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

Hello, and welcome to Immunovia press conference call. [Operator Instructions] Today, I am pleased to present Patrik Dahlen, CEO; Thomas King, MD, PhD; and Linda Mellby, PhD. Please begin your meeting.

Thank you very much. Good afternoon, everyone, and thank you for joining us today. And thank you for your continued interest in Immunovia. My name is Patrik Dahlen. I'm the CEO of Immunovia. With me on this call are Thomas King, Dr. Thomas King, who is our Medical Director; and Dr. Linda Mellby, who is our Vice President of R&D. We will be presenting the data from the blinded validation study performed in our Dx Lab in Marlborough, Massachusetts. And we will be presenting the data from a test performance improvement study performed here in the R&D lab in Lund, Sweden. On the next page, Page 2, please, you can read our disclaimers and our forward-looking statements, and I encourage you to read these at your leisure. Next page, please, Page 3. Today's agenda is as follows: I will start by giving an overview of the data, and I will discuss the importance of these 2 independent data sets. After my introduction, Tom will discuss the blinded validation study performed in our lab in Marlborough. Linda will then take us through the results of the test performance improvements performed here in Lund. In the end, before we open up for questions, I will discuss the next steps and what this all means for us at Immunovia and what it means for early detection of pancreatic cancer at large. Next page, please, Page 4. I wish to take this opportunity again today to remind everyone how important the mission we're on here at Immunovia. With the IMMray PanCan-d blood test, we will help in 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 1 and 2, the 5-year survival significantly improves. The survival rate goes to 50% survival rate after 5 years compared to less than 5% when pancreatic cancer is detected at Stage 3 or 4. Today, the median survival rate for newly diagnosed pancreatic cancer patients is as low as 4 to 5 months. And the reason for this is simply that 80% of all pancreatic cancers detected today are diagnosed too late. They're diagnosed in either Stage 3 or 4. And at these late stages, the tumor is no longer resectable. This is why I am so pleased to be able today to announce that we, yesterday, released the data from our blinded validation study in the U.S. And you see a detection rate of 85% of early-stage pancreatic cancer, that is Stage 1 and 2, against a control group of healthy individuals from the risk group of familial and hereditary risk group. As you know, people with a family history and/or genetic traits are demonstrated to give a significantly higher risk of pancreatic cancer. Tom will obviously go through much more detail of this blinded validation study and discuss the data. However, I just want to say that this is a major milestone to us. We will be able to launch this test in the U.S. with the aim to address the need for continuous surveillance of familial and hereditary risk group. In the U.S., this group of individuals is estimated to be almost 100,000 people, and they need to be monitored once or twice a year. This is today done with various scanning methods. And due to capacity constraints, not all eligible persons can be included. With a simple blood test as IMMray PanCan-d, this test could be used for all eligible persons in the risk group. Furthermore, we already now can see an interest in broadening the inclusion criteria in the future to include also people with only 1 first-degree relative. Currently, inclusion criteria is 2 first-degree relatives into surveillance programs, as persons with 1 first-degree relative has a nine- to ten-fold risk of -- increased risk of getting pancreatic cancer over the general population. The other great news we will discuss today is the test performance improvements that we have reported on yesterday. We see now a significantly improved performance in the early detection of pancreatic cancer versus symptomatic patients or patients with worrisome vague symptoms. Linda will give you the details of the results. However, stated briefly, we are extremely pleased with the better performance of the IMMray PanCan-d for early detection of pancreatic cancer Stage 1 and 2 against symptomatic controls. The test performance we now see with a specificity of 92% and a sensitivity of 82% for Stage 1 and 2 is in line with the performance we saw in the so-called CTMS study. And it is, maybe more importantly so, in line with performance expectations we have collected in feedback from key opinion leaders in the field. We now see a performance that will enable us to move forward and take the next steps towards launching IMMray PanCan-d for utilization in this symptomatic risk group also in the near future. Next page, please, Page 5. With this brief introduction, I will now hand over to Tom, who will present the blinded validation study data. Tom, please?

