Good afternoon, welcome to the Transgene KOL event. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this call is being recorded and a replay will be made available on the Transgene website following the conclusion of the event. I'd now like to turn the call over to your host, Hedi Ben Brahim. Please go ahead, Hedi.
Thanks, Sarah. Thanks everybody for taking the time to discuss about our program TG4050. I'm very happy to welcome today Professor Christian Ottensmeier from the University of Liverpool and La Jolla Institute for Immunology. We also have the chance of having our colleagues from Transgene, Maud, our CMO, Eric, our CSO, and Kate, our Program Director. Today, we want to focus on our individualized therapeutic vaccine TG4050. We'll also take the time to discuss, review our other programs. We will start with a brief introduction, then we'll listen to Professor Ottensmeier, who is really specialized in these kind of approaches. Then we'll have a global overview of what Transgene is doing right now and our projects for the future. Then we'll move to a Q&A.
First, I think it's clear for patients, for the industry and for investors that immunotherapy is really the fourth pillar of cancer treatments on top of surgery, chemotherapy and radiotherapy. Nevertheless, the number of responder can still be improved and the duration of the response still need to be significantly improved. We see, for example, ICI bringing a lot, but being far from achieving 100% of response rates. We think that treatment resistance could be overcome by better understanding of the tumor microenvironment and by offering the right combination of immunotherapies. Typically, virus-based cancer vaccine are perfect for that. Because of their great safety profile, because of their mechanism of action, they are perfect to combine with other immunotherapy and with other kind of treatments. They can become potential game changers in oncology.
Transgene is at the heart of this revolution. We have just presented eight posters at AACR, and we are very proud of that. It highlighted the quality of our portfolio from R&D program to product already in clinic. We will talk today about TG4050, our individualized cancer immunotherapy. It's a perfect example of a global approach of using the right vector with the right antigen in the right indication. Here we are using the MVA, modified vaccinia Ankara, which is a virus that we have proven with a great safety profile, has the ability to induce a broad and specific immune response, both from the innate and the adaptive immunity, and that strongly differentiates against mRNAs. What antigens are we putting in our MVA to make it TG4050?
Here we are putting individualized neoantigens that are selected by the artificial intelligence designed by our partner, NEC. NEC is very committed in the program. They have developed this artificial intelligence, and they are financing half of the 2 clinical trials that we are in right now. When we have designed this product, we then selected an indication that is the head and neck patients, where today patients have no solution to reduce the risk of relapse. We want to address that unmet medical needs, and we are talking about 77 patients per year. Until now, TG4050, part of the myvac platform, has proved its ability to induce an immune response linked to the clinical benefits. Based on these exciting results, we are already preparing for a potential original trial that will start before the end of the year.
Now I would like to hand over to Professor Christian Ottensmeier.
Hedi, thank you so much. Yes, I think this is a really exciting offer and opportunity for preventing recurrence in high-risk head and neck cancer, where currently, after standard surgery and chemoradiotherapy, really there is very little we have to offer these patients. Just contextually, we need to recognize that about half of these patients will relapse, and at relapse, the majority of the patients will die. This is a really important clinical puzzle. I think it will be really exciting to share with you some data why I also think it's a really important immunological puzzle that this program is addressing. Conceptually then, cancer immunotherapy is an intriguing challenge because if the cancer develops, then the immune system must have failed. Following from that, the puzzle then becomes can we reestablish immune control? What would that look like?
While at the patient level that's simple, cancer disappears, at the cellular level it's much harder. We don't really know what the optimal immune response is, nor what the targets should be that T-cells if they're then driving this should see. Of course this knowledge is critical to understand how do we get there. Cancer immunotherapy has been around for a long time, and really, the best evidence that the immune system can kill malignancy comes from allogeneic transplantation, where in hematological malignancies there were meaningful curates, and the first patients who had relapsed disease and had no other treatment options could be offered a chance at disease-free survival. The toxicity was significant. In solid tumors, this whole field changed in 2011 since when cancer immunotherapy has really become a standard of care with stunning benefit in responders.
