Earnings call transcript: Arovella sees stable cash position, prepares for trials in Q1 2025

Arovella Therapeutics Ltd (ALA) recently held its earnings call for the first quarter of 2025, outlining key financial and operational updates. The company, currently valued at $70 million, reported a robust cash position of $23.5 million, bolstered by a $15 million placement, ensuring sufficient funding for phase one trials of its lead program, LL-101. The stock currently trades at $0.06, down about 47% year-to-date, according to InvestingPro data. With 10+ exclusive ProTips available for ALA, investors can access deeper insights into the company’s financial health and market position.

Key Takeaways

• Arovella maintains a strong cash position of $23.5 million.
• Phase one trials for LL-101 are fully funded and planned for 2025.
• The company is developing innovative cancer therapies, including iNKT cell platforms.

Company Performance

Arovella Therapeutics continues its focus on pioneering cancer therapies, particularly through its invariant natural killer T (iNKT) cell platform. The company has made significant strides in its lead program, LL-101, which targets CD19+ blood cancers. Additionally, Arovella is advancing its Cloud 19.2 CAR technology aimed at treating gastric, pancreatic, lung, and ovarian cancers. Compared to its competitors, Arovella’s unique off-the-shelf approach to CAR iNKT cells positions it as a leader in the niche field of iNKT cell therapies.

Financial Highlights

• Cash position: $23.5 million, supported by a $15 million placement.
• Funding secured for phase one study of LL-101.
• No earnings per share or revenue figures were disclosed in the call.

Outlook & Guidance

Arovella aims to file an Investigational New Drug (IND) application for LL-101 by the second quarter of 2024, with phase one clinical trials slated to commence in 2025. The company is also actively exploring new technologies and CAR strategies to expand its platform capabilities. Analyst targets suggest significant upside potential, with a consensus target of $0.21. Future revenue forecasts project $2.12 million for FY2025 and $2.45 million for FY2026, with EPS forecasts remaining at -$0.01 for both years. For comprehensive analysis and detailed forecasts, access the full Pro Research Report on InvestingPro.

Executive Commentary

Dr. Michael Baker, CEO of Arovella, emphasized the company’s innovative approach, stating, "INKt cells have a number of anti-cancer properties that other immune cells don’t." He further highlighted the company’s unique position in Australia, noting, "We are still the only company in Australia working on IL-twelve." Dr. Baker also underscored the importance of data-driven decisions, saying, "We are data-led, and it’s important to follow where the science goes."

Risks and Challenges

• Potential regulatory hurdles with the FDA could impact timelines.
• The competitive landscape in cancer therapies is rapidly evolving.
• Achieving successful clinical trial outcomes is critical for future growth.
• Economic conditions may affect funding and investment opportunities.

Arovella’s strategic focus on developing cutting-edge cancer therapies and maintaining a solid financial foundation positions it well for future growth. However, the company must navigate potential challenges in regulatory approval and clinical trial success to realize its ambitious goals.

Full transcript - Arovella Therapeutics Ltd (ALA) Q3 2025:

Matt, Moderator/Facilitator, Aravalla: Function within Zoom. Appearing on behalf of Aravalla today, we have the CEO and managing director, doctor Michael Baker. To begin, I’ll hand it over to Michael. Please go ahead.

Dr. Michael Baker, CEO and Managing Director, Aravalla: Wonderful. Thank you, Matt. Thanks for putting this on for us, and 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 Aravalla. 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 knew the story, we’re very much looking forward to taking our lead program, LA One Zero One, which is an invariant natural killer T cell product, into clinic, this year. But I’ll just jump straight in. Please do note the disclaimer. Will be making forward looking statements.

And let me quickly start with the strengths or highlights of the company as we see it. So very clearly, what I’ve just mentioned a moment ago, we work on our invariant natural killer T cell platform, and we shorten that, for simplicity to I n k t. And it’s an immune cell that we’re developing, to target initially blood cancers, but looking to rapidly progress to utilize the same platform also to target solid tumors. Now we’re 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 have in the sector, and we believe our I and K T cells, go a long way to solving some of those challenges. Yeah.

As a company, we’re we’ve built, the 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 a, different cancers, but even b, 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. And as I said earlier, we’re very excited about our lead product, L101, which is being developed for CD nineteen positive blood cancers like lymphoma and leukemia, is progressing to phase one, and we’re expecting that to start in 2025.

