Good morning. My name's Dave Stanton, and I'm part of the Jefferies Australia Healthcare Research Team. Welcome to Day 2 of the Jefferies U.S. Healthcare Conference. Delighted to be hosting Immutep, Marc Voigt today. We've got a presentation, and if there's time at the end, I'll always open some questions. Marc, thank you very much for your time today, and over to you.
Dave, thank you so much, and thank you all for coming. Great pleasure to be here. Thank you, Jefferies, for making this possible. My forward-looking statement, and let's go right and straight to it. Immutep is a company which is focused, on the one hand side, on immuno-oncology, but we have also programs in autoimmune diseases. Two large disease areas which we are covering, and we are working with the patient's immune system. In oncology, of course, as we all know, you would like to have an active immune system. In autoimmune diseases, you would like to down-modulate it, bring it under control. I believe, given that we have been pioneering the LAG-3 space since years, that we have the right tools to actually achieve that. Talking for a second about LAG-3, it's very important to note that you have three validated immune checkpoints.
We all know PD-1, we know CTLA-4, and we, of course, know also LAG-3. These are the ones which are validated, where you have FDA EMA-based approved product based upon them. We work in different partnerships. We made recently a big step forward as we started our first phase III clinical trial, and actually one of the largest indications in oncology, first-line non-small cell lung cancer. That's always a big moment for a biotech company, but here we are in the fortunate situation that we don't do this step alone, but that we do it together with Merck here from the United States in the combination of KEYTRUDA, chemotherapy, and eftilagimod in a very exciting phase III clinical trial. I will talk more about it in a second.
We have also other collaborations, of course, and we have a strong balance sheet so that we are fully focused on execution of our different programs. Now, look at our pipeline, different assets. We have five programs in total. During the course of the presentation, I have, of course, to discuss eftilagimod and a bit in terms of IMP761 as well, where we expect also upcoming data in the remainder of this year. Eftilagimod, which I will call FD here and there, eftilagimod is a tongue breaker maybe, so FD. That is important to understand discussing LAG-3. FD is a unique asset. It is not anti-LAG-3. Typically, when you discuss LAG-3, you more or less automatically refer to the dozen different programs covering anti-LAG-3. That is not what we do here.
We have been taking LAG-3, the four extracellular domains, lysed off the T- cell, created a new fusion protein, and we activate via the major ligand MHC class II the antigen-presenting cells, the dendritic cells. If you like, we work on the other side of the LAG-3 MHC class II interaction. Extremely important point. Never mistake eftilagimod for an anti-LAG-3 program. It's a unique asset. No one else is doing that. We have, with our Chief Scientific Officer, Frédéric Triebel, the worldwide leading scientist for LAG-3 on board, he actually discovered LAG-3, hence we have pioneering the space since years. We have a lot of clinical experience. We have been generating data in different indications. We have a very, very good safety profile across a few hundred patients. I will talk more about non-small cell lung cancer. I will talk a bit about head and neck cancer.
We don't have enough time today to discuss soft tissue sarcoma, breast cancer, and so on and so forth. As we treat the patient's immune system, not a specific cancer indication, eftilagimod can work in a variety of different settings, in a variety of different indications. Importantly, we have an easy route of administration. It's given subcutaneously, and some of you may follow the top-selling drug in the industry called KEYTRUDA, which can now also be applied subcutaneously, which offers maybe some nice regulatory sweet spots. It's also an agonist. We give low dose, 30 milligram per patient. It's an agonist program, an exciting MHC class II agonist. Now, let's talk a little bit about non-small cell lung cancer. I believe most of you know that's the primary cause of cancer death. It's one of the largest indications with, unfortunately, still high unmet medical need.
