Pharma Mar, S.A. (PHM) Earnings Call Transcript & Summary

Hello, this is Martin Wermke from Dresden, Germany.

Good morning, Dr. Wermke. Thank you very much for joining today. Can you hear me okay?

Yes, I can hear you okay.

Okay. Great. And Dr. Girard should be joining any moment. Girard, are you there? Okay. It sounds like both doctors are here. Are you both there?

I'm still here, I am Martin Wermke.

Yes. I think Dr. Girard is there as well. Nicolas? Okay. Let me...

Can you hear me?

Yes. Okay. There he is. Great. Sorry for the delay, everyone. Okay. So doctors, I'm going to read through compliance points, and then you can both just say you agree at the end of them, okay?

Okay.

Okay.

So first, Dr. Wermke, let's start with you. This call is -- so first, this call is being recorded and transcribed. Second, you, the expert, attest you will not disclose any confidential or material nonpublic information. And finally, you attest that if you're a physician participating in the clinical trial, you will not discuss information not yet in the public domain. If you're a member of the Scientific Advisory Board, Clinical Trial and/or Data Safety Monitoring Board, you will not disclose any information that is not publicly available or any information that will break any confidential [ agreements ] by which you are bound. Do you agree to these terms, Dr. Wermke?

Yes.

And then Dr. Girard, do you as well?

Yes, I agree. Yes.

Okay. Perfect. And then as a call leader, I too am required to keep any material nonpublic information confidential. Either I will not share material nonpublic information or information that will break any confidentiality agreements by which I am bound. Lastly, I'd like to note this call is intended for informational purposes only, not investment advice. The contents of this call, including any and all information provided regarding individual securities and/or industries do not constitute financial, legal or tax advice. With everyone on the call today, I'd just like to note this call is being sponsored by PharmaMar. PharmaMar is an oncology-focused company that develops therapies derived from the sea and have been developing lurbinectedin for a number of years. And so this call is brought to you a brief charge by them today. So doctors, I'd like to start off with each of you may be giving a little bit of background. Before we get into the number of patients you treat and where you practice, could you just both tell me if you have any association or confirm that you don't have any association with PharmaMar and the clinical trial IMforte. And then also, there's a little bit of background. I know it's on the line from one of you. I don't know if there's...

No, I did not participate in IMforte. In France, we have access to lurbinectedin part of the Compassionate Use Program but we did not have this trial.

Yes. Similar here, I've not been part of the IMforte trial. We do have access to lurbinectedin in the Compassionate Use Program. I do not hold any shares of stuff in PharmaMar. I have been on a few advisory boards for PharmaMar and other companies as well.

But neither of you were in the IMforte trial, you've just done some compassionate use things and things like that.

Yes.

Yes.

Okay. Great. So just to maybe give everyone a sense of your background. I know we have bios for you both. But just how many patients -- where are you practicing? What type of setting? And then how many patients with small cell lung cancer are you currently managing if we could do that? And then we'll talk about how to compare the 2 trials or think about the trial.

Well, I'm Nicolas, I'm working in the cancer center in France. We see 600 new patients with lung cancer, advanced lung cancer every year, about 100 small cells. We participate in clinical trials and so on.

Okay. Perfect. Dr. Wermke?

Yes, I'm also a medical oncologist. I work at the National Center for Tumor Diseases in Dresden, Germany. We do have a lung program. It's not as large as Nicolas. We see about 250 lung cancer patients newly each year. But we do have a lot of referrals for clinical trials, which are focused on last-line immunotherapies. This is also due to the fact that I'm not only in charge for the lung cancer program but also for the Phase I unit. And in that function, I have a lot of trials ongoing with many different compounds also in small cell lung cancer.

Okay. Perfect. And maybe you could continue. I want to get through how you're currently treating patients first line and what you are thinking of how things may change. But maybe just give me a high-level Dr. Wermke to start and then Nicolas, you as well on your impressions of the IMforte data, how you think the caliber of the study design and how it was conducted? And just what did you think when you saw the top line results and the recently elaborated on information at ASCO?

Well, maybe I can start. Well, I'm quite convinced by the IMforte data. The 3 months benefit in PFS and OS is something that is clinically meaningful. This is why we implemented immunotherapy in small cell. So here, we are -- another incremental benefit that we see with the addition of lurbi. What I also know from my patients is that only 80% in my center, but maybe only 60% overall in France from real-world data do access to a second-line treatment. So having an early exposure to lurbinectedin actually avoids this loss of patients from first line to second line. And my point is that given what we have seen at ASCO with tarlatamab, and we know that tarlatamab has also been tested as maintenance, I expect that the magnitude of benefit with tarlatamab as maintenance will be higher. So there is, I would say, a slight time line for lurbinectedin to be there. But we have a compassionate use program in France for second line. But actually, I would like to treat my patients tomorrow with lurbi as maintenance based on the IMforte data.

