Immutep Limited (ASX:IMM) CEO, Marc Voigt, CSO & CMO, Professor Frederic Triebel and Director Clinical Development and Regulatory Affairs, Christian Mueller, provide a clinical update on eftilagimod alpha.Clive Tompkins: Good day ladies and gentlemen and thank you for joining us for another Immutep investor call to discuss 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 on a listen-only mode. We will conduct a question-and-answer session at the end of the call.
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 your time on the call today.
Our forward looking statement.
We are very pleased to give you an update on our clinical development strategy for our lead product candidate, eftilagimod alpha, also known as ‘efti’ or IMP321, as well as presenting data from our ongoing melanoma study, called TACTI-mel and new updates on our other studies.
On the call with me today, we have Prof. Frédéric Triebel who is Immutep’s Chief Medical Officer and Chief Scientific Officer, along with Mr Christian Mueller, our Director Clinical Development and Regulatory Affairs.
Before we dive into the slides, I’d like to firstly give you a little background on Immutep, particularly for those of you who are new to the Company.
Immutep is the global leader in the development of LAG-3 related therapeutics. This is a very promising area of biotechnology and immunology and one that is receiving increasing interest from big pharma.
LAG-3 is an immune system checkpoint and is widely considered by the industry to hold great promise for the next wave of immune therapies.
Immutep has - for a company of our size - many clinical trials of efti in different indications and combinations.
During the webcast today, we will go into these trials and the latest results and talk about how we plan to advance efti.
Let’s start the presentation now, moving to slide 4 with an overview of checkpoint therapies.
As mentioned, along with the wider immuno-oncology industry, we believe that LAG-3 has the potential to be the next meaningful checkpoint target for the treatment of cancer and autoimmune diseases.
In general, there has been a big change in the way cancer patients are being treated in recent years. This change is related to immuno-oncology.
As many of you know our CSO and CMO Prof Frederic Triebel discovered LAG-3 and devoted his career since then, to this immune checkpoint.
Two other very famous checkpoints, PD-1 and CTLA-4 have resulted in approved immuno-oncology therapies.
However, only 15 - 40% of solid tumors in patients respond to these existing monotherapies, being a therapeutic given on its own. And of course, this depends on the different indications.
To improve the patient response to these therapies, we must look at combining these existing approved treatments with other therapies to achieve an improved outcome for patients. And this applies also for other traditional therapies, like chemotherapy.
The timeline illustrates the trend towards combination therapies, with the first combination, Opdivo with Yervoy, being approved in 2015, and a Keytruda / chemotherapy combination reaching approval in 2017.
We believe that LAG-3 related therapies are strong candidates for a combination therapy with some of the existing cancer treatments, including anti-PD-1 treatments.
This validates our belief that LAG-3 has the potential to be the next meaningful checkpoint target in an immuno-oncology market that is expected to grow to US$34 billion by 2024.
On slide 5 now, as mentioned previously, Immutep is the worldwide leader in LAG-3 therapeutics.
On this slide, we have mapped out the industry landscape, detailing all other LAG-3 modulating therapeutics that we are aware of.
You can see in the top left, that Immutep’s lead product candidate, efti, has five active clinical trials. Just to the right of this, we have detailed the product candidates that our partners Novartis and GSK are taking forward and the number of trials they are conducting with the LAG-3 technologies. And those have been growing considerable in the last few years.
It’s worth just highlighting here that the number of products that have been originally developed by Immutep outweighs any other developer in this landscape and that we are active in immuno oncology as well as in autoimmune diseases. Now - after the acquisition of Tesaro - also GSK strengthened their position in the LAG-3 space significantly, becoming more active in immuno-oncology as well as autoimmune diseases.
Also, it is worth mentioning that three of our four product candidates are unique: efti is unique, our agonist antibody IMP761is unique and the GSK antibody. LAG525 from Novartis could be considered as a “me too” approach as all other players listed on slide are active in terms of the blocking LAG-3 approach.
So that gives you an overview of the landscape that we are working in and how we measure our leadership in this space.
We now like to focus on our lead product candidate, efti, for the next few slides to give you an understanding of how it works and an overview of our clinical trial program.
I would like to hand over to our CSO/CMO, Professor Frederic Triebel.
