Function within Zoom. Appearing on behalf of Arovella today, we have the CEO and Managing Director, Dr. Michael Baker. To begin, I'll hand it over to Michael. Please go ahead.
Wonderful. Thank you, Matt. Thanks for putting this on for us, and a big thank you to everybody for taking the time to dial in. We appreciate your time, and I am looking forward to giving you an update on where things are at at Arovella. For those of you that know the story well, bear with me. I'll go over some things that are important, but for those of you that are new to the story, we're very much looking forward to taking our lead program, ALA-101, which is an invariant natural killer T-cell product, into clinic this year. I'll just jump straight in. Please do note the disclaimer. I will be making forward-looking statements. Let me quickly start with the strengths or highlights of the company as we see it.
Very clearly, what I have just mentioned a moment ago, we work on our invariant natural killer T-cell platform, and we shorten that for simplicity to iNKT. That is an immune cell that we are developing to target initially blood cancers, but looking to rapidly progress to utilize the same platform also to target solid tumors. We are very comfortable that the cell therapy sector is a very important pillar for cancer treatment broadly, but we just see that the original generational version has a number of challenges that we think hamper the sector, and we believe our iNKT cells go a long way to solving some of those challenges. As a company, we have built the platform to date using a strategic acquisition model where we find, license the best IP that we can globally.
We will continue to take this lens, looking for IP that feeds into our platform, either strengthening it or broadening its use in different cancers, but even potentially in different indications as well. Now, in terms of our team, it's an exceptional group of people, both at board level and management level, with a lot of experience across drug development broadly, but specifically also within cell therapies, which is quite important. We're delighted that we now have a clinic-ready manufacturing process, a proprietary clinic-ready manufacturing process to produce CAR-iNKT cells. As I said earlier, we're very excited about our lead product, ALA-101, which is being developed for CD19-positive blood cancers like lymphoma and leukemia, is progressing to phase I, and we're expecting that to start in 2025. As I said, I just want to talk a little bit about CAR-T-cells.
For some of you that are less familiar, this won't be a deep dive, but certainly just to give an overview on how this broadly works. I'll start here with the version as it stands, which is now in seven currently approved blood cancer products. Essentially, a patient in this case would present with a particular form of blood cancer, lymphoma, leukemia, multiple myeloma, and blood is actually taken from that patient and collected T-cells, specifically little soldiers in the immune system that will naturally survey and eliminate things that don't belong, even cancer cells in some cases. Those T-cells are shipped off to a lab where they're genetically reprogrammed to introduce what we call a chimeric antigen receptor, or CAR for short, and that's the little blue and red bump there.
Now, for those of you that are less familiar, think about that as a homing missile that essentially would tell the immune cell, drag it towards the cancer cells and trigger their destruction. Once they've done that, those cells get grown up into the millions, and then they get infused back into that patient where once they find the particular marker on those cancer cells here highlighted in green, they're able to bind and then trigger to cause destruction of those cancer cells. What we've seen already is it's been a very effective modality for blood cancer specifically. We are now using the word cure for these particular cancers, and not surprisingly, we've already seen pretty strong sales for some of the products that are now approved. One of those, which was approved in 2017, is YESCARTA, and that's done over $1.5 billion in sales in 2024.
Now, it's important to note here, though, that like all therapeutic strategies in oncology, it's not perfect, and we do still see that there's a fairly high failure rate or relapse rate at about 40-60%. On a range of fronts, we do need to do better. Again, I think the major take home here for us is CAR-T does still have limitations. I mentioned it a moment ago that we actually start with the patient, their blood, and we manufacture the product, and that goes back to the patient. What that means is, in essence, every dose of CAR-T is made using the patient's raw material for that specific patient. It's made just in time every single time. What that does is it drives up the cost, largely because it's such a complicated manufacturing process and supply chain.
We see for blood cancer products, it's about $500,000 U.S. per dose. For solid tumor programs, it's in the order of about $750,000 for a slightly different version, a TCR-T program. Now, importantly, if we're taking the raw material from the patient, so it's the blood and the immune cells, these patients have already seen cancer. They have already seen usually pretty nasty treatments like chemotherapy, radiotherapy, and so forth. The T-cells aren't doing that well, which means that we're actually working from a substandard raw material. As I said, we plan to go around that by using an off-the-shelf approach. Not all treatment centers can actually do this, which means that patients could be eligible to take the therapy. They actually won't get access to it because it just can't be performed at particular centers.
Now, it takes in essence about three to six weeks for this therapy to be manufactured. It is an issue in terms of patients with aggressive disease because they can actually succumb to the disease while it is actually being manufactured. Because you're making it every time for every patient, there's always the risk of a manufacturing run failure. That just feeds back into adding into the complexity and the costs for this therapy. Arovella's solution is quite simple in its genesis. We simply replace the T-cell. We don't use a T-cell. We use an invariant natural killer T-cell. The idea being that we can actually take those immune cells from a healthy donor, and then we're able to manufacture them as we would for CAR-T. Same genetic engineering, but we're able to give them to many different patients after being manufactured.
