Welcome to Cantargia Q4 Report 2022. 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 five on their telephone keypad. Now I will hand the con ference over to the speakers CEO, Göran Forsberg, and CFO, Bengt Jörkel. Please go ahead.
Thank you so much. It's a pleasure to be here and present the full year report for Cantargia, and it's an extra pleasure to do it on the back of a very important press release this morning on new data in triple-negative breast cancer. Let's go into the story. Besides myself, as you said, it will be Bengt Jöndell, CFO, who will do a presentation. It's been a good period, and it's been a very good year for Cantargia, even though it's been a very, let's say, dramatic and difficult year for the world. During the period and after the period, we have re...
Significantly, let's say, focused our clinical activities, by stopping, three clinical trials, to let them read out during this year and focus on what we believe, is three very different but very promising opportunities with our lead program, nadunolimab, and we will go through that in detail later on. As I said, one of these opportunities, which are the TRIFOUR trial in triple-negative breast cancer, the first dose escalation part was completed, and we were very happy to disclose the first dataset this morning, which shows that, one, we have a acceptable, and good safety when we add nadunolimab to gemcitabine carboplatin in this group of patients.
What is just as important is that we have very promising efficacy, and we will go through the top-line data in a second. We also presented more results end of last year, giving more insight into the mechanism of action of nadunolimab and how it regulates the activity of several tumor-promoting molecules, and that was presented at the SITC conference. For our second program, CAN10, we also in the end of last year, we presented very interesting and strong efficacy data in several models of systemic sclerosis, which is one of the key indications. A month later, we could also conclude the toxicity study, which was done under GLP, showing that CAN10 was safe and without any significant safety findings.
We're now just finalizing a few administrative parts, including the clinical protocol and plan to submit the phase I application during Q1. Another point which has not so much to do with our clinical or preclinical development, but we also recruited Patrik Renblad as new Chief Financial Officer, and he will start no later than August. If we go into the projects in more detail, the strategy of nadunolimab is obviously to treat cancer. Treating cancer, it is really a buffet of various different opportunities. What we've picked up very quickly in our development is that when we add nadunolimab to standard therapies, and especially some chemotherapies, we have a chance to counteract resistance, which is always building up to various cancer therapies.
If you look at this cartoon to the left, you have a patient with a pancreatic tumor. Obviously, there can be a benefit and a short-term response. Unfortunately, which is the reality of pancreatic cancer, the tumor very quickly develop resistance mechanisms, and then the tumor progresses and obviously very bad news for patients. What our idea is to add nadunolimab, which you can see to below here, to get the response much more durable and long-lasting and obviously leading to lower tumor burden. Based on the data we have now in 73 patients treated with pancreatic cancer in combination with first-line chemotherapy, we do see that we have a much stronger efficacy than you would expect from chemotherapy alone.
We believe that this is really a great starting point to take this drug into randomized trials and a potential pivotal trial in pancreatic cancer. Just to remind you, we've seen similar results not only in pancreatic cancer, but also in non-small cell lung cancer, where we see strong responses, especially in the largest subgroup of non-small cell lung cancer, which is called non-squamous non-small cell lung cancer, where we all have a response rate of more than 56% and a very impressive and durable median response duration of 11.2 months. Very small data to come, both in pancreatic cancer and non-small cell lung cancer during Q2. The third dataset in the clinical space is one that we presented this morning, which is in triple-negative breast cancer.
Here, we're combining with gemcitabine and carboplatin in first and second line in metastatic triple-negative breast cancer patients. As this is an ongoing trial, we have recruited 15 patients. Three of these patients have not yet been exposed to CT cans, so we cannot really say anything about the efficacy. We have a 12 have been treated long enough to have two CT scans. It's clear that we have good response rates. We have one complete responder, we have five partial responders, and we have four patients stable disease. This means that we have an overall response rate of 50% and a disease control rate which is somewhere between 80% and 90%.
