Evaxion A/S (EVAX) Earnings Call Transcript & Summary

So welcome to this exciting webinar. On behalf of the entire Evaxion team, I would like to welcome you. This is our forward-looking statements and our disclaimer. I'm Birgitte Rønø, CSO at Evaxion. And today, I have the privilege to introduce a key collaborator Dr. Adnan Muhammad Khattak and Dr. Khattak is a medical oncologist at the Hollywood Private Hospital and a clinical trial lead at Fiona Stanley Hospital in Perth. Dr. Khattak is the primary investigator of many international cancer trials, focusing on novel anti-cancer therapies, including a personalized cancer vaccine. So this webinar is a 30-minute session and Dr. Khattak will begin by introducing us to the medical need of malignant melanoma and how Evaxion's personalized EVX-01 cancer vaccine is addressing this need. So following that, Dr. Khattak will provide a summary of some data that we have reported earlier on from our EVX-01 Phase 1 trial, and then he will share the current status of our ongoing EVX-01 Phase 2 clinical trial. So the session wraps up with a Q&A, and I would like to encourage you to post questions in the team chat and we'll read the question aloud and do our outmost to address them in the end. Thank you for joining. And now I will give the word to Dr. Khattak, so please go ahead.

Thank you, Birgitte. So first of all, I would like to thank Evaxion for giving me the opportunity to present at this forum. It's an excellent opportunity for future collaboration, particularly in the field of personalized cancer therapies. So hello to everybody, so good morning, good afternoon, evening, whichever part of the world you're in. So I'm dialing in from Philadelphia so it's sort of almost a new time here. From what I understand, the audience is mixed, particularly some of the audience might not necessarily have a medical background. Some of the slides might be quite simple for some of you so please bear with us. So I'll start off with what is melanoma. So melanoma is a fairly aggressive skin cancer, unfortunately, which starts in the melanocytes which, if you can see -- this is the top layer epidermis, the dotted one, then this pinkish one is dermis and then we got this yellow one, which is the hypodermis of the fatty layer and then the muscular layer. So at the junction of the epidermis and dermis, you can see the basal cell layer, and you can see these black dots. These are the melanocytes, which provide a pigment and the color to the skin and melanoma originated in these pigment cells. And unfortunately, can metastasize and limit the prognosis of our patients. So these are some quite confronting facts or statistics from Australian setting as well as from the U.S. setting, Australia where I work. Unfortunately, melanoma is Australia's national cancer due to the high exposure to UV radiation. And you can see about 17,000 patients were diagnosed with melanoma this year, out of which 1,300 unfortunately reported deaths this year. At least one patient is diagnosed in every 30 minutes in Australia with melanoma and unfortunately, one death happens every 6 hours in Australia due to metastatic melanoma. Coming to the U.S. setting. So, they've been estimated about a number that's approaching almost 100,000 new cases in U.S. and the percentage of all new cancer cases, melanoma was contributing 5%. The 5-year relative survival rates between 2013 and 2019, an excess of 90%. Please note, this includes early-stage melanoma as well as advanced melanoma. So research is definitely making a difference when I was a registrar about 10, 12 years ago. So these were the figures of 2011. This is when I was just about to go to the [indiscernible] in London. So these are the survival statistics. So in 2011, less than 10% 5-year survival rate for patients with advanced melanoma and at that point, just the first-line immune checkpoint inhibitors like ipilimumab were just being presented in clinical trials and the first data was published then. And then from 2021 onwards and now we can expect a 5-year survival of about 50% and melanoma was used to be the #7 killer cancer. Unfortunate Australia has now moved down unfortunately to #11. This is the survival curve for which you'll see in a typical presentation in immuno-oncology setting. We got a percentage of patients alive along the y-axis and then along the x-axis, you can see the time frame. And if you can look at 6.5 year time frame, this trial looked at a combination of ipilimumab and nivolumab, this is purple line. And then the blue line was for nivolumab and the green line was for ipilimumab monotherapy. And this is a 6.5-year survival statistics from the CheckMate-67 study where you can see that IPI-NIVO combination leads to various survival statistics of just over 50% and nivolumab closer to 50% and about 25% for ipilimumab. So this is good encouraging data, but it's still that almost half of patients unfortunately are dead at 5- to 6-year time points, the number of patients who fall off the Kaplan-Meier curve in this area, hence the need for better treatment. Another important point is that we also need to be able to predict who's going to respond to treatment. So when I -- in a clinical practice, when I'm talking to my patients, I tell them these good statistics that yes, we moved from 1-year survival of 25% to a 5-year survival of somewhere between 50% to 60% but I can tell an individual patient, are you going to be in the group of 50% of