Immutep (ASX:IMM) webcast for TACTI-002 data presented at ASCO 2022

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Immutep Limited (ASX:IMM) Executive Director and CEO Marc Voigt, Chief Scientific and Medical Officer Dr Frédéric Triebel, and Vice President Strategic Development Christian Mueller present on Immutep's latest clinical results.

Tim McGowen: G'day, ladies and gentlemen, and thank you for joining us for this Immutep (ASX:IMM) investor call to discuss the company's new clinical results from its Phase II TACTI-002 trial of its lead product candidate, eftilagimod alpha in patients with lung cancer.

My name is Tim McGowen and I'll be your moderator for today. The format today will be a presentation delivered by Immutep, and at the end of the presentation, we will open the call for analysts' questions. I will also relay any other questions received via e-mail prior to this call. I would like to now hand over to Marc Voigt, Immutep's CEO, to start the presentation. Marc, over to you.

Marc Voigt: Yeah, thank you, Tim. And, as usual, our forward-looking statement. And a warm welcome, everyone. I thank you all for joining us on the call today. Here with me is Frédéric Triebel, who is our Chief Medical and Chief Scientific Officer, and also the person who discovered LAG-3, and Christian Mueller, our Vice President of Strategic Development.

And we are very excited to walk you through the exciting results from our TACTI-002 clinical trial, which met its primary objective for first-line non-small cell lung cancer. The trial has been conducted in collaboration with MSD, or in the US known as Merck. And I will just make a few intro slides and then we try to come directly to the data.

First of all, I would like to note a few changes in the LAG-3 therapeutic landscape. So we see more trials being initiated, notably Phase III clinical trials by Bristol Myers Squibb, by Merck, by Regeneron, so more activity. That's quite good, especially for us. Also, I think it's pretty clear that we will focus today on eftilagimod alpha, or efti, here on the top left hand side.

And just to be very clear, and we have been showing it also at the ASCO at the oral presentation, with thousands of people being present and looking at our data, that we have with eftilagimod a unique MHC class II agonist, so not another version of an immune checkpoint inhibitor, but really a unique program. And we test eftilagimod in combination with, for instance, pembrolizumab or some of you know it may be better as Keytruda, or with chemotherapy, really in a variety of different indications, different combinations in, I believe, a good clinical program. That was already all and I would like to hand over to Frédéric because most important is the data here.

Dr Frédéric Triebel: Thank you, Marc. Turning to slide 10, let me give you an overview of the TACTI-002 trial, which is testing the combination of efti with Keytruda, also known as pembrolizumab, or pembro for short, in up to 183 patients at sites in Europe, the US, and Australia. So, today, we are presenting results from just Part A, first-line NSCLC patients. For a total of 114 patients with first-line NSCLC were enrolled and treated with efti plus pembro in six countries across 19 trial sites throughout Europe, the US, and Australia.

These patients were given the combination therapy of efti and pembro for up to a year and then progressed into pembro monotherapy for up to another year. And the primary endpoint for these patients is overall response rate according to iRECIST and local read. iRECIST is an accepted measurement standard in trials involving only immunotherapies.

So the data announced at ASCO and discussed here today represents the primary analysis of mature data of this endpoint. Of course, there are some secondary endpoints, including ORR by RECIST 1.1, DCR, Duration of Response, Progression Free Survival, OS, as well as safety assessments. And we will discuss some of these too.

Now let's look on the next slide at the epidemiology of non-small cell lung cancer, there are 1.8 million people diagnosed each year with NSCLC and it is the most frequent cause of cancer deaths. And roughly 1.3 million people develop metastatic disease and need to receive an anti PD-1 therapy such as pembro. So this is an unmet medical need as a median overall survival for patients receiving currently available treatments is less than 24 months.

The standard of care is doublet chemo plus pembro in patients with a TPS score less than 50 per cent and pembro alone in patients with so-called the hot tumour phenotype, meaning a TPS score of more than 50 per cent.

Slide 12 takes us through some of the statistical consideration for the trial. In fact, one of our key assumptions for this part of the trial is that 20 to 23 per cent of patients would have been likely to respond to pembro as a monotherapy, according to calculations made from the results of KEYNOTE-001 and KEYNOTE-042 trials.

In order to get a significant clinical benefit and an improvement by 50 per cent, we estimated that we should get a response rate of at least 35 per cent for the combined therapy compared to 23 per cent. So, the design here is, of course, assignment to stage design and after implementing stage one and two, there was an expansion phase with a total, as I said, of 114 patients recruited.

