Hello everybody. Welcome to today's webinar. I think most people have joined us by now. My name's Tim Oldham. I'm the CEO and Managing Director of AdAlta Limited, and I'm very excited today to talk to you about BZDS1901, our first-in-class CAR T-cell therapy offering new hope for mesothelioma patients. AdAlta's strategy to deliver highly original CAR T-cell therapies for solid cancers originating across Asia and globalizing those through Australia offers enormous potential to bring hope to new hope to patients with a whole range of solid cancers. Today's webinar is intended to exemplify that by overviewing the hope that we see and the excitement we see in BZDS1901. There will be an opportunity for questions towards the end of the webinar.
If you would like to ask a question, please post it in the chat, and we'll deal with as many of those as we have time for as we get to the end of the discussion. BZDS1901 targets initially a lethal and insidious disease called mesothelioma. This is a cancer, rare today fortunately, that is infamous for its association with asbestos exposure. Exposure to the fibers and dust from asbestos is almost universally linked to those patients who have mesothelioma. The cancer arrives 10- 60 years after exposure. You can see in the chart on the bottom left-hand side of this slide that the number of patients globally is not high, but it is still significant, and it is certainly not the rarest of cancers.
You'll note that the European incidence, that's the number of new patients who are diagnosed each year, and mortality is way ahead of the rest of the world, and that's a function of Europe not banning mesothelioma, banning asbestos until much later than many other markets. You'll also note that Australia and New Zealand has a relatively high incidence and prevalence of this disease relative to its population. Again, a function of our history, building with and mining asbestos. The market for asbestos drugs today is about $12 billion, and the segment that BZDS1901 can potentially address, we estimate has a market size of around about $4 billion. That is just in mesothelioma, just in these rare cancers.
Importantly, BZDS1901's target, a protein called mesothelin, which is expressed on the surface of cancers, is found not just in mesothelioma, but in varying degrees in more than ten other cancers, and particularly in some of the more difficult to treat gynecological cancers, which we anticipate will be the next wave of indications for this product, once its efficacy is reestablished in mesothelioma. If you're a patient with mesothelioma first diagnosed today, your prognosis is really poor. Firstly, your life, quality of life is going to be poor. Mesothelioma has been described to me as being like trying to breathe with cement in your lungs.
You will initially be treated with chemotherapy or immunotherapy. The chart on the top left is what we call an overall survival curve, and this shows the percentage of patients still alive after first treatment with chemotherapy or immunotherapy. You can see that the median survival at which 50% of patients have passed away is 14 months for chemotherapy and 18 months for immunotherapy. Between 27% and 41% of patients will survive beyond two years. It's a very lethal, very rapidly lethal disease. Importantly, you'll see that overall response rates, this is the rate at which, or the number of patients in which the tumor will be shrunk by therapy, is around 40% in both modalities. More significantly, what we call a complete response rate, where the tumor disappears completely, is incredibly rare, and this is in first-line patients.
Note that when immunotherapy was first introduced as a treatment for mesothelioma, a four-month gain in average survival justified reimbursement agencies funding the immunotherapy agents at around about $130,000 U.S. dollars per course of treatment, just for that four-month gain. This is not about curing cancer. Significant improvements, or in this case, a not particularly significant improvement in cancer, can still result in material and significant markets. Most patients are going to progress, i.e. their tumor will continue to grow and expand well inside the survival period, so well inside that 14-18-month window. When that happens, prognosis deteriorates even faster. You can see here, this is one of the best examples of second line, what we call second-line therapy, i.e. after the patient's tumor's started to expand.
You can see that the immunotherapy in this example doesn't give a lot of improvement in overall survival relative to no treatment at all. Significantly, the overall response rate falls to less than 10%. Typically for these immunotherapies, can be up to 30% in some cases, and the chances of a complete response, complete tumor elimination, are essentially zero. One-year survival rates have plummeted. The outcome for these patients is dire. This picture tells us just why we're interested in trying to find a better solution for mesothelioma. BZDS1901 CAR T-cell therapy already has results out of clinical trials conducted in China so far that point the way to a potential better outcome and new hope for these patients.
