Good afternoon, everybody. We'll just allow another minute for everyone to join. I'm looking forward to discussing our latest transaction with everybody. Good afternoon, everybody. My name is Tim Oldham. I'm the CEO and Managing Director of AdAlta Limited and our cellular immunotherapy subsidiary, AdCella. I'm delighted today to be sharing more details around our first and highly innovative CAR- T cell therapy for mesothelioma that we licensed at the beginning of the year. My prepared remarks will cover about 20-25 minutes, after which we'll have an opportunity for Q&A. The presentation should now be on everybody's screens. We're very, very excited to have announced at the beginning of 2026 execution of our first in-licensing deal to officially launch our East-to-West cellular immunotherapy strategy via co-development of the first-in-class CAR -T cell therapy asset, BZDS1901, from Shanghai Cell Therapy Group in China.
My remarks, of course, are subject to the usual disclaimers about forward-looking statements and a reminder of where our East-to-West cell therapy strategy fits within AdAlta's broader strategy. East-to-West cellular immunotherapy is our growth driver. It is operated through a subsidiary of AdAlta called AdCella. And the focus of the strategy is around in-licensing next-generation clinical stage CAR-T cell and related assets from Asia and westernizing those through Australia through the end of Phase I clinical data that positions those assets for partnering to larger biopharmaceutical companies. This opportunity leverages our unique skill set in AdAlta, AdCella, and Australia, together with a regional ecosystem and a unique business model that creates a win-win situation for ourselves and our partners.
Really, the objective is bridging the gap between the incredible innovation that is now happening across Asia and in China in particular in biopharmaceuticals with the companies and patients in global markets that can benefit from those therapies. Our objective is to create a series of capital-efficient, short investment-horizon assets with frequent clinical milestones. With that, I'll turn to BZDS1901 and focus the rest of our remarks on that product today, bearing in mind that we do also have other assets outside the AdCella business unit in AD-214 for fibrotic diseases and WD-34 for malaria. This slide summarizes the transaction. BZDS1901 is a next-generation CAR- T cell therapy targeting a molecule called mesothelin, which is overexpressed in multiple solid cancers. It also secretes an anti-PD-1 nanobody. This means it's secreting a molecule called a checkpoint inhibitor, which is designed to overcome immune suppression.
So we call this an armored CAR -T cell. It was developed to clinical stage by Shanghai Cell Therapy Group in China. It targets solid tumors. Lead indication is mesothelioma, best known for its association with asbestos exposure, but also lung cancers and gynecological cancers. The product has been developed through preclinical and early clinical development through investigator-initiated studies in China. And so far, it has been administered to 36 patients to date, giving us high confidence in the safety and clinical efficacy profile. The intellectual property portfolio that protects BZDS1901 comprises seven patent families in total, three related directly to the product, to which we have exclusive licenses outside of Greater China, and four others that support the proprietary manufacturing process. The second panel outlines in summary form the development roadmap. Our objective is to first establish manufacturing in an Australian-based contract manufacturing organization.
The clinical trials will be run under a U.S. Food and Drug Administration Investigational New Drug approval, and then the first global clinical trial, Phase I, will be conducted in Australia. That'll be a classic escalation and expansion study covering primarily mesothelioma, but also other solid cancers, and the objective is that at the end of that Phase I study, the next study could potentially be the last study prior to registration in mesothelioma. The collaboration will be governed by a Joint Development Committee comprising equal members of Shanghai Cell Therapy Group and AdCella. Operational support will come from AdAlta, which ensures that AdCella gets the best value and most efficient back-office project management, business development, investor relations, finance, IT, etc., support it could get.
The clinical development of this asset will continue in China through Shanghai Cell Therapy Group, and they retain the rights to the Chinese market. From an economic point of view, the budget for the overall development program is $14 million-$19 million to the completion of Phase I clinical trials in around four years' time. That includes all milestones that will be payable to Shanghai Cell Therapy Group. And so you can see that they are relatively modest, and they include provision of additional clinical data and key manufacturing components. We're leveraging the Australian advantage. So on top of that direct investment, we will benefit from around AUD 8 million-AUD 12 million of R&D tax rebate benefits, as well as being a much more cost-effective jurisdiction in which to conduct these studies relative to the U.S.
The return to both AdAlta, AdCella, and Shanghai Cell Therapy Group comes at the P hase I commercialization event. If we successfully license the product at that point, AdAlta or AdCella, I should say, will receive 60% of the proceeds of that commercialization event, so 60% of the upfront milestone, 60% of all further milestones, 60% of all royalties, and Shanghai Cell Therapy Group will receive 40%. The funding pipeline will be via third-party investment directly into AdCella. The initial tranche will be in the vicinity of $3-$5 million, and we're well underway in advanced discussions with a variety of investors across Asia and Australia in order to complete that initial tranche of financing. It's important to note that AdAlta will retain the option of co-investing with those investors to continue to increase its stake in AdCella over time.
