Welcome to the Cantargia Q2 2023 report. For the first part of the conference call, the participants will be in listen-only mode. During the questions and answer session, participants are able to ask questions by dialing star 5 on their telephone keypad. Now, I will hand the conference over to the speakers, CEO Göran Forsberg and CFO Patrik Renblad. Please go ahead.
Thank you so much. It's a pleasure to present the Cantargia H1 report, after what I believe has been a very strong period, as well as a very nice summer with a good news flow. To take you into the details then. Starting out with significant events, during or after this period or during the summer, we have presented new data both in pancreatic cancer as well as non-small cell lung cancer for lead program nadunolimab, and more specifically, it's been in chemotherapy combinations. The presentations have been made at the two major cancer conferences, AACR and ASCO.
We're coming back to, to all this data, but in essence, they are certainly strong and have created lots of external interest and attention around our programs. Based on these results, we're now also planning for a randomized, controlled clinical phase II-B trial in pancreatic cancer, where patients will get nadunolimab with chemotherapy or chemotherapy alone. As we progress with the planning, there will be much more details around this trial. Besides the new clinical results, we also finalized the enrollment to, in the CANFOUR trial in non-small cell lung cancer. And we can conclude that the safety continues to be very favorable.
This last piece of information was done in nadunolimab with carboplatin plus gemcitabine, and it wasn't really different compared to the good safety observed with other platinum doublets. During the summer, when we got approval from the German authorities to start the CAN10 phase I clinical trial. The final details and final preparations are ongoing, and I'll present more in this presentation. Finally, there has been a patent opposition, another one, I have to say, again, with the favorable outcome for Cantargia. This time, it related to kind of on nadunolimab variants, but the European Patent Office ruled that this patent should be remain in force with an updated patent scope, as has been communicated.
Going into the product status then, just to remind you a little bit about our pipeline. Lead program nadunolimab is in phase II for pancreatic cancer in 1st line with gemcitabine Abraxane. It's started in triple-negative breast cancer in first or second line metastatic patients in combination with carboplatin gemcitabine. This trial is advancing well, and it's also our 1st randomized trial. Finally, non-small cell lung cancer, a phase II part, which I just said has been fully recruited, and we're now working with the data to decide on what the potential next steps should be.
Outside the, the, the lead program, CAN10, which is our autoimmune program, an antibody directed against the same molecular target as nadunolimab, IL1RAP, but on a different epitope. We'll come back to that as well. It is starting a phase, the clinical phase I trial, as I said. We're also working to some extent in our preclinical assets in the CANxx programs to identify novel opportunities with IL1RAP targeting antibodies, which are not competing directly with nadunolimab or CAN10 development. Going into to the new data, in pancreatic cancer, we have treated 73 patients or we have evaluated the efficacy in 73 patients receiving nadunolimab in combination with gemcitabine and Abraxane in the first line setting.
If we start here to the left, we can see that the waterfall diagram, which shows the, the tumor, or anti-tumor effect on each individual patients, contains a large number of patients that have responses or, or even very good responses with the 50% or higher tumor reduction. Clearly an outcome which is much better than you would expect from chemotherapy alone, and that can then be translated into good survival, which is 12.9 months at this interim analysis, and a good progression-free survival of 7.2 months. This compares favorably to historical control data regardless if they were made in the original gemcitabine and Abraxane trial or, or recent trials, where survival is somewhere in the 8.5 to nine months region, and the PFS is in the 5.5 months.
Basically extending the PFS with about 1 CT scan and extending survival with three to four months compared to the historical control. What, what we discovered later on was that the patients that are getting the strongest benefit here are actually the patients that have the highest levels of the molecular target IL1RAP, where the survival is higher than 14 months in survival analysis, compared to about 10.6 months in the low IL1RAP group. And you can also see at the waterfall here to the right, that the patients with the high IL1RAP has much, much deeper, and they also have more durable responses.
Clearly, this is giving us another dimension in the development now, where we can go for either all, all comers, or we can try to enrich for, for patients most likely to respond. And that's one of the factors we're going to address in the phase II trial, which is upcoming. In non-small cell lung cancer, again, it's a similar story. If you look at the waterfall here to the left, you can see that we have a very high fraction of patients with in the range of 50% or better tumor response, tumor reductions. And we see good responses regardless if it's, let's say, first line, second line patients treated
with gemcitabine, cisplatin, or if they get the pemetrexed carboplatin, they still get very good responses.