patients who're going to die or are you going to be in a group of 50% of patients who are going to be alive. So it is unfortunately quite frustrating that we don't have a good biomarker still available to us in clinical practice that can help guide treatment and help guide our patients. So that's been the role for personalized cancer vaccine. So because if I get 10 melanoma patient, largely we're treating them in a fairly similar manner with immune checkpoint inhibitors, whether it's in combination or a single agent treatment, and I don't have a good predictive biomarker, whereas advantage of personalized cancer vaccine is that we know that we all look different, we behave differently. So our tumors are likely to be different as well. So in the personalized cancer vaccine field, and what Evaxion did as well through the Pioneer technology that individual patients' tumor samples as well as their blood samples are sent off to a central lab, where DNA sequencing is carried out to identify tumor specific mutations. These are called neo-antigens or what we call in common words as a fingerprint of the cancer, which is unique for that individual patient's tumor, which will be different than any other patient on that clinical study. And then through Evaxion's pioneer artificial intelligence technology, the cream neoantigen has really picked up the most optimal neoantigens that are identified and then peptide vaccines are Evaxion is manufactured for those new antigens targeting them. And then the treatment is then sent back to the site where the patient is already receiving immune checkpoint inhibitor treatment because we don't want to hold up the patient's treatment while the vaccine is being manufactured. And that time frame is roughly 6 to 8 weeks at this stage with a growing understanding and availability for [indiscernible] hopefully that time will become less and less. And that is given in combination with immune checkpoint inhibitor to produce the antitumor effect. So this is the Phase I data from Evaxion's Phase I study of personalized cancer vaccine in combination with immune checkpoint inhibitor patients. So there were 12 patients included, you can see that we got this peptide vaccine chains. And then we got a central liposomal adjuvant to stabilize the vaccine, as CAF 09 and there is some immunogenicity, immune response associated with the liposomal adjuvant as well. So 12 patients with metastatic melanoma and the primary endpoint in the context of our Phase I study with safety and tolerability, 3 dose levels were tested and selected secondary endpoint was immune responses induced by EVX-01. So I'd like to concentrate on the bottom end of the graph, you can see the anti-PD1 treatment as per standard of care was given. And then it took about 6 to 8 weeks of production of the Evaxion vaccine. And then 6 [indiscernible] doses is every 2 weeks were given in combination with the immune checkpoint inhibitor. This some of the efficacy data, which is very encouraging, so if you look at this graph, so this is 0%, anything above it is an increase in the tumor volume, anything below it, minus 25, minus 50, this is a decrease in tumor volume. As an oncologist, we like to see these bars as much as possible and as deeper as possible to gauge an idea about efficacy of a particular treatment. So out of these 12 patients, 8 of them were responders. So the blue lines and the green bars. So they reflect responses so you can see that there are 2 complete responders. And then we see 6 lines, 6 partial responders. So 8 out of 12 patients responding, equating to an objective response rate of about 67%. As to the 2 complete responders, the treatment was generally well tolerated and there was no significant toxicity associated with Evaxion vaccine. Now one thing, as I mentioned to you before that our ability to predict responders and nonresponders is poor at this stage. We also know that there is a significant financial toxicity associated with all these in our therapies. They're making a lot of difference but in a significant proportion of patients, unfortunately, ends up being a wastage up [indiscernible] because these are high-cost drugs and if it doesn't work for patient that's a double negative, unfortunately. So as clinicians, we'll always like the idea of a companion diagnostic or a companion biomarker, which has helped us to identify and enrich patients or differentiate between responders and nonresponders. So I mean [indiscernible] cancer vaccine therapies for other sponsors as well, but what is specifically unique for Evaxion is the Pioneer technology. There is also AI-based biomarker and what we call the Pioneer score, which predicts on the presence of high-quality neoantigens. So if you look at these bars, the blue bar is for high Pioneer score versus the Red bar for low Pioneer score based on the median Pioneer quality score. So out of these 12 patients, they were sort of dichotomized into high and low, with the top 6 going into the blue and the bottom 6 going into the low expressers. And you can see some really encouraging preliminary data. I'll caution the fact that there's only 12 patients, but it's very encouraging at this stage. You can see the progression of survival for the pioneer high patient quite significant. We didn't see any such similar correlation based on the tumor mutational burden. But again, there's only a limited number of patients at this stage. So Evaxion 01 induced dose-dependent immune