Most of the patients live, unfortunately, less than two years. To make a difference here for the majority of patients is very, very important. Of course, it's also commercially very attractive. The market is believed to be about $48 billion by 2031. Now, we generated data in the past. Everyone can look that up in a trial called TACTI-002 or KEYNOT- 798. It's a trial which we have been doing in collaboration with Merck. Typical patient population combination of KEYTRUDA and eftilagimod in 114 patients, so a sizable phase II clinical trial with a typical cancer patient population. Actually, the chances were stacked a bit against us as we had a lower so-called TPS high patient population. A patient population where KEYTRUDA tends to work very well as a monotherapy, and this was underrepresented here.
We had actually fantastic results across the Board of all the different efficacy parameters you can think of: response rate translating into progression-free survival, durability of response, and all of the efficacy parameters finally translating into very, very encouraging median overall survival. We had different oral presentations at ASCO, at SITC, at ESMO. The data has been very, very well received. If you compare that historically versus KEYTRUDA, you see that we make a difference everywhere. This is very important. As we all know, anti-CTLA-4, anti-CTLA-4, anti-PD-1 combination, which was focused on the TPS high patients, so where KEYTRUDA alone works relatively well anyway, we work across the board of the whole TPS spectrum, irrespective if KEYTRUDA is supposed to work very well, TPS high, not so much, suboptimally, one to 49, or not at all below one. We have been seeing improvements across the Board.
That is maybe also easy to understand because we activate the immune system differently. We create more CD8 T cells, more CD4 cells, more natural killer cells, and we kick off the interferon gamma cascade. The immune system is activated very broadly, and it works together very nicely with a program like KEYTRUDA focused on the T- cell. Also, if you compare this to best available standard of care, if I would have lung cancer tomorrow, I would possibly get one of those options here that you see in gray. Best available standard of care, if you compare the data which we generated in TACTI-002, it is very compelling, very strong median overall survival. Importantly, as it is also about quality of life for the patients, of course, regulators always look at the risk-benefit ratio. We do not see better efficacy with a compromise on safety.
If you look at the drug-related adverse events, leading to discontinuation of the treatment, we are actually having the same profile like KEYTRUDA monotherapy. We do see eftilagimod-specific side effects. These are, for instance, injection site reactions, as you have a lot of dendritic cells, antigen-presenting cells in the dermis. Correlated to the mode of action, we see some side effects. They are transient. They are very well manageable, not severe. We recently updated also data from our INSIGHT-003 clinical trial, also in first-line non-small cell lung cancer. You saw one clinical trial, TACTI-002, 114 patients. This is a completely separate clinical trial looking at KEYTRUDA, eftilagimod, and doublet chemotherapy, non-squamous cell carcinoma. You see here the response rate where, again, similar pattern, we make a difference across the Board.
Safety continues to be good, and we have here very strong results, actually in a clinical trial with 50 patients where the vast majority of the patients, more than 90%, have TPS below 50. Again, not enriched for patients who would do well where you would expect a response at a high response rate, but enriched for patients where you would not expect to see a high response rate. Very strong results with or without chemotherapy. Also, in terms of overall survival again and progression-free survival again, we looked at the patients with enough follow-up time, 22 months, and we saw overall survival again north of 30 months and progression-free survival north of 12 months. Very strong results, two separate clinical trials together round about 165 patients in first-line non-small cell lung cancer from two separate phase II studies.
This is a very robust basis for our phase III clinical trial. We have been teaming up with Merck mid of last year. It has actually been the first time for Merck since January 2022 where they teamed up with Gilead for a phase III collaboration. We take this as a big vote of confidence that we as a biotech company, and we know them for years, of course, receive the support, and the support is multiple-fold. First of all, we designed the clinical trial together. It's very important. You look here not at the biotech phase III clinical trial with all due respect, but you look here at the clinical trial according to highest pharma standards. About 750 patients in more than 25 different nations as we speak. We have more than 19 countries with regulatory go.
