Immutep Limited (ASX:IMM) CEO and Executive Director Marc Voigt discusses Phase III design for a trial in non-small cell lung cancer, positive results in head and neck cancer, and clearance for a Phase I study in autoimmune diseases.

Manny Anton: Hello. I'm Manny Anton for the Finance News Network, and today we're talking to Immutep. Immutep's ticker is "IMM" and they have a market cap of around $480m. Immutep is a clinical-stage biotechnology company at the forefront of developing novel LAG-3 immunotherapy for cancer and autoimmune diseases. Joining us today is CEO Marc Voigt. Marc, welcome back to the network.

Marc Voigt: Manny, thank you for having me.

Manny Anton: Marc, let's start with talking about your most recent announcement. The company has just announced the successful meeting with the FDA on Phase III design in non-small cell lung cancer. Can you tell us about the meeting itself and what it means for TACTI-004 Phase III trial?

Marc Voigt: Yeah, thank you. And indeed we had a very successful meeting with the FDA, and this has strategic relevance as it concludes our strategic regulatory interactions with different regulators around the globe. So, we spoke with the Spanish AEMPS, with the German Paul-Ehrlich-Institute and twice with the FDA. And you'd better do that if you run a clinical trial like TACTI-004. It's a Phase III clinical trial, so registration trial, the final clinical step, if successful before the drug can be on the market. 750 patients, and it's in the most relevant market in oncology in first-line non-small cell lung cancer, total addressable market US$24 billion. And we do that together with Keytruda, top-selling drug of the world, $25 billion annual sales. So, we teamed up with US Merck and announced that a few months ago. And now we have been putting the clinical trial design to the test in terms of regulatory interactions, and we found actually great support. So that the statistical setup for the trial is appropriate, that the medical setup for the trial is appropriate. So, before we actually start the clinical trial that we have all boxes checked for this massive opportunity.

Manny Anton: Can you give us something in terms of chronology? When can we expect to see some results and what is the expectation around timing?

Marc Voigt: Yeah, important question. Let's start the trial first. This will happen back end of this year, Q1 next year. We will be relatively aggressive in terms of the recruitment, and it should recruit very well because the patient has the option in this controlled clinical trial, so two groups of patients to have in both arms best available standard of care, that's Keytruda plus chemotherapy -- plus efti, a modern innovative immuno-oncology drug, or a placebo. So, from a recruitment perspective, it should happen very well. It should happen very fast and efficiently. We hope to have the trial fully recruited by mid of '26 and to have an interim readout by end of '26.

However, already by end of next year, we are talking here about so-called event-driven readouts. So, enough patients need to be on study and need to be adequately in shape and experience what you want to see. So, already by back end of '25, a futility analysis could happen, and if we positively jump over that hurdle, we can have all hopes for a good clinical trial. So, we will not hang out in this clinical trial without news flow, which is always important for the company, for its shareholders and potential new investors.

Manny Anton: All right, well, let's move on to the next piece of news. So, you've also had some positive results announced recently in first-line head and neck carcinoma patients. Can you tell us about those results and what implications come from them?

Marc Voigt: Yeah, indeed. We made two press releases in terms of a head and neck cancer trial called TACTI-003, in total 171 patients. In this trial, where we test eftilagimod plus Keytruda versus Keytruda in a certain group of patients -- so-called CPS greater or equal to one. I don't go into detail. And another group of patients, we test eftilagimod plus Keytruda, but without the control, simply as Keytruda is inefficient there -- it would be ethically not doable to have it controlled with an inefficient drug. So, as powerful as Keytruda is, it does not work in that specific group of patients.

Now we have been announcing the two different parts -- on the one hand side, the randomised part, and we saw a clinically meaningful difference for the so-called CPS greater or equal to 20 groups. Patients have been sorted into different CPS levels. These levels define if Keytruda is typically working very well, not so much, or not at all. And there we saw a relative close to 70 per cent difference in terms of overall response rate.

In the group 1 to 19, where Keytruda typically works suboptimally, there was practically no real difference between the two groups. Keytruda outperformed its historic standard by more than 120 per cent. So, it's a control group unheard of. And there were some imbalances in the trial arm, which is, quite frankly speaking, normal in smaller clinical trials. It's not a Phase III, unlike TACTI-004. It's a Phase IIb. And there we saw results which are more inconclusive for that group of patients.

In the CPS below patients, so where Keytruda does not work, we had actually, as a first Australian company, a so-called ESMO plenary session, which means with the European Cancer Organization, let me phrase it this way, there was a 70-minute discussion, only eftilagimod and CPS negative patients, with esteemed key opinion leaders from around the globe on 11 July, and 12 July a second session more on the Asian side of things with another group of esteemed opinion leaders.

