Immutep (ASX:IMM) Presentation, Immutep TACTI-002 Clinical Results & Update Global Webcast, February 2020

Company Presentations

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

Moderator: Good morning everyone. Thank you for joining us for another Immutep (ASX:IMM) investor call to discuss recent and upcoming clinical results from the company’s lead product candidate, eftilagimod alpha.

My name is Clive Tompkins, and I will be your moderator today.

At this time, all participants are in a listen-only mode. We will conduct a question-and-answer session at the end of the conference.

I would now like to hand the call over to Marc Voigt, Immutep’s CEO, to start the presentation.

Marc Voigt: Thank you, Clive, and welcome everyone. We very much appreciate everyone’s time on the call today with us.

Here is our usual forward looking statement.

Today, we are very excited to take you through the new data from our TACTI-002 trial and talk about the broader clinical program for our lead product candidate, eftilagimod alpha, also known as IMP321, or very often we refer to it simply as, efti. Specifically, we will talk about our AIPAC trial, which is reporting first data next month.

Joining me on the call today is Frédéric Triebel, who is Immutep’s Chief Medical Officer and Chief Scientific Officer. Frederic will talk about our efti program and give some insights into AIPAC ahead of next month’s data.

We are also joined by Christian Mueller, our Director Clinical Development and Regulatory Affairs. Christian will take you through the recent TACTI-002 trial results that were announced to the market last week.

Before I hand over to Frederic, I would like to give you a quick refresher on efti.

On slide 4, you see our LAG-3 portfolio with four different product candidates, two in immuno-oncology and two in autoimmune diseases.

Two are exclusively worldwide out-licensed to GSK and Novartis.

Today we will focus on efti on the top left-hand side.

Efti is distinctly different to our other product candidates. So, it’s not a monoclonal antibody. It’s a fusion protein - a unique APC activator where we use LAG-3 as a tool to activate the dendritic cells via the target MHC II molecules.

Turning to slide 5, this is our diverse program of clinical trials for efti.

Our largest and most advanced study is AIPAC. We will discuss this trial and the imminent data shortly.

Our other phase II trial is TACTI-002, and we have just reported very encouraging results from this trial last week. We’ll go into more detail on these results later during this session.

Efti is also being evaluated in solid tumours through our INSIGHT-004 trial, which is conducted with Pfizer and Merck KGaA, and in melanoma via our TACTI-mel trial that has already reported on 15 October last year encouraging phase I activity and safety data.

From our pipeline, you can see that we took care to pursue efti’s development via multiple trials in multiple indications and in different combinations.

I would now like to hand over to Frédéric, who – as many of you know – discovered LAG-3 and is the worldwide leading scientist for LAG-3 and who will now give you an update on efti and our largest and most advanced clinical trial, AIPAC.

Frédéric Triebel: Thank you, Marc.

Slide 6 explores the innovative aspects of efti.

A diagram of efti showing its structure is in the top left-hand corner of the slide.

Efti is a soluble LAG-3 molecule.

It is an antigen presenting cell activator, which means that it activates dendritic cells that process and present antigens for recognition by the T cell receptor on T cells.

Its mechanism of action is unique and first-in-class as a MHC class II agonist, which strengthens its value for Immutep.

Efti is not a blocking antibody, but a unique antigen presenting cell activator.

The diagram on the right-hand side shows the typical mechanism of action of an immune checkpoint inhibitor like an anti-PD-1 or an anti-LAG-3.

This "releases the brakes" on the T cell by blocking the LAG-3-MHC class II interaction.

In the left-hand diagram, efti stimulates the immune system by activating the dendritic cells, which leads to an increased number of monocytes, dendritic cells, natural killer cells and both CD4 and CD8 T cells.

Here efti "pushes the accelerator" on the immune system cellular responses.

Efti is the only antigen presenting cell activator targeting MHC class II molecules currently in clinical development.

The important thing to note here is that efti’s mode of action is possibly synergistic with many other therapeutic agents. We’ll come to that later.