The idea is that they'll be sitting in a freezer. If a patient is eligible, they will be able to get access to that within a week, let's say. Again, simplifying the procedure and reducing the complexity. Now, the way we're able to do that, it's not through us inventing the invariant natural killer T-cell. We've just worked out how to manufacture them at a suitable scale to be able to use them in this particular capacity. Here's just a snapshot of some immune cells that have been worked on. T-cells by far have been the most well-studied. Natural killer cells also for a little while were heavily studied as well and continue to be studied in the same fashion. For us, as I said, it's the invariant natural killer T-cells that we care about most.
Now, the reason being largely is that we can freely give iNKT cells from one human to another. This has now been shown in clinical trials, not by us, but by others, because they do not cause graft-versus-host disease. We are very comfortable that they will be able to be given freely from one person to another. Importantly for us, they are also considered the front line of the human immune system. They have a natural role in immune surveillance, and they constitute what we call the innate immune pathway or our fast-acting immune response. They also constitute part of the adaptive immunity, which is our longer-term response. These are both important arms of our immune system, and we are glad that they feed into both. They can kill like a T-cell. They also can kill like an NK cell.
Through this little red claw here, the invariant T-cell receptor, they can actually naturally target and kill cancers already. There are a number of other anti-cancer properties, and I'll just show them here in diagrammatic form, which is a little bit easier. We have here our CAR-iNKT cell in blue in the middle. We'd have a cancer cell up here in gray. When we have the CAR that recognizes the target on the cancer cell, we can have killing. iNKT cells also have something on their surface, which is called NKG2D. If the tumor cells are also positive for NKG2DL, we get killing. As I mentioned, invariant natural killer T-cells have an invariant T-cell receptor. If CD1d with a glycolipid is found on that cancer cell, we also get killing. Importantly, though, it's not just the direct killing that is of interest for us.
It's the ability for iNKT cells also to block and kill things like tumor-associated macrophages, myeloid-derived suppressor cells that naturally have been essentially hijacked by the cancer cells to start helping them exclude immune components and essentially support their evasion. In addition, iNKT cells can also cross-prime or activate other T-cells and natural killer cells to start joining in the fight against the cancer cells. Some of this has been shown in different studies over the last few years or so, but there's a very nice paper in Nature Cancer, which is one of the best journals one can publish their studies in. It tied all this together using a very elegant model, directly comparing natural killer T-cells to CAR-T, demonstrating both the ability to block these immune cells or cross-prime other immune cells, but also that they have superior anti-tumor activity to CAR-T.
Specifically, in this case, they tested that in solid tumors. A very nice paper and very supportive of Arovella's development efforts. In terms of the competitive landscape, we know that, as I said, there's a number of T-cell players still working on T-cell programs. Natural killer cell companies are also working on natural killer cell programs. When we look still at the invariant natural killer T-cell landscape, it is still tiny. There's only a handful of companies working in this particular niche area. We're delighted that we are in cell therapy, which we still consider to be a very important arm in oncology treatment, but we're delighted that we're in that niche area. I think we're also doing a wonderful job to be probably being considered one of the leaders within this small group of players, which is excellent.
In terms of our iNKT cell strategy, how do we do this? As I said, we license IP from all over the world. We have licensed our CAR-iNKT cell manufacturing platform from Imperial College London. We have also incorporated an armoring technology, and we licensed that from the University of North Carolina. We also entered into a research agreement with them quite recently. We are always looking for novel CARs where these unlock the ability for us to target different tumor types. For example, our CLDN18.2 CAR that we've now provided an update on, we licensed from Sparks, would enable us to target things like gastric cancer and pancreatic cancer. We overlay that with regulatory strategy.
These are a range of different programs, pathways that exist to enable companies to get exclusivity after approval or to also fast-track their ability to get drugs into clinic and through clinical trials, which is always the goal of getting these into the hands of patients that need them. Of course, know-how. For those of you that are familiar with the development of a cell therapy, it's now often utilized that the manufacturing process is the product. All that we've learned over the last couple of years developing the manufacturing process, while that might not sit in the form, every bit of it might sit in the form of granted patents, it does constitute important know-how and trade secret that becomes the property of Arovella.
Once we've got all our ducks in a row in terms of the intellectual property and the programs, how do we actually get these into patients? The idea is we have an acquisition event that we license the technology. We either have or we generate preclinical information that supports the development of the program. Here we generate one more raw material, I should say, a lentivirus, which is how we actually get the missile or CAR into the cells. That feeds into our manufacturing process, which is highlighted here in purple. Once we have the manufacturing for that program completed and we've performed the necessary IND- enabling studies, we're then able to package all of that up into a document called an IND that gets submitted to the FDA.