response in these patients. As you can see, new antigen-specific T cell responses, and this is the dosage that we go from 50 to 100 to 200 to 400 the peptide dosage, you can see that the magnitude of neoantigen-specific T cell responses is also increasing. And this immune response was seen both in CD4 positive cells, 12 out of 12 patients, and it was also seen in CD8-positive T cell with 712 patients showing a CD-8 T cell response. So on the basis of this encouraging Phase I data, so the Phase II Evaxion study, which we were involved with as well in Perth, in Western Australia. So this was initiated for patients with treatment-naive metastatic melanoma patients who haven't had any previous treatment, including neo-adjuvant treatment as well, and this was in collaboration with MSD. And with the new insights, the immune system based on data from the Pioneer AI, there's also plan to do the Pioneer scoring in the context of the Phase 2 study as well. So this is a design of the study. So the plan was to enroll 16 patients with metastatic melanoma in collaboration with MSD across Australia and Europe. And Pembrolizumab was given according to the standard dosing schedule, which is now 6 weekly. And then in the first 12 weeks, when the vaccine was being manufactured, even though the vaccine was made much earlier, so we decided to keep it fairly clean so that we can see what is the effect of Pembrolizumab in the first 12 weeks and then see what difference Evaxion 01 was making. So there are 2 components to the Evaxion dosing. So we've got a priming phase and then we go to maintenance phase or the booster phase. In the priming phase, starting at week 12, so we got 6 priming doses every 2 weeks apart, then there's an 8-week gap. Then we give another 3 booster doses 12 weeks apart. And then the last dose is given sort of between the dose 9 and those 10, there's a 24-week window in which the booster dose is given. This is obviously a work in progress. And hopefully, once we get more data of the booster doses, we'll be able to come up with the best regiment. What is important is obviously to see the new antigens that we've identified, are they able to initiate an immune response out of the peptide that have been made to target those new antigens? Are they able to initiate a T-cell response? As you can see in this graph, we got interferon gamma ELISPOT assay used to measure that response. And these are the 4 different time points: week 1, week 12. This is when Evaxion vaccine was introduced and then week of 10 and 30. So you can see we got 5 patients 1, 2, 3, 4 and 6. So these 5 patients, so at an introduction at week 12, you can see we start seeing these blue bars come through. And you can see from moving from week 12 to 18 to 30, in all these patients, we see new antigen-specific T cell responses and which we are identified by using the interferon gamma ELISPOT assay on the peripheral, sort of PBMCs. Graph B is summarizing. This includes all the patients and they're sort of summarizing the response that from week 1 to 2, you can see [indiscernible] from week 1 to 12 and then from 12 to 18, this is when Evaxion is introduced, you can see that the magnitude of antigen-specific T cell response is increasing. Now the new antigen-specific T cell rig activity, we sort of figured out, okay, is this happening? How much is affected in the CD4 T cells compared to CD8 T cells. As we saw in the Phase I study, all the patients had a CD4 T cell response. So 4 out of 4 patients who are available samples had a CD4 T cell response is 2 out of the 4 patients in the -- had a CD8 T cell response as well. And both CD4 and CD8 T cell can contribute to anti-tumor immunity. And I'd also like to highlight that the primary endpoint in this study was the best overall response. So it means that in the first 12 weeks, whatever was achieved from baseline to week 12 whatever was achieved by Pembrolizumab monotherapy to see if we can further improve on that. To see if somebody had stable disease or partial response whether that can be further improved to a partial response or a complete response. So you can see these 5 patients, so very early data. So we had 3 partial responders to Pembrolizumab monotherapy at week 12. So the bottom 2 partial responders, they continue to be in partial response, but the top patient #1, you can see at week 36, change from partial response to complete response that has been sustained at this stage. Patient #2, who started off with stable disease at the completion of the first 3 months of treatment with Pembrolizumab at week 24 transformed into partial response -- partial responder and that has been sustained so far. And then one of the most interesting patient is patient #4 who developed progressive disease at week 12 and 24. And through a collaboration with Evaxion, we continued both the treatments and now the team of volume is continuously decreasing and they've got stable disease from, obviously, the baseline, and I will explain that further in the next slides. Again, like in Phase 1 setting. So we did not see any significant negative safety signal associated with EVX-01. So I've got previous experience with the mRNA vaccines as well, so -- and I've had patients treated with mRNA vaccines as well. So it does lead to a response like the classical response that we expect with mRNA vaccines leading to flu-like symptoms for somewhere between 24 to 72 hours for many patients, which can be quite challenging for some