Good morning, everyone. Thank you so much for joining us today. Welcome to Canaccord's 44th Annual Growth Conference. Really happy to be joined by Immutep this morning. The CEO, Marc Voigt, will take you through the novel clinical stage immuno-oncology company. I'll hand it over to you, Marc, and then we'll go into Q&A. Thanks.
Perfect. Yeah. Thank you, Elyse, and thank you, Canaccord Genuity team, for providing us with the opportunity to present here. My forward-looking statement. Immutep is an Australian dually listed biotech company. We have been pioneering the LAG-3 space since years. You're well aware that the LAG-3 is one of the leading immune checkpoints. PD-1, CTLA-4 are others, and possibly a bit more prominent, but LAG-3 is within the next wave of therapeutics to come. We are working in immuno-oncology as well as in autoimmune diseases, and we have first-in-class products, and some of them are in clinical development. So we have multiple catalysts ahead. We are well-funded, with a cash life till end 2026, and we also work in collaboration with the big pharmaceutical industry.
So when I said we are pioneering the LAG-3 space, you can see here that we address and utilize LAG-3 either as a target or as a tool in every possible way. On the one-hand side, as mentioned, in autoimmune diseases, and on the other-hand side, in immuno-oncology. Most prominent is possibly eftilagimod alpha, which you see on your left-hand side, and efti, as a tool to activate the antigen-presenting cells. Our pipeline, I believe it's a relatively rich pipeline, and in terms of eftilagimod, we will actively become a phase III company, actually in one of the most important markets in oncology, which is first-line non-small cell lung cancer. Also, we actually press released today that IMP761 at the bottom is now reaching clinical stage. So we saw the first subject being dosed yesterday.
We have been receiving quite a high amount of scientific clinical recognition in terms of conferences we have been presenting at, especially in terms of first-line non-small cell lung cancer. You see here pictures from ASCO, SITC, and ESMO. We are very pleased and honored that we had the chance to discuss the data we have been achieving so far at those high-ranking forums. One study we have been presenting in the past, and I will not spend too much time on the old data, especially in order to leave some room for Q&A and discussion with Elyse, is TACTI-002 or KEYNOTE-798, a trial which we are running in collaboration with Merck, so combination of eftilagimod and KEYTRUDA, 114 patients.
So not a small clinical trial, but a sizable clinical trial, with typical baseline characteristics in first-line non-small cell lung cancer, actually looking at the whole so-called TPS range, so including all patients, where you can measure PD-L1. And, the results we have been seeing compared to historic control have been outstanding, so maybe not a surprise that we had all these, oral presentations. If you look at, overall response rate, progression-free survival, not on this slide, but also very strong durability of the response, and then finally, median overall survival, I believe we have been seeing remarkable efficacy, and again, in a multinational, multicenter trial in 114 patients, so not a small, biotech, clinical trial.
Also, when you compare our results, versus best standard of care, which is registered on the market, you see on the one-hand side, regarding safety, the drug-related adverse events leading to discontinuation are by and large within the range of KEYTRUDA monotherapy. We do see, of course, efti-specific side effects, like injection site reactions, but overall, very well manageable. And you see that we have been driving remarkable efficacy in terms of the most important endpoint for the patients. This is overall survival. We also have been combining eftilagimod, KEYTRUDA, and chemotherapy. We presented some results at ESMO last year. You see a remarkable overall response rate, and we will continue to generate further data from this clinical trial, which is called INSIGHT-003.
Overall, we have been discussing our data and our plans with our collaboration partner, Merck, and we are uniquely positioned for a phase III in first-line non-small cell lung cancer, and with this phase III, we will address actually the entire non-small cell lung cancer market eligible for anti-PD-1 treatment. Squamous, non-squamous cell, we have been discussing with the regulators, with the German Paul-Ehrlich-Institut, with the Spanish AEMPS, and most recently with the U.S. FDA, to discuss the setup of the trial to get their regulatory buy-in and support. I believe we all know how important first-line non-small cell lung cancer is for KEYTRUDA, the top-selling brand in our industry, and it's driving the revenues of Merck to a large degree.
We teamed up with Merck for a phase III collaboration. Actually, the first time since more than 2.5 years that Merck teamed up for a phase III collaboration. Last time has been, if I recall correctly, with Gilead, and now, they teamed up with us for a trial, which we call TACTI-004. It's a large clinical trial, about 750 patients, with the right statistical grid, so pharma standard in terms of robustness of the statistical design, which we, of course, also discussed with the FDA. And we are looking here at, KEYTRUDA plus chemotherapy, squamous, non-squamous, whole TPS range, ± eftilagimod. So it's obviously double-blind, placebo-controlled, with a dual primary endpoint, progression-free survival and overall survival, so two chances to, have a positive, readout.