As we all know, only about 25% of patients will benefit across multiple tumor types, with an anti-PD-1 or anti-PD-L1 antibody. While there are some examples how combination with chemotherapy in lung cancer, anti-CTLA-4, anti-LAG-3 in melanoma might alter this a little bit. Nonetheless, even those responders, by and large, or many of those patients will relapse. The question is, how might you overcome this lack of T cells that are recognizing and then attacking and ultimately eliminating a cancer tumor cells? I think the platforms that are being exploited with most detail are really aligned at the bottom.
Viral vaccines, which is of course what we're talking about here, RNA vaccines, which have set the world alight in coronavirus, but actually that's a really low bar for delivery of an immunogen against a virus that we really haven't experienced before. Peptide vaccines which have been developed by a number of groups. I think from our understanding of what viral vaccines or vaccine backbones that are viruses encoding interesting cargo can deliver is the delivery of an innate immune response identified here on the left-hand side, which is of course very rapid because it's pre-existing, as well as then in developing an anti-antigen CD8 and CD4 T cell response, so an adaptive response, which will ultimately be the key feature for protection.
From the data that are in the literature, we believe that the viral vaccines have the likelihood of being the best in class in that context. That would be really quite unsurprising because, of course, our immune system is geared up to eliminate viruses. Viruses contain all the signals that make the immune system really excited. It's from my perspective, as a clinical immunologist, not really a surprise that this would be a highly effective platform. The more challenging piece, I think, is what to put into the vaccine. This is a figure that I nicked from Kiger, really identifying that not all antigens that might be recognized by T cells, specifically antigens that are present in tumors, are born alike.
That is because we have this built-in mechanism which tries and direct our immune system away from seeing self-antigens. This process of self, of central tolerance in which our T cells go to school and are educated against a curriculum of what not to recognize in the sinus. The more interesting antigens that might not be subject to self-tolerance are shared antigens such as, for example, some cancer/testis antigens.
We already know from many bitterly disappointing trials that these have been less effective with perhaps some really intriguing targets such as MUC1, which biologically and immunologically really stand out, as well as oncoviral antigens, and I'm sure the Transgene team could spend a whole hour talking about those because these are, of course, antigens that are new to the patient's immune system but are mandatory for the tumor cells to retain them. The field overall is now converging on the group of antigens that are the result of the genetic manipulations that the tumors undergo as a part of process of the cancer becoming malignant.
While we know that from the genetic abnormality, if you were to count them up, say you've got 1,000 mutations that are naturally occurring in the cancer cells, only a small percentage of these will be ultimately visible to the immune system. There are many immunological features that makes them really interesting. There's no natural tolerance. They're most different from the bar, from the cells, and therefore, they're most likely to be immunologically visible and therefore conceptually offer a low hurdle. The key in this trial really is to try and translate these immunological concepts into patient outcomes.
The background for choosing the vaccine design as ultimately delivered was to try and set this up in a way where you would have the least non-immunological barriers to the vaccine per se, that the patient might bring to the table. We argued that in a minimal residual disease setting, there would be minimal immunosuppression. I've already identified that in head neck cancer there is a high unmet clinical need. The program therefore went from safety evaluations of feasibility to now identifying whether there is clinical benefit and ultimately whether this maps onto immunological features. The head neck cancer patients are in terms of their clinical outcome and their link to the number of T cells are relatively well understood.
Here's a dataset of our own in which I've split the tumors into blue. These are HPV-driven tumors and black HPV negative tumors. And we know that the viral antigens in HPV positive disease confer a significant benefit. Most patients who have HPV positive disease do not actually relapse. Conversely, and in HPV negative disease, the majority of patients do relapse in an immune cell related manner. If you have lots of T-cells, then the patients do better than if you have few T-cells. And please bear this in mind because I think it's really intriguing to take this concept into the data as we're going to present them. We know that anti-PD-1 antibodies have minimal benefits. 10-15% of patients have durable benefit.
