Cantargia AB (publ) (CANTA) Earnings Call Transcript & Summary

Okay. So let's restart again. I'm sorry, we had a power failure here. But to continue, we have presented very interesting data in pancreatic cancer, showing that patients treated with nadunolimab in combination with Gemcitabine Abraxane in the first-line setting, have the overall survival and the progression-free survival, which is much longer than you would expect from chemotherapy alone. So 13.2 months survival, which is longer than the approximately 9 months you would expect from Gemcitabine Abraxane and a PFS, which is about 2 months longer than expected from Gemcitabine Abraxane. So if we take the next slide. Yes, we can also see that if we do a subgroup analysis, patients that have high levels of the antigen IL1RAP have a better benefit than patients with lower levels of a target in IL1RAP. And that's very exciting because the prognosis for these patients is worse than -- so with higher on rep, you have worse prognosis, but you do better with the therapy. So this is clearly something we can build on in the upcoming clinical trial. And if we take the next slide, the trial, we're starting the summer and where we just recently got approval to start in the U.S. is designed as a 150-patient trial with an interim analysis after 60 patients. If we study 2 different doses of Natalizumab 80 milligram and 200 milligram in combination with chemotherapy and then having a controlled group of chemotherapy alone. And during the trial, we will allow all comers to enter the trial, but we will measure if a high or low IL1RAP, and that will then be used as a predefined subgroup analysis to take the next step. And if we go to the next slide now, I can show you a little bit on what time lines look like. So the plan is to start the trial mid-2024. We expect a rapid recruitment. We have had very good response from participating clinical centers. So we believe that during H1 2025, we will be able to do with first snapshot analysis of the 60 patients if data looks promising, that will obviously be the basis for an FDA meeting and also the start of Phase III preparations. There are there several opportunities here. So one, if the data looks positive, is obviously to continue to make the study bigger and extend it another opportunity, which is what we have to share your plans on here is the start of Phase III trial 2026, where we can have results in '28 and 5BLA submission during 2028. So we believe that doing this initial trial is derisking the whole development pathway, and it's also addressing the FDA project optimist and other guidelines. So we believe that we're in a very good position now to advance the program in pancreatic cancer in an efficient and risk-mitigated way. Next. So then moving over to triple-negative breast cancer. Again, we wish some positive results in the initial trial of 15 patients, which was some kind of lead in to the Phase II randomized study. But in the Phase I part, we saw a response rate of 60%, which is about twice as high as you expect from chemotherapy alone. In this patient population, the survival of PFS was much longer than you would expect from chemotherapy alone. The safety was very good. So we didn't really pick up any safety concerns or side effects, except those that you in principle expect from this combination and from chemo. And the randomized Phase II is currently ongoing, and we expect to have first results late this year. So that is all well up and running as well. So then moving in to non-small cell lung cancer. As you may recall, we have seen very positive data here as well with high response rates with good PFS and survival. But lung cancer being a very competitive indication with lots of new therapies entering the stage. We made the strategic decision to work with a biomarker approach to really identify the patients most likely to respond. And what's driving this decision that we have observed 2 patients with a complete response. And just to remind you that the complete responders are very rare in non-small cell lung cancer, even if the immune therapies, it's less than 1%. So having 2 patients out of 30 is a very good signal and we'll narrow it down to see that these are patients that have non-squamous non-small cell lung cancer. Okay.

Speaker please go ahead.