This chart shows what we call the response rate at a patient level for the 14 patients that have been treated with the current generation of BZDS1901 so far. These show how the tumor has shrunk or grown after therapy. Below the line in green is a good outcome, above the line is obviously not a good outcome because that's the tumor expanding. A complete response means the tumor is has been completely eliminated, can no longer be detected. That doesn't mean it will not recur, but it means we can no longer detect it. A partial response, or PR, represents a tumor that has shrunk by more than 30%.
You can see straight out the gate that in these patients, remember these are second line or later patients who've already progressed after that first line therapy, we already have two complete responses in this patient group. That's an incredibly rare outcome and something that got us very, very excited about this product. If you look at the therapy overall, we've got multiple response rates and there's, in multiple patients, and the response rates are more than double what we're seeing so far in those benchmark response rates for advanced second line disease. We've got complete tumor clearance in two of 14 patients. This is really difficult to achieve. The longest duration of those, that complete response is now out almost to two years. Both these patients are still alive, as we'll see shortly.
We see the tumor shrinking not just after initial therapy but continuing to shrink in some patients for up to four months after initial therapy. Remember, these patients are getting a single dose of BZDS1901, not a continuous course of therapy the way traditional chemotherapy is administered. We are not yet at the point where we can measure median overall survival. Fortunately, there are enough patients still alive that we haven't reached that point yet. In a first or earlier generation of this product, median overall survival of over two years was obtained. You can see that we are starting to achieve already those rare complete responses. In the higher doses, that's 20%. An overall response rate of 50%.
We are on course, we believe, to have a product that could transform outcomes for these patients. Let's turn to those two complete responses, and let's look at what these patients had experienced in detail. The first patient had advanced pleural mesothelioma. This is mesothelioma of the membrane surrounding the lungs and the heart. They'd been through four cycles of combination immunotherapy as first-line treatment, and then their tumors had started growing again six months later. They underwent second-line treatment, more immunotherapy. This is exactly following those slides that we saw in the, or those charts that we saw on the, on the slide a couple of slides ago. The tumors were not controlled by that second-line immunotherapy.
Third-line therapy with a single dose administered intravenously of BZDS1901, and the two target tumors that started out being over 5 cm long, and that's in the yellow boxes, you can see in the images on the right-hand side. A month later, they'd shrunk by 44%. Two months later, they'd shrunk by 80%. At three months, they were essentially undetectable. This patient is still in complete response at 18 months and still alive at 20-22 months. We're coming up to the 24-month assessment for this patient. We're hoping that they will still be in complete response. That size of tumor, you can imagine the pain associated with that kind of tumor, on your lung cavity. It would be incredibly difficult and incredibly painful to breathe.
Obviously, the prognosis for this patient having failed two lines of therapy was not good. The second patient has a slightly different lens on how BZDS1901 works. This patient had advanced peritoneal mesothelioma. They had been through three cycles of chemotherapy, and their tumors had started growing again after 14 months. They got one cycle of, or one treatment with an immunotherapy, essentially to maintain them because they did not think they could help this patient anymore. That certainly did not control the tumors. Now, this patient had multiple tumors, and you can see them. This is rather than a CT or a computed tomography scan, a bit like a high-end X-ray on the previous image, this is what we call PET-CT image.
You marry up the CT scan, gives you a location of the soft tissue and the organs in the body. The PET is essentially a radio imaging agent that localizes to the tumor. You can see in the patient in the top left, the dark blobs inside the yellow box are tumors. They're a bit harder to see as the bright blobs in the box on the right-hand side, on the right-hand colored image. The two right-hand images are that same patient a month after a single dose of BZDS1901. We can't see any tumors inside that yellow box. This is a complete response at 28 days. This patient is still in complete response at six months. This is probably, I can see one of the questions coming through here is around maximum doses.
We believe that we can further increase the dose levels that these patients are receiving. It's not always clear that an increased dose is gonna lead to a better outcome in CAR T-cell therapies. In this case, there is fairly strong evidence that the low dose was not necessarily as effective, that the higher dose that we're looking at the moment is the minimum effective therapeutic dose. We will be assuming adequate safety on the next few patients and the first few patients treated in our Australian trial, looking to increase that dose further. That's the story for BZDS1901 and why we're so excited about the results we've seen in China already, and that potential for this particular product to make a real difference to a desperately needy patient population.