These data are obviously early stage, but nevertheless, very, very interesting and fits very well with the ones we observed in lung cancer and pancreatic cancer. This trial has been designed to already now have a randomized phase starting. In principle, phase patients can get into a randomized phase any day now, and it will be two times 49 patients treated either with nadunolimab plus chemotherapy or chemotherapy alone. The next milestone here is that we're planning to do an interim futility analysis during Q4. We will also present the data from these first 15 patients once we have matured a little bit more, so planning for a scientific conference during the second half of this year. During 2022 and now into 2023, I think we have really focused our pipeline when it comes to nadunolimab.
It was a bit wider before with all the other early trials. We still really pick the ones where we think we have the best chance of opportunities. Now we are entering a phase II or phase III trial in pancreatic cancer with gemcitabine and Abraxane. We have ongoing phase II activities in non-squamous non-small cell lung cancer with carboplatin/gemcitabine. We have entered the phase II randomized trials with carboplatin/gemcitabine in triple-negative breast cancer. We also have a second project, the CAN10, which is another antibody. It's directed against the same target as nadunolimab, the IL1RAP, but a different epitope. It's been optimized for autoimmune inflammatory diseases and will be very exciting to test this in phase I or phase II, which is upcoming as quickly as possible now.
A little bit behind this, we have several hundred different antibodies, which have other properties than CAN10 and nadunolimab. Potentially, we can continue to feed the pipeline with new opportunities as we progress. Very quickly going into different trials and the clinical development status. The CANFOUR trial, which is the first trial we started in pancreatic and non-small cell lung cancer, it is basically continuing. There are still some patients being treated. Recruitment is ongoing in non-small cell lung cancer, and we're planning to update both the pancreatic cancer data and the non-small cell lung cancer data during Q2.
That would be not only, let's say, clinical efficacy and clinical safety from a long-term perspective, but we will also try to build in biomarker analysis into these long-term effects to get a much better idea of mechanism of action, which patients are most likely to respond, et cetera, et cetera. The second trial where we still also have patients on therapy is CIRIFOUR, which is a combination with pembrolizumab. We did present results at ASCO last year, and we will update the data once this trial has been completed. And we also started to investigate pembrolizumab plus chemotherapy combination with nadunolimab. We decided to stop these activities for cost reasons, and we will address this in a separate trial later on, and we'll come back on how that will be performed.
We have the CAPAFOUR and CESTAFOUR trials, which was also stopped to focus on the other opportunities. Nevertheless, there are more than 50 patients here in a few different indications and different combinations. We certainly are planning to present this data once they are more mature, but also given that there are relatively small patient numbers and relatively and quite a few different indications, we believe that this data will make more sense once we are mature, so we need to come back exactly when, during 2023 we're ready to present it. TRIFOUR triple-negative breast cancer. Obviously promising early data as I presented. We're starting the randomized phase.
We're doing the interim analy sis planned for Q4, as well as a presentation of long-term effects and long-term safety in the first 15 patients during second half. Finally, we have the upcoming phase II or phase III trial, Precision Promise, which we will do in collaboration with PanCAN in the U.S. We are in regulatory discussions with the FDA, which are necessary before we can start the trial. It has taken a little bit longer time than originally planned, and this is caused by FDA's new guidelines, Precision Promise, which requires some adaptations and some further discussions. We are certainly very motivated to continue, and I think the discussions with the FDA is also very constructive and helpful. Moving from the nadunolimab to CAN10, we have presented.
It's an antibody, if you look to the left, which is blocking several different cytokine systems contributing to diseases like both myocarditis and systemic sclerosis. Blocking IL-1, both alpha and beta, IL-33 and IL-36. All these cytokines contribute to the disease through different pathways. We believe we have a very powerful tool here to actually make a difference for patients. If you look to the right, we see it's a quick overview showing that we have really interesting effects both in viral myocarditis, in another form of myocarditis called autoimmune myocarditis, as well as in systemic sclerosis models, both of skin thickness as well as lung fibrosis. Where we are right now is that we have completed everything we believe is needed to start the clinical trial.
