Avacta Group Plc (AVCT) Earnings Call Transcript

Good afternoon, and welcome to the Avacta Group Plc investor presentation. [Operator Instructions] Due to today's meeting, the company won't be in a position to answer every question received during the meeting itself. However, the company can review all questions submitted today and publish responses where appropriate to do so. Before we begin, I'd like to submit the following poll. I'd now like to hand you over to the management team. Chris, good morning.

Good morning. Thanks, Lilly. Thank you to everyone who is joining us today. Brian and I are thrilled to be bringing you our interim results. And without further ado, let me dive in. So we are advancing our next-generation pre|CISION platform. This is a tumor-activated peptide drug conjugate that can deliver our payloads with optimized kinetics using a specific mechanism that is highly innovative and new in the peptide drug conjugate field, which is a mask and release. pre|CISION masks a potent payload behind that peptide that's cleavable only by FAP. And FAP is a protease that is abundant in solid tumor stroma and it's near absent in healthy tissue, which allows us then to widen the therapeutic index of highly potent payloads that are otherwise limited by their toxicities in the clinic. And so our lead asset, FAP exatecan or AVA6103 that we'll take a deeper look at. So it's the first of this next-generation peptide drug conjugate. This is a FAP activated, but it's importantly, it's a controlled release version of exatecan. When we initially looked at this potent payload as a potential for pre|CISION, it was really limited in the original clinical look at exatecan back in the late '90s, early 2000s. It was limited by both its potent toxicity. 90% of patients have severe neutropenia, but it was also limited by its PK. And so that's where these advances in pre|CISION came from. We'll talk a little bit about these inventions that led to this clinical program. The Phase I FOCUS-01 trial has been dosing since March across 6 indications, gastric cancer, colorectal, cervical, small cell lung, hormone receptor-positive breast cancer and pancreatic. And probably our favorite of these various indications are the GI cancers, where we have really good evidence that the TOPO1 mechanism works and as an added benefit in gastric cancer, we have evidence that a similar mechanism in an ADC, ENHERTU that uses a very similar payload deruxtecan has nice activity. We have -- out of our next-generation pipeline, we have 2 shots on goal that are coming to the clinic. AVA6103, as you can see there, we have published 5.5 months after the trial started. We have published our initial clinical proof of mechanism data. We will take you through some of the more, I would say, meaningful slides in today's presentation. We also have shown significantly higher tumor concentration. These are preclinical studies, selectivity and activity versus in ENHERTU. We're going to be updating these as we move towards our ESMO presentation. ESMO begins, as you know, in just 8 days. Our second of the next generation is AVA6207. We believe that this is one of the first dual payload peptide drug conjugate programs out there. We will be presenting a little bit later this year, the candidate selection and all of the data that goes into that. This is the clinical candidate selection. So the final drug will be presented in the second half of 2026. Also the data that will support moving towards that IND and launching the IND-enabling studies. Why does our next generation win? Well, it wins because it's been derisked in patients. So pre|CISION, the first generation of pre|CISION is AVA6000. We've demonstrated 3 important aspects in this program. The first is we've optimized the safety and the payload was concentrated. We've published these biopsy data showing 100:1 concentration of the payload in the tumor versus the plasma. We've also shown excellent cardiac safety. One of the key safety features or one of the key toxicities that we see with the payload doxorubicin in the clinic is cardiac failure, and it is incurable. And so the bar for the evidence to lift that lifetime maximum in the clinic was quite high. We published the data leading up to that. We're very proud. In a lots of factors there, and we will be presenting additional data. We've also seen durable RECIST responses in our lead indication in salivary gland cancer, even again, at the lowest levels of FAP expression, which we published back at ASCO and Bio International in May and June of this year. So updates on all of these programs will be coming in the next couple of months before the end of the year. So the time line there at the bottom. In September, we published the proof of mechanism data with AVA6103. We're going to take you through some of the key data slides here today. The dual payload will go through candidate selection that is coming. The AVA6103, the efficacy readout will be in the first half of 2027, but we will commit today that the tumor PK will be out year-end or early -- very early in 2027. We do have ongoing multiple discussions with multiple pharma partners. The IP estate is building. And as Brian will describe a little bit further, we are looking at a potential NASDAQ dual listing during 2027. So the next generation of our precision medicines, this peptide drug conjugate drug class, we are aiming to deliver activity that is more robust than the ADC class, which is probably one of the most successful classes of drug in oncology right now. So this innovative