Thank you, Patrik. Could I have Slide 6, please. Hello. Today, I'd like to describe for you the blind validation study, which we have just completed in Immunovia's state-of-the-art laboratory in Marlborough, Massachusetts. First, I wanted to highlight our many collaborators that provided samples for this validation that included 167 pancreatic ductal cancer samples from the U.S. and Europe, of which approximately were 1 -- approximately 1/3 were early stage, that is Stage 1 and 2 PDAC individuals, who are potentially resectable and potentially curable. Slide 7, please. In addition to the PDAC samples, we employed 203 samples from individuals at high risk for pancreatic cancer from our PanFAM clinical trial. The clinicaltrials.gov ID for this trial is listed here. These individuals are all enrolled in active PDAC surveillance programs because of their family history and/or known germline mutations that they carry. These samples came from our U.S. collaborators at Massachusetts General Hospital, University of Pittsburgh Medical Center and the University of Pennsylvania. To our knowledge, this is the first large-scale evaluation of individuals that define genetic risk using a blood-based biomarker signature with PDAC. Healthy controls from this study came from ethnically and geographically diverse populations, with approximately half of those individuals residing in the U.S. Slide 8, please. This validation was conducted in a fully blinded manner for both myself and the technologists performing the assays, with the sample key held by an individual not directly involved in the validation process. All samples were analyzed according to defined SOPs using duplicate arrays for each sample with defined quality control limits. CA19-9 was analyzed using a fully validated Roche cobas instrument with electronic transfer of data from the Roche instrument to our laboratory information system. Microarray slides for the study were imaged using a fully validated confocal laser microarray scanner. The data that was produced was then analyzed using our own fully customized and clinically validated software that performs both decision value calculation and QC assessment or quality control assessment using predefined cutoffs for sample classification and for quality control. The data from this were then automatically transferred to our Orchard Harvest Laboratory Information System for final result verification and report generation. All of these things are done exactly as we would do for clinical samples coming into our laboratory. Slide 9, please. First, I'd like to show you the results for the 3 cohorts we analyzed in this study in this histogram based on the decision values we attained. For the PanCan-d test, 8 protein biomarkers and the input from CA 19-9 are combined in a linear equation to give decision values. Decision values for PDAC samples tend towards negative values, while those for non-PDAC samples tend toward positive values. You can see the typical bell-shaped curve for healthy and PanFAM samples in green and blue towards the right of the histogram corresponding to a negative result in this test. Note that these 2 histograms are nearly overlapping, so that the performance of the test in individuals from PanFAM and healthy controls was very similar. Please note also that the 2 curves are quite tightly delimited. These are the typical bell-shaped curves you would expect for a healthy population for many clinical tests, including serum electrolytes such as sodium. In contrast in red, you can see the results for PDAC samples, which show a much wider decision value distribution, which is strongly shifted to the left in negative values. Also, please note the clear separation between PDAC samples based on this histogram and the PanFAM and healthy samples. Slide 10, please. These results produce the following ROC AUC curves and calculated sensitivities and specificity using predefined decision value cutoffs. First, comparing early stage, that is Stage 1 and 2 PDACs, in individuals at high familial/hereditary risk for PDAC, we observed a test specificity of 98%, with a sensitivity of 85% and an ROC area under the curve of 92%. Below, comparing all stage PDACs with these same individuals showed an even higher sensitivity of 87%, while maintaining 98% specificity. These are truly excellent results in this high-risk population. And as I previously indicated, this is the first large-scale evaluation of the defined high-risk population with a blood-based biomarker for pancreatic cancer. Slide 11, please. This shows a similar comparison of the results of testing PDACs versus healthy controls and shows results that are very similar to those we obtained with the PanCan cohort. We had slightly higher specificities of 99%, as you might expect in this population. But again, very good detection, high sensitivity of low-stage and all-stage PDAC samples. These results are very much in line with our prior observations in PDAC versus healthy controls that we reported several years ago in the Journal of Clinical Oncology. Slide 12, please. In conclusion, this large blind validation study has demonstrated 98% specificity and 85% sensitivity in detecting early-stage PDAC in a relevant high-risk population. The performance of this test in this high-risk population is very similar to that observed in healthy controls, suggesting that PanCan-d is a very robust test for the detection of early pancreatic cancer. I feel that this is a major step forward in improving care for at-risk individuals that can lead to earlier cancer detection and treatment with significantly improved survival. Slide 13. I thank you for your attention, and I'd now like to turn the discussion over to Dr. Linda Mellby.

