Immutep Limited (ASX:IMM) Executive Director and CEO Marc Voigt, Chief Scientific and Medical Officer Professor Frédéric Triebel, and Vice President Strategic Development Christian Mueller present on Immutep's latest clinical results.Marc Voigt: Welcome, everyone, and thank you all for joining us on this call. Actually, as mentioned, Frédéric and Christian are with me here in Boston, and we are if you like... we report live from Boston from SITC. As Tim mentioned, we are very excited to walk you through the new and, we believe, compelling results for patients with first-line non-small cell lung cancer, which was selected for late-breaking abstract and oral presentation at SITC and also featured in the official press conference on 8 November. So, we have been one out of nine abstracts being selected from over 1,500 submissions, so that's pretty big for us as a biotech company. Additionally, we are pleased to discuss the initial results from our first-ever triple combination trial, called INSIGHT-003, where we are combining efti in combination with anti-PD-1 and chemotherapy, also in first-line non-small cell lung cancer.
Here's my usual forward-looking statement, and before I hand over to the reins of Frédéric and Christian to dive into the clinical data, I would like to spend a brief moment to discuss the LAG-3 landscape in oncology and our unique position.
Turning briefly to slide four. As many of you on this webcast likely know, it's an exciting time to be a LAG-3 company, especially if you are the only LAG-3 pure play. This is driven by the fact that LAG-3 became the third validated checkpoint post FDA approval of Bristol Myers Squibb relatlimab in combination with anti-PD-1 in March 2022 and later this year also by the EMA. Similar to the initial work on both CTLA-4 and PD-1, relatlimab is an antagonist, better known as an anti-LAG-3 therapeutic that is designed to inhibit or block LAG-3 and thereby increase the cytotoxicity of T-cells to fight cancer. However, what is unique about LAG-3 among the three major approved checkpoints is that it can also be used as a tool to activate both the innate and adaptive immune systems. While Immutep was a pioneer in designing the first-ever anti-LAG-3 antibody many years ago, the majority of our focus today lies in pioneering the efforts on the activation side of LAG-3, which puts the company in a very unique position within the oncology landscape.
Moving to slide five. This slide details our deep pipeline of therapeutic candidates based on the company's extensive knowledge of LAG-3. We are fortunate to have Frédéric Triebel as a key member of our management team and board, as his discovery of and subsequent studies of LAG-3 are invaluable to Immutep, especially as we move forward, bringing our pipeline closer to commercialisation. Frédéric has truly been a visionary and pioneer in the field, and he also led the team's pioneering developments for numerous LAG-3 based therapeutics for both oncology and autoimmune diseases. And this is also something we felt today when many people walked up to Frédéric and congratulated on our results and the LAG-3 development overall.
Given today's focus on eftilagimod alpha, we are having many different clinical trials with different indications, such as metastatic breast cancer, non-small cell lung cancer, head and neck cancer, partly together with the industry, and we have, of course, the exciting autoimmune side of things. And I also would like to mention, even though it's at early stage, the small molecule anti-LAG-3 program in mid of this page, which could -- blue sky, of course -- but which could potentially replace the biologics there like relatlimab and others.
As detailed here on slide six, Immutep is the first company to capitalise off LAG-3's unique ability to drive the adaptive and innate immune systems against cancer. Efti, a soluble LAG-3 protein, acts as a key to unlock broad activation of the immune system, as shown here. It accomplishes this through its high affinity for a subset, a specific subset, of the MHC Class II ligand on antigen presenting cells. Once it pairs with its ligand, efti leads to a cascade of important immune cells, including T-cells, NK cells, dendritic cells, monocytes, as well as a significant increase in interferon-gamma and other serum biomarkers which we will provide new information on later in today's presentation.
Additionally, efti has an excellent safety profile, enabling its combination with a number of different checkpoint inhibitors and chemotherapy, and it has also an easy route of administration. It's given subcutaneously. As Christian and Frédéric will shortly present, efti has shown promising clinical activity when paired with the most successful inhibitor on the market, Keytruda, otherwise known as pembrolizumab, across the entire spectrum of PD-L1. Even in patients with low or negative PD-L1 tumours, which is particularly important as roughly 70 per cent of the patient population in non-small cell lung cancer falls into these categories. But, with that, I will leave it as an intro and will hand over to Christian, our Vice President of Strategic Development.
