Thank you, Lars, and thank you for the opportunity to present Zelluna to you. Zelluna is a publicly listed company on the Oslo Stock Exchange under the ticker ZLNA. We are a company that is developing a therapy that is designed to treat solid tumors, solid cancers in a scalable way. If I can perhaps bring some context to this, what do I mean by cell therapies? Cell therapies are the type of therapy that we have seen quite huge success with. They are a type of living drug.
They are generally made from cells that exist in our body, immune cells. We know these types of cells can actually fight cancer, but over time, they lose their way, they are unable to see the cancer. There has been a lot of activity in the field to try to really target these types of therapies towards cancer again.
We have seen some remarkable effects in doing that, particularly in the types of cancers that we call liquid cancers, so leukemias and lymphomas. In fact, for those types of cancers, we have seen a number of approved therapies that are now treating patients with such types of cancers. It is a type of treatment that we know can work, and not only can it work, but it also drives long-term responses. With these approvals and the excitement around that over the last 10 to 15 years, we have also come across some of the challenges faced with these types of therapies. There are three main challenges.
The first is to apply those therapies to solid cancers, so cancers like lung cancer, ovarian cancer, prostate cancer. These types of cancers collectively make up the dominant cancer burden globally. Really trying to have those cell therapies work in solid cancers has been problematic. The second is the actual production of these therapies. The approvals that we have in this space, in the cell therapy space, are for those types of treatments where a single batch is produced for every patient.
A batch is manufactured, the product is manufactured for each individual patient. You can imagine that can be costly and difficult to scale, and the access to that treatment takes time. It takes a number of weeks to actually get that treatment. The third challenge or hurdle has been, for some of these therapies, there has been some difficult toxicities, and that has needed to be managed. We have been developing a platform at Zelluna with our small and ambitious team to really address these three challenges.
We have designed and optimized a platform to be able to treat solid cancers. That is the first hurdle that we aim to overcome. We do that by bringing together highly compelling parts of the immune system, which I will come on to talk about in a moment. The second is that we generate a batch upfront of this therapy, freeze it down, multiple vials that can treat multiple patients that can be then accessed immediately. It is a different model. It is an off-the-shelf model, scaled, generated upfront, and then used to treat cancer patients when needed. That is a much more scalable model.
Thirdly, the components of the immune system that we bring together to form our product, we know are safe from clinical data on those components over the last tens of years. Excitingly, what we have been doing more recently is we have started to treat patients. We actually know from our lead product, at least for the patients that we have started to treat, that the therapy is relatively safe, has a favorable safety profile. With our platform, we are aiming to address these three challenges, and really building from the successes that we have seen in the cell therapy space.
What is it exactly that we do? If you think about cancer, in order to really drive shrinkage in cancer, to try to remove the cancer, there are two main aspects to it. The first is to target the cancer, so to recognize the cancer. This is where, on the left-hand side here, the TCR comes in, the T-cell receptor. This is a targeting mechanism. It is what finds and recognizes cancers.
It is a component that is actually clinically validated. It is known to be able to find cancers, and that is clinically recognized to do that. It is a validated targeting mechanism. We can sometimes call it a homing device to really understand what it does. The second component you need, so you find the cancer cell, the second component, of course, is to kill the cancer cell. What we use are natural cells that naturally are the most efficient killers in the human body. They are called natural killer cells.
We bring these two components together, the mechanism that finds the cancer, that we know clinically has been shown to find cancers well, that is a TCR, and bring that together with natural killer cells so that once the cancers are found, they can be killed by the natural killer cell. We call the platform TCR-NK, as shown here, and it is able to target and kill cancers in multiple ways. That is another important concept, that the cancer sometimes can escape treatment by losing the target, but in our case, with this therapy, the therapy is able to recognize cancer in multiple ways.