Thank you so much, Tom. Really excellent results for the familial/hereditary group and the healthy control group. I will now show you data that demonstrates an improved clinical performance of our IMMray PanCan-d test, also for the symptomatic high group -- high-risk patients. Please turn to Slide 14. And as described in the webinar we held last year in December, where we're not quite happy about the results in the clinical verification study when it came to the test performance in the symptomatic control group. So during this month where we have been working with improvements coupled to the production and to the quality control processes. So we have changed some parameters that have led to an increased analytical performance of a microarray. So to evaluate how these improvements affect the clinical performance of our tests, we performed this study where we combined samples already analyzed in the clinical verification study with also newly collected samples to increase the statistics, especially for the symptomatic control group because this is a very diverse control group, so this is the number we come up with. We had, in total, 433 patient serum samples collected from 7 different sites in Europe and U.S. We had 202 PDAC at all stages, where 89 were early stages and 231 were symptomatic controls from a very well-defined high-risk cohort. So these are non-PDAC controls having vague symptoms suggestive of PDAC. And it also includes patients having chronic pancreatitis, diabetes, liver diseases. So it's a very diverse set of cohorts. And please turn to Slide 15. So the results from this study show that we now can separate early-stage pancreatic cancer from symptomatic controls with a specificity of 82% (sic) [ 92% ] and a sensitivity of 80%. And when analyzing all stages of PDAC, the sensitivity increased from 80% to 81%. So I think this is really, really a great improvement compared to the results presented in the clinical verification study, and it shows also a better specificity than many of imaging technologies used in the current diagnostic workup such as CT, MRI and [ ES ]. Please turn to Slide 16. So I would like to conclude that we aimed with this study to show an improved clinical performance after implementing this improvement. And we really did improve 11% in the specificity and 2% in the sensitivity compared to the verification study, and this is for discriminating early stages of pancreatic cancer from symptomatic controls. So I think this is a really fantastic improvement performed in a very, very short time frame. And the current result showed 92% specificity and 80% sensitivity for detecting early-stage pancreatic cancer in symptomatic risk group. And this is also really great results, supported by our key opinion leaders, as Patrik earlier stated. And as I said, it's also better specificity than many imaging technologies used in the entire diagnostic workup for these patients. So detecting pancreatic cancer as early as possible in this high-risk asymptomatic patient group is very challenging. And so by adding the IMMray PanCan-d blood test into the current diagnostic workup would provide complementary information and support the clinicians to do accelerated diagnosis for these patients. And so we are very excited by these results, and these findings will be further confirmed in our laboratory in Marlborough, U.S. So with that, I would like to give the word to Patrik. And thank you very much, and please turn to Slide 17.

