Transgene SA (TNG) Earnings Call Transcript & Summary

Good day, and welcome to the positive interim analysis results of Phase II trial evaluating TG4001 plus avelumab conference call. At this time, I would like to turn the conference over to Madam Lucie Larguier. Please go ahead, ma'am.

Thank you, Nash, and hello, everyone. Thanks very much for joining this call at such short notice. The reason for the call, as you are aware, is the press release we issued today on TG4001 to communicate an exciting piece of news that we believe supports the value that our virus-based technologies can bring to the patients. During our call today, we have Hedi Ben Brahim, CEO; and Maud Brandely, Chief Medical Officer; who will discuss the positive interim analysis results that we obtained in our Phase II trial, evaluating TG4001 plus avelumab versus avelumab alone in patients with HPV-positive anogenital cancers. The presentation will be followed by a Q&A session. [Operator Instructions] You can find the slide on the website, too. I'd like to remind everyone that today's call will be recorded and that the discussion contains forward-looking statements, which are subject to numerous risks and uncertainties, additional details of which can be found in the press release and on our website. With this short introduction, I now turn the call over to our CEO, Hedi Ben Brahim.

Thank you, Lucie, and welcome, everyone. Today, I'm very proud and pleased to share the great news with you. The interim analysis for randomized Phase II clinical trial in patients with HPV16-positive anogenital tumors has shown that TG4001 plus avelumab has improved progression-free survival compared to avelumab alone. On Slide 4 that provides a quick overview of our company and the programs we are working on with our 2 platforms that you know very well, therapeutic vaccines and oncolytic viruses. As you can see, TG4001 is a key asset in our immunotherapeutic portfolio and a great example of the potential of our viral vector-based approaches in the treatment of cancer. Turning to Slide 5. TG4001 is an MVA-based therapeutic vaccine targeting HPV-positive tumors. It has a strong and long track record of safety. In combination with avelumab, we have already seen extremely promising size of efficacy in a single-arm trial in HPV-positive patients. We launched the current Phase II trial on the back of this good data last year. Let's turn to Slide 6. Today, we are discussing the positive outcome of the planned interim analysis of our randomized Phase II comparing TG4001 plus avelumab versus avelumab alone. Based on an interim analysis of the PFS data, we are pleased that the member of the independent data monitoring committee, IDMC in short, have recommended that the study continue to the final analysis. The trial will thus randomize a total of 120 patients overall, which is a meaningful reduction of the number of patients versus the number of 150 which had been initially communicated. You may recall that this Phase II trial was initially designed to enroll up to 150 patients with an adaptative design. Given these results of this interim analysis, we only need to randomize 120 patients in total to reach statistical significance at the time of final analysis. This reduction in the number of patients that we need to recruit show that the 2 arm of the trial are behaving differently. In other words, we are starting to see a clear trend in progression-free survival in favor of patients in the arm receiving TG4001 in combination with avelumab. We are so pleased to inform you that we share these results with our partners, Merck KGaA and Pfizer, who continue to be supportive. Going to Page 7. Based on this change in the trial, we now expect to complete patient randomization in the first half of 2024, with potential share of data release sometime around mid-2024 or in the second half of 2024. If the final results of the randomized trials are positive, we aim to continue the development of TG4001 with a pivotal trial to support the registration of this novel cancer vaccine in patients with anogenital cancer. This base case scenario is one that we at Transgene are confident we can execute successfully. Our goal remains to establish TG4001 as a therapeutic vaccine that can bring significant benefit to patients within the current and future treatment landscape for a range of solid tumor. Overall, today's announcement is very positive news for our most advanced clinical candidate TG4001 and for Transgene's value as it further validates our Invir platform. This, alongside our cancer vaccine expertise, which we believe have the potential to make an important contribution to improve treatment options for a broad range of cancer patients. Turning to Slide 8. As a reminder, the market we could address with the treatment in advanced or recurrent HPV-positive anogenital cancer, is estimated at 25,000 patients per year in the U.S. and Europe. I will now turn the call over to Maud, who will provide additional information on the trial and the interim analysis that we have conducted.

