, thank you all for joining. Before I give the word to our moderator and the panelists, I would like to give an update on Immunovia. These are our disclaimers and forward-looking statements, and I encourage you to read this at your leisure. Immunovia is at an historical point in time. We are ready to launch IMMray PanCan-d in the U.S. at Immunovia, Inc. as a laboratory developed test. IMMray PanCan-d is the first test available for early detection of pancreatic cancer, and it is a blood-based test, which will make it easy to use compared to current imaging methods. Early detection is important as today more than 80% of all diagnosis of pancreatic cancer is at the late stages of the disease, when it is too late and the cancer is no longer resectable. IMMray PanCan-d will be launched as an LDT from Immunovia, Inc., and the testing will be performed by our lab in Marlborough. We will start as soon as we have obtained a clear number. Financially, Immunovia is in a strong position. We had SEK 425 million at hand at the end of quarter 1 2021, and we are fully funded for the commercial rollout of the test. Obviously, our short-term focus is on the U.S., and we're working hard on a plan for Europe, a plan that we will communicate later this month. We have a goal to obtain 30% market penetration in the risk groups and the markets where we roll out our test. As we are first to market, we think this is a reasonable standpoint to take. The overall market size that we target in the U.S. and Europe combined exceeds USD 4.4 billion. I wish to take this opportunity again today to remind everyone how important on a mission we're on here at Immunovia. With our blood-based test, IMMray PanCan-d, we will provide an entirely new solution to early detection of pancreatic cancer. Early detection of pancreatic cancer is critical for improving the survival of pancreatic cancer patients. When pancreatic cancer is detected in stage I or II, the 5-year survival significantly improves. It goes to 50% survival rate after 5 years compared to less than 5% when pancreatic cancer is detected in stage III or IV. Today, the median survival rate for newly diagnosed pancreatic cancer patient is 4.6 months, and the reason for this is simply that 80% of all pancreatic cancers are detected too late in stage III and IV. I would like to take a moment to remind you of the performance data of our IMMray PanCan-d test and share with you the results of our final validation study that we presented in March. We obtained excellent results for all PDAC patients versus a familiar hereditary controlled group. Accuracy was 94%, specificity of 98% and sensitivity of 87%. However, more interestingly, we see that the detection of early-stage pancreatic cancer, that is stage I and II, versus a control group of familial hereditary individuals, we had an accuracy of 92%, specificity of 98% and a sensitivity of 85%. These are absolutely outstanding results. We're very proud of these results, and we've gotten good response from experts with regards to the performance of the test. In terms of CLIA, I can share with you that we filed our application in April. Normally, we would have expected to obtain a CLIA number in 30 days, so well within May month. We hear from CLIA office that they have been forced, due to the COVID-19 pandemic, to prioritize corona testing laboratories, and they have a backlog in terms of handling applications. At this stage, we do not have a more firm date for when to expect a final go from CLIA. However, we continue to believe that it should be imminent. We continue to strengthen the team in the U.S. We already have a strong team in place, of course. We are adding 2 new lab technicians. We're adding a Quality Assurance Specialist, and we continue to build our marketing team, customer support and the market access team. Naturally, we will continue to monitor progress, and we're ready to increase our efforts and resources in the U.S. as we progress. We're also launching our second payer study and here, we work closely with doctor partner from precision of medicine. In terms of the road to market, we obviously launched our test as an LDT for Immunovia, Inc. And as usual, the test will be paid for out-of-pocket by the persons who take the test. This is standard practice in the U.S., and we will seek a PLA code for the test. We will conduct a series of studies to demonstrate test performance and show clinical utility. These studies will be conducted in the U.S., obviously, by U.S. investigators. From these studies, we will compile the dossiers that we will present to the payers and use in our coverage negotiations with the payers. We argue, supported by our consultants and the relevant medical community, that our test is not a screening test for the general population, however, rather a test for surveillance of risk groups, either high-risk groups for familial hereditary nature or symptomatic patients that display vague and worrisome symptoms linked to pancreatic cancer. For this reason, we do not anticipate a lengthy process time for reimbursement, as our test is either diagnostic and/or an aid in diagnosis in high-risk groups. And we fully expect that the majority of the payers' agreements would be in place by end of 2022. With this, I would like to turn over to Dr. Thomas King, our Medical Director, who will moderate the panel discussion. Tom?

Thank you, Patrik. I'm Dr. Tom King. I am the Medical Director at Immunovia, Inc. I am a Board-certified pathologist who's been in practice in the United States for over 30 years in both academic medical centers, private practice and in pharma biotech. And I'll be moderating today's discussion with our distinguished panelists, Dr. Geoffrey Burns, Dr. James Farrell and Professor Stephen Pereira. I'd like to thank all of our panelists for participating in this program and for you as well for dialing in to participate today. I hope that the discussion will be informative and helpful for all of you. We will be accepting your questions. [Operator Instructions] I'd like to begin by asking each of our panelists to introduce themselves and give a brief sketch of their clinical practice and interest. Dr. Burns, would you like to start and also say a few words about concierge medicine? I think that would be helpful since this is not a common practice type in Europe. Dr. Burns?

Thank you, Tom. Thank you, everyone. As a family physician, often known as a general practice physician, I've been employed by the U.S. government as they put me through medical school and did my residency in California with the U.S. Air Force. I've been employed by Mass General Brigham as a primary care physician for 8 years. And now I've been in private practice for the last 7 years. It turns out that in most parts of Europe until just very recently, in the Czech Republic, concierge medicine was not available. And in fact, a practice just opened named Concierge Medicine Europe in Prague. The intent of concierge medicine is to really bring down the patient panel size, so this is a much more small doctor feel for the patient and that you are available to your doctor around the clock, that you have same-day appointments, that you have much more of a personalized and tailored presentation. So in the United States, we often would call someone like myself, a primary care physician. I prefer to use the acronym PCP just the same, but it's a personalized care physician. And I think Immunovia really will fit in well for that personalized care that I will continue to deliver to my patients.

Okay. Professor Pereira, would you introduce yourself, please, and thank you for being here.