Yes. So within neuropathy, we've seen some new data, which was presented not too long ago. And the background is that several of the chemotherapies used to treat cancer induced neuropathy, which is a very, very serious side effect which can lead to discontinuation of otherwise very active drugs giving responses to patients. So there is a very big medical need to counteract that or alleviate the symptoms. And what we've seen with nadunolimab in our pancreatic cancer trial is that we're getting much lower incidence of neuropathy or great free neuropathy than you would expect from historical controls, it's 1% versus 17%. And what we've done then is that we've done further analysis looking into grade 1 or 2 neuropathies. And without going into details, we see a very strong signal here as well. And those data together with what we've also seen in animal models as well as with ADC payloads in using the IL-1 system will be presented at the upcoming scientific conferences. So currently, we are working to get more and more details around this, but clearly, we wanted to inform the market about the find possible. So then moving away from nadunolimab into the CAN10 asset -- and to repeat, CAN10 differs from nadunolimab in that it's a very potent IL-1, IL-33 and IL-36 blocker, while nadunolimab is primarily an IL-1 blocker equipped with an ADCC feature. And the development is geared towards systemic sclerosis and myocarditis, which are 2 diseases with very high medical need, which involves these cytokines. So the first in-human study is already ongoing and we presented the first clinical data and this is showing a little bit on the study design. So we're doing an IV administration of healthy volunteers to start with a single doses to study safety but also to study the biomarkers -- and we're presenting more data on that. But in -- and we presented the first data on receptor occupancy. But interestingly, what we will do then is to move into psoriasis patients in multiple dosing, which is primarily a safety study, but we can do so much more by looking into biomarkers. And psoriasis is interesting as you show -- see in this slide in that several of the components we're addressing like IL-1, IL-36, IL-33 are elevated in this type of disease. And we will study this by taking both biopsies from patients as well as do something called skin tape strips which is basically just taking some tape and on the skin surface and then analyze for biomarkers. And thereby, we are planning to start to identify mechanistic differences as we continue to treat with CAN10. And the MAD part is planned to start during Q3 this year once we have reached enough high doses in the SAD part. And then the preparations for the Phase II clinical study is ongoing, and we will disclose much more around that once we have had advanced and have had various advisory boards around this. So -- but the status is that we have shown that it's safe in GLP Tox studies. We have several preclinical models showing efficacy. Phase I is ongoing -- as I said, it's done in Germany, and we have had good safety so far. We've done receptor occupancy studies, which are very positive. And in total, we will treat up to 8 individuals in this trial. So then coming back to VIP because there has been lots of discussions around Kantar gas IP. And what I would like to point out on this slide is that we have a very strong IP. We have -- first of all, we have a composition of matter patents on both the lead antibody CANFOUR, which expires 2035, or CAN10 which expires 2041. And all these expire dates are excluding any potential prolongations, which we may get along the way, but we have decided to communicate it in the most conservative way. We also have IP around the use of anti-IL-1 RAP antibodies in treatment of solid tumors, haematological diseases and some others. And it is really the more -- it's not the composition of matter patents that are in focus of the various positions. It's more, let's say, other details, which provides a further layer of protection and provides some protection against competitors that have been proposed and appealed. So overall, we believe we have a very strong IP situation and most of these positions and appeal has been sorted out and has been ruled in our favor. So by that, I would like to hand over to Patrik and to go through the finances.

Thank you, Goran. And I'm just going to show you a couple of slides on the financial highlights. Goran has already mentioned a lot of things that have happened at Cantargia during the fourth quarter of 2023, but also during the full year. We have had -- we've done a lot of things in R&D, less costs than we incurred in the year before, both in the quarter and in the full year. But we are still doing a lot of things. We have one activities for the Nadunolimab projects, such as the TRIFOUR study. We are winding down the Phase I/Phase Ib studies CANFOUR -- and we are -- and that's also why you are seeing that we are reducing our costs. We are offsetting that, and we have offset that by increased investments in the Content projects, the Phase I study that Goran alluded to and also the preparations that we have done for the upcoming PANFOUR study. But all in all, the R&D expenses in the fourth quarter amounted to SEK 68 million, a reduction of SEK 20 million or 21% versus Q4 of 2022. And if we look at the other expenses in the quarter, they were slightly higher. And -- but all in all, we ended at SEK 71 million, SEK 19 million or 21% lower than 2022. If you look at the full year, our R&D expenses were SEK 273 million, again, lower than prior year by approximately 25%. And again, the same reason that I explained for the Q4, mainly the wind down of the Nadunolimab earlier clinical program and less CMC production costs in the year than in the previous years. We are happy that we have been able to keep our G&A costs. So our general and administration costs flat, although we have experienced quite significant inflation pressure. So we've been able to mitigate that by savings and cost reductions to make sure that we're not allowing that to slip away. So the net loss, so the total operating expenses amounted to SEK 290 million, and we were able to offset that through gains from interest rates and short-term investments of approximately SEK 10 million to report a net loss for the full year of SEK 280 million. And in terms of our cash situation, you know that we report total available funds as a net of our total of reported cash and cash equivalents and the short-term investments. And those amounted to SEK 195 million in the end of the year, and that included the proceeds from the share issue of approximately SEK 55 million net. With our existing plans, we expect that the current available funds will last into 2025. And with that, I'd like to hand over to Goran for the close.