Thank you, Hedi. I am delighted to be able to share with you such good news. This is, as a reminder, TG4001 is a therapeutic vaccine based on MVA viral vectors, It's including the [indiscernible] E6 and E7 antigen of the papilloma virus that is responsible for HPV-associated tumor representing more than 100 of epitopes. It also occurred in IL-2. TG4001, as already been shown, use strong specific and long-lasting immune response in patients, including activation of CD4 positive and CD8 positive cells together with an activation of antigen presenting cells. In previous trials, we have shown that patients responding to the treatment are able to mount a clinically meaningful new response. It is also well documented and filing in the previous trial that MVA is able to increase PD-L1 expression in patients. That's why the mechanism of action of TG4001 combines perfectly with the use of checkpoint blockers and the anti-PDL1 avelumab. The current study with TG4001 is the first randomized Phase II trial assessing the combination of therapeutic vaccine and the checkpoint blocker in HPV positive anogenital cancer. Now let's turn to Slide 10. In this trial, we are holding only advanced patients with either recurrent metastatic disease after having resistant of care. New patients with liver met are included, but patients with any other kind of metastasis, including lung, adrenal, lymph node and so on can be [indiscernible]. These are a group of patients that considering the advanced stage of the disease and the number of previous line of treatment has typically progression around 2 months. The patients enrolled are all checkpoint blocker naive, but have already undergone several line of treatment with a maximum of one previous systemic chemotherapy line for recurrence and/or metastatic disease. We have also anogenital cancer in this trial. But unlike the previous Phase Ib, Phase II trial that we have discussed at our R&D event in September, there are no head and neck cancer patients in this trial. All PD-L1 status are eligible. A significant proportion of patients enrolled so far have cervix cancer, another perineal group of patients have anal cancer. Let's move now to Slide 11. As you can see on this slide, the current trial is designed to demonstrate the benefit of adding TG4001 to avelumab by comparing the combination versus avelumab alone in patient populations that have not received cryotherapy with checkpoint blockers. The primary endpoint is progression-free survival. On Slide 12, you have the administrative schedule and the timing of disease assessment and tumor and blood sensing. As shown here, TG4001 is a subcutaneously weekly for the first 6 weeks, then every 2 weeks until 6 months and then every 12 weeks until disease progression. Avelumab, as planned, is administered every 2 weeks until progression and tumor response is assessed every 6 weeks. Let's move now to Slide 13. I would like now to provide you some more background on the interim analysis. Progression-free survival being the primary endpoint of the trial, the interim analysis was launched when 37 events had occurred, meaning death or progression as per protocol. As we have announced today, we are starting to see a positive trend with the PSA differentiating between the 2 arms of trial. Further, we are seeing that the other turning points, such as response rate, disease control rate are also consistent with what we are seeing with PFS, although it is still too early to provide any further details. We can also confirm that the safety profile is very much in line with previous findings and expectations. We are also very encouraged by the evolution of the trial data, in line with our expectation and the previous finding we have seen with the treatment regimen. The IDMC agreed that the safety profile is good and consistent with the previous known safety profile of MVA and avelumab. The IDMC also agreed that a total of 120 patients with no disease progression to demonstrate the differential efficacy between the 2 arms of the study in a statistically significant manner. The fact that we now plan to only randomize 120 patients instead of approximately 150 previously planned lying in the difference in PFS, we have started to see between the 2 arm at the time of the interim analysis. Looking ahead, we will need to randomize another 66 patients into the trial, something we are confident of achieving as we now have more than 15 active sites in Europe and U.S. As Hedi mentioned earlier and based on the number of clinical site and patient accrual, we expect to complete randomization in the first half of 2024. Following release of the final data, we will then discuss next steps with the regulators. Please turn now to Slide 14. Actually Slide 14, it's a reminder of the good data we have previously generated with the combination of TG4001 and avelumab. In our Phase Ib/II trial, which was a single arm trial in HPV-positive patients, including head and neck and anogenital cancer, in a slightly more advanced setting, we saw a response rate of 32% in the subpopulation without avelumab. The median PFS was 5.6 months and the median overall survival of 13.3 months. This compares very favorably to the generated -- data generated using immune checkpoint inhibitor, a single agent and the rest of treatment development landscape and competition. Let's move now to Slide 15. Data from the previous Phase Ib/II show that this combination treatment was able to induce strong specific and durable immune response against the E6 and E7 antigen, which are the target of TG4001. Response was seen in PD-L1 positive and PD-L1 negative patients. At present, we are very happy to see that one patient is under treatment, it's more than 4 years and doing very well, and 2 other patients since more than 2 years, including a complete response and doing very well also. We look forward to presenting the final data from the 2 arm Phase II study. And assuming this will be positive, we have a clear and manageable plan to continue the development of TG4001 in this patient population. So I will now leave the floor to Hedi.

Thank you, Maud. I would like to finish by saying that we are very pleased with the outcome of the interim analysis, particularly with regard to the reduction in the number of patients that we will now need to be randomized in the study. This change clearly reflects the differential inefficacy we are seeing between the 2 arms in the trial. We are also encouraged by the safety data and the fact that the finding of the interim analysis are in line with the previous finding from the Phase Ib study with TG4001. Based on today's announcement, we are increasingly optimistic on the future of TG4001, and we clearly see it has the potential to make an important improvement in the treatment landscape for patients with anogenital cancer. This is the most important news regarding the progress of our portfolio this year. This reinforces our confidence in both our platform and especially the MVA one. Going to Page 17. Let me remind you that data on TG4050, as announced at our R&D Day, are also looking very encouraging. At the end of August, 20 patients have been randomized. Of the first 10 patients who received the treatment, all are stable, which is in sharp contrast with the control arm where with nontreated patients, where 30% of these patients have already relapsed. Here, again, we start to see a difference between the 2 arms of the trial. We plan to present the next data on TG4050 at the Scientific Congress in the first half of 2023. Now on Slide 18. On the oncolytic viruses side, we expect to present data of TG6002 in H1 2023. We also plan to deliver new data on BT-001 in 2023. If you are attending SITC next week, we encourage you to stop by the AstraZeneca and Transgene per se presenting very compelling preclinical data of a virus that we have designed with them. To conclude, I believe that we have a very attractive proprietary clinical and preclinical product portfolio. As a result, Transgene is ideally positioned to deliver multiple milestones in the coming 12 to 18 months, can be seen as a key inhibitor in immuno-oncology space. We are confident that by successfully delivering our programs and our strategy, we will be able to generate multiple improved treatment options for patients with solid tumors, and at the same time, create significant value for our shareholders. And we will now take your questions.