So as I said, I just wanna talk a little bit about CAR T cells. And for some of you that are less familiar, I won’t this won’t be a deep dive, but certainly just to give an overview on on how this broadly works. And I’ll start here with the the the version as it stands, which is now in six 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. And 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 cells, drag it towards the cancer cells, and trigger their destruction. And 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 a 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. So what we’ve seen already is it’s been a very effective modality for blood cancer specifically. 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 Yaskada, and that’s done over 1,500,000,000.0 in sales in 2024.

Now it’s important to note here, 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 forty to sixty percent. So a range of fronts, we do need to do better. And, again, I think major take home here for us is CAR T does still have limitations. And 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. So what that means is, in essence, every every dose of CAR T is made using the patient’s raw material for that specific patient, so it’s made just in time every single time.

And what that does is it drives up the cost largely because it’s such a complicated manufacturing process and supply chain. So we see for blood cancer products, it’s about half a million dollars, US per dose, and for solid tumor programs, it’s in the order of about 3 quarters of a million dollars for a slightly different version, a TCR T program. Now, importantly, if we’re taking the raw material from the patients, 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. So their T cells aren’t doing that well, which means that we’re actually working from a substandard raw material.

So as I said, we plan to go around that by using an off the shelf approach. Now, 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 six weeks for this therapy to be manufactured. So 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.

And because you’re making it every time for every patient, there’s always the risk of a manufacturing run failure. So, again, that just feeds back into adding into the complexity and the costs for this therapy. So Aravalla’s solution is quite simple in its in its genesis. It’s we we we simply replace the T cell. We don’t use a T cell.

We use an invariant natural killer T cell. And 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. So 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, so if a patient’s eligible, they will be able to get access to that within a week, let’s say. So 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. It’s we’ve just worked out how to work, manufacture them at a suitable scale to be able to use them in this particular in this particular capacity. So 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.

But 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 I NKT 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. So we’re very comfortable that they will be able to be given freely from one person to another. Now importantly for us, they’re also considered the frontline of the human immune system, so they have a natural role in immune surveillance, and they constitute what we call the innate immune, pathway or our fast acting immune response, but they also constitute part of the adaptive immunity, which is our longer term response.

So, again, these are both important arms of our immune system, and we’re glad that they fit into both. They can kill like a T cell. They also can kill like an NK cell. And through this little red claw here, the invariant T cell receptor, they can actually naturally target and kill cancers already. So there’s a number of other anticancer properties, and I’ll just show them here in diagrammatic form, which is a little bit easier.

So we have here our CAR NKT 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, can have killing. Iron KT cells also have something on their surface which is called NKG2D. If the tumor cells are also positive for NKG2DL, we get killing.

And as I mentioned, invariant natural killer T cells have an invariant T cell receptor, and if CD1D with a glycolipid is found on that cancer cell, we also get killing. So importantly, though, it’s not just the direct killing that is of interest for us. It’s the ability for IonKT cells also to block and kill things like tumor associated macrophages, myelodiraffe suppressor cells that naturally have been essentially hijacked by the cancer cells to start helping them exclude immune components and essentially support their invasion. In addition, IonKT cells can also cross prime or activate other T cells and natural killer cells to start joining in the fight against the cancer cells. So 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, and 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 antitumor activity to CAR T, and specifically in this case, they tested that in solid tumors.

So a very nice paper and very supportive of Aravalla’s development efforts. Now in terms of the competitive landscape, we we know that, as I said, there’s a number of T cell players still working on T cell programs. Natural killer cell companies also working on natural killer cell programs. And when we look still at the invariant natural killer T cell landscape, it is still tiny. So there’s only a handful of companies working in this particular niche area, and 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, And I think we’re also doing a wonderful job to to be probably being considered one of the leaders within this small group of players, which is excellent. So in terms of our iron K T cell strategy, how do we do this? As I said, we license IP, from all over the world. We have licensed our car I n k t 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 us unlock the ability for us to target different tumor types. For example, our Cloud9 18.2, CAR that we’ve now provided an update on, we licensed from Sparks, enable us to target things like gastric cancer and pancreatic cancer. And then we overlay that with regulatory strategy. And so 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 at the goal of, getting these into the hands of patients that need them, and, of course, know how.