Thanks very much. Good afternoon, everyone. I'm a consultant gastroenterologist based at 2 major [indiscernible] hospitals in Central London, which are affiliated with University of College of London here in the U.K. I'm also a pancreatic cancer researcher, and I lead a national early detection research alliance, which is focused on early cancer detection in the NHS, National Health Service setting, and that has contributed to validation of the PanCan-d test. I think we're all aware, as Patrik has mentioned, of pancreatic cancer's shocking statistics. And as you know, up to now, we've not had a single test for diagnosing. And the issue is a particular one in the U.K. where up to 50% of people in some urban settings are only diagnosed with pancreatic cancer when they come to an actual emergency with late symptoms. So we certainly need better effective treatments. And being on the front line here in COVID during the COVID pandemic over the last several months, it has shown that the picture of delayed and missed pancreatic cancer diagnosis is the worst I've seen, I think, in my career so far. But I think with PanCan-d, we now have a simple test, which is accurate, as we've heard. And from a U.K. perspective, as part of the on early detection research alliance, we're particularly interested in its use as an adjunct or an alternative to current imaging and industry screening programs for people with new onset type 2 diabetes. It's an area of active interest given the U.K. with a nationally funded study; patients with pancreatic cystic lesions, who normally undergo imaging and endoscopy screening, which were no longer able to meet requirements for the current situation; and also, obviously, individuals with a strong family history of pancreatic cancer, again, who were not able to meet requirements for annual endoscopic ultrasound of that group, and there's obviously a potential toward changing to biomarker tests. I think its biggest potential impact is likely to be in patients with so-called vague or nonspecific symptoms, both in primary and secondary care who wouldn't normally be investigated along urgent suspected cancer guidelines. Here in the U.K., we have a 2-week maximum before people with suspected cancer symptoms need to be investigated, and that's mandatory. So we've selected that group and in conjunction with refining current decision support tools, which again is a U.K.-specific thing based in primary care, where risk factors such as age, smoking, family history are combined with symptoms to alert general practitioners to patients with suspected cancer, widely used. And we're also interested in understanding the barriers to biomarker implementation within the U.S., which is different in the U.K., which is, of course, different to U.S. and other countries. So now I'll now stop there, and I'll hand over.

Okay. Thank you. Thank you, Professor Pereira. And Dr. Farrell, last but not least. Please introduce yourself.

Thank you, Tom. Good morning, good afternoon, everybody. Thanks for the invitation to participate. Thanks to Immunovia for setting this up. My name is James Farrell. I'm a professor of medicine at Yale School of Medicine here in New Hayden, Connecticut. I'm -- very similar to my clinical practice, and I think turning to Professor Pereira, I'm primarily a gastroenterologist involved in the world of interventional endoscopy, which involves procedures of the endoscopic nature, which allows us to take care of patients with a variety of pancreatic diseases, including pancreatic cancer. Unfortunately, more often from the palliation and treatment side rather than initially from the early diagnostic stage, it also gives us introductions into the world of pancreatic cysts high-risk individuals. So I am predominantly a clinician with a strong research focus in the area of pancreatic disease now in the realm of early detection, but in a previous life, more so on the treatment side. And very similar again to Dr. Pereira, we are involved with a high-risk patient screening program, pancreatic cyst disease and are also now beginning to jump into the world of new onset diabetes as high-risk groups for that, but also coming from the perspective of translational medicine and trying to understand the development and validation of biomarkers.

Excellent. Thank you. I thought it would be best to begin our discussion with a bit of an overview for the audience of the current situation in pancreatic cancer detection and diagnosis. So Dr. Farrell, maybe I can pick on you first. What do you feel are the major challenges in diagnosing and managing pancreatic cancer today?

Some of this has already been mentioned, Tom, but from our perspective here in the United States, at least, the numbers of pancreatic cancer are rising. So we're up to about 50,000 cases per year for a population of 330 million or so. In terms of total incidents, it's a lower volume issue, but in terms of cancer-related deaths, it's currently on its way to being the second most common cause of cancer-related death in pancreatic cancer. And a lot of those reasons go into, yes, there's a true increase in the incidence probably related to age, obesity issues, for sure. But as you know, there had been also tremendous progress in other cancers with respect to treatment and even early diagnosis. So a lot of it is kind of a relative change. And so we're in a scenario where there are treatments for pancratic cancer. Yes, we've talked about the patients presenting late, but the treatments are only smally, incrementally better. There's certainly not been that dramatic blockbusters. I'm not an oncologist, but there really haven't been that many blockbusters in the last couple of years from the perspective of treating patients. And again, the majority of patients, unfortunately, present with locally advanced where it's not a surgical resection disease or metastatic disease, where it's certainly isn't just a resectable disease. So I think the world, I mean, in terms of a medical oncologist look to us as gastroenterologists, patients look to us and say, "Well, what's going on in the world of early detection?" And so there is a real need here to try and crack this not from an early detection. For sure, there will be developments in treatments in immunotherapy and all those sort of things, but really, the issue is can we crack this and can we improve survival through early detection. And maybe kind of Stephen could allude to some of those challenges that we have with the early detection approaches.

Yes. Thank you, Geoff. Dr. Pereira, would you like to have additional comments?

We have a similar situation, of course, in the U.K. I think there's a big unmet need for improving public awareness for symptoms and signs of pancreatic cancer, and that's really been hugely successful in many other cancers, of course, with breast cancer screening, with colon cancer screening. But really, very few people know where the pancreas is or indeed, what's are the symptoms to look for. I think that's an important thing. And we know from our own studies and others, for example, we have access here to 2 databases of symptoms in patients going to their general practitioners of 40 million patients and 15 million patients, which we're currently looking at. So -- but we know from those data, which we published on a couple of years ago, that patients with pancreatic cancer have had symptoms, which could be attributable to their cancer at least 12 months before the final diagnosis. And I think there's certainly room for improving the pathways for those patients. Here in the U.K., based on clinical decision support tools, which I had mentioned, the National Institute for Clinical Excellence requires that patients with a pretest likelihood of having a particular cancer of more than 2% should go to appropriate imaging urgently, and that's within 2 weeks. The great majority of patients with pancreatic cancer do not fulfill those criteria and go down the slope, which I think there's a great potential for bringing biomarkers in that group to triage patients to a particular test, obviously, contrast-enhanced CT as the first test for pancreatic cancer.

Yes. I think we've all seen patients or known individuals who've developed pancreatic cancer and then been bounced around for a year or more before they actually get a diagnosis, so I agree with you. I think it's really important to prioritize. As Patrik mentioned, we expect to launch IMMray PanCan-d soon as a laboratory developed test at Immunovia, Inc. in Marlborough, Massachusetts. And as he said, we recently reported the results of our pivotal blind validation study that demonstrated a sensitivity of 85% in early stage, stage I and II pancreatic ductal adenocarcinoma, with 87% of sensitivity in all stage pancreatic ductal adenocarcinoma, with a specificity of 98% to 99%. Dr. Pereira, do you feel that these performance characteristics would be useful for evaluating individuals with increased risk for pancreatic ductal adenocarcinoma based on their genetic or familial history?

I think it's a highly accurate case based on that, and I think I'd answer it in 2 ways. One is from a patient and condition perspective, we've done work with stakeholder meetings as part of our national alliance and know that groups ranging from patients to clinicians to health authorities, view those -- would view those kind of levels of detection as acceptable for testing in the [indiscernible]. The other -- and one thing with that is that if you ask a patient, if you had a test, which was 90% accurate for cancers, would you like to have that test? And the condition at the same time, would you act on that test and send that person for appropriate imaging? And the answer to those questions are, of course, yes. And the other thing, which, of course, is important is that based on that -- those sensitivities and specialities, it's imminently possible to do confirmatory validation and implementation studies in defined cohorts to improve clinical and cost effectiveness. So for example, with those, you need only a couple of thousand patients, for example, to test in a particular cohort of people with a particular risk of having pancreatic cancer. So we can now go on and do those additional studies in an ideal setting to confirm effectiveness and acceptability.

Thank you. Dr. Burns, would you like to comment for your practice?