Okay. Martin, yes.

I may add from my view, I think situation is same here. We are usually treating our patients with first-line immunochemotherapy. At the moment, I think it's equally distributed between the atezolizumab and durvalumab-based regimen. I am impressed by the IMforte data. I think, as Nicolas just said, that will change our practice given on the overall survival and progression-free survival benefit observed. It will become a standard for maintenance in the first-line setting, which will probably mean depending on the wording of the label that we will switch to atezo-based immunochemotherapy for first line for the time being. Actually, I also look forward to treating the patients. And I share a bit of -- I would not call it concern but I'm curious on the data of the ongoing tarlatamab maintenance trial, which are ongoing. So we don't know what happens there. But we've had a paper at last WCLC showing that, that has promising activity. But I think at the moment, it's too early to really say if this is then going to replace lurbinectedin or if there may be room for combinations, I don't know. But certainly, the landscape in small cell lung cancer is changing quickly. So we pretty sure -- we are pretty sure that we need to adapt as quickly as the things change.

Okay. Great. That's a good start. And Girard, I think you touched on one of the questions I had in terms of the current landscape and how many first-line patients are currently able to get to maintenance and then progress to second-line treatment. Could you maybe both elaborate a little bit on that and how you see the data in IMforte potentially changing that?

That's a very good question. In IMforte, it's about 80% of the patients who get to lurbinectedin maintenance. The other ones are early progressors, and this is what we have in the clinic. IMforte is also restricted to patients without brain mets. So at the end, from 100 patients with small cell metastatic, you -- it's about half of the patients because you have something like 25%, 30% of the patients with brain mets upfront at diagnosis. And then it's 80% of those patients will go to maintenance without disease progression. So it's about half of the newly diagnosed metastatic small cell lung cancer patients.

Yes. I think if you look at the data from the IMpower133 trial, I think they even had some in the appendix of the paper, there's even the number of patients who received a subsequent therapy, and it was exactly a little more than 50%. So I think there is a great rate of attrition between treatment lines, and that is probably one of the keys to understand the benefit of lurbinectedin maintenance apart from potential immunomodulatory effects and deepening of the early responses. This is certainly something that is important for lurbinectedin as a second-line maintenance -- first-line maintenance, sorry.

Got it. Great. That's helpful. And I've been looking at some investor comments and some other conversation going on about the trials and people trying to think about IMpower133, which you just mentioned and CASPIAN. Maybe how can we compare those 2 trials? I know there's some differences in terms of induction and the maintenance components and things like that. So how -- if you're trying to look at the efficacy seen, my understanding is it's not a one-to-one basis. So could you talk about some of the nuances between those 3 trials and how we should contextualize the IMforte lurbinectedin data that we just got relative to what maybe some other people are looking at a little bit in wrong way or a little bit in incorrect way?

In the -- the first thing is it's always difficult to do these cross-trial comparisons. But here, you have to be extremely careful, especially when comparing absolute numbers, given that the survival times in the IMforte trial have been calculated from the date of randomization into lurbi or atezo or atezo maintenance and does not take into account the time that was needed for the induction treatment. So we lose in that sense about 3 months. So it's not wise to directly compare the survival times between these 2 trials. On the other hand, the lurbinectedin cohort is also a positively selected cohort because you lose all these early progressions during the first-line induction therapy. So it's really hard to definitely compare that. But you can be sure for those patients eligible, it is a step forward, and it is an increase in the survival times that it's real and clinically meaningful.

Yes. Could you maybe just elaborate on that point in terms of not including the first 3 months? And how does that -- I guess, if you were trying to make that comparison across trials impact the differences in efficacy seen if you were to try and further elaborate on that...

It's always difficult to compare one trial to another because also of the time needed to select and enroll and start the patient, especially in small cell, which is a negative disease. Obviously, I feel that the CASPIAN data have a better quality, longer follow-up as compared to atezo. I prefer to use durvalumab actually right now but it will change to atezo given the IMforte data. Durvalumab because of the 4 weeks' time interval for maintenance, which is better for the patient and the hospital. It's true also that atezo now is available as subcutaneous, which facilitate probably the delivery. And now that we have IMforte, we will switch back to atezo.