Moving to slide 7 now.

We consider efti to be a pipeline in a product. It has enormous and disruptive potential.

The diagram on the right-hand side explains where we see efti being able to impact the cancer immunity cycle, activating dendritic cells on step 2 and increasing antigen presentation to T cells in the draining lymph node on step 3.

Thus, efti could be combined with other agents like chemotherapy, which releases cancer cell antigen on step 1 or to antibodies blocking the PD-1/PD-L1 axis on step 7, which inhibits the killing potential of antigen-specific T cells returning to the tumour site after being activated by the APC in the draining lymph node.

Needless to say, these mechanisms of action are independent from each other and can therefore be combined synergistically for better anti-tumour responses.

In addition, efti has several other established benefits.

It is a first-in-class MHCII agonist

It has a strong safety profile and unique protective IP positioning.

What I mean by unique IP positioning is that the soluble LAG-3 molecule is unique and not highly variable -- like, for instance, the many different PD-1 or LAG-3 antibodies, leading to many different IP positioning and products.

To date, all efficacy data has been encouraging and it has a low cost of goods, which is very important given the drug pricing debates across the globe.

I will now delve into more detail about AIPAC, our largest and most advanced clinical trial.

AIPAC is our ongoing Phase IIb clinical trial in HER2-negative / Hormone Receptor positive (HR+) metastatic breast carcinoma patients.

It is a multicentre, placebo-controlled, double-blind, randomised study, making it a high-quality trial design.

It is evaluating the combination of efti with a taxane-based standard of care chemotherapy, called paclitaxel.

AIPAC is fully recruited with 227 patients participating in seven European countries.

The primary endpoint that we will report by end of next month is the progression-free survival of patients.

We will also give details of the associated hazard ratio, which is the relative risk of progression compared to placebo.

For example, if the hazard ratio were 0.75, that would mean that the risk of progression in the one group is 25% lower compared to the other group. As the hazard ratio gets lower, so does the risk. Therefore, the lower the hazard ratio, the better the chance is that a drug has statistically outperformed the placebo group.

Overall response rate is expected also to be reported on next month.

Two key features that are worth noting for AIPAC, if the study is positive: it is potentially pivotal, which means that strong final results from AIPAC could serve as a basis to pursue appropriate regulatory approval pathways for efti; and it is also a landmark study that could potentially mark the emergence of a whole new class of immuno-oncology products targeting the antigen presenting cells, ie Antigen Presenting Cell activators. Efti could be the first in this new category to have positive results generated from a randomized double-blinded placebo-controlled clinical trial.

Turning now to slide 10.

I will now just briefly touch on the epidemiology of HR+/HER2- breast cancer for those who are unfamiliar.

Across the globe there are more than 800,000 HR+/HER2- diagnoses per year. This is significant.

Approximately 250,000 of those develop metastatic disease and become eligible to receive chemotherapy.

At the moment, and despite many advances in earlier treatment options, there has been no improvement for patients receiving chemotherapy for the first time. This means there is high unmet medical need.

Taxane monotherapy remains widely used, and there are no approved active immuno-oncology treatments in the AIPAC patient population.

If efti were to be approved as a combination therapy with chemotherapies, it could become more widely used than the single-agent paclitaxel is currently.

Looking at slide 11 now, here we show some recent examples of products approved metastatic breast cancer across the different MBC indications.

In the results columns, you can see that PFS benefit of the experimental combinations compared to the placebo combination, with the experimental product combination (in the middle) always providing longer progression free survival.

The Hazard Ratio is related to PFS. You can see that range is between 0.63 and 0.76.

Of course, there were many other endpoints like overall survival which formed part of the data package presented to the regulators.

We’ll now talk about our other phase II trial, TACTI-002, which combines efti with an anti-PD-L1 therapy.

Looking at slide 13.

There is a strong rationale for combining efti with an anti-PD-1 therapy.

Efti is known to increase monocyte numbers in cancer patients.