Once that's accepted, then we're in a position where we're able to start phase I clinical trials. For ALA-101, as I said, we're expecting that to be 2025, which is quite exciting for the company. What we've highlighted, the manufacturing here in purple, is that we've essentially, once this has been done for one program, it's now in good shape for the remaining programs. It doesn't mean that there will be no tweaks or enhancements or modifications, but it does mean broadly it would stay the same. We don't need to repeat a lot of the work that we've had to do for ALA-101. For example, for CLDN18.2, we've acquired the technology. As I said, I'll provide a small update here on the preclinical information that we've been generating.
Once we're happy with that, that's when we generate the lentivirus, which would feed into the manufacturing to do the studies to file our IND to start phase I. For any other CAR that we bring in, we'll essentially use the same manufacturing process. Very important that this work is now in good shape and delighted with where it stands today. Over the quarter, we had a pretty eventful quarter. I'm pleased to say that a lot of positives for the quarter. We completed an AUD 15 million placement, and that now provides us with funding to fully enroll the phase I study for ALA-101 and generate and report initial safety and efficacy data. We successfully transferred ALA-101 manufacturing process into the GMP environment, which now is in readiness for the production of the clinical batches.
In line with ALA-101, we also held our first clinical advisory board meeting, which now feeds into our clinical trial protocol design, which I'll touch on. We entered into a sponsored research agreement with the University of North Carolina to advance our solid tumor programs that will incorporate IL-12-TM armoring. We did generate functional CLDN18.2, a functional CLDN18.2 chimeric antigen receptor, which we tested in T-cells. Good progress for the quarter, and I'll touch on some of these as we move through. Just starting with ALA-101, I think this is our primary focus. This is the program that's closest to clinic, which we're aiming to do in 2025.
The way we do that, the way we get there, I think this is a good roadmap where we have already excellent KOL engagement, and that's now seen through the assembly of our clinical advisory board. GMP manufacturing is ongoing. As I said, we need to have the GMP batches produced to complete the final IND- enabling studies, which all of that work gets written up into our IND. Once that's written up, we submit that to the FDA, which enables us to get regulatory approval for the commencement of phase I clinical trials and ultimately leading to the first patient being dosed. In parallel with that, we also engage with and would onboard clinical trial sites. We're also in the process of selecting our clinical research organization who would essentially act as our partner to help manage the study.
Let me just touch on the manufacturing progress that we made over the quarter. Just as a reminder, the way this works for us is we collect blood from a healthy donor. We then isolate the iNKT cells from that donor. We have our raw material, the lentivirus that we use to essentially bring the CAR into the iNKT cells. They are expanded. We grow them into the billions, and then they ultimately get stored in vials and frozen. They are stored away at very cold temperatures, ready for use. We made good progress progressing the tech transfer into the GMP suites. I'm pleased to say that all what we call, and that's good manufacturing practice, all GMP inputs have now been acquired and tested.
We've managed to complete runs using all those GMP materials and GMP suites at a scale sufficient for phase I. As I said, importantly, all the little tweaks and modifications that we've learned over that journey become Arovella trade secret and IP, and they will be useful for future programs that we work on. We're currently completing the clinical batches to support IND filing and ultimately would be used in phase I clinical studies. Now, just a little bit more on the IND- enabling studies. As I said, this has been a good development over the quarter. We tested the ALA-101 that was manufactured using our clinic-ready manufacturing process. This is a long way away from where we started with research-grade material that was produced in a research environment at ICL . We incorporated this into a Raji lymphoma model.
The tumor cell has CD19 on its surface. Just to point out, this is a very aggressive lymphoma model, and it does not express CD1d, which is one of those targets of iNKT cells. This is a more difficult model for the iNKT cells to treat. We treat only two groups in this case, phosphate- buffered saline, which is essentially salt water, so it's vehicle or placebo. Then we use ALA-101, the cells manufactured using our process. We administer the tumor cells, they engraft, then we treat them with the particular therapeutic intervention. Some of you will have seen these curves. It's a survival curve where, in this case, we look at 28 days. We are looking for how many animals survive over that particular time period.
As the lines drop down, that means the animals are succumbing to the disease. Quite clearly, you can see here in the salt water samples that they all die at around the 17-day mark or by the 17-day mark. Whereas for the ALA-101 group, we're seeing 70% alive at the 28-day mark. This constitutes a highly significant extension of lifespan. Again, we're delighted that we're seeing that level of survival with the material that's being manufactured using our process at scale, which is great. Importantly, we also check in the blood, bone marrow, and brain, and we're able to detect CAR-iNKT cells at this time point as well, which is nice. In terms of now moving into our clinical capabilities, we've been preparing quite a lot already for the first in human phase I clinical study.