To help avoid cancers from hiding, in essence. I mentioned the production, as shown on the right-hand side. It is a batch that is made upfront. We take healthy donor blood from any blood bank. We take out the cells that we need, the natural killer cells. We plug in the homing device, the T-cell receptor, that is grown, and that is stored in vials, ready to use for patients, and that is what we are currently doing. It is different to the individual batches that are made for individual patients, which is where we are currently with cell therapies.
This is looking to the next stage to generate a single batch that can treat a multitude of patients. It is a novel platform where, as far as we know, the only company that is doing this, bringing the T-cell receptor together with the natural killer cell to form the TCR-NK. As I mentioned, the components, we believe, are clinically validated. The homing device has been validated to successfully target different types of cancers. Natural killer cells have been validated to be used safely and are very strong natural killing machines. Actually, there is an academic study, a couple of academic groups that have been looking at this type of approach, the TCR-NK.
What they have announced, or what one of the groups have announced recently, it's from the MD Anderson, a group in the U.S., well-known academic group in this space of treatment with these types of cell therapies. They've shown that when you do bring together the T-cell receptor and NK, so it's a similar platform to ours, you can actually drive responses in late-stage cancer patients, and they announced a complete response in a patient with late-stage multiple myeloma, so a type of liquid cancer.
So what that shows for us is that the approach can work. By bringing together this homing device with natural killer cells, you can potentially drive responses and shrink tumors in late-stage cancer patients, as shown by this group. A word on the manufacturing and the production. I mentioned this is generated from healthy donor blood, any blood bank. We take the blood, and then we take out the natural killer cells, which is the killing machine for our therapy. We add and plug in the homing device, the TCR, and then we grow that and freeze that down, ready to be used for patients. So we have generated a batch of this, and that's now being used to treat patients.
Some few slides on the lead program. It's a lead program that recognizes a specific target on cancers that is not on healthy tissues. So it's a targeted therapy to cancers. This target is the most validated target for the homing device that we use. There are a number of companies that are pursuing the target, but with another type of therapy, which we believe has limitations, and I can show that in the next slides.
The target is made across different types of cancers, so our lead can be used to treat a whole range of different types of solid cancers. We've chosen four for our clinical study: lung cancer, ovarian cancer, head and neck cancer, and sarcoma. But across different cancers, we believe that there are over 50,000 patients potentially that can be treated if the therapy is proven successful.
There's actually one approved therapy using the same target, which demonstrates that it's a valid target to go after. It's a therapy which follows the model of one batch is generated per patient, so it suffers from the ability to scale, very difficult model to scale. But what it shows us is that the target is valid and can drive responses in tumors when targeted.
We're the only company that is going after this target with a TCR-NK platform, a natural killer cell platform. When we've been developing our lead program targeting MAGE-A4, we also compare to the approved therapy that I just mentioned, which goes after the same target, but uses a different cell, uses a T-cell rather than a natural killer cell. What we show here, I'll play these videos in a moment, is when you expose each of those treatments, so our TCR-NK, shown on the right, or the T-cell, this is based on the approved therapy. When you expose it to a mix of cancers, shown here in red and green, where the homing device is able to recognize the red cancers, so it targets and recognizes the red cancers, and you'll see killing of those cancers when I play the video.
But the homing device itself is not able to recognize the green cancers. What happens is, when you have a therapy that can only go after one target, the rest of the cancer that does not present that target will continue to grow. We see that on the left, when I play the video. Whereas with our platform, whilst we have the homing device to direct the cells to the target, once in the tumor, the natural killer cells can kill and recognize cancers in different ways. So, helping to prevent cancers from hiding, in essence. With the videos played, you will see both populations are killed with the TCR-NK, both green and red, very quickly. Whereas with the T-cell, the approved therapy goes only after one of those populations.
This is what we see in the clinic when treated with these types of therapies, is that parts of the tumor then grow out that do not contain the target, which we believe we can address with our platform technology, because it is able to recognize different features on cancers, not just one. So it is an exciting time for the company. We have been building the science and the platform, and now we have entered the clinic.