So thank you. So I hope we've shown that it's been a good period for Cantargia that we have lots of things in the pipeline, and by showing this slide on upcoming milestones, I hope you share my enthusiasm for 2024 and what we have in front of us. So in pancreatic cancer trial would start of the Phase IIb trial mid this year with the Phase IIb top line data in 2025, including both, let's say, perhaps on all 150 patients as well as early results on 60 patients. We have much more to provide in non-small cell lung cancer once we have a long-term effect in all patients and biomarker data. And in triple-negative breast cancer, we expect to be ongoing randomized trials to be fully recruited and to have randomized Phase II data later on this year. And CAN10, we will continuously update the market when we have relevant news in the dose escalation and especially once we start to generate biomarker data. And finally, we have a number of clinical trials, which were basically stopped last year. Several patients have continued therapy as they've done well, and we are hopefully soon ready to present the results from those trials. And also, we have a number of preclinical translational studies ongoing. And once we have results from those that will be presented. So by this, I'd like to thank you for your attention. I'm very happy to take questions.

[Operator Instructions] The next question comes from Richard Ramanius from Redeye.

I have a few questions. Let's start with the financial ones. You reported liquidity of almost SEK 200 million, and you stated that will fund this year's activities. So that would imply a burn rate of around SEK 50 million per quarter. Do you have -- that seems low compared to your expenditure last year? Do you have any comments?

Yes, I can take that question. So during 2023, we still have several expenses in the CIRIFOUR, CAPAFOUR and CESTAFOUR the trials. Even to the trial stop recruiting quite a few patients continue to get therapy and the documentation monitoring. So with those studies terminated now, we certainly have a much lower burn...

Great makes sense. I'd also like to ask if you could discuss your funding options, if possible for the pancreatic cancer trial.

Yes. I think we have a number of parallel discussions ongoing and I don't want to go into to more concrete details around that until we are through with the financing of the Phase IIb trial.

Yes, I understand. And considering the readouts for this trial, when did you say the interim relate would be and the full readout from the 150 to 200 patients?

So the trial -- so it will be 150 patients, which would be 3x 50 patients. We will do the first analysis on 3x 20 patients, which is equal 60. And we hope to have those data early next year if recruitment rates can keep up as promising as the feasibility studies suggest. And then we will have data on the 150 patients towards the end of '25.

And then continuing on the same trial, you have an idea about the possibility of obtaining accelerated approval? Will you power the study to demonstrate a statistically significant overall survival?

Yes. So I think one of the options we have here is to have a discussion with the FDA based on the first 60 patients and together with the FDA to start to discuss the opportunities for breakthrough designation, accelerated approval? And if this means that the PANFOUR trial should be, let's say, expanded into a bigger patient population or if we should go another way, I think it's very much data-driven, but we're not excluding anything.

Okay. And my last question about the breast cancer study. I my assumption was that the ongoing Phase IIb or Phase II study will be Phase III enabling. Is that correct? And as a follow-up to that, this makes it a late-stage asset. How does -- how would that affect partnering these discussions and interest?

So yes, the Phase II is obviously a randomized trial in triple negative breast cancer. And if results are good, obviously the next step would be a Phase III trial in triple-negative breast cancer. And then exact details is pending. And when it comes to, let's say, partnering interest, again, it's one of these things where we always have ongoing discussions, but I don't want to, let's say, comment on more details around that.

The next question comes from Luisa Morgado from Van Lanschot Kempen NV.

I have a few. Maybe starting with PDAC indeed. Could you remind us how much is the PANFOUR study projected to cost? And in terms of operating expenses for this year, can we expect a further decrease or now to maintain stable? Yes, if you could comment on that, please.

So we -- so the pancreatic PANFOUR trial, we have not disclosed the exact cost, but I think you can estimate that each patient in an oncology trial like this would cost somewhere around EUR 100,000 to EUR 200,000 each, a little bit dependent on the territory they come from. So then you can probably make the calculations of how much a 250-patient trial could cost. And then for the runway, so without a pancreatic cancer trial, you should definitely expect the cost level to go down during 2024 compared to 2023. Once the trial is up and running, obviously, you will add this cost compared to what we've been guiding for. But currently, the cash we have on hand will take us into 2025 without the pancreatic cancer trial.

Okay. Very clear. And maybe could you elaborate a bit more in terms of PDAC. What is the FDA exactly looking? And in your view, what are the most important endpoints. So does the FDA indeed only look at million overall survival? Or is PFS also, yes, quite important.

So I think the short answer is that if FDA would value a survival advantage very high. And if you look at the recently approved nalirifox, it was approved based on overall survival. And then I guess if you have very convincing differences in PFS, that's definitely an opportunity to have a discussion with the FDA.