Christian Mueller: Thank you, Marc. And thank you all for joining us today on this very important call to discuss the new and exciting results of Part A, efti plus pembrolizumab in first-line non-small cell lung cancer. Moving on to slide number eight. There are in total more than 1.8 million cases diagnosed every year, and roughly 1.3 million develop metastatic disease and are in general eligible to anti-PD-1 therapy such as pembrolizumab. In addition to its sheer size, first-line non-small cell lung cancer represents an area of unmet need given the median overall survival is mostly, for most of the patient cohorts, here less than 24 months.
And then, besides that, there are in general two other limitations of the available treatment options. For one, for some combinations, you have a high discontinuation rate limiting the efficacy and obviously leading to a lot of toxicity for the patients unnecessarily. And second, there are the patients with low or negative PD-L1 status who represent about two-thirds of the patients and will have a poor outcome to checkpoint inhibitor therapy. These two factors open a significant opportunity, we feel, for a well-tolerated regimen that synergises with the standard of care and improves the outcomes across the PD-L1 spectrum. As the clinical data that will be covered throughout this webcast with detail, efti has substantial promise to fill this large unmet medical need.
Turning to slide nine. The left side of the slide has an overview of the TACTI-002 or KEYNOTE 798 trial which is being conducted in collaboration with Merck, also known as MSD outside the US. TACTI-002 is testing the combination of efti with Merck's drug Keytruda, also known as pembrolizumab, in more than 180 patients across 19 sites in Europe, the US and Australia. And I think the most important feature of the trial is it's unselected for PD-L1, which means irrespective of the PD-L1 status, the patient could have been recruited into that trial. Today, as mentioned by Marc before, we will focus on Part A, a total of 114 patients with first-line metastatic non-small cell lung cancer who were enrolled and treated with efti plus pembro.
The primary endpoint was overall response rate according to iRECIST. Secondary endpoints include or ORR by RECIST 1.1, duration of response, progression free survival and others. On the right side of the slide, we present an overview of the baseline disease characteristics of the patients as they enter the trial. The median age was 67 years. Sixty-two per cent had an ECOG of 1. Basically all patients had metastatic disease at study entry, and there was a fair mix of squamous and non-squamous cancer. Most important is the PD-L1 status, which was assessed centrally by an MSD lab with the FDA-approved Dako kit. Seventy-five per cent of the patients in the trial here in this cohort had a PD-L1 TPS score of less than 50 per cent and 34 per cent were completely negative for PD-L1.
Turning to slide 10. This is where we present the encouraging key efficacy results. Let's start with the table on the left. As of 1 July 2022, the data cut-off, the overall response rate has increased to 40.4 per cent according to iRECIST in the intent to treat population and up to 45.5 per cent in the evaluable patient population. This tops by far the assumptions which we had when we started the trial, when we considered the trial to be positive at an ORR of 35 per cent. The table on the right breaks down the tumour response by PD-L1 status, and we were very excited to see overall responses across all PD-L1 subgroups. And they have increased further from the data which has been reported at ASCO 2022. Notably, for the TPS group of larger or equal to 1 per cent, where we have received the FDA fast-track designation, the overall response rate is 48.3 per cent.
Also of note, we were encouraged to see comparable ORR and DCR with RECIST 1.1 compared to iRECIST as well as comparable overall response rate in the different tumour histologies, squamous and non-squamous, which is shown on the bottom right table. So, overall, just taking this primary objective here into account, we're actually more than excited, very, very happy, to see this data coming in. Besides the sheer presence of responses, we believe that the quality of the responses is decisive in order to translate later into overall survival benefits.
On slide 11, we provide a waterfall chart where you can see the deepness of the responses across the PD-L1 subgroups. Green is for patients with a TPS score of less than 1 per cent. Red is for 1 to 49 per cent and grey for above or equal to 50 per cent. And the black ones are the ones where the TPS score could not be evaluated.
Approximately 70 per cent of the patients have seen a decrease in their target lesions. And as you can see here with this waterfall plot, there are the responses and also deep responses in patients with PD-L1 low or PD-L1 negative tumours. It is encouraging to see that many deep responses are actually in patients that expressed less than 50 per cent PD-L1, because, as mentioned earlier, these patients represent over two-thirds of the first-line non-small cell lung cancer patient population.