In July, we announced that we treated the first global patient. We have a couple of sites that are very excited and engaged. Our lead site is in Manchester with Professor Thistlethwaite as the lead investigator, and we have a site in London with Dr. Andrew Furness, both engaged and both recruiting patients. Highly specialized sites that see many patients across the various cancer types.
Recently in our Q3 updates on just some days ago, November 5th, what we announced is that we have treated two patients out of the three at the first dose level. The format of the study covers and defines three dose levels. This is the amount of the cells, the amount of therapy we give to patients. The first dose, all dose levels will have three patients at each dose level. When you fill one dose level, you move on to the next dose level. You can see here on this chart, the difference in amount of treatment per dose level. So dose level two is three times the amount of dose level one, and dose level three is six times the amount of dose level one.
We have treated two of the three patients in dose level one, and we have really strong momentum now in identifying patients across the four cancer types I mentioned, and recruiting them for the study. Because of that, we have been able to guide on when we expect to fill dose level two , which we estimate to be, based on the current schedule and patients identified, estimate to be by early Q2 2027. So a very exciting time, breaking into the clinic, beginning to treat patients. Wh at have we seen so far? The first aspect of any type of therapy, and particularly a first in class, a world's first cell therapy, and to put it into context, cell therapies, these types of therapies, or others within this space can have toxic effects. So safety becomes very important to demonstrate.
Thankfully, at this stage, we have seen an encouraging initial safety profile with no dose-limiting toxicities, and that has also been assessed by an independent review committee. So, so far, patients are responding well from a safety perspective, and that is very important, and can become a differentiator when it comes to these types of therapies. The second thing is we analyze patients very deeply. We look at blood samples, tumor samples, and also imaging of the cancers, ultimately to see whether the cancers are shrinking.
From the blood samples, we have seen some interesting preliminary changes in immune markers, some suggestion that we are seeing some immune activation. It is early right now, but it is at this low dose level, it is encouraging that we are seeing some signs of changes in immune markers. So, why is it important, and why does it matter now that we are in the clinic? Well, we are developing a very novel technology, and this is a technology that we believe can address the challenges we have seen in cell therapy, particularly around scaling and to target solid tumors. What we have seen generally in the cell therapy space is the high value commanded by small patient datasets.
It is a different concept and model perhaps to other modalities, where hundreds of patients may be needed really to understand value. In the case of cell therapies, high value is commanded from small patient datasets, and that is shown in the next two slides. This one here shows that for cell therapies, and these are some of the approvals we have seen, that tens of patients can actually be sufficient to get an accelerated approval for those therapies, some of which have then consequently began to generate revenue and annual sales.
Tens of patients can be sufficient to drive an approval. Also, another perspective around the value of small patient datasets is we have seen a number of platform technologies that are also promising to provide off-the-shelf scalable cell therapies, so some of these examples shown here, where they have commanded high-value transactions on the basis of small patient data sets. An example, EsoBiotec, small patient data, one patient in that case, demonstrating translation of science into that patient that really commanded the transaction in that case, and the acquisition from AstraZeneca. In other cases, a handful of patients demonstrating the science translates into the clinic has triggered the transaction.
Early clinical evidence can really transform platform value, and now we are entering into that early clinical evidence arena and very excited to get through that and treat patients and begin to understand the potential translation of the science into patients. Importantly, these deals have concentrated on platforms that are mainly targeting liquid cancers, which are 10% of global cancer burden. We are targeting solid tumors with our platform technology, which is 90% of global tumor burden.
So, the pipeline behind the lead is one where we have other targets that are complementary in the expression of the and where they are made in cancers. So KK-LC-1 and PRAME, a couple of other targets, and you can see the different cancer types that products against those targets would be relevant for. The important thing to mention here is that we have a platform technology, and so in developing our manufacturing process, we believe that becomes a plug-in process where one can then drive other products from that manufacturing process. To summarize, we have over the last years been moving and advancing our platform and our lead, each time de-risking various aspects as shown here. We've now moved from concept into patients, so now we're in the patient phase where we're treating patients.
