Welcome to the Global Investor Call for Exact Therapeutics. My name is Maha. I represent the healthcare investment banking team here in DNB Carnegie, which is supporting the company on their ongoing warrants exercise right now. And we have this global investor call to go through a refresher on the case, to give you some updates on all the exciting things that are going on with the company, all the exciting developments with the incredible technology platform that the company has. Before I leave the word over to the management, introduce the management that will be presenting today, let me just give you a few pointers as to the Q&A.
We will be having a little Q&A at the end of the presentation, so once the management is done presenting the case, there should be a Q&A tab that you will find on your screens. You may click on that and post questions, and I will read them out loud for the management at the end of the presentation. So, today we have the pleasure of hosting the management team from Exact Therapeutics. Representing Exact, we have its CEO, Per Walday, we have the CFO, John Edminson, and we also have the CBO, Caspar Foghsgaard. I'll leave the word then over to you, Per, to go take us through your presentation.
Thank you very much, Maha, and everyone, welcome to this Global Investor Call, and thanks to DNB for hosting this. We are doing this in connection with the very important TMC announcement we now have for our ongoing phase II study in locally advanced pancreatic cancer. And we come back to which was the trigger for the warrants exercise that Maha mentioned, and we'll come back to all the details around that a bit later. But as Maha said, we'll go through the case generally first to update you all on where we are and what we are developing. So, let me just this has all been presented by Maha, so thank you for that. So I have with me John Edminson and Caspar Foghsgaard, who are the CFO and CBO of the company.
I am Per Walday, the CEO. We are developing a non-invasive treatment. This is based on a proprietary ultrasound-activated product that can enhance and target the uptake of therapeutics into specific areas of the body. And what we're doing with this is focusing it now on cancer and primarily now first on locally advanced pancreatic cancer, where there is a real need to get a better uptake of drugs into solid tumors. That is a problem today, getting sufficient drug into solid tumors, and we have a solution for that. On the basis of this, we are building this biotech company, where we use this proprietary agent to really unlock the ability to enhance therapeutics in areas where it's very difficult to treat today in cancer.
Our strategic focus is, as mentioned, a very high unmet need cancer, pancreatic, so we're developing that first. This is all based now on the phase I study, which was in another indication, liver metastasis, but where we saw a four times increase in tumor shrinkage and an excellent safety with our technology. We have now started a phase II trial, the next level trial, in pancreatic cancer, locally advanced pancreatic cancer, and this is where we now have the TMC, the Trial Monitoring Committee, announcement on the safety of the three first patients. We also are presenting today what we have so far of the efficacy responses in those patients. We have patent protection, which is really broad across all major markets, and we have now, with the warrants, the runway well into 2027 and beyond.
What are the key readouts from this phase II trial? An interim read and a final read. We are focusing on pancreatic cancer. That's our first priority. As I said, liver metastasis, that was our clinical proof of concept, where we translated the excellent results we have in preclinical in animal models, where this has been shown excellent results across a number of different tumors across a range of different drugs. We are also doing work in glioblastoma and immunotherapy within the oncology space. We come back slightly to that, but that's not really the focus. Our focus today is to talk about pancreatic.
We're also having some activities in generally CNS, or central nervous system, brain diseases, because of the blood-brain barrier, which protects the brain and makes it difficult for therapeutics to come in, and we can use our technology to target that into certain areas of the brain. And also, a very exciting new development, gene therapy, which has a huge hurdle of trying to get sufficient of the gene therapy into, different organs, and this is also an area where we are exploring the utility of our platform technology. So what is it that we are developing? We call it PS 101. It is a proprietary drug that consists of microclusters of gas bubbles and oil droplets, and they are free flowing in the blood when we inject them intravenously, as you can see on the right-hand figure here...
and we can give this together with standard of care. So standard of care, whatever the patient is receiving, will be given, and we can give an intravenous injection of PS101, and then we can activate that PS101 with ultrasound in the area of the body where we want the drug, the standard of care, to be enhanced, to work better. I'll come back to PS101 in the next slide and how this works, because it's, it's, it sounds a bit like magic, but it's actually a very neat and, and, an understandable technology. The PFP microbubble and the PFMCP droplet, they have different electrostatic charges, so they form, form small clusters that stay together.