And for those of you that are familiar with the development of a cell therapy, it’s now often, utilized that the the manufacturing process is the product. So 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 Aravallo. So once we’ve got all that ducks in a row in terms of the intellectual property and the programs, How do we actually get these into patients? So 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 raw material, I should say, a lentivirus, which is how we actually get the missile or car into the cells, and 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 are 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 one clinical trials. And for LA One Zero One, as I said, we’re expecting that to be 2025, which is quite exciting for the company. Now while 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.

And it doesn’t mean that it’s, there’ll be no tweaks or enhancements modifications, but it does mean broadly it would stay the same, so we don’t need to repeat a lot of the work that we’ve had to do for l one zero one. So, for example, for Cloud918.2, we’ve acquired the technology. So we’re I’ll provide a small update here on the preclinical information that we’ve been generating. And once we’re happy with that, that’s when we can generate the lentivirus, which would fit into the manufacturing to do the studies to file our IND to start phase one. And for any other car that we bring in, we’ll essentially use the same manufacturing process.

So very important that this work is now in good shape delighted with where it stands today. So over the quarter, we had a pretty eventful quarter. I’m pleased to say that a lot of positives for the quarter. We completed a $15,000,000 placement, and that now provides us with funding to fully enroll the phase one study for LL-one hundred one and generate and report initial safety and efficacy data. We successfully transferred LL-one manufacturing process into the GMP environment, which now is in readiness for the production of the clinical batches.

In line with LL-one hundred one, we also held our first clinical advisory board meeting, which now fits into our clinical trial protocol design, which I’ll touch on. And 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, and we did generate functional 19.2 a functional clad 19.2 chimeric antigen receptor, which we tested in T cells. So, again, good progress for the quarter, and I’ll touch on some of these as we move through. So just starting with LL one zero one, think this is so this is our our primary focus. This is the program that’s closest to clinic, which we’re aiming to do in 2025.

And the way we do that, the way we get there, I think this is a good road map where we have already excellent KOL engagement, that’s now seen through the assembly of our clinical advisory board. GMP manufacturing is ongoing, and as I said, we need to have the the GMP, batches produced to complete the final IND enabling studies, which all of that work gets written up into our IND. And once that’s written up, we submit that to the FDA, which enables us to get regulatory approval for the commencement of phase one clinical trials and ultimately to the first patient being dosed. So in parallel with that, we also engage with, and would onboard clinical trial sites, and we’re also in the process of selecting our clinical research organization who essentially act as our partner to help manage the study. So let me just touch on the manufacturing progress that we made over the quarter.

And just as a reminder, so the way this works for us is we collect healthy blood, blood from our donor, I should say. We then isolate the I and k T cells from that donor. We have our raw material, the lentivirus, that that we use to essentially bring the car into the I n k t cells, and then they are expanded, so we grow them into the billions, and they ultimately get stored in vials frozen. So they’re stored away at very cold temperatures ready for use. So so we made good progress, progressing the tech transfer into the GMP suites.

Now 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 one. And as I said, importantly, all the little tweaks and modifications that we’ve learned over that journey become Arabella trade secret and IP, and they will be useful for future programs that we work on. So we’re currently completing the clinical batches to support IND filing and ultimately would be used in phase one 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. So we tested ALLO-one hundred one that was manufactured using our Clinique Ready manufacturing process. So then now this is a long way away from where we started with research grade material that was produced in a research environment at ICL, and we incorporated incorporated this into a Raji lymphoma model. So they have the tumor cell has c d 19 on its surface.

And just to point out, this is a very aggressive lymphoma model, and it does not express c d one d, which is one of those targets of iron k t cells. So this is a more difficult model to to for the iron k t cells to treat. And then we treat only two groups in this case, phosphate buffered saline, which is essentially salt water, so it’s vehicle or placebo, and then we use allo one zero one, the the cells manufactured using our process. So we then administer the tumor cells they engraft, then we treat them with the particular therapeutic intervention. Now some of you will have seen these curves.