And we see similar compelling results on slide 12, where we have a look into the durability of the responses, which we can now for the first time define with the promising interim median duration of response at 21.6 month, which is shown in the Kaplan-Meier plot on the right side. The spider plot on the left shows each patient's response over time from the point that they started the trial, and the patients in gold actually are the ones with the PR, and the arrow shows that the patients are still under therapy. And I think, besides the patients with PR, who usually become a lot of attention, it's notable that also some patients with a stabilisation of disease have a long-term disease control, as indicated by the grey lines.
Overall, we are more than happy. We are very, very happy to see the deepness and the durability of the responses. It looks very, very promising, and maybe what we feel a key differentiator compared to chemo-IO combos, but this will be discussed a little bit later. Let's first of all have a look into the progression-free survival as a key secondary endpoint, moving onto slight number 13.
Despite this trial being a PD-L1 all-comer trial, and we have 75 per cent with a PD-L1 TPS score of less than 50 per cent, both of whom are known to respond less to anti-PD-1 monotherapy, we have achieved promising results in terms of interim median progression-free survival, with a median of 6.6 months. The data is almost completely mature, except for a few patients which are indicated here with grey dots, who have been censored just around six months, and those are all patients who have a partial response and are still ongoing in the trial. So, we are very confident that the final median PFS may increase slightly, and it's expected to stay in the range of seven months.
The chart on the right has median PFS by their central PFS assessment for all PD-L1 subgroups, and it builds on what we have shown at ASCO. Just to pick out one group, maybe, where we have the fast-track designation, the patients with TPS of larger or equal to 1 per cent have a median interim PFS of 9.3 months. And these positive PFS results support ORR results and will be further monitored. With this, I would like to hand over to Frédéric to discuss the initial results from our pharmacodynamic studies and the safety. Frédéric.
Professor Frédéric Triebel: Thanks, Christian. Before I begin, I would like to reiterate thanks to all for joining us on this important call. Now turning to the initial pharmacodynamic data from the TACTI-002 trial, we are pleased to share that we have seen a significant increase in both interferon-gamma and CXCL10 serum biomarkers for systemic TH1 response in the blood at three and six months, compared to baseline as seen on the chart on the right. We also saw an increase as early as under 24 hours after first efti administration.
Similar to the pharmacokinetic data from the randomised double blind Phase IIb trial that combined efti with chemotherapy in over 200 metastatic breast cancer patients, the data here further substantiate efti's unique systemic stimulation of the immune system. Furthermore, the biomarker analysis in the AIPAC trial that show a significant increase in monocytes, CD8 T-cells and CXCL10 was significantly linked to improve OS in the efti group but not in the placebo group. We believe the same positive impact may be unfolding with efti when combined with the checkpoint inhibitor Keytruda here. In particular, increased interferon-gamma levels have been associated with objective tumour response with anti-PD-1 therapy, and CXCL10 has been shown to contribute to a hot tumour micro environment that is known to be necessary for anti-PD-1 therapies to have their greatest effect.
Moving on to the important safety data on slide 15, we continue to be very pleased with the data we are seeing. Efti plus pembro was yet again safe and well tolerated, further building upon efti's strong safety profile to date. It is quite encouraging to see the strengthening of efficacy with improving overall response rate across all level of PD-L1 certification in first-line NSCLC patients, with no new safety signals. Importantly, this additional clinical benefit is occurring with a safety profile consistent with that observed in previously reported studies for pembrolizumab monotherapy, except for the addition of local injection site reaction with efti delivered subcutaneously. In particular, the adverse reaction leading to discontinuation of treatment at 9.6 per cent remains in line with pembro monotherapy and is well below other combination approaches with checkpoint inhibitors. With that, I will turn the call over back to Christian with some benchmarking data on other updates. Christian.
Christian Mueller: Thank you for, Frédéric. Moving to slide 16. I think the question we ask here is, "What does this all mean?" What are the take home messages? On the next slides, I would like to guide you through that. You can see that efti plus pembro is leading to a superior overall response rate, which is the figure on the left side, and PFS, the figure on the right, compared to historical pembro data across all PD-L1 levels. The addition of efti is increasing efficacy by a large margin compared to historical data and in a comparable patient subset. What we feel is most compelling is the increase in overall response rate in patients with TPS negative tumours or tumours with a TPS score of 1 to 49 per cent.