We are now compiling a package to submit it to regulatory authorities during Q1 this year. Timelines here are a little bit outside of our control. Depends on how quickly the regulatory review will go and ethics committees. The first subjects may enter the trial as early as the first half this year. The design will be phase I in healthy volunteers, which will then be followed by multiple dosing in psoriasis patients. We will do an ambitious program here on biomarkers to understand more about mechanism of action and get some early signals of activity. Having said that, I would like to hand over to Bengt and to finance part.
Okay. Thank you, Göran. Let's start with the full year 2022. The operating expenses increased slightly with 3% to SEK 381.5 million . As you can see in the left part in the graph, we had very focused spending on R&D, 96% of the operating expenses. Looking at the main cost drivers or main cost components during 2022, it was our main project, first of all, nadunolimab, CAN04, with the clinical programs in TRIFOUR and Precision Promise, but also investments in CMC. We also had increased spendings in the CAN10, our second project, with preparation for phase I clinical study as one component. The personnel ended at 26 full-time employees end of December 31. Next slide, please.
If we look at quarter four, you can see a decrease in spending with 15% to SEK 89.7 million. This is an effect of the focus of the clinical program as described by Göran before, and it also affects the CMC costs. Next slide, please. The financial position end of December 2022, we had available funds of SEK 426.7 million. Looking at the runway forward, our estimate is that this will last to approximately mid 2024 with the present plans, still with the flexibility to stretch it out further if necessary. I think that concludes the financial part. Back to Göran.
I would just then like to thank you for your attention and just say that we believe 2023 will be a super exciting year for Cantargia. We have several upcoming value inflection points. It is the new clinical results in pancreatic lung cancer, triple-negative breast cancer, as well as the KEYTRUDA combination. We're obviously starting to the start of the Precision Promise phase II or phase III trial in pancreatic cancer. We have During the development, been ambitious to analyze blood as well as biopsies. Now that we're generating long-term efficacy, we can also start to make some very hopefully very interesting observations on mechanism of action, patients most likely to respond, as well as other effects of the therapy. We believe that this will be a significant milestone once ready.
We also have the trials we stopped a little bit earlier, where we still believe that the clinical data will really guide us on how broad we can go in the cancer field, where do we have the best opportunities and which opportunities are perhaps less likely to be part of our sweet spot. Both in pancreatic cancer with FOLFIRINOX in small cell lung cancer with docetaxel, colorectal cancer with FOLFOX, as well as biliary tract cancer with gemcitabine. In CAN10, we obviously it is the start of the clinical trial, which is the major milestone, but we are definitely also doing more scientific parts here on the preclinical projects and our development milestones, which we will share. By that, I'd like to thank you very much for your attention, and we will be very happy to take questions.
Thank you. 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 Mark Breidenbach from Oppenheimer. Please go ahead.
Thanks, guys. Congrats on the new data from TRIFOUR. I guess I have a couple questions on that. I'm trying to figure out, you know, what the implications are, you know, in terms of prioritizing development in triple-negative breast cancer versus PDAC and lung. Is the new data kind of shifting the priorities at all? That's one question. I'm also wondering, you know, I'm noticing that you're going into a randomized portion, a randomized study much more quickly than you did in lung and pancreatic. If you can just comment on reasons for advancing into a randomized study so soon relative to the other indications.
Then a final question is just on the treatment histories of the responders in TRIFOUR. Are all of the responding patients newly diagnosed and previously untreated, or are any of them in a second line setting? Thanks for taking the questions.
Thanks, Mark. Obviously some very good and, let's say well-thought through questions. The first one, the priority now that we are starting to get strong data in three different indications. Obviously the main goal for Cantargia now is to get a proof of concept in a randomized setting. The triple-negative breast cancer opportunity is the one which has advanced the most. Having said that, we still believe that we have strong and interesting data in three different indications. With the pancreatic cancer study together with PanCAN coming up, obviously we're very motivated to go ahead with that one as well. The third opportunity, which is the non-small cell lung cancer, we are still recruiting patients, and I...