Frederic.
Professor Frederic Triebel: Thank you, Marc.
Turning to slide 7, here we give a description of efti’s structure to illustrate how it works.
Efti is a soluble recombinant fusion protein. It brings together a portion of a human antibody, which is the small molecule on the left-hand side, with the four extracellular domains of LAG-3, which you can see on the right-hand side. The first domain of LAG-3 is the MHC class II binding site.
In the middle is the combined dimer IMP321, or efti.
It is an antigen presenting cell activator which means that it is successful in activating dendritic cells that process and present antigens for recognition by the T cell receptor on T lymphocytes.
Its mechanism of action is unique and first-in-class as a MHC class II agonist, which strengthens its value for Immutep.
Now on slide 8, we go into further detail on the innovative aspects of the efti.
It’s important to highlight that efti is not a blocking antibody, but a unique antigen presenting cell activator. Very often LAG-3 is a term used in conjunction with blocking antibodies like LAG525 from our partner Novartis, but it is important to understand that efti is very different and unique.
The diagram on the right-hand side shows a different mechanism of action that does apply toto LAG525, an immune checkpoint inhibitor. These immune checkpoint inhibitors essentially release the brakes on the T cell by blocking the LAG-3-MHC class II interaction.
In contract, in the left-hand diagram, you can see efti stimulates the immune system and leads to an increased number of monocytes, dendritic cells, natural killer cells and both CD4 and CD8 T cells.
In other words, efti pushes the accelerator on the immune system cellular responses.
So just to reiterate, efti stimulates the immune system which leads to an increased number of circulating immune cells known to be involved in anti-tumor responses.
Efti is the only antigen presenting cell activator targeting MHC class II molecules currently in clinical development.
Moving onto slide 9, we would like to give you an overview ofImmutep’s deep pipeline of clinical trials evaluating the safety and efficacy of efti.
Focusing on the clinical trials that we are advancing ourselves in-house, the most advanced trial is AIPAC, our Phase IIb clinical trial in metastatic breast cancer.
Working in collaboration with our partner Merck, US Merck that is, we are evaluating efti in another Phase II study in non-small cell lung cancer and head and neck squamous cell cancer - this trial is called TACTI-002.
INSIGHT-004 is a phase I clinical trial that is being conducted in collaboration with our partners Pfizer and Merck KGaA, the German company which is a separate company to US Merck, and IKF in Frankfurt.
As mentioned at the start of the webcast, there is also our TACTI-mel phase I trial of efti in melanoma where we have more mature results to take you through today.
INSIGHT is an investigator-initiated trial testing new routes of administration of efti, like through direct injection into the tumour nodules, a kind of in situ vaccination. We should just note here that, INSIGHT-004, which we mentioned a moment ago, is being conducted as a part of this trial.
I will just highlight here that Immutep retains the global rights to efti, excluding China.
The last trial in the pipeline is being conducted by our Chinese partner, EOC which holds the rights to commercialise efti in China.
EOC is conducting EOC 202 which is a Chinese phase I trial in metastatic breast cancer patients treated with paclitaxel like in AIPAC.
That gives you an overview of the clinical trials that we are advancing ourselves and the additional trials being conducted by our partners on efti.
Moving on, we’d like to explain the three broad strategies we are pursuing to develop efti.
On slide 11 now, we are fortunate that as part of a combination strategy, there are a number of types of therapies that we can combine efti with.
The first type of combination therapy pairs efti with chemotherapy.
In the box below we show the clinical trials that are relevant for this type of combination. For the chemo combination, this is the approach that we are taking for our most advanced clinical trial, AIPAC, where efti is working alongside paclitaxel. EOC is also investigating in parallel with the same chemo-immuno combination in its Phase I trial.
The second type of combination therapy pairs efti with an immune checkpoint inhibitor, such as PD-1 and PD-L1 antagonists like pembrolizumab oravelumab. This approach is being explored through TACTI-mel, TACTI-002 and INSIGHT-004.
The third and final type of combination is with a cancer vaccine as adjuvant, such as our new collaboration with Cytlimic and parts of the INSIGHT trial through in situ vaccination.
Therefore,Immutep has multiple shots on goal and gives efti the potential to be a pipeline in a product.