Delighted that we've recently appointed Jacqui Cumming as Senior Director of Clinical Development. She's got an exceptional background in clinical development and clinical operations and experience more recently at the Peter MacCallum Cancer Centre working on cell therapy trials. Also previously at CSL in clinical roles and also on the CRO side at IQVIA and PPD. A terrific level of experience both within company and within the CRO, which will be immensely helpful for Arovella as we continue to move forward. Over the quarter, we continue to have engagement with potential sites and I'm pleased that we are getting good feedback and excellent interest around the sites that we would like to be participating in the clinical trial. As I said, we're in the process of selecting our clinical CRO, which we expect to do in the short term, and we'll update on that.
We will also finalize the clinical trial protocol based on the feedback that we've had from our clinical advisory board, which was only quite recently. Just to touch on that again, just putting that in context, the clinical advisory board is a group of people that we utilize essentially to shape our clinical development plans and our protocol. I'm pleased that our board is absolutely world-class with a very deep amount of experience in not just early stage, but also late-stage cell therapy trials. Dr. Sam Fiorenza chairs that board. He's now in Melbourne, but he'd spent time at the Fred Hutchinson Cancer Center in the U.S., sorry, at Seattle Children's. Debora Barton, who's also on our board, has spent time as the CMO of at least two cell therapy companies working on both early-stage and late-stage CAR-T programs.
Professor Sattva Neelapu , who was the lead investigator for the phase II study for YESCARTA. I mentioned that one a moment ago that generated $1.5 billion in revenue in 2024. He was the lead investigator for that study that led to its approval. Taking all the feedback that they provide to us and incorporating that into our clinical protocol design is immensely helpful. Let me just touch on that. What does that clinical, what will that phase one clinical study look like? It is a dose escalation and dose expansion study in patients with CD19-positive blood cancers. This will be patients, as I said, where we either have lymphoma or leukemia.
The idea is we have a single dose of ALA-101, and that would be following what we call lymphodepletion, which is essentially preparing the patient's immune cells or immune system to receive the therapy. As always, for a phase I study, despite the fact that this will be done in patients, the primary objective will be to evaluate safety and tolerability of ALA-101 in these particular patients. Naturally, because it is in patients, we do have some important secondary objectives. The first being, we'd like to determine the most appropriate dose of ALA-101 to take into later stage, say, phase II clinical trials.
We also will have a keen eye to look at the preliminary efficacy that we see for ALA-101 in these studies and also to characterize what we call the pharmacokinetic or PK profile, which is looking at where the cells go, how they behave once they've been administered into the patients. There are two parts to the study. The first part is what we refer to as dose escalation. We start here at a lower dose, and then we work our way up to higher doses. That is provided we do not see any safety issues, which we do not expect to. We expect overall that part of the phase one study to have about nine to 12 patients.
For part two, once we've found a dose that we're happy with, where we see good levels of activity but no safety issues, we have dose expansion. That is then taking patients either in particular subtypes of lymphoma or leukemia, and we expand the number of patients treated at that particular dose. We'd expect that to end up being about 20 patients total. All up, we'd expect the phase one study to have around the 30-32 patient mark. As I said, we've made good progress over the quarter on a range of fronts. We'd already, I think, made good progress at least on the KOL engagement and clinical trial design, but very happy that we've now completed runs in the GMP suites using the GMP reagents.
Very happy that the in vivo animal model pre-IND-enabling study has been completed, and we're working through some of the remaining studies. Of course, this all feeds into our IND document, which we're intending to submit to the FDA in Q2, calendar year, and of course, then getting regulatory approval for startup and getting the phase I study going. As I said, also, we're going to make progress in the short term around the selection of our clinical research organization and continue to prioritize working and engaging with the sites that we'd like to have involved in the study. I'll just switch gears briefly so I can provide the context on our recent updates for our CLDN18.2 targeting program. Now, just for context, I think many of you may know this already, but 90% of every newly diagnosed cancer will be some form of solid tumor.
Already, we know that there's a huge unmet need here. Also out of that, there's a very large commercial opportunity that exists for the right programs. Importantly for Arovella, we also know there are a number of properties for iNKT cells that we think set them up to be very useful in the context of solid tumors. We do have a fairly aggressive strategy to expand into this space. There are three major arms to that. The first is to license novel cancer targets. Again, when we think about the iNKT cells and we have different CARs or missiles, that gives us the ability to target a different cancer type. We're also working to incorporate our armory strategies to give the cells a bit of an extra boost when thinking about using them for solid tumors.