We are further excited to note that the confidence intervals do not overlap in the ORR chart, as indicated with the yellow circles, for three of the most important groups, indicating that these findings are most likely not due to chance. The strengths of the data here in both of these important endpoints speaks for themselves and we believe that efti has potential to substantially increase the number of patients that respond to anti-PD-1 therapy due to this orthogonal mechanism of action. And I think it's really worth to mention that this trial was a clear success and exceeded all our expectations we had when we started it. As mentioned earlier, the bar was set at 35 per cent, and then we are more than 5 per cent higher than that.
As briefly outlined earlier, and let's turn with that to slide number 17, we would like to benchmark the data also against pembro plus chemo for a couple of key endpoints. This comparison centres in first-line non-small cell lung cancer patients with a PD-L1 expression of larger or equal to 1 per cent to focus on where efti has received the fast-track designation by the US FDA. On the left and middle charts you can see the overall response rate and median progression-free survival for efti plus pembro, always in green, which is always well ahead of pembro mono, which is blue. And then, in yellow, you have the pembro plus chemo, where you can see the ORR is slightly lower for pembro plus efti, but the median PFS of efti plus pembro is already in the range of what you would expect with doubled chemotherapy plus an anti-PD-1 antagonist. And, as discussed earlier, it's not just about having a response, but also about the deepness and the durability and how it translates into improved PFS and then later on overall survival. And we believe that especially durability plays a key role here.
And as you can see on the right chart, the median duration of response drops from 20-plus months for pembro alone -- that's the left blue chart -- to 9 to 12 months if pembro is combined with chemo. That means there's a price for the increased ORR from 27 to 55 per cent. The durability of the responses decreases by 50 per cent. Whereas the interim median duration of response for efti plus pembro is exactly in the same range as for pembro alone at 20-plus months. And, hence, we believe that the increase in overall response we see here may translate favourably into survival compared to the combination of chemo plus pembrolizumab. As is clear from the chart on the right, the addition of chemotherapy has a deleterious effect on the duration of response as compared to pembro mono. And this is key to why the prospect of chemo-free regimen of efti plus pembro driving superior ORR and median progression-free survival without sacrificing duration of response is so enticing and has so much promise to positively impact outcomes in first-line non-small cell lung cancer.
At this point in the presentation, we will move on to cover the promising initial clinical data from INSIGHT-003, which was shared via a poster presentation here at SITC earlier today. So, let's turn to slide number 19. INSIGHT represents the first triple combination approach utilising efti in combination with carboplatin and pemetrexed in anti-PD-1 therapy. This part of the study is focused on first-line non-squamous non-small cell lung cancer and is assessing safety, tolerability and initial efficacy. Up to the data cut-off, 14 patients were enrolled. Eleven were evaluated for efficacy.
Let's move to the next slide, where we can show that there were favourably early results in terms of overall response rate and disease control, with 73 per cent and 91 per cent respectively. Of the 11 patients who have been evaluated here for response, 82 per cent, so 9 patients out of these 11, had a TPS score of less than 50 per cent, and leading to an overall response rate of 67 per cent in this subset. The combination has been well tolerated and appears to be safe, with only one immune-related SAE related to the study treatment. In general, there have been no new safety signals detected so far.
When taken in conjunction with the data reported from our other trial, these results give us continued confidence in the flexibility of efti to be safely combined in various novel formats and enhance various therapeutic approaches for multiple solid tumours. I think that's a good segue into slide 21 that concludes our prepared discussion and data provided for first-line non-small cell lung cancer. We really feel the maturing data from TACTI-002 and the initial data from INSIGHT-003 continues to build our understanding of efti's ability to boost the innate and adaptive immune system and provides important insight into how efti may ultimately meet diverse first-line NSCLC patient needs in both chemo and chemo-free settings. The large data set of 100+ patients in this patient population provides a robust basis for phase three planning. And importantly, due to its orthogonal mechanism of action, efti has the potential to greatly increase the number of patients who respond to anti-PD-1 therapy, including low and negative PD-L1 expressing patients, who are making up 70 per cent of the patient population in first-line non-small cell lung cancer.