The graph on the left shows that, in melanoma patients, the base line of a patient’s monocytes is important in determining their overall survival response to pembrolizumab therapy. High monocyte levels help a patient respond and therefore survive longer. Adaptive immunity driven by monocytes or dendritic cells is indeed necessary for T cells to thrive and survive and therefore for anti-PD-1 antibodies to succeed.

Low monocyte numbers at baseline are associated with poor efficacy of anti-PD-1 therapy in melanoma patients.

What we learnt from AIPAC and other trials is that efti boosts this baseline adaptive immunity, lifting the number of monocytes. This is shown on the right.

I would now like to hand over to Christian Mueller to give an overview of the TACTI-002 trial.

Christian Mueller: Thank you very much Frédéric for this introduction.

Looking at slide 14, we have an overview of the trial design of TACTI-002 which we are conducting in collaboration with Merck Sharp & Dohme, known as MSD.

As you can see, it is evaluating the combination of efti with MSD’s KEYTRUDA, also known as pembrolizumab, an anti-PD-1 therapy, in up to 109 patients.

The trial is a multi-national, open label phase II trial.

The study recruits into three very interesting indications.

Part A: First line non-small cell lung cancer addressing the unmet need for an effective chemo-free regimen.

Part B: Second line non-small lung cancer truly (confirmed) refractory to PD-1/PD-L1 therapy -- a very challenging but very future-oriented cohort thinking of all the indications with PD-1 therapies approved.

Part C: Second line squamous head and neck cancer where pembolizumab alone is approved but showed modest response rates of 15-18%.

The trial employs a Simon’s 2 stage design, enabling us to expand each of the cohorts independently when a predefined response threshold is met.

A very important feature (as we all know PD-L1 is a well-known predictive marker for pembrolizumab monotherapy, especially in NSCLC) is that this trial recruits all PD-L1 comers, meaning that patients can participate no matter what their PD-L1 status is. This will then be tested later centrally with a standardised method for every patient which will also increase the quality.

The primary endpoint is Overall Response Rate by iRECIST allowing treatment beyond progression.

Recruitment is progressing well, and we have already been able to expand to stage 2 for two parts meaning Part A and Part C as you can see in the table - due to an encouraging response rate.

Recruitment is ongoing across all Parts.

Lastly, we should mention that the trial is taking place across Europe, Australia and the US, where efti received its first IND approval last year.

Turning to slide 15 now.

TACTI-002 results are continuing to build efti’s very favourable safety profile.

48 patients have been enrolled into all three parts until data cut off end of January 2020.

To date, no new safety signals have been observed in combination with pembrolizumab which is really encouraging.

There were two fatal TEAE related to the underlying disease and not related to therapy.

For only two TEAEs, hepatitis grade 4 and diarrhoea grade 3 study drugs were discontinued.

As expected, we observed mild injection site reactions related to efti.

Overall we saw what we expect from the two different monotherapies and we continue to be very happy with the safety profile for patients.

Moving on to the baseline characteristics of patients from part A, first line NSCLC, which are displayed on slide 16.

As you can see, the majority of patients are male, have an ECOG of 0, and almost all patients were former/current smokers. There is an almost equal distribution between squamous and non-squamous subtype. Basically, everything is as you would expect in such a cohort.

More interestingly, we were able to show by central lab analysis that distribution across the three different PD-L1 subgroups is as expected as well. About 23% have a PD-L1 expression of less than 1%, 46% an expression between 1-49% and only 31% of larger or equal to 50%. It was confirmed that the trial is a PD-L1 all-comer trial and meets expectations from historical distribution pattern.

From the 17 first line non-small cell lung cancer patients in part A, eight responded, giving us an Overall Response Rate of 47% according to iRECIST.

You can see the eight responding patients indicated by the green bars in the waterfall plot on the right-hand side. Each of these patients had a decrease in their target lesion of more than 30%.

Seven out of these eight patients are still under therapy, and responses were confirmed for six already. One patient with a PR stopped treatment due to the hepatitis and response could not be confirmed.

