Circio Holding ASA (CRNA) Earnings Call Transcript & Summary

Welcome. My name is Magnus Jäderberg. I'm the Chief Medical Officer of Targovax. I have the pleasure today to present to you our hot off the press data in mesothelioma, and specifically, malignant pleural mesothelioma. So this is a highly malignant solid tumor disease in the lining of the lungs. And one of the real diagnostic challenges with this disease is that the symptoms of the disease comes very late in the disease process, which means that when you've finally diagnosed a patient, very often, in fact, in most cases, it's too late for surgery, that all we can do as physicians is to provide chemotherapy. Now there is one combination, pemetrexed/cisplatin, that is the standard of care for these patients, and it's been around for about 15 years, so nothing new has actually happened in those -- that time period. And that's the main reason why we have decided to study this disease when we add ONCOS-102, our oncolytic virus to standard-of-care chemotherapy. Now the trial that we have conducted, and where we're now releasing the first set of data, is this one. It's a small randomized trial. We're specifically looking at patients who are not just naive to chemotherapy, but also those who have had several courses of chemotherapy. So that could be 1, 2 or 3 different cycles of different kinds of chemotherapy, all the same chemotherapy indeed. And what we did there was to start with a safety lead-in, so we combine the chemotherapy with ONCOS-102 just to make sure that we are not seeing anything that could be worrying. We had a good review with an independent safety group. And after that, as you can see here on this slide, we had a randomized phase where we ended up with 20 patients in the experimental arm receiving ONCOS-102 and chemotherapy and 11 patients just receiving chemotherapy that we call the control arm. Now what are the data like? Well, I wanted to tell you first that when you look at the 2 patient groups, it's important to compare, of course, before you analyze data. And one thing we did see was that there was quite a big difference between the 2 groups of patients in terms of their tumor, the malignant pleural mesothelioma. Firstly, there were more lesions on average in the experimental group; secondly, those lesions were larger; and thirdly, if you look at the patient in totality, more patients had advanced disease in the experimental group compared to the control group. So there was a little bit of a difference in the sense that the experimental patients were actually sicker than the control patients. Further down the slide, we are presenting some clinical data. Firstly, we're talking about progression-free survival. Now progression-free survival is a measure of time from the point when the patient receives a treatment until that patient has either progressed, meaning the tumor has grown further, or the patient has died. And in first-line disease, there is a close to 2-month difference in favor of the experimental group. I should say that these are early data, a lot of the patients are censored, that means that we will later on get further updates. But at this stage, we're quite excited actually about the fact that there is this difference and they can indicate that patients may actually benefit from adding ONCOS-102 to chemotherapy. Another way of looking at clinical response or clinical efficacy is to look at what we call the overall response rate. And overall response rate means that we're looking at the size of the tumor. And after treatment, has that tumor grown further? Has it stayed the same? Or has it shrunk or disappeared? And ORR represents those patients whose tumor has either shrunk or disappeared. And in first line, as shown here, about 1/3 of the patients have actually had shrinkage of the tumors. DCR, or disease control rate, that follows, is one where you also add the patients who had stabilization of the disease. And 90% in the experimental group and 83% of the control group have very good figures in this highly malignant, fast-growing cancer disease. In other words, patients are really benefiting from this combination as suggested by these preliminary data in a rather small trial. After that, we're looking at second-line patients and the progression-free survival of 4.3 months is pretty well what one expects. There's no figure yet for the control group, and that's because we're so early in the follow-up of patients that we haven't actually reached a point where we can calculate the median progression-free survival for the control group. An ORR of 11% in the experimental group is pretty well what you expect in clinical practice. The 60% is a little bit of a surprise. It's not in line with what we see clinically or have seen in publications and represents a chance finding in very small number of patients, as you can see, about 5 patients, and that's what sometimes happens in small randomized trials. Now how do these data compare when we look at how the data has been published. What I'm trying to do here is to show you the activity when it comes to response rate and progression-free survival all in one slide. And we're excited because there is another way here that we can see that there is a signal of a benefit for patients receiving our experimental treatment, which is ONCOS-102 plus chemotherapy. Maybe just to explain the left-hand side of the slide, you'll notice there's a trial called the Vogelzang trial. Well, in fact, the Vogelzang trial was a very large trial conducted about 15 years ago, and that actually formed the basis for the approval of pemetrexed in this indication. And you may wonder why there is sort of a shaded area between 40% and 20%, and that is because the authors who did the trial and published the trial has suggested a 40% response rate. But in fact, when the FDA reviewed the trial, they disagreed with the authors. It's quite unusual, but they did. They still approved the drug, but they felt that the true response rate was actually closer to 20%, and that's why we have this gray shading. And on the right-hand side, you can see there the experimental group in the Targovax trial, represented by the blue bubble, being a bit of an outlier. And as I said, another reason why we are encouraged by these data and look forward to further follow-ups. So with an immune therapy, we're always interested in what the patient's immune system will do when we inject ONCOS-102, which is an oncolytic virus. And this slide then shows how those patients responded, and specifically with an immune cell called CD8+ T-cell, so this is an important -- one of the most important immune cells when we talk about cancer disease because it's able to kill cancer cells. And so what this slide shows is that when we look at the fold increase of that important immune cell and look at the response clinically, represented by the different colors, so the dark blue colors represent partial response; the light blue, stable disease; and the red bars represented by progressive disease. You'd see a rather nice association here between those patients who had an immune response of this important immune cell and those who responded clinically. And of course, that's extremely important and very exciting for me as Chief Medical Officer of this company to think about what we next can do. So there are some rather nice bits here in terms of just looking at the average increase of the experimental group of about 3.3 fold compared to no difference in the control group. So mechanistically, I feel that we have a good reason to go further. And that's very much the rationale for now discussing our next trial in the same disease. This is a trial of malignant pleural mesothelioma in first-line patients. So these are the patients who never received chemotherapy. There is a very good immunological and clinical reason for combining our current treatment, which is chemo and ONCOS-102, with a checkpoint inhibitor. As you know, checkpoint inhibitors have been around for about 10 years. They've made a massive inroad in a number of solid tumors. And so we are proposing that we should do a trial with about 100 patients in first-line disease where we combine ONCOS-102 with chemotherapy and a checkpoint inhibitor. And so we will start with the safety lead-in phase, where we make sure that, that combination is well tolerated by patients. And that will be followed by a randomized phase where in one arm, you'll have that experimental treatment. In the other arm, you'll have the checkpoint inhibitor plus chemotherapy. So in summary, we are very excited about the fact that this combination is well tolerated. It was actually the primary endpoint of the trial. So that's an important point. When we look at the clinical activity, we see some interesting things here that makes us excited. Firstly, that there are some emerging data that will point towards the benefit of this combination. And actually, not just in the trial, but also looking at the comparison with historical data, it looks like we may be on to something encouraging and interesting. We have good immunological responses coming through, including PD-L1 expression. And we have the important association, as I said earlier on, between immune response and clinical response. So what are we doing next? Well, as I said, we are planning now to do a first-line trial. There's a good rationale for combining with a checkpoint inhibitor, and indeed, we are now at a fairly advanced stage talking to a big pharma partner, who has a checkpoint inhibitor, about collaboration for such a trial. So thank you very much for listening.