We even see some patients that are third line or beyond that are getting very good response rates. Overall, we see response rates of 50% or higher, which is about twice as high as you would expect from a chemotherapy alone. If we then look into more detailed analysis, we can see that the subgroup, which is strongly driving this tumor response, is the non-squamous group, where the survival of 15.9 months is four to five months longer than you would expect from chemotherapy alone, based on historical data. Clearly indicating that nadunolimab is making a difference. Progression-free survival is much longer, 7.3 months versus about five months for chemo alone.
What's really notable here is that we have actually two patients with complete response, which is very rare in non-small cell lung cancer, even if they get pembrolizumab with chemotherapy, you still expect less than 1% to get complete responders. In this small dataset, we have two out of 16 patients with non-squamous non-small cell lung cancer, so it's actually more than 10% of the patients with complete response. We're now working to understand more on how to identify these patients, so we can really do a good clinical trial in the patient group that is most likely to respond. This is clearly due to competition, where you need to advance in the most promising subgroups. The third indication is triple-negative breast cancer.
We have not presented any new data during the period, but just to remind you that, again, we have very good response rates here when combined with chemotherapy, in this case, gemcitabine carboplatin. This is data from the phase I part of the ongoing phase I/II trial. Based on a positive outcome here, we, the trial was moved into a phase II part, which is a randomized part of two times 49 patients. We expect the first data set from a randomized trial during Q4, where we have an interim futility analysis planned. We also will present the updated phase I data from the 15 patients, with, with obviously long-term efficacy, at a conference during second half of this year.
If we then have a quick look into the clinical trials where we have investigated nadunolimab, so the CANFOUR trial, which is obviously the biggest trial where we have the most data to date, and, and it was done in both pancreatic and non-small cell lung cancer. We have presented results recently, but there is still much more to squeeze out from, from these trials. We are planning for, for more data during H2 or, and or 2024. Based on the PDAC results, we're now preparing for phase II-B trial, as communicated. In the other trials, outside CANFOUR, CIRIFOUR, CAPAFOUR, CESTAFOUR, you may recall that these trials were stopped, or we stopped the recruitment, last year or early this year. This.
data sets are now maturing, and due to, let's say, relatively small number of patients, we want to have a good control of the data before we go out and present anything. Our plan is that during H2, we should probably have data that are mature enough to be meaningful to be presented, and we like to be transparent, and that's the plan for these pre trials as well. The final trial, which is a TRIFOUR trial in triple-negative breast cancer, as I said, we have presented a promising early data. There is much more to come during second half, both the interim analysis in Q4, as well as update of the phase I part in the 15 patients.
Moving now from the nadunolimab to CAN10 and autoimmunity. CAN10 is it's a really unique antibody. It's binding IL1RAP, but it's binding in a way, so it is a very potent blocker of not only IL-1 signaling through this receptor, but also IL-33 and IL-36. All of these cytokines, IL-1, IL-33, and IL-36, are driving disease severity in a large number of autoimmune inflammatory diseases. Sometimes they also work together to drive these diseases, and that's really the segment where we believe that we can have major advantage. Our, our lead indications selected have been systemic sclerosis and myocarditis.
The story behind is that it's diseases with great medical need, and it's also diseases that from independent research are clearly driven by at least two or all three of these cytokines. As an example, you, you, you can look at the biology here to the left, where you can see that there are several different immune cells that are activated by these different forms of inflammatory cytokines. IL-1 is driving one part of a disease, IL-33, another part, and IL-36, a third part. What the all results is, is an inflammatory response, which is later becoming more severe and ending up in a fibrotic response, which can be lethal in both myocarditis and systemic sclerosis.
What you can see to the right is animal data showing that we have good treatment effects in both the viral form of myocarditis, in the autoimmune form of myocarditis, that the CAN10 antibody is more potent in, in the treatment effect than just blocking IL-1 alone. For instance, here to the left with anakinra, or to the right with an antibody against the interleukin-1 beta. In systemic sclerosis, which is a very severe disease and difficult to treat in animal models, we, we see effects on both skin thickness and lung fibrosis in several different models. We are super excited to have advanced with this program through, through the GLP tox study earlier this year, and through a successful clinical trial application in Germany.
We got the approval last week and are now basically doing all preparations and screening of healthy volunteers for the SAD part, the single dose part, to be followed by a multiple dose part in psoriasis patients. Altogether, this protocol allows for up to 80 individuals to be investigated. Besides safety, we will also look into pharmacokinetics and also biomarkers to, to get early evidence of biological activity and also some kind of mechanistic proof of concept. By that, I, would like to hand over to Patrik and the finance part.