We are well underway in terms of ramping up sites, ramping up countries. The guidance we have been putting out more than nine months ago in terms of first patient in has been met. In March, we saw the first patient dosed actually in Australia, and we are getting KEYTRUDA for free, commercial value round about $100 million. We have been jointly designing the clinical trial. We have been discussing the protocol with the FDA already last year. We discussed the concept with the German Paul-Ehrlich Institut as well as with the Spanish AEMPS. We have also a very robust regulatory setting for this clinical trial, which is looking at the one-to-one randomized setting, dual primary endpoint, overall survival, progression-free survival. Multiple chances to be successful, very important. It is stratified for the TPS score, for the histology, squamous, non-squamous, for the region, and for ECOG.
It's an exciting clinical trial, which is with KEYTRUDA in the active arm, the broadest clinical trial. This clinical trial can set an improved, or if you like, new standard of care in the entire first-line non-small cell lung cancer patient population eligible to anti-PD-1 treatment. This is a very, very important statement because the other clinical trials with KEYTRUDA in the active arm look at certain subsegments. Our data, which you saw, allows us to broadly position the clinical trial and to win overall and to help also, of course, KEYTRUDA to prolong exclusivity. A broad clinical trial. This is not only strategically important, it's also important from an operational point of view because if a clinical trial should recruit very well, then this one, the patients and the PI do not need to make a compromise.
They get best available standard of care in both arms, and they do not need to discriminate according to the TPS score. Irrespective if it's below one or if it's high, patients can be included. Squamous, non-squamous, that's all fine. If you look then at the next slide, it works actually, that's good. At the commercial potential of eftilagimod in non-small cell lung cancer, obviously it's a blockbuster opportunity. We do not need to create a new market. We do not need to establish an entirely new regime. The PI, the treating physician, just needs to push the syringe one more time. Easy route of administration, sub-Q, and KEYTRUDA is the strongest brand across the whole pharmaceutical industry and especially in lung cancer. Seven to eight out of 10 patients are getting KEYTRUDA. We would walk if this trial is successful into the clinical trial.
I should update you on a few timelines. We have been treating the first patients. We expect futility analysis back end of 2025, first quarter 2026. We do believe, always subject of course to actual recruitment, we do believe that we could see last patient in by third quarter 2026. The first interim on which we could file could kick in back end 2026 to mid- 2027. I believe also very exciting and interesting timelines. Of course, one of the very logical thoughts looking at the loss of exclusivity, which starts in the United States by 2028 for some of the big brands, including KEYTRUDA, in Europe by 2031 actually. We have a patent for the combination, and we could help of course to prolong the exclusivity by driving a better benefit for the patients.
If we are recruiting well, the timing may well coincide with this so-called patent cliff. Another area which has been exciting for the industry, the biotech industry, I trust you all know [MRIs] , and so on and so forth, a lot of noise and data in head and neck cancer. This is something we look at as well, but we are focusing on CPS below 1 where almost no one else is clinically active. We have here from a competitive point of view as well as from a data point of view identified, I believe, a very nice sweet spot.
A few weeks ago, we have been press releasing a data update in terms of overall survival where we again see the same pattern actually compared to historic control, a seven-fold increase of the overall response rate, complete responses round about 12%-16% depending if you look at RECIST 1.1 or iRECIST. Strong progression-free survival, durability of response, 12 months landmark analysis, and now mature overall survival north of 17 months where you would expect with KEYTRUDA out of the KEYNOTE-48 clinical trial, round about seven to eight months. With best available standard of care, that's KEYTRUDA plus chemotherapy or cetuximab plus chemo, you would expect round about 11 months. I believe very strong results. These results are coming into a situation where you have the highest unmet medical need in CPS below one in head and neck cancer.
Why is that the case? Because all approved therapies contain chemotherapy there. CPS greater equal one, you have Pembro approved also as monotherapy. That's not the case here. Pembro mono is not approved. You always need to go to Pembro chemo in the United States predominantly, in Europe more cetuximab plus chemotherapy. The patients have no choice to avoid chemotherapy. Chemo here is very aggressive in head and neck cancer. It's an aggressive disease, chemo screen relatively aggressive. Many patients outright refuse to take it. We press release that we have been submitting a meeting request with the FDA. I'm very happy that we can meet with the FDA soon. You heard yesterday the FDA commissioner talking about their capabilities. From our end, we are able to confirm that we have a long-standing relationship with the FDA. We don't notice any changes.