On slide 13, we provide details around the baseline characteristics of the patients as they enter the trial. So, the trial was designed to be unselected for PD-L1 status. And, as you know, PD-L1 is a very important biomarker indicating the likelihood of response to pembro. So, this is quite rare as a trial design, as most trials focus on patients with PD-L1 expression or TPS score more than 50 per cent. And there are examples for that, like, for instance, anti-TIGIT plus anti-PD-1.

In TACTI-002, we had patients across the PD-L1 expression spectrum, and in fact, more than 70 per cent of patients at a TPS score of less than 50 per cent. So, it's really making it an all-comer trial. Other patient characteristic reflects what you expect for late stage non-small cell lung cancer.

And now moving to consider safety on slide 14. Yes, as you see here, a combination of efti and pembro was safe and well tolerated. And now if you look in the table on the left, you see grade four TEAE and grade five. But of course that doesn't mean this TEAE is related to treatment. And only 11 patients are to be permanently discontinue treatment. So, less than 10 per cent. And that is what is expected with pembro alone.

On the next slide, you see that the frequency of adverse events that are related to some immune etiology like pneumonitis, we had one grade four, one grade five. Hepatitis, we had one grade four. This is typical of what you see with pembro alone. So, overall, the safety profile, including, of course, immune-mediated adverse events due to pembro, is comparable to pembro monotherapy. The only additional toxicity or tolerability symptoms are in 20 per cent of patients, any type of local injection site reactions, inflammation like erythema at the subcu injection site. And this is due to the mechanism of action of efti, which is the activation of cells locally.

So now I will hand over to Christian Mueller to take you through the key efficacy results. Christian.

Christian Mueller: Thank you, Frédéric. I hope everybody can hear me well. And more than happy to guide you through these exciting efficacy data today.

Looking at slide 16, here we present the key TACTI-002 efficacy results, and their overall response rate, and then also disease control as detailed in the table with the cut-off of 15 April 2022.

The primary objective of the trial, the overall response rate according to iRECIST, as reported here at ASCO, was 38.6 per cent in the intent to treat population, which means the most conservative approach in all patients who have been recruited. If you just look for patients who are evaluable for efficacy, meaning they have at least one CT scan after baseline, the response rate, according to iRECIST increases to 42.7 per cent. So, overall, the trial has met its primary objective. As Frédéric just explained, we were looking for response rate equal or higher to 35 per cent. So, clearly, 38.6 is above that. More importantly, RECIST 1.1, one of the standard methodologies, the overall response rate here is 37.7 per cent. So, very consistent with what you see with iRECIST.

Now let's look at the ORR breakdown by PD-L1 status on slide number 17. As mentioned, the PD-L1 status is very important for pembrolizumab alone in terms of the likelihood that the patient will respond to pembrolizumab. Firstly, it's important to note that the responses we observed were across all PD-L1 groups, and we will come later to the benchmarking and what that means and what the increase is.

In PD-L1 negative patients, we saw a response rate of 28.1 per cent. In patients with a PD-L1 score of 1 to 49, 41.7 per cent. And in patients with a PD-L1 of 50 or higher, 52.6 per cent. And the disease control rate as also reported here was between 68 and 79 per cent. So, it's really great to see actually that even patients who would normally not be expected to respond to pembro, respond to the combination therapy with efti. Importantly, the reported ORR is favourable compared to historical trials of anti-PD-L1 monotherapy in all the different PD-L1 subgroups, and I will guide you through that later when we come to the benchmarking.

Given the trial size, the number of patients in each of the subgroups was also sizable and was one of the reasons for us to enlarge the trial. And I think it's very important for us to maybe highlight that again, that based on that extension, we have a very robust patient number in each of the groups and the results are really reliable.

On the next slide. On the top chart, you see the waterfall plot, by PD-L1 levels. So the different colours represent different PD-L1 subgroups, and one can see that in each of the subgroups, as explained before, we see responses according to iRECIST and to RECIST. Overall, 19.4 per cent of the patients had a decrease of 50 per cent or more of their target lesions. And the charts tell us that the responses are deep and there's a significant decrease in the size of the tumours in all the PD-L1 subgroups.

Let's have a look at the bottom chart here on the left. The spider plot. Gives you an idea of the patients or the tumour journey basically while the trial is moving along and the chart helps us to understand the duration of response or the duration of stabilisation of disease, which is equally important to the depth of the response, which is shown in the waterfall plot above. The waterfall plot here, it's not splitted by PD-L1 level, but by response. So the blue chart is the patient with the complete responses, the greenish yellow, the patients with the partial response, gray, patients with stabilization of disease, and pink, red, the patients with progressive disease.