drug class achieved a robust efficacy, but using small molecule chemistry. We'll take you through a little bit of how our scientists invented this. And what are the 3 goals? So first, it's to release the payload in a tumor-selective manner. This is really to address some of the key toxicities that we've seen with both ADCs and PDCs similarly. The second is to protect normal tissues. And that's through this masking effect. We've seen this and shown it clinically with AVA6000 that we can protect normal tissues. We alter the biodistribution of the payload by using the pre|CISION mechanism. And finally -- and this was big for the next generation. We modulate the PK of the payload. Recall back, I mentioned that exatecan had a real PK problem in the clinic. It has a very short half-life. So it had to be dosed daily, which is incredibly inconvenient for patients. And so we want with a single dose of our drug to deliver just like an ADC with controlled exposure in the tumor. And what we found is that we do get a nice Cmax. So we get a nice hit of payload in the tumor right upfront. And so the pre|CISION next-gen controlled release PDC platform is designed then to achieve all 3 of these goals using our innovative small molecule chemistry. The added benefit of this being a small molecule is that we save a lot of cash on the GMP manufacturing. It's about 1/3 to 1/2 of what you would spend to manufacture an ADC. Now the pre|CISION platform, it has a very large market opportunity. About 90% of all solid tumors express FAP. This is a large experiment that we did -- study that we did, both internally with immunohistochemistry, but also with our collaborators at Tempus looking at about 160,000 human solid tumors using these combined methods. We didn't do immunohistochemistry, which is a bit more labor-intensive. But the RNA analysis looks across all of these tumor types. And what I can tell you is that we have not found a single solid tumor that does not have very robust expression. And so that represents a very large market opportunity. There isn't a single pre|CISION medicine that will work for every one of these, which is why IP and managing that pipeline delivery, again, with capital efficiency is critically important for Avacta going forward. What do we mean? Let's unpack a little bit about first generation versus next generation, the whys and the how. So the first is why. Well, let's look at the first generation. This was a direct peptide link between the payload, doxorubicin and the peptide. And you can see the actual chemical structure of the drug there. The peptide is in gray and the payload is in light teal. A couple of things to note here. Doxorubicin has a chemical structure that sits nicely in the active site of FAP. And that is required for FAP to be able to cleave this peptide. It turns out that this direct peptide link is actually a highly efficient substrate -- and so it enables very rapid cleavage. So the main mechanism of metabolism of this drug when it enters the human bloodstream is actually cleavage within the tumor. And so we had to do a couple of things in order to get a drug like exatecan to work. The first is that we needed to slow down the cleavage. We really -- we know from a very old theory, it's called the Norton-Simon hypothesis, was published back in the '70s. We know that we need for some of these enzymes that are important in DNA metabolism, we need at least 3 days of coverage. We need to shut that enzyme down for 3 days. And that just isn't going to work with an 8-hour half-life. And so that's where the capping group comes from. The capping group that we've introduced, you can see over there in navy blue, the capping group is designed to hold our peptide drug conjugate in the active site of FAP and create almost a reservoir within the tumor. So we want the tumor to hold on to the drug. Otherwise, it gets eliminated by the kidney pretty quickly. The second part, and these 2 inventions work together, but the second part is a chemical linker that is essentially to mimic that part of doxorubicin that sits in the active site. And we've invented and borrowed some of these -- there's multiple chemical linkers that have been used in the ADC field and small molecule field. And what we found in these inventions and investigating this is that we can get very variable speeds of release. And so that's why we call this controlled release. Now for exatecan, we needed to create sustained release. So we needed to really slow it down. But we have various levels. And so we can dial in the PK that we want of any given next-generation pre|CISION medicine that we make. And so this controlled release enables 3 important things. The first is we get very, very much so greater PK control. We now know that we can keep the drug right in the active site. We can have the tumor take it up and be a reservoir. The second thing is that we can control the release in the tumor. As I mentioned, we can get it to release very quickly or in the case of exatecan, we can get that to slow down given the very short half-life of this drug. And because we have multiple linkers and it allows the drug to sit outside of the active site, we've now been able to really expand the pipeline potential here and get many more -- a large number of small molecules to work with pre|CISION enabling. That brings me to the Avacta pipeline. We do have 3 programs that are now deploying our pre|CISION platform. Our first 2 next-generation programs, AVA6103, which is releasing exatecan. You can see the indications as we've talked about