We go into the meeting in the next few months, and then we are going to discuss the path forward to approval in first-line head and neck cancer CPS below one. Of course, we need to see what exercises would be required. We have fast track designation, and it would be great if we would get the chance to make a difference for the patients which are in dire need of a chemo free regimen. It's a smaller group of patients. It's about 20%. Again, on the other hand side, from a competitive point of view, it seems that we are more or less the only ones having a good way and good approach in that respect. Now, let's switch gears. Let's talk for a minute about IMP761 and autoimmune diseases. Given the strong dominance of eftilagimod in our story, this is very often overlooked.
We do have also two programs in autoimmune diseases. We actually created with IMP761 the world's first agonist to LAG-3 position autoimmune diseases. It took actually about a decade to get to that program. Why is that actually relevant? It's relevant because it's addressing the root cause of up to 80%, 90% of autoimmune diseases. Our own T- cells being exposed, constantly exposed to the self peptide, rogue T- cells, they express LAG-3 as an exhaustion marker. We can use LAG-3 here conceptually as a marker to specifically identify those rogue T- cells and switch them off. We do not destroy the immune system. We do not wipe it out like some other approaches. We specifically target the chronically LAG-3 activated T- cells. We switch them off, but otherwise a naive T- cell repertoire, everything B cells, everything being left intact.
Of course, you see here some blue sky numbers. We could address a variety of different indications as it is an upstream approach. It's not a symptomatic approach where you try to get rid of some of the symptoms. It's a potentially curative approach, and it could work in a variety of different indications. We will focus first of all on TH1 diseases. Anyone who would like to read more can look up our publication in Journal of Immunology and also have a look at the competitors. J&J is with a PD-1 agonist active in AnaptysBio, Eli Lilly and others are looking into immune checkpoint agonism in autoimmune diseases. It is an upcoming important fashion wave.
I should not forget to mention that LAG-3 might be particularly interesting here in this setting because PD-1 agonists, if you look at the T- cells expressing PD-1, they are predominantly in the bloodstream. LAG-3 is more a tissue marker accumulating at the disease site. About 40% of T- cells at the disease site express LAG-3. These are the bad guys, and we are after those bad guys. They are, based on the biology of LAG-3, some very, very nice sweet spots for our approach. We are actually now in clinical development. It is not a preclinical story, some fancy articles as important as it is, of course, but we are now in clinical development. We started together with the CHDR in the Netherlands and Leiden a double-blind placebo-controlled phase I clinical trial. Typically, phase I, boring, safety oriented, of course.
We also look at safety, but this trial allows already to have a read-through into the biology and into the immunosuppressive properties of IMP761. So, what do we do? The CHDR is recruiting healthy volunteers, no patients, healthy volunteers. We are here in autoimmune diseases and is deliberately irritating the skin with a local inflammation. And then you give either placebo or IMP761, and via blisters you extract also immune cells so that you can measure the immunosuppressive effect versus placebo in a double-blind fashion of IMP761 alongside the dose escalation. We will update the market in the second half of this year how it's going. Last time we have been doing that in December 2024. Safety so far, so good. Let's see what else we have to say. We are highly excited about IMP761 as it is a potential game changer the way you treat autoimmune diseases.
Now coming to the outlook, we had a very, very busy first half of the year. Of course, operationally everything is dominated by our phase III clinical trial ramping up more than 150 sites in more than 25 countries. I'm just coming from ASCO. We had very encouraging PI meetings, very interesting industry meetings. It's a lot of work. We are focused on that. We will, of course, deliver also data in the second half of the year to pick maybe also one program, one trial out which I haven't discussed at all for the time being in soft tissue sarcoma. We press released a few weeks ago that this phase II clinical trial in this orphan indication has been meeting its primary endpoint. There will be detailed data in the second half of this year at the major medical conference.
