Good morning, ladies and gentlemen. My name is Elizabeth Stoner, and I am the Interim Chair of Arovella Therapeutics Ltd. On behalf of the Arovella Board of Directors, I'm pleased to welcome you to the Annual General Meeting of Arovella. It's now 11:00 A.M., and there being a quorum present, I declare the meeting open for business and confirm the meeting has been properly constituted. I would like now to introduce my fellow directors and company secretary who are with us today: Dr. Michael Baker, CEO and Managing Director; Dr. Debora Barton, Non-Executive Director; Mr. Gary Phillips, Non-Executive Director; and our company secretary, Mr. Tim Luscombe. The order of events for today's meeting will be as follows. I will firstly provide an overview of Arovella's performance during the 2025 financial year. We will then hear from the CEO and Managing Director, Dr.
Michael Baker, and then we will proceed with the formal business and the resolutions of the meeting. I joined Arovella's Board of Directors at a pivotal time in 2021. It was a pivotal time in the company's history, which was shortly after licensing its invariant natural killer T cell platform from Imperial College London. At the conclusion of this financial year, Tom Duffy stepped down from the Arovella Board of Directors, and I became the Interim Chair. We wish Tom well for his future endeavors, and this is now a very exciting time for the company as we embark on important milestones which will mark the first time the CAR-iNKT cell platform is included in a clinical trial for patients with CD19 lymphoma and leukemia.
The Arovella team has been busily working to secure a new member capable of transitioning to chair, who has an extensive background in drug development spanning biotechnology and large pharmaceutical companies. We are pleased to have selected our preferred individual from a pool of exceptional candidates interested in joining the company and look forward to announcing the new board member this quarter. Arovella is well positioned for growth as we continue to make great steps building our pipeline to target a range of high unmet medical needs in solid tumors with a very unique cell therapy. The progress we have made is largely due to the excellent work of the Arovella team, which I will touch on more in just a moment, coupled with a capital raise which allowed us to do that work that we have done, positioning the company well to accelerate the development opportunities.
Firstly, let me thank all of you shareholders for their continued faith and support of the company. Drug development is a challenging process, especially when one is breaking new ground with a unique technology that ultimately becomes the opportunity to create life-altering therapies that drive shareholder returns. Despite a challenging start to this calendar year, combined with several sector-specific issues that suppress the biotechnology sector, Arovella was delighted to raise AUD 15 million before offer costs. This provides capital for Arovella to advance its programs and positions the company for success and to move to its first clinical trial.
Reflecting the sentiment of our shareholders, we too are disappointed by the decrease in share price over the course of 2025, but we are buoyed by the continued progress across all of our programs, superb enhancements that have been made to the team, and have confidence that the company is more advanced and in a better position both financially and developmentally since the commencement of the year. Since our last annual meeting, we have made significant progress for our lead asset, ALA-101, and you will hear in a moment more from Dr. Michael Baker about the recent developments regarding our positive interactions with the FDA and our planned milestone to take ALA-101 into phase I after receiving the acceptance of the IND from the FDA early next year. Let me reiterate the importance of the investigational new drug application.
An accepted IND represents a significant advancement of Arovella's novel CAR-iNKT cell platform beyond the ability to commence the phase I clinical trial for ALA-101. The IND for ALA-101 will serve as a blueprint for the Arovella platform and all of the future programs. For example, ALA-105 is our next product that includes a CLDN18.2 targeting CAR incorporated into our CAR-iNKT cell platform. This is being developed for gastric cancer and pancreatic cancer. Due to the work invested in delivering the manufacturing process for ALA-101, the manufacturing process for ALA-105 is largely already established, and the only raw material that we will need to change is the lentivirus used to introduce the CAR. This is expected to reduce the amount of time and risk and expenditure to take ALA-105 and all future programs into clinical trials.