What is it about BZDS1901 that has enabled these results when everything else that we've seen before, is not delivering anywhere near these kind of results and certainly hasn't delivered a complete response? The answer is that we're using technology called CAR T-cell therapy, which is the cutting edge of cancer care today. Remember, the overall treatment goal in cancer is firstly to shrink the tumor. That's a partial response, or ideally clear it. That's a complete response. It becomes undetectable. The ultimate measure of cancer outcomes is improved overall survival. Ideally that is without tumor growth, which is called progression-free survival. A century ago, we had surgery as pretty much our only option. Radiotherapy and chemotherapy were starting to emerge as possible options for cancer patients.
Unfortunately, both of those therapeutic modalities are poisons, and they poison the cancer faster than they kill the patient, primarily because the cancer is growing faster. In the 1990s through 2010, immunotherapies or targeted therapies started to emerge. You heard me talk about those as the next line, the next advance in, or the most recent advance in mesothelioma care. These are drugs that target specific molecules that are overexpressed on the surface of cancer cells. That means there's more of them on the cancer than there is on the patient's healthy tissue. They modify the way cancer interacts with the immune system. You know, cancer is a patient's own cells gone rogue, it's very, very good at hiding from the immune system that's designed to clear these, clear pathogens away.
Cell therapies, on the other hand, are a living drug that no longer just about taking the brakes off the immune system, but now putting a turbocharger in it. They're an engineered living drug that is delivering some amazing outcomes. It's that underlying technology that underpins our East to West cell therapy strategy because it's these CAR T-cell therapies that we believe are gonna be the transformation of cancer outcomes for difficult to treat cancers in the future. What is a CAR T-cell? It is a living drug that has been engineered to turbocharge a patient's own immune cells so they can see and kill cancer. It's usually administered by a single or very few doses. It is durable because it lives. It becomes part of the patient's own immune system.
It is always there should the cancer come back. A single dose is potentially curative. We manufacture these CAR T-cells today by taking a sample of the patient's own blood and isolating a special immune cell called a T-cell. From that sample, we then genetically engineer this in the laboratory to insert a gene for what we call this chimeric antigen receptor, or CAR. Essentially that's a targeting tool. It enables the cancer to go and find a protein on the surface of cancer that is not present on the surface of healthy tissues. We grow these engineered cells in the laboratory to enable us to administer millions or potentially hundreds of millions of these cells to patients.
That CAR T-cell is then capable and primed to find and kill the cancer cell using the patient's own normal immune clearance mechanisms. These therapies have already transformed outcomes for a large number of blood cancers already. There are seven FDA-approved CAR T-cell therapies for blood cancers. The first was approved in 2017. The market already exceeds $2.5 billion a year. The future obviously is can we translate that same success into solid cancers, which is a 10 x larger market. The first two T-cell therapies for solid cancers were approved in 2024. That market is opening up right now, and we are on the beginning of a wave of that progress.
Another example, it's really the poster child, pardon the pun, of the potential for CAR T-cell therapies, is a young lady called Emily Whitehead, who was first treated with a CAR T-cell therapy in a clinical trial in 2012. She was six at the time. She had aggressive leukemia. She'd undergone 16 months of chemotherapy already. She'd relapsed twice. She was ineligible for bone marrow transplant and was essentially considered terminal. A single dose of CAR T-cells made from her own immune cells, and she is cancer-free 13 years later. That is not an accident and is not an isolated outcome. In blood cancers, we're seeing 83% complete response rates, unmeasurable cancer in childhood leukemia. We're seeing 51%-60% in lymphomas, adults. We're seeing 78% in myeloma.