So I think, again, so many patients that get referred to general counseling or to specialty clinics like Dr. Farrell's, they're in their queue. They know what they're doing, but to really -- do take a family history to see if somebody is at risk and then like, "Oh, that's great." You have people that have pancreatic cancer who I wish we had early detection, I wish we had a way to monitor you earlier. We're just sort of waiting for that shoe to drop. It's very fatalistic for the patients and to even -- to counsel them in that way with this new tool and to say, "Well, actually, there is something that we can do, and there is something we can do sooner." I'm very encouraged, and I think my patients will be as well.

Yes. And James, would you like to comment as well?

I think when you look at the current state, and I know that we're not really primarily talking about a general population in an asymptomatic approach, but when you see what's going on in the clinical practice for good or for bad, it's reliant on an older technology, the CA19-9, ,which doesn't really have a particularly good sensitivity or specificity, but it's kind of used often in this scenario. It's a much bigger discussion than today, so it is great to have an opportunity to see kind of updated 2021 technology, improve the possible signature for pancreatic disease. And ultimately, I think we would all want this world to go to general population screening. Also obviously, we're talking about going in the direction of symptomatic management. But again, specifically to your question about the high-risk group, so I think, really, for the folks listening in, when we talk about high-risk groups, in our minds, at least, we're thinking about people who are at a high risk in the general population. We're talking about groups who, by and large, asymptomatic. And the 3 big groups that we think about, again, are just the familial cohort with or without a genetic mutation that they carry pancreatic cyst and diabetes. And it's really the first group that we have the most information on from perspective of these types of biomarkers. And this group, we believe, has a higher rate of developing pancreatic cancer, be it showing up in either an early-stage cancer or a preinvasive lesion. And one of the issues with even CA19-9 and any sort of potential suitor to this field is really what we're talking about, which is the operating characteristics. And to remind people that when you don't have great operating characteristics, you end up with, for sure, missing things and, for sure, over calling things. And those are really a central issue here that you have to keep in mind. When you start quoting sensitivity of the region of 85% for stage I and stage II cancers, that's actually a pretty good number, but probably as important. So that basically means that you're going to find those early cancers. But almost as important and maybe from a societal perspective, the very high specificity, so if the test is positive, that it turns out to be cancer is also important because what that means is in an enriched population, it decreases the chance that there's going to be false-positive test, which will really be kind of a societal deterrent for something like this in terms of justification. So in summary, I think when you look at these initial numbers that are coming out, when you look at this, when you compare it to what's out there already, as we get a growing understanding of high-risk groups, particularly the genetics and familial group, this is a very promising point in history to be at.

Okay. Thank you. I mean, I certainly agree the specificity is very important because not only in terms of the cost and inconvenience of the workup of false positives. You have the psychological burden of getting a positive test, which is certainly substantial. Professor Pereira, any further comments for you, particularly in terms of specificity?

So we know that we don't have a test for the general population, and [indiscernible] published on that. If you look at people over the age of 50 and bringing a test, which is almost perfect, 99% sensitive and specific for every -- you can pick up almost every patient in pancreatic cancer. But for every -- in 100,000 patients, you'll have 1,000 false positive patients. So there's a societal and a patient cost of that in terms of anxiety generation and, obviously, financial costs. The other thing I would say, again, we have a real need, particularly in the risk groups that James mentioned. We've again published on our experience with screening individuals with an increased risk of pancreatic cancer in 300 patients followed up for many years, and only found 1 patient with pancreatic cancer after several hundred endoscopic ultrasounds and MRI scans. So it really is -- the current screening programs for pancreatic cysts and for -- and in individuals with strong family history are expensive and invasive, but there's a need for a noninvasive, accurate test for those groups.

Thank you. And Dr. Burns, how important is test specificity for you in your practice?

Well, I think it was, as is mentioned, trying not to freak our patients out with false run and a task that says it's positive, and they're already hearing the worst, and then it's turned out not to be, you really want to be able to reassure them ahead of time that the likelihood -- that prior testing criteria have been met, the likelihood of it being a true positive is strong, and that we want to act on it because it's all about doing it early. And by waiting and then having a test because I'm not sure about this test, it's a new test, to a year later, we've already heard, a year later is late-stage cancer for that person. So I think we're going to have a fair amount of early adoption with people that are adequately concerned and that are proactive. Part of what American health care has become, unlike what is happening in the U.K., is we're very reactive to our care. People have symptoms. People have issues, but -- they've had their first heart attack. Let's try to prevent their second heart attack. We really haven't moved very far into proactive care, and I think this Immunovia test really is certainly at the vanguard of moving proactive care to the right high-risk group, certainly, not the general population. I don't -- I'll buy that, but really allowing it to trickle down to primary care, where a lot of this risk can be assessed and adequately deem just because diabetes is that third group. That new onset diabetic is an epidemic. If we can dial in a little bit more of the characteristics of these new onset diabetes patients and the risk for pancreatic cancer and have something to weed it out very early on, I think that's going to save a lot of heartache and a lot of cost to the American health care system. And it's going to forward this type of proactive approach.

Thank you. And we have a question from the audience. It's clear to me about the importance of early detection, but I'd like to understand a bit more about how the treatment plan differs in different stages of pancreatic ductal adenocarcinoma, both from the patient's experience point of view, but also from a cost point of view, if possible, that is, is there a stage where you would avoid invasive surgery? Dr. Farrell, maybe you can begin.

Sure. So broadly, and hopefully succinctly put, which I have issues with, but I think about pancreatic cancer in terms of 3 stages of presentation. We think about a stage where it's confined to the pancreas, away from significant blood vessels, has not spread to the liver. And broadly speaking, we think of that -- we call that an early resectable stage. Those are patients who do better. Those are the sorts of patients that we are trying to find through these sorts of programs. The next stage up is a -- what's called a locally advanced stage, whereby it's still confined to the pancreas, but it's involving significant blood vessels and important blood vessels. There's no overt evidence that it's spread outside. But down the road, it may be come on. And those patients are typically treated with chemotherapy and/or radiation therapy. As we mentioned before, not particularly great options, like you would hear with other diseases currently like colon cancer, kidney cancer and so on and so forth. The final stage is called metastatic disease where it's spread to the liver. And for sure, those patients are not candidates for surgery. There's really no point removing the primary tumor and leaving additional tumor at; metastatic sites. And again, chemotherapy is an option for those patients. When you look at survival across those 3 groups, optimistically, we think about 5-year survival is maybe 50% for the first group in really good hands and good centers, but then jumps down to 20% and 10% for the second group and even smaller again. When you think of the percentages of what those groups actually are, we think for that first group, it probably only represents about 10% to 15% of patients, honestly. And for the other 2 groups, maybe an equal 40%. So those are the challenges. I hope that kind of helps the person who asked the question.

Yes. Thank you, James. And Professor Pereira, would you like to add anything?

Yes. It's the same here in terms of patient proportions and approaches. And the other aspect of the question was, is there any alternative to surgery. I think an unexplored area so far is certainly surgery is the gold standard for small pancreatic cancers that appear resectable on imaging, and that's the standard approach. But we are entering a realm of better and better imaging, functional imaging. We're all hoping to be able to see smaller and smaller early cancers with appropriate imaging and maybe even precursor to that, and we don't yet know how biomarkers will operate in that group. And obviously, people having more and more scans, that may again be a role for the PanCan-d test. And there are -- and James and I have and others have been involved in trying to develop ablation techniques to small lesions, which may not be cancerous, particularly in the cyst, et cetera. So there are some possible other approaches coming online over the next few years. But certainly, surgery is the gold standard and will remain so for the cancer.