patients if you're receiving the drug every 3 weekly. But in this trial and from what we know from the data from the Phase 1 study as well, patient did not have any significant reactions, so there were only grade 1 and 2 adverse events or the adverse event that do not lead to any significant patient mobility, grade 3 or higher adverse events are the ones that lead to pressure mobility and often hospitalization as well. So fortunately, we didn't see any extra or additional safety signals on top of the standard Pembrolizumab. This is the case study for patient #4. So he's one of my patient. So he is [indiscernible] gentleman from Western Australia. He is diagnosed with unresectable stage 4 melanoma and the target lesion that he had was in the right adrenal gland. He did not have -- [indiscernible] BRAF mutation and his LDH level was normal. So he was treated with Pembrolizumab monotherapy for the first 12 weeks, probably changed the next slide, I'll give you a better understanding. So this was his baseline scan in October last year, so when he hear the right adrenal gland as you can see in this arrow. So it was 28-millimeter and this was intensely FDA avid on the PET scan. As part of this trial, in which we see in many trials or most of the trial is that we do CT scan to assess responses. But obviously, the PET scan gives us additional information that we do from time to time for some of the patients, particularly in the standard practice. So at week 12, so where the patient only had Pembrolizumab monotherapy, 2 doses, 6 weeks apart. The tumor volume increased from 28 to 44 millimeters, you can see is around unfortunately, almost doubled in size. And then at week 12, Evaxion was introduced. And you can see there's a reduction in the tumor volume from 44 to 38 and in all the subsequent scans, so far, it has started to decrease. You can see the tumor volume in the graph between week 1 and week 12 increased and then started to decrease in volume after that. And what we can see in the PET scan in the baseline PET scan, you can see the dark black spot, which we can't really appreciate on the scan anymore, yellow spot. But I think if you go to the previous slide, yes, we're seeing about 27-millimeter left. But we look at where the Evaxion vaccine was started, look at the bulk of the tumor and see is only a narrow streak, so that's one of the criticism of the resist is that, obviously, you can still see some disease. But when you look at the metabolic profile or the more comprehensive imaging, you can see that there's no FDG ability seen, there's no metabolic activity seen in that tumor bed, which is a very, very encouraging activity that we saw in this patient. So moving on to the personalized cancer vaccine feel. So it is rapidly expanding. So you can see there's a number of sponsors evaluating their personalized cancer vaccines. And most of them in the Phase 1 setting. So with some of them just moving into a Phase 3 setting, like I'm involved with Phase 3 melanoma mRNA study of collaboration between Merck and Moderna, but the vast majority of them are in Phase I setting and some are just moving into Phase 2, including the Evaxion study. Again, this bar sort of summarizes that in the vast majority of activity in the Phase 1 setting. So this is very encouraging data coming through. So hopefully, in the next 3 to 4 years, we'll see more development in this field and we'll see more number of patients treated. So we'll get a better idea what is the efficacy of these treatments. And then this graph summarizes the number of new antigens, which has been used in different vaccines in different trials. We can see which is quite mostly variable and then it has been used in different cancer types. So almost half of the patient in the context of basket studies to try to get an efficacy signal in a particular tumor type. And then you can see the more immunogenic tumors like melanoma and non-small cell lung cancer, where most of the activity is happening. But then also tripling the breast cancer and some gyne cancer, it is being evaluated as well. It is being validated as monotherapy as well as in combination with other checkpoint inhibitors, including anti-PD-1 monotherapy, chemotherapy and also combination checkpoint inhibitor treatment as well and what route we use, subcutaneous, intravenous, so that's an area of development as well. So to conclude, all of the outcome of melanoma patients is improving, and it has improved over the last decade, but there is unmet area of need where there are certain patients who do not benefit from the current treatment and our ability to identify those patient remains poor to different share between responders and nonresponders. So moving on from chemo to immune checkpoint inhibitors and then from immune checkpoint inhibitor, now the field is moving on to the personalized vaccines, where we say to treat the right patient with the right drug at the right time through the personalized cancer vaccine. So they thought would be feasible, safe, on the basis of early data that we have. And we're seeing immunogenicity, as I showed in the slides earlier, related to Evaxion. Evaxion 01 has shown promising early clinical activity with a good safety profile. And then one thing unique about the Evaxion is the Pioneer scores ability to differentiate between responders and nonresponders is to see if we can tailor a treatment or combination treatment, the patients who really need it. So thank you.