And what's important, take-home message from that chart, is that basically after six months, only very few patients have progressed when they had a response to the combination therapy. In numbers, 8.6 per cent of the patients with a confirmed response progressed within the first six months until the data cut off. And that's quite comparable to what you see with pembrolizumab alone.

And we believe that's actually one of the key differentiating factors of IO/IO therapy compared to IO plus chemotherapy. It's maybe not as prominent in non-small cell lung cancer as in head and neck and maybe gastroesophageal cancer. But you also see it there that you get higher response rate with chemo IO, but the duration of response drops. And it's very important for us to track that. And until now, this tracks really well compared to pembro alone. Importantly, the median duration of response has not yet been reached. And obviously we will monitor that further.

Turning to slide 19. Here we are looking at interim progression-free survival of the patients. This endpoint is not final yet, and we are still tracking the patients as a lot of those are still under therapy. On the left hand side, the plot shows all 114 patients grouped together, regardless of the PD-L1 status. Here, the interim PFS is 6.9, so almost seven months, meaning the median timeframe patients continue without getting worse is 6.9 month.

If you then look on the right hand chart, we break it down by the different PD-L1 subgroups, and the interim median PFS for those with a TPS score of 1 to 49 was 9.3 months, and it was 11.8 months for those with a PD-L1 of 50 per cent or higher. Overall, we feel that median PFS and overall and in all PD-L1 subgroups is really encouraging and supports, actually, the overall response rate results and, as discussed before, will be monitored further.

Let's conclude on the data itself and let's have a look into the benchmarking. And on the next slide and the next two slides, actually, there are a couple of important benchmarkings to be done with this data. Let's start on slide number 20 with a comparison against pembrolizumab monotherapy, which was the main aim of this trial to show that efti plus pembro is better than pembro alone. And across two endpoints of overall response rate and PFS, and across all PD-L1 subgroups, efti increased the efficacy by a large margin compared to all available historical data reported for pembrolizumab monotherapy in a comparable patient subset.

The objective of the trial is to demonstrate that efti and pembro increases the overall response rate in a PD-L1 unselected patient population compared to historical pembrolizumab monotherapy. And if we have proven that this, in this case, in TACTI-002, is actually the case as we have met the primary objective for this patient group. The chart on the left here compares the overall response rate for efti plus pembro in the green bars and pembro alone in the blue bars. For overall, that's the first two columns. And then by the different PD-L1 subgroups.

As you can see, the biggest effect absolute you see, and also relative you see for patients with a PD-L1 start of less than 1 per cent or PD-L1 of 1 to 49. And the same is actually true if you look on the figure on the right where we displayed that for median PFS. So the median PFS in 1 to 49 increases from 4.1 month to 9.3, and it increases from 7.1 month to 11.8 in above equal to 50 per cent.

And I would like to highlight again that we are seeing the highest effects in the PD-L1 low and PD-L1 negative patients. And, to our knowledge, efti is the only immuno-oncology treatment with such a therapeutic effect in low and negative PD-L1 NSCLC tumours, which has data not only from 10, 20 patients, but in a larger patient population.

On slide number 21, we make a second comparison to the current treatment landscape for patients with a PD-L1 level of 1 to 49 per cent. I think it's well known and accepted that pembro alone works well in PD-L1 high, so above 50 expressing patients, and is widely used there as a chemo-free option. Here, we compare the overall response rate on the left and the median progression-free survival on the right of efti plus pembro and pembro monotherapy, along with pembro and the deep double chemotherapy for patients with a PD-L1 level of 1 to 49 per cent.

There are two bars here for the pembro plus IO combo, pembro plus chemo combo because there are different chemos for non-squamous and squamous cell cancer. On the left figure, the ORR is almost comparable to what you achieve with chemo. And PFS exceeds what you see with chemo plus pembro. Hence the combination of efti and pembro could offer a chemo-free regimen for this patient population, with a much preferred safety profile, as Frédéric just explained, and durable responses, something which has never been reported for an IO combination, especially not with such an excellent safety profile.

Looking at slide number 22 now, here we provide a benchmark of our results against other IO combinations in development. ORR and PFS from TACTI-002 trend favourably. And the data is more compelling than for anti-TIGIT and anti-LAG-3. The efti combination benefits a much larger patient population due to its orthogonal therapeutic effects coming via the APC activation and not another ICI that complements the ICI effect of pembrolizumab.

Overall, we are more than pleased with the data, and to maybe give you an insight from ASCO, basically, we're approached by everyone who congratulated us to the results here at ASCO. And obviously that supports our confidence in the data.

