Oncopeptides AB (publ) (ONCO) Earnings Call Transcript & Summary

Welcome to the Oncopeptides conference call. [Operator Instructions] Today, I'm pleased to present CEO, Jakob Lindberg; and the CFO, Anders Martin-Lof. Please go ahead with your meeting.

Thank you very much and good morning, everyone, or in the middle of the night in the U.S. The aim of today's call is to go through a bit of data that we showed and disclosed at the European Hematology Association Meeting. Technically, the meeting is not done yet, but we have now gone out with all the information. I will not go through all pieces of data that we disclosed but rather the key topics. And that will be a little bit of preclinical data, but then, of course, the main focus is the final data set from the HORIZON trial. That is also our first pivotal trial that is the foundation of the registration to the FDA later this month. Please go to Slide #3. Thank you. This is a slide you all have seen before, and it shows the technology platform that forms the foundation of the company. It shows the backbone of the peptide drug conjugate structure that we are running with, and the 2 enzymatic motifs that in the carrier structure, that is the 2 amino acids that bind to the toxin, actually delivers a very high load of toxin into cancer cells and also drives the whole molecular fingerprint of the construct. As you are aware, the key motif is the peptidase motif where, actually, this structure binds the aminopeptidases inside the cell, which leads to a very specific micro distribution of the toxin inside the cancer cell. And that is -- that drives the whole delta between us and alkylators as a class. Next slide, please, Slide #4. What we have stated before, and I'm going to come to the data on this slide, is that aminopeptidases are intrinsically linked to malignancy in the transformation process. We see as patients progress in their disease, as the clones or the cancer becomes more and more vicious, that aminopeptidases, in general, the activity of them goes up. It's a very complex pattern. And a poster from Finnish Institute of Molecular Medicine and Caroline Heckman showed some great data on patient samples in myeloma. The key finding here is what you see to the left in this chart. The y-axis is a logarithmic scale disclosing how potent various molecules are at killing the cancer cells. The lower, the better. So it's a bit counterintuitive, but the lower number means that you may need less molecules to kill the cancer cells. And within each column for these drugs, melflufen, melphalan, selinexor and bortezomib, for example, you then see patients that are newly diagnosed, that is NDMM; and patients that have become relapsed/refractory, RRMM. And as you can see, the potency of melflufen increases in more advanced disease. And this just highlights the whole aminopeptidases story and how important it is to target this class of enzymes to actually treat hard-to-treat patients. And for anyone that is technically interested, this poster will be possible to look at on our website in great detail, and we are happy to take more questions around it, of course. Next slide, please, Slide #5. This is another data set that was disclosed by Ana Slipicevic. And this actually highlights how different we are from alkylators as a class. Now it might look like a complicated chart, but I'll go through it. First, you have 2 sets of lines in the graph: the lines to the left belongs to melflufen; the lines to the right, belongs, in this case, to an alkylator, melphalan. The red lines is just a myeloma cancer cell. And already, first, you see, of course, that the red line for melflufen are far off to the left of the red lines of melphalan, meaning that melflufen is much more potent. Please note, it's a logarithmic scale along the x-axis, so the difference is almost 100x. The next one is, if the same cancer cell gets a deletion in what is called p53 or mutation, this is a very common cancer mutation that makes the cancer exceedingly hard to treat. It makes the cancer -- I wouldn't call it, immortal, but it becomes -- it's a machinery that most cytotoxics use to kill the cancer cell. And alkylators use it all the time. And as you can see, if the cancer cell then, at the defense, mutates or deletes p53, you can see that melphalan, in this case, almost becomes inactivated. It has a very hard time killing these cells. With melflufen, you see no difference. What this means is that we don't kill the cancer cell in the same way as other alkylating agents. And this just highlights that this peptide drug conjugate platform belongs to a separate class that behaves very differently from a molecular point of view than alkylators as such. We have been talking about this a long time, but this is a very solid data set. And the same is true here. This poster will be found on our website. You can download the poster, and we're happy to take more detailed questions. So to the HORIZON data set. Please go to Slide #6. Thank you. The rationale for this whole study is, of course, that myeloma patients have a cancer that is incurable, and at some stage, become resistant to all existing treatment modalities. At this stage, you need to switch class to even have a chance to keep the cancer at bay. Our early study, O-12-M1, showed very promising activity in late-stage myeloma patients. And hence, we started the HORIZON trial to explore what melflufen, in combination with dexamethasone, could do for these patients. What is very important to note is that, when we started this trial, triple-class refractory patients was something that was found very late in the treatment paradigm. Today, when we do demand studies, actually, we see an equal amount of triple-class refractory patients at first relapse as a third or later relapse. That is, we see the same amount of triple-class refractory patients in second line, in third line and in fourth line. Of course, the patient population is bigger in second line so the percentage is lower, but in absolute amounts, it is equal. What this actually means is that we have front-loaded the treatment algorithm so much that the question that this study