Thank you, Dr. Khattak for presenting the EVX-01 clinical data and for sharing your perspectives. It's highly appreciated. And we now have time for a few questions. So please type in your questions in the chat. So we have a question regarding the CD4 and CD8 T Cell responses in the Phase 1 and Phase 2 studies so I will read it aloud. So CD4 T cell responses were higher than CD8 response in both EVX-01 in Phase 1 and Phase 2 data. Why is it and how would it impact your ability of the immune response. Should I answer that?

Yes, I can start, and you can add it as well. So I think, as I mentioned, it's a good observation. So -- but I think we can't make any strong claims based on very limited number of patients at this stage. I think that what we're seeing specifically with the Evaxion vaccine is the durability of response. And hopefully, once we get more sample analyzed at the later time points because we only presented only to 4 time points, we'll get a better idea about the durability of the response as well. And then we're seeing the antitumor immunity, where both CD8 and CD4 T cell count can contribute to it. But I think once we get more data, we'll get an idea about durability but it's interesting observation at this stage that there's more CD4 T cell responses compared to CD8, which you correctly identified.

Yes. So we have observed in our EVX-02 Phase 1 trial that we have a higher CD8 response. And that is due to the fact that EVX-02 is a DNA-based vaccine. So that automatically leads to a higher CD8 T Cell response. But for peptide-based vaccines, there is a tendency that they drive a stronger CD4 T cell response. And I think that it's important that we have both CD4 and CD8. So we are not -- we don't commit to either or we believe that there should be a balance between these 2 types of T cells. And I think what we have seen in both EVX-01 and EVX-02, that is that we do actually induce a very durable response, and that's not related necessarily to the modality of the compounds, but related to the fact that we have a nice balance between CD4 and CD8, T cell responses. Yes. We have a question from [ Thomas Flaten ] and a point was made to call out patient force stable disease being measured from baseline. Are not all responses calculated from baseline.

So I think what happened in this patient, obviously, you can see the tumor volume increase. So if we measure from the peak diameter, which was 44-millimeter and has dropped now to 27 millimeters. So we can't just say this is response for this patient. Even though we're seeing that the patient has had a complete metabolic response that's one point. But number two, the volume increased to 44-millimeter and had progressive disease. So by resist once somebody has developed progressive disease, you can't just say that on the basis of resist 1.1, you can't say that if somebody has progressed that they can be responder later on, once they progress, they progressed. So what we're saying that with the [indiscernible] is that compared to baseline, you can see that it has remained stable disease. But if you look at how the tumor kinetics are reflected. You can see there's an ongoing decrease in tumor volume. I'm fairly confident this will drop off in the next one or two scans completely. Then there's also a question, I think, regarding how long does it take to, I think, the question by Doug. Thank you for the presentation. Can you please elaborate how long does it take to produce vaccine? And can you reveal who prepares peptides and vaccines for the trial? So I mean, from my experience with mRNA vaccine as well as with the peptide vaccine in this trial. So even though we started the vaccine a 12-week time point, but that was not because we couldn't start the vaccine earlier, but this is just to keep that 12-week window clean because the overall -- or the primary endpoint was to try to identify what can we do further on top of Pembrolizumab as the best overall response. That was one thing, even though if you look at the Phase 1 slide that I showed you in the beginning, so you can make the vaccine within 6 to 8 weeks, and that is sort of the time frame that we're also seeing in the mRNA vaccine as well. But I think all the companies are trying to shorten that time frame because particularly in the metastatic setting, you want to get a sample center quickly and get your personalized cancer vaccine, started as soon as possible. In terms of who makes the peptides, I don't remember the name of the lab Birgitte, do you remember, sorry, for the vaccine?

Yes. So the peptides are being manufactured at a Dutch company called [indiscernible].

Yes.

Yes. So thank you for all the questions. So unfortunately, we are running out of time. So I would like to conclude the session by thanking Dr. Khattak for presenting our encouraging EVX-01 Phase 2 findings and to all the participants for joining this webinar. Thank you all.

Thank you.