Okay. Thank you. And a few more questions from the audience. Do you see PanCan-d as being strong enough to change clinical guidelines in the United States? James, I think, probably, to best answer that.

I guess the first point to say is that there are some well-established clinical guidelines at a national level that have now moved into more decisions and guidance on diagnosis and early diagnosis and surveillance. And so what I mean by that is that in prior times, these guidelines focused almost 100% on treatment and what options were available for different stages. So the first thing to say is that there are guidelines. They are taking an interest in early detection and diagnosis and even looking at high-risk groups. I think it depends on how the data plays out and how the pivotal studies play out and how even post-marketing surveillance plays out to the point of saying that it would become a formal recommendation within those groups. I think people are beginning to understand that we have several guidelines for surveillance of particularly high-risk groups such as pancreatic cyst and the genetics group, but what we're beginning to appreciate is the issue that the success of that is very much limited by resource issues. So Dr. Pereira mentioned how often can patients really be getting good quality endoscopic ultrasound, how often do they want to show up, how often can we be getting them MRIs and CT scans. And so there's a real need to look at noninvasive blood tests to try and replace that or streamline that to stratify patients. And I think that might also be a direction that this is going from a guidelines perspective because it's better. A bit like the colon cancer story, although not identical in certain ways, it's more important that a patient have some test than no test. And so with colon cancer, we're running into issues, again, of resource availability. And so the attractiveness of, for example, the stool studies right now, it's not that it's the perfect or best competitive test, but it is a test that brings people, brings physicians, brings patients into the form. So I'm optimistic that guidelines will address the role of markers in diagnosis because they will have to because these guidelines are now addressing issues of diagnosis.

Thank you, James. And Professor Pereira, another question from the audience. What do you think would be needed from PanCan-d in terms of further development to make it widely adoptable?

Well, if I can answer that from a U.K. perspective, we have a National Health Service and a minority of patients, predominantly in the larger cities with private health care. And obviously, that includes London [indiscernible]. So with commercialization of PanCan-d that will be available to patients if they wish to purchase that, there won't be -- they won't have very much impact in the National Health Service, and they won't be paid for by the National Health Service at present, as that would be my understanding. And patients in the U.K. have had free access to health care for many decades and not used to paying for test. So there is some that is changing a little bit with some of the genetic profiling on offer for patients with cancers who wants to know more about the cancer, but it hasn't been accepted by the NICE. So I think what we would want to see is an assessment of the technology by NICE, and I know that we have had discussions with NICE to get that started. The likely outcome of that will be that the assay International Health Service should be -- continues to be tested in good quality clinical trials. And an example of that is -- would be post-commercialization implementation of the assay in a randomized study, for example, against standard of care and then showing that there's a clinical effectiveness in terms of improving diagnosis, and that is cost-effective compared with standard pathway. So those types of studies we're in discussion about, and they're really doable with the sensitivity and specificity that you've pointed.

Okay. Thank you. And operator, do we have any questions on the call on the phone?

Yes. We do have one question on the line at the moment, and that's from the line of Viktor Sundberg of ABG Sundal Collier.

So my first question is related to the U.K. collaborative trial of ovarian cancer screening that was published in the Lancet a couple of days ago. I don't know if you have seen it, but they found 47% more cancers in stage I compared to no screening. However, there was no survival benefits in -- with early detection, leading [ reporters ] to conclude that mortality should be the primary outcome maybe of larger trials that investigate screening or surveillance for patients to find cancer early. So I guess my question is, do you believe that a mortality-based outcome study is needed in pancreatic cancer to avoid bleed and length time biases? I guess my question is especially related to the Nord Europe, which could be 1.5 million patients and also the hereditary and familial risk groups that we have been discussing today.

Yes. No. Thanks for the question. And the UKC tox cohort is based here at UCL, and we've been looking at that in detail over the last few years for pancreatic cancer and other cancers as well. It's the largest randomized trial in the world, and it's been very useful in trying to detect biomarker profiles years before a clinical diagnosis of pancreatic cancer in a group of post-menopausal women who were part of an ovarian cancer screening program. I think I wouldn't equate -- obviously, no one is doing that, but I wouldn't equate the outcome of ovarian cancer with pancreatic cancer. I'm not sure that we can expect the same conclusions that UKC tox have arisen from the trial of using CA-125 and with ultrasound in conjunction with biomarker profiles. So I think -- I don't -- I can't speak for NICE, but I expect that a biomarker, which is showing utility in terms of improving stage disease will be effective. And I know that because the Cytosponge trials, which were led by Rebecca Fitzgerald here, they are studies, which have really gone on for 20 years from conception to implementation into NHS as a test. It involves swallowing a small sponge, which then takes cells from the lower esophagus to determine if a person has a precancerous condition in the lower esophagus without the need for endoscopy. And those studies were not based on mortality. They were based on detection and improved detection of high-grade changes of the esophagus and people having a noninvasive test. So I think if we can show that the improved staging of pancreatic cancer, so from stage III, IV disease to stage I, II disease is improving with implementation of biomarker tests. That would be very important, and that's actually one of the goals of the National Health Service 5-year plans is to improve overall early stage diagnosis to 75%. That's not going to be possible for pancreatic cancer in 5 years, but that's what the overall guidance in all cancers in the U.K.

Viktor, did you have another question?

No. I think that was pretty interesting to hear other KOLs' perspective as well, if that's possible. I have some other questions as well, but I don't want to take too much of your time.

Okay. Thank you. Well, certainly, it's an open question. What we know now is that early-stage disease has longer survival. Will that translate into durable cures if we can really detect the disease early? I think that's an open question, right? We don't know for pancreatic cancer at this time until there's a way to detect cancer early enough to be able to address it in terms of survival. James, would you like to comment?

I think it is a key question. I think mortality is an outcome, is the direction that we should be aiming for. However, I think we're at a point where I feel like even though there has been tremendous work in the realm of pancreatic cancer for the last 10 or 15 or 20 years, like really intense to work at a molecular level as I can understand it, I still feel we're at the beginning. And so we're at the beginning of these long journeys where maybe colon cancer, maybe Barrett's esophagus are now or at least coming to those points. And so that's -- I mean that's a hope, which is not always a great strategy, but it's a hope, but that's really what's going on. We're just getting started. Meaning, we're trying to figure this out. We're trying to figure out the high-risk group, we're trying to figure out how we can study the high-risk groups. But yes, the ultimate goal would be to do pivotal studies that show impact on mortality to get these issues of lead time bias and so long that affects all these sorts of studies. I think one piece of interesting information that is small, that kind of has me thinking about is that -- and again, it's a limited data set, but from a high-risk population, showing that for some reason, patients that are detected at an early stage in high-risk surveillance programs do better than patients who present sporadically at the same stage. So small numbers, but an interesting signal. I don't have a simple explanation for you as to why. But maybe it has to do with the symptom presentation versus asymptomatic presentation. And so that is kind of a cause for hope. But it also brings up kind of an issue for pancreatic cancer, which is we talk about early stage, but we would love to be also be talking about precursor stage and pre-basal stage. And that's really what we would want to be talking about to make a significant dent here. And again, we probably, through the cyst world, hopefully, there will be some advances in that. The cyst world collides with the high-risk world. And so again, I feel like we're at the beginning of this, and it's a long process and a long haul, but there have been some small important signals.