You may have seen recently in Australia, Sam Neill's discussion with Professor Miles Prince around how CAR T-cell therapy cured his myeloma. That product has now just been funded in Australia. It's an amazing and important breakthrough for these patients. Our mission at AdAlta is to bring this same hope to solid cancer patients. Why are we doing this? What's it worth? It's worth potentially at the end of a phase I clinical trial in Australia, $85 million in an upfront payment and a total deal worth $780 million. That's the median deal value for phase I stage CAR T-cell therapies made from a patient's own T-cells over the last five years or so. Importantly, I'll focus on the last of these transactions, which was between Atara and Bayer, because this transaction related to a CAR T-cell for mesothelioma.
In this transaction, Bayer took an exclusive worldwide license to two products. The first had completed a clinical trial. The second was an off-the-shelf version that was still very early in preclinical development. Bayer paid AUD 60 million upfront to Atara and up to AUD 610 million in total development milestones, plus low double-digit royalties, which meant that Atara would have been making 10% + of every AUD of sales that Bayer eventually made commercializing this. The product was what was called an armored mesothelin CAR T. It's very similar to BZDS1901, except for what we call the armoring technology that overcomes immune suppression was slightly different. Importantly, the lead product, ATA2271, had less data than BZDS1901 has today, let alone by the time we've moved manufacturing into Australia and completed a phase I clinical trial. ATA2271 had 25 patients of data from a first generation of the product.
The second-generation product that Bayer licensed had undergone a complete product redesign with no additional clinical data on that. That product had delivered zero complete responses and an overall response rate of 12%. Median overall survival was about two years, which was a good outcome, tumor control was very, very poor. Compare that with BZDS1901 today, where we have 26 patients of data, 11 with a first gen product, 15 with a second generation of the product. The only change from Gen 1 to Gen 2 was a method of manufacturing the product, we've got superior response rates. By the time we've replicated that in an Australian trial, we believe that we will be well on track to command the kinds of transaction values we saw in the previous slide.
This model is something that is being launched with BZDS1901, but it's a very replicable and scalable model. We're focused on licensing leading technology from Asia, particularly from China, where we can acquire these technologies at very low cost. Why China? Because China is becoming the world's R&D lab, as exemplified by 30% of all big pharma licensing deals in 2025 were from China-originated assets. Major pharmaceutical companies like Johnson & Johnson, AstraZeneca, GSK have all done cell therapy deals in China in recent times. The quality of the science, the quality of the clinical data can be relied on, obviously once we've done appropriate levels of due diligence. The limitation that many of those Chinese companies have is that they cannot globalize those programs without Western clinical data. This is even more exemplified by a U.S.
House of Representatives Appropriations Committee that is trying to prevent the U.S. FDA from reviewing or including Chinese clinical data in any application for a clinical trial approval or ultimately a new drug approval. That means that the role that we play of generating first Western clinical data in Australia, which is recognized by the FDA as being a high-quality clinical trial location, recognizes that that adds significant value to our large pharma partners and significantly reduces the risk. For conducting that phase I clinical trial in Australia and moving the manufacturing to Australia because we can't ship human cells out of China, then we establish a global reference manufacturing site and the asset is totally positioned for globalization. At that point, we would seek to on-license that asset to companies like Bayer, Novartis, AstraZeneca that you saw on the previous slide.
The next steps for AdAlta from here, for BZDS1901, our immediate next steps are U.S. regulatory advice in the form of a pre-IND meeting to confirm that our interpretation of their guidelines and the preclinical data package we need is in line with theirs. We have already commenced the manufacturing technology transfer. We announced the signing of that work order with Cell Therapies a couple of weeks ago. We will continue to receive ongoing results from the clinical trials in China.
Towards the end of this calendar year, we anticipate starting to close out the IND-enabling studies that we need to do. Outside of BZDS1901, we're continuing to screen additional East to West cell therapy assets to enable us to expand the pipeline with assets that can be advanced to inflection points rapidly at low cost, and particularly re-leveraging our recent collaboration with Ori Biotech, which is a next generation automated manufacturing platform. We're continuing to work towards monetizing our previous developed IP in WD-34, an antibody for malaria, and AD-214 for fibrosis. In closing, today's discussion was designed to communicate our enthusiasm for our overall business, but built on the type of impact that we can have with products like BZDS1901.