Okay. Very clear. And maybe just a last question on the triple-net breast cancer trial. What is the benchmark here that you're trying to surpass with the data that you're presenting at the end of this year?

So tripling at our breast cancer trial, it is primarily in hypothesis generating trial to understand the triple-negative breast cancer is a good indication. So the trial is not, let's say, fully powered for statistical significance. But we're clearly looking for strong signals of activities and the opportunity to perhaps also do some subgroup analysis.

The next question comes from Arvid Necander from Carnegie.

So first, on the PANFOUR studies, within terminal is being baked in and the sort of adaptive study design, do you see an opportunity for sequential financing where you wouldn't need to raise the amount for the whole study upfront?

So yes, in Prince, as long as we can finance our commitments, it's possible to do it in tranches.

Okay. And then secondly, on triple-negative breast cancer and the readout towards the end of the year. How should we think about positioning here? And what are the most relevant comparisons. I guess, with TROP-2 targeted ADC combinations being investigated both in the frontline and setting of the advanced setting and the new adjuvant setting, how do you expect nadunolimab to sort of fit into the paradigm here? And what are the most relevant comparisons?

Yes. So triple negative breast cancer, just like non-small-cell lung cancer, it is a landscape which is currently changing a lot. And I think there are various opportunities on how to advance nadunolimab in triple-negative breast cancer. So one is if you make it simple saying that if we have combination data with GemCarbo suggesting that this is a, let's say, an active combination, which is better than GemCarbo alone, clearly you need to figure out if this can be done in first-line, second line or if it's more a third-line opportunity in the future. The second, which I think is, let's say, a very exciting opportunity that we've seen -- we're starting to develop data suggesting that nadunolimab in combination with ADCs could be a very attractive way forward. So clearly, drop 2 combinations or whatever would come up in triple negative breast cancer could also be a way forward. So we're trying to figure out what is the best way, and we will have more advisory boards around this during the year and probably be in a better position to exactly communicate what is the best way forward in triple-net breast cancer once wharves and there is also more data to be generated with the Trop-2. So more to come, but I see several opportunities, both as a GemCarbo combination as well as an ATC combination.

Okay. And I guess just assuming that you go ahead, at least in the first step with the GMCAR combination. Is it fair to assume that the at least immediate opportunity would likely to be the second or third line setting of advanced triple-negative breast cancer, that's a fair assumption?

It's a reasonable assumption.

[Operator Instructions] The next question comes from Richard Ramanius from Redeye.

And I had another question about CAN10. Could you just remind us about how you're studying the IV versus the subcutaneous version and which you intend to go forward with?

So the subcutaneous is most likely the commercial opportunity, we're looking for, especially if you go into chronic diseases like systemic sclerosis for, let's say, very acute indications that could -- like myocarditis could be an opportunity for IV. But most of the diseases that could come in play, both systemic sclerosis as well as other dermatological or, let's say, more autoimmune chronic diseases would be subcutaneous formulation?

Yes. So we similar to the commercial version, how are you implementing this in your current Phase I study?

So based on the toxicity studies, we've seen, let's say, a very good translation between IV and subcutaneous. And in the single dosing where you're seeing IV infusions and in the multiple dosing, we will use subcutaneous.

The next question comes from Sten Westerberg from Analyst Guide.

Just a clarification on the dosing. There is -- you show a flat dosing in your schedule for the 4 study. Just to understand, is this equivalent to the dosing, which is used in TRIFR study 1 milligram per kilo, 2.5 milligram per kilo. That is my first question. The second one is if the top line data that you expect to release from Triple the -- by the end of this year will be based on the fully recruited population. Thank you.

So the first one, the flat dose versus the previous dosing per kilogram is basically based so they should be equivalent. So assuming that 1 mg/kg for an 80 gig patient would be 80 milligram. So that's a logic behind and 2.5% would then correspond to the 200 mg that we're using in the trial. We also done that PP analysis to show that this is a sensible way forward. The second one, the try-for data. So the goal is definitely to present data on all patients. But clearly, it will be short-term data for patients that are recruited later during the -- so it will certainly -- you can call it top line, you can call some kind of interim data, but it's -- it will be the first data set.

There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.

So thank you all for your attention. So I'm very positive about, let's say, how Cantargia can continue to evolve during 2024. And I look forward to give you an update during the next Q1 conference call, and I'm sure we'll have some exciting news in between. So thanks a lot.