Avacta Group (LSE:AVCT) Q2 2026 Earnings Call

0:01 Good afternoon and welcome to the Avacta Group Plc investor presentation. Throughout this recorded presentation, investors will be in a listen-only mode. Questions are encouraged and can be submitted at any time by the Q&A tab situated on the right-hand corner of your screen. Simply type in your questions and press send. Due to the significant attendance of today's meeting, the company won't be in a position to answer every question it receives during the meeting itself. However, the company can review all questions submitted today and publish responses where it's appropriate to do so. Before we begin, I'd like to submit the following poll. and now that time to the management team, Chris, good morning. Good morning. Thanks, Lily. 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.

0:48 We are advancing our next generation precision 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. Precision masks a potent payload behind that peptide that's cleavable only by sap. and FAS 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, FAS Exotecan or ABA6103 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 importantly, it's a controlled-release version of ExaTcan.

1:53 When we initially looked at this potent payload as a potential for precision, it was really limited in the original clinical look at ExaTcan back in the late 90s, early 2000s. It was limited by both its potent toxicity, you know, 90% of patients of severe neutropenia. But it was also limited by its PK. And so that's where these advances in precision came from. We'll talk a little bit about these inventions that led to this clinical program. The phase one FOCUS-01 trial has been dosing since March across six indications, gastric cancer, colorectal, cervical, small cell lung, hormone receptor positive breast cancer, and pancreatic.

2:45 Probably our favorite of these various indications are the GI cancers, where we have really good evidence that the TOCO1 mechanism works. And as an added benefit in gastric cancer, we have evidence that a similar mechanism in an ADC in HER2 that uses a very similar payload, duroxacan, has nice activity. We have, out of our next generation pipeline, we have two shots on goal that are coming to the clinic. ABA 6103, as you can see there, we have published five and a half 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.

3:34 We also have shown significantly higher tumor concentration. These are preclinical studies. Selectivity and activity versus in HER2. We're going to be updating these as we move towards our ESMO presentation. ESMO begins, as you know, in just eight days. Our second of the next generation is ABA6207. We believe that this is one of the first and many other 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.

4:23 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 de-risked in patients. So precision, the first generation of precision is ABA 6000. We've demonstrated three 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 to 1 concentration of the payload in the tumor versus the plasma. We've also shown excellent cardiac safety. You know, one of the key safety features or one of the key toxicities that we see with the payload, Dr.

5:11 Rubison, in the clinic is cardiac failure, and it is incurable. and so the bar for the evidence to list that lifetime maximum in the clinic was quite high. We published the data leading up to that. We're very proud. You know, lots of factors there and we will be presenting additional data. We've also seen durable rhesus 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 timeline there at the bottom in September we published the proof of mechanism data with ABA 6103.

6:06 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 ABA 6103, 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 IT 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 and oncology right now. So this This innovative drug class achieves 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 three goals?

7:21 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 And that's through this masking effect. We've seen this and shown it clinically with ABA 6000 that we can protect normal tissues. We alter the biodistribution of the payload by using the precision mechanism. And finally, and this was big for the next generation, we modulate the PK of the payload. Recall back, I mentioned that Exotecan Thank you for joining us.

8:23 Thank you for joining us. to manufacture an ADC. Now, the Precision platform, it has a very large market opportunity. About 90% of all solid tumors express fat. This was a large experiment that we did, study that we did, both internally with immunohistochemistry, but also with our collaborators at Tempus looking at Thank you for joining us.

9:42 That represents a very large market opportunity. There isn't a single precision medicine that will work for every one of these, which is why IT 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 hows. 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.

10:31 A couple of things to note here. Doxorubicin has a chemical structure that sits nicely in the active site of fat and that is required for fat 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 exit he can to work. The first is that we needed to slow down the cleavage. We know from a very old theory, it's called the Norton-Simons hypothesis, was published back in the 70s.

11:24 We know that we need, for some of these enzymes that are important in DNA metabolism, we need at least three days of coverage. We need to shut that enzyme down for three days. And that just isn't going to work with an eight-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 FAPT. 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 two 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. You know, 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 exit CCAN, we needed to create sustained release.

12:45 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 precision medicine that we make. And so this controlled release enables three 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 Exotecan, 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, you know, a large number of small molecules to work with precision enabling.

13:46 That brings me to the ABACTA pipeline. We do have three programs that are now deploying our precision platform. Our first two next generation programs, ABA 6103, which is releasing ExaTcan. You can see the indications as we've talked about already. This one is working through its dose escalation period of the phase one trial. Our next milestones with this one, as I mentioned, we are going to be publishing the tumor PK. That started at cohort three. That'll 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 that very early in the first quarter.