I will now hand back to Marc, who will talk about how efti is positioned in the treatment landscape. Thanks a lot. And Marc, please take over.

Marc Voigt: Yeah, thank you, Christian. So I'll make it rather short again. This is practically the slide Frédéric has been explaining a few minutes ago. So, the efti positioning in the treatment landscape, especially keeping in mind the still high unmet medical need, with a median overall survival in general below 24 months. The low efficacy of anti-PD-1 monotherapies for the vast majority of patients. So around about 70 per cent of patients. And the compromise you need to make if you take a chemo regimen in terms usually of shorter duration of response and a more toxic option for the patients and also more co-medication in order to cope with the tox profile.

So, we believe that overall and in the different categories, eftilagimod has very good chances to be positioned. And I'm not aware, just to stress what Christian has been mentioning, I'm also not aware of an IO/IO combination, a PD-L1 all-comer clinical trial with a sizeable patient population. Achieving that, it was maybe not a surprise that we got an oral presentation at ASCO with the data you just have been seeing, and it's noteworthy that this is interim data. So it's a primary readout of the primary endpoint, meaning we have practically been logging in the bar for overall response rate. And there is, of course, more to come.

So we saw an overall response rate by iRECIST of more than 38 per cent, exceeding what we presented at ASCO last year for the 36 patients, where we saw 36.1 per cent. And we actually expanded together with our collaboration partner, the first non-small cell lung cancer group in order to see, first of all, is the signal we detected holding in a larger patient population? And if that's the case, to generate from the data options to move further, to move possibly into Phase III.

Also, if you look into the data, iRECIST, RECIST 1.1, so different qualifying factors. I think we transparently showed that at ASCO. And also here. There is, as mentioned, more to come in terms of, for instance, central read, duration of response, progression-free survival is interim, but the very first data cut from the 114 patients, it's fair to say that we are very excited, and that this excitement I believe is also reflected in the community. So I would like to thank you very much for these results.

A brief outlook before we turn to Q and A. ASCO is, of course, not a full stop. There is a second half of this year. You will see more data coming from TACTI-002, for instance. Please do not forget that we have also INSIGHT-003. And the strategic importance of INSIGHT-003, where we test anti-PD-1 plus eftilagimod plus chemotherapy, also to have a look there, has just been increasing.

Also we have TACTI-003 in first-line head and neck cancer currently recruiting. We will qualify how the study is tracking from second half of this year onwards. We are working on the scale up, on regulatory, of course. So there's a lot to expect in terms of data and other meaningful updates also in the second half of this year. And of course also in 2023. And there will be more talking points around LAG-3 in general. So we expect the BMS drug being approved. They had a big booth here at ASCO, being approved in Europe. We expect also more data coming out of that space.

And now I will pass it back to Tim for questions from analysts and also for questions which have been submitted to us in writing by the audience. Thank you.

Tim McGowen: Thanks, Marc. We'll now open the call to analyst questions, and we request that analysts just limit their questions to one at a time, and you can re-join the queue to ask a second question if you like, unless that second question is just a clarifying question, in which case we'll just move ahead straight away. We've got lots of questions coming in, Marc. If you want to ask a question, please raise your hand, and I'll invite you to turn on your microphone when it's your turn. The first question comes from Ahu Demir, who is from Ladenburg.

Ahu Demir: Thank you very much for taking my question. Congratulations on the data. I do have a couple questions, but as per Tim's request, I will get back on the queue. I think my initial question would be, you have shown clinical activity across multiple PD-L1 expressions. Where do you see the sweet spot for efti? Is it the 1 to 49 per cent separation that you show in one of the slides? And how would you position it if you would pursue the lung cancer space?

Marc Voigt: Yeah. Well thank you. That's obviously very important. Good question, indeed. I think especially 1 to 49 per cent PD-L1 expression, where we did not see an overlap of the confidence intervals between the historical pembro data and the combination data, is a special sweet spot, without ruling out the others. So you could broadly position eftilagimod in the field on the one hand side as a chemo-free option, maybe above 1 per cent TPS score, but potentially you can also include chemo if you look, for instance, at below 1 per cent or at an all-comer patient population.

The initial safety data from INSIGHT-003 was positive. So there are actually a variety of different options. The data is so strong that, unlike anti-TIGIT, where they needed to focus after the first data set on PD-L1 high, because it was simply not really working in 1 to 49 and below 1, we have a variety of different development options which we can pursue.

Tim McGowen: Thank you, Marc. Next question is from Andrew Paine from CSLA. Over to you, Andrew.