This raises many possibilities for Arovella in the short term and represents an attractive platform for potential third-party partnering initiatives. Of significance, Claudin 18.2 continues to be an important target for pharmaceutical companies, and we are pleased to be developing a unique CAR invariant NKT cell therapy going after this target. The company continues to expand the focus on high unmet need in solid tumors. This was highlighted through the company securing an exclusive option agreement from Baylor College of Medicine for two new CARs targeting solid tumor cancers of high unmet need. Should Arovella decide to proceed and exercise this option and enter into a license agreement, this will add two new CARs targeting very important cancer types. Lastly, the team has continued to grow.
In readiness for the phase I clinical trial for ALA-101, Jacqueline Cumming was recently appointed as Senior Director of Clinical Development, and she joins us from an excellent pedigree, having led clinical teams at both CSL and Peter MacCallum Cancer Centre. To enhance our R&D capacity, we welcome Dr. Clinton Heinze to drive the Claudin 18.2 CAR-iNKT cell preclinical work within Professor Gianpietro Dotti's lab at the University of North Carolina. In addition, we appointed Dr. Alfie Baker to establish our first research laboratory within the Jumar Bioincubator to allow for the completion of preclinical studies in-house and to generate data for our two new programs. At Arovella, the future is bright. The company is very well funded currently, and each program is developing nicely.
We are on the precipice of the most important milestone in the company's history, namely receipt of the IND acceptance and the commencement of the first-in-human study for ALA-101. On behalf of my fellow directors, I would like to extend a heartfelt thank you again to all of our shareholders for their continued support and faith in the company. We look forward to striving to create additional shareholder value over the next 12 months and the years to come. I will now hand over to our CEO and MD, Michael Baker, who will run through the latest company activities, and thank you very much for your attention.
Thank you very much, Liz, and thank you very much to everybody that's taken the time to dial in today. I'm looking forward to taking you through some of the latest activities of the company, but also some of the activities that we have planned moving forward. Next slide, please. This presentation does contain forward-looking statements, so please do note the disclaimer. Next slide. Right, so let me start here with some of the key achievements for the fiscal year 2025 and a little bit thereafter. We have had a transformative year, and I think the focus continues to really be on ALA-101, which is our product that we're developing for CD19- positive blood cancers. And the first key step for that, or key steps or achievements, revolve around the manufacturing. So we have done quite a lot in readiness for phase I clinical trials.
We have secured all the GMP reagents that are required to make those batches. We have already completed manufacturing runs successfully in the GMP environment, and we've already completed the manufacturing runs that we are required to do for the IND submission, which is terrific. In terms of the regulatory steps, we have had substantial progress after completing many of the studies and work that we need in compiling the documentation for our IND application in preparation for its submission. I'll talk about it in a moment. We had a very positive Type D meeting with the FDA this week, which was terrific to confirm the pathway forward for our IND submission, and also yesterday, we selected our contract research organization as our partner for the phase I clinical study.
So we have had a very clear focus, and we continue to do so on enhancing our iNKT cell platform or broadening its utility. We were delighted to get very promising data for our Claudin 18.2 program when used in CAR T cells. And we also entered into an exclusive option for two new CARs, one targeting GD2, which is found on neuroblastoma, a central nervous system indication targeting young children, and GPC3, which is also a form of liver cancer called hepatocellular carcinoma. And we did continue to search many universities and research institutes as well as companies globally for unique technologies to add to our CAR-iNKT cell platform. Next slide.
In terms of the financials, we are currently valued at about AUD 110 million, and to Liz's point, we are in a very strong position cash-wise, finishing the September quarter with just under AUD 22 million cash in the bank. We do have a series of options that, should they be in the money, we'll also generate an additional AUD 23 million for the company. We are very appreciative and thank all of our shareholders for their support, particularly our largest shareholders certainly have continued to be supportive of the company and our activities, so we're very appreciative for that. Naturally, when we look at the share price chart on the right, there is a disappointing decline, and we're in some ways pleased that that had very little or nothing to do, I should say, with our technologies being developed.