This trial is scheduled to start by end of this year or Q1 next year, and it's following rigorous operational preparations. I believe we will, at the end of the day, see round about 150 hospitals, certainly in well above 20 countries. And we have also implemented a futility analysis, which could kick in by end of 2025, and then the interim read could happen in 2026, with last patient in during 2026. And I do believe that this trial has a chance to recruit actually relatively well because we provide the patients with best available standard of care, and KEYTRUDA gets 7- 8 out of 10 metastatic lung cancer patients anyway, ± a modern IO drug, which is eftilagimod, and which is, for the time being, very, very safe.
So no downside for the patient, but potential upside, and operationally, of course, recruitment is very important, and I believe this should go well. So we are very much working on the study preparations for this important clinical trial, which is designed to set a new standard of care in the most important market in oncology. We have also a clinical trial in first-line head and neck cancer, and I know that there is a lot of interest in terms of head and neck cancer, driven by a number of different biotech companies. We have here a trial also in collaboration with Merck, called TACTI-003, which is partly randomized in terms of cohort A and partly not randomized in terms of cohort B.
So cohort A, we look at CPS ≥ 1, and cohort B, CPS < 1, KEYTRUDA plus efti versus KEYTRUDA, and in cohort B, KEYTRUDA plus efti. I think we all know that the KEYTRUDA alone is relatively ineffective there. We have seen a continued strong safety profile, and we saw in this randomized, relatively small randomized clinical trial, a good relative difference of close to 70% in terms of CPS ≥ 20. We have a good result for eftilagimod in 1- 19. However, we have also an outlier there in terms of the KEYTRUDA group in 1- 19, which is more than 33%. Unfortunately, the trial arms are a bit imbalanced in favor of KEYTRUDA monotherapy.
However, we will present more data from this clinical trial, and I believe we all know that there are other therapies out there which are driving a very high response rate. But, for us, it's specifically important to drive high durability of the response, turning into good overall survival, which is especially important in head and neck cancer. So this is something where we need to focus on durability of the response, overall survival, and you will learn more data from this randomized clinical trial in the remainder of this year. The cohort B, we have been the first Australian company presenting at an ESMO Virtual Plenary Session. Outstanding, remarkable results, among the highest recorded response rate for CPS < 1. It's a less competitive space. You see here the results around about 35% overall response rate.
Of course, we may see in the future more responses coming for cohort A or cohort B. And also importantly, we saw responses regardless of HPV status. Deep, durable responses, as you see here, we also measured according to RECIST 1.1, the primary endpoint in evaluable patients, and iRECIST. And we see an excellent duration of treatment, which gives very high hopes in terms of durability of response, which is known for many EGFR-targeting drugs to be around six months only. So we see here, you see the six months mark in the slide.
When you look at the responses, most of the patients are continuing with treatment, so we have high hopes for this chemo-free treatment in an environment where all approved treatments for CPS below one contain chemotherapy to see good responses and also overall survival driven by chemotherapy in the second line, which has not been exhausted yet. So there are many, many sweet spots for cohort B. I think I mentioned this already. If you benchmark versus historic control, it looks quite nice also in terms of complete response rate, which we have been driving to a good degree. I have to speed up a little bit, otherwise Elyse gets nervous, I trust. We have also a late-stage trial in metastatic breast cancer, phase II, phase III. It's ongoing. We will have some data before end of this year.
We have here a single case. I don't go into detail, but it's for us, of course, very rewarding to see another complete response. We saw that in lung cancer and head and neck cancer, first line, second line. We see it in metastatic breast cancer. Here, a 35-year-old woman, and she is under eftilagimod monotherapy since 4 months, maintaining the complete confirmed response. IMP761, just a few seconds on, on autoimmune diseases. First-in-man has been achieved successfully. We are going to see first data before end of the year. 49 healthy volunteers, and also with the chance to read into the biology of the drug, because it's a double-blind, placebo-controlled phase I.