Andrew Paine: Morning, everyone. And congrats on the data. Just a bit of a follow up to that one. So the 1 to 49 separation, just trying to think, how material is the uplift to current patients on Keytruda monotherapy. Just thinking about how many patients would respond to this therapy versus the currently treated either Keytruda mono or Keytruda with chemo.

Marc Voigt: Yeah. Typically in terms of response rate in 1 to 49, you see a response of around 17 per cent with pembro mono if you look at the KEYNOTE-001, KEYNOTE-42 trials. While we saw 41.7 per cent, it was no overlap of the confidence interval, so we would actually significantly increase the response rate. And we saw also an increase of the median progression-free survival by twofold or more than twofold. I don't know, Christian, if you would like to add to that.

Christian Mueller: I think it's important if you think about the patient perspectives here… and that's what we try to do, right? We try to improve the patient's treatment options. And in case you could offer a patient a chemo-free regimen in the first-line setting, not just to above equal to 50 per cent, but maybe above equal to 1 per cent, where actually pembrolizumab is approved in the US as such. You have more options in the second line setting, then. You're not out of options as it is nowadays when you have given the triplet combination. Thereafter, only docetaxel. So there's a lot of thoughts, us together with the regulators, we need to put into the best trial design to move forward here. But from a scientific point of view, I feel that the 1 to 49 really opening up a sweet spot. And I think we should not just think about non-small cell lung cancer on the long run, because if you see that here, you could also expect that this could probably hopefully be the case in other indications. So you could enlarge the patient population eligible to chemo-free treatments with an excellent safety profile.

Tim McGowen: Thank you. We'll move on to our next question. The next question is from Tanushree Jain from Petra Capital. Over to you. Thank you.

Tanushree Jain: Thanks guys. And congratulations on the very good data. Just a quick question for me. Around the squamous and non-squamous results that we've seen, it doesn't look like there's been a huge difference in overall response rate on these two. Going forward, especially if you go against chemo and Keytruda, where they actually had two different trials for squamous and non-squamous. what would you expect would be your target?

Marc Voigt: Christian, would you like to take that?

Christian Mueller: Yes. Sure. So, I think it's important to note that the main reason why there are two trials for the pembrolizumab and the different entities for non-small cell lung cancer is the chemo backbone. So, they just wanted to have a clean trial at the time with one chemo backbone. As in KEYNOTE-042, they also enrolled, which is pembro mono, they enrolled squamous and non-squamous, if I'm not mistaken at the same percentage we have. So whatever you would go ahead, you would probably try to have a trial where you could combine that in one trial. And I think that's what most of the competitors are doing nowadays, running a trial with both entities in one trial, and then obviously a mixed statistical assumption. So, long story short, we do not expect that the combination works differently in squamous and non-squamous. Obviously with the chemo, there's a little bit of a difference expectation, but this would be taken care of by a stratification.

Tanushree Jain: Thank you.

Tim McGowen: Thank you. The next question's from Tara Speranza from Bell Potter. Tara.

Tara Speranza: Yeah. Hi. Thanks kindly. Great results. Well done. Congratulations everybody, Immutep. I have a very similar question to the last one. I know that stratifying by PD-L1 levels is really important for you, and I understand that and that result was really clean and clear. So, I also wanted to know about the histological pathology and whether or not you stratified by other variants. So, squamous cell and non-squamous cell, of course, was just asked in the previous, but what about adenocarcinoma or any other histological variants? Given that you sort of answered that question just now, I'm going to add in there a quick cheeky second half. What about stratifying by stage of cancer? Thank you.

Marc Voigt: Yeah. Thank you, Tara. Christian, I hand over to you.

Christian Mueller: Yeah. In the TACTI-002 trial, as reported by Frédéric earlier, we had 93 per cent with metastatic disease at study entry. So, if you would expect a similar patient population in a Phase III, which is basically all the patients have metastatic disease to stage four, you would not stratify for that as the other group is too small, but definitely something to consider that you to know, to make sure that you have similar stage of disease in all the patients in both arms.

Tara Speranza: Thank you.

Tim McGowen: Next question's from Melissa Benson from Wilson Advisory.

Melissa Benson: Thanks very much. Hi, Frédéric, Christian, and Marc. I just had a question around progression-free survival. So, obviously this was just an interim readout, but if we focus on those PD-L1 negative patients, that's sitting around that 4.2 months, how should we think about expectations and benchmarking in that particular group? Given that it's not that easy with some of the other trials excluding those patients.