Thank you very much, Linda, and I will now discuss the conclusions and the next steps. So if I could have the next slide, please, Slide 18. As you well understand, we are, for very good reasons, over the moon of excitement for these breakthrough data that we have presented. I want to point out that the data on this very slide that we're looking at is data for early Stage 1 and 2 sensitivities and specificities. Very often when we see data presented, it's for all PDACs and all stages. And we just want to emphasize once more that we really have understood and our key opinion leaders have led us to understand that it's early-stage detection that is meaningful because that is the time point where the tumor is still resectable. And the key to success for us and for the community at large for pancreatic cancer is really early-stage detection. So this is truly outstanding data. And also, it's -- we're very happy that for the first time to see the performance, also including the highly relevant control cohort of the familial and hereditary risk group as a background. So very pleased with that. And we also show data where, after technical improvements in the IMMray PanCan-d blood test, we see a great specificity and sensitivity for early detection, again, of pancreatic cancer Stage 1 and 2s against symptomatic -- asymptomatic cohort. We will, of course, run a confirmation of these test results in our U.S. lab so that we can generate U.S.-based data. With that, I'd like to move to the next slide, please, Slide 19. So what are the next steps? We will be filing for a CLIA license as soon as it's practically possible. We're finalizing the paperwork and should be filing the paperwork very soon. So it's just a matter of finalizing the paperwork. As we have stated a few times, the CLIA process takes normally 30 days. We hope that despite the COVID-19 pandemic that the process will run smoothly, and we have all reasons to expect that 30 days should be the time to obtain a CLIA registration number. Because when we have a CLIA registration number at hand, we can start invoicing for tests performs. And this should, as you all understand, be well within quarter 2 2021. We are, of course, and have already initiated significant marketing and sales efforts. And specifically, now that we have generated U.S.-based data, we will, of course, be marketing the IMMray PanCan-d for the risk groups that we have discussed, and we'll be going full force forward. So we're very, very excited about the forthcoming period of time. If I could have the next slide, please, Slide 20. I want to touch briefly upon the reimbursement plan for IMMray PanCan-d. We have already initiated a second payer study following the study we did in 2019. The focus will, this time, be particularly on Medicare. The first study already gave us valuable insight, and we feel confident that the payer willingness to reimburse a blood-based test for early detection of pancreatic cancer in risk groups is very high indeed. It is important in this context to point out that the test is not a screening test, but it's rather a surveillance test for specific risk groups. We will run a few clinical studies in the U.S. This includes the PanFAM study to demonstrate clinical performance and clinical utility in the U.S. These studies will be focused studies, not very large studies, and they will be run by independent investigators in the U.S. In terms of the process to obtain reimbursement, we will, of course, seek a PLA code for the IMMray PanCan-d test as soon as possible, following data from the PanFAM study and other studies. We will then conduct further studies as needed, illustrating analytical and clinical validity and clinical utility. We will monitor and collect clinical data from our ongoing out-of-pocket commercial testing. We will obtain endorsement from key opinion leaders and leading institutions. We will then use all of this data and supporting evidence to build a dossier, with which we can seek a local coverage determination from the local government services, who is the Medicare administrative contractor for Medicare service providers in the New England region of the U.S. And with this dossier in hand, we will then start negotiations for coverage agreements or reimbursements as it's also cause -- as it's also called. Because the test is for surveillance and not for screening and screening at large, we do not anticipate any major hurdles underway. We have also obtained information that for the surveillance that's currently done for risk patients in the familial and hereditary risk group, the scanning methods are currently reimbursed by payers. So we don't see a major question with regards to obtaining reimbursement for surveillance in the familial and hereditary group as we obviously not foresee any issues either in the symptomatic group, of course. Next slide, please, Slide 21. In conclusion, we can say that this data we have presented are true breakthroughs. This data are important for the future of early diagnosis of pancreatic cancer. And all of us at Immunovia are very proud to present such great data. And we look forward to the role we will play in helping saving lives in the future. This is truly what we come to work for every day at Immunovia, and all our employees are extremely proud of the role that we play and will be playing in the future. Next page, please, Page 22. I would, in the end, like to thank you very much for your attention and for your participation. With this, we will go and open up the call for questions and answers. Please.

[Operator Instructions] We have a question from the line of Lars Hevreng from Danske Bank.

I was just wondering whether you're yet, at this stage, are considering any further changes to the array? I mean, I guess you now have 8 biomarkers or antibodies that you do include on the test kit, whether that's a set design? Or whether you're considering any changes there?

So I'll start, and then hand over to Linda. I think where we are right now, when it comes to the performance of the IMMray PanCan-d for the familial and the hereditary group, we're extremely pleased with the performance and really don't see a huge need for further improvements as such. The specificity is very high, close to 99%. The sensitivity for Stage 1 and 2 is as high as 85%. So obviously, one would always wish for more. But to be quite honest, I think we're really, really, really pleased with the performance there. With regards to the symptomatics, this is equally so. I mean, we -- with the improvements that we made so far, we think that we see specificity which lives up to the expectations of the key opinion leaders and what they have informed us to be their set of specifications that are needed in the diagnostic workup for symptomatics. That said, obviously, as one always does with this type of diagnostic tests, there might be ideas and possibilities to continue over time to improve. That is not unusual at all for a test setup like IMMray PanCan-d is. With that, Linda, do you have further comments or additions to what I...

No, I don't think, Patrik. I think you answered very good, Patrik. And I agree with you 100%, so...

Okay. And sorry, it's Lars here again. And could the data, I mean, the antigen expression between risk groups -- or would that -- in sometime in the future, would that warrant, let's say, a development of the separate tests? Or was it -- will it be one test for all?