It’s a survival curve where we now in this case, we look out to twenty eight days, and then we’re looking for how many animals survive over that particular time period. And as the lines drop down, that means the animals are succumbing to the disease. And quite clearly, you can see here in the saltwater samples that they all die at around the seventeen day mark or by the seventeen day mark, whereas for the ALLO-one hundred one group, we’re seeing seventy percent alive at the twenty eight day mark. So this constitutes a highly significant extension of lifespan. And 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.

And importantly, also check-in the blood, the bone marrow, and brain, and we’re able to detect CAR NKT cells at this time point as well, which is nice. So in terms of now moving into our clinical capabilities, we’ve been preparing quite a lot already for the first in human phase one clinical study. Delighted that we’ve recently appointed Jacqueline Cumming as the senior director of clinical development, so she’s got an exceptional background in clinical development and clinical operations, and experience more recently at the Peter MacCallum Cancer Center working on cell therapy trials, also previously at CSL in clinical roles and also on the CRO side of IQVIA and PPD. So a terrific level of experience both within company and within the CRO, which will be immensely helpful for Arabella as we continue to move forward. Now also over the quarter, we continued 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.

And 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. And we’ll also finalize the clinical trial protocol based on the feedback that we’ve had from our clinical advisory board, which was only quite recently. But 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, And I’m pleased that our 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. So doctor Sanfi Renza chairs that board. He’s now in Melbourne, but he’d spent time at the Fred Hutch Cancer Center in The US sorry, at Seattle Children’s.

And Deborah 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. And professor Satvanilapu, who was the lead investigator for the phase two study for Yaskata, and I mentioned that one a moment ago, that generated 1,500,000,000.0 in revenue in 2024. So he was the lead investigator for that study that led to its approval. So, again, taking all the feedback that they they provide to us and incorporating that into our clinical protocol design is is immensely helpful. And 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 c d nineteen positive blood cancers. And this will be patients, as I said, where we either have lymphoma or leukemia, and the idea is we have a single dose of LL one zero one, and that would be following what we call lymphodepletion, which is essentially preparing the the patient’s immune cells or immune system to receive the therapy. As always, for a phase one study, despite the fact that this will be done in patients, the primary objective will be to evaluate safety and tolerability of L one zero one in these particular patients. Naturally, because it is in patients, we do have some important secondary objectives.

The first being we’d like to do determine the most appropriate dose of LL one zero one to take into later stage, say, phase two clinical trials. We also will have a keen eye to look at the preliminary efficacy that we see for LL-one hundred one in these studies and also to characterise 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 patients. So there are two parts to the study. The first part is, what we refer to as dose escalation. So we start here at a lower dose, and then we work our way up to higher doses, and that’s provided we don’t see any safety issues, which we don’t expect to.

And we expect overall that part of the the phase one study to have about nine to twelve patients. And then 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. And that’s then taking patients either particular subtypes of lymphoma or leukemia, and we expand the number of patients treated at that particular dose, and we expect that to end up being about twenty patients total. So all up, we’d expect the phase one study to have around the thirty, thirty two patient mark. So 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 q two, calendar year, and, of course, then getting regulatory approval for start up and, getting the phase one study going. So as I said, also, we’re going to make progress in the short term around the selection of our clinical research organization, and we’ll continue to prioritize working and engaging with the sites that we’d like to have involved in the study. So I’ll just switch gears briefly so I can provide the context on our recent updates for our cloud 19.2 targeting program.

Now just for context, I think many of you may know this already, but ninety percent of every newly diagnosed cancer will be some form of solid tumor. So already we know that there’s a huge unmet need here and also out of that there’s a very large commercial opportunity that exists for the right programs. But importantly for Arabella, 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. So we do have a fairly aggressive strategy to expand into this space, and there’s three major arms to that. The first is to license novel cancer targets.

So, again, when we think about the IKT 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 armoring strategies to give the cells a bit of an extra boost when thinking about using them for solid shimmers, We are also still working at evaluating potential partnerships with groups where we think that this the opportunity for combination products to have synergistic effects, so they not just work additively with each other, but they genuinely work better than each individual drug on their own. So when we think about solid tumors, think this is, again, important to point out conceptually. It is quite different. They are quite different to a blood cancer setting, and I’d certainly never say that a blood cancer is an easy an easy bar in terms of treatment.

But, 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 a higher incidence 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. And 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. So certainly a much higher bar. And why, again, we think iron K T cells are well positioned is we know they naturally harm to tissues.