First of all, safety, but also then the biology of the drug versus placebo run at the world-class institute in Leiden, in the Netherlands, called CHDR. A lot to expect in the remainder of this year and next year. We are turning into a phase III company in the most important market. We have data to come in head and neck cancer, first-line and metastatic breast cancer. Other clinical trials are ongoing in soft tissue sarcoma, for instance, in urothelial cancer, also in collaboration with German Merck, and IMP761, autoimmune diseases, and our other collaborations and products are hopefully moving forward as well. So, I stop here, and thank you so much for the time being, and sit right next to you maybe.
Great. Thanks, Marc. So, you know, maybe just looking at the mechanism, most LAG-3 assets are anti-LAG-3. Efti operates a little bit differently. Can you run through some of the key differences in the rationale for the mechanism?
Yeah, thank you. That's an important question because very often when we discuss and refer to LAG-3, it's automatically seen as a kind of special anti-LAG-3, eftilagimod, but it's not. What we do there mechanistically is that we use LAG-3 as a tool, not as a target, with anti-LAG-3, anti-PD-1. The immune checkpoint is a target focused on the T cell. Here we use the unique biological properties of LAG-3 and fused it to human IgG1 and then we have created an MHC Class II agonist. So the major ligand of LAG-3 is MHC Class II, and via this way, we activate the antigen-presenting cells, dendritic cells, monocytes. So it's very important to keep in mind because there's no other product like this.
It's not a me-too, with all due respect, and we, we like it, of course, like anti-LAG-3, which we exclusively worldwide out licensed to Novartis, or anti-PD-1 or anti-CTLA-4.
We know that you kind of help activate then some tumors for some of the anti-PD-1s. But are you synergistic with those assets as well?
The data indicates that. Of course, you need to look at the contribution of components and all the data we have, and also the unique immune activation profile indicates that indeed that there are synergistic effects. Because what we do is activate the APCs, and then via the physiological way, we see more CD4, more CD8 T cells. We also kick off the interferon gamma cascade so that the right chemokines are being released, and guiding the important immune cells to the tumor site, including NK cells.
Got it. And then with that, you know, you're kind of looking at different TPS and CPS subgroups, both in lung and in head and neck. Where do you see the highest unmet need, and where do you think you'll be able to make the most clinical impact?
Yeah, first of all, we clearly focus on first-line non-small cell lung cancer. We have the largest dataset there, including median overall survival, so a very, very robust setting where we go after the entire market. Of course, we will also follow the different TPS strata. For head and neck cancer, clearly, I see it in CPS < one. There are a number of patients who can't tolerate chemotherapy or outright, outright refuse to take chemotherapy. Now, in this setting, all approved therapies contain chemotherapy, so what should these patients do? They have no approved treatment option. Especially for those patients, we do see a good chance with this chemo-free treatment to drive responses, to drive a good durability.
And finally, and most importantly, without that, you will not get approval or it will not hold median overall survival, and we will discuss the path forward with the FDA before end of this year.
That makes sense. And, you know, we know, we know not all PD-1s are made equal. You've got a partnership with Merck for KEYTRUDA, which is great to see, but is there a rationale for being able to work with any of the other players in the space as well, or even expanding, as you mentioned earlier, into, into the CTLA-4 space?
CTLA-4 is maybe not our first priority, to answer that question straight, but indeed, we work in other collaborations. We teamed up with German Merck, with avelumab, for instance, in urothelial cancer and earlier in a successful phase I clinical trial. We are in discussions with some additional other top pharmaceutical players in that respect. And also, it's fair to say that in first-line non-small cell lung cancer, we had the choice, but we decided to go with KEYTRUDA. It's clearly the market leader. As mentioned, 7-8 out of 10 metastatic lung cancer patients get KEYTRUDA, and I believe it's the best choice in terms of recruitment, in terms of commercial and global brand and day-to-day clinical care.
Great. Maybe switching gears to head and neck and the data that you've seen there. You know, why do you think you got such a good response in the CPS < 1 patients and, you know, just trying to kind of frame the uplift in the response to the CPS > 1 or the CPS > 20 patients?
Yeah. First of all, CPS or TPS is irrelevant for eftilagimod. That's a biomarker being relevant for anti-PD-1. We look at different other biomarkers, and there is, in terms of first-line non-small cell lung cancer at SITC, in November last year in San Diego, a poster release with very insightful biomarker data. We have been driving responses above 30%, regardless of CPS score. And of course, there are debates regarding CPS, TPS, the relevance, how you measure it validly. We do see, in terms of the disease control rate, an increase of the disease control rate from below 1 to greater equal 20. From 58% patients with clinical benefit and CPS < 1, up to 76% disease control rate in CPS ≥ 20.
