Transgene SA (TNG) Earnings Call Transcript & Summary

Hello, and welcome to the Transgene Reports Results from Clinical Study with TG4001. My name is Monique, and I'll be your coordinator for today's event. Please note, this call is being recorded. [Operator Instructions] I will now hand you over to your host, Lucie Larguier, to begin today's conference. Thank you.

Thank you, Monique, and hello, everyone. So I'm here today on the call with Philippe Archinard, our Chairman and CEO; as well as Maud Bradley, our Chief Medical Officer. And we're very happy to be discussing with you the promising results that we obtained with TG4001 in combination with avelumab in our exploratory Phase Ib/II trial. Before I turn over the call to Philippe, I'd like to remind everyone that today's discussion contains forward-looking statements, which are subject to numerous risks and uncertainties. So we would also like to remind you that this call is being recorded and that it will be available on our website. The webcast can be also accessed via the home page of our website and our Investor page. If you are listening to the webcast via the Internet, you will not be able to ask questions. So if you wish to ask questions, please make sure that you join us via the conference call numbers that are available in the press release that we distributed earlier today. With this short introduction, I now turn the call over to Philippe Archinard.

Thanks, Lucie. Hello, everyone, and thanks for joining us. As you can imagine, I'm really happy to be talking to you today, finally. We are very proud of the data we have generated with TG4001, which we believe establish a very encouraging clinical proof-of-concept for our virus-based approaches in combination with immune checkpoint inhibitor and of course, for the product itself. Before covering the trial and providing more color on the data, I would like to briefly provide you some background on the product itself. So TG4001 is a therapeutic vaccine based on our MVA platform vectorizing E6 and E7, which are known oncogenes, from HPV, human papillomavirus type 16 and co-expressing human IL-2. It's been designed to [ educate ] the immune system against cancer cells carrying these viral antigens. Here, we are targeting nonself antigens that are known to elicit a stronger immune response than tumor-associated antigens, which are by definition closer to the cells. For this trial, as you know, we team up with Merck Serono. In addition to providing avelumab for the trial, they also obviously validated the original design of this trial. I remind you also that there is no specific treatment option for patients with HPV-positive cancers and that the current standard of care do not address specifically the different etiology of these cancers. With our Phase Ib trial -- Phase Ib/II trial, sorry, evaluating TG4001 together with avelumab, we wanted to assess both the safety and efficacy of the combination in a very diverse group of patients with very advanced HPV-positive cancers. We are happy to report that the study has delivered a positive and promising outcome. Importantly, we have seen a clear clinical activity in the overall study population. This covers 34 evaluable patients with, again, a very diverse range of HPV-positive cancers, including oropharyngeal, anal, cervical and others. We have not released specifics from the study as the data are still maturing. However, it already seems clear that the combination regimen compares favorably with published data from HPV16 targeting -- targeted competitive approaches and very favorably with current standards of care. I will now hand over to Maud who will give you more flavor on how we can -- we have interpreted these positive findings.

Thank you, Philippe. So our Phase Ib/II study included young patients, median age of 56 years, with oropharyngeal or anogenital HPV-positive cancers that progress or relapse after 1 to 3 line of prior chemotherapy regimen given for their metastatic disease. This means that it's clearly a group of patients with very hard and advanced -- hard-to-treat and advanced HPV16-positive cancer. In the overall population of 34 evaluable patients, TG4001 in combination with avelumab achieved a greater response rate than the 10% to 15% response rate seen with approved ICI used as single agent in that setting. And of note, this -- our trial included a number of patients with very aggressive disease. Importantly, and this is consistent with the data which were presented at ESMO 2019, the responses seen in this study were durable. We have nice example of patients who have been able to return to normal life after receiving 1 to 2 years of treatment and still under treatment. We have also been able to identify a clinical criterion, which should allow us to select patients who show particularly promising clinical activity. Of course, we have discussed with KOLs this criterion and this criterion will be used clearly in all our future clinical trials. Importantly, after applying this criterion to our trial, we see that at 12 weeks more than 50% of the patients have not progressed. This compares very favorably to the median progression-free survival of 8 weeks that is reported with standard therapeutic option, including, of course, approved ICI. So the results are obviously impressive. As we said, the study data are maturing. Patients are still in follow-up. As an example, we got a couple of weeks ago a new confirmed response. We are also completing translational analysis, including assessment of specific response using [indiscernible][ processes ], phenotyping of lymphocyte in the tumor and in the blood, PD-L1 expression in the tumor. So the data will complement our clinical data and will provide compelling body of evidence, and we are working on that, of course. And therefore, this is not appropriate to give more detail, but we will present them by the -- before the end of the year in the context of a scientific conference. Based on the data we are compiling to date, we have stopped the trial -- our trial in this current design, and we intend to continue the clinical development of TG4001 in a larger, controlled confirmatory study. Of course, this is in the discussion with the participating investigators, who are very keen to continue treating their patients, who are young patients with aggressive and devastating cancer, and to allow them to benefit from this novel TG4001 base combination regimen. This is reflected by the quote from the principal investigator of the study, Professor Le Tourneau from Institute Curie. And it represents the opinion of the treating physicians who are really very keen to go on treating their patients. So obviously, the medical need is high while pursuing the clinical development of the combination therapy, and we are currently actively working on it and we'll keep you informed in due time.

