Avacta Group Plc

Good morning and welcome to the Evactor Group CLC investor presentation. Throughout the recorded presentation, investors will be in the scenario mode. Questions are encouraged and can be submitted at any time by the Q&A tab situated in the right corner of your screen. Simply type in your questions and press send. Due to the high attendance on today's call, the company may not be in a position to answer every question it receives in the meeting itself. However, the company can view all the questions submitted today and publish responses where it is appropriate to do so. Before we begin, I'd like to submit the following poll. I'd now like to hand over to CEO Christina Coughlin. Good morning.

Good morning, and thank you for having us. I'm joined today by our Chief Financial Officer, Brian Hahn, and we will be presenting the fiscal year 2024 preliminary results for AVACTA Therapeutics. Let's jump in. We will be making forward-looking statements, and our disclaimer is noted here on the second slide. Let me start with a few of the highlights for AVACTA. The company has essentially, over the last year, undergone a complete transformation, and we are now positioned as a pure play oncology biopharmaceutical company. When we joined you last year, this was a joined-up diagnostics and therapeutics company, and over the course of this last year, with the divestment of one of the aspects of the diagnostics company with the second one coming. We are now focused on our proprietary precision peptide drug conjugate platform within the company and are poised to move this into the next stage. Let me tell you a little bit about that and how we are accomplishing that. Our first entry into the clinic and really The program that created all the buzz and all the excitement around precision is FAPDOCS. This is a FAP-enabled doxorubicin. It is the first precision program. There are two highlights for this one. The first is that we completed the Phase Ia, the dose escalation portion of the clinical trial, and multiple presentations have been made in peer-reviewed settings with those data. We opened the Phase 1B expansion cohorts. We will show you a bit more on the design of these today. And we anticipate releasing the initial data in salivary gland cancer in late 2025. We have also, over the course of this year, moved our ExaTCAN, our TOPA1, our second program. That one has moved into the IND-enabling status. What that means is that we have selected the clinical candidate late last year and have begun GMP, or good manufacturing practice, manufacturing of this drug for use in patients, and we anticipate filing this IND and getting this clinical trial started early in 2026. Importantly, we entered into a strategic collaboration with Tempest This has been leveraging AI to capture the full market opportunity, but also to drive smarter trials. I'll describe during the presentation of exactly how we're going to use these Tempest data, both capturing the market opportunity, but also that concept of driving a smarter trial with the FACT ExaPCAN program. You'll see there our cash information. At December 31st, $12.9 million. And as of April 30th, 2025, this year, $17.3 million. This was following the divestment of the diagnostics cash runway into the first quarter of 2026. We have strengthened our leadership of the company. We have our new chief financial officer here with me today, Brian Hahn. We have added our chief scientific officer, Michelle Morrow. And we have also appointed very recently two non-executive directors that will help direct the company into the next stage. Let's dive in a little bit further. Our two new additions to the leadership team. Brian Hahn joined us after a long, successful career with a NASDAQ-listed biotechnology company, Glycomimetics. And Michelle Morrow joins us as our chief scientific officer last year after coming to us from FSTAR that was acquired by Invox. Both of them have had very successful careers and join Avacta and will help take us to the next stage of the company. Let's dive into our research and development highlights and show you a bit of the pipeline progress that we are making. Just to reset the stage here, the precision platform is a peptide drug conjugate that leverages the enzymatic activity of a protein that is expressed specifically in the tumor microenvironment known as fibroblast activation protein, or FAP. While the peptide does bind to FAP, The important part or the important aspect of our platform is the ability of FAP to then cleave the drug and remove that peptide from the drug, releasing essentially that free payload into the tumor microenvironment. This happens extracellularly, so outside of the cell. Importantly, then, the released payload is able to leverage the bystander effect, meaning it can now move into a FAP-negative tumor cell, a FAP-positive calf. That released drug now able to move into and kill those local tumor cells. And so our highlights now of the precision platform first, our Tempest collaboration really allowed us to define the addressable population for the precision platform. And it also allowed us in the second part of that collaboration to really refine indication selection for our FAP Exit TCAM program, essentially leveraging AI to drive these smarter clinical trials. Describing that a little bit further is, it allows us to now walk into the trial with Exotecum knowing what are those tumor types where we really expect that greater activity. The intellectual property for the precision platform