It was due to a corporate issue, but naturally, with the events that we've got planned, we certainly look forward to the future in building shareholder value in the months and years to come. Next slide, please. Now, I think this is just an important place to stop very briefly. It's not to say that Arovella is up for sale. It's to demonstrate the importance of the cell therapy sector broadly for mid-tier and large pharmaceutical companies. So this encompasses a range of different cell therapy types and across a range of different indications, but what we've tried to keep consistent is the stage, and you'll see many except one of phase I and some are preclinical with one phase II technology there. Out of the last few, over the last few months, we've seen several billion dollar plus transactions for these early stage cell therapy platforms.
So again, the main thing here is to demonstrate the importance of the cell therapy sector. Next slide, please. And when we think about that more broadly, T cells and natural killer cells have historically dominated the field in quantity and number, and that still seems to be the case with a snapshot of the different players here depicted. But what we see for the iNKT cell field in the middle, there is still just a handful of companies working with iNKT cell platforms. So Arovella is delighted to be in a very important sector, namely cell therapy, and delighted even further to be a niche part of that sector working on iNKT cell therapy programs. Next slide, please. So just a refresher here on how we actually take products from inception to patient, and we've essentially borne out of using acquisition. So we take an example here for ALA-101.
We acquired the iNKT cell therapy platform, and that we did successfully. It had preclinical information. If the technology doesn't, we generate it. We generate one more raw material there, a lentivirus, and then we utilize that in our manufacturing platform, and just to reiterate, that was an extensive process to establish that manufacturing process, taking somewhere around two and a half to three years, but now we have that done. We compile all the information that we have around preclinical efficacy, safety, the manufacturing, as well as clinical documentation, and package that up to file our investigational new drug application or IND application to the FDA, and then we look to start phase I clinical trials, and for ALA-101, that's anticipated to be early 2026. Now, as I said, for ALA-101, we have already. Can you click the next slide, please? Thank you.
We have already had our pre-IND meeting late last year. We've established the manufacturing process, and as I said, we've just had a positive Type D meeting with the FDA, and we intend to file that IND before the end of this calendar year. Now, the reason we have the manufacturing platform there highlighted in pink is because now that that has been done for ALA-101, we expect the process to remain largely the same for all future programs. And in the dark blue in the middle there, we have ALA-105, which we're developing for targeting gastric cancer and pancreatic cancer. We have already acquired the technology from SparX Group. We have already generated some very solid preclinical information, but we're continuing to do that, and we'll get to animal models before we go to the next step of developing or manufacturing the GMP lentivirus.
But as I said earlier, that would feed into the manufacturing process, which is already largely established before we file with the regulator and before starting phase I clinical trials. And then for all future programs, just reiterating that we have two additional CARs under option targeting GPC3, it's the same approach. So what we're building really is a roadmap for the first IND, namely ALA-101, being prepared for all future programs so we're able to take therapies into clinic in a way that's more cost-effective and more time-effective. Next slide, please. So just to stop here for a moment just on what the pathway to a U.S. FDA IND looks like. As I said, we had a pre-IND meeting late last year. We have three major arms: manufacturing, which is referred to as Chemistry, Manufacturing, and Controls, non-clinical work, as well as our clinical documentation.
The idea is all of that's compiled into a very large document that is called the IND. It's submitted to the FDA, and they have a 30-day review window. Now, what we don't want to happen in that case is that that goes on clinical holds and an IND resubmission is required after answering any queries or questions from the agency. Can you please click the button, Matthew? We decided around the middle of the year that there was a sticking point around the analytical testing for one of our GMP reagents. So we decided to have a Type D meeting with the FDA.
The reason we decided to do that was because we wanted to be in a position where we felt we were going to be better positioned to have a no clinical hold outcome once we submitted our IND, which is then ultimately when the study is safe to proceed. Next slide. I'm pleased to say that that interaction with the FDA in the form of the Type D meeting was very positive for Arovella. During that meeting, the FDA provided very clear guidance on the testing requirements for this particular reagent that we use in our manufacturing process. I'm pleased to say that much of that testing has been completed. We do have a couple of additional things to do, but we'll be able to do those swiftly. As I said, we believe we're in a great position to file the IND this quarter.