addresses is really, really important because we have a significant group of patients that already, when they are supposed to get their second line of treatment, are, on paper, out of treatment options. Next slide, please, Slide #7. When we started this trial, and the final result includes 157 patients, you can look at the box to the left, adult patients with. At this stage, anti-CD38 therapy of daratumumab had recently been approved, so we stated that patients that were refractory to pomalidomide or anti-CD38 therapy, i.e., daratumumab at the time, could be included in the trial. As the trial progressed, of course, daratumumab became part of standard of care, and the vast majority of patients in this trial had both become resistant both to pomalidomide and anti-CD38-based therapy. And that is the data that we're going to show today. And the primary endpoint that you can see to the far right of this picture is ORR, or overall response rate with a plethora of secondary endpoints in the study. And as you can see in the middle, melflufen was given once monthly as a 30-minute infusion. Next slide please, Slide #8. Once again in this study when we have the final results 157 patients had been recruited when we finished recruitment the 14th of October last year. An at the time of the data cut the majority, 83 of the patients had discontinued the therapy. The most common reason for discontinuation was of course that the cancer had come back. These are very ill patients. And we have a median follow-up time of 14 months, which means that the study result is very, very robust at the time of the analysis. Slide #9. Thank you. Here you see breakdown of the patient groups. The ITT is the full patient population which is the full column here, 157 patients. And as I stated before, the majority of the patients are refractory both the anti-CD38 therapy and pomalidomide and that is found in the middle column with triple class refractory patients. There of course also they're refractory to [ pomalidomide ] inhibitors and this was 119 patients out of the 157. I want you to look at the number here because this number has gone up as we have continued the trial and this is one of the bigger deltas to the results we reported at ASH. And that is that you see EMD at study entry, i.e., patients with metastatic myeloma is now up in -- at 42%. It's almost that you can say it's half the patients. Of course it's 43%, it's not full 50% but it's a very large number. And it really represents the largest clinical trial cohort of myeloma patients with metastatic myeloma. Something -- and this is the patient group with enormously bad prognosis. So one should have that at the back of your mind when you look at all the data we have, that our data is as good as it is despite the amount of EMD patients. And then, of course, we also show data specifically for the EMD patients, that were 55 in total in the trial, since this is a group of special interest. Next slide, please, Slide #10. And you can see here the response rates that we disclosed earlier this spring, the top line results, where we had a 29% response rate overall in the ITT population; 26% for triple-class refractory; and 24% for the EMD group. Please note that for the EMD number, this is more or less in -- really in patients that really have -- got their EMD at relapse. This is more or less the highest number reported. You will find scattered results of a few patients where the numbers are higher, but they normally include patients that had EMD at diagnosis, which is a completely different disease, actually. Next slide, please, Slide #11. This is a key graph. This is what is called a swim lane. So here, you see how long the patients have been on therapy and how long they have been progression-free from their disease. These are all the responding patients. And 0 means the time point when they received the first dose in the trial, and then you see how long they have gone. If the patient has an arrow in the end, it means at the time of the data cut, they were still disease-free. If there is an x, it means the time point when they progressed in their disease. I really urge you to look at this swim lane, and when you compare drugs, because this is the key clinical outcome, see how long patients really are disease-free on melflufen. This is a fantastic swim lane. And there has been some discussions regarding that the duration of response number went down to 5.5 months. In reality, nothing had happened since December. The reason is that we have so many extramedullary disease patients now that what is called the time to response has gone up. The time to response is the time it takes from the first dose until you can measure the response. And in this graph, that is depicted in the light gray and the light green. That is stable disease and minimum response. And you can see that it goes all the way up to 7 months here. Most of these patients are EMD patients, meaning that it took a long time to verify that the metastases in the patient had gone down. It requires imaging such as PET or CT, and these are not done on a regular basis. It means it drives up the time to response number. But from a clinical point of view, this doesn't matter. But as time to response goes up, it means duration of response technically goes down, even though in reality, nothing had happened. And this is what we see here. And once again, when you compare it to competing drugs with much less EMD patients, you more or less see that the time to response is around 1 month or even less than 1 month, between 0.75 to 1 month. And you don't see a single patient with a lower time to response than 1 month in this graph. So going to the next slide, Slide #12. This is, of course, why now the numbers are fairly high. The median time to response was 1.9 months. It's almost at a median a month later than for our competitors. And as I said, that is clinically completely relevant. The median duration of response was 5.5 months, but then the median progression-free survival among responders was 8.5. So duration of response plus time to response is your progression-free survival for responders. So if you look at the median