saw a big boost in that we developed and invented a sustained release mechanism. We were able to take that foundational IP and move it now into a whole new realm where we can now dial in the exact kinetics that we want of that release mechanism. That IP was filed in September and now essentially creates a reset for the company in terms of our intellectual property. The first program that will come out with that new IP is the FAP Exit TCAM program. Our two programs that we'll talk about today, SAP Dr. Rubison, ABA 6000. We have advanced into the expansion cohorts for this one. We have achieved a safety proof of concept. We have essentially eliminated the cardiac toxicity. This was a main goal as we were walking into this clinical trial. And one of the reasons that Dr. Rubison was selected is it is one of those therapeutics with a really problematic toxicity the cardiac tox. We felt at the time of moving precision into the clinic for the first time that if we were able to eliminate that cardiac toxicity, this would be a big gain and essentially show the proof of mechanism of the precision platform being able to reduce the toxicity. The clinical development path for ABA6000 has been defined with both salivary gland cancer and triple negative breast cancer. And we are in the planning stages towards the phase two trial. And that phase two planning is as well subject to funding. The FAP-EXD highlights, this one has moved now into IND enabling status. The clinical candidate has been selected. It is in manufacturing, and so the manufacturing process is being defined and worked on for that drug to be moved into clinical trials. The IND is anticipated late this year with the clinical trial of this one beginning in the first quarter of 2026. I like to think of our IP and our pipeline like an iceberg. And so what we can see out there are two of the medicines that have been invented by Avaxa, FAPDOX and FAPEXD. These are the two that we have shown the preclinical work. We have shown now multiple times the clinical work with FAPDOX. FAPEXD will go to the clinic in months. And this is what we can see. But what we can't see is the rest of that iceberg. And so we do have a confidential pipeline, and we have a number of aspects of this. We held onto and did not disclose our SAP EXD program until we had filed that important new foundational IP for the platform, that sustained release mechanism. That sustained release mechanism is almost a plug and play. The cap and the linker can be adjusted, and we can dial in the exact kinetics that we want of different therapeutic classes. And so what we can see now, that tip of the iceberg, we have two cytotoxic drugs. What we now have in the pipeline are multiple therapeutic classes. This isn't just a delivery mechanism for cytotoxics. We can deliver targeted therapies as well. Our Tempest collaboration was started to really allow us to understand the addressable market, the patient populations that we can help with this pipeline. And so turning then to our Tempest collaboration to understand the full scope here, We then started this collaboration with our first question to Tempus, which is, where are we seeing the fat-positive cancer types? How can we understand the exact patient populations that we can address? And so we developed two what we call cut points. This is RNA-seq data, and we have essentially taken our immunohistochemistry protein data and layered it now to understand using AI, where are the fat-positive cancers? It turns out that it's essentially all of them. Solid tumors express a tremendous degree of fat, which allows us now to essentially understand that fat-positive disease settings. With that tip of the iceberg, our two first programs, FAPDOCS and FAPEXD, let me call out for you now. Here are the disease settings that we will be going into. Think triple negative breast cancer and salivary gland cancer. Then let's look at some of the top indications that we are thinking about for FAPEXD, pancreatic cancer, gastric cancer, small cell lung cancer. These aren't the only ones that we will be taking forward. But if you just add up there the fat positive disease settings, we will be impacting with just these two drugs over a million lives a year. Now, to address the other diseases that you can see here, it will require additional precision medicines. And that's where This reset that we did with the intellectual property is so important because we now understand to a much greater degree how to deliver individual medicines with the exact kinetics that we want in the tumor and the plasma. We can dial in exactly what we want with that new foundational IP that was filed in September of 2024, just a few months ago for the company. A big, important development for us was that sustained release mechanism. We'll talk a little bit about that later. First, let's do a little bit of a dive into FAPDOCS and where we are with this program. We've seen this slide before. This is the design of the completed dose escalation trial that happened with FAPDOCS in the clinics. We will be showing you the updated data that was just published in April of this year in the salivary gland indication. And you can see there the number of cohorts that have been enrolled and the recommended dose for expansion, the RDE, has been identified. We will be looking at these doses and these cohorts that have been analyzed for efficacy. It's important to note in a phase one trial, such as what was conducted for FAPDOCS, that there is a heterogeneous patient