So, as we have mentioned, we would like to take you through the clinical data that the Company presented in early March at the World Immunotherapy Congress USA 2019 as well as some newer aspects like more detailed safety data and the combined analysis.
Let’s focus on that now on slide 13.
I will just briefly give you an outline of the trial design for our TACTI-mel clinical study in melanoma.
Some of you will be familiar with the trial, but for those of you who are new to the Company, TACTI-mel is a Phase I explorative trial that evaluates the combination of efti with an anti-PD-1 therapeutic, called pembrolizumab, also known by its brand name, Keytruda.
Keytruda is Merck’s marketed immune checkpoint inhibitor.
As a Phase I trial, we are primarily focused on the safety and tolerability of the combined therapy, but we have also looked at efficacy.
The trial involves a total of 24 patients, split into 4 cohorts, with 6 patients in each cohort. Recruitment was completed more than 6 months ago and some patients are still receiving ongoing treatment.
The first 3 cohorts are considered Part A of the trial and they start their combination treatment after they have already received a number of cycles of pembrolizumab. Safety is of foremost importance when starting a new IO-IO combination and we didn’t want to expose the few patients with autoimmune adverse reactions to pembrolizumab to an additional IO product. So, at cycle 5 of Keytruda, they also start receiving an escalating dose of efti every 2 weeks.
The 4th cohort has a different study design and is termed Part B. Since part A of the trial has shown that the combination is safe, patients in Part B start their efti/pembrolizumab combination treatment from the beginning of cycle 1 of pembrolizumab.
After the conclusion of the combination treatment, patients have the chance to continue receiving pembrolizumab as a monotherapy.
All patients are followed up every 12 weeks to record progression free survival, or PFS, data as indicated on the slide.
Our TACTI-mel trial is taking place across 7 clinical trial sites in Australia and is one of the main programs of work that makes Immutep eligible for the Australian Government’s R&D tax rebate program.
Looking at slide 14 now, as mentioned, safety is the primary outcome that we are reporting for TACTI-mel, so I will start off the results section of our webcast by giving you an update on the safety results we will report for both Part A and B of the trial here for the first time.
The tables on the slide give you an outline of the number of patients that have reported adverse events, or side effects, during the treatment.
The frequent adverse events, like cough, headache and fatigue are detailed on the left-hand table and the severe/life-threatening adverse events are listed in more detail in the table on the right-hand side of the slide. No new safety signals have been reported.
9 SAEs were reported, one of them related to pembrolizumab but none to efti. Therefore, most SAEs were related to the underlying condition, like progression of disease.
From these safety results, we can say that efti has a very favorable safety profile in doses up to 30 mg when administered subcutaneously every 2 weeks with pembrolizumab, with no dose limiting toxicity, known as DLTs. And there was no need to increase the dose and reach the maximal tolerated dose for efti as we have previously shown that a 5-fold lower dose, that is 6 mg, is already capable of inducing a good T-cell based immune response in most patients.
Turning now to the blood pharmacodynamics of the study on slide 15, here we are looking at first signals in the blood that tell us what the combination is doing on the immune system cellular responses.
The left-hand graph gives us insight into the induction of a key cytokine for an anti-tumor cellular response to be effective, interferon gamma, or IFN-γ, after an injection of the combination therapy.
You can see that serum interferon gamma concentration is increased after efti injection at 24 hr but more importantly the serum IFN-γ is elevated pre-dose at 6 months, indicating that there is a continuous and sustained increase of IFN-γ in the blood with a boost every two weeks induced by the subcutaneous injections of efti.
This means that the Th1 status of our patients, an important component for the fight against tumors, has been upgraded by the addition of efti to the treatment.
Indeed, we know that patients with a hot tumor defined by the presence of interferon gamma at the tumor site are much more likely to respond to pembrolizumab and therefore finding increased and sustained interferon gamma levels in the serum of our patients is really the desired biologic effect when adding an APC activator to pembrolizumab.
Looking at the middle and right-hand graphs, we have observed that there is an increase in the absolute numbers of activated CD4 and CD8 cells for all patients. This is in Part B where both efti and pembrolizumab are combined and given from day 1 onwards.
These two key results, the improved Th1 status and the increase in the number of activated T cells numbers in the blood have also been reported for our combination of efti with chemotherapy in a poster at ASCO last year.