[Operator Instructions] It appears that there is no participant queuing up for the question. Ms. Lucie, you can go ahead with any questions from the e-mail.

Yes. Thank you very much. I received a question via e-mail from Martial Descoutures at ODDO BHF. The question is, do you plan to give more details on the interim analysis? And do you plan to publish it later? What do you mean by positive outcome? Does this mean that we already see an improvement of PFS without statistically significance? And there are other questions that I can ask later. And if you want, I would.

Yes. So indeed, we have seen, as I mentioned, the difference between the 2 arms in terms of PFS, improvement, obviously. So the interim analysis was indeed to adjust the sample size according to the magnitude of this difference. And so fortunately enough, we have only 66 patients to enroll so that we will be in a position to detect the statistical significance.

Thank you. Can you precise your relation with Merck? How are they contributing to the trial?

I can take that. We have a partnership with Merck, Pfizer who manage together avelumab, is the clinical supply agreement so that provide avelumab for free in the trial, plus they have a privileged access to the data that we have generated. And we were very happy to share this result before communicating to you today. But beyond that, they have no specific rights. So we keep 100% of the rights of the program.

Thank you. And last question I have from Martial is what do you expect in terms of PFS between the 2 arms in the design? Is it something you can share?

I cannot because actually, we have hypothesis. We have now hypothesis, but we can be even better than our hypothesis. So that's a good under trial. So no, I cannot comment more than that.

Thank you, Maud. I think we have a question from the audience. I will handover to Nash.

Okay. We will take the question from [ Mr. Khalid ].

Congrats for the positive data. I have 3 questions for you. Could you provide some color on the powering of the study? Second question is in terms of the different indications in the study. How does the statistical analysis account for the potential differences in PFS between the tumor type? And third question is, could you provide some color on how the recruitment of patients without liver metastasis is going? And could you estimate the percentage of such patients in the clinical study sites?

So I will address the question 2 and 3 because I'm not sure to have understood question 1. Regarding statistical difference between the primary tumor location, so the trial is designed such as we stratified the patients on the primary chemo location, meaning that we have the right balance in terms of indication between the 2 study arms. At the moment, what I can say is that's the most prevalent tumor types because it's obvious they are not frequent cervix, number 1, and anal cancer. And we will be in a position since we have been balanced in this certification on primary tumor location to have some flavor of what is the activity depending on the primary location. I would say that so far, based on the Phase Ib/II, we have seen activity, whatever the primary tumor location. In terms of recruitment of patients, we are without avelumab. It's not an issue actually. We have an ancillary cohort to build a development and we have difficulty to recruit by the way patient in this ancillary cohort. But in the primary, in the principal cohort actually because the patients are second line patients and because of the location of the tumor, we are very, very sure given this stage. The most frequent location at an advanced stage with the development I can say actually, and we are not so advanced stage. And the first question, sorry, I don't know what you mean by the statistical power. I understand the name, but what do you mean? [indiscernible] what do you mean?

Am I still on line?

Yes, you are.

Yes, yes, it is alpha, yes. I will try...

It's 5%, as usual. And as a result, actually, why we don't share the results of the interim analysis because we want to keep this alpha at 5% for the final analysis.

[Operator Instructions] Ms. Lucie, I think we don't have any more questions from the participants. We have one. We have from [indiscernible].

Luisa from Kempen. First of all, congratulations for the results. And I have one question. There are any well foreseeable, any problems that you think you might encounter for the rest of this trial?

No, we have not. On the contrary, I think that sharing positive news today will only encourage the sites, both in Europe and the U.S. and the patients to join such trials. So it will enable it to continue a strong and smooth trial for the rest of the trial until 2024, where we will be happy to have the final results. No other question, I think. So thank you very much for listening to us today and the discussion. Once again, it was a great pleasure. That was our most important news of the year. I'm very confident that the news today provides further company evidence to support the potential of our portfolio of immunotherapy to generate important benefits for patients and in parallel, create significant value for our shareholders. We look forward to sharing additional updates in the coming months and quarters. We thank you for the support. And with that, I would like to conclude today's call. Thank you very much, and goodbye.

That concludes today's event. Thank you for your participation. You may now disconnect.