Beyond non-small cell lung cancer, clearly a focus head and neck cancer FDA discussion coming soon. There is more in, I believe, also financially intelligently organized clinical trials because soft tissue sarcoma is paid for by the Polish government predominantly, and it's run by an investigator. It's an interesting setting also in urothelial carcinoma and metastatic breast cancer. Data from IMP761 and, of course, other updates and news on different initiatives we are working on. Let's see what that means. This from a financial position of strength. We have more than AUD 146 million, round about $95 million cash on bank according to our last quarterly so that we are now fully focused on the execution of what we are doing. That's it. Thank you so much.
Thanks, Marc. We've got a bit of time for a question. If anybody's interested in asking a question, there's a microphone at the back of the room. I might start. As you sort of mentioned, Marc, we've seen a lot of, I guess, news about bispecifics and in combination with pembro, particularly in non-small cell lung and in head and neck. Firstly, where do you see that going in terms of as an option for patients going forward? How is FD different in terms of its approach compared to those bispecifics?
Yeah, very good questions. Indeed, bispecifics have been a kind of fashion wave, if you allow me to make that comment. We saw and see a lot of excitement around bispecific deals being done. Clinical reality needs to show if this is justified in the long run for the patients.
Of course, I do hope that this is going to be the case. We are in need of different options. The latest updates from the bispecifics have been showing that there might not be a one-to-one translation from Chinese clinical trials into global clinical trials. Also with a hazard ratio which has been going down and it has been noted by the market. Clinical game is on. A big indication that especially in oncology, you always face competition. I like that because it's for the benefit of the patient. If we execute, looking at Immutep, if we execute our clinical trial and we see sufficiently positive results, we will be registered. Of course, we will have a share of the market irrespective if bispecifics are approved or not, if ADCs are approved or not.
Also, ADC is another fashion wave which turns out to be here and there, maybe a bit more toxic than originally expected. Clinical reality is important. If we are successful, we will have a commercial space, a very attractive commercial space. In one of the slides, you saw that there are different approved standards of care for non-small cell lung cancer as in many other indications. We would be one of those. In the largest market, this will always be attractive. From a mode of action point of view, entirely different game.
I guess, you know, as I analyze those biospecifics across the Board, I would note that they're mostly looking at what we, in inverted commas, hot cancers, whereas FD has very good results, early days of course, but very good results in cold cancers.
Would it be fair to sort of think that even if biospecifics do work in hot cancers, that there's nothing really else out there that's going to address the cold cancers, the TPSs and CPSs of less than one?
Indeed, thank you for that comment. Indeed, it's a specific sweet spot that in non-small cell lung cancer, we work in TPS below 50 predominantly and especially also in TPS below one. Importantly, and this is often overlooked as in oncology, you want to drive efficacy, but also the safety aspect is extremely important. We do not see an increased number of drug-related treatment discontinuations so that you have good quality of life. Of course, in phase III, the quality of life assessment is mandatory.
This has been a specific sweet spot for the regulators and later on also for reimbursement, thinking about co-medications, thinking about the pharmacoeconomical debate. Eftilagimod, typically no co-medication needed, straightforward, very safe, very well manageable, easy route of administration. It is ideal also for the setting in terms of the pharmacoeconomical debate of tomorrow. Very important point.
Excellent. Any questions from anyone? Just very quickly then, and then because we're getting the wind up, Marc. Cash burn per month and near- term and over the medium- term, can you sort of give us a bit of color on how you look at that?
Yeah, we have a very strong balance sheet, cash live till end of 2026. We have a number of very good industry discussions. We are focused on the execution. We have been seeing very good support from our great register we are having.
In Australia, predominantly, we are dually listed. IMMP is a ticker in the U.S., IMM in Australia. We are confident moving forward in multiple respects, but very much focused on the execution of our program, including business development.
Understood. We are going to have to end it there. We could talk all day, Marc, but we better not. We are going to wind it up. Thank you very much for your time. Thank you, everyone.
Thank you.