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 Madame 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're 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-Talbot, 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. Their presentation will be followed by a Q&A session.
If you're listening to this webcast via the Internet, you will not be able to ask questions unless you join us via one of the conference call numbers that are available in today's press release. You can find the slides 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 this great news with you. The interim analysis for randomized phase II clinical trial in patients with HPV-16 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 two platforms that you know very well, therapeutic vaccine 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 signs 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 adaptive 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 we need to recruit show that the two arms 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 also 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 shared data release sometime around mid-2024 or in the second half of 2024. If the final results of these 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 cancers. 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 landscapes for a range of solid tumors.
Overall, today's announcement is very positive news for our most advanced clinical candidate, TG4001, and for Transgene globally, as it further validates our MVA platform. This, alongside our cancer vaccine expertise, which we believe has the potential to make an important contribution to improving 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. TG, as a reminder, TG4001 is a therapeutic vaccine based on an MVA viral vectors. It's encoding the full length E6 and E7 antigen of the papillomavirus that is responsible for HPV associated tumor, representing more than 100 of epitopes. It's also called IL-2. TG4001 has already been shown to induce strong, specific and long-lasting immune response in patients, including activation of CD4 positive and CD8 positive T-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 immune response. It is also well documented and finding 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-PD-L1 avelumab. The current study with TG4001 is the first randomized phase II trial assessing the combination of a therapeutic vaccine and a checkpoint blocker in HPV-positive anogenital cancers. Now let's turn to slide 10. In this trial we are enrolling only advanced patients with either recurrent or metastatic disease after having received standard care. No patients with liver met are included, but patients with any other kind of metastasis, including lung, adrenal, lymph node and so on, can be enrolled. This is a group of patients that, considering the advanced stage of the disease and the number of previous line of treatment, has typically a progression around two months.
The patients enrolled are all checkpoint blocker naive, but have already undergone several lines of treatment with a maximum of one previous systemic chemotherapy line for recurrent and/or metastatic disease. We have all types of anogenital cancer in this trial, but unlike the previous phase I-B/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 predominant 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 prior therapy with checkpoint blockers. The primary endpoint is progression-free survival. On slide 12, you have the administration schedule and the timing of disease assessment and tumor and blood sampling. As shown here, TG4001 is administered subcutaneously weekly for the first six weeks, then every two weeks until six months, and then every 12 weeks until disease progression. Avelumab as planned is administered every two weeks until progression, and tumor response is assessed every six 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 have occurred, meaning death or progression as per protocol. As we have announced today, we are starting to see a positive trend with the PFS differentiating between the two arms of trial. Further, we are seeing that the other trial endpoints 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 detail. 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 agrees that the safety profile is good and consistent with the previous known safety profile of MVA and avelumab. The IDMC also agrees that a total of 120 patients will now be sufficient to demonstrate the differential efficacy between the two 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 lies in the difference in PFS we have started to see between the two arms 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, 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 I-B/II trial, which was 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 liver met, a median PFS of 5.6 months and a median overall survival of 13.3 months.
This compares very favorably to the data generated using immune checkpoint inhibitor as single agent and the rest of treatment development landscape and competition. Let's move now to slide 15. Data from the previous phase I-B/II show that this combination treatment was able to induce a strong, specific and durable immune response against the E6 and E7 antigen, which are the target of TG4001. Responses were observed in PD-L1 positive and also in PD-L1 negative patients. At present, we are very happy to see that one patient is under treatment since more than four years and doing very well. Two other patients since more than two years, including a complete response and doing very well also.
We look forward to presenting the final data from the current phase II studies and assuming this will be positive, we have a clear and manageable plan to continue the development of TG4001 in this patient population. I will now give the floor to Hedi.
Thank you, Maud. I would like to finish by saying that we are very pleased with the outcome of the IDMC, 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 in efficacy we are seeing between the two arms in the trial. We are also encouraged by the safety data and the fact that the findings of the IDMC are in line with the previous findings from the phase I-B 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 cancers.
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 had been randomized. Of the first 10 patients who received the treatment, all are stable, which is in sharp contrast with the control arm, with non-treated patients, where 30% of these patients have already relapsed. Here again, we start to see a difference between the two 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 on 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 poster 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 12-18 months and be seen as a key innovator 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. At the same time, create significant value for our shareholders. We will now take your questions.