We all know that non-small cell lung cancer is a much more competitive indication, and we're now planning to have new advisory boards to discuss the data we have and how to best advance the program in non-small cell lung cancer. Once we have had those discussions, we'll probably and have more data, we will be in a much better position to guide on what the next step would be in non-small cell lung cancer. We are very enthusiastic about what we're seeing, but there is also a reality of how many randomized trials a company of Cantargia's size can manage at the same time. Your second question was the reasons for doing the randomized part so quickly.
The story is that the non-small cell lung cancer and the pancreatic cancer, data was really generated in our first safety trials, which were then expanded because we saw signals. In non-triple-negative breast cancer, we certainly thought that we have much better control now of the safety, and we want to be more aggressive and really go into the randomized part if, let's say, if the initial data didn't guide us to go in a... to do something else. I think this has been part of a strategy. It's been a little bit under the radar, but we are very happy to take this step. The treatment history of the triple-negative breast cancer patients. In the trial, we have predominantly second-line metastatic patients.
We have a few first-line. It's not that we see with 12 patients, I think starting to see if first-line or second-line patients are responding better or worse than the others. We just don't have that information. I think you should also assume that most of these patients received neoadjuvant and/or adjuvant treatment at an earlier stage during their disease. The majority are second-line metastatic.
Okay, got it. Can you give us your best estimate as to when Precision Promise might kick off in terms of getting nadunolimab into that trial?
We have upcoming meetings with the FDA, and I think the difficulty here is that, yes, we could conclude the all remaining questions at the upcoming meetings, but it could also be that there is something new, unknown coming at this point in time, which will basically delay everything by, let's say, three months or so. I don't know, but I think what we can assure everyone is that we will not sit and, let's say, just have a continued discussions. At some point in time, we obviously need to implement some kind of plan B here so to continue to generate randomized data in pancreatic cancer. Plan A is to go ahead with Precision Promise and make sure that we get into patients as quickly as possible. We're probably talking about second half before we have patients.
Okay, that's helpful. Thank you so much for taking the questions. Congrats on the news.
Thank you.
The next question comes from Viktor Sundberg from Nordea. Please go ahead.
Yeah. Hi, guys, Viktor Sundberg from Nordea. First of all, congrats on the promising data in triple-negative breast cancer. I have a few questions on this data set. My first question was just, if we could get a bit more details on maybe the baseline characteristics of these patients, perhaps age, also in the previous questions that some had had chemo in the neoadjuvant setting before. Just wondered if you if any of these patients got carboplatin, for example, in that setting. Also wondered if some of these patients had, you know, PD-1 immunotherapy, PARP inhibitors, et cetera, and perhaps ECOG status as well, if that's possible to get a sense of that as well.
Okay. I don't have all this information. It has not been disclosed, you should assume that we have a mix here of women, but basically from anything from the 30s up to the 60s, 70s in the patient material. You should also assume that they may have very changing histories of treatment in the neoadjuvant setting or adjuvant. We have not, or at least I have not, seen a summary of all this rather than that, this is really the standard first/second line population.
Okay. Thanks. Just to confirm how the patient population will look here going forward for the randomized part, is it kind of the same type of patients with similar characteristics, would you say, as the phase Ib study? maybe, you know, a split maybe here, for first- and second-line patients that you will recruit to the second stage here, of the study. That would be helpful also.
Yes. There is as far as we know, there is really no change in upstream treatment paradigms changing the types of patients we'll get, and there is no changes in inclusion, exclusion criteria. Yes, we believe we will get the same type of patients.
Okay. I mean, where in the treatment algorithm for triple-negative do you think this combo could fit? Is it for PD-L1 negative patients with wild type BRCA status? If you consider this to be more of a second line option, how do you view this versus, say, sacituzumab govitecan and Enhertu, datopotamab deruxtecan, et cetera, coming for this market as well? I guess my concern is there's a lot of moving parts here in triple-negative. I just wonder where you see this potentially being approved and where it can, you know, take a significant market share, et cetera. Thanks.