14:36 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 Potentopo-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'll all be in the next eight weeks, essentially, as we move towards the end of 2026. And then some really important updates that we have on pyridoxal rubicin, our first generation drug.

15:31 This one, we're going to be updating that lead indication in head and neck cancers, the salivary gland subset. We are going to be looking across the Phase 1a and the Phase 1b data. We will be updating in the second half of 26, as most starts in eight short days. and some really important data will be coming for both varidoxorubicin. 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 ABA 6103 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.

16:23 So taking a look at the precision platform as a whole, we've designed precision and especially the next gen to look at four 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 non-specific 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 ABA6000 and as well through the first several cohorts of ABA6103, we have no pneumonitis, no hepatitis, and importantly, as I mentioned for ABA6000, no cardiac toxicity.

17:22 We can now use a dose-dense regimen to treat resistant disease. And so the idea here is that by increasing the dose density regimen, 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. 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.

18:19 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, you know, 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.

19:09 That saves a lot of money as we move towards the GMT manufacturing of our drugs. So let's look at the clinical trial for ABA 6103. As I mentioned, we have both the standard arm, which is an every three weeks there at the top, and we have the every two weeks arm at the bottom. This is the dose-dense regimen. And in bold, and below the dose levels, you can actually then compare that 50% increase in the dose intensity that we get with the every two 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.

20:00 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 seven if the safety allows. So these oncology trials, especially using the Bayesian design, the Boyne design, really allow us to be flexible with dose levels and respond to safety as we see. Arms are enrolling in parallel. It really does increase our ability to treat patients and to move towards all the data collection 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.

20:55 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 three cohorts in the trial. And we're comparing here with two different programs, FIRST and HER2. This is an ADC that uses a very similar payload direct to CAN compared with our exit ECAN. and the dose levels are very similar in the first three dose levels in the MHER2 trial and the first three dose levels in terms of payload dose with the ABA6103 trial. And then ExaTcan, it's important to note that the MTD in pre-treated patients was dose level two in our trial. and so by the time we moved 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.

22:05 So the neutrophils are part of the immune system. They're part of the white, 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 three cohorts. We were thrilled by that. It really shows that we're able to keep the drug out of the peripheral blood. We do see a single grade one case of paramycytopenia and then nausea and vomiting through the first three cohorts. and a couple of cases of grade one anemia. So a really favorable safety profile. We're thrilled with this despite, again, getting 50% higher dose of payload above the MTD of Exotecan, the payload in the clinic.

22:59 And so now we're gonna 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. Again, this isn't a made-up drug. This is a drug that needs to go through a cleavage event by a resident enzyme stack. that exists in the tumor. And so what happens, you can see here, this is just a schematic of ABA6103 describing where the capping group and the linker are and how exotecan sits out outside of the binding pocket.

23:48 So the drug fits nicely then into the fat binding pocket. We can't measure this. So this is the reaction complex that is formed and the speed with which that reaction Thank you for joining us. in its initial development back in the late 90s, early 2000s.

24:36 Even shorter half-life, though, is our released peptides, only two to three 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 mil. 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 four 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.

25:26 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, ABA6103, we get a nice peak there at number one 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 five days later in the tumor. So that's where we're creating this reservoir.

26:15 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 exotecan. So the released exotecan 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 exotecan in the tumor, we're now able, over the course of those five days, to slowly release the exotecan. and what you can see is if we look way out to day five there, we still have it being released above the IC90 of Exotecan. Now, the IC90, it stands for the inhibitory concentration where 90% of tumor cells in a dish are being killed by Exotecan.

27:08 It's a key factor that we use to sort of describe the potency of a drug. Thank you so much for joining us. but that we don't get that in the bloodstream. And that's over there at step three. So in very light heel, we see that the exit tecan, 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 two to four hours. And the whole idea there is that masking. So the drug itself, ABA-6103, is not going to cause the toxicity.

28:01 But it is that release 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 in understanding the PK. And three important observations. First, we see a rapid decline in navy blue of the plasma level of the joined-up drug, ABA6103, or the peptide drug conjugate.

28:49 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 exotecan in the plasma. Now, recall, the half-life of exotecan is only eight to nine hours. So, as you're getting out days after the dose was administered and the exotecan is still being detected, Thank you for joining us today. Probably even more important because of that really short half-life is the slow sustained release of the peptide.

29:43 Now, the peptide is detectable in the bloodstream of the patients. It's detectable two days after that dose was administered. It's actually the highest level. You can see there, you know, the confidence intervals are going to overcome each other. But the absolute value there of the peptide, it's detectives. Two 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 two slides together and understand, is our modeling happening in the clinic? Are we seeing, is the drug doing what we designed it to do?