On slide 16 you see an overview of some key baseline characteristics of the patients in Part A, Part B and the combination of the two parts.
Firstly, I will give you an outline of the baseline characteristics of the 18 patients in part A of the study. These characteristics are in the left column of the table.
Most of the patients, 78%, had M1c stage of disease which means the disease has already spread beyond the lymph nodes and the lung to other organs like the liver.
39% of participating patients had elevated LDH which is a poor prognostic marker in melanoma.
28% of the patients had been pre-treated, for instance with ipilimumab or BRAF/MEK inhibitor. This pre-treatment means they are considered 2nd line patients and unfortunately have smaller chance of a positive outcome.
The baseline characteristics of Part B are largely the same for this group, however 100% of them had M1c stage of disease, or very late stage disease.
It is also remarkable that 50% of all patients had liver metastasis and 67% lung metastasis.
Overall, we enrolled patients in late stage of disease and often with multiple risk factors.
Looking now at slide 17, I will take you through the efficacy results for Part A, remembering that Part A patients received an escalating dose of efti, but not until after they have received several doses of pembrolizumab on its own. In other words, they start receiving the combination therapy at cycle 5 of pembrolizumab.
Looking at more mature data from the study, you can see that the results from patients after they have received the combination treatment are very encouraging.
After the combination treatment started, 56% of patients had tumour shrinkage.
Encouragingly, the Disease Control Rate was 66%. Disease control, as per our assessment criteria, means patients had a benefit like tumour shrinkage or stabilisation of disease.
The patient response to the combination therapy was measured according to irRC. irRC stands for immune-related Response Criteria.
The overall response rate after the start the combination therapy was 33%.
It is interesting to note that we had two complete disappearances of all target lesions. This is especially encouraging given that all patients in the trial, including these two, had a progression or suboptimal response to pembrolizumab prior to inclusion in the study.
Of course, these results need to be considered in the landscape setting of other therapies that are available to be fully appreciated. We will do this later in the presentation.
Just briefly, the spider plot in the middle of the slide shows you each patient’s response to the combination therapy, reflecting the percentage change compared to their baseline, or starting point. 10 patients, or 56% of the patients, had a negative percentage change, which is the tumour shrinkage we mentioned earlier. This is also plotted in the waterfall plot on the right-hand side of the slide.
A complete response is where the target cancerous lesions have disappeared altogether. On the spider plot, their data reaches the X axis. The first one occurs after 11 months of treatment and the second at 18 months of treatment with pembrolizumab.
Aside from being very encouraging for us, this gives us crucial information supporting our statement that often immunotherapies take time to deliver their benefits.
Moving to slide 18 now, we present the same data but for the 6 patients that are participating in Part B of the study. Remembering that they started their combination therapy at cycle 1 of pembrolizumab treatment.
Moving to the new results from Part B,50% of patients had tumour shrinkage, confirming a deep partial response to the combination therapy.
The Disease Control Rate was also 66% for Part B patients.
The overall response rate to the combination therapy was 50%.
The study treatment is ongoing for 4 patients in this group.
On slide 19 now, we mentioned that in Part A, we had two patients that showed a complete disappearance of their target cancerous lesions. We have had similarly encouraging case from Part B.
This slide shows a single case study of a 69-year-old male who entered the study with multiple lung, bone, liver and lymph node metastases from melanoma. He was considered a very late stage patient.
The images show his CT scans before he started treatment, on the left-hand side, and after 6 months of treatment.
The top row shows the CT scans of the lungs and you can see the complete disappearance of the circled lesion after 6 months of treatment.
The bottom two images are of the liver, where you can see clear regression of the lesions which get smaller.
We are very pleased that this patient is doing so well, and his treatment is ongoing.
Now, I would like to hand over to Christian, who is our Director of Clinical Development and Regulatory Affairs
Christian.
Christian Mueller: Thank you, Frederic for taking us through the results from the TACTI-mel study. As we have seen details for part A and part B separately, I would like to guide you through a more exploratory analysis of our TACTI-mel results, putting together the results from part A and part B.
As you have seen from Frederic, the Part A design is slightly different from Part B but we still try to put that together even though it is a little artificial, especially for Part A.