Thanks, Maud. So based on these promising findings, we believe that these data establish a very encouraging, again, proof-of-concept for the combination of our vaccine with immune checkpoint inhibitors in this patient population with HPV-positive cancers. As a result, we intend, as Maud said, to continue the clinical development of TG4001 in a larger, controlled confirmatory study. We are finalizing the study protocol with KOLs, and we look forward to presenting you the complete and mature data later this year and give you some more specifics on the upcoming study as well. With that, we will now take your questions.

[Operator Instructions] Our first question comes from the line of Jean-Jacques Le Fur from Bryan Garnier.

Congrats for these positive results. Good news for Transgene and for all of us. I have 3 questions, if I may. The first one is I probably understand that you don't want to describe this subpopulation for which TG works best. But could we have an idea or rough idea of the proportion of HPV-positive patients it represents? My second question is regarding the confirmatory trial. Is it stupid to think that you may be directly in second line like monotherapy checkpoint inhibitor, I think particularly about pembrolizumab, instead of having a third line? And my last question, sorry if I didn't understand you, Maud, or did not -- if I missed. The -- you mentioned the response rate. Is it the overall response rate at more than 10% to 15%? The reason why I'm asking the question is that if we look at the KEYNOTE-012 or CheckMate 141, the overall response rates were -- I think for -- if I remember well, for KEYNOTE-012 it was much higher and for CheckMate it was more or less in line, but just to be sure I well understood.

Thank you, Jean-Jacques. So regarding your first question, I want to make clear that we are not dealing with a subpopulation actually. It's just a refinement of selection criteria which will help us to better identify the patients who are more prone to benefit from the treatment. So it's just a refinement. And so in terms of proportion of patients, it represents a majority, if not all patients, excluding the -- some patients who are in any case not responding to any type of treatment, including chemotherapy, ICI, anything. Second question, our confirmatory trial actually will target not only second line but also first line. Third line, we have seen response in third line, meaning that actually our clinical benefit is independent from the lines of treatment, which is quite nice, I think. So we are not sticking to the most advanced stage in third or fourth line. And regarding the objective response rate, so probably you advise better than I do all the response rates in the Phase III trial of ICI. So -- but in second line for sure. So the response rate is close to 15% from the top of my head. In first line, it's true that avelumab single agent reported a higher response rate, which is, from the top of my head, around 19%, but -- which was obviously lower than the response rate of the extreme chemotherapy regimen. So I hope I answer your question, Jean-Jacques.

Yes, yes.

What's difficult -- maybe if I can just add -- what's difficult in this comparison, if you -- I mean nobody really did an HPV-only -- HPV-positive-only trial. We know that there are some substantial difference if you do oropharyngeal only or if you add anogenital cancer. So you have to compare with the pool of data and really look at the inclusion criterias very carefully to make the comparison. So when we try to look really apple-to-apple, your comparator or line is closer to 10% than anything else.

[Operator Instructions] Our next question comes from the line of [ Sebastiaan van der Schoot ] from Kempen.

I was wondering whether you could provide some time lines regarding when we will learn more about the specific details about the specific response rates of the -- in the different indications.

Well, actually, the plan is to send an abstract so that the full -- that asset will be presented in the Congress by the end of the year. So there is a number of Congress which are positioned here. Unfortunately, it's likely to be virtual meetings. But anyway, so we will have the presentation included in one of those Congress.