They have been shown to infiltrate tumours and even to the point where in some studies they have been prognostic. So patients have low levels of iron K T cells. Their outcomes are worse than patients with higher levels of iron KT cells. And 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, 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.

So in terms of adding new cars into our programs, again, I’ll just reiterate the manufacturing process. We collect blood from a healthy donor. We isolate the cells, and it’s 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. So the steps largely stay the same.

It’s just this raw material that we feed in that would change, and then we have the ability to grow them up as we normally would, violin freeze them, and then we have a new program targeting a different cancer type. So we have selected clad eighteen point two as a 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. And with the approval of the first monoclonal antibody last year in Japan and The US, we also know that a validated target. So we’re 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.

And naturally, the gastric cancer market is quite large, and that’s not surprising. Just some quick numbers here which I won’t go through in detail, with almost a million cases per annum of gastric cancer, half a million cases of pancreatic cancer each year, and really dismal survival rates between six and thirty three percent for regional and distant here for gastric, and three to fifteen percent for pancreatic. So there really is not a lot of treatment options for these groups of individuals, and we see that as a really important opportunity for our NKT cells to go after. So how do we actually do this? What a monoclonal antibody would look like in a diagrammatic form is something like this, and this is the sequence we licensed from Sparks.

The area of interest for us is the area in this little green square, and that’s the that’s the portion of a monoclonal antibody that knows how to find platinum 18.2. So what we actually do is we take that portion, and then we graft it onto the CAR here where that’s fused now to all these different components that will tell an immune cell like a T cell or an iron K T cell to turn on. And when this then recognizes cloud 19.2, that’s when the CAR will tell the immune cell to to start killing. So we have already tested the CAR. We’ve produced the CAR and tested that in T cells, and we’re pleased with the data that we’re we’re generating.

The next step is now to incorporate that CAR into our I n k t cells and test that and see how that’s functioning as well. So just on that data for the cloud 19.2 targeting CAR, as I said, we’ve now successfully made that using the SPX one zero one sequence. And what we’ve done is compared our cloud 19.2 targeting CAR to a what we call a control CAR, which we would expect to have robust killing for cells that have cloud 19.2 on their surface, and we’ve compared both when we have cells that have cloud 19.2 sticking out on their outside. And what we’re looking at on the curve here is we’re looking at a very small time frame, so we’re going out from two hours to eight hours. And what we’re looking at on the vertical axis here is how much how many of the cells as a proportion, so as a as a percentage have been killed in that short time frame.

So in the control group, we see that there’s quite good killing, and importantly for Aravalla’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. So we’re very happy, and I should say that’s all in comparison to a T cell here that does not have a CAR at all, which don’t demonstrate killing. So we’re pleased with the fact that we’ve got this CAR. Of course, now our key goal in the short term is to take that CAR and incorporate it into our I and K T cells. And once we’ve done that, we’ve assessed its performance, we’ll optimise 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 I NKT cells.

So we’re, again, pleased with the update for the quarter. This is our pipeline. It’s still developing, and we’re pleased with where the program sit. L o one zero one for c d nineteen positive blood cancers will be aiming to get our IND filed this quarter and start phase one in 2025. L o ’1 zero ’5, 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 I and K T cells.

And for IL 12 TM, as I said, we’ll feed that into our solid tumor programs as they develop as well. So we do have a very busy end of the year plan naturally for ALLO-one hundred one. This is going to be the key focus for us. So 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. And all of that would precipitate getting an IND accepted, would enable us to commence the phase one first in human study for ALLO one zero one, which we find tremendously exciting for the company, and, of course, excited that we’d be in a position then to generate initial data from patients in those early dose cohorts.

And 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 is is sets us up to be in a great position to do that. Now for l one zero five, as we’ve just now we’re comfortable that we’ve generated a functional CAR, and the key is to integrate that into our I and K T cells, assess the functionality, and optimize that for solid tumors. And, again, looking forward to generating animal data once we’ve got that CAR and I and K T cells, and we’ve used gastric cancer and also probably pancreatic cancer models to demonstrate the activity of that. And 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.

And as noted, IL 12 will be integrating into the, l l one zero five or cloud 19.2 program. And something I haven’t had a whole 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’ve got a very strong chance of having better fit in patients with particular cancer types. So we’ll look forward to updating you on those activities in due course as well. So just to summarize, I think we’ve got a really exciting platform. IKT cells have a number of anti cancer properties that other immune cells don’t.