This exploratory analysis gives us an understanding of how the patient efficacy data looks if the response is assessed from cycle 1 of pembrolizumab onwards.
You can see that the overall response rate,as outline on the table on the left, is 58% for all the 24 patients involved in the TACTI-mel trial.
More importantly, 58% of patients are disease progression-free 6 months.
On the one hand, you want to have responses showing that the patients have shrinkingtumours and the other side, you should have a sustainable effect.
This is illustrated in the waterfall plot showing the responding patients with a decrease of at least 50%. As you can see most of them have really deep responses of their target lesions.
In summary, we are really encouraged with this data.
And would like to continue slide 21.
Looking at the swimmer plot, also shown for the first time, on the left-hand side, here we have plotted out the treatment course for all 24 patients in the TACTI-mel trial, that is Part A and B together. The patients are listed according to their progression free survival duration time starting with the longest on the top.
It illustrates their combination treatment phase in blue and the PFS follow up or pembro monotherapy in orange. It also indicates their best overall response rates and shows that mostly patients with partial responses or complete responses were benefitting longer.
We believe this is a very important cross validation because you can see patients having deep and sustainable responses at the same time.
At the data cut off in February 4 patients in Part A, and 4 patients from part B were still under treatment.
As a whole, the important points from this analysis are that: (a) treatment has not been terminated for any patient due to safety issues relating to the combination therapy; (b) and that we have very sustainable and deep responses have been observed.
Using the efficacy data from the exploratory analysis, on slide 22, we compare the results of the combination treatment to patients that participated in other clinical trials where pembro was given as a monotherapy. We are aware that these comparisons to historical controls are artificial, but the clinical data for pembrolizumab is relatively consistent.
The two trials were chosen for comparison, one trial investigated treatment naïve patients, KN-006 and the other pre-treated patients, theKN-002, which has an impact on the outcome. As you can see TACTI-mel baseline characteristics are mostly in between these two trials.
Pop-up: One of the best prognostic baseline characteristics is the disease status described by the M1x-status. The further the tumor has spread already the worse is the prognosis independent from the type of intervention.
M1a indicates that the disease has only spread to lymph nodes (green line), M1b indicates that it has gone into the lung; and finally, M1c indicates it has spread to the liver or other visceral organs than lung or the patient has elevated LDH. M1c clearly has the lowest probability of survival. Although this figure is some years hold it holds true. M1 status is an excellent prognostic marker.
As you can see here on the left of the table, the TACTI-mel base line characteristics we have 83% of the patients had the worst score with M1c here.In the KN-006 this is 68%, and in the KN-002 it is 82%.
Despite the poor prognosis markers we have seen an overall response rate of 58% from the TACTI-mel trial.
In TACTI-mel, 58% of patients are currently progression-free 6 months. This compares favourably to the KN-006 study where the ORR was 33%, while the KN-002 study showed an ORR of just 22%. And progression-free rate of 46% and 34% for the KN-006 and KN-002 studies, respectively.
This comparison to other trial results despite their artificial nature suggests that efti is a potentially effective combination partner that augments the benefits of pembrolizumab for patients with melanoma.
I really hope we have given you a good overview of the results we are seeing so far. The data from our TACTI-mel trial is very encouraging.
Now, I would like to briefly run you through our other clinical trials and highlight the progress we are making.
I would like to start on slide 24, with our TACTI-002 trial which we are conducting in collaboration with US Merck, known as MSD.
The trial will evaluate the combination of efti with pembrolizumab in 109 patients with three different types of solid tumours. This is the same combination therapy that we have just been discussing in the TACTI-mel trial.
One of the differences is that the combination therapy will be given for 12 months and can then go onto pembrolizumab monotherapy for up to 12 more months.
TACTI-002 is a phase II trial that will take place across multiple clinical trial sites in three different continents Australia, the US and Europe. We are very proud that we found excellent interest from different Principal Investigators across the world.
The primary outcome as you would expect for a phase II trial, will be the overall response rate.
For TACTI-002, you will have seen our recent announcement that the first patient had been dosed in early March. We are pleased to say that we now have enrolled more than 10 patients already which is clearly showing the interest of the community in our trial, despite all the competition which is ongoing in the IO field at the moment.