PFS for responders, that's the real number, and that is a very good result that we are very happy about. And of course, this is also the number that we go to the FDA with. Next slide, please, Slide #13. Here, you see the progression-free survival for all patients in the graph. And you can see that it is around 4 months for the full population in the triple-class refractory group. But here, you can see how poor the prognosis are for patients with extramedullary disease. It's 2.9 months, very short. But now if you look at the PFS among responders, once again, you see that it was 8.5 for the full population as well as the triple-class refractory population. This is depicted in the bullet on this slide. But you see it was actually 17.3 months for patients with extramedullary disease, the hardest to treat patient group here. This is a fantastic result. Next slide, please, Slide #14. And the survival numbers tell very much the same story. These are very ill patients. You see that the median overall survival, both for the total population and the triple-class refractory group, is just short of a year. Patients with extramedullary disease, they don't survive more than 0.5 year as a median, just highlighting their poor prognosis. But once again, if you look at the median overall survival for responding patients, depicted in the bullet on this slide, you see that it is around 17 months for both the overall population and the triple-class refractory population; and it's 18.5, the same for patients with extramedullary disease as the other response groups. This just highlights that the response is clinically meaningful for this very hard-to-treat patient group. As you can see, 18.5 months is very different than the 6.5 for the median number for EMD -- when you include all patients with EMD. Just saying, if you respond to melflufen plus dexamethasone with extramedullary disease, the signal is that this is a highly clinically relevant response. And once again, this is a patient group with no remaining treatment options. Next slide, please, Slide #15. The safety profile is consistent with what we have talked about before. And the main comments are in the bullets to the right of this slide, where we had -- hematologic-adverse events were common, non-hematologic events were infrequent. 70% of the patients could maintain the full 40-milligram dose, but 58% of patients had either dose reduction or a dose delay. What that number tells you is that most patients have 1 cycle where the cycle is longer than 28 days. It needs to be longer by 3 days to be dose delay. So that -- you basically schedule the dose for 1 week later. So it has a 35-day cycle at some point. And half the patients had a serious adverse event in the triple-class refractory group. Next slide, please, Slide #16. So in summary, you can now see the 3 data sets that have been fully reported in triple-class refractory patients. And just to highlight then the same differences as before. Here, you can see our long time to response by looking at the third line, median duration of response and median PFS for responders. You see that the other drugs have more or less the same number, up to 1 month delta between the 2. And we sit with the full 3 months. And as I've stated, this is because of the extramedullary disease patients, that it takes longer to do the imaging to verify response. And you also see the share of patients with EMD where we are -- not fully at the double the amount, but almost a double, at 42%, when the others are at 22% and 23%, respectively. And that's the hardest to treat patient group. The other differentiating factor here is, of course, the non-hematologic toxicities, where all these 3 drugs are good when it comes to infections. And that is the only grade 3, grade 4 toxicity we have in more than 5% of the patients. While both XPOVIO and belantamab -- in the case of XPOVIO, have a lot of gastrointestinal and metabolic side effects, grade 3, grade 4; and belantamab, of course, has the blurred vision, that is keratopathy, the ocular toxicity. In our mind, obviously, it's our mind, not the regulators' mind, it means that out of these 3 drugs, we have the best risk/benefit profile right now. But obviously, we need to convey this to the regulators, and that is what we're about to do with the submission. And hopefully, we also will be successful. And you see that the patient studied in these 3 trials are very similar. We have 119 patients in the triple-class refractory group; XPOVIO had 122; and belantamab, 97. Next slide, please, Slide #17. As to the news flow, it is consistent with what we have said before. We had the last patient in an OCEAN. We had the data update at EHA now, and we're going to have the NDA submission before the end of the quarter. But obviously, it hasn't happened yet, so we haven't done the checkmark there yet. In the third quarter this year, we're going to have the first patient in the amyloidosis study. As you remember, we had to put that study on pause due to COVID-19, but it has now been unpaused. And we're going to have the first patient in the expanded access program or early access program in the U.S. In the fourth quarter or at the beginning of next year, we're going to have a potential accelerated approval in the U.S. Once again, we don't know the exact date, but it is somewhere between December and February if nothing negative happens along the way; and of course, in conjunction with that, also a U.S. launch. In the fourth quarter, we will have the first patient in a LIGHTHOUSE. Might be earlier, but we'll see. Probably not because we're going to -- we will be able to start everything after the summer, and there are not many weeks once the vacations have ended in August when the rest of the world has vacation compared to Sweden. And then, of course, in the first half of next year, we will have the top line results from OCEAN, last patient in an ANCHOR and last patient in a BRIDGE. ANCHOR and BRIDGE are also 2 studies that we had to pause due to COVID-19 but have now been unpaused. For this -- with this, I thank you very much for joining, and I open the floor for questions and answers. Thank you.