We do see an increase because a KEYTRUDA effect eventually kicks in, but CPS, TPS for eftilagimod is not really relevant.
Got it. And then looking at that, is pembrolizumab monotherapy the right comparator here, or should we be kind of comparing pembro in combination with chemo?
For CPS ≥ one, pembro is approved. For CPS < one, pembro has been tested unsuccessfully. As we all know, it's not very effective, driving there about 5% overall response rate in evaluable patients, and about seven months median overall survival. You saw the swimmer plot. So indeed, you would compare in CPS < one with the EXTREME scheme, so cetuximab, chemotherapy, and pembro plus chemo. There are differences between the U.S. and Europe in terms of the approvals and in terms of the landscape. But, if you look at pembro chemo, if you look at the EXTREME scheme, you see response rate between 30%-40%, and median overall survival around 11 months only. And this is certainly something where you need to improve.
Maybe one comment regarding the relevance of overall response rate and the challenge in head and neck cancer. I believe most of you know the LEAP-010 trial run by Merck and Eisai, where you saw a statistically significant in phase III, 511 patients, a statistically significant overall response rate, statistically significant progression-free survival benefit for the combination versus KEYTRUDA monotherapy. But in overall survival, KEYTRUDA mono has been two months better. Trial failed. So you need to look at the totality of the data, including the safety aspects.
Great. And, you did have an astronomical response in the CPS < 1 patients, materially beating available standard of care. Is there a potential regulatory pathway forward just in that specific subgroup where there's such a high unmet need?
Could very well be. Of course, you could either look at the whole patient population, CPS < one, where you then would need to benchmark and compare yourself with the treatments we have been discussing, pembro chemo, the extreme scheme. You can focus on the chemo-free approach for more specific patient population. Give or take, half of the CPS below one patients either can't tolerate it or outright refuse to take it. So this is something which we can discuss, which we will discuss with the FDA before end of the year, so I can't make any promises, as you will understand. But we, as usual, as we do it normally in a methodical and sober way, move forward based on the data and regulatory advice.
Great. And then switching gears to lung, you know, going into phase III, you've got the collaboration with Merck. It's a really interesting trial design, both in terms of the use of chemo and the fact that you're assessing all TPS subgroups in the one trial. Can you run through some of the highlights of that trial design and give us some context as to the key factors that went into that?
Yeah. First of all, it's a result of a very fruitful dialogue with Merck and the right working groups and people. It's a very rigorous process to come to such a trial, so it's a very robust design, not the biotech way to cut corners and make compromises. But it's 750 patients. It's adequately powered, so you can assume a very, very high power to drive benefit in terms of progression-free survival, and separately, as it's a dual primary, not a co-primary endpoint, overall survival. Also with chances around the alpha to regain it, actually. So, I believe a very clever design, actually.
A TPS score 0-100, we do expect, TPS < 50 to be over-represented because patients with a TPS score of 90, so a high expression of PD-L1, will certainly get a pembro monotherapy. But overall designed to get approval in the whole range, squamous and non-squamous cell. The right inclusion, exclusion criteria, and, yeah, we are looking forward to the start.
Great. We do have some context as to how the efti pembro chemo combination works with what we've seen in INSIGHT-003. What other learnings can we take from that trial? What are the next catalysts there in terms of some new data points that we can expect?
Yeah, more data will come from that trial before end of the year. In general, chemotherapy is known to have an additive effect, not a synergistic effect. We have experience in other clinical trials with chemotherapy, as well as in metastatic breast cancer with paclitaxel, and it's a good rationale to combine eftilagimod with chemotherapy because chemo will destroy some cancerous cells. They will unload the debris, the tumor-specific antigens, and the tumor-specific antigens are chopped up by the APC and presented to the T cells, and we boost that function. But overall, we expect an additive effect from chemotherapy.
And the results we saw on INSIGHT-003 so far, and about 70% overall response rate versus, around 40% you would compare it to, is very encouraging, and the data has been tracking well in terms of PFS and OS. So, we are quite optimistic for, also for the safety, and then quite optimistic for the phase III clinical trial.
Got it. And then just quickly, on the phase III clinical trial, what's the timing to first patient in? And, are there any interim looks or non-inferiority analysis, or futility analyses planned?
No, regarding non-inferiority, start end of this year, Q1 next year. Futility analysis, event-driven, as well as interim readout, potentially back end of 2025, dependent on the recruitment and the events occurring. Same applies for the interim analysis, which could be there back end of 2026.