Thank you for that, Göran. Good afternoon, good morning, to you. I'm happy here to hear now after Göran's introduction, share the financial highlights from our interim report for the second quarter and first six months of 2023, as we reported this morning, European time. Our operating expenses in the quarter decreased by 35% from the previous, from the same period last year to SEK 63 million from SEK 96 million. This reduction is driven by the strategic decision to focus the development of nadunolimab to randomize clinical trials in the fewer cancer indications that Göran mentioned earlier, mainly PDAC, triple-negative breast cancer.
Cantargia's R&D investments amounted to SEK 57 million in the quarter, and that comprises 90% of the total operating expenses, when general and administration were kept at SEK 4 million, with SEK 2 million in other operating expenses, totaling SEK 6 million for admin and other. We have realized and excuse me, and reported positive net financial items from interest, income, exchange rate gains, and gains from selling short-term investments of SEK 6 million, which improved the reported loss of the quarter to SEK 56 million, which is 40% better than Q2 of 2022. For the first six months, our operating expenses amounted to SEK 140 million, 36% lower than the first half of 2022.
The same explanations apply for the year-to-date period as I gave you for the quarter. We reported net financial items of SEK 8 million year-to-date, implying a total reporting loss of SEK 132 million, down by 37% from the same period last year. We move to the next slide, which is showing our available funds and Cantargia's available funds consists of cash and bank balances as defined by IFRS and short-term investments, which is basically bond mutual funds and fixed interest accounts. By end of June, our cash and cash equivalents amounted to SEK 159 million and short-term investments were at SEK 128 million, totaling SEK 287 million in available funds.
A decrease by SEK 66 million in the quarter. On the graph here, you see the development of total available funds for the past five quarters. The current available funds will enable Cantargia a runway to mid-2024. We have flexibility built into our plans that could enable extension of the runway through prioritizations by at least two quarters. As Goran alluded to, the team is now preparing for a phase II-B clinical trial with nadunolimab in PDAC. Importantly, budget financial plans, and we will come back with more information once those plans have matured. With that, I hand over to Goran for the upcoming news flow. Thank you.
Thank you so, so much. Obviously, we come from a situation where we're very, very happy to have strong signals of activity of our lead program, nadunolimab, in both pancreatic cancer, non-small cell lung cancer, and triple-negative breast cancer. Obviously, it's very exciting to, to know that we also have a rich news flow around these programs, both in PDAC with the new translational data, with the new trial, and obviously, with the goal of getting randomized data in pancreatic cancer as quickly as possible.
Also we have more data to present in non-small cell lung cancer as the last set of patients are, the efficacy data are maturing, and we're also doing much more work on biomarkers to identify the patients that are the real winners when it comes to this combination therapy with chemo. In triple-negative breast cancer, as I said a few times, the randomized trial is already ongoing, and we expect the first data set in Q4, and also we expect mature phase I data during the second half of this year.
It, it is a great moment to know that we're now not completely dependent on nadunolimab, but we actually have two clinical programs, so two, two, two clinical legs to stand on in the development. We really believe that the CAN10 program is filling a very important medical need, and we have a unique mechanism of action here. Again, we like to be transparent on what's happening here, and once we have meaningful data in 2024, we will certainly start to present that. We have these other trials as well as translational and preclinical research, where we again like to be transparent and present more data.
By that, I would like to say that I'm very happy about where we are right now and also very much looking forward to the upcoming quarters. By that, I'm very happy to take questions and together with Patrik.
If you wish to ask a question, please dial star five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial star five again on your telephone keypad. The next question comes from Viktor Sundberg from Nordea. Please go ahead.
Yes, hi. Thanks for taking my question. I have two, if I may. One from me on, on costs first. As you mentioned, you have a lower R&D cost base now, but I just wanted to understand how you or how we should extrapolate this going forward. You will start a couple of trials here in PDAC and for the CAN-10 program.
I just wonder how you see this going forward. Do you need more cash on hand to be comfortable to start the PDAC program, for example? I think I'll start with that one. Thanks.
I can, I can start, and then if Patrick need Patrick to fill in. The trial is obviously not fully funded yet. We are working on, let's say, different alternatives on, on how to do this. Once we have a final trial design, we can probably address your question much better. I have to say more to come.
Okay, thank you. One on CAN10 also. Is the main focus here going forward, looking beyond the psoriasis trial here on the myocarditis part of that disease in systemic sclerosis. I've seen some data, for example, on rilonacept, for example, that did not show efficacy on skin endpoints. On the other hand, you know, anakinra and canakinumab have shown some effects on myocarditis. Of course, I see your preclinical data here, but just wanted to understand the rationality and perhaps unmet needs, future trial design, et cetera, that you would be going for here in systemic sclerosis, or what kind of sub-endpoints you would be looking for.