Delighted that we’ve gotten now a proprietary clinical manufacturing process to reduce CAR NKT cells. Very excited that we’re going to be taking to LA 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 cloud 19.2 program and our IL 12 TM armoring. And just as I and said it before, but I think for all these reasons, the fact that we are still the only company in Australia working IL-twelve just I said I’ve said before, I think for reasons, fact we are still only company working on IL-twelve TM-twelve, 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.

And of course, big thank you to all the shareholders that have taken the time to dial in. We we really appreciate it, and I’d be absolutely delighted to take any questions.

Matt, Moderator/Facilitator, Aravalla: Thanks, Michael. As you mentioned, we’ll move on to the q and a. So, again, if anyone has any questions that they’d like to submit, please feel free to do so using the q and 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, etcetera.

Do you have anything to worry about on that front?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. It’s a good question, Matt. Look. The answer is, I’d say not yet. I don’t think we we have seen enough in terms of impacts, 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. So I don’t think it’s something we can worry about just yet. And whether or the effects of, you know, cuts, to the FDA through what’s been going on in The US will actually impact this year or next year. We we still don’t have good line of sight on that, Matt. So probably best just to continue as planned and just get on with our development efforts and get things completed and filed.

Matt, Moderator/Facilitator, Aravalla: Thank you. In addition to that, another hot topic has just been the market volatility recently. So I guess with regards to your cash position, etcetera, how do you feel your place there, and are you worried about the ability to raise money given that volatility?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. Look. It’s I think it’s not lost on its side, but it’s been a pretty difficult few months, I think, with everything that’s going on around tariffs and and and movements in markets and so forth. But, you know, I think, as I said, we finished the quarter with $23,500,000. We’re we’re in really good shape financially.

So I don’t think we have to worry about raising capital for quite some time, which is excellent. And I’d expect that there’s multiple readouts both for l o one zero one and also for other programs, that would come well before we need to raise capital. So, you know, I think we we raise capital at a good time, and and happy that we’ve got the cash in the bank.

Matt, Moderator/Facilitator, Aravalla: Thank you. Next question is, are you looking at other or new technologies, and can you provide an update on developments in this regard?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. Look. It’s always a bit hard to provide updates, because they usually pop out when they’re when they’re done and and and deals are done. But all I can say is that we are actively screening the globe, still for new new cars, strategies to enhance the cells, and that won’t stop. And I think the the reason being, I think, is, you know, as we look to to move into potentially different indications, making sure that we’re building the right products to target those indications, I think, is very important.

And despite the fact that it is a pretty nasty market, it does mean, unfortunately, for companies that, you know, that may not have the requisite funds, but there’s certainly opportunities for technologies to be to be brought in, and and we’ll absolutely explore those.

Matt, Moderator/Facilitator, Aravalla: Thank you. All clinical and nonclinical IND enabling studies now being completed?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. So as I said, we aim to submit our IND in Q2 calendar year, so we’re working through the completion of those studies at the moment. But as I said, very pleased with the progress, in terms of the manufacturing, the GMP suites, completion of the the in vivo animal model. Now there’s a few more things to complete, but I think we’re in good shape.

Matt, Moderator/Facilitator, Aravalla: The next question is, are we still looking to receive platform designation from the FDA?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. Good question, actually. So that’s something that came out, I think it was late last year. Yes is the short answer. The reality is to get access to platform designation, one does actually need to have a a product approved or BLA accepted.

So that’s some way off for us, but naturally, we’d like to explore that program as and when we can because we do see that there’s a lot of a lot of pieces for our manufacturing process that we’d we’d utilize over and over again for different programs. So when the timing is right, we we would like to explore those programs for sure.

Matt, Moderator/Facilitator, Aravalla: Thank you. A couple of questions here. We’re just in regards to the interview you recently did with Tim Boorum on Stockhead. So the first question in regards to that is do we have all the Australian approvals in place to start dose escalation in Australia before we move into dose expansion in The US?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. Okay. Fair enough. Good question. And so the idea and maybe I can explain this.