Great. Thanks so much for attending today. Thank you, Marc, for the presentation.
Marc Voigt will take you through the novel clinical stage immuno-oncology company. I'll hand it over to you, Marc, and then we'll go into Q&A. Thanks.
Perfect. Yeah. Thank you, Elyse, and thank you, Canaccord team, for providing us with the opportunity to present here. My forward-looking statement. Immutep is an Australian dually listed biotech company. We have been pioneering the LAG-3 space since years. You're well aware that the LAG-3 is one of the leading immune checkpoints, PD-1, CTLA-4 are others, and possibly a bit more prominent, but LAG-3 is within the next wave of therapeutics to come. We are working in immuno-oncology as well as in autoimmune diseases, and we have first-in-class products, and some of them are reaching a decisive, a decisive stage in terms of late-stage development or entering into the clinical development. So we have multiple catalysts ahead.
We are well-funded, with a cash life till end of 2026, and we also work in collaboration with the big pharmaceutical industry. So when I said we are pioneering the LAG-3 space, you can see here that we address and utilize LAG-3 either as a target or as a tool in every possible way. On the one-hand side, as mentioned, in autoimmune diseases, and on the other-hand side, in immuno-oncology. Most prominent is possibly eftilagimod alpha, which you see on your left-hand side, and eftilagimod alpha is an MHC Class II agonist, so we use LAG-3 as a tool to activate the antigen-presenting cells.
Our pipeline, I believe it's a relatively rich pipeline, and in terms of eftilagimod, we will actively become a phase III company, actually in one of the most important markets in oncology, which is first-line non-small cell lung cancer. Also, we actually press released today that IMP761 at the bottom is now reaching clinical stage, so we saw the first subject being dosed yesterday. We have been receiving quite a high amount of scientific clinical recognition in terms of conferences we have been presenting at, especially in terms of first-line non-small cell lung cancer. You see here pictures from ASCO, SITC, and ESMO, and we are very pleased and honored that we had the chance to discuss the data we have been achieving so far at those high-ranking forums.
One study we have been presenting in the past, and I will not spend too much time on the old data, especially in order to leave some room for Q&A and discussion with Elyse, is TACTI-002 or KEYNOTE-798, a trial which we are running in collaboration with Merck. So combination of eftilagimod and Keytruda, 114 patients. So not a small clinical trial, but a sizable clinical trial with typical baseline characteristics in first-line non-small cell lung cancer, actually looking at the whole so-called TPS range, so including all patients where you can measure PD-L1. And the results we have been seeing compared to historic control have been outstanding, so maybe not a surprise that we had all these oral presentations.
If you look at overall response rate, progression-free survival, not on this slide, but also very strong durability of the response, and then finally, median overall survival, I believe we have been seeing remarkable efficacy, and again, in a multinational, multicenter trial in 114 patients. So not a small biotech clinical trial. Also, when you compare our results versus best standard of care, which is registered on the market, you see on the one-hand side, regarding safety, the drug-related adverse events leading to discontinuation are by and large within the range of Keytruda monotherapy. We do see, of course, FD-specific side effects like injection site reactions, but overall, very well manageable. And you see that we have been driving remarkable efficacy in terms of the most important endpoint for the patients.
This is overall survival. We also have been combining eftilagimod, Keytruda, and chemotherapy. We presented some results at ESMO last year. You see a remarkable overall response rate, and we will continue to generate further data from this clinical trial, which is called INSIGHT-003. Overall, we have been discussing our data and our plans with our collaboration partner, Merck, and we are uniquely positioned for a phase three in first-line non-small cell lung cancer. With this phase three, we will address actually the entire non-small cell lung cancer market eligible for anti-PD-1 treatment. Squamous, non-squamous cell, we have been discussing with the regulators, with the German Paul-Ehrlich-Institut, with the Spanish AEMPS, and most recently with the U.S. FDA, to discuss the setup of the trial to get their regulatory buy-in and support.
I believe we all know how important first-line non-small cell lung cancer is for Keytruda, the top-selling brand in our industry. And it's driving the revenues of Merck to a large degree. And we teamed up with Merck for a phase three collaboration. Actually, the first time since more than 2.5 years that Merck teamed up for a phase three collaboration. Last time has been, if I recall correctly, with Gilead, and now they teamed up with us for a trial which we call TACTI-004. It's a large clinical trial, about 750 patients, with the right statistical grid, so pharma standard in terms of robustness of the statistical design, which we of course also discussed with the FDA.