30:29 And that is this busy figure looking across the three dose levels, 1.5, 3, and 4.5. And there's four 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 ABA 6103, the parent drug. and then in light teal is going to again be the released eggs of tecan. 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.

31:14 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 Thank you for joining us today. When we move to the next dose level, we have a very interesting observation, one outlier in the trial that we call out there, in 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.

32:10 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 exotecan, but we also get that nice increase and spot on with what we modeled with ABA 6103. Now, if we move to the 4.5 megs per meter squared, spot on with what we expected from the animal studies. And you can see there the rapid decline of ABA 6103 dashed lines in patients. in the plasma, down to the lower limit of detection out two days. But we're still getting that sustained release of exotecan. And so this is exactly what we expected to see as we continued that dose escalation. And so these findings are really increasing our confidence that this non-clinical to clinical translation is performing exactly as intended. And we ask, you know, 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 FAP. And that will be some of the next data along with the tumor PK that

33:44 we have guided will be late this year. And so last data figure that we're going to look at here, we compared The known PK of the release of Daruxtecan from NHER2, and this is essentially using AI to recreate these data sets from the published data within HER2 and its release of Daruxtecan, versus what do we see with the release of Exotecan from ABA6103. Now, we're looking at the first three dose levels for each of these. And the message here is that we're seeing about, you know, estimates three times lower release in the plasma of the payload than was seen with equivalent doses of NHER2. Why is that important? Well, you can see our exposure, just as we saw in animals, the exposure in the bloodstream disappears pretty quickly with those first three dose levels of ABA6103, 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 milt.

35:10 and you can see at dose level 2, which is in the very light green, as well as dose level 3 in the rusty color of Exoticam, or I'm sorry, of Durasticam released from Inher2, 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 ABA 6103 is behaving in the clinic thus far. And this slide sums that up. So we have a very favorable safety profile of ABA 6103 in the clinic. Compared to both conventional exotetan as well as in HER2, we think those are two 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 three 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 ABA 6103 is performing exactly as we intended and that our robust preclinical data will translate into the clinic. We think ABA 6103 is really

36:42 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 developed new linkers that actually had a couple of different pods where we could attach two different payloads. Now, similar capping groups, 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-immolative linker.

37:38 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 two drugs that are going to be released from that single precision event are going to be the combination of a highly potent TOPA1 inhibitor. This one, again, induces single-strand breaks.

38:29 This is the exact drug class that Exotecan 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 Thank you so much for joining us. 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.

39:45 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 eight 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 $12.5 million, this helps strengthen our financial position to support these R&D programs as we move them through the development process.

40:41 This was the third oversubscribed placement subscription we completed this year, raising $10 million in March and $9 million in June from institutional and existing shareholders. Cash in short-term deposits at 30th June was $20.27 million, up from $16.9 million at year-end, and cash held at August 31st was $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 Jeffries Healthcare Conference in London next month. This represented an important step in broadening institutional awareness of our platform and communicating its significant potential to a highly relevant investor audience.

41:27 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 summarize now, and I want to take a look. Lastly, before we get to the questions on what's coming next, what have we accomplished this year and what is coming next? So, as you can see there, we have five really important updates that will be coming, to be honest with you, it's about eight weeks left in June. Thank you for joining us today. as I guided to, we are going to have that tumor PK.

42:29 We've mentioned that that started at cohort three 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, you know, following Using this platform to really address high-end needs, where could we go next for patients? We will be looking at disclosing those payloads. We will be presenting at the triple meeting and the candidate selection data late in the fourth quarter of this year.

43:17 and then finally some data that we know everyone has been waiting for is the salivary gland cancer with ABA 6000, the salivary gland cancer progression free survival. The ESMO updates 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 ABA 6000 program. Understand, you know, 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 mechanism, you know, and really studying that, not just in the animals, but really studying it in the patients and understanding, you know, a bit more of the biology there.

44:06 So, a number of big updates still coming in by the end of the fourth quarter. We will be looking at, again, then in 6-1-0-3. 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 eight 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 a formal presentation to a close. and turn it back to Lily. Let's answer some questions. Thank you Chris Bryan for the overview of the interim results and the business update.

44:54 Now in terms of the questions which have been sent in to 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 two important presentations. So let me start with ABA 6000. We are going to be presenting 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 tests.

45:47 The team has really been focused on the regulatory aspects of this program. We disclosed previously that we had a successful end of phase one 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 1B and combining it with the phase 1A, 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.

46:40 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 designs, 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.