And then when we have injected them, and they pass through the body, through the blood and blood vessels, as you can see here in this schematic figure, and we put the ultrasound specifically on the target area. When the ultrasound waves hit these clusters, they get activated, and by activation, it means that the oil droplet converts to gas, and the bubble gets much bigger, and it gets trapped in the capillary, in the smallest blood vessels, where the exchange of medicines, of nutrients, of oxygen, everything happens.
And there they sit for up to 10 minutes, and during that period, we can then change the ultrasound frequency to a lower frequency, which is close to the resonance frequency of these larger bubbles, and when they then start to resonate, they oscillate back and forth like this, and they produce shear waves and streaming and open up the capillaries, and that provides a prolonged, targeted drug delivery, specifically in the area where we have used the ultrasound. And by using ultrasound for this, we also can see with ultrasound where in the body is it that we are delivering this. And therefore, we can look with ultrasound at tumors, and we can use this for tumor treatment.
So our phase I trial, going to clinical to our first experience in patients, was based on a number of preclinical animal model studies with fantastic results in a number of different cancers, including colorectal cancer and pancreatic cancer. The ACTIVATE trial, which we called it, was really a clinical proof of concept, translating that this will also work in man. And the way we did this was. And this is a really innovative assessment of how you do anti-cancer activity evaluation. We used the insonation of only one of the tumors in the liver. These patients had metastasis from colorectal cancer to the liver, and to be included, they need to have more than one of these metastases.
All patients then received standard of care, which was either FOLFOX or FOLFIRI chemotherapies, and then we only exposed one, and everyone get PS 101, of course, but then we only exposed ultrasound to one of the tumors, and then we can compare that tumor with the other tumors in the liver. By this, we get an intra-patient response comparison. To be sure that this was not biased by the radiologist knowing which one has been exposed with our technology, we actually sent it to a central review, which were blinded. They only scored the different tumors. They didn't know which one had been treated. We used two different dose levels of PS 101, and on the right-hand side, you can see the results. The gray bars represent the control tumors.
The colored bars, blue and green, represent the two different dose levels of PS101. As you can see, when we increased from 20- 40 microliter per kg... excuse me, of PS101, in combination with chemotherapy, what you can see is that we get a better response with a higher dose. Also, what we've done in this figure, we've taken all the control tumors where you saw some kind of response. These patients were really hard to treat patients that had been through a number of lines of different treatments and are normally very resistant. But some of them had some minor responses, and if you isolate them, because then you know they're not resistant to the treatment, and those are the ones that you can enhance.
Then you can see within this circle that we can strongly enhance all of this. Four times greater tumor shrinkage we saw in the high-dose PS101 group, when we looked at the responders, and that was, statistically significant, and it should be less than 0.05, not more than 0.05. This is a mistake, as you know. And we saw also an excellent safety profile, almost no effect, whatsoever, adverse effect, and no worsening of the, adverse effect of the chemotherapy, and these results were presented at ESMO last year. So, on the basis of this, we were starting to think, where do we best take this? Where is it really difficult, where is it a really high unmet medical need and really difficult to get, chemotherapy or drugs into tumors?
Pancreatic cancer is the obvious answer to this because they have very dense tumors. I leave it up to Caspar to talk a little bit about pancreatic cancer and the high unmet medical need, and why our technology fits so well with this disease.
Thank you, Per. So, Exact's whole purpose and vision speaks to improving the life of cancer patients. Our mission is to change the global standard of care for exactly the patients with locally advanced pancreatic cancer. Here in the slides, you see the huge challenge, the unmet need, so please do remember this slide and understand why we're on this mission. Pancreatic cancer is the 10th most common cancer. However, there are no proper treatments out there, so the result is what you see on this slide. Every third cancer death is pancreatic cancer, and it's now nearing the 2nd position. Nothing significant has happened in the survival in pancreatic cancer in the last 30 years, so we are on a journey to change that. Next slide, please.