That's no doubt related to the fact that checkpoint inhibitors activate what's already there, and the majority of patients don't have many T-cells. Therefore, clinically, this is the HPV negative tumors are the bad end of the spectrum of immune low cell cancers with a median progression-free survival of about 1 year. The design of the trial was to try and unpick both immunogenicity as well as safety and of course, feasibility, because making a new virus per patient was a tall order. Also, we aimed to set this up in a way that it might be able to allow us to get some efficacy data in a relatively small trial.
We argued that early randomization at the completion of standard of care treatment would allow us to make a vaccine for everybody. Entry criteria to the randomized arm is successful vaccine production, but would then allow us to have the vaccine off the shelf and give the vaccine to half of the patient and see what happens. At relapse, add in standard of care treatment and increasingly that's becoming checkpoint inhibitor treatment. Follow the patients only and then at relapse, re-biopsy, re-sequence, but deliver the vaccine that already is in the fridge or in the freezer, more likely in combination with standard of care treatment.
We calculated that from the from the numbers of patients at risk in this condition, from the setting that we had chosen, very high risk disease, extracapsular spread, large tumors, nodal involvement, we would need about 30 patients to detect a clinical signal. What has emerged since we started dreaming up this trial, and is really that transcriptomic analysis has allowed us to categorize patients in this case with head neck cancer. These are data not of my own, but these are data from Keck et al. and Kaïdre pulled the slides together. What it really identifies is that there are 4 sort of big pots in this case in head neck cancer. One is the tumors that have lots of immune cells. There are these ones here.
These would be in my previous graph, the TIL-high tumors. There are no other obvious immune escape mechanism detectable from this kind of transcriptomic analysis. There are the tumors that have no T-cells, and then there are the tumors that don't have very many T-cells or no T-cells at all, but are characterized by a fibrotic stroma. There is sort of mixed bag that has fibrotic stroma and T-cells all in one. You would predict that the failure of checkpoint inhibitor treatments would be dominated in these two groups, the tumors that don't have immune cells or that are fibrotic, fibrosis-driven. We know in head neck cancer, the cancer-associated fibroblasts sort of form a hedge around the cancer cells, protecting them against immune attack.
I think that particular feature I've just mentioned, this immune exclusion, is mainly driven in this particular group on the left. We would predict then that the group of patients who benefit from standard immune therapy would sit in this pot, but these are the groups that we really need to do something about. From that background then, it is most intriguing that just by happenstance we seem to have done just that. These are data that the Transgene team have assembled, looking at transcriptomic data, essentially identifying this kind of transcriptomic information and allocating the patients to the expression of PD-L1 on the 1 hand, but also the 1 of these 4 categories.
You can see that the majority, more than half of the patients in both groups are really in this immune deserted category. Any immunological event that might be driven must be a direct effect of the vaccine. If it turns out that there is a clinical benefit, that would really make a very strong case that we found a way to overcome this particularly immunologically challenging hurdle that so far no checkpoint inhibitors can actually address. The data look really promising. We are still in early days, and clearly this needs to mature. I'm always a little bit hesitant to review data on of an ongoing randomized trials.
So far, we know that there have been no relapses in the treatment group, while there have been relapses in the patients who have been observed only. So far so good. It looks as though we are ticking all the right boxes. Additionally, we know that the vaccine has been super immunogenic. Of the 30 new epitopes that were encoded in the vaccine, we see a median of 9 responders. In other words, over a third of the targets are actually able to activate T-cells. This is, I think, really critical because it identifies that we've picked the right clinical setting. Patients whose immune system are able to handle the vaccine and to mount immune responses. The immunological data, of course, compare what was there before to what happens after vaccination.