We are looking here at Keytruda plus chemotherapy, squamous, non-squamous, whole TPS range, plus minus eftilagimod, so it's obviously double blind, placebo controlled, with a dual primary endpoint, progression-free survival and overall survival, so two chances to have a positive readout. This trial is scheduled to start by end of this year or Q1 next year, and it's following rigorous operational preparations. I believe we will, at the end of the day, see round about 150 hospitals, certainly in well above 20 countries, and we have also implemented a futility analysis, which could kick in by end of 2025, and then the interim read could happen in 2026, with last patient in during 2026.
I do believe that this trial has a chance to recruit actually relatively well because we provide the patients with best available standard of care, and Keytruda gets 7-8 out of 10 metastatic lung cancer patients anyway, ± a modern IO drug, which is eftilagimod, and which is, for the time being, very, very safe. So no downside for the patient, but potential upside, and operationally, of course, recruitment is very important, and I believe this should go well. So we are very much working on the study preparations for this important clinical trial, which is designed to set a new standard of care in the most important market in oncology.
We have also a clinical trial in first-line head and neck cancer, and I know that there is a lot of interest in terms of head and neck cancer driven by a number of different biotech companies. We have here a trial also in collaboration with Merck called TACTI-003, which is partly randomized in terms of cohort A and partly not randomized in terms of cohort B. So cohort A, we look at CPS ≥1, and cohort B, CPS <1, Keytruda plus efti versus Keytruda, and in cohort B, Keytruda plus efti. I think we all know that the Keytruda alone is relatively ineffective there.
We have seen a continued strong safety profile, and we saw in this randomized, relatively small randomized clinical trial, a good relative difference of close to 70% in terms of CPS greater equal 20. We have a good result for eftilagimod in 1-19. However, we have also an outlier there in terms of the Keytruda group in 1-19, which is more than 33%. And, unfortunately, the trial arms are a bit imbalanced in favor of Keytruda monotherapy. However, we will present more data from this clinical trial, and I believe we all know that there are other therapies out there which are driving a very high response rate.
But, for us, it's specifically important to drive high durability of the response, turning into good overall survival, which is especially important in head and neck cancer. So this is something where we need to focus on durability of the response, overall survival, and you will learn more data from this randomized clinical trial in the remainder of this year. The Cohort B, we have been the first Australian company presenting at an ESMO Virtual Plenary Session. Outstanding, remarkable results, among the highest recorded response rate for CPS below 1. It's a less competitive space. You see here the results, around about 35% overall response rate. And of course, we may see in the future more responses coming for Cohort A or Cohort B. And also importantly, we saw responses regardless of HPV status.
Deep durable responses, as you see here, we also measured according to RECIST 1.1, the primary endpoint in evaluable patients, and iRECIST. And we see an excellent duration of treatment, which gives very high hopes in terms of durability of response, which is known for many EGFR-targeting drugs to be around 6 months only. So we see here, you see the 6 months mark, in the slide. When you look at the responses, most of the patients are continuing with treatment, so we have high hopes for this chemo-free treatment in an environment where all approved treatments for CPS below 1 contain chemotherapy to see good responses and also overall survival driven by chemotherapy in the second line, which has not been exhausted yet. So there are many, many sweet spots for cohort B.
I think I mentioned this already. If you benchmark versus historic control, it looks quite nice also in terms of complete response rate, which we have been driving to a good degree. I have to speed up a little bit, otherwise Elyse gets nervous, I trust. We have also a late-stage trial in metastatic breast cancer, phase 2, phase 3. It's ongoing. We will have some data before end of this year. We have here a single case. I don't go into detail, but it's for us, of course, very rewarding to see another complete response. We saw that in lung cancer and head and neck cancer, first line, second line. We see it in metastatic breast cancer. Here, a 35-year-old woman, and she is under eftilagimod monotherapy since 4 months, maintaining the complete confirmed response.
IMP761, just a few seconds on autoimmune diseases. First in men has been achieved successfully. We are going to see first data before end of the year. 49 healthy volunteers, and also with the chance to read into the biology of the drug, because it's a double-blind, placebo-controlled phase one. First of all, safety, but also then the biology of the drug versus placebo run at the world-class institute in Leiden, in the Netherlands, called CHDR. A lot to expect in the remainder of this year and next year. We are turning into a phase three company in the most important market. We have data to come in head and neck cancer, first line, and metastatic breast cancer. Other clinical trials are ongoing in soft tissue sarcoma, for instance, in urothelial cancer, also in collaboration with German Merck.