As Per mentioned, we started off with liver mets of colorectal origin, and now we have moved to first-line locally advanced pancreatic cancer, adding our proprietary drug, PS101, on top of standard of care. First of all, as described, there's a huge unmet need, and secondly, there's a perfect technology match. The challenge is that in general, less than 2% of drugs reaches their target, but specifically for pancreatic cancer and dense fibrostroma, it's very, very difficult to get the medicines in, and with PS101, we try and change that. We have a very good clinical approved concept that Per demonstrated earlier, and we have amazing clinical work done together with the world-renowned clinical Daniel Von Hoff from TGen in Arizona. Last, our ultrasound equipment is well-suited to reach the pancreas, so we're in a very good position to succeed here.
That's why we have gone for LAPC in our phase II ENACT trial. Next slide, please. So with PS101, we in LAPC, we aim to increase the conversion to resectability, so making the patient available for surgery. We look to treat the borderline resectable, locally advanced unresectable patients, which make up 30%-40% of the overall pancreatic patient population. And with that, we going from non-resectable, resectable, we look to more than double their median overall survival from around 16 months to around 3 years. So a huge difference for the patient. Next slide, please. So looking at the opportunity and the incidence, so in both in the U.S. and in the E.U., which will be our, our main focus areas, initially, there are around 70,000 individuals per year that get pancreatic cancer.
35% of those have a LAPC, which we address here in ENACT, and yeah, as a side note, more than half have metastasized, so it's outside. 70% of the ones that we treat in LAPC are treated with FOLFIRINOX as standard of care, so that's what we're using in ENACT trial. And all in all, that brings us down to 35,000 addressable patients, which equates to a potential blockbuster opportunity, given the price of oncology drugs. Later on, if we want, we can expand outside FOLFIRINOX to cover the remaining 30%. Thanks.
Okay, so, then, going back to me, the way we do this is... And, and the nice thing about this really is that we can enhance standard of care, and we can enhance the first-line standard of care. So we go in, not as you normally do with oncology treatments at the late line, but we actually go in first line. Newly diagnosed patients that has not yet received any treatment, they get in our ENACT study, what is standard of care with our technology, PS 101, and the acoustic cluster therapy on top of that. This study is the first study we're doing in pancreatic cancer.
It's a 25-patient study that we want to have at the selected dose, and the planned geographies are in the U.S. and Europe, and we have now 10 activated sites across the U.S. and U.K. The way this is done, because this is the first time we use our technology in the pancreas, which is a more fragile organ than the liver, is that we do, we have agreed with the FDA to do a staggered start of the first three patients. So to monitor the safety for 14 days, and then for seven days, and then for a total of 28 days at least, and two treatments at least for all three patients, and then have the experts in the Trial Monitoring Committee to go through this in a safety review and recommend what to do further.
Their recommendation, which I will come back to, was to increase the dose even further to 60, because the safety is so clean. So we're gonna do that to try to optimize to get as much value as possible out of this study, and there will be a new safety review in the first half of 2026 of 60. And then we include 22 participants on the selected dose of PS101, plus what is called modified FOLFIRINOX, which is a slightly less toxic dose, which is mostly used on FOLFIRINOX, which is a combination of chemotherapies, and we expect to have an interim analysis in the mid of 2026, and the final analysis from this study in the first half of 2027.
So looking at what the Trial Monitoring Committee, TMC, what they recommended, this was scheduled, as I said, after three patients agreed with the FDA. And overall, early safety results support continued dosing and trial as planned. Nothing unexpected have happened. Adding PS101 and the treatment with the ultrasound equipment to the standard of care chemotherapy, has shown no added safety concerns. So no added safety concerns whatsoever with the technology so far in these three patients. It was actually four patients, because one discontinued because it didn't. That patient didn't tolerate the chemotherapy, so we had a bit more. Had nothing to do with our technology, actually. But we had a bit more safety data than that, than just three.