A further six patients had stable disease. They are indicated by the grey bars on the plot. One patient is invisible here as the target lesion did not change at all.

Importantly, responses were observed in all PD-L1 subgroups. You can see this in the green table in the bottom right-hand of the slide. We have a 33% response rate for the low PD-L1 category, 50% response rate for the medium PD-L1 category, and 75% for the high PD-L1 category.

Seeing substantial response rates even in low and medium PD-L1 expression groups is very encouraging for us as this is normally only observed in the high expressing groups.

On the next slide, slide 18, the same patients are displayed as a spiderplot.

The spiderplot describes the development of the target lesions over time and the black arrow you can see here indicated patients who are still under therapy.

Each coloured line represents one patient.

While you see here the spider plot presented at the German Cancer Conference (by best overall response), I would like to show you now a modified version according to the PDL-1 expression status.

The colour of the line indicates which PD-L1 expression category they belong to.

At data cut-off, ten patients, or 59%, were still under treatment after more than seven months of observation.

In other words, 59% of patients are progression free after more than seven months and still continuing treatment, so median PFS has not yet been reached, which is a very favourable sign in this late stage patient population.

Overall, summarising, we are very excited by the results seen in first line NSCLC patients!

Moving on to the results from the second line Head and Neck Squamous Cell Carcinoma patient on slide 19.

Patients in this group have a median age of 66 years and are predominantly male. ECOG is 1 in about 50 % of the patients.

Although not all patients have been staged yet, at least once after baseline 6 out of 18 patients had a partial response, which is remarkable in such an aggressive tumour.

This gives us an initial Objective Response Rate of 33.3 %

Three patients have not yet been evaluated, so we will see where they fit soon.

All patients with stable disease or partial response indicated by the yellow or grey bar indicated in the waterfall plot are still under treatment, with median follow-up of 6.4 months. Although very early numbers, we are very encouraged by the number of responses we have seen.

This brings us to the end of the TACTI-002 results and I would now like to discuss the relevant comparison and benchmark results on the next slide.

On slide 21, this table sets out the three patient Parts for the TACTI-002 trial.

As we have announced already, stage 2 of both Parts A and C have been opened for additional patient recruitment after we saw responses to the therapy, and we have seen remarkable progress here already.

As you can see, we have recruited 10 out of 19 in Part A, stage 2 and have recruited 3 out of 19 in Part C, stage 2.

In the second last line of the table, we summarised the initial results from TACTI-002, and in the line below what has been published for pembrolizumab alone in a comparable patient population. We all know that historical comparisons should be interpreted with caution. Based on the initial ORR results observed in TACTI-002, the combination of efti and pembrolizumab has a two times higher response rate on first line NSCLC and second line HNSCC compared to pembrolizumab monotherapy.

Looking at the TACTI-002 results, we can see a clear benefit emerging for patients, and this has made us very excited about the opportunity for efti as part of a new combination therapy with pembrolizumab.

On that good note, I will now hand over to Marc, who will summarise for us before we take questions.

Marc Voigt: Thank you, Frédéric and Christian.

Returning now to the point that was made early on in the presentation, so we see given all the clinical trials underway, efti as “a pipeline in a product” because of the multiple different therapies that it could be paired with.

It has huge potential to be paired with taxane-based therapies, such as paclitaxel, and we hope to demonstrate through the PFS and ORR data from our AIPAC trial, along with other chemotherapies.

We also believe it has enormous potential to enhance other immune-oncology treatments, such as PD-1 inhibitors like Pembrolizumab. This is supported by the exciting results that we are seeing from TACTI-002 already and, to a certain extent because it is a Phase I study, from TACTI-mel - in NSCLC, HNSCC and metastatic melanoma.

If our AIPAC trial results are positive, the significance of these results would go well beyond the immediate clinical perspective.

They would help to validate antigen presenting cell activators as a completely new class of active immuno-oncology products. This could be a landmark achievement after, quite frankly, many disappointments in the IO field with other approaches.