You're absolutely right here, Viktor. It's very much a moving field. There are lots of trials ongoing in parallel, which may affect the outcome here. The interest to participate in a phase III trial will probably very much be dependent on that we keep these types of signals. Basically, I think you can assume that we may position this as first, second, or third line, it's very much dependent on how, let's say, the rest of the field is evolving. You're absolutely right. There are opportunities in PD-L1 low. There are obviously the BRCA mutations and how to deal with those as well as everything else which is coming now.
I think TRODELVY which is probably going to take a market share here, at least in the second line. Lots of things to keep an eye on. Our understanding is that GemCarbo will be used in a group of patients regardless of what's happening, and I think that's what's important for us at this point in time.
Okay. Thank you, guys. I appreciate the answers to my questions. Thanks.
Thanks.
The next question comes from Sten Westerberg from Aktiespararna. Please go ahead.
Hello, Göran. Thank you for taking my question. Since you referred to Project Optimus in the FDA discussions, should we conclude that the topic of these discussions is dosing? That would be my first question. Also, if you could elaborate a bit on how you are planning dosing the patients in the second part of the TRIFOUR study. Also, out of curiosity, it is an open label study, but how do you randomize an open label study? Thank you. That concludes my questions.
Thanks. Let's start with Project Optimus then. What Project Optimus... To give a background of Project Optimus. The reason for Project Optimus is that there has been, let's say, a demand for new oncology drugs, and several drugs have been approved during, you know, various accelerated approval programs, et cetera. What has become clear here is that obviously there has been lots of new drugs entering the oncology field. Some of these drugs, it has also been clear that they have safety problems once they have been marketed, and there is a concern that the dose finding was not done properly.
FDA has a new initiative where they basically require all new drugs to undergo phase II testing with at least two different dose levels in a randomized phase. Cantargia was aware of part of these concerns from the FDA when we designed or at least the second part of the CAN04 trial. We have studied four different dose levels. We have. At three of these, we have at least 20 patients on each. In a way, we have addressed FDA's concerns or for dose finding, but not in the randomized way. The most likely scenario here is that the Precision Promise trial is going to start with two different dose levels, and then we will stop recruitment to one of these arms after a certain number of patients.
There are lots of technicalities around this, and that's what the discussions with the FDA is focused on. We are, let's say, to some extent in unknown waters here because the initiative has been launched already, and that's why it takes a little bit longer for both us and FDA to come to conclusion of how we should do this. I don't see this as dramatic, even though I would have been happier if we had started already. The second question was the TRIFOUR trial and how dosing was going to be done in the phase II part.
What we have done is that we have selected one dose level now, in accordance with the protocol, and that dose level, which is the same dose level as we're also proposing in pancreatic trial, is now the one to be used, and it's 2.5 mg per kg, and it's going to be added to the chemotherapy. Basically at the same time as the chemotherapy's been given, s o no extra visits or anything like that. I don't know if you, if you wanted more details or if that's enough on that point.
That's fine. Thank you.
Yeah. The question is the open label study, how do you randomize it? Basically, this will be computer-generated. Once a patient is being screened and found eligible, there will be a program doing a randomization to tell if you're entering the active arm or if you're only getting the chemotherapy. Obviously, the clinicians and and patients will know which arm they are in.
Okay. Is it your belief that this phase II part will be valid for introducing a pivotal or registrational study afterwards?
It's definitely designed to be, let's say, the next step for a randomized pivotal trial. Also we need to consider how will Project Optimus evolve here, and it's possible that you need to start a randomized trial with two different dose levels as well. I think that's more an issue for 2024 rather than now when we're trying to get the proof of concept in a randomized setting.
Thank you. That concludes my questions.
The next question comes from Joseph Hedden from Rx Securities. Please go ahead.
Good afternoon, and thanks for taking my questions. Just one on the Precision Promise trial. Do you have any assurance from the FDA that that's acted as a pivotal trial, or is that part of the ongoing discussions? If it is intended as a pivotal trial, would it serve in Europe as well, or is there a separate plan there? Thanks.