Next slide. So when we think about broadly what's left or what's been done in taking ALA-101 into clinical trials, as I've said, for a few things, but we have completed our IND-enabling non-clinical studies, which supports safety and efficacy of the therapeutic. We have formed a clinical advisory board and engaged with key opinion leaders to inform our clinical trial design. We just conducted the Type D meeting to align on the reagent testing for IND filing. We also announced yesterday that we've contracted our contract research organization to support the phase I clinical study. So what remains is to finalize the clinical trial protocol and what we call Investigator's Brochure, select and contract clinical trial sites, file the IND with the FDA, complete the manufacturing of the clinical batches, get ethics approval for the study in Australia, and ultimately culminating with the first patient dose.
A lot's been done, but we're certainly looking forward to ticking off these milestones in the near future. Next slide. Now, in terms of the phase I clinical trial design, we have mentioned this before, but just to reiterate, it is a first-in-human study, and it will consist of two parts, the first being what we refer to as dose escalation. We will start at a lower dose of 50 million cells, where we would still expect to have good efficacy, but no safety issues, and then we'll continue to titrate up to 100 million, 150 million cells, sorry, 300 million cells, and 500 million cells. This part will consist of about 13 - 21 patients and will be lymphoma patients for that part. Once we find a dose level that we're happy with in terms of efficacy, we'll move to part two, which is called dose expansion.
Then we have the dose level that's preferred, and we continue to enroll more patients, and this will include lymphoma and leukemia patients. And we have the opportunity here, if we see equivalent efficacy at two dose levels, to potentially have two dose expansion dose levels, which then means we're able to get data. And if it was supportive to use the lower dose, this would be the preferred outcome because it would mean we have more doses per manufacturing run, but also less chance of any adverse events with the lower cell therapy dose. So as I said, as a phase I study, the primary objective here is always to evaluate the safety and tolerability of the therapeutic.
Naturally, the secondary objectives firstly are to identify what we refer to as the maximum tolerated dose, but also the dose that we'd like to take into future stages of clinical development. Importantly, we would expect to be able to receive preliminary efficacy of the product. Remember, this will all be done in patients, and these patients will be largely very unwell. If they're surviving, we'll be able to get readouts quite quickly on the benefit of the therapeutic. We'll also wish to characterize what we call pharmacokinetic profiles, so where the cells go and how they behave, and also to assess if the product has any immunogenic aspects as well. Next slide. Let me just switch gears a little bit here to talk a little bit more about our ambitions to use our iNKT cell platform to target solid tumors.
Just noting that nine out of every 10 cancer cases diagnosed will be some form of solid tumor, and we do expect iNKT cells to have, well, we know they have unique benefits that we think will position them well to target solid tumors. Next slide, please. So why do we believe iNKT cells are well placed to tackle solid tumors? This is largely through not just the data that Arovella has generated, but data that comes from other groups. What we know already is that iNKT cells are naturally programmed to recognize markers that are on the surface of numerous different solid tumors, and those include NKG2DL and CD1d. So they're already naturally ready to kill tumor cells. And we also know if patients with certain solid tumors have low levels of iNKT cells, their prognosis is quite poor.
So again, this is quite fascinating to us and suggests already a role for them naturally. If you can click, Matthew. The second is that they are able to kill what we refer to as pro-tumor cells, which make up what we call the tumor microenvironment. They also are capable of activating helpful immune cells in the host, which means after they're eliminated, that some of those other cells may still play a role in eliminating cancer cells. And we've seen multiple examples in blood cancers and solid tumors, not just from our work, but from others, where CAR-iNKT cells outperform CAR-T. And one more, Matthew.