So, this data has been clearly very positive. We saw actually a sevenfold increase versus normal expectations you would have for those patients if they would take Keytruda. And it's important to note that we have not been releasing final results for the Cohort A, the first group of patients I discussed. We will see more data in the remainder of this year, potentially at a major medical conference. And it's important that we present more detail because the share price has been some waves in reaction to that. So, there will be more explanation, more details, but also, with that, the trial is not finished actually.

What is the most critical point for patients? The most critical point for patients is overall survival, and shrinkage of the tumour overall response rate. What we reported is of course an important early point in time, but it's not guaranteed that a good overall response rate automatically means you have a good overall survival. So, we do need to wait a little bit longer to see how our overall survival tracks. In the past, we saw very good overall survival, and if you look carefully at the data which has been disclosed, you can have some very good hopes, especially as more data has been disclosed so far for the Cohort B. At the ESMO Plenary, you'll see how patients have been doing over time.

So what I'm trying to say with a lot of words is there is more to come and more important things to come for this clinical trial.

We will also discuss with the FDA prior to end of the year in order to detect the best ways to move forward. There are certain sweet spots for this very aggressive disease, which is also very heterogeneous. We will have robust discussions. We are also very glad that our collaboration partner, Merck, is supporting us, and you will see us come up with more data and more defined ways how to move forward.

Manny Anton: Okay, understood. What role is Merck currently playing in this?

Marc Voigt: Merck is collaborating with us. They are providing supply in terms of Keytruda. And of course we have discussions with our collaboration partner, but those are not for the public domain. And we also collaborate with them in non-small cell-lung cancer. And we entered into this collaboration for TACTI-004 Phase III registration trial prior to the results coming out. And this has been the first time since more than two-and-a-half years that Merck is entering into a Phase III collaboration.

Manny Anton: You've recently also announced that the company has received regulatory clearance for the Phase I study of the LAG-3 agonist antibody designed to treat autoimmune diseases. Can you tell us about that study and what the implications are and what you hope to achieve?

Marc Voigt: Yeah, definitely, especially -- I'm glad about this question -- especially as it's often overlooked. We are not a one-product company, not a single-study company, but we have actually another asset which is coming out of so-called preclinical development and now entering a first-in-human study. This program is designed to address autoimmune diseases, so to bring the immune system back into the right balance. Oncology would like to have an active immune system, your body actively fighting cancer. Autoimmune diseases, your own immune system has been running wild, so we bring it back under control. That's the aim of this program -- by the way, potentially addressing more than 90 per cent of autoimmune diseases as we go to the root cause of the disease, which are the chronically LAG-3 activated T-cells. Not a symptomatic approach, where you try to get rid of the symptoms in case of psoriasis, in terms of the plaques for instance, but addressing the root cause of the disease.

The Phase I study now is a trial which will take place in Leiden in the Netherlands. We have been receiving regulatory and ethical clearance to start it. So you can expect first patient in soon. And this is designed first of all to see some safety -- unlike in oncology, not in patients, but in healthy volunteers. But we will also detect biological activity in that trial. So, there will be a deliberate irritation of the skin once the dose is defined. And then we will treat either with placebo or with a drug this local inflammation, which allows them to read into the biological activity of IMP761 in a blinded fashion. So, a Phase I trial with many different aspects. And the good thing about autoimmune diseases is you'll see results relatively early on. So, we will have first results in the remainder of this year and then more results in first half of next year.

Manny Anton: To finish up, let me just ask you, the remainder of 2024, what can we expect in terms of news flow?

Marc Voigt: Yeah. Most important things are of course on the one hand side progress for TACTI-004 to get that Phase III study underway. Then TACTI-003, head and neck cancer, more data. Regulatory discussions, define the path forward. Metastatic breast cancer, another clinical trial, should deliver the right dose for the whole program. It also gives some insights how the drug works together with chemotherapy in metastatic breast cancer. We have other smaller clinical trials in soft tissue sarcoma, urothelial cancer, and this is eftilagimod alone. And then you have the study start for IMP761 in autoimmune diseases and first data there. Plus potential updates from the other programs, partly partnered. And other potential normal, let's say, milestones and catalysts as well.

Manny Anton: Thank you for your time today. As always, that was a great update, and we hope to see you back soon to hear about even more progress.

Marc Voigt: Manny, thank you so much. It's been a pleasure.

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