Great. That's a great question. The Precision Promise protocol was launched and agreed with the FDA before we entered this stage. In principle, there is an agreement that it's a pivotal trial, and that would. This is a platform trial and the idea is that all arms should be pivotal. The answer is yes. When it comes to Europe, obviously, when it comes to these platform trials, they are something which has been designed very much together with the FDA, and EMA is less exposed to them.
I would say if the data are strong enough, I'm sure it could be pivotal in Europe or at least be the basis for some kind of accelerated approval here with a demand for a confirmatory trial. But given the big medical need, I hope that it would serve the same purpose here. You're... I think you're assuming that it's mostly discussed with the FDA and that's correct.
Okay, great. Thank you very much.
The next question comes from Luisa Morgado from Van Lanschot Kempen. Please go ahead.
Hi. Here Luisa dialing in for Sebastian. First of all, congrats on the results for the TRIFOUR study today. I was wondering if you could elaborate a bit more for triple-negative breast cancer. Can you speak a bit more about the current standard of care, both for first-line and second-line setting, which chemotherapy is used in these settings, and which do you think are the values to beat, so which is the benchmark?
When it comes to the current therapies, I think it is a changing landscape where... Typically or traditionally it's been chemotherapies and it could be both platinum-based chemotherapies, it could be taxane-based chemotherapies first line. Typically you would in the second line go for a single chemotherapy, obviously not of the same origin as the first line, or you could go for a doublet. Very often it's a single chemo. Typically, if you go to a platinum-based doublet in first line, you would probably get a taxane-based second-line opportunity. Different countries and different hospitals have different practices here.
As was discussed, there is new data showing that PD-1... No or PD-L1 may have an effect, at least in PD-L1 high patients. That's certainly an option. It's also PD-1s and PD-L1s have also shown very good efficacy in the neoadjuvant settings. It is a change in landscape here, and I think a discussion whether it should be primarily a neoadjuvant therapy or if it should be more the downstream. PARP inhibitors have shown efficacy in BRCA-mutated patients. There are TRODELVY, which is an ADC, has shown some efficacy in the second line and it is expected to enter the stage here as well. I have to say it's a landscape with lots of opportunities right now and lots of different practices in different geographies, but perhaps due to the new agents or also a standardization to come.
Very helpful. Thank you.
The next question comes from Richard Ramanius from Redeye. Please go ahead.
Hello. I'd like to start asking about CAPAFOUR and CESTAFOUR. You mentioned it might take more time for the data to mature. When, could you say when you think you will publish the results and what kind of results you will publish?
I. Yeah, it's a good question. What we said is that we still have patients on therapy in these trials. Given that, let's say if you have 15 or 20 patients in a complete trial, we think it makes more sense to present the data when they are complete rather than doing interim analysis during the progress. Unlike, for instance, TRIFOUR, where we're now presenting data from the first part with knowledge that we are continuing to second part. The data are maturing at different paces in the different arms here as well. We have not decided that we will lock the database at a certain time point and then present data.
It is going to be driven a little bit by how quickly the patients deteriorate and leave the trials. We also believe that it will be of interest not to see the short-term safety and short-term efficacy results. It will be much more valuable to see the long-term effects here. I am a little bit vague here and I know, but because we are still discussing when is the right time point, but definitely during 2023, if we are talking first half or let's say during the autumn, it is a little bit too early to say.
Okay. That's good to know that it's in 2023 in any case. I was also analyzing or thinking about the data, the waterfall plot you presented in triple-negative breast cancer, which was quite interesting to see as it was really similar to the waterfall plot you presented in pancreatic cancer. Also I noticed that the overall survival in these diseases for chemotherapy-treated patients are quite similar.
Yeah.
My question is, or is there some commonality in these two diseases? Is there some biological similarity which makes nadunolimab function good in combination with chemotherapy?