We expect to report the first patient data already in the middle of this year!
Beside the global presence one of the highlights of this trial is that we explore a PD-1 refractory patient population in NSCLC as we believe is a key potential patient population in a few years from now.
Next, on slide 25, I will talk about our phase I trial called INSIGHT-004 which is an extra arm to the trial which we are conducting in collaboration with Pfizer and German Merck and IKF.
It will be a dose escalation trial evaluating the combination of efti with avelumab, which is a PD-L1 antagonist, in patients with solid tumours after the standard therapy has failed.
Patients will receive this new combination therapy for 6 months and can then continueavelumab monotherapy for 6 more months.
The primary outcome is, of course, safety and we will also assess efficacy by looking at overall response rates.
As mentioned already, INSIGHT-004 is taking place as an extension to our INSIGHT trial, which is being run by our partner IKF.
The trial protocol has now been approved by the competent authority and we are expecting to dose the first patient in the current quarter, Q2 of calendar year 2019.
The results of this would enable us to continue the development of efti in combination with avelumab.
Finally, on slide 26, we look at our most advanced, most mature clinical trial, our AIPAC study.
AIPAC is a potentially pivotal trial in 226 metastatic breast cancer patients across more than 30 clinical trial sites in 7 EU countries.
It’s a two-stage trial, whereby the first phase was a safety run-in that determined the appropriate dose for the second stage. This stage has already been completed a while ago and will not be discussed today. Latest updates were presented at ASCO 2018.
We now have more than 200 patients recruited out of the 226 patients to the second stage of the trial which evaluates the efficacy of efti in combination with paclitaxel, an approved chemotherapy, by comparing it against a placebo / paclitaxel combination.
The primary objective is progression free survival, or PFS which is a well-accepted endpoint by Competent Authorities for this patient population
The target enrollment is 226 patients and is expected to occur in May or June this year, setting the time line for reporting first results.
The primary read out of first PFS data is expected within the next 12 months but not before Q4 2019, depending on the number of predefined progression events. So obviously this is a moving target. In follow-up analyses we will also look for overall survival.
This data will be very meaningful for Immutep
Last but not least, having talked about the importance of our AIPAC trial on metastatic breast cancer (slide 28), I would like to give you an insight in to the landscape for efti.
On the figure on the left side you can see how the landscape looked like at the time we started AIPAC.
For HER2neg/HR positive metastatic breast cancer patients which accounts for 65% of all breast cancers, approximately 40 to 60% have received 1 to 2 lines of endocrine therapy and then move on to chemotherapy, while the rest got chemotherapy in the first place.
The landscape today has changed. Now approximately 2/3 of the patients receive a combination of endocrine therapy plus CDK4/6 inhibitors and some of them also receive everolimus. Only a small fraction is directly treated with chemotherapy.
Despite of these changes, chemotherapy remains the mainstay.
It is important to understand that the patients enrolled are heavier pre-treated. Thus, as Frederic mentioned earlier, chemotherapy may be less effective.
However, since in our AIPAC study the patients are randomized, there should not be any bias in the trial because treated arms are well balanced.
Besides the metastatic breast cancer indication, we tackle other indications based on different combinations.
Efti is investigated in melanoma together with pembrolizumab, which is forecasted with sales of almost US$10 billion for 2019. In addition, efti is investigated as part of a the same combination therapy in head and neck and two different treatment lines of NSCLC.
Overall,it is important to understand we are in a very fortunate position. Since the mechanism of action of efti is not specific for certain cancer or mutation, it can theoretically work in every indication or in multiple combinations. Once we have shown the proof of concept, we have the opportunity to target many large markets.
With that I would like to finish and hand back to Marc.
Marc.
Marc Voigt: Thank you, Christian.
In the interest of time: Just to summarise, the data that we reported on efti from our TACTI-mel trial is very encouraging and supports our decisions to continue this combination approach.
Efti continues to have a very favourable safety profile, making the combination with pembrolizumab both feasible and safe. As we have explained, this is also a good signal for our TACTI-002 trial which uses the same combination.
We have seen that efti is able to induce the expected immune response in the blood and we have observed very nice efficacy data in the TACTI-mel trial.
We are very pleased to be investigating efti in combination with pembrolizumab in 3 new indications this year and that we made such good progress with AIPAC.