Let's turn to the market opportunity for mesothelioma. The chart on the left shows the number of patients diagnosed incidence every year with mesothelioma. 90% or more of those will highly express the mesothelin molecule. You can see that the outcomes for these patients are terrible. Of 21,000 patients diagnosed every year in the AdCella territory, nearly 18,000 of those will die, and 13,000 will relapse. The global market for mesothelioma drugs is forecast to be over $12 billion by 2034. The 901 addressable market, we estimate at potentially $4.2 billion. This represents the relapsed refractory marketplace multiplied by the lowest current global price for CAR- T cell therapy in a Western market. You can see that the need here is significant. The current outcomes for advanced mesothelioma patients or relapsed refractory patients are very, very poor.
Response rates to second-line therapy are less than 30%, and the chances of a complete response to second-line therapy are essentially zero. Overall survival is less than nine months, so the unmet need here is significant. Importantly, for BZDS1901, the opportunities go well beyond mesothelioma, and this chart shows the percentage of a variety of other cancers that express mesothelin at high levels. For example, esophageal cancer in the top left, 35%-40% of patients will have high expression of mesothelin and therefore be a potential target for BZDS1901. Adding all of those up, we end up with a potential cancer mortality of mesothelin-positive solid cancers of 1.7 million patients a year, so a very, very significant indication extension opportunity.
One of the key features of BZDS1901. It is one of the very, very few drugs targeting mesothelin that's actually demonstrated activity in some of these other cancers, not just in mesothelioma. Let's talk about why 901 is differentiated. It's a standout opportunity to solve for those terrible unmet needs in mesothelioma. The advantages are outlined in the boxes on the top of this slide. Firstly, it's a well-established target. Mesothelin is known to be an excellent solid cancer target. It has been targeted a number of times by a number of therapeutic programs. To date, none of those have made it all the way for reasons related to lack of efficacy and/or safety, and they have been associated with the fact that it's only targeting mesothelin. What differentiates 901 is that the armoring process improves the opportunity for success significantly.
It is the first product to secrete its own PD-1 blocking molecules to overcome tumor immune suppression, and the cartoon at the bottom of this slide is designed to show the benefits that provides. In the cartoon on the left, you can see a tumor cell that not only expresses mesothelin in the triangles, but also expresses a ligand called PD-L1 that engages with PD-1 on the CAR- T cell, and that essentially is the body's own don't-eat-me signal that suppresses the activity of the CAR- T cells. By blocking this with the secreted PD-1 nanobody, that signal is turned off, and the CAR- T cell can activate and kill the tumor cell, and the consequences of that you can see on the right-hand side.
Not only do we kill the cancer and then get a whole range of additional proteins secreted that then activate existing T-cells in the body's immune system, but the PD-1 molecules can also protect what we call the endogenous T-cells. These are the T-cells that are included or that are already penetrating the tumor. And so the result of that is we have what's called a bystander effect. Not only is the CAR- T cell protected from immune suppression, but we're taking away that immune suppression for all of the other T-cells that have been infiltrating the tumor. And as you'll see shortly, that's been shown in preclinical studies to have a significant impact on the potency of this product. Now, it's fairly common to see CAR- T cell therapies that have been proven in animal models and particularly mice.
901 is differentiated because we have real clinical data in real advanced mesothelioma patients, 36 in all across three investigator-initiated trials so far, that give us confidence that responses superior to the current second line and potentially superior to everything else we see in the pipeline are possible. And importantly, we've seen these really difficult-to-achieve complete responses in a number of these patients. So 901 has got proven promise in clinical studies that, again, differentiates it from other programs. And finally, not just efficacy has to be a step change for CAR- T products to be successful, but manufacturing also requires simplicity and cost-effectiveness. And 901 addresses that with a two-day manufacturing process that does not use expensive lentiviral vectors.
We're positioned with a higher degree of confidence than a preclinical-only asset of superior clinical efficacy and a solution to the challenges of manufacturing and scalability that are so critical to the commercial adoption of CAR- T cells. Let's look at the preclinical package. In the next couple of slides, I am going to go into a little bit of science. The preclinical data that we've been provided by Shanghai Cell Therapy Group shows that the PD-1 molecule has much higher affinity and blocking power than the approved checkpoint inhibitor molecules. This means that small quantities are going to be absolutely effective at blocking the PD-1 receptor and therefore improving the activity in the tumor cells. Importantly, the mesothelin binder has only got moderate affinity, which means that it requires lots of mesothelin in order to be activating the CAR- T cell.