We’ll have an IND filed. And once we have the IND filed and accepted, that enables us to start clinical trials in Australia, and 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 US, we can go through the expansion portion because we will already have the data through the open IND for the dose escalation. So we wouldn’t need to repeat the dose escalation in The US. In fact, we’d be in good shape because The US has already said they they accept the IND to enable us to start in The US.

So the IND, just to be very clear, that’s a that’s an FDA facing document, and we just use that FDA focusing document to help us start phase one in Australia.

Matt, Moderator/Facilitator, Aravalla: Thank you. Next question is, when can we expect to see an update on Cloudin eighteen point two data? When we licensed this from Sparks Group, it was a phase one ready antibody, which had already shown to outperform Astellas preclinical studies and had an open idea with the FDA. Were we able to use any of this in our studies?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yes. No. Good good question. And so I’m pleased in that last section, we’ve just provided an update on the CLATIN eighteen two program, and it has taken longer than we’d hoped, but I’m pleased now that we have a functional Cloud 19.2 targeting CAR. And just to be clear, even though Sparks did have an open ID, that was for the you may recall the image of the the y shaped picture.

That’s the monoclonal antibody. So we still need to once we transfer 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 it’s a different therapeutic at that point. But pleased with where we stand, pleased that we’ve now got a functional CAR, and looking forward to getting that into IONKT cells and doing some further testing in animal studies.

Matt, Moderator/Facilitator, Aravalla: Thank you. The next question is with regards to the manufacturing platform. So question is once this has been completed for ALLO 101 with the second target, about 98.2, what time savings are expected for the company as in weeks or months in taking it to IND?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. It’s it’s a it’s a how long is a piece of string question almost, but what I can say is to take l one zero one into clinic, we’ve had to learn a lot. And now that’s taken, you know, probably the better part of two and a half years to get that manufacturing process correct and into a position where we can take them to clinical trials. I would not expect it to take anywhere near as long for another program. And as I said, it’s it’s now in in the shape where I think the main thing is to change is that lentivirus.

That does take some time to produce, probably six to nine months. But once you have that lentivirus, as I said, I think you’d be you’d be integrating that pretty quickly into what we call process development and then transferring that hopefully in not in in pretty quick succession into the GMP suite. So it’s difficult to quantitate exactly what time saving and cost savings one will will will be able to derive from that, but think it would be significantly quicker to take those into IND enabling studies and to get INDs filed and accepted.

Matt, Moderator/Facilitator, Aravalla: Very good. Next question is, what is lymphodepletion, and how does it happen? Why is a necessary stage prerequisite for treatment?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Good question. So lymphodepletion is now something that’s used in all approved CAR T programs where it is a form of chemotherapy. And the reason it’s used in cell therapy specifically is it it essentially depletes the natural immune system in the patient that’s 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 the administered cells from from what we call proliferating, which is a nice term for growing well. And if you stop them from growing well, then you stop them from being able to expand and start killing the tumor cells.

So the idea for Arabella is we will use the same approach where we 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 iron KT cells so they can freely come in, grow well, and start eliminating the tumor cells. And then after about two weeks post lymphodepletion, the natural immune system starts to return, and then that can function normally as well. So, again, one of the safety features we like for our program is because it is off the shelf, we don’t expect it to last in the body for forever unlike CAR Ts, the original CAR Ts.

So if we do see any side effects from our CAR Ts, for example, our cloud 19.2 program, that will be temporary because we’d expect that therapy ultimately to be, eliminated at some point.

Matt, Moderator/Facilitator, Aravalla: Next question, Michael, is can you explain why we use T cells to test nineteen point two first instead of using I and k T cells?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. Absolutely. So it’s it’s a a simplicity and functional assay, which we we just wanna screen that quickly to see if the car works the way we want it to. And T cells are more abundant. Most labs have the ability to work with them quite quickly, and so it’s a study that we can actually perform much faster using T cells than having to get groups to learn how to use to isolate and manufacture I and k T cells.

The other side of that is if that that work was being done externally, we do not want necessarily to transfer our iron KT cell manufacturing process out. Now I should say, I’m delighted that I said over the quarter, we formalized our relationship with Gianpetrodotti in the University of North Carolina through that research agreement. So now we can actually start doing some of that work with a scientist that’s employed by Arabella that’s in that lab. We’ll be able to do a lot a lot of that work much faster. So that’s that’s going to be beneficial, and that work would be done in iron KT cells.