Thank you, James. And James, another question for you from the audience. How many patients are currently enrolled in surveillance programs for familial hereditary PDAC in the United States? Do you have a sense of the numbers?

That's a great question. I don't have the absolute number. I know that there are the CAPS5 program. But in all honesty, the PanFAM study is also an equally large number. We're talking of several thousand, anywhere between 3,000 to 5,000 studies in these individual studies. They range across anywhere from 6 to 9 centers. There are other health systems that have also evolved to develop their own, somewhere in the realm of 10,000 patients, have taken off and are starting. And then recently, a large NOD study was announced. But -- and we're talking about numbers in the realm of 10,000 to 15,000 patients enrolled over 15 years. Again, alluding to my prior comment, we're not in this for instantaneous gratification and so, we're in this for the long haul. And these sorts of studies take these sorts of numbers in this amount of time. And I think a lot of us are willing to put that effort in and to be patient. So it's a great question. I think, again, the critical guidelines have supported surveillance programs in high-risk genetics groups. And so individual -- for sure, individual centers have their own programs. When it comes to formal prospective studies, the individual studies that are out there typically have anywhere between 3,000 to 5,000 patients enrolled.

Okay. No, thank you very much. And just for clarification, PanFAM is Immunovia's prospective trial to look at familial and hereditary pancreatic cancer patients to sample their blood and to follow them by imaging. And I think, as you alluded to, there certainly is a collision of hereditary and genetic factors with cysts as well. Since at least in the few PanFAM samples we've analyzed thus far, about 1/3 of the patients do have cysts in their pancreas. So we're hoping to be able to learn much more from that. And certainly, addressing pancreatic cyst is something we're very interested in the future. Okay. Thank you. Now if I could go back to some of our other questions. How does genetic testing and counseling fit into the management of patients at high-risk for PDAC and their relatives? And maybe Dr. Burns, you could start with that question?

Sure. Again, covering somebody's family risk, their own personal first-degree relatives, overall, it is important to get them tested but yet at the same time, that doesn't occur. So they go to a genetic center, and they go through family screening of sorts. And then there's an opportunity to be added further. But again, it definitely is throughput into centers that have likely a limited stream of counsellors, have a limited stream of people to get in, probably distance. These are not tertiary or quintenary centers where this exists. So even though there's lots of health care, it's still a very small percentage of patients that are going to be able to get there readily. Where it'd be nicer, again, like a national health service has, where you can have some type of pre-predictive screening tests that we have that's a bit more proactive and not just sort of whimsically, it seems, assessment.

Thank you. And Professor Pereira, would you like to comment?

Well, we are increasingly seeing people who've had DNA testing for, for example, for breast cancer diagnosis or family history. And some of the issues that come up then is that there are several, certainly, up to 20 different genetic risk factors for pancreatic cancer, which have been identified, the quantitative risks for having an individual risk factors such as the BRCA2 gene, et cetera. There's lots of minor genetic changes as well. And increasingly seeing people who get these long reports, who then come to me asking for advice from genetic cancer about what is my risk of pancreatic cancer? And what should I do about that in terms of surveillance or lifestyle? And that's becoming an increasing issue. I don't have an answer for that because we don't have the data set necessarily. We try to quantify the relative risk in terms of not only genetic profiling, but also family history, and we follow here in Europe. It used to be in Europe. We're still in EUROPAC. We follow the respective base of having 2 family members or a predisposing mutation and 1 family member who has had pancreatic cancer or having 3 family members in different generations over time. So if people fulfill those criteria, they go into a screen program of annual MRI -- sorry, 3 yearly MRI, annual endoscopic ultrasound here. And that's obviously an area of interest for bringing in PanCan-d with us.

Okay. And James, in your surveillance program, how does genetics and genetic counselors interact with your patients?

Just to add to what's already being said, there has been a significant increase in standard cancer genetics programs throughout the United States. So primarily for breast cancer and colon cancer, through the kind of tremendous amount of information that's available for those diseases. And so really there's been this trickle down into the world of pancreas because of awareness, because of educations, because of all the research, that has then resulted in formal guidelines about not only who should undergo high-risk surveillance. So the stories of the interplay between the family history of pancreatic cancer and the presence or absence of germline mutations, but also who should undergo genetic testing. And so that has been built into the idea that if now someone has a diagnosis of pancreatic cancer, whereas in former times, we would do genetic testing of the tumor sample and these are the patients who has a diagnosis to help guide treatment. Now there's a recognition that we should also be testing it and doing germline testing on those patients to help us identify these germline mutations with a view to reaching out to asymptomatic family members and talking to them about their risk. So this is kind of flipping things around. And there are several ongoing studies, the largest -- which one is called the CASCADE study. So this is called CASCADE testing, whereby an asymptomatic family member is invited to get genetic tested based on a family member in a very prospective and proactive way. So that's one way that we have noticed that things are certainly changing. Again, we still have to deal with the data and the recommendations to make sure it's correct. And then, of course, on a kind of a more global scale as in certain parts of the world, but for sure here in the United States, for $99, you can get your portion of your genome tested. And that is opened up through these commercial firms, and that is opened up. Just a general interest in germline mutations, it's not, by all means, would be recommended for this sort of entity, but it's the start of the discussion and the awareness. And certainly, there are patients who get an interest in genetics and family history through that, and then we hear about them. And we do get them formally retested with the proper kind of CLIA-certified test. But this is definitely a very active area that's being pushed from many, many, many different directions.

Right. We certainly are in a changing environment now in the U.S., I think, in terms of that kind of testing and the availability of it. Dr. Farrell, how would you use a blood-based biomarker like PanCan-d in your surveillance program?

So that is a very loaded question. The simple way for me to start thinking about that is to start with the issue that there is a need. Without kind of getting into the efficacy issues right now, there's a huge need. I'm in one of these rooms, and I need to activate my spotlight here. There's a huge need for this. And one of the concerns I have with high-risk surveillance in its current format is just the resource utilization. The volume of MRI scans, the volume of endoscopic ultrasound and some of the cost issues that then ultimately may result in compliance issues, and we're beginning to see a bit of that. For sure, during the COVID pandemic, we did -- now we've actually just published on this, we didn't see a dramatic drop-off in patients coming in for procedures, but it became an issue. There's more financial issues. So I think, in my mind, and we're keeping an eye on this, if this affects compliance, then it affects the overall issues of how do we conduct effective surveillance programs. So the simple response to that is, well, let's replace it with a different tool. And that tool will hopefully be a blood test. So that's the first thing to say. And when we talk to these patients who are relatively young individuals in their 50s and 60s. And we're talking to them about -- if they're buying into this, and we're advising to this, this is somewhat a lifetime commitment. But it's somewhat daunting to think that you will be coming in for endoscopies and MRIs on an annual basis with all the costs. And so to kind of give them some hope or vision for what the future might hold is the hope that we would have a blood test, that would at least really stratify certain groups endings, and we could decide which patients do or don't need yearly or biyearly studies. So for me, I think that's where these tests will become very important in this population so that we can identify subgroups of patients who really need a good going over with imaging. And then we can identify other groups of patients that we can truly leave alone for long periods of times, be it 4 years or 5 years. And so that would be my goal for when we see data, post-marketing data and even some of the PanFAM data to understand that that's how we would incorporate it. So -- because there's a real -- I think there's a real need for that, there's going be a practical need for it to really get away from the resource utilization that we have with, again, this very specific high-risk genetics population.