Marc Voigt: Yeah, I believe the PD-L1, no representative patients. We saw an increase in terms of PFS, by the way also an increase from last year's ASCO, where we reported, if I'm not mistaken, 4.1 months and not 4.2, which is good, but of course you can ask yourself the question, if for instance, the addition of chemotherapy could help there. So, in a triple combination or not. This would be one consideration, but in any case, it's something where pembro mono is obviously not been given or approved and to make those patients eligible to treatment, and one needs to dig a little bit further into that, could indeed be very attractive. I don't know, Christian, if you have additional thoughts on that.

Christian Mueller: I think it's, as you just mentioned in outline, I think it's very hard to compare to anything as there's just KEYNOTE-001 with a very small number of patients, but there was a good reason why it wasn't further developed. So you can expect that whatever you compare to is basically zero activity, or let's say 10 per cent... Around about 10 per cent response rate, but probably a PFS which is very inferior. And how to take that forward, I think it's something to be seen. First of all, it's interesting to have this positive signal on the overall response rate side of things.

Tim McGowen: Next question is from Dennis Hulme, who is from Taylor Collison. Dennis?

Dennis Hulme: Good morning and thank you. My question's probably more for Frédéric and Christian. With the Keytruda monotherapy benchmark data, that's based on confirmed response rates. So once you adjust for the proportion of confirmed responses in the efti combo trial, if you can compare that to Keytruda monotherapy, it looks like there's only a modest benefit compared to the PD-L1 high group, but a very strong benefit in the intermediate PD-L1 expression group. In contrast in head and neck cancer, the biggest benefit you saw was in the PD-L1 high expressing group. So, what do you make of that difference? And does it tell you anything about the way efti works in different cancers or different patient populations? Thank you.

Marc Voigt: Christian or Frédéric.

Christian Mueller: I can start. So maybe let's start with confirmed versus unconfirmed. So obviously this trial here is ongoing, and so most of the responses as reported have already been confirmed and other responses may come on top of that, and the responses which have not yet been confirmed, they may still be confirmed. And there's high likelihood that this will be the case.

Second, looking into KEYNOTE-001, which is a major contributor here, I tried to find it actually out, and drilling deep into the SAP and the protocols, and that looks to me that the response rates MSD reported at the time was not confirmed, but unconfirmed, as they just want to report a confirmed response rate with the final data. But they brought out the paper three months after last patient. So, probably not the final data, but it's just of note.

I think there's a key difference between non-small cell lung cancer and head and neck. This is TPS or tumour proportional score, and the combined proportional score, CPS, in head and neck. So, I think comparisons between the two trials are rather difficult. And another caveat is that in the TACTI-002 trial, the negative patients were just very few. Top of my head, I think it's five patients with a CPS negative score. So it's very difficult to actually draw that comparison. And the 1 to 19 look pretty well in the head and neck space as well.

So the way we see efti working on top of pembrolizumab, as pointed out today in the presentation, is that you increase the number of T-cells of the tumour. You increase the interferon gamma signature. And thereby probably increase the PD-L1 expression in the tumour, hence pembrolizumab works better. But Frédéric, maybe you want to comment on the scientific side of things.

Dr Frédéric Triebel: Yes, sure. I think from an immunological perspective, it is clear that non-small cell lung cancer is more immunogenic than head and neck, and there are many more neoantigens there. And therefore, pembro is more likely to work in non-small cell lung cancer with high TPS, the so-called hot tumours, while in head and neck, even though patients may express high level of PD-L1, you may consider these patients are thought of as having tepid tumours comparable to what you see in 1 to 49 per cent TPS in NSCLC. So that may be why efti seems to work well in head and neck, even in patients with a high CPS score. That's one way to look at it. But of course I have no definitive answer on that.

Dennis Hulme: Okay. Thanks for that.

Tim McGowen: Thank you. There's a further question here from, on e-mail, from Jackie De Donder. She says, congratulations on the Phase II TACTI-002 data. I would like to hear from management how they plan to approach Phase III strategically. If the data is that convincing, why wouldn't Merck take over the trial?

Marc Voigt: Yeah, that's of course an important question. On the one hand side, you have the results, then on the other side, you have a number of strategic options. So, let me say one thing very, very clear. So, we will not go crazy. And I said it before ASCO, I will say it thereafter, and start now on our own multiple different Phase III clinical trials and risk our existing cash life, which we, by the way, extended in the last activities report to the beginning of 2024. So, we will take that as a very important number, especially in a market like this, where I would also, and I did that before ASCO and I will do it thereafter, I would like to clearly rule out any short-term capital raise. Of course, this can't be an indefinite statement, but we are of course not pleased with the share price right now. This may be as a private comment here. But there are a variety of different options.