already. This one is working through its dose escalation period of the Phase I trial. Our next milestones with this one, as I mentioned, we are going to be publishing the tumor PK. That started at Cohort 3. That will be in late fourth quarter or very early in the days of the first quarter of 2027. We won't be dropping data in at Christmas time. But -- so either late in the fourth quarter or early -- very early in the first quarter. The efficacy data then will be in the first half of 2027. As I mentioned, this trial started in March. First data came out in 5.5 months, showing the proof of mechanism, and we're looking forward to those few updates. The dual payload, which we have not disclosed the indications. We'll show you some of our ideas later. This one is combining a potent Topo 1 inhibitor along with one of the key resistance mechanisms targeting DNA damage. With that one, we will be looking at announcing the payloads and then all of the data that's going to be supporting that clinical candidate selection that will all be in the next 8 weeks, essentially as we move towards the end of 2026. And then some really important updates that we have on faridoxorubicin, our first-generation drug. This one, we're going to be updating that lead indication in head, neck cancers, the salivary gland subset. We are going to be looking across the Phase Ia and the Phase Ib data. We will be updating in the second half of '26. ESMO starts in 8 short days and some really important data will be coming for both faridoxorubicin. Critically important, we're going to be looking long term. there with that update, really understanding how patients have been doing that have been on the trial for quite some time. And then we will also be updating AVA6103 preclinical as well as a trial in progress at ESMO. So lots of important data will be coming out in Madrid in just a short period of time. So taking a look at the pre|CISION platform as a whole. We've designed pre|CISION and especially the next-gen to look at 4 key opportunities that we think we can make the drug conjugate aspect look a bit better. And the first is payload release. We know with the ADCs that one of the challenges are these organ-specific toxicities because of the nonspecific protease cleavable linkers. These are lung toxicity and liver toxicity, pneumonitis, hepatitis. And because we get tumor-specific release by FAP, we aren't seeing any of those toxicities now deep into AVA6000 and as well through the first several cohorts of AVA6103, we have no pneumonitis, no hepatitis. And importantly, as I mentioned, for AVA6000, no cardiac toxicity. We can now use a dose-dense regimen to treat resistant disease. And so the idea here is that by increasing the dose density, putting those doses closer together, we actually increase the amount of payload that we can deliver. That is limited in the ADC field by the PK of the antibody, but also the safety of the payload as some of it is released in plasma. And so the whole idea with the next generation was to really keep that payload out of the plasma. The internalization dilemma. So -- with an ADC, payload is released following the slow process of internalization because it is targeted to a tumor antigen through that antibody. But our peptide drug conjugates have a very simple extracellular release. FAP is an extracellular enzyme expressed on the cancer-associated fibroblasts. And that simple release results in the killing of FAP-positive and FAP-negative cells. It's important that in salivary gland cancer, every single patient has FAP-negative tumor cells, FAP is only expressed in the stroma. So that indication and just the number of patients that we see that durable tumor shrinkage is critically important in that program. Tumor penetration, also critically important. It can take up to 24 hours to see that payload release within the tumor, whereas we see it within minutes. with the PDC. So we have a very rapid Tmax in the tumor. We actually get a very nice Cmax in our animal models. And all of that, importantly, is delivered with small molecule chemistry and manufacturing. That saves a lot of money as we move towards the GMP manufacturing of our drugs. So let's look at the clinical trial for AVA6103. As I mentioned, we have both the standard arm, which is in every 3 weeks there at the top, and we have the every 2 weeks arm at the bottom. This is the dose dense regimen. And in bold below the dose levels, you could actually then compare that 50% increase in the dose intensity that we get with the every 2 weeks arm is critically important. And we can keep this one going as long as we continue to see that very favorable safety profile that we have described with the proof of mechanism data. As we move through the dose escalation, this will only be limited by toxicity. We will be escalating -- we can even escalate beyond dose level 7 if the safety allows. So these oncology trials, especially using the Bayesian design, the BOIN design really allow us to be flexible with dose levels and respond to safety as we see. These arms are enrolling in parallel. It really does increase our ability to treat patients and to move towards all the data selection that we see there. On the right-hand side, you can see we've sketched out a number of expansion cohorts. We're going to determine based on the data, make a data-driven decision, which of these will move forward once we've identified the dose in the trial. So if we look first, at the time that we reported data last month, we had completed and analyzed the data, including the