[Operator Instructions] The first question we will have from Patrik Ling with DNB Markets.

Just one short question. On Slide 10, when you presented the overall response rate, those were the investigator-assessed response rates. But you have already in March published an Independent Review Committee response rate. Do you have or will you have any independent review committee evaluation of the other results, like duration and efficacy and so on?

So we have both the -- they both have the response plus the progression events. So yes, we have basically PFS, duration of response and response rates as part of the Independent Review Committee as well, yes.

And the duration of response that you presented today, is that the investigator-assessed? Or is it the Independent Review Committee-assessed?

All of this is -- sorry, all of this is investigator-assessed since that was the primary endpoint of the study. But you're absolutely right that the regulators, of course, look at the Independent Review Committee data. And it's completely consistent. So -- and as you know, the Independent Review Committee data is actually slightly better, including duration of response number as such. But as I hope I conveyed today, that number in itself doesn't say much because it is the whole swim lane that is the relevant portion, and there are very small differences actually to the benefit of the IRC data set rather than the investigator-assessed.

The next question is from Erik Hultgård from Carnegie.

Do you expect to have an ODAC meeting for melflufen? And if so, at what time point in the regulatory process will you know what date it will be?

So we do not expect an ODAC, but ultimately, that is something that we don't control at all. But looking at the history in myeloma, there are 2 drugs that have had ODACs, and both of them had it because of non-hematologic toxicity, a category where we are actually very good. And that was FARYDAK, the HDAC inhibitor due to gastrointestinal side effects; and it was selinexor due to metabolic and gastrointestinal side effect. So based on that, we don't expect it, but it's not -- it's totally out of our control. If we have one, there are no rules that guides when the FDA makes that decision, except that it would then happen during the review process when they have made up their mind on that, to call for an ODAC. So there's no rule of thumb, except during the review process, which I know is not much of a guidance, but that is the best guidance I can give if that were to happen. But we don't expect it.

The next question is from Philippa Gardner from Jefferies.

Jakob, I was wondering -- I think at ASH, you gave some information on the median duration of treatment. I was wondering if you can give us any updated numbers on that. And then I was just wondering if you can maybe comment on sort of dose intensities in melflufen in respect of how many patients have skipped or interrupted doses in the trial.

So if we do the dosing, as I said, 70% of patients could maintain the full 40-milligram dose, meaning that only 30% had a dose reduction, which is actually a good number. When it comes to dose delays, that is roughly half the patients. If you go to -- in this deck later, Slide #15, again, you can see that 58% of patients had a dose delay or a dose reduction. So -- which is still a very good number. The majority of those that had a dose delay, which then is roughly 1 in 2 patients in the study, they had it once. It was uncommon that it happened more than once. So net-net, I can provide you -- I don't have it at the top of my head now, the dose intensity. But it is a very good number, the average dose intensity. I'll make sure I e-mail that to you after this call. Sorry for that, that I don't have it from the top of my head.