Makes sense. And Professor Pereira, would you see using a blood test such as ours in terms of facilitating or more rapidly bringing patients into treatment for pancreatic cancer, whether they were early stage or late stage?

Yes, for sure. I mean that's perfectly said, James, as well because we don't have cost issues for patients in having surveillance with MR, endoscopic ultrasound but we still find that the individuals who are coming in for those programs tend to be very health conscious. They're nonsmoking, they're not obese. And so I think we're missing a lot of people who don't like to come to hospitals. They don't like they have invasive tests. And I think there's a great potential to improve the application of noninvasive tests in high-risk groups. And also, we are learning in the familial pancreatic cancer groups. There is a way to stratify people based on their family history and genetic following into low and high risk. And so maybe future programs will be high risk, we're looking at them very carefully with imaging and endoscopic ultrasound or in people who've got a raised PanCan-d test, et cetera. So those are things for that group. For individuals with symptoms, was that what you had asked me beforehand? We know that any minority of people go down the rapid assessment pathway, and we need to improve that. We've got a big innovation in the U.K., which started, again, at our university with rapid diagnostic centers in 2016. And that's going to be rolled out nationally when everything gets a little bit under control. And that's going to be -- that's an avenue for general practitioners who have concerns about their patients who don't fulfill 2-week wait criteria to still have the patient assessed in an urgent manner. So we will have a new way of being able to access individuals for testing. And that will be a particular place, maybe if we're putting blood tests as well. Nevertheless, we know that the 9% of people with sporadic pancreatic cancer generally go down -- have vague symptoms, coming late, and they usually have an average tumor size of 3 centimeters. They often have late-stage symptoms like jaundice, going yellow in the previous few weeks. And certainly, there's a great potential for bringing a noninvasive test, not only in secondary care in terms of triaging patients to a CT, et cetera, but also in primary care. And we're really actively trying to see how to apply biomarkers in a primary care setting When GPs are seeing a patient every 7 minutes and need to try and assess all sorts of things with the patient, not just the risk of pancreatic cancer.

Yes. I think that really highlights the stress on different types of practices. And it's great having all 3 of you here today to give really very different perspectives, but the true perspective of what you're facing in your practices. I think you bring up also an important point that probably the number of individuals and actual surveillance programs, at least in the United States, is a fairly small fraction of individuals who really are a genetic or familial high risk. And some of that may be the onerous issue of going in for imaging. As you've mentioned in the U.K., there's been some migration away from the national health service into private pay. I think in the U.S., that's been accelerated. Certainly, my own insurance policy is $7,000 deductible. So paying for a test is something I'm quite used to doing. So the landscape is changing. Dr. Burns, how would you use a test like PanCan-d in your practice?

So again, it's going to be something where patients look to their doctor for guidance on appropriateness of testing. At the same time, I would be considered an early adopter, a lot of technology traditionally. My patients know that. I'm teaching 2 medical schools, teach nurse practitioners, physicians assistants over these last 20 years. So keeping up with that. And so having access to a test like this that really is novel, it is tip of the spear. It is something that is appropriate. It likely won't be as aware or available to them as early as they would be in my own practice. I mean I have a handful, almost a dozen people that introduce -- that I've been thinking about offering this test to and my practice is in 300 patients. So these are people with high risk, that have new-onset diabetes, a parent died of pancreatic cancer, we don't know, genetic stuff. So it's -- they're not in surveillance. But these are people that would want to do more because they are interested in taking care of themselves. Hopefully, the listeners know that the pancreas is different than all the other organs around it. Unlike the ovary you have 2 of them and you can take it out and live very well without an ovary. You can't live without a pancreas. And all of these rescreenings are done because we don't want to mess with the pancreas. A surgeon that does surgery on the -- does their best not to touch the pancreas at any point during any surgery because the pancreas is a very, very reactive angry organ even when healthy. So to do any surgery or any procedure on the pancreas usually puts the patient in a lot of risk and pain. And so to have an opportunity for studies to say, "Oh, we're going to take a breast off, we're going to take a lump out," we're really loath to do that with the pancreas because of how upset it is as an organ and how devastating it can be as just a consequence of a corrective procedure. So to have a test that really, again, further characterizes who is it worth taking them, the risk of a procedure to the operating room, I think, is something I can -- I look forward to counseling my patients about.

No, that makes sense. A question from the audience as well. Even with the tests such as PanCan-d with a very high specificity and good sensitivity, there still is the possibility of false-positive results as there is with any clinical test, I'll say, is my role as a laboratory director for many years. No test is perfect. Would that be a problem in presenting it to your patients or in managing them, the possibility of a false positive? Dr. Burns, you can begin?

Again, you need adequate talking points and understand that all tests are set for sensitivity and specificity. It was talked about before, when you take a large group of where the risk is low, that number becomes much greater that you'll have much higher number of patients that will have a false positive. So that's in a screening kind of way. That's why things aren't appropriate right away. Certain time, you want to catch with them. And it's -- again, patients can still have imaging. This test doesn't -- isn't diagnostic by itself. This doesn't say prepare for surgery, you've got a positive PanCan-d test. This says, "Hey, guess who's getting a referral to Dr. Farrell's clinic? And then it is not a nail in the coffin.

Dr. Farrell, how would you answer that?

Yes. I think it's an issue. I think with proper discussionary priority with patients, it's one way to start to begin to address the issue. The other issues relate to what degree of false positivities that we're willing to accept with any diagnostic test. I think as we use and hope to use these tests for -- particularly in rich population, such as high-risk groups, the hope is that the positive risk to value, which is the metric that I would be kind of interested to see how it plays out, will rise to 0.4, 0.5, get in that sort of realm. I think that's -- for that patient population that is motivated, but very anxious admittedly, who are undergoing imaging, I think that might be acceptable, but it's going to have to be done with lots of counseling and discussion. I think in the general population, it's another beast altogether. Again, there is no such thing as a perfect test. There probably never will be the perfect test for anything that we try to do. But this is certainly better than a lot of the other tests that we even routinely use in this fashion. So CA19-9s are falsy elevated all the time, and we've managed to live with them and understand the limitation that can be done. I think the issue will be just the magnitude of the false-positive things. But I think, again, the hope is in just kind of looking at the numbers, that we're probably getting into the ballpark where it becomes an acceptable issue. And again, we would be starting with this in a clinical trial scenario in a very well-controlled area to kind of figure out how this plays.