That's important because it preserves and protects healthy tissue that might express mesothelin at low levels. The significant benefits of secreting the PD-1 armoring have been demonstrated in preclinical studies in the top panel. You can see in chart A that the secretion of the PD-1 molecule is blocking the PD-1 expression and access in the tumor. You can see that a mesothelin-only CAR- T has negligible effect on the amount of PD-1 when you compare the hollow bar from the solid bar, whereas with the PD-1 binder, you get a significant reduction in the accessible PD-1. This means the tumor has got no access to that switch to turn off and suppress the immune system. The second panel shows that relative to a—I think we've just lost sharing. Apologies for that. Let me see if I can bring that back. Apologies for that, folks.
The second panel shows that relative to a mesothelin-only CAR- T, i.e., not armored, you get a lot more T-cells infiltrating the tumor. And so that helps with the potency of the product. And finally, on the right, you can see that in a mouse model of solid cancers, the addition of the PD-1 secretion has a marked and statistically significant improvement in the efficacy of the armored CAR- T product relative to the unarmored product. The preclinical data has also shown that we get higher in vivo expansion with the newer versions of BZDS1901 compared to the original version. And this is going to further improve potency. And so we're comparing what's called the PB transposon system, which was generation one of the products versus the current generation JL transposon system in the bottom panel.
You can see that you get much higher expansion, 3.4-fold higher expansion in panel A. You can see that it has no effect on efficacy and tumor volume in panel B and no effect on safety in panel C, and that in vivo efficacy in animals has been demonstrated in mesothelioma models, lung cancer models, and ovarian cancer models, and so an incredibly powerful preclinical package, but importantly, this has been backed up by clinical data, so the early version of the product for which we've had the longest follow-up of these patients showed more than 63% overall response rate, i.e., tumor shrinkage in patients with advanced mesothelioma, including a 9% complete response rate, and 73% of patients survived more than 12 months. These are patients that, remember, on current standard of care, half of them would survive less than nine months.
The later version of the product is still in the dose escalation phase and still hasn't completed follow-up, but at 10 times lower doses than the first-generation product, we're already seeing 42% overall response rates, including 17% complete response rates, 92% disease control rates, and we're already at a third of patients surviving greater than 12 months, and most patients haven't been followed for that long yet, so this significantly exceeds the benchmark, which you can see here, and what we're really excited about in particular is on the bottom of this chart, the two complete responses from this second-generation product, so the next steps are outlined on this page. Over the next 9-12 months, our objectives are finalizing the initial tranche of funding for AdCella. We just raised another AUD 1.2 million into AdAlta earlier this week that will enable AdAlta to contribute into that round as well.
We're expecting further dose exploration in up to seven patients under an ongoing investigator-initiated trial in China. We will complete a pre-IND meeting with the U.S. Food and Drug Administration to confirm our technology transfer program and the design of the clinical trial so that we'll go into that next steps of development knowing exactly what the FDA expects. We expect to commence any remaining non-clinical studies in that period and commence technology transfer. We're also working on adding a second product into AdCella's pipeline, which would significantly increase the value of the subsidiary and hence AdAlta's stake. And the timelines and potential news flow for those activities are outlined in the Gantt chart at the bottom of this slide. How does AdCella operate and how does AdAlta generate its return? At the moment, AdCella is a 100% owned subsidiary of AdAlta.
AdAlta has the founding shares in return for creating the entity and securing this initial license. Shanghai Cell Therapy Group have licensed BZDS1901 to us for all markets outside of Greater China. The development activities will be conducted and funded by AdCella with support from a management agreement covering project management and administration from AdAlta, for which it will pay management fees that essentially cover costs. That ensures that AdAlta continues to have its corporate costs covered and managed, and AdCella gets those services at a lower cost than it would have if it had to do it themselves. The collaboration and development of 901 itself is managed outside of Greater China by a joint development committee comprising members of AdCella and Shanghai Cell Therapy Group, and the China R&D will be conducted and funded by Shanghai Cell themselves.
The joint development committee will ensure those two R&D programs are all running in lockstep. How do we finance that development? Essentially, as I've mentioned, we are working with a number of financial investors who will invest directly into AdCella. And as soon as that first investment comes in, there will obviously be visibility to the value of those founder shares that AdAlta retains. And AdAlta will continue to have the option to invest alongside or co-invest alongside those financial investors. And then from a return on that investment, the commercialization or exit opportunities come for the product itself through sublicensing that for Phase II development and beyond to larger pharmaceutical and biotech companies. And as I mentioned, 60% of the proceeds of that deal flow back to AdCella and 40% flow back to Shanghai Cell Therapy Group.