PK data for the first 3 cohorts in the trial. And we're comparing here with 2 different programs. First, ENHERTU. This is an ADC that uses a very similar payload deruxtecan compared with our exatecan. And the dose levels are very similar in the first 3 dose levels in the ENHERTU trial and the first 3 dose levels in terms of payload dose with the AVA6103 trial. And then exatecan, it's important to note that the MTD in pretreated patients was dose level 2 in our trial. And so by the time we move to dose level 3, we were looking at a 50% higher than the maximum tolerated dose. And the safety that we're presenting here is the safety that is published at that MTD. So now we're 50% higher. And you can see there, we have no neutropenia. This is the most important barometer. So the neutrophils are part of the immune system. They're part of the -- one of the key parts of the white blood cell component of the bloodstream. We can't transfuse neutrophils. They are the infection fighters. And we see no neutropenia through these first 3 cohorts. We are thrilled by that really shows that we're able to keep the drug out of the peripheral blood. We do see a single grade 1 case of thrombocytopenia and nausea and vomiting through the first 3 cohorts and a couple of cases of grade 1 anemia. So a really favorable safety profile. We're thrilled with this despite, again, getting 50% higher dose of payload above the MTD of exatecan, the payload in the clinic. And so now we're going to turn to what we think are some of the most important data, which is really understanding the pharmacokinetics and starting with the plasma PK and really understanding what is going on in the patients through sampling in the bloodstream. And I'm going to take you through, first here, the chemical reaction that we are measuring because again, this isn't a made up drug. This is a drug that needs to go through a cleavage event by a resident enzyme FAP that exists in the tumor. And so what happens, you can see here, this is just a schematic of AVA6103, describing where the capping group and the linker are and how exatecan sits out outside of the binding pocket. So the drug fits nicely then into the FAP binding pocket. We can't measure this. So this is the reaction complex that is formed and the speed with which that reaction occurs, again, is determined by the gray portion there, which is the linker. That gets broken down, as you can see there, all the way over on the right-hand side, and we released now reactants or 2 products of this chemical reaction. The first is released exatecan, and the second is the released peptide. Now importantly, I measure -- I mentioned that released exatecan has a very short half-life in the clinic, only 8 to 9 hours. It was one of the things that was very challenging in its initial development back in the late '90s, early 2000s. Even shorter half-life, though, is our released peptides, only 2 to 3 hours. And so in order to measure this in patients, if we get the drug -- if the drug is doing what we designed it to do, these are going to be released into the bloodstream at very low levels. And so we drove those assays way down to a very low limit of detection of 0.1 nanograms per ml. What we're going to do next is look at exactly what the animals were telling us and what the preclinical data told us of how this drug was going to work in the clinic. So the first, I'm going to take you through the 4 colors here. It's a very busy figure. But if we break it down by colors, I think you'll see that the drug is designed exactly to behave as we've chatted about. So each dot here represents a small group of animals, and we're looking at both plasma as well as tumor in this figure. So let's start with the joined-up drug, which is in gray and navy blue. Gray is in blood and navy blue is in the tumor. So the joined-up drug, AVA6103, we get a nice peak there at #1 in -- as soon as the drug is infused into the bloodstream. It drops down then very quickly to a pretty low level. And what's happening there is depicted in navy blue. The drug is now being taken up by the tumor. And what you can see there is that we get joined up drug out 5 days later in the tumor. So that's where we're creating this reservoir. We want the drug to sit right in the tumor and be able to reload the tumor from the low level that's in the bloodstream. Now we're going to look at the product of the reaction, which in this figure is exatecan. So the released exatecan in the tumor is in dark teal and in the bloodstream is in very light teal. What you can see here now is in the released exatecan in the tumor, we're now able, over the course of those 5 days to slowly release the exatecan. And what you can see is if we look way out to day 5 there, we still have it being released above the IC90 of exatecan. Now the IC90 is -- it stands for the inhibitory concentration where 90% of tumor cells in a dish are being killed by exatecan. It's a key factor that we use to sort of describe the potency of a drug. This one is somewhat low because exatecan is such a potent drug, but it was critically important in the design of this drug that we get multiple days of coverage, again, back to that Norton-Simon hypothesis. We get multiple days of coverage within the tumor, and that's step 2, but that we don't get that in the bloodstream. And that's over there at step 3. So in very light teal, we see that the exatecan, it comes out in that initial burst of cleavage that we see in the tumor. It comes out into the bloodstream and it disappears within 2 to 4 hours. And the