Yes. So both patient selection for being at high risk, so having a fairly reasonably high pretest probability and also preparation in terms of understanding what the test can do and what it can't do or both.

Yes.

Professor Pereira, would you like to comment?

Sure. Yes. So we're looking at people, for example, with vague nonspecific symptoms. And you can use various tools to identify patients with, for example, 2% pretest likelihood of having pancreatic cancer. And in that group, you have 1,000 people in a group like that, you'll have 54 positives with those tests, which is not very many, but you'll pick up 18 of the 20 patients with cancer, which is fantastic. So I think those kind of figures are -- we know from stakeholder meeting that they're acceptable to patients, and they're also acceptable to providers of imaging and things like that. That area, which I think it will have an impact potentially, is in the group of people with a lump in their pancreas. So when we see something, which looks like a pancreatic cancer on a CT and take that patient straight to theater, we can be wrong in 10% to 15% at the time. But in combination with the positive PanCan-d test, that may increase the confidence of surgeons to be able to take patients straight to surgery rather than rely on people like James and myself to get diagnostic tissue before surgery. I think in the majority of people with the cancer of the pancreas, which looks like a cancer of the pancreas but it's not resectable will still be needed to get tissue confirmation for downstream decision-making for chemotherapy and genetic testing, et cetera.

Yes, absolutely. And for pathologists, such as myself. So we very much appreciate the tissue. Operator, do we have any questions waiting on the line?

Yes, we have a further one from Viktor Sundberg of ABG.

So in terms of a prospective study, what would you -- or what kind of data would you like to see for the PanFAM-1 study that could lead you to conclude that IMMray could be, say, practice-changing for detecting pancreatic cancer early for this group of patients? And also, it will be great if you could add some color on what added value does a prospective design give you as clinicians compared to the retrospective data that you now have seen that, of course, have strong data? What why could we remove with the prospective study design, I guess, my question is?

yes. And James, maybe you can comment on that?

Well, I think that the...

Yes. Go ahead, sorry.

The first thing to say about in terms of comparison between retrospective and prospective data that's there. Because the prospective data in prospectively controlled studies actually are very similar to what we would want to do in clinical practice. I think that's obviously the benefit of a prospective study, to understand how this plays out in a longitudinal fashion and kind of closer to the idea of what happens if you get a positive test and following up with imaging and expecting. So yes, the retrospective data is good. But having prospective data that kind of mirrors what actually goes on in clinical practice with actual patient management is obviously going to be better. So that's the first statement. I think the other issue relates to what would you expect to see in a -- effectively in a study design? I think you would want to understand the follow-through of all these issues that we're addressing in a prospective study, false positives, following patients through longitudinal information. I think something that will hopefully come out of the PanFAM study is issues of when might markers be positive before obvious development -- I'm sorry, in patients who ultimately are diagnosed with pancreatic cancer and markers turn out to be positive, either situations where they're positive and there's no obvious imaging correlates such as on a CT or MRI or even endoscopic ultrasound. And so we do get signatures from that from other more invasive types of biomarkers. So it will be interesting to see in the PanFAM cohort whether the signature is positive 1 year, 2 years, 3 years prior to it. And so those are kind of areas of questions of interest for pancreatic cysts as well as the new-onset diabetes story. So I hope that answers your question. I think it's -- prospective mirrors what we're actually doing in clinical practice. I think the lead in to the development of cancer, that period is something that we're all very interested in. Yes, these cancers develop as masses, but there's something else going on in the pancreas before it presents to the CT scan. It still may well be invasive cancer, but there's also preinvasive stages. And if that could be captured on a signature, then life becomes even more interesting. So look, that's why I'm optimistic about these studies. They take a long period of time. But when we do get signatures like this, I think it's very exciting.

Yes. I mean it seems to me that's the only way we can really address the issue of whether -- of patterns, which you don't see as clear morphologic lesions or cysts within the pancreas. I don't know any other way that we can address that than by looking back at earlier samples from these patients and seeing if the test is positive. So I think to me, that's one of the most important things we may get from PanFAM. And Professor Pereira, would you like to comment as well?

I think, James has covered. I think we're looking at appropriate trials in different patient cohorts. And we have -- it's certainly feasible to design studies in the hospital-based group of patients to show clinical and cost effectiveness and have answers to those quickly. And there's much bigger challenges in primary care, of course, when the proportion of patients with pancreatic cancer that a GP is seeing every month or several months is so much smaller. And those kind of studies have been done successfully with different study designs like nested case-control design, so bringing in the biomarker in one region and looking at its impact compared to another region of matched patients. So we're currently looking at issues like that.

Thank you. And initially, IMMray PanCan-d will be available as a self-pay only until we acquire insurance coverage for it. Do you feel that this out-of-pocket cost to patients will impact the way you use PanCan-d in your practice for surveillance program? Maybe we could go to Dr. Burns first.

Again, I think for the right patient, I don't think cost is an issue in my practice. And that's the benefits of having patients expect to, at times, pay for what they're getting. Certainly, I still curate tests for them. I don't always -- I'm not ordering the most expensive laboratory possible for their cholesterol screening. There's a cost effectiveness assessment that is done. And when that is the only show in town, and this is what it costs, and this is what your risk is, people are willing to pay for it.

And James?

I think it's a very important question. Obviously, we would all like everything to be free or as cheap as possible, goes without saying. I think in that context, for again, for the high-risk group of patients, these are incredibly motivated group of people. If they are seeing it as an isolated cost, then they have to look at their own finances for insurance reasons there are issues as -- complex issues such as things called co-pays, where they have to pay a portion of what goes on, that would not have to be the situation here. But if they're balancing between this versus paying for a portion of an invasive imaging study or a CT or MRI, then it becomes a kind of more realistic discussion for this sort of price range but again, listen, I think we would like everything to be free.

Absolutely. And in the U.K., it still is, at least largely. Professor Pereira?

I think in the U.K., we'll be looking at the impact of implementation of PanCan-d in the U.S. and other health environments. Because there's an important amount of information that will come from that because that will be able to answer some of the questions of its impact on clinical decision-making by clinicians, of course. We have a specific -- not we, but nationally, Cancer Research UK and other big bodies have a cancer biomarker road map going on from small -- single hospital studies to national implementation studies. And that kind of implementation fits right in the middle of the various stages going to adoption into the NHS for a new biomarker.

Okay. Thank you. Another question from the audience. And the question is, what is the broader view on how disease-specific tests such as PanCan-d would interact with broader pan-tumor tests such as Galleri so -- which is designed for general population screening rather than a high-risk screening? And Professor Pereira, maybe you could speak first?

Yes. No, that's a real interesting question. The previous CEO of Cancer Research UK, Harpal Kumar, is now -- is part of GRAIL. And those studies are coming into the North London community within the next several months. So there'll be data coming into the -- in the U.K. setting in symptomatic individuals and asymptomatic individuals for that. My understanding of looking at assays like that be even so far published, and obviously, there's probably more data on the way with that and also with CancerSEEK is that relatively small numbers have been looked at in pancreatic cancer. And secondly, that the sensitivity of the assays are diminished in early-stage disease. There may be more data coming from that. So it may be that certainly for pancreatic cancer that there'll be a need for a more specific, more cancer -- pancreatic cancer-specific assay or maybe utilizing PanCan-d as a confirmatory biomarker in individuals with the positive test in that group. I don't know the answer to that. I think we're all waiting for more details.