It's been most intriguing to see that there is a significant group of new T-cell responses which have no pre-existing counterpart by immunological analysis in the blood, and that we also amplify responses that are present. I think this is a super exciting data set where everything seems to hang together in the particular immunological group of highest clinical unmet need. I think we know that T cells are the critical condition, the condition without which nothing can happen. No T cells, you can't do immunotherapy with clinical success. We've already identified the checkpoint inhibitors awaken what's there before, and they've made, I think, a case for why this vaccine enables a T cell infiltration at a time point when the tumors per se don't actually have any T cells of their own.
Overcoming a really big gap in our current armamentarium. Of course, we know that vaccines are the only tool that we currently have to train T cells, because of course, that's how we've used vaccines over many, many decades, and we know that it's safe and highly immunogenic. I think I would like to reiterate that the viral delivery makes biologically so much sense, because that's exactly what our immune system is good at. I think we've ticked the boxes that we can also induce T cell responses of the right flavor. We know that this kind of approach is clinically feasible. It's really quite exciting to see this program developing.
Of course, we haven't talked about the parallel study in ovarian cancer, which really backs up the data in a way that is entirely coherent with what we are seeing in the TG4050 study. Clearly the next step, we'll need to demonstrate the efficacy in a larger study. I think the data comes at a time when there is enormous enthusiasm that has, that is filling everybody that cancer vaccines can play a role. Except that I think our data here demonstrate that vaccines can do this without the help of PD-1, in contrast to what we've learned from the Moderna study, in which, of course, if you were to top up the numbers, only about 10% of all the patients vaccinated actually benefit from the vaccine.
I think we're now really set to go for a larger multi-center trial that, you know, reduces all the problems that are associated with a 4-center randomized, admittedly, and international trial. I think to persuade the community that this really has legs and will make a big difference. If I summarize this, the vaccine seems to be safe, it's immunogenic, it doesn't require anti-PD-1 to see effect. The early data are consistent with, but don't yet prove clinical benefit. The fact that this is visible in a small data size, small sample size, argues that we are observing a large effect. Therefore, I'm very optimistic that the next study will confirm this.
I think it will be really exciting to see whether at recurrence in those unfortunate patients, vaccination is able to rescue the recurrence. Of course, co-coherent with the ovarian trial, there'll be very careful immunological data, something that I think I've been astounded Moderna hasn't been able to offer us so far. At the moment we're, I think, sitting really rather sweet and looks very beautiful. I'm super excited to be part of this program. With that, I think I've said all of these things already.
I think the bit that I would really like to finish on is I genuinely believe that this kind of approach offers hope to cancers that are not only devastating to the patients, but also to their families, and are often, terribly, rapidly causes of death of the patients who are suffering from them. Thank you very much. I'll hand back to Hedi Ben Brahim.
Thanks, Professor Ottensmeier, for sharing your analysis about the program and giving also your view on the whole field. We share the same enthusiasm about the fact that this field is moving really in the right direction. There is a strong momentum around cancer vaccine, and you mentioned Moderna, of course. We think that we compare favorably with what we bring in term of safety profile, immunological response rate, and of course, called the first sites of clinical activity. So far TG4050, and we've shown that in the poster that we had this week at AACR, has shown a great safety profile.
We have signed off clinical activity in high-risk patients, and we show that in monotherapy without the support of ICI by delivering this broad and specific T cell response. That's why we are already preparing the future of the program, which will be a Phase 2, potentially targeting registration that will start in the second half of 2023. We're addressing a total need of more than 70,000 patients per year that could represent a market of more than $1 billion. This is talking only about head and neck in adjuvant setting, but it's obvious that this program, because it's patient specific, can address a huge number of indication, especially in adjuvant or maintenance setting, but maybe also beyond that.
It can be a number of cancer listed here, a few like ovarian, urothelial or many others. TG4050 is very exciting and we had a great poster at AACR, but that was not the only one. We had a lot of news on our other programs. We talked about TG4001, our other therapeutic vaccine with fixed antigen, supporting patients suffering from HPV positive anogenital cancer. We are very happy to announce that we will have a new cross-sectional data presented at ASCO, just a few months from now.