The next question is from Viktor Sundberg from ABG.

So first of all, I just wanted to hear if you have any updates from the FDA process, basically, what we are waiting for there before you can file at the end of June, as you have stated before.

So basically, we have already booked the date with the FDA. When you submit the file, there needs to be a person on the other end. It's not like you send an e-mail. It's already booked. And we have also scheduled -- we have tentative dates for meetings with the FDA post submission already booked. So we are very much on track to deliver on the timeline that we have communicated.

Okay. And a question on the OCEAN trial. So you communicated that you expect results to come in the first half of next year instead of the end of this year. Could you -- do you have any more flavor on why that was and maybe how we should interpret that data? If you think it's positive? Or...

Yes. I mean -- so basically, there were 2 things that had a slight deviation compared to the original plan. We had a slight increase in patients that is what is called permanently censored, that is that they can never have an event. The most common reason was that they initiated their therapy due to that the investigator claimed that the patient had a disease progression, and then it turned out that we cannot verify that disease progression with lab data, and the patient has already initiated the next therapy. Now if the most reasonable assumption is, of course, that this patient actually had progression, so there is a sensitivity analysis around that in the statistical analysis plan. But for the hard event number, that means that we sort of lose -- we leak patients to that category. This is very common in myeloma. It was just a small deviation. But actually, small deviations make a big difference when it comes to these timings. The second one was, of course, that patients stay longer on treatment that we initially expected since pomalidomide plus dex is very well studied in more than 1,000 patients in various randomized settings. We don't know, of course, where this longer treatment comes from. Does it -- is it derived from patients on pom? Or is it derived from patients on melflufen? But from a probability point of view, it is much more reasonable to assume that pomalidomide behaves as the historical average because, there, we have so much data, while melflufen probably can surprise because you have a smaller database to support the melflufen treatment duration. So net-net, we see this actually as a positive in terms of what type of result the study can give. But obviously, we don't know because we only sit on blinded data. In total, this resulted in a 90-day delay according to the models to reach the 339 events, compared to the original plan.

Okay. So there's no difference in the way that they were treating these patients with pomalidomide compared to the previous studies or in the inclusion criteria and so on that you would quite know?

No. I mean -- so there is a difference compared to the -- when we did the study, we did -- the whole statistical foundation was based on 2 studies, right, O-12-M1 and MM-003. Those patients had roughly 5 prior lines of therapy. In OCEAN, we would have roughly 3 prior lines of therapy. But we did that calculation when we did the model. So -- and if you look at that, there are plenty of -- there's plenty of data around pom-dex, where pom-dex should have roughly 5 months of progression-free survival in that patient group if they're [ early in ] refractory. In the ELOQUENT trials, there is ample of data on this. So that means that when you have a 1:1 ratio between the 2 groups of patients in OCEAN, patients that receive melflufen and patients that receive pom, and a hazard ratio of 0.7, assuming a superiority result, pom actually had 4.7 months in this ELOQUENT study, 4.7 to be exact. You should have 5-point something in median PFS for both groups taken together. And obviously, that number is now higher than expected. And as I said, pom is very well characterized, so it is more unlikely that, that deviation is due to pom. But we don't know that until we have the final result, obviously.

And just a final one for me. So GlaxoSmithKline, of course, sent in their application here in January, but they never communicated anything about accelerated approval. But I guess they -- it must be an accelerated approval because of their study design. But do you have any comment on that? Because I think their PDUFA dates is here in August for their [indiscernible] compound.

Yes. No. It is absolutely an accelerated approval because it's a single-arm trial without comparator. And we expect to hear something around this within short, right, because July, August should be the time period when something is communicated either if there's an ODAC or whether they get closer to a potential accelerated approval. Yes. I would just like to go back to the question from Jefferies. I now have the number. So the mean duration of treatment in -- for melflufen plus dex -- sorry, I'll send the mail later instead of going through the numbers. I'll send the mail. Thank you. Sorry for that.

[Operator Instructions] And we don't have any more further question. I hand back to you for any further remark.

So once again, thank you for joining us for today's webcast, and do not hesitate to send e-mails to the Investor Relations function or myself for any clarifications or any further questions you might have. Thank you very much, and I wish you all a great midsummer. Thank you.