So what could be potential next steps? Regarding the outlook ahead, the planning around intelligent registrational relevant trials, for instance, adaptive Phase 2/3, is in progress and under discussion with the regulators. Potential design options are proceeding and include, potentially, superiority in terms of overall survival against pembro monotherapy restricted to patients with this combination could potentially be useful, or superiority in terms of overall survival versus established chemotherapy plus anti-PD-1 in appropriate first-line non-small cell lung cancer patients. Trials are being planned as we speak in a most cost-effective and time-efficient manner, pending feedback from agencies, final trial design, including targeted patient population, is expected in the first half of 2023. And with that exciting news and this summary, I would like to hand over to Marc for a summary on our developments there.
Marc Voigt: Yeah. Thank you, Christian. So, a bit of progress in head and neck cancer and metastatic breast cancer. I will be brief. To date, we have generated, I believe, very encouraging data across a wide spectrum of solid tumours in combination with anti-PD-1, anti PD-L1 and chemotherapy. And we believe that efti has the potential to play a significant role in a variety of different cancers. And, beyond non-small cell lung cancer, there are two areas that we are particularly excited about to make a real difference in the lives of patients. These areas are first-line head and neck cancer and metastatic breast cancer. As detailed on the left side of this slide, though there has been progress for first-line head and neck cancer patients through the approval of pembrolizumab, or Keytruda, in combination with chemotherapy as well as monotherapy for patients with a CPS score greater or equal to 1, there remains an unmet medical need. As you can see in the graphic, there's a significant increase in overall response rate for patients when pembro is combined with chemotherapy, but that gain is severely offset by a large decline in duration of response from roughly 22.6 months for pembro monotherapy to just 6.7 months when combined with doublet chemo. So, we see not only in non-small cell lung cancer but also in other indications, that the combination with chemotherapy, while increasing overall response rate, that this increase is often bought with a compromise on the quality of the responses. And here lies a substantial opportunity for efti. The efti-pembro combination can achieve a comparable duration of response while attaining a higher overall response rate with improved overall survival, potentially, and a similar safety to pembro mono. So, we can make a material difference in the lives of patients with first-line head and neck cancer. Just to remind everyone, we have also a fast-track designation in first-line head and neck cancer.
We were pleased to recently report that the IDMC recommended continuing the trial, the TACTI-003 trial, with no modification after review of initial safety data. It's worth mentioning also that they reviewed initial efficacy data, and we look forward to providing more updates on this important trial as we move into 2023.
Moving briefly on to the metastatic breast cancer side, there remains also a large area of unmet medical need, and one needs to improve overall survival while maintaining quality of life in hormone receptor positive and receptor negative metastatic breast cancer patients. Based on the encouraging clinical data from the AIPAC trial, where we established a significant correlation between overall survival and a substantially higher CD8 T-cell count that was driven by eftilagimod and we maintained a better quality of life, whereas the placebo groups saw a material decline in quality of life, we believe that efti in combination with standard of care chemotherapy can play an important role for these patients. So. while we prioritise non-small cell lung cancer, our preparations for potential future clinical developments at MBC, including engagement with the regulators, CROs, and other stakeholders, are also progressing.
So 2022, to come to the end of the presentation part of the webcast, has been a very busy year for us, and the year is not yet over, so we will remain busy in the next coming weeks. I believe we presented compelling data at an oral presentation at ASCO. We had the late-breaking oral here at SITC from the TACTI-002 trials. But we also saw good progress in the other clinical trials. Also, I would like to mention that we are working on the manufacturing side of things actually for both, for IMP761, our unique LAG-3 agonist in the autoimmune space, as well as for eftilagimod, and I hope for updates before end of the year, and in general updates on the different programs. We are well funded, we have very strong institutional ownership and good base. And, with that, I will turn it back to Tim to open up for questions from analysts or those which have maybe been asked in between online.
Tim McGowen: Thank you, Marc. We'll now take some questions from analysts. If you'd like to ask a question, press the "raise your hand" button at the bottom of the screen. In the interest of time, we'll just have one question only, and then we'll come back if we need to. We'll start by opening up the questions. I'll pass over to Ahu Demir. Could you please ask your question?