Strategically, 2019 will be a very important year: all our clinical trials for efti will either have an interim or final read-out. It is very exciting that we expect data from AIPAC and TACTI-002 which we rank as equally important.
I would like to thank you all for your time and now I will pass you back to our moderator to commence our analyst Q&A session.
Clive.
Clive Tompkins: OK. Thanks, Marc. The time for Q&A today is approximately 10 minutes. Panelists will aim to answer as many questions as possible. Look our first question today comes from Dennis Hulme, here in Sydney. Dennis could you please go ahead with your question.
Dennis Hulme: Thanks Clive. You've put up some comparisons of your pulled tactidata to temper monitor therapy, but it's hard to make a meaningful comparison without knowing how many patients entered the screening period of the Part A, and how many failed during that screening period, due to early progression on Pembro. When do you expect to release that data to the market?
Marc Voigt: So we will put the data in general in context, also then when we have the final data later this year, but the actual baseline for measuring the response. The baseline is set for Part A at day one of Cycle 5. Then the analysis putting together from Cycle 1 Day 1 so to speak, obviously retrospective and resetting the baseline to Cycle 1 day one but you can expect, of course, with the final data everything QC checked as usual. I mean this is always interim data so a robust update in that sense in the second half of this year.
Dennis Hulme: OK great, that'll be... Look forward to seeing that. And just in a more general question, what are potential partners wanting to know about efti. What are the key questions that they want to see answered in your ongoing studies? And I suppose I'm wondering, would an ongoing study in melanoma be a quick way to answer those questions?
Marc Voigt: That's actually a very, very good question. Originally we started tackling Melanoma as a kind of feasibility study, we have not been teaming up with Merck and relied in Australia on the public reimbursement. And then with IDO and all the promise IDO had, some companies of course are still working the concept, and the space for melanoma was so crowded. And now it seems to be more open and indeed the results are suggesting that one should continue.
We will evaluate that based on the final results and we will actually have three other indications ongoing. And actually, I believe the questions to be answered are the results in terms of responses of course, when you look on the trial like TACTImel it's even more based on cases, but with AIPAC, you have double blind placebo control setting. So real objective tests, I mean you see a number of smaller clinical trial, Phase 1, Phase 2, 40, 80, 60, 20 patients, not controlled, so it's very hard to... and let's say to qualify the results, especially when you see all sorts of definitions in terms of temporary refractory resistant and the like. For Tacti 002 and then I will stop, I believe we have been chosen the best design for a non controlled clinical trial.
One of best trial designs was a Simmons 2 stage design so where you actually have predefined hurdle for the first group of patients. A predefined number of responses you would like to see before you enlarge. I believe we have appropriate contact to the pharmaceutical industry and of course we try to incorporate all the feedback including monitoring data into our clinical trial program.
Dennis Hulme: Great, thanks very much. That's all from me.
Marc Voigt: Thank you Dennis.
Clive Tompkins: OK, thanks, Dennis. Next question comes from Matt Cross. Matt, just in the interest of time, can you keep your question to just one on this occasion? Go ahead, Matt.
Matt Cross: Sure, of course. Thanks Clive. Hey guys, thanks for hosting another helpful webcast for the wide range of oncology work ongoing with efti. … My question this afternoon, I just wanted to get your take on the utility of an immune activator in combination with therapy design to lift the inhibition of immune activity. And most notably check point inhibitors, it kinda seems that... We've seen, using this old analogy of a car that when you're lifting two brakes, so to speak, so there's an anti-P1 and maybe a mechanism which reduces the macrophage induced suppression. You often don't produce the substantial or sustained responses you might be looking for without another mechanism, as in pushing on the gas at the same time. We've even seen some pretty severe toxicity if we consider combinations of anti-PD-1 and CTLA-4. To me this seems as though if makes efti an agent with a high degree of potential in IO as an immune activator but could you comment on this, and maybe contrast it with the LAG-3 blocking antibody approach and development for oncology as well?
Marc Voigt: Thank you Matt. Frederic, would you like to comment on that?