We are also still working at evaluating potential partnerships with groups where we think that there's the opportunity for combination products to have synergistic effects. They not just work additively with each other, but they genuinely work better than each individual drug on their own. When we think about solid tumors, I think this is, again, important to point out conceptually. It is quite different. They are quite different to a blood cancer setting. I'd certainly never say that a blood cancer is an easy bar in terms of treatment. Naturally, I think one can appreciate that if things are in solution, the cancer cells as well as the immune cells, that there's a higher incidence that they're able to engage with each other, which enables the immune cells to find and eliminate the cancerous B- cells in this case.
When we think about a solid tumor, I think, again, synonymous, most people probably use the word lump or know about that word. That essentially is the result of a whole host of things working to surround the cancer cells to protect them from our immune surveillance and help them and support their growth. Certainly a much higher bar. Why, again, we think iNKT cells are well positioned is we know they naturally harm tissues. They have been shown to infiltrate tumors. Even to the point where in some studies, they have been prognostic. If patients have low levels of iNKT cells, their outcomes are worse than patients with higher levels of iNKT cells.
As I mentioned earlier, we know that they can start to block or kill these other immune cells, which normally would help us, but have been hijacked and become part of that tumor microenvironment. They can block and kill them, which we think will help start to shape the tumor microenvironment and may provide better access and also bring in components of the natural immune system to start eliminating the cancer cells. In terms of adding new CARs into our programs, I'll just reiterate the manufacturing process. We collect blood from a helper donor. We isolate the cells. It is this step here where we integrate what we call nucleic acid or DNA into the cells, which helps us to produce the CARs. We can change the lentivirus or the nucleic acid sequence here, which enables us to put in a different CAR, which targets a different cancer.
The steps largely stay the same. It's just this raw material that we feed in that would change. We have the ability to grow them up as we normally would, vial and freeze them. We have a new program targeting a different cancer type. We have selected CLDN18.2 as a target that we think is quite fascinating and interesting to go after. It is now a widely expressed target in things like gastric, gastroesophageal, pancreatic, some lung, some ovarian cancer types. With the approval of the first monoclonal antibody last year in Japan and the U.S., we also know that it's a validated target. We are excited that we've got the potential to use this program in conjunction with the cell therapy, which we think has got an exciting chance at tackling some of these pretty nasty cancer types.
Naturally, the gastric cancer market is quite large. That is not surprising. Just some quick numbers here, which I will not go through in detail, but with almost 1 million cases per annum of gastric cancer, 500,000 cases of pancreatic cancer each year, and really dismal survival rates between 6-33% for regional and distant here for gastric and 3-15% for pancreatic. There really is not a lot of treatment options for these groups of individuals. We see that as a really important opportunity for our iNKT cells to go after. How do we actually do this? What a monoclonal antibody would look like in a diagrammatic form is something like this. This is the sequence we licensed from Sparks. The area of interest for us is the area in this little green square.
That is the portion of a monoclonal antibody that knows how to find CLDN18.2. What we actually do is we take that portion, and then we graft it onto the CAR here, where that is fused now to all these different components that will tell an immune cell like a T cell or an iNKT cell to turn on. When this then recognizes CLDN18.2, that is when the CAR will tell the immune cell to start killing. We have already tested the CAR. We have produced the CAR and tested that in T cells, and we are pleased with the data that we are generating. The next step is now to incorporate that CAR into our iNKT cells and test that and see how that is functioning as well. Just on that data for the CLDN18.2 targeting CAR, as I said, we have now successfully made that using the SPX- 101 sequence.
What we've done is compared our CLDN18.2 targeting CAR to what we call a control CAR, which we would expect to have robust killing for cells that have CLDN18.2 on their surface. We've compared both when we have cells that have CLDN18.2 sticking out on their outside. What we're looking at on the curve here is a very small time frame. We're going out from two hours to eight hours. What we're looking at on the vertical axis here is how many of the cells as a proportion, so as a percentage, have been killed in that short time frame. In the control group, we see that there's quite good killing.
Importantly, for Arovella's new CAR in the light blue, we're seeing great killing at around the eight-hour mark of somewhere around the 70% elimination of those cells, which is great. We're very happy. I should say that's all in comparison to a T cell here that does not have a CAR at all, which do not demonstrate killing. We're pleased with the fact that we've got this CAR. Our key goal in the short term is to take that CAR and incorporate it into our iNKT cells. Once we've done that, we've assessed its performance. We'll optimize it for activity in solid tumors or in the solid tumor microenvironment and also integrate our IL-12-TM armoring, which we expect to enhance the activity of the CAR-iNKT cells. We're pleased with the update for the quarter. This is our pipeline.
It's still developing, and we're pleased with where the program sit. ALA-101 for CD19-positive blood cancers will be aiming to get our IND filed this quarter and start phase I in 2025. ALA-105, as I said, we're just now happy that we've updated on the generation of the CAR and looking forward to getting that into our iNKT cells. For IL-12-TM, as I said, we'll feed that into our solid tumor programs as they develop as well. We do have a very busy end of the year planned. Naturally, for ALA-101, this is going to be the key focus for us. Completion of manufacturing of the clinical batches, completion of the IND-enabling studies, and finally, the IND application with the FDA are two of the major goals for us in the short term.