Ahu Demir (Ladenburg Thalmann): Hello. Thank you so much for taking my question, and congrats on the recent developments again, one more time. My first question is Libtayo was approved earlier this week. I am curious to know does it change anything for the company's strategy in the non-small lung cancer? And the second part of my question, as a follow-up, is could you remind us the overall survival benefits or PFS that you have obtained depending on the PD-L1 expression? Thank you.
Marc Voigt: Yeah, thank you, Ahu. A good question. We are actually excited by the approval of another anti-PD-1 in non-small cell lung cancer. We actually believe that this brings more dynamic to the field. Of course, pembro for the time being remains the number one drug. The others have to catch up. But it's good to see that movement. It's good to see dynamic and more players entering the field, and it's underpinning the relevance of first-line non-small cell lung cancer. But, at the end of the day, it's also not -- with all due respect of course to this great accomplishment -- it's not a differentiator. And differentiation is what you need here in terms of the combination strategies, and this is why eftilagimod can play a very good role there with pembro or potentially with other anti-PD-1s. The second part of the question I may hand over to Christian.
Christian Mueller: Thanks, Ahu, for the question. So, overall survival is a secondary objective in the TACTI-002 trial, but has not been reported yet, and you can expect it for the future.
Ahu Demir: Thank you.
Tim McGowen: Thank you. Next question is from Melissa Benson.
Melissa Benson (Wilson's Advisory): Thank you for taking my question. I had a question around the next steps you spoke to in the slide around Phase 2/3, and you've obviously spoken about these initial INSIGHT results with the triple combination as being potentially informative of what you're doing next. I guess the first part is, is that small kind of sample set enough to really inform any kind of late-stage design? And then, secondly, when we're talking about... you mentioned kind of the appropriate patient set and what you can show superiority. Should we be thinking that that's kind of aligned to the fast-track designation, being just those TPS greater or equal to 1 patients? Thank you.
Marc Voigt: I believe, from a regulatory point of view, a greater, equal to 1 TPS could be a good way to move forward. As we saw, we wouldn't be limited to that, but, of course, as a company you need to make some choices. You are right in terms of your comment of not the biggest sample size for INSIGHT-003. But, from a safety point of view, we feel that the feasibility is there. We also saw encouraging signs of activity. Of course, the study is not yet fully recruited, but we hope that this will be the case in the next few months so that we have also additional data coming in. And we feel it's a valid option among a number of different options with or without chemotherapy. But of course, mentioning adaptive trial design Phase 2/3, these could be smart and cost-effective ways to move forward, and also, for instance, with chemotherapy to have the right risk-balance approach. I don't know, Christian, if you would or, Frédéric, if you would like to add to that?
Professor Frédéric Triebel: This is Frédéric speaking. What can we say about this is that the two data sets don't have the same timelines. Pembro plus efti versus pembro alone, we have Phase 2 data now, ready for Phase 3, while the triple combination with chemo, it will take us a little bit more time to assess what we're doing next.
Melissa Benson: Thank you.
Tim McGowen: Thank you. The next question is from Joel Beatty.
Joel Beatty (Baird): Hi. Congrats on that progress and thanks for taking the question. I think with a lot of different ways and indications and approaches to move efti ahead, could you kind of outline maybe what some of the highest priority next steps are and then what some of the lower-but-nice-to-have next steps are as well?
Marc Voigt: Yeah, thank you, Joel. Good question. So, first of all, one should take a look where the bulk of the data is. So, indeed the top priority is first-line non-small cell lung cancer, and indeed we have most data around the chemo-free option. That could be a natural way to go. For late-stage development, we have the randomised ongoing TACTI-003 clinical trial in first-line head and neck, so that's a priority by definition so to speak. And then we have some optionality in terms of metastatic breast cancer. So, this is one way we look at it.
The other way is the horizontal rollout, so more signal detection studies. We have been announcing a few weeks ago a new clinical trial in soft tissue sarcoma, which we do with the National Reference Center in Warsaw in Poland, funded by the Polish Government. We believe it's a cost efficient way to test there, for instance in the neoadjuvant setting. And together with radiopharmaceuticals, additional indications, potential other combinations. And this could also be something moving forward that we see some more of these signal detection studies in order to show the breadth of the program. So, vertical as well as horizontal in a responsible manner.
Joel Beatty: Thank you.
Tim McGowen: Andrew Paine, a question from you, please?