Matt, Moderator/Facilitator, Aravalla: Thank you. The next question is with and a lentivirus is being made and works in T cells in a test tube, when will data for iron KT cells be expected, and how long after would you expect to see mouse data?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. It’s it’s in vitro data, we can get quite quickly, so we’d probably expect that in the next few months. And then 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 ninety days, that’ll be a few more months on top of that. So, again, we expect some of that data for the IKT cells to happen in the short term, and animal models will be following shortly after that as well.

Matt, Moderator/Facilitator, Aravalla: The next question is looking back at the original LL one zero one mouse data, does the company look to expand on or explore secondary remission or brain cancers as seen in the secondary remission response?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. It’s a good question. So that 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, so it’s difficult to replicate it, but 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. So this is telling us very clearly that the INKT cells can traffic there.

And there is an indication called primary central nervous system lymphoma where patients, once they’ve relapsed or it’s recurrent, they do very poorly. We feel that know, those patients have in the order of weeks, months to live. So think about manufacturing a CAR T program from that particular patient’s cells would be quite challenging. But 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 to look at exploring. So, again, I think we’re very it’s important to reiterate as a company, we’re data led, and it’s it’s it’s important to follow where the science goes.

So we’ll certainly look at, brain cancer models like primary central nervous system lymphoma. And if that looks promising in the animal model setting, then we’d look to to take that further into potentially into clinical studies as well.

Matt, Moderator/Facilitator, Aravalla: Thank you. There’s a fair few problems to this question, Michael, but I’ll let you tackle it now if you like. In terms of safety, how would you review the DLT events in order to standardise 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?

Dr. Michael Baker, CEO and Managing Director, Aravalla: Yeah. Look. And I think the nice thing is there’s been one phase one c 19 targeting CAR NKT cell program that was unfortunately, the company did poorly, but we did get gleaned 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.

And in that study and, of course, GVHD, which we don’t have to worry about. In that initial study, they did see very low frequency of cytokine release syndrome and ICANS, which is great. And so we would expect our product to behave the same way. In fact, we think for certain reasons that ours would likely be safer. So we’re not we’re not expecting to see any any DLTs certainly at the low doses, and our low dose, I think, is two and a half times above the low dose in that particular study.

So for the DLT levels, though, they’re naturally on a patient by patient basis, and they’re graded one through five. And I think anything that’s quite severe in terms of grade three or four, that’s when you’re starting to get into the realm of having dose limiting toxicities. But I think just going back to what I’ve said, we’re pretty confident we won’t see that at the low doses, but, of course, we do need to show that in phase one and with the dose levels that we’re we’re anticipating using.

Matt, Moderator/Facilitator, Aravalla: The last question I’ve got, Michael, is Araville considering peptide MHC presented TIAs as in cancer testis antigens, splice mutations, etcetera.

Dr. Michael Baker, CEO and Managing Director, Aravalla: Short answer is yes, but it’s difficult. Right? So this is just for folks that are less less familiar with these things. It’s we use chimeric antigen receptors, so we we we essentially use an antibody that will find the target. This is a little bit different in that you use a a T cell receptor that finds a peptide that gets presented on the cancer cells.

So what it does, it enables you to target something that’s typically found on the inside of the cancer cells. And 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 I and K T cells being used in that setting, then we will look at it. And I I I can say openly that we, you know, we have reviewed several in the past, and they haven’t they haven’t passed our tests. So we haven’t licensed them in, but we I’d never say never. I think having the ability to target not what’s just on the surface, but also intracellularly in tumor cells could be an advantage.

So we’ll continue to look at them.

Matt, Moderator/Facilitator, Aravalla: Thanks, Michael. I’ll throw it back to you just to provide a closing comment.

Dr. Michael Baker, CEO and Managing Director, Aravalla: Thanks, Matt. No. Not nothing much more from me. Just, again, thanks thank you to everybody for joining the call today. I really appreciate it.

And as I think we’re we’re set for a big next quarter and and certainly a big finish to 2025. So, again, thank you very much for your attention, and looking forward to creating shareholder value over the months and years to come. Thank you.

Matt, Moderator/Facilitator, Aravalla: Thanks, Michael, and thanks to everyone for joining today.

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