All of that would precipitate getting an IND accepted, which would enable us to commence the phase I first in human study for ALA-101, which we find tremendously exciting for the company. Of course, excited that we'd be in a position then to generate initial data from patients in those early dose cohorts. Just reiterating, thank you to the investors that participated in that recent capital raise. We are now funded to obtain preliminary efficacy readouts, safety and efficacy readouts for that study, which sets us up to be in a great position to do that. Now, for ALA-105, as I said, we're just now, we're comfortable that we've generated a functional CAR. The key is to integrate that into our iNKT cells, assess the functionality, and optimize that for solid tumors.
Again, looking forward to generating animal data once we've got that CAR-iNKT cells. We've used gastric cancer and also probably pancreatic cancer models to demonstrate the activity of that. Once we're happy with how that's functioning, that would kick off the formal manufacturing activities, like getting things like the lentivirus ready and then putting that into our manufacturing process. As I noted, IL-12-TM will be integrating into the ALA-105 or CLDN18.2 program.
Something I have not had a lot of time to discuss today is the fact that we will continue to be pretty aggressive at looking at identifying and acquiring novel technologies that we think either, A, feed into our platform and enhance its ability to eliminate cancer cells, and also looking to find new CARs where we think that they have got a very strong chance of having benefit in patients with particular cancer types. We will look forward to updating on those activities in due course as well. Just to summarize, I think we have got a really exciting platform. iNKT cells have a number of anti-cancer properties that other immune cells do not. Delighted that we have now a proprietary clinic-ready manufacturing process to produce CAR-iNKT cells. Very excited that we are going to be taking ALA-101 into clinical trials quite soon.
Happy with where the platform sits, and we will continue to expand, I think, over and above what we've got, but very excited to be developing our CLDN18.2 program and our IL-12-TM armoring. Just as I said, and I've said it before, I think for all these reasons, the fact that we are still the only company in Australia working on iNKT cells and one of few globally, we do see that we continue to be well positioned for success. With that, I'd just like to say thank you again, Matt, for organizing the webinar. Of course, big thank you to all the shareholders that have taken the time to dial in. We really appreciate it, and I'd be absolutely delighted to take any questions.
Thanks, Michael. As you mentioned, we'll move on to the Q&A.
If anyone has any questions that they'd like to submit, please feel free to do so using the Q&A panel within Zoom. We've already got quite a few to get through, so we'll jump into it. Michael, the first question is just a broader one with everything going on externally with regards to the FDA, etc. Do you have anything to worry about on that front?
Yeah, it's a good question, Matt. Look, the answer is, I'd say not yet. I don't think we have seen enough in terms of impact, and particularly where we sit in the IND-enabling stage and IND submission stage. We have heard anecdotally that potentially things like accelerated approvals and other programs may have been delayed in their review period, but we haven't heard anything for IND submissions review periods to date.
I do not think it is something we can worry about just yet. Whether or not the effects of cuts to the FDA through what has been going on in the U.S. will actually impact this year or next year, we still do not have good line of sight on that, Matt. It is probably best just to continue as planned and just get on with our development efforts and get things completed and filed.
Thank you. In addition to that, another hot topic has just been the market volatility recently. I guess with regards to your cash position, etc., how do you feel your place there? Are you worried about the ability to raise money given that volatility?
Yeah, look, I think it is not lost on us, right?
That it's been a pretty difficult few months, I think, with everything that's going on around tariffs and movements in markets and so forth. I think, as I said, we finished the quarter with AUD 23.5 million. We're in really good shape financially. I don't think we have to worry about raising capital for quite some time, which is excellent. I'd expect that there's multiple readouts, both for ALA-101 and also for other programs that would come well before we need to raise capital. I think we raised capital at a good time and happy that we've got the cash in the bank.
Thank you. Next question is, are you looking at other or new technologies? And can you provide an update on developments in this regard?
Yeah, look, it's always a bit hard to provide updates because they usually pop out when they're done and deals are done. All I can say is that we are actively screening the globe still for new CARs, strategies to enhance the cells. That won't stop. The reason being, I think, is as we look to move into potentially different indications, making sure that we're building the right products to target those indications is very important. Despite the fact that it is a pretty nasty market, it does mean, unfortunately, for companies that they may not have the requisite funds, but there are certainly opportunities for technologies to be brought in. We'll absolutely explore those.
Thank you. Have all clinical and non-clinical IND-enabling studies now been completed?
Yeah.