The recommendations was that the study can proceed in accordance with the current protocol, and that we should increase the dose to 60 microliter per kg. And that patients also now with borderline resectable disease, which were not allowed in the first safety cohort, because this was the first time in pancreas, they can also now be enrolled. This is a subpopulation of the locally advanced, which are closer to maybe achieve a resection. We also got the efficacy results out of the two first patients. We haven't reached the first efficacy time point for the third patient yet, but for the two first, we have. We're measuring one important biomarker, the only FDA-approved biomarker to monitor pancreatic cancer disease, and that is called CA 19-9. Early and substantial CA 19-9 decline is strongly associated with improved survival in locally advanced pancreatic cancer.
That is well known, and that is why it's an important biomarker for this patient population. Normally, what you say is, if you have more than 50% decrease of CA 19-9, which represents broadly the tumor burden of the patient, then that's a strong response, and we had more than 85% reduction in CA 19-9. We also had tumor shrinkage in both patients, 46% shrinkage in the first patient at 16 weeks, and 90% in patient number two at 16 weeks. This means that patient number one is what is called a responder, more than 30%. We will have one more reading from patient two, so we'll see whether that also becomes a responder or stays at a stable disease.
But at the least, with a good reduction and with a strong response in CA 19-9. The very nice thing about this is something that doesn't happen very often, is that the patients who have locally advanced, not borderline, but locally advanced pancreatic cancer, not borderline resectable, I mean, that they actually get resected and that they get resected successfully with what is called an R0 margin. That is, no tumors in the margin of the resection of the tumor and clear lymph nodes. And this patient one was converted to surgical tumor resection, and there was a completely successful resection with completely clear lymph nodes and surgical margins. So this study couldn't have had a better start than this. So a very good start to our ENACT clinical study, and we really look forward to getting in more results from this study.
Preclinical. Just going through this very quickly because there is an opportunity to expand the pipeline quite dramatically. CNS cancer is a Blood-Brain Barrier. We have had some results in glioblastoma that was presented last year. We have some encouraging data that was presented at SNMMI conference in 2025. We had a press release on that. Immuno-oncology, combining this with checkpoint inhibitors, we have some early signals that are promising, so we do some further evaluation, and all those data were presented at CICON in 2025, the Cancer Immunity Therapy Conference. And there is another area which is really of interest, gene therapy, non-viral gene delivery, which is very hard to do. Everything ends up normally in the liver, but this is potentially a way to actually deliver more genes into a specific organ or specific tissue.
We have some exploratory work ongoing to see what we can do in that area. And then I leave it to John to talk briefly about the financing and the use of proceeds.
Thank you, Per. The ongoing warrants exercise that we have right now has a potential of up to little more than $6 million or NOK 62 million. Already for now, we have secured more than 75% of that amount with the support from our major shareholders, GE HealthCare, Investinor, Sundt and Canica. What we will do with the proceeds from the warrants? So is to ensure the execution of the ENACT study, and it will take us through the major readouts of the interim and the key results expected in mid-2026 and the first half of 2027, respectfully. In addition, the proceeds will be used for the continued non-clinical activities that support our primary focus on locally advanced pancreatic cancer and other expansions in that area, as described earlier in the presentation.
Furthermore, we will continue the expansion of our IP portfolio across other applications as well. And all in all, the warrants will secure us well into 2027 for the company to reach the major data readouts from the ENACT study. Per?
Thank you, John. So this was all planned. I mean, it was part of what we wanted to do in the financing. We set up these warrants, which were to be possible to exercise after the first safety readout, when we would know that we could treat pancreatic cancer from a safety perspective. So it was a risk reduction in that sense. We have delivered what we said we were going to deliver since the December 2024 financing. We have completed the ACTIVATE trial, and this was presented at ESMO in 2025. We have done the start of the phase two ENACT. We had the IND approved by the FDA. We had the CTA approved by the MHRA in the UK, and the first patient dose and initial safety readout now of three patients.
And then we have had some technology expansion presentations as well, and really important updates on IP, where we have IP not only on the clusters PS101, but also important applications in major markets and important markets, including treatment of pancreatic cancer. We have a strong potential news flow in 2026. The phase one ACTIVATE trial will be published. We have a safety readout. We'll have the first patient dosed in Europe. We will have the interim readout, and then the enrollment completed, all of this in 2026. And we will come with technology expansion news as they appear in our collaborations with different academic partners. So our long-term strategic ambition, win in locally advanced pancreatic cancer and beyond.