Again, we need to come back on the details in this question. What we're currently doing is that we're working together with KOLs to, let's say, make sure that the phase II development is, let's say, according to the standard of the 2020s. And there are lots of things happening around both biomarkers as well as thoughts around endpoints. So we will be much clearer on, on this, let's say, probably during 2024, well ahead of the trials are starting. You, we also need to decide if the first trial should be more based on, on a biomarker trial or, or if it should be, let's say, more trying to address the disease.
Okay, thank you very much. I jump back in the queue. Thanks.
The next question comes from Richard Ramanius from Redeye. Please go ahead.
Good afternoon. I had a few questions, so let's start with the economic one. Patrik mentioned that you have the flexibility of extending your run rate-
Mm-hmm
... of at least two quarters. Could you define or specify how we would do that? Would that be by, for example, delaying the PDAC study?
No, it, it will be looking at, non-clinical trials and the phasing of, those activities.
So non, non, non-
More, more than non-clinical trials, so more than looking at our clinicals. Yeah. Yeah.
I can, I can fill in to say, say that, we have lots of flexibility around the CMC development and when to, to take certain investments in both our programs.
Okay, I had some... I wondered about the psoriasis patients you will include in the CAN10 trial. What, what's the purpose, and will you have any efficacy measures for these patients compared to the healthy volunteers?
The rationale for using psoriasis patients, obviously, we're looking at patients with mild to moderate psoriasis. In a way, you could call them healthy subjects with mild psoriasis. The idea is to get biopsies, so to get skin biopsies from these individuals to get a mechanistic proof of concept at a very early development stage.
Yeah. Okay, that make, makes sense. I also wondered, this, this, my, my last question about the analysis of biomarkers in non-small cell lung cancers. Could you expand on, on that? What kind of biomarkers are you looking at? I guess, IL-1RAP would be included.
We're doing a deeper analysis here on... I agree, IL-1RAP is super important, but it's also what type of other proteins in the tumor cells or tumor microenvironment are working together with the IL-1RAP to, let's say, make these tumors more sensitive to nadunolimab. We're also trying to, let's say, take the other way around, looking at the patients with complete response or almost complete response to see are anything specific with these patients. We know, for instance, that they are all non-squamous subtypes, but we would like to know more.
Okay.
basically working from two different directions. One from, let's say, the biology, and the other one from patients that are doing best.
Okay, got it. Thanks. Those were my questions.
The next question comes from Joseph Hedden, from Rx Securities. Please go ahead.
Good afternoon. Thanks for taking my questions. I just have a couple relating to the PDAC phase II-B. just wondering if I could get a couple more details on the design of that. Is this to prove further the difference that, that you saw from previous data in IL-1RAP high expressions, high expressers and, and low expressers, or is it exclusively in, in the high-expressing population? Apologies if I missed this, but what proportion of the overall patient population in PDAC is expected to be IL-1RAP positive? Thanks.
No, that's a great question. The background for phase II-B trials, there are two aspects. The first one is to get randomized or controlled data on patients with high versus low IL-1RAP, getting the combination therapy versus chemotherapy alone. The fraction... we believe that slightly more than 50% of the patients are high IL-1RAP. In the previous phase II trial, it was about 60% were in the high population. And it's also to get more robust and efficient development of an IL-1RAP assay compared to what we have today.
The second part is that we will study two different dose levels, which basically is a request from the FDA in relation to Project Optimus, and do that in a randomized setting, which has been, let's say, the desire from them.
Okay. Got it. You've, you've been interacting with the FDA over the design of this, then?
We were planning to do a phase II/III trial together with PanCAN-
Yeah
... and got a request from the FDA to start that trial with a lead, randomized lead-in phase, looking into two different dose levels. It became very complex as that was a platform trial already up and running, and it just became too complicated to redesign the whole trial to build in these types of lead-in phases. Obviously, that was one part, but with the new data on the IL-1RAP, we thought that we could probably do this much, much better to really increase the likelihood of success in this program, either in all comers or in a subgroup of patients, by doing this in a really phase II-B program.
Got it. Given the high unmet need in, even in the first line setting, do you, do you think that this could be a potentially registrational study in, in terms of even if it's an accelerated approval, and then, and then you do go into the, assuming it's still an option for you, into the Precision Promise trial?