Okay. Thank you very much. And...

I actually have used GRAIL testing already, and it's a methylation of DNA fragments for organ-specific or region -- gland-specific cancers. And again, the idea is that it's methylation of DNA. So it's a single type of test where PanCan-d and these others are inflammatory markers and other matrix-type testing so you're not just getting organ-specific or other, say, glandular cancer data in this way. They are very different.

And one more question from the audience that, say, is a very direct and cheeky question. If the KOLs were at high risk for pancreatic cancer, would they be seeking out a test like PanCan-d themselves? And I'll answer that first. For myself, my mother died to pancreatic cancer. So I would personally. And don't answer this if you feel uncomfortable, but James?

Yes, it's uncomfortable question, but I will answer it. I will answer it. The short answer is, I think you want as much information as possible. We come from an advantage of knowing the limitations of the different tests and strategies that are out there. I certainly am no longer the person who puts his head in the sand. I do want to know what's going on. Understanding the benefits and risks of an endoscopic ultrasound, an MRI, CT scan, even a blood test, I think, is useful. So I would be in support of it in the situation of being high risk and will certainly, when looking at more of the data, be supportive of it for our general population. With -- also just a caveat because I thought the prior question about the multi-panels is really kind of a hot topic. Again, specifically for our patients with high-risk genetics, if we just focus on that group and even to some extent for the symptomatic patients, again, we are very pancreatic-centric clinicians and researchers, you want to go with the best test for the patient in front of you. And so for patients in that group having a test such as Immunovia that is really pancreatic-centric, giving up the advantages of the multi-panel test that, yes, might be much better for colon cancer, breast cancer, which are big clinical needs and unmet needs but, to my knowledge, are not particularly good for pancreas right now and in terms of numbers, I think that's how I see that particular discussion going. And if they will have certain needs in different environments, so maybe for general screening of the population, so on and so forth. But for those of us who are dealing with patients who have concerns or we're concerned about their risk for pancreatic cancer, I think reaching for test that have just kind of the best data for that particular clinical scenario is -- will be my approach until I see data to the contrary.

Professor Pereira?

I don't have anything add, I think, to what the others have said.

Yes. Thank you. Another question. Are you -- and this sort of goes to issues like pan cancer test. Are you concerned implementing expanded screening or surveillance programs based on this? Could this be something that could be socially or detrimental or detrimental to the health care system in terms of putting many more individuals into balance surveillance programs? Hard question to know, I think?

Yes.

I mean I -- we can just jump in and tell you, I mean people have studied the psychological effects of surveillance. And by and large, it's more positive, again, particularly -- again, if we're just talking about high-risk groups. I think, again, we have to be very careful with the issue of specificity and positive predictive values. And that's kind of what's the fine line there, and it is an issue of patient counseling and patient selection. But it's a reasonable question. I think all the different aspects, not just the cost and the clinical aspect, even the psychological aspects of what we do are things that we do address and we do address in our studies. And I think time will tell.

Dr. Farrell?

Yes, we're in an environment of more testing, in general, I think, more opportunities for individuals who have concerns or symptoms to have tests that's going to lead to more imaging. It's going to lead to more detection of things like pancreatic cysts for us. So we're going to have more patients referred for surveillance. We won't be able to do that endlessly with MRI and endoscopic ultrasound. And so it will be -- there'll be more needs for noninvasive tests for surveillance as well.

Well, but also technology leaders of large companies, academics are often taken with pancreatic cancer. They're very publicly acknowledged. And most of these people are dying during their highest productive and earning years, their 50s and 60s, when they're contributing most to society. So I think that even if we are screening and catching these folks and putting into the surveillance, they're very highly valuable people at the peak of their career, and the community will benefit from their assessments.

Thank you. And I want to thank all of our panelists. Thank you so much for participating today. I think our time is about up. And at this point, I'd like to turn things back over to Patrik to make some closing comments.

Well, thank you very much, Tom, for that. I, too, would like to start my closing remarks by really thanking Dr. Pereira, Dr. Burns, Dr. Farrell for participating this morning, this afternoon in this Key Opinion Leader event, a very, very interesting discussion. And Tom, I think you did an excellent job as the moderator. I come away from this discussion with very clear answers to some of the sort of key questions that you always have as a company that's been working on a test like IMMray PanCan-d. First of all, you always have to -- your first question is, is there a clinical need for the test that you were very confident and with a very clear message that there is not only a need, but there is a huge need, a huge unmet medical need for a test like in IMMray PanCan-d. And that early detection of pancreatic cancer is one of the key questions. So I think from an Immunovia point of view, I think we got a very clear and resolute response and that I'm very, very thankful for that. Then, of course, second question that we need to ask ourselves is that, do we have a test that fulfills the need and will it make a difference? And I think we clearly hear that the test performance fulfills the requirements. There is a very specific view that for the familial hereditary side, we can complement, and we can potentially enhance how surveillance is done with IMMray PanCan-d. And when it comes to the symptomatics, we clearly hear that we can enhance and accelerate the diagnosis, either if it's in early-symptom groups or in lat-symptom groups where even the slightest more information that we can give to the patient might accelerate the diagnosis and be helpful. So from that point of view, I think we come away confident that we will make a difference. Obviously, the third last high-risk group that we did not discuss that much, but it came up a few times is obviously the new-onset diabetes group, where we, hopefully, later this fall will be able to generate some data with regards to IMMray PanCan-d's performance in the cohort of Swedish new-onset diabetics, where we have participated in collecting some 6,000 samples from Swedish new-onset diabetics, and we'll get the first insight into the performance of IMMray PanCan-d in this particular group. The third aspect from Immunovia's point of view is obviously to sort of go-to-market and the marketability and the sort of business aspects. And here, obviously, things like getting a clear approval, which we would have expected to have already, and we think is imminent is important. But obviously, also developing strategies to get the reimbursement in the U.S. is an absolute key for us. And here, we continue to believe through our consultants as well as from our discussions with key opinion leaders that first of all, there is, in fact, reimbursement in place for individuals who are enrolled in high-risk surveillance programs and have a family and hereditary disorder, they do get reimbursement and payment for the cost. And then -- and secondly, I think it's, again, important to emphasize that from a reimbursement point of view, our test is not intended as a general screening population tool but rather a very focused tool in order to follow high-risk populations. And therefore, the inclusion criterias are tight, et cetera, and we're clearly set aside from the very cumbersome criteria put forward for tests that are intended to use for the general population screening, which, again, is certainly not what we are intending to do with IMMray PanCan-d at this instance. We're coming up on our time. And I would really like to, again, thank the panelists. I would like to thank you, Tom, for being such an excellent moderator. And I would like to thank the audience who dialed in to the webinar. I really truly enjoyed the webinar, and I hope you did likewise. So thank you very much. Thank you.