Actually, in terms of efficacy, I don't see a real difference between durva and atezo. And actually, with durva, we have the option to use cisplatin, which I hardly ever do. So I think for me, it won't be an issue to switch to atezo once we have the approval for lurbinectedin maintenance. And going back to the cross-trial comparisons, I think, I mean, IMforte is very clear in saying that if you meet the eligibility criteria, you will live longer by adding lurbinectedin to your treatment. So it's a clear positive trial. And I don't think it's wise to compare any absolute numbers between this trial, which is a maintenance trial and other trials, which started with induction therapy. So it's just an add-on to the -- to what we've seen and what we've learned with the immuno-chemotherapy trials.

Got it. Yes, that's helpful. Yes, I mentioned it just because I think some other investors trying to contextualize this have looked to those trials but I understand the difficulties comparing across trials in different formats and designs. But then I guess just to put a fine point on the IMforte data, the benefit on overall survival and progression-free survival, you view as clinically relevant and meaningful to the patient journey. Maybe talk about that in context with the safety profile seen? And just is that efficacy benefit tolerable in your opinion and something that lines up for the majority of your patients, all your patients? How do you think about this applying across the people you see? Maybe Dr. Girard first.

This is a significant benefit for sure. Obviously, we pay the price of chemotherapy like toxicities. But at the end, it's really worth because otherwise, the patient, there is a risk that the patient will never get the first line, the second line. So -- and all of these side effects are manageable at the end. It's mostly digestive. It's mostly something like hematological but that's quite easy.

Yes, I totally agree. I think the toxicity is worth risking because there is a clear survival benefit. Of course, there might be patients not eligible for such a treatment because they're too frail. But if you're able to tolerate platinum doublet chemotherapy, you're usually also able to tolerate lurbinectedin. And in my view, from the experience we have with the Compassionate Use Program, I usually think it's probably similar to the pemetrexed maintenance we have in non-small cell lung cancer. This is chemotherapy. Of course, it has side effects in terms of hematotoxicity and also some fatigue and GI problems. But it's usually a chemotherapy, which you can tolerate for prolonged cycles just because it's a pretty mild chemotherapy. That's my perception of lurbinectedin as a drug from the Compassionate Use Program, and I expect it to be the same in the IMforte regimen.

Excellent. Okay. And then just if we can look at some of the -- just to explicitly look at the side effect profile, the toxicity profile both look very tolerable to you and nothing that raises concerns from what you're able to manage in patients who are out of line. I have seen a few investors look to that but not as many as have talked about the efficacy. So just the side effects and toxicities, how do they compare to other options? And how comfortable are you with that treating all your patients?

That's true that there are some toxicities. We know them -- the toxicity quite well in second line, meaning in patients who had a kind of pause of chemotherapy in between the platinum and lurbinectedin. Here, we will have also to manage those patients who just received platinum-based chemo, maybe some remaining toxicities and we'll start directly to lurbinectedin.

Okay. Great. And then in terms of trial design, we've mentioned that it's different than IMpower133, CASPIAN. How do you view the trial design overall? Does it answer your questions? And do you think that it's a strong, well-designed trial? How do you feel about IMforte as a...

First of all, I think it is a well-designed trial. It has relevant endpoints. It has hard endpoints, and it has a clear structure with the randomization and it really answers the clinical questions. The only issue I have with the trial design is the exclusion of patients with brain mets, as Nicolas just pointed out. I mean that excludes a relevant portion of the patients. And I don't really see the rationale why they have been excluded. I wouldn't have done it that way because we don't have any reason to believe that lurbinectedin is increasing any CNS toxicity that might be expected. So why not give it to these patients as well? So if I was to design the IMforte trial another time, I would probably skip that exclusion criteria. But if you take that away, I think it's a pretty well designed and a pretty strong trial giving a clear answer to a clinical problem.

Yes, I agree. The design is pretty straightforward, easy to understand. We have PFS, we have OS. That's very clear. And we have not seen that for long in small cells. So that's good.

Okay. Great. And then before we get into how expanded access is hitting or impacting things in France and how you're thinking about everything. If it was approved today, how do you see the uptake in Germany? How do you see this working into your practice? And how aggressive would you be in rolling it out?

Yes. I think in Germany, it will be easy to use that. Usually, we get -- with the approval, we have market availability. So I can prescribe it tomorrow if it's approved today. And I think the uptake will be fast because it's a simple chemotherapy. Every oncologist knows how to do that. You do not need any special precautions, no changes in your practice setting. You can just incorporate this into your infusional department and everything will work as usual. So I don't expect there will be any difficulties. In terms of reimbursement later on, I also think that the odds are high that this will get a permanent reimbursement given that we have an adequate comparator arm that we have a relevant setting and a hard endpoint. So I don't think that there will be too many issues in uptake of this new option.