It's, it's a great question, and obviously, it, it is a phase II-B trial, but if you, if you get good, good results, I guess, there is always an opportunity to get an accelerated approval. The medical need in pancreatic cancer is enormous, and there is very little happening when it comes to, to, to new products or from what we see in, in late-stage development now as well. It is a discussion that probably will take place once we have advanced.
Okay, great.
Then also, the trial is not designed for that, it is.
Yeah
... with a great outcome, that's certainly a possibility.
Okay, great. Thanks, Göran. Thank you.
The next question comes from Sebastiaan van der Schoot from Van Lanschot Kempen. Please go ahead.
Hi, team. This is Louisa, dialing in for Sebastiaan. I have a couple of questions. The first one regarding the trial with nadunolimab in lung cancer. Considering that you're still gonna release data this year and next year, do you have an idea already, when do you expect to make a decision regarding, well, the development of the drug in this setting?
We, we'll probably know much more later on. I guess everything is data-driven. If we can see that we have a well-defined subgroup where we can be competitive in the current landscape. Obviously, that could be a good decision point for designing next step trial, either on our own or together with a partner in the future. I think we need to see those data exactly to have a good idea about the strategy around next step. In the end of the day, we know that there are patients that are doing really well, so at some point in time, there has to be a movement forward in the development.
Clear. Thank you. On the, on the triple-negative breast cancer trial, could you pro-provide a bit more color? We have two sets of data coming out this year, right? Could you provide a bit more color on what kind of data can we expect, and also the, the number of patients and that kind of details?
Sure. The first data set is obviously an update of the 12 or 15 patients that were already presented during Q1. It will now be efficacy data in all 15 patients, and they have been treated for or been treated or followed for, I would say at least six months at that point in time. We would probably have a good idea about both response rate, safety, and PFS, and obviously, the depth and the durability of response. I think a pretty mature data set, perhaps not survival data yet, but definitely all the other relevant efficacy points. The second data set is the first randomized.
The interim analysis will be done once, two times 14 patients have been treated for at least or have been followed with at least two CT scans, which means at least three months treatment. It we will have an idea about safety and response rates in these patients, or, or a relatively small, small subset, but at least it will give some signals of where we're going, and it's designed as a futility analysis.
Very helpful. Thank you. That's all for my questions.
The next question comes from Sten Westerberg from Analysg uiden. Please go ahead.
Yes, thank you. Two questions on the TRIFOUR study. Just so I understand correctly, the interim analysis will be carried out after 14 patients treated in the active arm. Is that correct?
So 14 in each arm, yes.
Yes. Okay. The second question, if you please could remind us, of the patient setting in the TRIFOUR study. Is it primarily second or, first or second line, metastatic, TNBC patients, or can you give some more details about the, the, status of the patients?
Absolutely. It's a good question. The protocol allows for both first and second-line patients to be included, and obviously, they need to be with good performance status, so ECOG 0 or 1. They, what's happening, right? Obviously, we're not the only one in treating patients in triple-negative breast cancer, and there have been, for instance, recent approval of Trodelvy in the second line segment, and we believe that the uptake of Trodelvy will have an impact on, let's say, recruitment rate, but we don't see that yet. But it will, let's say, drive the patient population more towards first line, in that case, if Trodelvy is used second line. If for some reason Trodelvy is moving into first line, obviously, it would be a different situation.
We expect a good mix of first and second-line patients, and all metastatic.
Okay, thank you. That concludes my question. Very helpful.
As a reminder, if you wish to ask a question, please dial star five on your telephone keypad. The next question comes from Matthew Biegler from Oppenheimer. Please go ahead.
Oh, hey there, guys. Thanks for taking the question. I also wanted to ask about the biomarker as you prepare for the PDAC trial. Can you just talk a little bit about its current state of validation? Have you defined boundaries for IL-1RAP expression levels, and has that been validated, or is that validation part of, I guess, the goal for this phase II trial? Thanks.
The biomarker assay right now, it's an assay which is developed and run at a central lab in Europe, and very smart. It's been, let's say, some validation done, and it's basic, is done under GLP, but there is still work to do to, to get it more effective and to work more, more, let's say, at the, at the bedside. Very certainly much more work before we have a real assay, and that's something we will do in parallel with, with the phase II-B trial.
Got it. Thanks for the question.
There are no more questions at this time, so I hand the conference back to the speakers for any closing comments.
There's no questions coming from the web, so I'll hand over to you, Göran, for a final comment.
By that, I would like to thank you all for the interest in our program and obviously, for several very great questions, which I hope could be clarified. I'd say look forward to continue the development of our lead programs, and I'm sure it will be an exciting time at the next report as well. Thanks a lot for your attention.
Thank you very much.