population. Multiple disease settings were enrolled in this particular trial. And we will now analyze the efficacy based on those indications that we will be taking forward. And you can see now we are enrolling the expansion cohorts in triple negative breast cancer. high-grade soft tissue sarcoma, and salivary gland cancer. We'll take you through the design of these cohorts as well moving forward in the presentation. As I mentioned earlier, we have achieved a safety proof of concept with precision. Walking into the clinic with this first drug program, FAPDOX, we took doxorubicin forward as the first entry into the clinic for a number of reasons, one of which is depicted on this slide. We knew that there was a key toxicity with doxorubicin that if we could eliminate it, it would essentially show proof of mechanism, proof of concept of the precision platform, and it was the cardiac toxicity. Now, there were a few steps that we had to take to get to this conclusion. The first is entering the clinic and going through the dose escalation, where we achieved nearly four times the dose level of this extremely toxic drug in the clinic. And extending beyond the key lifetime maximum that we usually use in oncology with doxorubicin, Doxorubicin is usually halted at a lifetime maximum of 450 milligrams per meter squared. But because of the cardiac safety that we were observing through the course of the trial, we have been able to extend that to the lifetime maximum of 550 milligrams per meter squared. In the doxorubicin label there, noted by the aster or the arrow, is that the cardiac toxicity would be observed in 6% to 20% of patients treated at that lifetime maximum. If we compare that with the other arrow, it is zero with AVA6000, and we call that proof of concept of precision in terms of eliminating toxicities. We also see a dramatic reduction in the bone marrow toxicities, we see a dramatic reduction in alopecia or hair loss. And there are zero, no reports of ADC-linked toxicities, probably the most important one being the pneumonitis or the lung toxicity that is seen with pretty much all of the ADCs, and that is because of nonspecific release. The key difference with precision is our release mechanism based on FAP is going to be highly tumor-specific, and so we do not see release of the active free payload in organs such as the lung to create that lung toxicity. So several important safety conclusions for FAPTOX. Importantly, we also want to see that this impacts efficacy. And here we need to look at specific indications, and that allows us to make predictions of what will happen when we move into expansion cohort phase two. And so what we see here in an indication salivary gland cancer that is known to be highly chemorefractory, we see patients with multiple minor responses, one patient with a deep, durable partial response, and a disease control rate of over 90%. These data are very exciting to our investigators, very exciting to our team at AVACTA, mainly because the unmet need here is so high. There is really no standard of care here other than androgen deprivation therapy, and most of these patients on this slide have received that. And so you can note the asterisks, which are indicating patients who are still ongoing, their bars can only get better, and the patients with the diamonds where we are still observing them for PFS. Progression-free survival. How much time will patients get out of this drug? How long will these responses last is important for us. Patients generally don't ask, how much did my tumor shrink, doc? They usually ask, how much time do I have? And that's where progression-free survival as an endpoint is so important. And so we have not reached the median PFS in this cohort of patients being observed, but it is at least 5.9 months, which compares very favorably and is almost doubling the benchmark 3.5 months that was published by the EORTC last year in a large cohort of 54 patients at ESMO. We're very excited about these data and look forward to moving into the expansion cohort data, which will be later this year. We will also continue to update on these patients as we have not reached median PFS. Let's now move to this is my favorite slide in the deck. Second favorite, as I noted, is that Tempest slide at the beginning. But this one is my favorite. Why? It shows proof of mechanism. This is exactly how we designed the precision platform to work in the clinic. On the left-hand side, what we see are the tumor biopsy data. These biopsies were taken across the phase one, and so across different doses. And the biopsies were taken, they were optional for patients, and they were taken 24 hours after the first dose. So only a single dose of drug was administered in these patients. And we asked the question, are we seeing concentration of the released free payload, or doxorubicid, in the tumor versus plasma? And the answer was a resounding yes. The animals would have predicted a 10 to 20x, and what we see is a median of 100-fold concentration of doxorubicin in the tumor microenvironment. Why was this so exciting? Well, we knew that conventional doxorubicin in red here was going to produce about a one-to-one ratio. That's what we expect with cytotoxics. There's no concentration mechanism. It is with the precision peptide attached, that micropeptide, two amino acids, that we now see this concentration of the warhead in the tumor microenvironment. Now, this is 24 hours later. We didn't need a sustained release mechanism because the half-life of doxorubicin alone