Okay. And regarding the clinical responders in the first update of the Phase Ib last year, are those still responding to therapy? Or have those progressed?

No. The good news is the 3 patients -- the one I mentioned, that some patients have gone back to normal life and still under treatment and enjoying life. And one of them -- we amended actually the protocol for her. She's perfectly well and after more than 2 years of treatment. For another one, it was more than 1 year before the patient relapsed, and the third one as well. So -- but we are very happy. Patients treated in third line, having the huge tumor burden and responding still after 2 years is something which is significant for us.

Our next question comes from the line of Bertrand Delsuc from Biotellytics.

Just to make sure I got it well about your criterion, this is not a biomarker. This is what you say.

No. You are perfectly right. It's not a biomarker. It's just the clinical criterion which is easy to use, which is a good news because, as you know, biomarker is nice to have, but sometimes it's difficult to apply because it requires sampling, it requires validation, it requires a lot of stuff. So here, we are speaking about a very simple clinical criteria that every physician can use, and it will make the trial much easier to set up.

Okay. Okay. The second question is about the PD-L1 status. I'm not sure I have seen on ClinicalTrials.gov or in previous slides, did you include the patients only PD-L1 positive? Or were there also patients PD-L1 negative?

Also patients with PD-L1 negative tumors. We characterized the tumor, but it was not a selection criteria to have PD-L1 positivity. So it was regardless of PD-L1 status.

Okay. This is what I thought I understand. And could you say if at least -- there was at least an objective response here in PD-L1 negative?

Yes, I can. I can tell you that. Yes. Yes.

Okay. Interesting. And the final question is how do you think that TG4001 differentiate versus the data or, let's say, the approach of GX-188E, which were data that have been presented at AACR this year?

I'm sorry, but I'm not sure we understood the name of the drug that you mentioned.

Yes. It's from Genexine, the DNA vaccine which is bivalent as well, HPV16 and 18, where data were presented at AACR in combination with pembrolizumab.

Well, it's probably early stage because I'm not sure I've seen that. We know about INOVIO, which is also a DNA vaccine. We knew about ISA, which is using long peptide and which is actually conducting a randomized trial as well. So -- and we compare very favorably with those data. But sorry, I'm not sure -- Philippe, did you know about...

No. I mean we know this company, we -- because they have also developments. But honestly, I don't recall, I didn't see the specific data. Can you tell us more? Maybe we can just give you some flavor if you tell us what the results were. Sorry, we should know...

What the results -- well, I have the slide. Basically -- well, I can't really count. They mention a 47% response rate, if I'm not mistaken, in HPV16-positive patients. And...

And on how many patients?

Roughly, I would say, 20-something.

So that's a bit surprising, to be honest. If it was -- sorry, we should know, but we have to look at this data. But I'm surprised by the extent of the overall response rate. We need to dig further to make sure that we make a smart comment, but we will do that and make sure we get back to you.

Okay. I can send you an e-mail with some slides.

Yes. We need to see the details of the patient population because, obviously, the line of treatment and so on. There are so many criteria, indications, so many indications that it's always difficult. As I was saying earlier, it's a very heterogeneous patient population. So we need to make sure that we compare apple-to-apple. Here, we had all patients with a large portion of patients which were having a very specifically aggressive disease within an already aggressive setting and so on. So each -- the devil is in the details. But we'll get back to you on that.

There are no further questions in the queue, so I'll hand you back over to your hosts.

Okay. So thanks. So just a few concluding words. So as you can imagine, we are very happy with the data we have generated. What we described today really makes us confident that TG4001 could contribute to change the treatment landscape for patients with HPV-positive disease. Addressing this patient population and its diversity through a targeted approach is the first step to our precision medicine. These data are also very encouraging for our individualized vaccine, myvac. As you saw at AACR, our algorithm performs really well at identifying immunogenic mutation. And with exoantigen like HPV antigen, we are indeed very close to new antigens. So we think that it's quite -- could be quite optimistic, let's say, for the outcome of TG4050. So we think we have here a very exciting immuno-oncology candidate, and beyond this candidate, a sound base for our therapeutic vaccines. Our technology platforms are strong, and the different poster presented earlier last month in the virtual AACR meeting are a good illustration of their breadth and depth. So we are very confident that by delivering on our strategy, we will be able to generate significant value and improved option for the patients. So with this, I would like to conclude today's call, and thanks for your attention. Bye-bye.

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