It would be the birth of the first new class of immuno-oncology treatments since the so called Immune Checkpoint Inhibitors, putting cell therapy aside.

And for Immutep, metastatic breast cancer would just be the start. We would be able to explore many other cancer indications and combination therapies - not to mention, shall we say, strategic corporate options.

Next month will give us a great deal of insight into what lies ahead.

We are certainly very, very excited. AIPAC took about 4 years and, of course, it is great to come to the first stop of this journey.

And now I will pass back to Clive for questions.

Moderator: Thanks very much, Marc. The time allotted for questions is approximately 10 minutes. We'll be taking questions from panellists, and after the questions from panellists, Marc and the team will answer questions that have been submitted ahead of time.

So, our first question comes from Matt Cross. Matt, can you go ahead, please?

Matt Cross: Hey, guys. Thanks for taking a question from me, and I'll limit it to one, given the sake of time. Assuming data from AIPAC is pretty demonstrably positive relative to approved therapies for metastatic breast cancer. And I know that you indicated that this may be sufficient for approval in the EU. As you said, potentially pivotal where paclitaxel is more commonly standard of care for these patients when they receive chemo, but given that there's a differential reimbursement and treatment pattern in the US, how do you think about a design for a pivotal trial in the US? And specifically the multiple parts I'm looking for here are, would you still want to combine solely with paclitaxel? Would you be focusing on patients who have failed CDK 4/6 combination therapy or more or go more broadly? And lastly, would you need to demonstrate an OS benefit for approval in the US, as well as PFS prior to an approval there?

Marc Voigt: Thank you, Matt. So first of all, of course we will take the results from AIPAC and discuss with the relevant regulatory bodies in the EU. So the EMA, as well as of course the FDA. You may notice that we are about to initiate a new clinical trial, AIPAC-004, a small trial with an IND for metastatic breast cancer in the US. So that enables us also to have further appropriate regulatory interactions with the US.

Indeed, we would look to improve the existing standard of care. Paclitaxel is used predominantly in Europe, but of course also in the United States, and there is also in the States a trend to low-dose a single chemo compared to doublet chemo. When you have benefit for the patients and refine or improve the existing standard of care, of course, we believe that the standard of care will be used more widely than before. However, we are not limited to taxane. We are not limited to hormone receptor positive, or even negative from the mode of action point of view. You could, for instance, also expand to triple negative breast cancer or we can take on other combinations.

The US is, of course, a very important part in our industry, in our business, and of course also for AIPAC or our metastatic breast cancer approach. So, as the data generated is high quality in Central Western Europe, we have to discuss with the FDA the level of acceptance of the current data packages and what would be the requirements beyond that. Unfortunately, I can't be more precise, but there are certainly decent chances of taking the AIPAC results directly to the United States.

Matt Cross: That's very helpful context. I appreciate you framing it that way ahead of next month's read-out. Thanks, Marc.

Moderator: Thank you, Matt. OK, next question comes from Tanushree Jain.

Tanushree Jain: Thanks, Clive and thanks, Marc and Frédéric for taking my questions. I actually have a few, but I'll come back in the queue. So, just on the results from TACTI-002, just a couple of ones. Why has the recruitment in the part B, compared to part A and C, been so slow?

Marc Voigt: Thank you, Tanushree, for that question. So indeed, the recruitment for part B, second line, non-small cell lung cancer is lower. One reason, is that patients, when they progress under one therapy, in this case pembrolizumab, are sometimes reluctant then to take the same drug again even though in combination with something else. So, there is a kind of very understandable human factor here. The second reason, which Christian mentioned early on, is that we are really looking here to recruit confirmed progressors, so truly refractory patients according to industry definitions, meaning that they have a confirmatory scan in order to not have, for instance, pseudo-progression included. So where a patient just seemed to not progress under pembro, in reality coming then to a response. So, to exclude any false positive patients, we run here the hardest tests, and this goes, unfortunately, so to speak, hand in hand with a lower recruitment rate.