We're addressing the largest market in cancer, the solid cancer market, using assets acquired from what's becoming the world's R&D lab. We believe BZDS1901 is a groundbreaking asset, bringing new hope to mesothelioma patients, exemplifies everything we're trying to do with this East to West strategy. As you can see, we've got multiple clinical regulatory and manufacturing milestones ahead of us. We have the collaborations in place to solve the second challenge of CAR T-cell therapy, which is how do you manufacture it, this business is scalable to enable us to build a pipeline of highly differentiated cancer cell therapies at low acquisition costs. With that, I'll pause and take questions that are starting to appear in the chat. To the person who asked, "Is this where we can ask questions?" Absolutely, it is.
I touched on the first question a little earlier: Have the trials reached the maximum dosage levels? We believe that we do have potential to increase the doses further. There is certainly a lot of work being done on safety management for this program, and we're confident that the safety profile that we've seen at the current maximum doses is just something that supports increased dosing in the future, and that'll be something that'll be built into the phase I Australian clinical trial. Second question was, what's the possibility of improving the outcome if BZDS1901 is administered earlier than after the second-line therapy? It's a really good question, and we believe, based on the mechanism of action, the industry believes that the earlier you can administer a CAR T-cell therapy in the hierarchy of treatment, the better.
We're starting to see some of those blood cancer products, particularly in myeloma, the clinical studies are now being run to test them against earlier and earlier lines of therapy. The challenge with CAR T-cell therapies today is that because they are patient-specific, made individually for every individual patient, we do need, or it is very expensive to manufacture them, and the cost per dose is very high, even though you need only one. As a result, and as is conventional with all cancer therapies, you start with the sickest patients, and then bring them forward and move up the lines of therapy over time. It's unethical to treat a patient on a first line of therapy with an investigational drug when there's an existing first-line therapy available.
This mechanism of treating the sickest of sick patients is something that happens for all cancer drugs, but we will move them forward and up through the lines of therapy as time goes on. Question's roughly when would a phase I trial occur in Australia? We're anticipating that the phase I trial in Australia would commence in the later part of 2027. We've started technology transfer at the moment. That is a process that does take nine-12 months, and we are adding some additional process optimization steps in order to ensure that the process is scalable. We also need to conduct a final toxicology study using the process, the product that is manufactured from the process we've established in Australia, which will take a little bit more time. Along the way, however, we're gonna see some significant steps.
I can't underestimate or understate just how significant having control of the manufacturing process is and demonstrating that it can be moved from one site to another. While we often find that manufacturing processes and manufacturing development is undervalued by the markets, in cell therapies in particular, manufacturability is the number one issue that comes up in due diligence after clinical data. Big Pharma want to know that your manufacturing process is scalable and can be delivered at low cost. We selected BZDS1901 deliberately because it already had a two-day manufacturing process compared with the usual nine-10 days for a conventional CAR T-cell and used a relatively cheap gene modification technology.
We then want to add some additional steps in that process that enable us to ensure that it is really easy to scale without having to add hundreds of people on as you go to hundreds of patients. There's a question that says, "Given the Bayer deal was based on minimal data, has 1 AD had any real corporate interest given the data set we have is more superior?" We only licensed BZDS1901 at the beginning of this year. Up until that point, we had no rights to talk to big pharma companies about it. For that reason, we have not had, we ourselves have not had any direct engagement. The other difference between the Bayer-Atara deal was that the data that Atara had was generated in the U.S. at Memorial Sloan Kettering Cancer Center.
At the time, that was with the geopolitical environment between China and the U.S. happening, that was a far stronger position for Atara to be in than Shanghai Cell Therapy Group are at the moment, that's our licensing partner in China, and that we are given that we haven't got the manufacturing process out of China. We don't have Caucasian clinical data yet. Until that data gap is closed, there will be a gap to potentially realizing that deal. What we find often is that CAR T-cell therapies are licensed with varying degrees of data. There was one deal that was done with only two patients of data. There are other deals that have taken much more data than that.
It depends on exactly where in the partnering cycle, where in the therapeutic portfolio, these types of assets sit for pharma companies. Typically, what we see is when one deal happens, then other deals rapidly follow. We'll also continue to get data from the Chinese clinical trials as well. That key point around durability of response, we won't actually get that from the Australian phase I study quickly. It's time from treatment, we will continue to see that. About every quarter we would anticipate there'll be a clinical update from the Chinese program. We will have clinical data emerging even in the period before the Australian study starts. The next question was, when can we expect results from the Australian-based trials?