Professor Frederic Triebel: Yes. I already have shown in slide comparing the new checkpoints in detail on removing the brake on the T cell and what the activator is doing, which is quite different. It is key that if you are have a hot tumor, or even maybe a tepid tumor was interferon gamma, the tumor site, removing two brakes like blocking P1 and CTLA-4, PD-1 on mark 3 may had a few patients more, above the threshold in terms of tumor response.
But if you have cold tumor, indeed in most carcinoma of this is very often the case in majority of patients, what are you going to do? There is no T cells, there is no interferon gamma, so if you remove the brake the car will not go up the hill, but down the hill. You already have to push the gas and activate all the T cells and that's why Marc has been saying that...we are quite encouraged to see that at AACR in Atlanta two days we ago, we heard about results from Apexigen and Dr. Robert Vonderheid from Pennsylvania University showing that with an anti CD 40 agonist plus chemo or anti CD 40 agonist plus chemo plus anti PD-1, most pancreatic cancer patients, which is typically a case of cold tumor, not hemogenic with no T cells, you get tumor responses.
We hope that this will sort of imprint the brain of many objective department in the proforma [inaudible 00:07:53] and to explain what it is about on that we need to push the gas.
Matt Cross: Got it, no, that's a very helpful insight, Frederic, thank you for explaining, maybe a little bit context dependent here, but the activator is really the way to go in some of these combinations. Thanks.
Marc Voigt: Thank you, Matt.
Clive Tompkins: Good, thanks, Matt. Next question comes from Brigitte. Brigitte, go ahead, please.
Brigitte de Lima: Hi, hope you can hear me, I'll keep it brief to one question. So what I was wondering is that you've got enough studies ongoing in combination with pembro who you're covering the combo with anti PD-1. You've got an avelumab study ongoing as well, so you've the combination with anti PD-L1. Do you see any benefit in starting trials with any additional immune checkpoint inhibitors, you do have all your basis covered now that you've got two slightly different anti PD-1, PD-L1's that you're working with.
Marc Voigt: Good question.Of course there would be a variety of different other combinations and that's the beauty but also the challenge of efti that it has relatively broad mode of action. A lot of potential other combinations which could make sense, including maybe even also CAR T let's say, we have CYTLIMIC a collaboration in terms of cancer vaccines.
For a company of our size, I mean in total our clinic trial programs is not more than 400 patients, we feel that currently we should concentrate on what we do and move forward. But yes, of course if there was a good meaningful opportunity you should not rule that out from start. Right now we concentrate on our major clinical trials.
Clive Tompkins: OK. We got a question from Jason McCarthy. I'm gonna read it out because Jason's having problems with his microphone. Here's the question: "As it relates to the AIPAC study in breast cancer with much of the focus in our view on melanoma and other programs in partnerships. This trial is the most advanced and heading towards what could be a significant readout that could lead to registration. Can you discuss where enrollment is and are there ongoing partnering discussions for Europe? And what are the plans for development in the US?"
Marc Voigt: Right. In terms of AIPAC, recruitment is mentioned more than 200 patients recruited from out of 226, so we're actually very close. We cannot comment on any potential partnering discussions. I think that our collaborations with the industry, with GSK Novartis, Merck, Pfizer and also German Merck is showing that we know our customer. That's our business model, to license at the right point in time. But of course I can't comment on that specifically.
The US of course a key market for us, for eftilagimod and for everyone in the industry of course. We look for appropriate ways to bridge AIPAC into the United States. There is a number of different possibilities, opportunities we are discussing, and have been discussing already with the regulators. And we will inform the public once these plans are more mature.
Clive Tompkins: OK thanks, Marc and I trust that answers…. That's Jason. I think we can hear Jason there.
Marc Voigt: Thank you, Jason.
Clive Tompkins: Look, Marc, that concludes the questions from the analysts. There are no more at this stage. With that I'll hand back to you and let you wrap up the webinar for today.
Marc Voigt: Thank you, Clive. On behalf of the whole team we would like to thank everyone for listening today. Special thanks also to the analysts and partners at Edison, Maxim, Goetz Partners and Jones Trading. We are very pleased with the results that efti has been generating in the clinical trials to date and look forward to providing you with updates in the future.
As promised or mentioned we will have a very data heavy year 2019, especially in the second half. A copy of this webinar is available shortly on our website Finance News Network and other media channels. Thank you very much for listening and goodbye.
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