As I said, we aim to submit our IND in Q2 calendar year. We are working through the completion of those studies at the moment. As I said, very pleased with the progress in terms of the manufacturing, the GMP suites, completion of the in vivo animal model. There are a few more things to complete, but I think we are in good shape.
The next question is, are we still looking to receive platform designation from the FDA?
Yeah, good question, actually. That is something that came out, I think it was late last year. Yes, is the short answer. The reality is to get access to the platform designation, one does actually need to have a product approved or a BLA accepted. That is some way off for us.
Naturally, we'd like to explore that program as and when we can because we do see that there's a lot of pieces for our manufacturing process that we'd utilize over and over again for different programs. When the timing is right, we would like to explore those programs for sure.
Thank you. A couple of questions here were just in regards to the interview you recently did with Tim Boreham on Stockhead. The first question in regards to that is, do we have all of the Australian approvals in place to start dose escalation in Australia before we move into dose expansion in the U.S.?
Yeah. Okay. Fair enough. Good question. The idea, and maybe I can explain this, we'll have an IND filed. Once we have the IND filed and accepted, that enables us to start clinical trials in Australia.
That goes through the clinical trial notification scheme, which is the CTN pathway, which is the form of a dose escalation into dose expansion. If we then choose to start dosing patients in the U.S., we can go through the expansion portion because we'll already have the data through the open IND for the dose escalation. We wouldn't need to repeat the dose escalation in the U.S. In fact, we'd be in good shape because the U.S. has already said they accept the IND to enable us to start in the U.S. The IND, just to be very clear, that's an FDA-facing document. We just use that FDA-focusing document to help us start phase I in Australia.
Thank you. Next question is, when can we expect to see an update on CLDN18.2 data?
When we licensed this from Sparks, it was a phase 1- ready antibody, which had already shown to outperform Astellas preclinical studies and had an open IND with the FDA. Were we able to use any of this in our studies?
Yes. No, good question. I am pleased in that last section, we have just provided an update on the CLDN18.2 program. It has taken longer than we had hoped, but I am pleased now that we have a functional CLDN18.2 targeting CAR. Just to be clear, even though Sparks did have an open IND, that was for the, you may recall the image of the Y-shaped picture. That is the monoclonal antibody.
We still need to, once we transfer it and take that targeting region into a CAR, we still will need to do additional work and IND-enabling studies for that program because it's a different therapeutic at that point. Pleased with where we stand, pleased that we've now got a functional CAR and looking forward to getting that into iNKT cells and doing some further testing in animal studies.
Thank you. The next question is with regards to the manufacturing platform. The question is, once this has been completed for ALA-101 with the second target, CLDN18.2, what time savings are expected for the company as in weeks or months in taking it to IND?
Yeah, it's a how long is a piece of string question almost. What I can say is to take ALA-101 into clinic, we've had to learn a lot.
That has taken probably the better part of two and a half years to get that manufacturing process correct and into a position where we can take it into clinical trials. I would not expect it to take anywhere near as long for another program. As I said, it is now in the shape where I think the main thing to change is that lentivirus. That does take some time to produce, probably six to nine months. Once you have that lentivirus, as I said, I think you would be integrating that pretty quickly into what we call process development and then transferring that hopefully in pretty quick succession into the GMP suite.
It is difficult to quantitate exactly what time saving and cost savings one will be able to derive from that, but I think it would be significantly quicker to take those into IND-enabling studies and to get INDs filed and accepted.
Very good. Next question is, what is lymphodepletion and how does it happen? Why is it a necessary stage prerequisite for treatment?
Good question. Lymphodepletion is now something that is used in all approved CAR-T programs where it is a form of chemotherapy. The reason it is used in cell therapy specifically is it essentially depletes the natural immune system in the patient that is going to take the therapy.
The reason being, if you don't do that, there's always the risk that the immune cells, when a CAR-T is administered, will actually stop the administered cells from what we call proliferating, which is a nice term for growing well. If you stop them from growing well, then you stop them from being able to expand and start killing the tumor cells. The idea for Arovella is we will use the same approach where we dampen the immune system or the immune cells. We then say we create, the word is we use, we create space. We give the iNKT cells so they can freely come in, grow well, and start eliminating the tumor cells. After about two weeks post-lymphodepletion, the natural immune system starts to return, and then that can function normally as well.
Again, one of the safety features we like for our program is because it is off the shelf, we do not expect it to last in the body forever, unlike CAR-Ts, the original CAR-Ts. If we do see any side effects from our CAR-Ts, for example, in our CLDN18.2 program, that will be temporary because we expect our therapy ultimately to be eliminated at some point.
Next question, Michael, is can you explain why we use T cells to test CLDN18.2 first instead of using iNKT cells?
Yeah, absolutely. It is a simplicity and functional assay, which we just want to screen that quickly to see if the CAR works the way we want it to. T cells are more abundant. Most labs have the ability to work with them quite quickly.