It is one test. We obviously continue always to look at future opportunities. If I mention one area that continues to our interest going forward for pancreatic cancer is IPMNs, the sort of 3 stages of cancer for pancreatic cancer. And that's an area where we would obviously like to continue to work and see if we can broaden out the utility of IMMray PanCan-d. And if we were to do that, it would most likely require some addition of our signature with regards to biomarkers. But we will always be on the lookout for whether there will be additional interesting biomarkers to add to our signature, of course, for pancreatic cancer in general. And again, Linda, do you have additions to that? Or...

No, no. I think it's -- I mean, a long, long time improvement. Of course, I mean, you can add biomarkers, but we are happy now for the launch, so to say. But -- so for long term, yes, but not at this moment. Yes?

All right. And just a final one from my side. Could you just please remind us about the time lines for the ongoing prospective trials? I'm thinking now, of course, about PanSYM and -- PanSYM and PanFAM and PanDIA. And I guess, yes, the PanFAM was mentioned in the press release yesterday, but if you just could please remind us what that.

Yes. So PanFAM, we will run in the fall. So that will definitely be done before -- well before the end of 2021. And it's also one of the steps we're taking with regards to building on clinical this year for the U.S. and for the reimbursement. And now that we have a validated test, we will, of course, run that in the U.S. with the validated test protocol. PanDIA, we have collected a great deal of samples. We will also run that now that we have a validated test. So that will also be run well within 2021 to get the first very, very exciting data to view what does new onset diabetics type 2 over 50 actually look like in our hands, so to speak, when run on IMMray PanCan-d. And this is, of course, a very, very exciting study. And then we will continue to collect PanSYM patients and samples, as we had earlier indicated, obviously, because of the pandemic. Particularly for the symptomatics, there's been a little bit of delay for PanSYM-2, but of course, we still work towards being able to get that cohort also collected for now. So all of the studies continue, and we are well on track to report data for that within 2021.

[Operator Instructions] We have another question from the line of Viktor Sundberg from ABG Sundal Collier.

So first one, on the design of the validation study. In the verification study, you had 2 groups, healthy and symptomatic. In this validation study, you have hereditary, familial and healthy controls, but not symptomatic. So when was that study design decided? And why wasn't that study design communicated before? That's my first question.

Yes. So obviously, we communicated earlier that we are performing some test improvements with regards to IMMray PanCan-d, because we saw that we needed to lift the performance post the verification study. And this obviously had a priority before running symptomatics through again. So it became very clear to us that we wanted to make sure that we had improved the test performance for the symptomatic control group before running a blind validation study on that in the U.S. The second reason is, obviously, that for us, it was equally important to get a cohort of healthy controls and healthy familial and hereditary risk group individuals included in our blind validation in the U.S. Whilst we did not anticipate, and of course, now the data also shows that there is basically no difference between healthy controls and the familial and hereditary risk group controls, but we felt this was very important prior to launching the test for clinical utility in the U.S. to also make sure that, that happens. So we gave the priority to the healthy controls and to the familial and hereditary risk group for that reason. And that, I think, it's completely logical and straightforward.

Yes. Yes, sure. And the validation of the symptomatic controls, is that what will be done in the U.S., as you said here? Or will that be a further next step for the company to validate that specific cohort?

So yes. So I'll start, and then Tom can add. With regards to the symptomatic control group, actually, once we are accredited for running the early detection of pancreatic cancer tests in the U.S. based on IMMray PanCan-d, we, strictly speaking, don't need a validation study for the symptomatic control. We have, however, decided that it makes sense for us to run a confirmation of the data that we have generated in Lund, also in Marlborough, so that we have a data set and a data dossier generated on the symptomatic control group in the Marlborough lab as well. With that, Tom, you want to add something to this?

Certainly. Well, I mean, it's necessary for me to be able to provide guidance to the clinicians that utilize our test. So we have to have in-lab experience in terms of symptomatic individuals and probably not just in terms of symptomatics in general but in terms of specific symptoms what the test performance is like. So I think my job is to really try to provide the most useful guidance at hand as we possibly can in terms of how to utilize this test in different clinical situations. So that's a necessary thing for us. Certainly, the PanFAM studies are initial target group in terms of individuals to test. So I think it was a very appropriate and important group for us to test.