Tanushree Jain: Right. Thanks. And then just another one. Just with the results you've seen in first line, non small-cell-lung cancer. Obviously we've seen almost a double response rate to pembro mono. But I guess at the moment the pembro chemotherapy is used as first line. How would you compare your current results to that setting and also, do you see the pathway forward being like a head to head with pembro chemo or do you actually think efti could be added like a triple regimen in the pembro chemo combination?

Marc Voigt: Thank you. I will allude to the last part of your question first and then hand over to Christian. So indeed also before we started TACTI-002, we were thinking of maybe doing a triple combination, pembro plus efti plus chemo. Of course, one always has to be careful in terms of patient safety. So, I believe it was better to start this way, and then it turned out that the results are very, very encouraging. So, one would need to explore if it would be necessary, or recommended, or wise to do a triple combo compared to the pembro-efti approach. So this is, so to speak, open during the results, and if the results are confirmed, we may go a head to head. There is no final decision yet. But in terms of the relative positioning, I would like to hand over to Christian.

Tanushree Jain: Thanks.

Christian Mueller: For pembro chemo, one must differentiate between squamous and non-squamous, which is not the case for pembrolizumab monotherapy. So, there is the KEYNOTE-407 for the squamous one, and for the non-squamous, the KEYNOTE-189, and they have slightly different results because they use a slightly different chemo. Overall, what you can see is that the response rate, the triple combination of chemo to double chemo plus pembro, leads to a response rate of about 50%, and the median PFS in that subgroup is about 6.5 to 7 months in the squamous part and about 9 months in the non-squamous part, all with huge toxicity and tremendous costs for the health care. What we have seen so far here, is we have a response rate of 47% already, which can still change, meaning increase and a median PFS, we have not yet reached and we are far beyond the 7 month mark already. So, we are pretty confident that the data we have seen here, if confirmed in a larger patient setting, is sufficient to take on the combination and is comparable.

Moderator: Okay. Next question comes from Chris Redhead.

Chris Redhead: Hi, guys. I was going to ask the same question as Tanushree, but just to follow on from that. Clearly, with non small cell lung cancer, the standard of care would probably be... For PD-L1, low expression or below 50%, would be chemo plus pembro. Would it not be that the treatment regime would probably be now, if you went for the checkpoint plus plus efti, and then in the non-responders, maybe you add all three together. If you've got synergy between PD-L1 and synergy between chemo, that would seem to be that you add it all afterwards.

Marc Voigt: Yeah, indeed, this would be a possibility, and we are actively discussing this along the way, also with of course other parties. So, there are multiple avenues to explore the different combinations according to PD-L1 expression. So that's absolutely right.

Chris Redhead: You've got the advantage of course, of having one of the fact that it seems to be relatively well... You've begun to show potentially from the AIPAC trial, that chemo and efti work well and also, importantly, that it's very well tolerated. That's the big thing, really, isn't it? That efti is very well tolerated. It has efficacy and tolerability. Therefore, you get the potential to do more combinations, right?

Marc Voigt: Indeed, Chris. This is a very important and very often overlooked point. So, the safety profile and the ability to be combined with one, or two, or maybe three, whatever it is, different drugs is a key advantage of eftilagimod. As you are well aware, for instance, the anti PD-L1, anti CTLA-4 combination was undergoing a lot of scheduling, rescheduling, and testing in order to be better bearable for the patients, and the same applies for pembro plus chemo. So there has also been, at the beginning, some talk associated with that as far as I know. Some PI's were not really in favour of that combination. Of course, there's a lot of work then on optimising this. But the key advantage of eftilagimod is given that it is an agonist and you give low dose, 30 milligram per patient subcutaneously, that you have a very mild safety profile.

So indeed, yes, if you would, for the sake of argument, come up with about the same response rate, PFS, overall survival, whatever it is, but you have a key advantage in terms of safety, this is a very strong argument to, for instance, replace another combination.

Chris Redhead: Right. Well, that's great. Thanks.

Moderator: Next question comes from Dennis Hulme.