We target to end the enrollment in the first half of 2024. If we look at the oncolytics part, with TG6002 in the new poster, we have further demonstrated the great safety, the selective replication, and the expression of the payload in the tumor. We have the evidence of T-cell activation and immune checkpoint receptor expression. We've been able to share more about our latest oncolytic virus that is in TG6050 that has shown in preclinical model outstanding antitumor activity. We expect the first patient to appear in the coming weeks. We talked at AACR not only on our existing program in clinic, but also our projects for the future.
We are happy to share news covering hot topics in our industry such as novel payloads, new virus backbones, tumoroids, and also extracellular vesicles. That's the overview for our portfolio, and you know that Transgene has multiple shots on goal. We have 2 therapeutic vaccine. We've talked a lot about them, TG4050 and TG4001. That's also now 3 oncolytics in clinic and also the very important partnership with AstraZeneca around oncolytics. If we look at 2022, we have achieved great results on all program, which gives us now a lot of confidence for the milestone that will happen in the coming 18 months. TG4050, we have shown repeatedly last year, and each time we've confirmed again at AACR, that we have promising data as a single agent.
We expect to start the treatment of the last patient in the head and neck trial very soon and to start the Phase 2 before the end of the year. TG4001, we had a positive interim analysis end of 2022. Now, we are looking at the end of randomization in 2024, and we intend to rapidly start a registration-directed trial. On the oncolytics part, we have proven the feasibility of the intravenous administration, which is the key difference we want to bring in the oncolytics. That has been translated with the arrival of TG6050, that will be injected intravenously in lung cancer with the first patient care very soon. BT-001, our other oncolytic that is already in clinic.
We will finish the part 1A as a single agent very soon. It will move into the combination with pembrolizumab in partnership with BioInvent. I think we've covered all what Transgene is doing right now with 5 products in clinic based on our deep expertise of bioengineering and our approach of choosing the right vector with the right antigens in the right indications. This technologies is bringing now great news in clinic, and it's supported by various partners, especially AstraZeneca in the oncolytics, Merck and Pfizer who are supporting TG4001, for example, NEC, which is really central for TG4050, and BioInvent for BT-001. Today we have a reminder that we have a financial visibility until early 2034.
Thanks again for listening to this to this discussion. Now I'll be very happy to turn to question and answers.
Great. Thank you, Hedi. Please hold for a brief moment while we pull for questions. Our first question comes from Brandon Folkes from Cantor Fitzgerald. Please go ahead, Brandon.
Hi. Thanks for taking my questions, and congratulations on the data. Maybe just firstly on the data, any color on the patient backgrounds and characteristics of the patients who relapsed in the control arm? Then just any commentary in terms of, are those patient characteristics similar to some of the patients, or are they patients with the same characteristics in the TG4050 arm, apparently, who are responding well?
Yeah. Maud, would you take this?
Yeah. Just as a reminder.
Sorry, there's a lot of echo.
There is an echo.
Hey, Eric, can you please mute your computer?
Yeah.
To answer your questions. A reminder, we enroll patients with advanced stage disease, we take T3 or T4 disease. To answer very precisely to your question on the 2 patients who relapse in the observation arm, actually one was Stage 3 with new especially poor prognosis features. The other one was Stage IVb , sorry, with extracapsular lymph node invasion. You know, it's normal behavior of patients. There were no especially good, and especially the one with Stage 3 was not especially expecting that patients will do that. Are you happy with my answer or do you want more details?
Yep, that's fantastic. Thank you. Maybe if I just follow up with the second trial. Granted, you know, you sort of, the Phase 2 is not designed yet. Just maybe any thoughts in terms of how large and how many patients effect are needed in Phase 2, especially for a safety perspective? Then secondly, you've presented very promising single agent data, but do you expect to run a combination arm in the Phase 2?