is so long. It's a full 35 hours. Why is that important and why did we now have to develop and invent? Why did we go after that sustained release mechanism? Why did we develop all of that new IP? It was to be able to take payloads that have a half-life mechanism, that have a pharmacokinetic problem, and be able to take those forward. And that's exactly what has happened with our next drug. Let's look now, FAPDOCS. How are we gonna take this one forward? So here's our projected timeline. We are now in 2025 enrolling the phase one expansion cohort in salivary gland cancer. And that is to set us up for that next trial that you can see there as we move towards a phase two, three. The idea here in a rare disease such as salivary gland cancer, being able to go forward in a pivotal trial, this one would be designed as a phase 2-3. The two endpoints would be progression-free survival and overall survival. And as we project it now, we could be in an NDA in 2028 with launching then in 2029. That would be based on something called an accelerated approval strategy. Again, all of these conversations will have to be had with health authorities. What will happen then, and the second part, would be the triple negative, and we are enrolling that expansion cohort currently, looking at a potential setting of a non-registrational phase two trial that would set up then that phase three. This development scheme is based on exactly how Tredelvi just moved into that first line setting, opening up a very nice market opportunity in the second line setting. We have been clear that we are looking for and having many conversations around a potential partnership around this SAP DOCS program. Our Phase 1B expansion cohorts are enrolling now. A little bit more about the design here. They are designed to provide us additional clinical data that will allow us to better understand and better plan those next trials. So additional patients understanding exactly what is the progression-free survival we would be seeing, how many responses are we seeing. All of these data will then be used to plan the statistics around the next trial. All of the expansion cohorts are using the same dose. The recommended dose for expansion that was selected is 310 milligrams per meter squared, and it is being dosed every three weeks in three different expansion cohorts. The first one being triple negative breast cancer, up to 30 patients will be treated here, and patients are being treated in the first to the third line setting, so up to two prior lines of therapy. The second and the third cohort are high-grade soft tissue sarcoma, again, up to 30 patients. UPS or undifferentiated pleomorphic sarcoma and de-differentiated liposarcoma. Patients are treated here in the first and the second line setting, so zero or one prior lines of therapy. And salivary gland cancer, up to 30 patients. Any histologic subtype, important to note that this is somewhat of a heterogeneous disease setting, one of the key questions we have here is do we need to limit those histologic subtypes or can we treat every patient with salivary gland cancer? So some important questions that will be answered in the expansion cohorts, allowing us to then essentially plan out and understand better, be able to risk manage those next trials that we will move towards. We are knee-deep in our ongoing commercial analysis of the FACT Docs program. There's a couple of key highlights here. We intend to seek an initial approval in a small population. This is a rare cancer, salivary gland cancer. Rare cancers can often garner a high price point. That will then move into the triple negative breast cancer in an approval that is slated now based on data that were released at ASCO just a couple weeks ago in terms of the second line setting. In terms of the price point, the advantages of that first indication, rare cancers often get orphan pricing. It could potentially avoid the IRA. And we are unlikely to see diminution of that price given the high price point that we see in triple negative breast cancer with that ADC, TRODELV, there. We are currently ongoing and working on label expansion opportunities for AVA 6000, an important analysis for us to be doing now as we move through the expansion cohorts. That's our update on FAPDOCS, our first program. Let's talk about a little bit around our second program. I mentioned earlier that Given some of the data with FAPDOCS, we were going to be able to take now much more potent payloads into the clinic with our precision mechanism. Exotecan is an ideal payload for us to move forward for three key reasons. The first is it was tested. It was never approved, but it was tested in many patients. Many Phase II trials were run. A single Phase III trial was enrolled in pancreatic cancer, and so we see single-agent activity of this drug. It is the most potent TOPO1 inhibitor out there. But you may ask, why TOPO1? Well, we know that TOPO1 is a very active ADC payload. It is on multiple ADCs that have been very successful in the clinic. That gives us, you know, a leg up. Duruxtecan, very similar to Exotecan in terms of their potency and their molecular structure. So we have evidence that Duruxtecan works in a couple of disease settings, gastric and breast cancer. And that is an important piece of evidence for us taking this one forward. But finally are the inventions made over the course of 2023 and 2024 that form the basis of that new IP, we're now able to take a drug with a very limited therapeutic index and significant PK issues