whole idea there is that masking. So the drug itself, AVA6103 is not going to cause the toxicity. But it is that released exatecan, and we wanted it to disappear very quickly from the bloodstream. And so we use this figure. This is exactly what we designed this drug to be, and we're going to use this figure as we move into the clinic because understanding is the drug doing what we designed it to do in the patients is critically important. And so now we're going to move into the clinic. This is the first figure. This is the first cohort of patients in the trial and understanding the PK and a couple -- 3 important observations is, first, we see a rapid decline in navy blue of the plasma level of the joined up drug, AVA6103 or the peptide drug conjugate. That's -- importantly, it's going to be retention in the tumor, but also that slow rate of clearance that we've seen, and that's the capping group was designed to affect both of those for us. We also see in the patients here a very low sustained release of exatecan in the plasma. Now recall, the half-life of exatecan is only 8 to 9 hours. So as you're getting out days after the dose was administered and the exatecan is still being detected, it has to be being produced somewhere. It's being produced in the tumor. And that's based on our preclinical data that we showed in the previous slide. We're getting that reservoir navy blue in the tumor, but we're also getting dark teal. We're getting that drug being produced within the tumor. Probably even more important because of that really short half-life is the slow sustained release of the peptide. Now the peptide is detectable in the bloodstream of the patients. It's detectable 2 days after that dose was administered. It's actually the highest level. You can see there the confidence intervals are going to overcome each other. But the absolute value there of the peptide, it's detected 2 days later. So it's both of those products being produced, that's going to be cleavage that is occurring within the tumor given that reservoir. Now the next step that we're going to do is pull these last 2 slides together and understand did our -- is our modeling happening in the clinic? Are we seeing -- is the drug doing what we designed it to do. And that is this busy figure looking across the 3 dose levels, 1.5, 3 and 4.5. And there's 4 different lines in each of these. Let me walk you through. We're going to look at both what we anticipated and modeled in the animals, and that's going to be in the solid lines. And then what we see in the clinic is going to be in the dashed lines. In dark navy blue is going to be AVA6103, the parent drug. And then in light teal is going to again be the released exatecan. And let me walk you through a couple of factors here. We look back -- this is the figure that we just looked at, at 1.5. This is the first dose level. It's actually pretty spot on with what we anticipated. We get asked the question a lot, why do we see this little peak of the light teal in the animal modeling. And that's because mice have about tenfold, 10x times the soluble FAP in their bloodstream. And so we do see in the animals that little peak that happens in the plasma. And similarly, with AVA6000, we saw this in that program as well. We just don't see that peak in humans because we don't have very much FAP in our bloodstream. So 1.5 mg per meter square first dose level worked out quite nicely. When we move to the next dose level, we have a very interesting observation, one outlier in the trial that we call out there and that we do see this figure of the extended exposure of the peptide drug conjugate and that's driven by a single patient. It's exactly what we saw though in a very low FAP model is that we see sort of that extended exposure. That's exactly what the CAP was designed to do was to prevent that rapid kidney filtration of the drug. So we were incredibly encouraged by observing this in that second dose level. And you can see there, we do get -- these are log scales, but we do get that nice dose responsive increase -- slight increase in the plasma level of exatecan, but we also get that nice increase and spot on with what we modeled with AVA6103. Now if we move to the 4.5 mgs per meter squared spot on with what we expected from the animal studies. And you can see there the rapid decline of AVA6103 dash lines in patients in the plasma. Down to the lower limit of detection out 2 days, but we're still getting that sustained release of exatecan. And so this is exactly what we expected to see as we continue that dose escalation. And so these findings are really increasing our confidence that this nonclinical to clinical translation is performing exactly as intended. And we ask those who have been following us to think back to all of the animal models that we published where this drug is really nicely shrinking, both low FAP, high fat, and that will be some of the next data along with the tumor PK that we have guided will be late this year. And so last data figure that we're going to look at here, we prepared the known PK of the release of deruxtecan from ENHERTU. And this is essentially using AI to recreate these data sets from the published data with ENHERTU and its release of deruxtecan versus what do we see with the release of exatecan from AVA6103. Now we're looking at the first 3 dose levels for each of these. And the message here is that we're seeing about estimates 3x lower release in the plasma of the payload than was seen with equivalent doses of ENHERTU. Why is that important? Well, you can see