Regarding the sample size, we have some precise idea and especially in light of what has been done by Moderna. You all know the controversy around the statistic and the fact that Moderna trial conducted the one-sided statistical design. Therefore, we are working on the two-sided. We believe that it's something which is valuable if we want really to have a trial which persuade the community, the scientific community that we are going in the good direction. Obviously it will be a trial of more than 100 patients. The important feature I want to underline is that thanks to the design of Phase 1, our Phase 1 trial, which is already a randomized trial, we can benefit from the...
Now we have 32 patients who have been randomized in our Phase 1. We can benefit of those patients and have a good analysis with the patients who are going to be enrolled in our Phase 2. That's for your first question. For your second question, as you know, as Christian mentioned, so far, the PD-1 or PD-L1 has been very disappointing in the adjuvant setting. There is 2 large Phase 3 trial, one with pembrolizumab and the other one with avelumab, which were negative. There is an ongoing trial testing perioperative pembrolizumab for which data are expected by mid 2025. For the moment, we are not considering combination because of the lack of efficacy of the ICI. Why to increase the toxicity burden of the patient if there is no benefit?
Having said that, depending on what can be released from the ongoing trial of perioperative pembrolizumab, we are open to possibility of combining with pembrolizumab, by the way.
Great. Thank you very much. That's all my questions. Congratulations again on the data.
Thank you.
Thanks for the questions, Brandon. Our next question comes from Olga Smolentseva from Bryan, Garnier. Please go ahead, Olga.
Good afternoon. Thank you for taking my questions. Maybe firstly just, I was wondering, acknowledging that you've seen preliminary responses, or relapse free, I guess, rates in PD-L1 negative patients. It seems that there is a slight imbalance between PD-L1 status in TG4050 and control arm. Do you expect that to somewhat impact the final data?
Yes. Can you hear me, Juan?
Yes. Sorry. You expect answer to the question?
Yes.
Yes, there is, there is indeed, somehow imbalance, as you put it, into across the two arm of the study. The reason is that the PDL1 staining is an exploratory parameters and was not intended, and the study was not designed to be calibrated with respect to the two arm because the two arm are not actually comparative arm in this study. Nevertheless, all data is not available. As you could have seen on the poster, there's still analysis ongoing. I don't know, I don't know to which extent this is going to be flattened with the additional data.
Last, even if you see the other imbalance and you want absolutely to keep the idea of having a comparative view across the two arms, the difference between the two arm is not really going in a sense that is favorable to the vaccine. When you look at the overall data you can see that even in the vaccine arms, the pretty much an enrichment for very desert tumor microenvironment and many patients with also low or very medium expression of PD-L1. Last, we are also giving the vaccine in monotherapy, so it's not an ECA combination.
The expression of PD-L1 and its impact on the activities is not something that we can straightforward interpret. Yes, there is difference. Today it's hard to make an assessment on how impactful is that and how this is meaningful on the vaccine.
Thank you, Kaïdre.
Thank you.
Professor Ottensmeier , wanted to comment?
Yes, please. I think it's really important to note, first of all, the data are randomized, so there is no choices made on the PD-L1 stated up front. Of course, with an N of 30, you just have to live with what the randomization ultimately reveals. That's point one. Point two is the data are incomplete. About a third of the patients in the randomized observation alone have not yet been evaluated in this way. I think we need the full data set before we can come to a conclusion that there is an imbalance. I think we have no suggestion from any of the data that vaccines would work better or worse in PD-L1 low, moderate or high disease.
I think the, therefore, at the moment, we can only note that in the incomplete data set, where 30% of the data are still missing, there appears to be an early imbalance, but that may very well balance itself out once the whole data set is available.
Thank you. Thank you. That's very helpful. Maybe just the last one. I was curious, out of the neoantigen positive T cells, what % of CD8 positive and CD4 positive cells, you're seeing, if you have such data available?