Andrew Paine (CLSA): Yeah, thanks, and congrats on the results. I just want to talk about the revenue growth that Opdualag is seeing, BMS' LAG-3 therapy. I just want to get your thoughts on what you think it means for efti and the LAG-3 sector, which has obviously seen a lot of interest, but now we're also seeing the attractiveness of the end market in those revenues for Opdualag.
Marc Voigt: Andrew, excellent point. Because the commercialisation point of view and that at the end of the day, you need to make some dollars, to put it bluntly, is of course very important, while delivering benefit to patients. And we're, of course, very glad that Opdualag is doing better than the analyst consensus, and the first quarter has been beating it by 100 per cent and also the uptake thereafter was actually very good. That shows the commercial attractivity of LAG-3 and the potential there, which is estimated for very few indications which could be modelled already to be in a few years US$4 billion annually, and potentially more. If you look back to anti-PD-1, the original modelling was also reduced.
And, of course, we believe that with a true original and true unique drug like with eftilagimod, that this paves the way as an option as well and shows the attractivity. Because, unlike anti LAG-3 Opdualag combination, we have here something unique and a clear cut differentiator. And, of course, we have a certain understanding of the market potential of the drug, as you would expect, and also a certain understanding of potential price points for such therapy, with the advantage maybe that you need to give, as it is an agonist, low dose, and that the route of administration is not intravenous but it's subcutaneous. So I believe these are also important features if you look at the pharmacoeconomical debate, third-party costs and future potential.
Andrew Paine: Great. Thank you.
Tim McGowen: Next question's from Tanushree Jain. Over to you.
Tanushree Jain (Petra Capital): Thanks, Tim. Congratulations, everyone, on the excellent data. I think this is probably the most consistent data I've seen across PD-L1 subgroups in non-small cell lung cancer. So, congratulations, and congratulations, Frédéric. I've got a two-part question just around the Phase 2/3 design. One is a follow-up to Ahu's question before. With Libtayo's approval in this setting now, is that a consideration when you're thinking about the comparator arm in your study? And secondly, just on the overall endpoint, I think you mentioned that you are looking at OS as the primary endpoint to show superiority. Some of the other combo trials in recent times have had PFS and OS as co-primary endpoint. If you could just talk through the rationale behind not including PFS as a co-primary endpoint, that would be great. Thanks.
Marc Voigt: Yeah, thank you, Tanu. First of all, regarding the comparator arm, at the end of the day you would need to look in the discussions with regulators what is appropriate and what is feasible. The most natural way to go and the established drug is pembro. So, you would need to assess if you were able to have the chance to go in a clinical trial, let's say with a TPS greater or equal to 1 versus pembro mono, and there are always different points of consideration. Or if you need to compete versus pembro plus chemo. Other clinical trials, Phase 3s of course, you'll see sometimes still, and this depends on when the study has been started and which regulatory environment, as a comparator doublet chemo.
So this is really something where we need to drill down in the design and discuss with the regulators. But we very welcome the approval of another anti-PD-1. We believe that's great, and as mentioned, is providing more dynamic to the field and is something which we may see also in the future. But, ultimately, it may cannibalise some of the sales from pembro, could be, but it's not necessarily adding new potential, because the limitations for anti-PD-1 therapy at the end of the day remain the same. For the question regarding the co-primary endpoint that you, for instance, see in the anti-TIGIT, anti-PD-1 trial from Genentech Roche, I may hand over to Christian and Frédéric.
Christian Mueller: Yeah. Thank you, Marc. And thanks for the question. Obviously, endpoints and the overall design of those adaptive Phase 2/3 studies is key and decisive. And I think what we could show today is that response rate is increased, whereas duration of response is maintained. So, you could consider that maybe as an interesting early sign of efficacy, which translates hopefully later into overall survival. So, it could be used to make some decisions early on and through the trial. And the final primary, co-primary and what have you endpoints is up to the discussions with the regulators in the very end. And very specific trial design comes down to indication and it comes down probably also to the patient population. So, maybe as a concluding remark, take those two examples mentioned there just as examples, first of all.
Tim McGowen: Thank you. We have time for two…
Tanushree Jain: Great. Thank you.
Tim McGowen: Excuse me. We have time for two more questions. The first one is from Chris Redhead.