Lastly, there haven't been many clinical trials for CAR-iNKT cells to date, but two, what we refer to as autologous clinical studies have shown some very promising data, both in solid tumors, one for neuroblastoma and the other one for renal cell carcinoma or kidney cancer. That image down the bottom there is actually a young patient with neuroblastoma, that central nervous system cancer that's referred to. You can see from the left-hand side and the right-hand side that that young patient actually underwent a complete response. That's very exciting data for that particular CAR, and that's the CAR that Arovella has under option from Baylor College of Medicine. Next slide. How do we actually go about creating new products to target solid tumors? In essence, what we'd like to do first is work with new CARs.
Our first program, ALA-101, has a CAR that targets CD19. Let me explain how we do this, and we're able to do this quite efficiently. To get our product manufactured, we collect healthy donor blood. We isolate the iNKT cells specifically. We then use that little gray hexagon with the DNA molecule in pink to infect the iNKT cells, and then you end up with the CAR, which is the little red, sorry, the little blue and yellow bump sticking out on the surface there. That's the missile that's going to recognize and help to target and eliminate the cancer cells. By changing the pink DNA molecule inside that little virus, we're able to generate any CAR that we want to target a different cancer type. Then once we've done that successfully, we grow the cells up into the billions.
They go into a freezer after they've been manufactured in vials, actually liquid nitrogen, where they're stored frozen ready for use, so the beauty of that is, as I said, for any new product that we want to work with, we're able to change that DNA sequence, and that's the case for our next program, Claudin 18.2, but it would also be the case for the GD2 CARs and GPC3 CAR from Baylor College of Medicine. Next slide, please, so let me talk more about Claudin 18.2 and why we're excited by it. It is a very promising solid tumor target. It's found in multiple different cancer types, like gastric cancer, gastroesophageal cancer, pancreatic cancer, and some lung and some ovarian cancers. It is a validated target. There's only one product approved to date that targets Claudin 18.2, and it was approved last year in Japan and the U.S..
And that was tested in two phase III clinical trials with what we refer to as a monoclonal antibody with chemotherapy versus chemotherapy alone. And the difference between chemotherapy alone was an extension of 2.5 months for that product. So we don't think that's doing a huge amount more than just chemotherapy alone. So we see this as a very good opportunity for a very strong Claudin 18.2 targeting cell therapy to have meaningful impact for these patients. So naturally, it is a big market. There's about a million cases annually per year for gastric cancer. And I'm pleased that Arovella has successfully generated a functional CAR. Next slide.
This is some data to that point that we generated and present or released a few weeks back now, where we took the monoclonal antibody we had from SparX Group, we converted it into the CAR molecule that goes into, in this case, T cells. What we do once we've got those CAR T cells made is we mix them in a dish with, in this case, a pancreatic cancer cell line that has Claudin 18.2 on its surface. What we decided to include here is a very good control, which is a different Claudin 18.2 CAR-T product, which is the one that's most advanced in development from a company called CARsgen. We generated our own internal version of those cells and included that in this study.
And I'm pleased to say that on the left, you can see in the blue column, we had close to 100% killing of the pancreatic cancer cells. We saw the same for the CT041, the control CAR. And then when we look at CARs that had no CAR at all or no CAR, we see that there was really no killing. And looking at the graph on the right, you can see the inverse here when we look at how many of the pancreatic cancer cells were made in the dish, sorry, alive in the dish. And you can see that there's really very few cells remaining. So this is terrific. We're delighted that we're in the same ballpark as the leading Claudin 18.2 CAR-T. But I should reiterate, the goal for Arovella is not to stop there.
It's to use our CAR-iNKT cell platform, which has been shown and demonstrated to be more potent when tested versus CAR-T. So that is the next step for that program. Next slide, please. So just in terms of ALA-105 and taking that to IND filing. So we again will tick just what's been ticked off. Licensed the Claudin 18.2 antibody. We've converted that successfully into a CAR. Importantly, which takes quite a lot of time, we have developed in vitro and in vivo models ourselves to be able to test these particular therapeutics that we're developing. We have generated CAR-T cells with Claudin 18.2 targeting CAR functionality and confirmed their functionality. And now next, we'll incorporate the CAR into our iNKT cells and evaluate its activity in vitro. And then we'll look to incorporate our cytokine armoring technology, IL-12-TM, into the CAR-iNKT cells and complete mouse models.