Thank you, sir. A reminder to the participants, if you would like to ask a question, please signal by pressing star one on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Please state your name before posing a question. Again, press star one to ask a question. We will wait for just a moment to give the opportunity to signal for question. It appears that there is no participant queuing up for the question. Ms. Lucie , you can go ahead with any question from the email.
Yes. Thank you very much. I received a question via email 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?" There are other questions that I can ask later if you want, Maud.
Yes. Indeed, if we have seen, as I mentioned, a difference between the two arms in terms of PFS, meaning improvements, obviously. The aim of the interim analysis was indeed to adjust the sample size according to the magnitude of this difference. Fortunately enough, we have only 66 patients to enroll, so that we will be in position to detect statistical significance.
Okay, thank you. "Can you precise your relation with Merck KGaA? How are they contributing to the trial?"
Sure, I can take care of that. We have a partnership with Merck KGaA and Pfizer, who manage together avelumab. It's a clinical supply agreement, so they provide avelumab for free in the trial. Plus, they have privileged access to the data that we have generated, and we were very happy to share this result before communicating to you today. Beyond that, they have no specific rights. We keep 100% of the rights of the program.
Thank you. Last question I have from Martial is, "What do you expect in terms of PFS between the two arms in the design? Is it something you can share?"
I cannot because actually we have hypothesis. We are now hypothesis, but we can be even better than our hypothesis. That's the goal of the trial. No, I cannot comment more than that.
Thank you. Thank you, Maud. I think we have a question from the audience. Hand over to Nash.
Okay. We will take the question from Mr. Khalid. Your line is open. Please go ahead.
Thank you very much. Congrats for the positive data, and thank you for taking my questions. I have three 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 types? 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 base patients in the clinical study sites? Thank you.
I will address the question two and three because I'm not sure to have understood the question one. Regarding statistical difference between the primary tumor location. The trial is designed such as we have stratified the patients on the primary tumor location, meaning that we have the right balance in terms of indication between the two study arms. At the moment, what I can say is that the most prevalent tumor types, because of its prevalence, they are more frequent, are cervix number one and anal cancer. We will be in a position since we have this balance and this stratification on primary tumor location to have some flavor of what is the activity depending on the primary location.
I will say that so far, based on the phase I-B/II, we have seen activity whatever the primary tumor location. In terms of recruitment of patients, we are without liver met; it's not an issue actually. We have an ancillary cohort with liver met, and we have difficulty to recruit, by the way, patients in this ancillary cohort. In the primary, in the principal cohort, actually, because the patients are second line patients and because of the location of the tumor, we have very few liver met at this stage. The most frequent location at an advanced stage with liver met are anal cancer actually, and we have not so advanced.
The first question, sorry, I don't understand what you mean by the statistical power. I understand the name, but what do you mean? The alpha, the beta? What do you mean?
Am I still on line?
Yes, you are.
Yeah. It is the alpha, yeah. Alpha and beta.
The alpha. It's 5% as usual. Yeah.
Okay. Thank you.
That's the reason actually why we don't share the result of the interim analysis because we want to keep this alpha at 5% for the final analysis.
Thank you.
You are welcome.
Again, as a reminder, if you want to ask any question, please signal by pressing star one on your phone keypad. Ms. Lucie, I think we don't have any more questions from the participant. Oh, we have one. We have from Luisa Morgado. Your line is open. Please go ahead.
Hi. Yeah, here Luisa from Kempen. First of all, congratulations for the results. I have one question. If there are any, well, foreseeable problems that you think you might encounter for the rest of this trial?
Foreseeable problems.
Are there any foreseeable problems you might encounter?
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. I think it will enable it to continue a strong and smooth trial for the rest of the trial until 2024, where we'll be happy to have the final results.
Clear. Thank you.
Thank you.
Thank you.
No other question, I think. 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 accompanying evidence to support the potential of our portfolio immunotherapy to generate important benefits for patients and, in parallel, create significant value for shareholders. We look forward to sharing additional clinical updates in the coming months and quarters. We thank you for the support. 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.