We know that this is an arena, particularly in the cell therapy space, that can really drive high value. We're very excited by entering this phase, treating patients, and looking towards dose escalation, where we can potentially really drive the effects that we want to see on the cancers. Where perhaps the most important slide here, the people, it's all really run by exceptional people. I'm privileged to work with exceptional management team, deep experience in this space, have developed these types of therapies, including marketed agents. Really understand what is necessary to drive value and build value in this field. I'm conscious of time, so perhaps I will stop there and give some time for questions in case there are any.
Thank you very much, Dr. Hassan. Let me start off with a question from our audience. There's a question regarding immune response from the body. If you take someone else's NK cells and inject them, would you get the negative immune response from the host, the patient, or how do you deal with that?
Yes. It's a good question. We haven't seen, in the field of natural killer cells, we haven't seen what's called graft-versus-host disease, a massive response in patients because they receive, let's say, foreign natural killer cells. That hasn't been a phenomena. What's been a phenomena is how long the natural killer cells can last in the body because they're outside of the body. That's something that we're monitoring.
This is a type of therapy that you can think of in a different model, and our lead clinician puts it well. It's a living drug and can be considered as a drug by injecting and re-injecting, if necessary, patients. If the natural killer cells disappear over time, and you need to reintroduce the effect, you can re-inject this type of therapy because it's off the shelf, frozen, and the cost of goods are low.
Very interesting, and I think that answers a second question from the audience too, if you can re-treat patients. You can actually repeat it until you get the desired result.
Correct. Correct.
Yeah.
That is what we have in our protocol to the possibility to re-treat.
You talked extensively about the advantages of, well, can I say production, that you do not have to do a one-on-one batch per patient, which sounds really, really like a very solid, strong advantage. When I have read about TCR-based drugs, another advantage could be that you get more targets because you can target intracellular proteins as well. Is that true?
That's a very good point.
Because then I guess it opens up a bigger field.
That's a very good point, and this is why these types of T-cell receptors have been shown successfully to target solid cancers, because there are more choices of targets that avoid healthy tissues and target solid cancers. Whereas other types of targeting systems haven't been able to do that very well. And this is why we say it's a validated targeting system, because the approvals we've seen use that targeted system to target solid cancers. And it's to the reason that you state, which is there are more choices of targets when you use a T-cell receptor.
Mm-hmm. Sounds very exciting. I guess it's very easy to compare your TCR-NK drugs with the current CAR-T as a sort of benchmark. CAR-T was lauded and very much in focus for a lot of investors and companies for a couple of years, but we've also seen a bit of bad news flow there with adverse effects and even deaths. I think both Novartis and BMS have had problems. I mean, you're still quite early in the clinical development, but do you see the same kind of mechanism that could potentially create the same kind of problems for you?
Very good point, and this is an important differentiator that we have with natural killer cells. There is an inherent safety mechanism with natural killer cells. We are not treating patients' own cells as CAR-Ts do that may be linked to some of the deaths. We generate this material outside of patients, and there is an inherent safety mechanism there by generating outside of patients. Also, going back to an earlier question, natural killer cells have a finite time in the body.
We do not expect to see, and there have not been any reports to suggest that they can then become cancerous, for example, within patients. They have a finite lifespan within the body, and they are also generated outside of the body. There are inherent safety mechanisms, and I would say this is one of the major advantages of this type of therapy over a CAR-T. That is why I mentioned safety becomes a key differentiator now.
Well, I think maybe that is good as a closing remark to get that question off the table. Now we can rest assured that it is a different animal, the TCR versus the CAR-T. Thank you very much, Dr. Hassan, for your presentation, and I hope to read more about Zelluna in the future.
Thank you, Lars. Thanks for the opportunity. See you.
Good evening.