Once we're happy with the data in those mouse models, that would trigger us to manufacture the GMP lentivirus. And then we complete process development for manufacturing before taking all that documentation and repeating the process for going through the IND write-up and putting all that into the IND and submitting that to the FDA or another suitable regulator. Next slide, please. So we do have a very exciting pipeline. I think it's maturing at the right rate. We do have an exciting time ahead for ALA-101, which we're looking to take into clinic quite soon. And ALA-105, still preclinical, but looking to rapidly capture data for that program. And so far, it is looking quite good. And IL-12-TM, looking forward to integrating that into all of our solid tumor programs. Next slide. Great. And one more update that Liz referred to in her address.
We have had a rigorous process since the beginning of the quarter, last quarter, to find a world-class addition to the Arovella board. And we have identified and selected an exceptional candidate, and we're currently negotiating the final details. The individual has been at a high-profile Australian life sciences pharmaceutical company, has a deep scientific and commercial background with a high level of experience in biotech operations, strategy, capital raising, as well as M&A. And the intention is for the individual to join initially as a non-executive director with the anticipated transition to the non-executive chair. And excited that we are looking to announce an appointment this quarter. Next slide. So with that, I'll just summarize by going through the upcoming milestones for the remainder of fiscal year 2026. So for ALA-101, we have largely completed all the IND enabling studies and looked to file the IND this year.
We're completing the preparatory activities for the first-in-human phase I clinical study as we speak. And then looking to, at the start of next year, complete the manufacturing of clinical batches and commence the phase I study and start generating data from those patients in those initial dose cohorts. And just to reiterate there, we are funded to already funded to obtain preliminary safety and efficacy readouts for that program. So for ALA-105, we'll continue to optimize the CAR for solid tumors and integrate it into iNKT cells and test the CAR in iNKT cells in gastric and pancreatic cancer cell models before moving into in vivo efficacy studies. And as I said, assuming the data for those is as we expect, we would move into the activities to manufacture, which includes lentivirus and process development, for example.
For IL-12-TM, we'll look to include that into all of our solid tumor programs. And for pipeline expansion, we will have a heavy focus on identifying new technologies that feed specifically into our iNKT cell platform to either enhance it or to give it more shots on goal against different tumors. And for the option with Baylor College of Medicine, that's something we are still continuing to be excited by. And we have the exercise date for that in November 2025, but making good progress with our due diligence and looking forward to the next steps for that program as well. Next slide.
So with that, I'll just summarize there and just say I think it's really clear, and it's not data from just ourselves, but from other groups, that we do have a very novel platform in the CAR-iNKT cells and that they have unique properties that we think set them up for success, not just in blood cancers, but more so in solid tumors. We already have established the clinical manufacturing process, which will feed into all of our other programs. Delighted that our lead is on the cusp of going into phase I clinical trials. Delighted that our programs continue to expand with our Claudin 18.2 targeting CAR and our armoring, as well as other CARs that we may bring on.
And again, I think for all these reasons, we are in a great position as a company and certainly looking forward to continuing to grow nicely and to deliver value in the months and years to come. And skip this slide. I think it's references, Matthew, and then I think we can move to the Q&A.
Thanks, Michael. One question that's just come through during the presentation. Does your company do exosome EV studies and have such products in your pipeline?
No, thank you for the question. We don't work on exosomes at all. It's just for those of you that are less familiar, it's a little bud that can carry material that buds off a cell therapy like an iNKT cell therapy. No, we don't work on those.
Thanks, Michael.
We might just give it another 20 seconds to see if any other questions come through on the presentation before we head on to the formal business. Nothing further has come through at this point, Michael, so I'll hand it back to you.
So Liz, I'll hand it back to you to go through the formal proceedings of.