because we have that new sustained release mechanism that could now be implemented in the clinic to take a drug with a significant half-life liability into precision and completely transform it in the clinic. What do I mean by that? This is a key figure, and this is a key experiment that was run. These are modeled data based on animal studies that have been conducted, and I choose this one because it is a low-dose experiment. We are taking 15 mg per kg forward when we can dose up to 40 in patients with this program. We know that the half-life there that we depict in the concentration time plot is only nine hours of exotecan. And so what the new invention does is depicted right here. We take the precision mechanism, which includes high tumor concentration, low plasma concentration, which you can see comparing the blue and the red lines, concentration time plot. And what's important is that we now extend the half-life from only nine hours out to over 60 hours in the tumor. And so we take it from only hours to days with this sustained release mechanism. We didn't talk about this until we first published it in October of last year, and that was because the IP was filed in September. This IP now forms almost a reset for the company in terms of the intellectual position. What this allows us to do is to implement this new IP across all of the programs going forward. This was a very exciting figure. I can still remember the day that these data came in showing that the sustained release mechanism works. Looking at the timeline for the SAP EXD program, We will be moving into the GMP. We're moving through the GMP manufacturing over the course of 2025, toxicology studies. All of these form the basis of the IND enabling studies. As well, the clinical trial is being written, conversations had with health authorities, which we expect then the IND to be filed late this year with a phase one start in the first quarter of next year. This trial is going to be driven by another part of our TEMPEST collaboration, looking at what are those sensitive tumor types for us to move into. And that converts the, essentially, the empiric nature that we used of the DOCS trial of looking for those indications, those sensitive indications, allowing us to understand payload sensitivity using AI, and that allows us to walk right into a clinical trial limited to those disease settings where we anticipate seeing activity. We expect to have the initial data from the Phase I trial at the end of next year and potentially be moving in the first quarter of 27 to the expansion cohorts for this one. I mentioned we have an enviable IP position in the company. Let me explain why. There are three main IP families that we talk about. Our foundational IP, which formed the basis of the therapeutics company as it was started, was licensed from Bach Bio, which grew out of Tufts University. And this is the foundational IP. This is the IP around the peptide drug conjugate. which has now hit a reset button with the filing date in September. This is a sustained release mechanism where we implemented the CAP and the linker, allowing us to essentially design and to dial in the exact kinetics that we want of the precision program. It opens up a number of different therapeutic opportunities, not only cytotoxic, but as I mentioned, targeted therapies, multiple other types of therapies can now be used because we can implement multiple different linkers, multiple different capping groups, and dial in those exact kinetics that we would like. So this IP is not just FAP-EXD. It's now going to go across the entire pipeline. The third thing, patent family that we have is the biologic drug conjugate IP. And what that allows us to do, think of this linker, think of precision as being a linker in an ADC-like mechanism. And that is deep in the research. That's part of the iceberg that isn't necessarily always seen. But deep and enviable IP position for the company moving forward. And I'm going to turn it over now to Brian for our financial highlights. Brian, the floor is yours.

Thank you, Chris. So top priority is to establish a sustainable long-term financing strategy in order to realize tremendous opportunity going forward, which requires additional funding. So, we've invested $14.27 million. In 2023, it was $13.11 million restated and researched in line with expectations relating to the precision and aftermarket therapeutic programs. Admin expenses increased to $12.05 million compared to $7.89 million in 2023, primarily related to executive management changes and professional expenses relative to shift toward a pure play biotech company. Overall loss from continuum operations was $28.98 million. compared to a loss in 23 of 29.15 million. Operating cash outflows from continuing operations was 24.5 million compared to 14.87 million in 2023. This reflects elevated R&D expenditures and one-off costs associated with organizational realignment that occurred during the year. Net cash inflow from CCM and financing activities of 26.1 million as compared to 1.3 million in 2023. This is primarily from proceeds of issue of share capital of $31.1 million compared to nil in 2023, plus repayment of convertible bonds of $3.1 million in July of 2024. Cash-to-cash equivalents was $12.87 million at December 31, 2024, compared to $16.63 million as of December 31, 2023. Cash as of April 2025 was $17.3 million following the divestment of the launch diagnostics business, which extends the cash runway into the first quarter of 2026. Back to you, Chris.