Okay, great. And I have another question as well, maybe towards to Linda here as well. Just on the design of the second study that you did in the symptomatic -- with the symptomatic controls. Just out of curiosity, why didn't you take exactly the same samples used in the verification studies, so to speak, lock that variable and to introduce your improvements in other variables, as you said with arrays and so on? Because now you add new samples that, I guess, could differ in their profile compared to the samples collected in the verification study. So how have you made sure that the improvements are not coming from the fact that you've added new samples with a different profile compared to the test used during the fall, for example?

Yes, sure. So this is exactly the same PDAC. It's just a few PDACs that we added. We had 195 in the verification study, and these are exactly the same in this study. So you can think of the PDAC cohort as exactly identical. When it comes to the symptomatic controls, we added because we wanted to get a better statistics. And then we also had from the same cohort that was the new shipments but from the same cohort. So just to add samples to get various statistics because this was very, very important results for us to understand what specificity and sensitivity we will have after the improvement. So to get as good statistics as possible, we added these samples. And I mean, this is also a very -- this symptomatic group is a very diverse group of patients. As I said, we have diabetes. We have chronic pancreatitis, liver diseases, different kinds of symptoms. So it's very important also to have as large group as possible to get as good -- as close to the true value as possible. So that's why, it's just to get as good and most true data as possible, and that's why we added those.

But the new samples in themselves cannot have added to the performance, so to speak. You're sure about that?

No. Yes. I mean, it's the same type of cohort, and we have run several -- I mean, we had around 500, 600 of these in the CTMS. So -- and we don't see any difference. So I'm very sure of that.

Okay. Yes. And could you also be a bit more specific, I guess, on the improvements you've made? You spoke more in general terms what you have done, but maybe in specific terms, that would be interesting as well.

Yes. Yes. So what we have done is that we have improved some parameters in our production and quality control process. And these adjustments have led to a better analytical performance, and that means that we are a bit more sensitive in our measurements of the analyte, which then gives us a better sensitivity in detecting biological differences, and that's why we are seeing a better clinical performance in this study.

Okay. Yes. And before -- back to Patrik, just a final question here, before we -- you spoke about the sales start in Q1. And then now I guess that's pushed into Q2. That is not a big thing, I guess, but did anything in the validation process take longer than expected compared to what you anticipated earlier this year?

It was a tight time schedule. And at this moment, I just -- to those Immunovia employees who are listening to this webinar, I would really like to extend a big thank you. We worked extremely hard just to meet these time lines, and it was extremely excellent teamwork, both here in London as well as in Marlborough to get to this. So from that point of view, it was a very tight time line. We don't see this as a delay. We can split hairs and discuss it. But basically, from my chair and from my -- from the way I see the world, I think we came out with the blinded validation study before the end of quarter 1, which is basically the key to file for CLIA, and that's what we generated and obtained as -- by great teamwork. So very pleased with that and do not really see it as a delay by any stretch of the work, so to speak.

So for that, I would think -- sorry.

No, I'm sorry. I would also say we wanted to take advantage of the improved manufacturing controls for the blind validation study so that we'd have most reliable reagents that we can use clinically.

[Operator Instructions] There are no further questions registered, so I hand back to the speakers.

Great. Thank you very much. Again, I just want to say thank you very much for your interest in Immunovia. Thank you very much for your interest in the work we do for early detection of pancreatic cancer. We think we have, yesterday evening in the press releases and today in this press conference, discussed what we think to be breakthrough data. We are now in a position where we really have demonstrated the power of IMMray PanCan-d, not only for familial and hereditary risk group, which in itself is an interesting market to approach and where we think there is a clear line of sight, not only to a good market but also to reimbursement. But furthermore, also demonstrated that our original performance from the CTMS study with regards to early detection of pancreatic cancer against the symptomatic risk group, we now also have data at hand to say that we have a performance that is at the level that the key opinion leaders in the field are expecting. And with this information at hand now, we can proceed as quickly as possible to start marketing and selling these products to a patient group that so desperately needs this type of early detection methods. So thank you, everyone, for listening in. Thank you so much, and have a great day. Thanks.