our exposure, just as we saw in the animals, the exposure in the bloodstream disappears pretty quickly with those first 3 dose levels of AVA6103 as opposed to -- and in PK figures like this, when you stop the lines, that was when you stopped detecting it above the lower limit of detection, which is depicted there at 0.1 nanograms per ml. And you can see at dose level 2, which is in the very light green as well as dose level 3 and the rusty color of exatecan -- or I'm sorry, of deruxtecan released from ENHERTU, we still detect that out multiple days later. Now low levels, but even those low levels in the plasma can create some of those toxicities. So we are thrilled with how AVA6103 is behaving in the clinic thus far. And this slide sums that up. So we have a very favorable safety profile of AVA6103 in the clinic compared to both conventional exatecan as well as ENHERTU, we think those are 2 really important comparators as we start to measure what this drug is doing. Now the comparison of the preclinical model PK and the clinical trial PK demonstrates just a really exceptional alignment for the first 3 dose levels. I've been doing this a long time, 20 years now. And this is really the best preclinical to clinical translation that I've seen in my career. So this remarkable consistency really increases our confidence that AVA6103 is performing exactly as we intended and that our robust preclinical data will translate into the clinic. We think AVA6103 is really -- is performing exactly as intended, and the dose escalation continues. The biopsy data will be coming soon and the efficacy data as we get into the first parts of 2027. So turning back to the pipeline, an invention that we were extremely excited about from our chemists and our biologists was to adapt this next-generation platform, develop new linkers that actually had a couple of different pods where we could attach 2 different payloads. Now similar capping group, so we're going to create that reservoir similar peptide, which is going to be cleaved by the FAP enzyme. But importantly, the invention here is around the self-emolative linker. We still have the ability to guide the PK and how slowly or how quickly should we want it, will the linker allow those payloads to be released. The first way that we're going to implement this in the clinic is really to use it to go after resistance mechanisms. And so there are some patient populations out there, some well-known resistance mechanisms that really predict for high unmet need in the clinic. And that's exactly where we've decided to go first. And so the combination mechanism of action, the 2 drugs that are going to be released from that single pre|CISION event are going to be the combination of a highly potent Topo 1 inhibitor. This one, again, induces single-strand breaks. This is the exact drug class that exatecan comes from. And we're going to hit one of the most important resistance mechanisms out there, which is the DNA damage response. And so bring forward one of these drugs. We've looked at a number of them and published some of that information. What that allows us to do in planning the combination clinical development is really to look at that mechanism of action. We know that there are cancer cells that harbor specific genetic changes in the DNA damage repair pathways, and we know that they would be highly sensitive to this particular combination. And very helpful to us is that these genetic changes are actually very simple to measure in the clinic. And this becomes sort of the next level of pre|CISION medicine for us. And these unmet needs, ATM loss, Schlafen-11 loss, MSI High, Cyclin E1 Upregulation, we know that these are patient populations really looking for new approaches, easily measured in the clinic, and there's a large set of diseases there. We're now working through some of the preclinical studies that will help us to focus in on exactly what are those patient populations that would be the most sensitive to this particular mechanism. Really looking forward to publishing a very large amount of the data here and selecting this candidate to move into IND-enabling studies. All of that will happen in the latter part -- well, within the next 8 weeks, the latter part of 2026. So with that R&D update, let me turn it over to Brian for the financial results that we're here for.

Thanks, Chris. As we recently announced the oversubscribed equity placing and subscription of GBP 12.5 million, this helps strengthen our financial position to support these R&D programs as we move them through the development process. This was the third oversubscribed placement subscription we completed this year, raising GBP 10 million in March and GBP 9 million in June from institutional and existing shareholders. Cash and short-term deposits at 30th June was GBP 20.27 million, up from GBP 16.9 million at year-end, and cash held at August 31 was GBP 10.6 million. It's also worth highlighting that we have been actively engaging with a number of specialist institutional investors who have a deep understanding of the biotechnology sector. We are particularly pleased to have been invited to formally host investor meetings at the Jefferies Healthcare Conference in London next month. This represents an important step in broadening institutional awareness of our platform and communicating its significant potential to a highly relevant investor audience. We believe these efforts will help strengthen our investor base and position us for greater success as we advance our plans for a dual listing on NASDAQ.