It is a study that we can actually perform much faster using T cells than having to get groups to learn how to isolate and manufacture iNKT cells. The other side of that is if that work was being done externally, we do not want necessarily to transfer our iNKT cell manufacturing process out. I should say I'm delighted that, as I said, over the quarter, we formalized our relationship with Gianpietro Dotti at the University of North Carolina through that research agreement. Now we can actually start doing some of that work with a scientist that's employed by Arovella that's in that lab. We'll be able to do a lot of that work much faster. That is going to be beneficial. That work would be done in iNKT cells.
Thank you.
The next question is, if the lentivirus has been made and works in T cells in the test tube, when will data from iNKT cells be expected and how long afterwards you expect to see mouse data?
Yeah, it's in vitro data we can get quite quickly. We probably expect that in the next few months. In an animal study, just given the nature, if it's a solid tumor program and we'd like to look at that out to say 90 days, that'll be a few more months on top of that. We expect some of that data for the iNKT cells to happen in the short term. Animal models would be following shortly after that as well.
The next question is, looking back at the original ALA-101 mouse data, does the company look to expand on or explore secondary remission or brain cancers as seen in the secondary remission response?
Yeah, it's a good question. That secondary remission data that we saw from the original studies, that was not planned in that experiment. It was a byproduct of the experimental setup. It is difficult to replicate it. We'd certainly look to investigate that further, given also when we looked at the brain tissue of the animals in our IND-enabling in vivo study, we were able to detect the cells, the iNKT cells in the brain. This is telling us very clearly that the iNKT cells can traffic there. There is an indication called primary central nervous system lymphoma where patients, once they relapse or it's recurrent, they do very poorly.
We feel that those patients have in the order of weeks, months to live. To think about manufacturing a CAR-T program from that particular patient's cells would be quite challenging. If you had the right program or the right product sitting in a freezer also going after that particular target, we think that's a very interesting avenue to look at exploring. I think we're very, it's important to reiterate as a company, we're data-led, and it's important to follow where the science goes. We'll certainly look at brain cancer models like primary central nervous system lymphoma. If that looks promising in the animal model setting, then we'd look to take that further into potentially into clinical studies as well.
Thank you. There are a few proles to this question, Michael, but I'll let you tackle it however you like.
In terms of safety, how would you review the DLT events in order to standardize a dose? How many DLTs will lead to an exclusion of a dose? How do you evaluate DLTs? Is this per patient or the number of DLTs occurring?
Yeah, look, and I think the nice thing is there's been one phase I CD19 targeting CAR-iNKT cell program that was unfortunately the company did poorly. But we did glean some information from that study that the major safety events that we'll need to be mindful of, there's two. One is called cytokine release syndrome and then ICANS, which is essentially a neurotoxicity issue in patients that we've observed for classic CAR-T programs.
In that study, and of course GVHD, which we do not have to worry about, in that initial study, they did see very low frequency of cytokine release syndrome and ICANS, which is great. We would expect our product to behave the same way. In fact, we think for certain reasons that ours would likely be safer. We are not expecting to see any DLTs, certainly at the low doses. Our low dose, I think, is two and a half times above the low dose in that particular study. For the DLT levels, though, they are naturally on a patient-by-patient basis, and they are graded one through five. I think anything that is quite severe in terms of grade three or four, that is when you start to get into the realm of having dose-limiting toxicities.
I think just going back to what I've said, we're pretty confident we won't see that at the low doses. Of course, we do need to show that in phase I and with the dose levels that we're anticipating using.
The last question I've got, Michael, is Arovella considering peptide MHC-presented TAAs, as in cancer/ testis antigens, splice mutations, etc.?
Short answer is yes, but it's difficult, right? This is just for folks that are less familiar with these things. We use chimeric antigen receptors. We essentially use an antibody that will find the target. This is a little bit different in that you use a T cell receptor that finds a peptide that gets presented on the cancer cell. What it does, it enables you to target something that's typically found on the inside of the cancer cells.
If we could find a target that we think, or a TCR, let's say, that we think is going after a particular cancer target that we see there's benefit for iNKT cells being used in that setting, then we will look at it. I can say openly that we have reviewed several in the past, and they haven't passed our tests, so we haven't licensed them in. I'd never say never. I think having the ability to target not what's just on the surface, but also intracellularly in the tumor cells could be an advantage. We'll continue to look at them.
Thanks, Michael. I'll throw it back to you to just provide a closing comment.
Thanks, Matt. Nothing much more from me. Just again, thank you to everybody for joining the call today. Really appreciate it.
As I said, I think we're set for a big next quarter and certainly a big finish to 2025. Again, thank you very much for your attention and looking forward to creating shareholder value over the months and years to come. Thank you.
Thanks, Michael, and thanks to everyone for joining today.