Chris Redhead (goetzpartners): Hi, guys. Yeah, I want to really congratulate you on this data. It's remarkable. I think it's something that's worth pointing out that hundreds of trials have been done in this area trying to get combinations that have been able to improve PD-L1 and haven't worked. And then to see that the durability of the response is extended is, in my view, truly remarkable. So, it's very, very exciting, I think. And I don't think there is anything out there in the pipeline that really matches up to this, as far as I'm aware. You guys, maybe you can enlighten us, but I don't think there is. The issue about the chemotherapy, just sort of off-track a little bit, what's happening with the Chinese partnership?
Marc Voigt: Chris, thank you for that question and the remarks. So, our Chinese partner, EOC Pharma, I hope we hear some more publicly. Of course, we have a dialogue with them, and they definitely have plans to move ahead. Just to remind everyone, we have been out-licensing the Chinese rights to eftilagimod some time ago, and they are fully funding all the parts of the Chinese development. We collect milestone payments and royalties and, of course, we expect some movements as you would expect as a partner. We have joint development committee meetings, and of course they carefully track the data and would definitely like to move ahead. But I would need to leave it to them to announce or co-announce a potential new study start in that area. Could be in MBC, could be in other parts, as we have been showing in the meantime a number of different indications and combinations which work. As a local partner, of course, you need to always consider the local background. So partly the treatment landscape is a bit different, and this is what needs to be considered.
Chris Redhead: So, is it possible that the Chinese guys will do something in non-small cell lung?
Marc Voigt: It's possible that they do something, let's say, in an anti-PD-1 combination. That's definitely possible.
Chris Redhead: Okay. Okay. Because, clearly, lung cancer's a very, very big issue in China.
Marc Voigt: Absolutely. I agree 100 per cent. That's a high incidence rate there.
Chris Redhead: Because of all sorts… There's high smoking and pollution. Okay.
Marc Voigt: Thank you.
Chris Redhead: That was sort of following on from the fact that the chemo that you used in the original AIPAC trial, they were going to use it on extended basis, weren't they, in that trial? But, clearly, they're thinking about doing something else. Doesn't apply so much.
Tim McGowen: Thank you, Chris. We've got time for one more question. It's from Dennis Hulme.
Dennis Hulme (Taylor Collison): Okay, thanks very much. My question's just about the TACTI-002 in non-small cell lung cancer. The first is what proportion of those responses have been confirmed? And secondly, with those fatal adverse events, can you give a little more colour around those and how that compares to what's been seen for pembro monotherapy? Thank you.
Marc Voigt: Thank you, Dennis. Christian, would you like to take that one?
Christian Mueller: Yes, sure. So, as mentioned on one of the slides, 87 per cent of the responses have been confirmed so far, and I think that's a pretty good number. And in terms of the adverse events, I think the ASCO presentation contained a little bit more details on the respective adverse events. It's not on the slides here, but if you take the data we have shown at ASCO and today here at SITC and you compare it to what's available out there for pembrolizumab alone, I believe it's fair to say that there is no negative synergy in terms of the toxicity. So, you'll see a similar rate of immune-related adverse events compared to what is out there for pembrolizumab in the public domain and then also what we have access to. And we did that in a very detailed fashion, really going through it line by line. So, we feel from a safety point of view, we are in an excellent spot.
Dennis Hume: Okay, thank you.
Professor Frédéric Triebel: And maybe I can comment on that. With Opdualag, you do see a doubling of the immune-related adverse events from about 9 per cent to 18 per cent by adding anti-LAG-3 relatlimab to nivolumab. And that makes sense because you block two brakes on the T-cell. So, they are becoming even more wide in a sense. With efti, it's totally different because we're not touching the T-cells directly, so indirect T-cell activation through the physiological mechanisms, through the dendritic cells. And we haven't seen any additional immune-related adverse events in the TACTI trial and that was expected because it's a very different mechanism of action compared to ICI.
Dennis Hume: Okay, thanks. That's a very helpful comparison.
Tim McGowen: Thank you, everyone. Thank you for your questions. That's all we have time for today. I'd like to hand back to Marc to make his concluding remarks.
Marc Voigt: Yeah, thank you so much. Not lengthy concluding remarks. I would like to thank everyone for calling. As mentioned, we are very excited. We hope to update you, and you will hear from us before the end of the year. And, with that, I would just like to thank you again and say goodbye.
Ends