Thanks, Brian. Let's take -- let's summarize now. And I want to take a look lastly before we get to the questions on what is -- what's coming next. What have we accomplished this year and what is coming next. So as you can see there, we have 5 really important updates that will be coming to be honest with you. It's about 8 weeks left in in 2026. And so we will be presenting with AVA6103 at ESMO. This will be a trial in progress presentation with some important preclinical updates. We're really excited about those. That's about 8 days away. As I guided to, we are going to have that tumor PK. We've mentioned that started at cohort 3, and we are going to be looking at that late Q4. We won't drop data at Christmas time or in the very early days of 2027. So we will be updating data there. With our dual payload, which we're super excited about, really going after some areas of really high unmet need, following -- using this platform to really address high unmet needs, where could we go next for patients. We will be looking at disclosing those payloads that we will be presenting at the triple meeting and the candidate selection data late in the fourth quarter of this year. And then finally, some data that we know everyone has been waiting for is the salivary gland cancer with AVA6000, the salivary gland cancer progression-free survival. The ESMO update is going to be so much more than that, though, with this program. This is going to be our first opportunity to really look very long term in the AVA6000 program, understand there's many patients that have been on for quite some time. And understanding, again, going back to the basics of drug, really understanding the PK how durable is the FAP mechanism and really studying that not just in the animals, but really studying it in the patients and understanding a bit more of the biology there. So a number of big updates still coming in by the end of the fourth quarter. We will be looking at again then in 6103, that efficacy readout in the early parts of 2027. The expansion cohorts will be designed and begin there. So lots of work over the next several months, but the next 8 weeks look to be very busy for Avacta. We're really excited about a number of the pieces here. So with that, let me bring the formal presentation to a close and turn it back to Lilly. Let's answer some questions.

Thank you, Chris, Brian, for the overview of the interim results and the business update. So let's turn to the questions which have been sent into the management team. We have had a very strong response, and thank you to everyone who has submitted a question. Given the length of the presentation, let's just focus on a few that were not addressed yet. Can you expand on what data will be presented at ESMO? It seems that everything has already been presented. What are we looking to learn at the meeting?

So as we announced yesterday, at ESMO, we are going to have 2 important presentations. So let me start with AVA6000. We are going to be presenting the final -- the PFS data for the salivary gland cancer indication. I know we've been waiting for that. Durability is critically important, especially in the PDC where we haven't had big durability just yet. The team has really been focused on the regulatory aspects of this program. We disclosed previously that we had a successful end of Phase I meeting with the FDA. That meeting went well. We received good advice on the pivotal. There are aspects of the pivotal trial that we still have to decide in the company with the help of the health authorities and then present those data from our setup trial. So the Phase Ib and combining it with the Phase Ia, it's really important to show that we're ready to move forward. We're very happy now to be at that stage of finalizing those data sets. And some of those data sets are going to support the pivotal trial. So it's important now that we present that data set in that subset of patients that would be eligible for the trial. As you know, we've shown many patients in different subsets of salivary gland cancer. For example, some have had very extensive pretreatment, but we know that these patients would be excluded from the pivotal trial based on our conversations with the health authorities. So what we're going to be doing at ESMO is really understanding and presenting who are those patients that based on the conversations and the advice and the design, what is that subset that would be eligible for the trial. And this is based on not just prior therapy, but histology of the disease, the ECOG or the performance status of the patients. And so we're going to disclose all of this. This is going to allow us to plan for that enrollment. We're also looking very long term, as I mentioned, PK safety, rolling all of that out long term. It's critically important that we not just show durability of efficacy, but that we show why. What is the PK there. I should mention that we know that the wait for the PFS data has been long, perhaps painful. But it is a paradox in oncology. Longer the wait, it just generally translate to better outcomes for patients. Oncology drug development here, it's a long game. I've been doing this for a long time, but it's a long game. The first question we asked, the PFS is how long can we control the tumor. We're going to answer that at ESMO. We know that so many have been waiting. But the bigger question then becomes how long do I have, doc, and that's the overall survival. The important point that we announced is in the design of the pivotal trial, only PFS is needed for approval. And so the -- we have to show nondetriment, so we can't make the overall survival short. But the key data for the approval of the drug will be the PFS. So that's an important data set that will be coming. I know that's long, but we think that this is going to be really a platform validating set of data that will be coming. There's some important biology that's coming out of this trial that actually will impact and show us some things that will impact next gen like AVA6103.

Just turning to the next question. It has been noticed that the pivotal design -- trial design is agreed, and we have had so much data already presented. Why has this program not advanced? And what are we waiting for in the AVA6000 program?