Most of the... It's... Yeah, thank you for the question. It's hard to answer because, actually 70% of the CD8 T-cell of CD8 T-cell response are also associated with the CD4 response for the same target. As we are essentially targeting CD8 epitopes, we put 25 CD8 epitopes and up to 5 class II epitopes in the vaccine. Still, most of the class I epitope, because of the design of the vaccine, are also associated with the class II epitope. It's hard to give you, like, a percentage of class I and class II. They are essentially class I, but most of those class I are associated with the class II.
I would say that we have an calibrated response between CD8 and CD4 response, which is a classical feature of the MVA vector.
Got it. Thank you. That's very helpful.
Okay.
Thanks for the questions, Olga. This concludes the verbal portion of the Q&A. I'll now turn it over to Lucy to read the remainder of the questions from the web.
Thank you, Kai. We have a first question here. Do you plan to meet with the FDA or EMA ahead of initiating a registration trial with TG 4050? If so, will you be communicating to investors the feedback from this program? I hand over to Maud.
That's, of course, it's a very important question. We do intend to meet first the FDA to discuss all the details, not only on the clinical aspect, CMC aspect, but discuss that with the FDA. This is something which is quite important. I am not sure that it will be of great interest for the investor to share the conclusion of the FDA, but for sure it will translate into maybe some adjustment of some slight modification of the protocol we are at the moment de-designing. This is something which will come in the coming month.
Thank you very much. Maud, we have another question. For TG4050, do the results, neoantigens of the first patients allow to refine the target for the following patients so that the self-improving process? This is a question that I will hand over to Kaïdre to answer.
Sorry, I couldn't hear the beginning of the question.
I think the question is to know whether we use the data, what we learned from the ongoing trial in patients to feed the database and the artificial intelligence we're using to select neoantigens.
Yes. The principle of the machine learning system is that it will improve over time by being looped with the data we generate from the patients. Up to now. No need to change the Slide, I think. Up to now, we have been using the Basel system. It has been updated once throughout the Phase 1, and it will be updated then regularly. We had the recent exchanges with the FDA, where although they do not have a process for those adaptive machine learning system, they are kind of putting in place a good practice on the go.
I had an exchange with them recently on how we should be updating them and informing them of when and how we are adding data to the system. We're moving from a fixed system.
I would call that a semi-adaptive system with time points where we'll update the system at given time point and inform the agency of those evolutions. We're pushing forward and moving forward fully adaptive systems where we have a continuous improvement and a continuous feedback loop on the machine learning and the improvement of prediction starting from the data we're generating from past patients. It's by design, it's on the go, and we're working with the regulator to make sure we implementing these new approaches into clinical setting.
Thank you very much. We have a final question which I will direct to Hedi. Will the initiation of a registration driven trial of TG4050 be contingent on the company raising additional capital to fund this program?
You know that today we have a financial visibility until early, 2024. We will start the trial before the end of the year. Of course, the duration of the of the trial will be much longer than existing current financial visibility. I think that considering the momentum that is in our field of therapeutic vaccine, and especially individualized therapeutic vaccine, and the data we've brought and the new milestone we'll have on this program and the other programs, we will have support from our existing shareholders and also new shareholders in the in the future.
Thank you, Hedi. I'm reminding everyone that, yeah, if they want to ask questions, they can do it in the Q&A session. I think we don't have any questions arriving, we can turn to closing remarks.
Thank you, Lucy. Thank you, Professor Ottensmeier. Thank you, Eric, Maud, and Kaïdre Bendjama for the organization and being part of this session. I think you've been able to hear our enthusiasm about this program and the analysis from Professor Ottensmeier about the field and TG4050. We will continue to bring new data on this program, on the existing trial. Without waiting, we'll move into a new trial before the end of the year, because it can be a key solution for patients in this adjuvant setting in head and neck cancer. Thank you very much for your time, and have a great end of the day.