First of all, we have options within our existing budget. We carefully planned and allocated our resources. We said publicly that we are going to expand our eftilagimod pipeline, on the one hand side horizontally, meaning potential additional signal detection studies in other indications. And on the other hand side, we have been talking about a Phase III -- to be more precise, about a Phase III in metastatic breast cancer. And if we can entertain one Phase III, then we have to make choices and we have to take the right priorities. And we will in very due course inform the market about the priorities.

I think it's pretty clear that non-small cell lung cancer is a commercially more attractive target than the space in metastatic breast cancer, where we saw also some more data coming at ASCO so there could be... The final decision needs to be taken by the board, but there could be a certain tendency towards non-small cell lung cancer.

These are options within our own control. Now, in addition, of course, data talks and the talks to the community, the data has been published at Friday. Christian made the comment that we have been approached, or we have a number of meetings, and of course you can do clinical trials alone, or you can do it in collaboration. Actually, TACTI-002 is done in collaboration with Merck, where we have with Merck and with others discussions. So you can assume that there are meetings. You can assume that the data and the press releases have been reviewed and so on and so forth.

So there are, of course, also usual options, opportunities within the normal parameters of our industry from licensing. The question indicated a takeover, obviously M and A this year. We all noted the deals with Sierra Oncology and we noted the deal in the APC activator space. Eftilagimod is an APC. There has been a transaction of Checkmate Pharmaceuticals being acquired by Regeneron for four times the share price. So we are, of course, not blind. We need to see, we need to assess the different options, and this might not be the place to speculate too much around that, but of course we are fully aware of all different strategic options, but I would like to clearly point to our cash life, to our commitment to work carefully and in a responsible manner with the funds we have been entrusted with, just to make that very clear.

Tim McGowen: Thank you, Marc. We have a couple more analyst questions, one from Ahu Demir, over to you.

Ahu Demir: Thank you very much for taking my question again. This time I wanted to ask, Christian did a great job putting the efti combination in comparison to the benchmark. I would be interested in hearing, after the ASCO presentations, as we saw a mixed bag of lung cancer data. So, just curious, how you think efti combination compares to other combinations as well?

Marc Voigt: So, Christian, that's directly to you.

Christian Mueller: I think, given the data been released here at ASCO, I think we can be very confident with the data we have been reported here in such large patient subset of more than a hundred patients. I haven't seen data which comes near to what we have reported here, especially not in the PD-L1 negative or PD-L1 intermediate patient population. And without adding any chemotherapy. It's definitely an evolving field, but I think we can be very confident as we also work with pembrolizumab, which is the, obviously, the strongest PD-L1 antibody in the market.

Tim McGowen: Thank you. A further question from Tanushree Jain from Petra Capital.

Tanushree Jain: Thanks guys for taking a follow-up question. This is just talking about strategically. Given that we've seen some TIGIT data where a Phase II was really successful and then the Phase III didn't work out, do you think there would be, especially because we've got two different PD-L1 expressions to look at… We've also worked at the high expressions where the benchmark is Keytruda monotherapy. We've also worked in the 1 to 49 per cent expression where the benchmark is really Keytruda plus chemo. Do you think given that there might be any merit in going for, say, two Phase IIb trials versus a Phase III immediately? We could just discuss around that.

Marc Voigt: I believe that we have indeed different options to go to late-stage development. We feel, and maybe it's fair to say that maybe also some others feel that the data would indeed support different Phase III options. We have been discussing some of those options directly or indirectly during the call. You could, of course also go into another randomised setting. Biotech time to market and the robustness of the data could speak for a direct Phase III option. Within everything, I have been mentioning two, three minutes ago, so I can't give you a definitive answer, but we will make up our mind, but I believe we have the option to go to Phase III, but from a clinical development point of view, there would be of course also other options as well.

Tanushree Jain: Yep. And just one more question, if I may squeeze in here, just with your chemo plus efti plus anti-PD-1 trial that you mentioned is going to report also sometime this year, do you think that would be enough of data for you to go directly into a Phase III chemo plus efti plus Keytruda? Or do you say you'll need to do a safety run-in before you do that?

Marc Voigt: I believe the 20 patients from a safety perspective are already a sizeable group. We have, of course, also experienced for the chemo combination, different chemo in metastatic breast cancer, but we should look first of all at the data, if the safety profile remains as clean as we reported in December. So that was the first time we have been mentioning some data out of the triple combination and it was very favourable for the triple combination. But I would prefer to look at the data first before I can further comment.

Tanushree Jain: Thank you.

Tim McGowen: Thank you.

Marc Voigt: That's okay.