There's also the potential in the long run for a trade sale or other listing of AdCella. And to give us an idea of what that transaction may be worth at the end of Phase I, comparative transactions for autologous T-cell therapies, and in general, these are for smaller indications, over the last five years show an upfront value of around $85 million and a total deal value in the vicinity of $782 million. Importantly, is there a market for these? 72% or 18% of the top 25 oncology pharma companies have invested in an autologous cell therapy in the last five years. We also know there's a rise of in vivo CAR- T cell therapy is getting a lot of attention at the moment where you avoid the need for patient-specific manufacturing. We anticipate that that's probably 10 years away for solid cancers at this point.
But once those delivery systems are proven, they will be looking for payloads. And the opportunity to then translate the 901 CAR construct into an in vivo delivery system gives us additional exit opportunities. So turning now to how does this fit within our overall business model. As I mentioned upfront, there's a really rich pool of innovation in CAR- T cell therapies across Asia-Pacific. 61% of global CAR- T trials are happening in this region. Within China alone, there are 970 clinical trials and 350 cellular immunotherapy companies. We identify and screen the market for those that meet our selection criteria, which essentially is highly differentiated solid tumors with clinical data. Our licensing model is a low-cost upfront payment. We're investing the $15 million USD per asset over three to four years, essentially to advance the value of the asset.
Our partner is deferring their return as a result, but they're also getting the asset advanced into global Phase I trials essentially at no cost to themselves. The program is around 12 to 18 months of tech transfer and then about two years to two and a half years of clinical trials before we achieve that high-value-out licensing event that we spoke about on the previous page. So what does this mean for all of our stakeholders? For our in-licensing partners, Shanghai Cell Therapy Group in this case, they're getting their asset financed into global ex-China clinical trials at no cost to themselves. At the end of the process, the asset will have enhanced partnerability. It'll have demonstrated clinical proof of concept in a more diverse patient population and with the U.S. FDA seal of approval.
And it will have manufacturing scalability and portability proof of concept because of the work we'll have done with our contract manufacturing partners, which means that we are offering them essentially turnkey execution of global expansion. For our ultimate customers, our out-licensing partners, they'll be getting, assuming success in Phase I, a first-in-class asset with demonstrated superiority over other modalities, an asset that's ready for pivotal registrational studies, and an asset that we've already demonstrated can be migrated onto their manufacturing platform and their manufacturing network, whatever that might be. It's a much lower-risk transaction than if they were taking on that transaction now. And then for our shareholders, firstly, for the AdCella shareholders, but also for the AdAlta shareholders, we've got de-risk exposure to a novel asset class. We've got rapid capital recycling. It goes three to four years per project to an exit.
It's capital efficient in the sense that we're not paying a lot of money upfront to acquire IP that's sunk cost. Everything's going into developing the value of the asset, and it's stage-gated along the way with substantial value creation potential along the way. For our AdAlta shareholders, we're essentially getting that as carried interest through our founder shareholding. Our team that we're assembling is deeply experienced across the cell and gene therapy and oncology space, particularly with our strategic partners, Cell Therapies and Dark Horse Consulting. Our Consultant Chief Medical Officer, Kevin Lynch, has worked in oncology across Amgen in China, Celgene, and Novartis for many years. We're in the process of hiring a China-based director for AdCella and a head of Asia operations for AdCella as well. In summary, we have reached the starting point of our east-west cellular immunotherapy strategy.
We've officially launched the business now. We think this is a significant opportunity to create a regional powerhouse in this incredibly powerful new cancer modality. And we're looking forward to providing updates not just on this program, but on the future programs and financing in the very near future. My contact details are on the screen here and are available for anyone to reach out to me afterwards. So we'll now turn to the Q&A part of the program today. Thank you for those who've already asked questions. I'll address those as we go, but feel free to add those through the chat function at the bottom of your screens.
The first question we received in advance was whether investigator-initiated trials in China are the same as Phase I, II, III trials elsewhere, and what's the really comparable phase of development that the Shanghai Cell Therapy Group have achieved for this asset. Investigator-initiated trials are not company-sponsored. The sponsor, and therefore the person carrying the legal liability for these trials, is a clinical researcher in a hospital. In that sense, they don't fall into the classic Phase I, II, III clinical trial classification, and they are not a substitute for a Phase I clinical trial. They're probably best thought about as a Phase zero trial, although in the case of Shanghai Cell Therapy Group, they've essentially completed a large part of what a Phase I trial would look like. The difference with a formal Phase I trial is we'll have tighter recruitment and patient selection criteria.