Yes. So let me assure everyone first that the program is advancing right on track. We know that there is a perception of the delay in this one because it's taken a long time to collect the PFS data. Like I mentioned, we base our predictions of when data will be available based on some of the observations that we made. Now it really does translate in oncology, when you're collecting PFS data, the preliminary look at the PFS in the Phase I portion, we anticipated it could be 9 months. And that was ESMO of 2025 that we -- so a year ago. Now why has it taken so long? Well, PFS takes a long time, and you have to wait for the patients to progress. We did disclose some of the early data in the Phase Ib patients, and that was back at ASCO and Bio that was back May and June of this year. And so these were sort of the first looks in the expansion cohort. And these data sets did show us some really similar efficacy in terms of tumor shrinkage. The waterfall plot that we showed was very similar to what we saw with the Phase Ia patients and the PK in those first 2 cycles were critical. ASCO, we also showed the cardiac safety. But now at ESMO, now we're really looking long term and PFS in the joint patient set, in the patient set that's going to be relevant for that pivotal trial, safety, efficacy, long-term PK, looking at FAP expression in a couple of different ways, taking that long-term view. So my advice here is stay tuned. ESMO is a short time away. We will be in Madrid soon. And we believe that there's there's some good data sets coming in both of the presentations that are going to be very meaningful for both the program as well as the platform.

That's great. And just turning here to the next question. You have hinted here to a biology presentation at ESMO platform data. What will we be looking at? And why is more biology needed?

So let me answer this 2 ways. The first is the biology studies at ESMO are going to be both in patients with AVA6000, but also AVA6103. And some of it will surround the role of the enzyme, FAP that we rely on. So FAP is we need FAP to cleave the drug. It's a mask and release. We're really trying to understand more about durability of responses and the tumor shrinkage that we've seen with AVA6000, how does the enzyme behave in patients and in our models and how can we use the models to make predictions for AVA6103 and whatnot. There's a big key difference between targeting a tumor antigen, which is essentially using the antigen as a destination, a location for a drug like an ADC. And then what we're doing with pre|CISION, which is we're leveraging a tumor-specific enzyme FAP to cleave a peptide and release the drug. They are 2 pretty different approaches, but similar. And so the pre|CISION platform is based on that concept of mask and release. Other peptide drug conjugates don't use a masking approach to spare the normal tissues, and they don't use this release mechanism. And we think the tumor-specific release and the masking capabilities are really some of the most innovative and they're quite unique to precision. So a deeper understanding of the biology of FAP, and some of this will come out at ESMO, preclinical and clinical, like I said previously. And we believe these data sets are critically important, not only for the program, but the platform. And to note, again, it is going to be across both of them. And as I've mentioned before, biology leads to new IP. And so if we think about the second reason to look at more biology, the controlled release mechanism, it started with some biology questions and that led to some of the most important IP for the company. We have to continue to evolve. We have to continue to understand how the platform works. And that brings us to brand-new IP. And as we've committed to, once we have new IP, we will be disclosing. And so much more coming in the next 8 weeks.

That's great. Just turning to the next program, AVA6103. We have had a number of questions coming in on the trial design, the data that were reported recently and also the data to come. I'll ask a few more frequent ones in the submitted questions. Just the next question here we've got is AVA60103 (sic) [ AVA6103 ], it appears that enrollment is going well. Can you comment on this? Are the dosing cohorts still lining up with the ENHERTU trial?

Yes. Enrollment is going very well. We're thrilled with how that trial is progressing. We have -- we mentioned previously we have completed 4 dose levels with respect to enrollment. As you know, the collective experience with AVA6000, until a trial shows something on proof of mechanism, it's tough. It can be tough days. But we were thrilled that we really saw from -- as we showed you from the first cohort that 6103 was really doing what we designed it to do. And so we have not seen that kind of challenge in enrollment. Our CMO, Dave Liebowitz and his team, they're doing a fantastic job in a challenging space. We have 4 dose levels, 2 arms in parallel and all of that has been completed in 6 months. Just terrific execution by Dave and the clinical team. We have both the every 2 weeks and the every 3 weeks in parallel. Dose level 3 is where we started collecting biopsies. It's also -- let me just note, it's important to note the differences between 6000 and 6103, the statistical design. We get a lot of questions about the Bayesian design, BOIN. It allows flexible dosing. It allows backfilling of cohorts, mandatory biopsies starting at dose level 3. And none of that was permitted in the design of the 6000 trial. So we do continue to progress and advance this trial. We are still lining up, and we're going to be comparing with the doses of ENHERTU, but also conventional exatecan. We think that, that's important. There were single-agent responses to conventional exatecan in the early days. So we'll continue those comparisons. And the flexible BOIN design really allows us to make some important decisions during the conduct of the trial.