Dennis Hulme: Thanks very much. My question is also about recruitment in TACTI-002, but relates to part A. We see at stage two the expansion cohort recruitment seems a lot lower than in stage one. Can you talk about any factors which are affecting recruitment in that expansion cohort?

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

Christian Mueller: I wouldn't confirm that, actually.

Dennis Hulme: OK.

Christian Mueller: So, once we initially really officially opened the cohort for the investigators, it was about one and a half months to Christmas, and then we had Christmas, which always slows recruitment down all over the world, and then only just got back in January. We are very happy with the recruitment we see, and investigators are very happy with the drug, with the trial, so nothing, nothing which concerns us yet at all.

Dennis Hulme: Okay. Well, that's good to hear. Thanks very much.

Moderator: There is another question from Tanushree. Go ahead, please.

Tanushree Jain: Thanks, Clive and thanks, Marc. So, just a quick couple from me, just on AIPAC. Can you tell us what the minimum bar is you will have to achieve in order to get conditional approval, and what your study has done in terms of showing the difference in PFS?

Marc Voigt: Right. So first of all, we have here for AIPAC, a changing landscape, in terms of PFS expectation for paclitaxel monotherapy, because you saw the introduction of CDK 4/6 inhibitors, like Ibrance, into this space, meaning that the expectation of PFS for paclitaxel -- you will see in a second why this is important -- is now lowered. Used to be between six to eight months. This is what has been reported. These days, it's believed to be three, four, five months maybe. There are no big data sets yet available. It doesn't concern us, as we have the effect in both arms, but maybe Christian can explain a little bit why this is relevant, especially then in terms of the EMA setting.

Christian Mueller: Yes, thanks, Marc. Generally regulators, so FDA and also EMA, they look into two different things... If we take PFS as the main endpoint here, they look into two different things. They look first of all into the absolute gain, and into the relative gain, which is the Hazard Ratio and the absolute number of months you would increase the median PFS. And there are certain scales which have been defined by the different clinicians and the groups. There's the ESMO Magnitude of Clinical Benefit Scale, which for instance, describes the highest benefit you can achieve on that score for. If the control therapy has a median PFS of six months, an increase, an absolute increase, of 1.5 months would give you the maximum score on that scale. Which is a very important scale for regulators and also for reimbursement agencies later on. There's a similar scale with slightly different numbers from the ESCO, which is done for the American market.

So having said that, it all comes down to what we see in the placebo group, and that Marc has already spoken about. We believe it will be below six months, and then, if we have an absolute gain together with a certain Hazard Ratio of 1.5 months, we believe it's a very good data set to start discussions with the regulators. What they will say then together with the safety profile remains to be seen.

Moderator: Thanks, Christian. Time permitting, is there anything else you'd like to answer or address or should we or are we out of time for today?

Marc Voigt: I received about 20 additional questions from different parties. There was, for instance, one question also regarding the AIPAC-002 bridging study. It's a small study with 24 patients. The dosing is slightly different and this is why we have this trial. So it's important for us, of course, to have as a basis to discuss in the United States, to have an open IND for metastatic breast cancer. This is one key reason we have that clinical trial. Of course, if you can then look at pharmacodynamic, pharmacokinetic, or schedule, which is slightly different. So you give it on the same day. This might also be a benefit if it works out, but really key is to have the right platform to discuss with the regulators.

So this was one question I just wanted to answer, but we shouldn't take more of the precious time from the audience, I believe. I can't answer all the other 19 questions I have here.

Moderator: On that note, I think that concludes the presentation. A copy will be made available shortly after on the FNN website and also via Immutep.

Marc Voigt: Yeah. Thank you so much. On behalf of the Immutep team, we would like to thank everyone for listening today. Also, a big thank you to the analysts who participated and asked questions. We are extremely excited over here. At Immutep, we are working very hard as we approach the PFS data and Overall Response Rate from AIPAC, and we look very much forward to sharing this with you next month. And, as Clive mentioned, this webcast will be available as a replay on our website. So, thank you again and goodbye.


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