We focus on this first, LAPC with PS101 plus modified FOLFIRINOX, and then to expand to other standard of cares to cover the 30% that are not receiving modified FOLFIRINOX, and also potentially into oligometastatic patients, those who only have a few metastasis in the liver, because we know we can treat liver. And then, the next wave is more oncology into GBM and immune oncology to the brain cancer, and then platform expansion as a third wave into gene therapy and other CNS applications. So to wrap this up, key takeaways from today, we have strong clinical proof of concept. We have 4 times increase in tumor shrinkage when we add our technology upon standard of care. We see really encouraging early tumor responses in the now ongoing ENACT trial. It's early, but really encouraging in locally advanced pancreatic cancer.
We have GE HealthCare as a vetted device and supply partner, and GE HealthCare is No. one medical equipment company globally. We have broad, granted patents which cover across major markets, including U.S., and we've seen strong execution. We've shown that we can deliver, and we have a rich news flow in the coming year. Now, with the warrants, we have a financial runway through the major readouts of interim and key results. Thank you. Maha, over to you.
Thank you, Per. Just as a reminder to everyone joining the call, you can post questions using the Q&A tab. We have received a couple of questions. Let me start off with the first one. As far as I know, the most common reduction for biomarker CA 19-9 is between 50%-70% when you use FOLFIRINOX alone. So your results are much better than the normal response so far. If you get a similar result for the interim readout, how would such a result be viewed in the cancer community?
I think that you can... You, you need to look at the biomarker in context of what else you find in the patient, of course. The biomarker is an important signal that you, that you follow when you often do a disease monitoring. But you will also need to look at, so what happened with these patients? Did they have a strong shrinkage of the tumor? Were some of them converted to resection? Because that is really what we're trying to achieve here. If you can go, and convert patients from, life-extending treatments, where you try to give something to sort of slow down or, or regress the disease, and if you can convert some of those to actually what is potentially a curative treatment through resection, then this is really important, and that is why we're focusing on locally advanced pancreatic cancer.
They only have cancer in the area of the pancreas, and if we can shrink that sufficiently, they can potentially go over to become potentially curative. At interim read, if all of these point in the right direction, then that's a fantastic results, and we will need to discuss how we, if we want to, at that stage, open up to a randomized study, for example, and start discussing with the FDA how to take this to the market as well, and to the patient as quickly as possible.
Thank you. We have a question related also to the tumor shrinkage. So what is the typical tumor shrinkage you can expect to get when you only use FOLFIRINOX to treat pancreatic cancer?
So it's a, this is a binary number when you're looking at it, because you say that you either have stable disease or you can have progressive disease, stable disease, partial response, or complete response. And these are all just binary hurdles or thresholds. So if it's more than 25% increase, it's progressive disease. If it's between 25% increase and 30% decrease, it is stable disease. If it's more than 30%, but not completely disappearing, then it's partial response. And normally, when you talk about tumor response, you talk about those who have partial response or complete response, that is, all tumor disappear completely. And the level of that is, if you look into the literature, and we've also done advisory with experts in the field, it is approximately around 30% response rate.
So 30% of the patients will get the tumor shrinkage that is more than 30%.
Thank you. I see we have another question. When in 2026 can we expect update on the preclinical work you are involved in?
So I think this is something that we don't guide on, specifically when things are going to happen, because these are collaborations that we have with academic institutes, and we don't have full control of all the timelines on this. And these updates will come as they appear. But we've shown that we're coming with the updates on this every year, but exactly when I do not want to guide on.
Thank you. I don't think we have any further questions at this point in time. So, thank you so much, Per, John, and Casper, for the great presentation. And, to everyone joining the call, if you have any further questions, please feel free to reach out to either the management team or, if it's about the warrants exercise, you may also reach out to us at DNB Carnegie, and we'll be happy to help you out. Thank you so much.
Thank you. Thanks, Maha.