Excellent. And Girard, Expanded Access Program in France -- and yes, how does the Expanded Access Program, I think nearly 4,000 patients in it impact how it can be used and how you think it will roll out in your country, in your practice?

No, I think it will be very, very easy because everyone knows lurbinectedin at second line. We see the benefit. So many people will be willing to start and so eager to have an early access program for sure.

Okay. And then I have a few questions coming in from my colleagues but just to maybe put a finer point on it, if you could each walk me through what you see the sequencing from kind of diagnosis to the full treatment journey for a patient? Dr. Wermke, could you may be start with the, how you see diagnosis through? Now if you had this approved today and the IMforte data was within the label and available to you, how would you view it first, second, third line and maintenance and things like that?

Yes. I mean the usual -- I can easily paste it into my routine practice. So usually, we start with the diagnostic work, we will include a brain MRI scan at baseline just to know if there are preexistent brain mets. So we know if we have a patient that fits the label of the lurbinectedin maintenance. We will probably switch to carboplatin, etoposide, atezolizumab as first-line induction treatment. And after we've proven that the patient is not progressive after first cycle, then we will include them into the IMforte regimen and treat them. I don't think that lurbinectedin as a second-line drug will play a role for most of the patients then. Of course, it will play a role for those patients who started their maintenance before availability of lurbinectedin as a maintenance treatment. What happens when we will have an approval or more data for tarlatamab-based maintenance, I don't know. But at the moment, my sequence will then be maintenance with lurbinectedin until disease progression or intolerability and upon progression, then switch to tarlatamab second-line treatment.

Okay. Excellent.

Agreed. Yes, same for France, exactly the same.

Okay. Perfect. And you mentioned tarlatamab. We actually had one of my colleagues had sent in a question on that as we look at potential first-line competition between lurbi and tarla. Do you think that tarla needs to have the same level of efficacy or potentially a higher bar given the risks and precautions associated with that drug? How do you think evaluating that data or that competition will be on an efficacy basis given the profiles of the 2 therapies?

Well, actually, tarlatamab is better tolerated than lurbinectedin based on the DeLLphi-304. So I don't feel that there is that much of an issue and tarlatamab is better tolerated than chemo. And because the safety effects -- side effects are actually related to CRS, which is better, which is not really an issue. On the contrary, with chemotherapy, including lurbinectedin, we have more side effects. So from a patient standpoint, I mean that the safety of tarla is better.

I do agree. And I think the issue is also that with chemotherapy or not with tarlatamab, you have the -- most of the problems in the beginning. So once you pass cycle 2, usually, this is easygoing. I see a bit of a problem in uptake of tarlatamab for the first infusions, not at the big hospital centers but at least in Germany, we have a lot of private practice oncologists. For some of them, it will be challenging to find a way how to safely administer the first infusion of a bispecific T cell engager. I'm sure with time, there will be solutions for that, so collaboration between bigger hospitals and smaller practices. But that might, in the beginning, limit an uptake of tarlatamab if this was to be approved as a maintenance therapy as well. But I agree with Nicolas that if it's -- if you have both options, I feel that most patients and most practitioners will probably opt for tarla. But at the moment, we don't have the positive trial. So I would rather wait for this to occur before I draw a final conclusion.

Right, of course. I think the question was just if that first dose would raise the bar of efficacy but I understand. Touching on something you had mentioned in the trial design, considering patients with brain mets at baseline were excluded, would you prescribe this regimen to those patients? It seemed like you had mentioned, Dr. Wermke, that you didn't see any toxicity issues with the patients who had brain mets. So would those be patients you would still include or potentially treat with this regimen if it was allowed or if it was available?

Yes. I mean, if I would be allowed to, I would do so. But the problem is I fear that the label will be pretty strict because nowadays, the labels are usually referring you to the inclusion criteria of the studies. And if they do that in the SMPC for lurbi in the IMforte regimen, then I won't include any brain met patients just because I fear that the insurance companies will not pay for it. So that's probably an issue. And I've seen it. I mean with the neoadjuvant immunochemotherapies in non-small cell lung cancer, we are strictly following the in an exclusion criteria of the trials just to make sure that they are not charging us with the cost for the checkpoint inhibitors. And I expect the same to happen here.

So from a clinical standpoint, you wouldn't have any hesitation that would be...