We will have tighter management of adverse events, and we'll have more robust and consistent data collection across all patients. What we can think about is that the Phase I clinical trial that we are planning to conduct in Australia is essentially going to replicate and extend a program that has already been run in China. In that sense, we believe it has much higher probability of success than if we were relying on an initial Phase I trial from a study based purely on animal mouse data. The second question we've received is, could you explain the dispute and resolution process between AdAlta, AdCella, and Shanghai Cell Therapy Group? Good question. Essentially, there is a defined charter of responsibilities for the joint development committee.
Ultimately, we have to make unanimous decisions around the design of a clinical trial, the selection of a contract manufacturing organization, and the interpretation of results. In the event that we can't agree, there are standard escalation mechanisms to senior leaders in both companies. There is then a process for discussing and bringing in scientific experts on technical questions, or there's an arbitration mechanism in Singapore in the event that it gets really terribly bad. But it's really important from the point of view of AdCella having multiple products in its pipeline in the long run that each partner feels that their asset is being treated fairly and equitably with everybody else. That's why this equal membership joint development committee is a really important mechanism. We've been working very closely with them, obviously, through the due diligence process over almost 12 months now.
And so we feel as though we understand the rapport, we understand the differences of where everyone's coming from. But ultimately, we have a written mechanism in the contract to ensure that anything we can't agree on is dealt with by a defined process. And the incentives are for us to actually reach an agreement within the joint development committee. Question, what percentage of AdCella will AdAlta own post the private funding round in AdCella? We can't answer that question right now because we're still in negotiations on the final pricing of that round. What we can say is we expect after the initial round, even at the top end, that AdAlta will own well over half AdCella and potentially higher.
And that if investors wanted to look at what the pre-money value of AdCella looks like, take those deal comparators at the end of Phase I, make some assumptions around the timing of the future milestones, discount back four years, multiply by 50% success rate of a Phase I clinical trial, which obviously we think will do better. And then you'll have a fair and then deduct, I guess, the value or the cost of exercising the option, the $15 million, and you'll get a reasonable idea of where the deal value could come. As soon as we get that first financing completed, we'll be able to make an announcement in relation to that and that that value will become transparent. There's a question that says, are the R&D rebates of AUD 8-12 million used to offset the Phase I CapEx, the AUD 14-19 million?
I.e., what's the actual number we'll have to raise from investors? We will raise AUD 14-19 million from investors. The total cost of the program is between AUD 22 and 31 million. Deducting off the AUD 8-12 million of R&D tax benefits gives us the AUD 14-19 million budget. Can Phase I in Australia be fast-tracked due to the Chinese data? Yes and no. No in the sense that we will still need to do a classic dose escalation exercise. We've had a number of potential investors who've looked at this business model before and tried to go from formal Phase I in China to Phase I in the U.S., and the FDA has said that's not possible. They want to see that full characterization on the way through. But what it does mean is that, firstly, that Phase I trial is significantly de-risked.
We already know how to manage adverse events such as they are. And we'll probably be able to start at a higher starting dose than we would have otherwise been able to because of the Chinese experience. So that creates efficiencies in cost and timeline of that Phase I trial in Australia. Okay, that appears to be all the questions we have right now. I'll just leave the chat open for a couple more moments. One more has just come in. What's the timing on the close of the private funding round? So as you'll have seen in ASX release on the 2nd of January, we're expected to be able to commit a minimum of $3 million to the collaboration within 70 days of signing. So that gives you a window on when we need at least a first close on that initial funding round.
We anticipate being earlier than that, but that's the sort of drop-dead timeframe, if you like. Well, fantastic, everybody. Thank you so much for your attendance today. I really enjoyed talking to you. I've really enjoyed being able to bring this really exciting development for AdAlta and AdCella to you. We have believed for some time in the opportunity and the importance of innovation in China and the opportunity to bring some of that incredible technology to global patients. And I'm really proud that we're going to be able to bring and enable Australian patients to get first access to this incredible therapeutic option for an indication where patients really have very, very poor prognosis and outcomes. And so we have launched AdCella. We have an incredible asset to begin with.
In fact, I couldn't have described a more perfect asset in terms of its highly differentiated and engineered beyond just a standard CAR-T. It's got a short, cheap manufacturing process, and it has got existing compelling clinical data demonstrating efficacy. So it's a great way to start this business unit, and we're really looking forward to sharing the updates with you as we progress in the coming weeks and months. Thank you for joining us. We'll speak to you again soon.