We estimate the trial itself will take around two years to fully recruit and then to have sufficient follow-up to have some meaningful results. Based on the sort of outcomes we're seeing at the moment from BZDS1901, the full long-term follow-up and duration of survival may take three, four or five years. Because this is an open-label trial, we will receive the results of every patient pretty much in real time. We won't necessarily disclose that. We'll typically talk about each group as we go up through the dose levels. We'll get ongoing data from the Australian trials almost from, call it month three, if you like. First patient in, 28 days to first assessment, then treat the next patient.
By about three months, we'd have the first cohort done, first results in about four months after starting. A great question on what are the key factors that will make therapies like 1901 accessible therapeutically and economically? The first requirement is that we have a step change in clinical results. These are complex therapies, as we've seen, and I haven't really talked about the complexities of actual the patient administration end either. Although most hospitals today are familiar with doing stem cell transplants, the mechanics aren't new, but the logistics are very complicated. We need to see a step change in efficacy, and that's why we're selecting products like BZDS1901, where we're going from essentially no complete responses to having a 20%+ complete response rate.
That's step number one. Step number two is having a logistics and a supply chain that works. We now have significant experience across the U.S., Europe, and Australia in administering these therapies increasingly in Japan as well. The supply chains are starting to be worked out, but it's really important that we can guarantee to physicians that every patient that cells collected, we will deliver a dose back to them. Some of the early CAR T-cell therapy products had difficulties with that, and up to 25% of patients were not getting their cells back as drug, either because the manufacturing process was too slow and they couldn't the patient progressed before the therapy was available, or the cells simply didn't expand. That's, again, why having that robust manufacturing process is so valuable early on.
Automating that is important as well. These are highly manual processes in their first incarnations, scaling that to 10,000 patients a year involves building out a facility of thousands of people that have to do the same job over and over again. Automation is key. This is why we've entered the collaboration with Ori Biotech to ensure we have access to that next generation automation technology. Then the third thing that's happening, which is transforming the CAR T-cell therapy industry, is the concept of what's called an in vivo CAR T. This is a CAR T-cell that's actually manufactured in the patient's own body. In this instance, we give the patient their own a vector, as it's called, that delivers usually a virus or an mRNA particle that we're familiar of from COVID vaccines.
That goes and finds the patient's T-cells in their own body and transforms them in the body. That is a much easier process if we can make it work. There are some enormous challenges still to be overcome there in targeting. Can the virus or the mRNA only infect T-cells? Because you certainly don't want to have certain other cell types expressing these CARs. Can you actually get enough CAR T-cells created, given the competition for the normal replenishment of T-cells in the patient's body? We're starting to see the first data come for autoimmune diseases, which will be the easiest ones. In the longer term, probably around 10 years away, we'll see that get to solid cancers. Our approach has very much been that in vivo approach is a delivery system.
It's how do you deliver the vector into the patient? For us, we're proving that the CAR construct, the design of the CAR works, getting it into the hands of patients or the veins of patients as quickly as possible so they can benefit from it before the delivery technology is available. Once people have worked out how to deliver an in vivo CAR, they're gonna be looking for payload, and we're gonna have a proven payload, which is way easier than designing one from scratch. Our strategy for in vivo CAR, which is the next generation to accessibility for these therapies, is very much have the payload available when the delivery systems are worked out. There's a question on: How does this study trial compare with the one being conducted by the Sunshine Coast University Private Hospital?
I will follow up with you on that one. I just need to check exactly what is being done in that study. All right. It looks as though we've answered all of the questions now. Just give everyone a few more minutes to put any additional questions up. All right. There being no more questions, thank you everyone for your attendance today. I hope you've left today as excited as we are about the potential of BZDS1901 and, by extrapolation, our broader strategy. We look forward to providing updates on a very regular basis on our progress to delivering this product into a very needy Australian patient population as soon as possible. Thank you very much.