IMP761, autoimmune diseases, and our other collaborations and products are hopefully moving forward as well. So, I stop here, and thank you so much for the time being, and sit right next to you maybe.
Great. Thanks, Marc. So, you know, maybe just looking at the mechanism, most LAG-3 assets are anti-LAG-3. Efti operates a little bit differently. Can you, can you run through some of the key differences in the rationale for the mechanism?
Yeah, thank you. That's an important question because very often when we discuss and refer to LAG-3, it's automatically seen as a kind of special anti-LAG-3, eftilagimod, but it's not. What we do there mechanistically is that we use LAG-3 as a tool, not as a target. With anti-LAG-3, anti-PD-1, the immune checkpoint is a target focused on the T cell. Here, we use the unique biological properties of LAG-3 and fused it to human IgG1 and then we have created an MHC Class II agonist. So the major ligand of LAG-3 is MHC Class II, and via this way, we activate the antigen-presenting cells, dendritic cells, monocytes. So it's very important to keep in mind because there's no other product like this.
It's not a me-too, with all due respect, and we like it, of course, like Anti-LAG-3, which we exclusively worldwide out licensed to Novartis, or anti-PD-1, or anti-CTLA-4.
So we know that you kind of help activate then some tumors for, and some of the anti-PD-1s. But are you synergistic with those assets as well?
... the data indicates that. Of course, you need to look at the contribution of components and all the data we have, and also the unique immune activation profile indicates that indeed that there are synergistic effects. Because what we do is activate the APCs, and then via the physiological way, we see more CD4, more CD8 T cells. We also kick off the interferon gamma cascade so that the right chemokines are being released, and guiding the important immune cells to the tumor site, including NK cells.
Got it. And then with that, you know, you're kind of looking at different TPS and CPS subgroups, both in lung and in head and neck. Where do you see the highest unmet need, and where do you think you'll be able to make the most clinical impact?
Yeah, first of all, we clearly focus on first-line non-small cell lung cancer. We have the largest dataset there, including median overall survival. So a very, very robust setting, where we go after the entire market. Of course, we will also follow the different TPS strata. For head and neck cancer, clearly, I see it in CPS below one. There are a number of patients who can't tolerate chemotherapy or outright, outright refuse to take chemotherapy. Now, in this setting, all approved therapies contain chemotherapy, so what should these patients do? They have no approved treatment option.
Especially for those patients, we do see a good chance with this chemo-free treatment to drive responses, to drive a good durability, and finally, and most importantly, without that, you will not get approval or it will not hold median overall survival. We will discuss the path forward with the FDA before end of this year.
That makes sense. And, you know, we know, we know not all PD-1s are made equal. You've, you've got a partnership with Merck for Keytruda, which is great to see, but is there a rationale for being able to work with any of the other players in the space as well, or even expanding, as you mentioned earlier, into, into the CTLA-4 space?
CTLA-4 is maybe not our first priority, to answer that question straight. But indeed, we work in other collaborations. We teamed up with German Merck, with Avelumab, for instance, in urothelial cancer and earlier in a successful phase I clinical trial. We are in discussions with some additional other top pharmaceutical players in that respect. And also, it's fair to say that in first-line non-small cell lung cancer, we had the choice, but we decided to go with Keytruda. It's clearly the market leader. As mentioned, 7-8 out of 10 metastatic lung cancer patients get Keytruda, and I believe it's the best choice in terms of recruitment, in terms of commercial and global brand and day-to-day clinical care.
Great. Maybe switching gears to head and neck and the data that you've seen there. You know, why do you think you got such a good response in the CPS less than 1 patients and, you know, just trying to kind of frame the uplift in the response to the CPS greater than 1 or the CPS greater than 20 patients.
Yeah, first of all, CPS or TPS is irrelevant for eftilagimod. That's a biomarker being relevant for anti-PD-1. We look at different other biomarkers, and there is, in terms of first-line non-small cell lung cancer at SITC, in November last year in San Diego, a poster release with very insightful biomarker data. We have been driving responses above 30%, regardless of CPS score, and of course, there are debates regarding CPS, TPS, the relevance, how you measure it, validly. We do see, in terms of the disease control rate, an increase of the disease control rate from below 1 to greater equal 20, from 58% patients with clinical benefit and CPS below 1, up to 76% disease control rate in CPS greater equal 20.
So we do see an increase because a Keytruda effect eventually kicks in. CPS, TPS for eftilagimod is not really relevant.