Yes. No limitation from a clinical standpoint. But from a reimbursement perspective, I see a limitation, and I will probably not use it in brain mets patients if the label refers to exclusion of patients with brain mets.

I will play with the limit, I think. And [indiscernible] is so aggressive that probably some patients with brain mets, minimal symptoms, well, I will do it.

Yes. Okay. Great. Then another listener had asked about some of the eligibility from health and frailty standpoint. So at the time of diagnosis of SCL, non-small cell lung cancer or after the induction therapy, what percent of eligible patients are just too frail to receive maintenance therapy? Do you have an estimate on that at the time of -- either at the time of diagnosis or after induction therapy?

I mean if you are able to receive induction therapy and if you're not progressing on that, if you're not having any septic complications, I think 80% to 90% should also be able to receive maintenance therapy, at least from the patients I treat. We usually try to deselect those patients who are not fit enough for chemotherapy pretty early on and send them to palliative care in the beginning, unless their general status is due to the underlying disease. So I don't see that much attrition between the end of the induction treatment and the beginning of the maintenance treatment, at least not for those patients who are not progressive.

I agree because the patients are actually doing better after the first cycle, if they are not progressors. They are doing better than at the time of diagnosis because chemotherapy is highly effective and improves the general condition of the patients. So...

Okay. Great. And then the last question is just another maybe request to elaborate on the Compassionate Use Program. How quickly can the Compassionate Use Program be adapted to prescribe first line ahead of a potential European approval? Or how does that transition look? And how quickly can it go from compassionate use to first line once it is approved?

I mean once it is approved, it's available in Germany. So I can switch immediately from compassionate use to prescribing the drug. If you're asking on how fast you can expand the current compassionate use program, which is focused on pretreated patients to the maintenance setting is probably a question you need to PharmaMar instead of us. So far, I can say the Compassionate Use Program is pretty well managed. So it's pretty easy to get your patients on. And it's -- after your setup, it's pretty easy to get new patients on. And so it will be easy to start ahead of the approval of the compassionate use program if appropriately broadened in its inclusion criteria.

So my [indiscernible], there is no control about the Compassionate Use Program. So if I do -- if I say the patient has a progression, they will believe me. And actually, I will be able to start to do IMforte tomorrow.

Yes. But then you would have to lie to PharmaMar, right, Nicolas?

Yes, I know. I mean many people will do that. I'm not doing it because I'm a [indiscernible], so I have many patients who I don't want to actually play with those limits. It's not good for the company. And -- but discussing with colleagues, they are actually thinking about that. So that's the point.

Yes, that's a good point. I mean it's the same here. I mean there is no regulatory oversight for a Compassionate Use Program. So basically, no one is monitoring what you're doing. But of course, if you're working at a center, you will be strictly following the criteria of the Compassionate Use Program.

Yes.

Got it. Okay. Well, those were the questions that I have here submitted. Maybe we could each just leave -- have a moment for each of you to just give a final thought on everything or takeaway and how you think once the IMforte data looks and how it will be used? Just kind of any questions you have or any last thoughts you want to leave everyone with? Maybe, Dr. Girard first.

No. But I think this is a positive trial. It's very convincing. The point is the competitive landscape. And we know that the tarlatamab maintenance trial has completed the enrollment. So if the data are released next year, there would be at least for the full reimbursement, some competition and the authorities probably will prefer tarlatamab if they have to make a choice at the same -- with the same timing or even if there is an early access program for tarlatamab at maintenance as well. So I feel that the time frame and the time lines for lurbinectedin maintenance are quite short actually, given the competitive landscape, not because of the value of the data.

I agree. I mean, this is practice-changing data. It's pretty good to see at a single ASCO meeting having 2 practice-changing trials, IMforte being one of them. I mean we've had years and years with zero progression in the treatment landscape in small cell lung cancer. So it's certainly a move forward. I do agree that it is difficult to judge on what the future of maintenance therapy look like once all the trials that are currently ongoing have been completed. But I do think we need to wait for it because there are many different things, also pricing, side effects, applicability to the broad community that need to be taken into account. So it will be pretty interesting to see how the next years evolve in terms of study treatment. But at least for the next 1 or 2 years, I think there will -- IMforte will probably be the standard of treatment, at least in my country.

Well, doctors, I appreciate both of your time this morning walking through this. It sounds like very good news for patients with small cell lung cancer, and we will have to watch and see how approval and rollout goes for both drugs. So thank you for your time, and have a great day.

Thank you. Bye-bye.

Thank you. Bye.

Bye-bye.