Tim McGowen: Marc, just one last question from Melissa Benson. Melissa, over to you.

Melissa Benson: Oh, apologies. I will ask one more question. Just why you guys have chosen the iRECIST versus the RECIST 1.1? Obviously, you do both comparisons, but just remind us again, please.

Marc Voigt: Yeah. Maybe Christian, if you go back in time when we started.

Christian Mueller: Yeah. The main reason is, it's easier to also continue treatment beyond progression. You could implement it as well with RECIST, but it's much easier as it is already foreseen with iRECIST. And it makes a lot of sense if you just have IO/IO combination therapies. Wouldn't probably make much sense if you have chemotherapy in there as well. And that was the main reason to do so, but as we have reported today and on Friday, there's not a big difference between those two, but gives the investigator a better flexibility.

Tim McGowen: Might just squeeze in one last question from Dennis Hulme. Dennis, over to you.

Dennis Hulme: Thanks very much. Just in relation to potential late-stage clinical investigation, I note that in the NCCN guidelines for intermediate PD-L1 expression 1 to 49, they say that pembro monotherapy is useful for… the Keytruda chemo combo. So it really looks like there's potential for potentially a pivotal trial for the combo versus pembro monotherapy. Now, do you think that's a potential path that you might go, and how attractive does that option look to you? Particularly in comparison to the breast cancer alternative.

Marc Voigt: In terms of the general alternative, again, we would need to make a decision at board level of course, about the prioritisation, but I think I indicated already that it's really interesting to look at non-small cell lung cancer and to potentially move forward there, but we will do a very rational process around that. And, Christian, would you like to comment on the first half of the question?

Christian Mueller: Thanks, Dennis, for the question. I think especially in the US, it's approved and as you just mentioned, it's probably used predominantly in patients who cannot tolerate the chemo IO setting. The main benefit, if we add efti to it, is that you get the same efficacy as you get with the chemo. So you probably would also try to have those patients on the trial as well. And I think it would be the natural and quite an interesting study setting to look for that, but obviously needs to be discussed with a lot of different stakeholders.

Dennis Hulme: Great. Okay. Thank you very much for that.

Tim McGowen: Thank you, everyone. I'll now hand back to Marc for his concluding remarks.

Marc Voigt: Just Tim, I don't know if you mentioned, sorry that there were also some questions from the audience. At least we should maybe take two of those.

Tim McGowen: Sure, Marc. There's a question here. For TACTI-002, do the subgroups of AIPAC experience high clinical benefit from receiving efti? Put differently, is there any crossover subgroups from AIPAC to TACTI-002 that would support efti biomarkers?

Marc Voigt: Yeah, indeed. We have been reporting -- and thanks for that question -- we have been reporting some biomarker data in early May from AIPAC. In terms of increase of CD8, CD4, CXCL10 level of monocytes. We have been discussing also the absolute lymphocyte count. There could be some readthrough. We need to analyse more data, also more data from the TACTI series. But even though there's of course a different combination, there could be some readthrough in terms of different biomarkers need to be evaluated if there would be likely adjustments in terms of the combination, but there could be something. Maybe Frédéric, if you have an additional comment there.

Dr Frédéric Triebel: Yeah, sure. Looking at subgroups, always interesting, but here in contrast to AIPAC, we don't have the placebo group, so we cannot really analyse whether younger patients would respond better to the combination compared to pembro alone. Because if you do that, you really have, by definition, small subgroups and compared to historical trials. So it's much more difficult than in a clean clinical setting such as AIPAC.

Marc Voigt: But that could come of course, from TACTI-003, but Tim, back to you.

Tim McGowen: Yeah, just a further last question. What is your opinion on the adverse event rate for dyspnea compared to pembro alone or pembro plus chemo where grade two and above dyspnea warrants sending a patient in for a scan of the lungs?

Marc Voigt: Frédéric, that might be for you.

Dr Frédéric Triebel: Well, as said before, our patients, 93 per cent of them are metastatic, and dyspnea is very common symptoms in these patients due to the underlying diseases. So, I don't have any concern about the percentage you have seen on the slides. So, I don't see why we should be concerned about that. And, of course, in case of severe dyspnea, another CT scan will be the form, for sure.

Tim McGowen: Thanks, Marc. That's all the questions from the floor. Over to you.

Marc Voigt: Yeah. Thank you. And on behalf of the Immutep team, I would like to thank everyone for listening today. I hope we have been able to share some of the excitement we see, to share some of the strategic options we are having. And just as a reminder, the webcast will of course be available in due course on our website. And, again, thank you and goodbye.


Ends

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