Got it. Then looking at that, is pembrolizumab monotherapy the right comparator here, or should we be kind of comparing pembro in combination with chemo?
CPS greater than or equal to one, pembro is approved. For CPS below one, pembro has been tested unsuccessfully. As we all know, it's not very effective, delivering about 5% overall response rate in evaluable patients and about 7 months median overall survival. You saw the swimmer plot. So indeed, you would compare in CPS below one with the EXTREME scheme, so cetuximab, chemotherapy, and pembro plus chemo. There are differences between the U.S. and Europe in terms of the approvals and in terms of the landscape. But if you look at pembro chemo, if you look at the EXTREME scheme, you see response rate between 30%-40%, and median overall survival around 11 months only. And this is certainly something where you need to improve.
Maybe one comment regarding the relevance of overall response rate and the challenge in head and neck cancer. I believe most of you know the LEAP-010 trial run by Merck and Eisai, where you saw a statistically significant phase III, 511 patients, a statistically significant overall response rate, statistically significant progression-free survival benefit for the combination versus Keytruda monotherapy. But in overall survival, Keytruda mono has been 2 months better. Trial failed. So you need to look at the totality of the data, including the safety aspects.
... Great. And you did have an astronomical response in the CPS less than 1 patients materially beating available standard of care. Is there a potential regulatory pathway forward just in that specific subgroup where there's such a high unmet need?
Could very well be. Of course, you could either look at the whole patient population, CPS below one, where you then would need to benchmark and compare yourself with the treatments we have been discussing, pembro chemo, the EXTREME scheme. You can focus on the chemo-free approach, for more specific patient population. Give or take, half of the CPS below one patients, either can't tolerate it or outright refuse to take it. So this is something which we can discuss, which we will discuss with the FDA before end of the year, so I can't make any promises, as you will understand. But we, as usual, as we do it normally in a methodical and sober way, move forward based on the data and regulatory advice.
Great. And then switching gears to lung. You know, going into phase 3, you've got the collaboration with Merck. It's a really interesting trial design, both in terms of the use of chemo and the fact that you're assessing all TPS subgroups in the one trial. Can you run through some of the highlights of that trial design and give us some context as to the key factors that went into that?
Yeah. First of all, it's a result of a very fruitful dialogue with Merck and the right working groups and people. It's a very rigorous process to come to such a trial, so it's a very robust design, not the biotech way to cut corners and make compromises, but it's 750 patients. It's adequately powered, so you can assume a very, very high power to drive benefit in terms of progression-free survival and separately, as it's a dual primary, not a co-primary endpoint, overall survival. Also with chances around the alpha to regain it, actually. So I believe a very clever design.
Actually, a TPS score 0-100, we do expect TPS below 50 to be over-represented because patients with a TPS score of 90, so a high expression of PD-L1, will certainly get pembro monotherapy. But overall designed to get approval in the whole range, squamous and non-squamous cell. The right inclusion, exclusion criteria, and yeah, we are looking forward to the start.
Great. We do have some context as to how the efti pembro chemo combination works with what we've seen in INSIGHT-003. What other learnings can we take from that trial? What are the next catalysts there in terms of some new data points that we can expect?
Yeah, more data will come from that trial before end of the year. In general, chemotherapy is known to have an additive effect, not a synergistic effect. We have experience in other clinical trials with chemotherapy as well as in metastatic breast cancer with paclitaxel, and it's a good rationale to combine eftilagimod with chemotherapy because chemo will destroy some cancerous cells. They will unload the debulked tumor-specific antigens, and the tumor-specific antigens are chopped up by the APC and presented to the T cells, and we boost that function. But overall, we expect an additive effect from chemotherapy.
And the results we saw on INSIGHT-003 so far, and about 70% overall response rate versus, round about 40% you would compare it to, is very encouraging, and the data has been tracking well in terms of PFS and OS. So, we are quite optimistic, also for the safety, and then quite optimistic for the phase three clinical trial.
Got it. And then just quickly, on the phase 3 clinical trial, what's the timing to first patient in? And, are there any interim looks or non-inferiority analysis, or futility analyses planned?
No, regarding non-inferiority. Start, end of this year, Q1 next year. Futility analysis, event-driven, as well as the interim readout, potentially back end of 2025, dependent on the recruitment and the events occurring. Same applies for the interim analysis, which could be there back end of 2026.
Great. Thanks so much for attending today. Thank you, Marc, for the presentation. Good luck with the trials.
Thank you. Thank you.