I believe so. Yes. We selected the pancreatic cancer and the triple-negative breast cancer because there is obviously a high expression of the target IL1RAP. And it's also two diseases where two. Let's say tumor promoting and immune suppressive inflammatory systems are well documented, like Interleukin-1. There are biological similarities here. A third point was that it was, let's say, related chemotherapies being used. The potential synergies we picked up in pancreatic and non-small cell lung cancer would be valid here as well.
Okay. If I'm allowed to speculate a bit, the results you present now are quite early, but what if, what if the progression-free survival and the overall survival demonstrate the same, should we say, increase as in pancreatic cancer? Would that be good enough for an accelerated approval based on the phase II data? Let's say if the overall survival is now it's 11 months in the study you referred to. If you put it like that, what's the limit? How much better do you need to perform? Would it be 15, 16 months overall survival?
I think the challenge here with that question is now that Project Optimus has entered the field, I'm sure also the FDA standards for accelerated approval is going to change. I just don't think I'm the right person to speculate of what would be needed for an accelerated approval at this point in time. Let's say our starting point is that this is a proof of concept trial, and then we need to take the next step based on the data. Of course, if data is stellar, we There might be another opportunity here for sure.
Okay, that makes sense. In fact, no more questions from me.
The next question comes from Arvid Necander from Carnegie. Please go ahead.
Okay, good afternoon, and thanks for taking my questions. My first question is on the TRIFOUR readout. In the press release, you basically said that the safety was in line with what you've seen in prior studies. How exactly should we interpret this, given that G-CSF was given prophylactically? Should it be read as initial signals not indicating any added benefit at all of this treatment strategy? Could you just shed some light on this?
I'm not sure if I fully understood the question, but I'll try to. You have to correct me if I'm wrong. Obviously, there is a side effect profile with gemcitabine carboplatin, which very much involves neutropenia, which is side effect we've seen before. Yes, we have not seen any new strange side effects when we add nadunolimab to carbo gem. We're adding G-CSF. We're learning how to use G-CSF. We believe that we're in control here. Going into, let's say, details about percentages of neutropenia, what is expected and where we have right now. There hasn't been, let's say, anything really serious standing out. When it comes to all the details in safety profile, I think we need more data and longer treatment times to start to present that and speculate around that.
Okay. Yeah.
What I should say also, there is this. The trial has been followed by safety review committee, which has met and discussed all the data after each group of three patients.
Okay. Yeah, that's fair. I guess my question was mainly around, you know, is this strategy likely to make it into the protocols of future trials, and how much benefit did you see of this versus using G-CSF, let's say, on demand, instead. Fair. A small study. We'll hold out for additional analysis. Okay.
Mm.
My second-
Can I just comment? I think the G-CSF. When it comes to lots of our trials of G-CSF or the need for a prophylactic G-CSF or let's say signal neutropenia has very often been found at the early stage of chemotherapy. Once the patients have stayed on chemotherapy and nadunolimab, the safety profile looks very much like the chemotherapy alone. There has been a little bit of signal of neutropenia at the early stage, and that's what we're trying to mask with G-CSF.
Right. Very good. Thanks.
The safety committee has been, let's say, happy with what we're seeing.
Okay. Yep. Thanks. Very good. My second question was just on costs and how we should think about R&D spend going into 2023, given your more focused clinical program. How should we think about that directionally?
Yes. You can get some guidance if you look at profile spending per quarter for 2022. We peaked the first quarter, the first half year on 2022 was above the year before. The second half of the year, we actually had spendings per quarter less than last year. We have in a way, initiated a downwards trend. I think that that's the direction for the spending per quarter looking forward. That's also necessary if we shall be able to have the money last for the mid of 2024.
Right. Okay. Yep. Fair. Thanks a lot, guys, and congrats on the new data. That was everything for me.
Thanks.
There are no more questions at this time, so I hand the conference back to the speakers for any questions from the web.
There are no questions on the web either, so I'll hand over to Göran.
Yeah. By that, I would very much like to thank you for the attention and hope that we managed to answer all the questions. We also hope that you share our enthusiasm for all the opportunities we have in front of us during 2023. By that, we will be in touch again next quarter.