47:25 This is going to allow us to plan for that enrollment. We're also looking very long term, as I mentioned, at PK safety, you know, rolling all of that out long term. It's critically important that we not just show durability of efficacy, but that we show why, you know, 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 translates 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 ask the PFS is how long can we control the tumor?

48:14 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 we have to show non-deferment 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, you know, 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 involved.

49:00 that's coming out of this trial that actually will impact and show us some things that will impact next gen like ABA 6103. Thank you. Just turning to the next question. It has been noted that the pivotal design and 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 ABA 6000 program? So let me assure everyone first that the program is advancing right on track. We know that there is the 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 are all available based on some of the observations that we made. Now, it really does translate in oncology, you know, when you're collecting PFS data, the preliminary look at the PFS in the Phase I portion, we anticipated it could be nine months, and that was ESMO of 2025 that we, so a year ago.

50:06 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 1b 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. You know, the waterfall plot that we showed was very similar to what we saw with the Phase Ia patients. And the PK in those first two cycles were critical.

50:51 ASCO, we also showed the cardiac safety. But now at ESMO, Now we're really looking long-term and, you know, TFS 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 some good data sets coming in both of the presentations. They're going to be very meaningful for both the program as well as the platform. That's great. Just turning here to the next question.

51:39 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 one two ways. The first is the biology studies at ESMO are going to be both in patients with ABA6000, but also ABA6103. And some of it will surround the role of the enzyme, FAP, that we rely on. So FAP is, you know, we need FAP to clean 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 ABA6000. How does the enzyme behave in patients and in our models?

52:26 And how can we use the models to make predictions for, you know, ABA6103 and whatnot? There's a big key difference between targeting a tumor antigen Thank you so much for joining us. Thank you for joining us. A deeper understanding of the biology of FAP, and some of this will come out at ESMO, preclinical and clinical, like I said previously.

53:32 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 We will be disclosing. And so much more coming in the next eight weeks.

54:27 That's great. Just turning to the next programme, AVA 6103, 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. But just the next question here we've got is, for AVA 60103, it appears that enrolment is going well. Can you comment on this? Are the dosing cohorts still lining up through the NHER2 trial? and enrollment is going very well. We're thrilled with how that trial is progressing. We have, you know, we mentioned previously we have completed four dose levels with respect to enrollment. As you know, the collective experience with ABA 6000, until a trial shows something on proof of mechanism, it's tough.

55:17 It can be tough days. But, you know, 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 four dose levels, two arms in parallel, and all of that has been completed in six months. Just terrific execution by Dave and the clinical team. We have both the every two weeks and the every three weeks in parallel. Dose level three is where we started collecting biopsies.

56:07 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 three. And none of that was permitted in the design of the 6,000 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 Inher2, but also conventional Exotecant. We think that that's important. There were single agent responses to conventional Exotecant. In the early days. So we'll continue those comparisons and, you know, the flexible boing design really allows us to make some important decisions during the conduct of the trial.

57:03 That's great. We have spoken quite a lot about the tumor PK, understanding that the tumor biopsies were later in the trial. When will we see the biopsy data? Your CMO, Dave, mentioned in one previous R&D spotlight that biopsies are now mandatory. How does that work? Yeah, so once again, we started collecting those at the third dose cohort level. We used the backfill mechanism. It's occasional that a patient that enrolls in the main dose cohort would consent to a biopsy. There are some pretty solid rules around where biopsies can be mandatory, and so that is both institutions as well as FDA. And, you know, so these collection requirements, you know, the mandatory biopsies really didn't start until That third dose cohort, we get asked what does Baxill mean? Baxill means that a patient who's not granted a slot in the main dose escalation cohort can be treated at that lower cleared dose level. And so the trial is moving rapidly.

58:09 The biopsies were sort of, you know, it didn't move in until dose level three. But it is going well right now. And so, yes, we are guiding that we're hopeful end of year. It's possible it leaks into the early days of January. But we are collecting. We already have a few in our back pocket. So really excited to be showing tumor PK. It's a really important part of this program. Thank you. Just moving on to the next question here. Your CMO also suggested previously that the trial might stop at dose level 5 or 6. Is that true? How does the dose selection work, and how does this volume sign work? Yeah, that's a good question. We've gotten this one by email.

58:54 No, we will not be stopping until we define that MTD. We stopped with ABA 6000 at tolerability. We hit unacceptable toxicity, but 6103, we are knee-deep, and we will not be stopping until we see Maybe we should do a Vaxxer Academy on the Asian stats. It's a very different trial design, but suffice to say, no, we will not stop early. The next question here we've got is on AVA 6207. At the Q4 AVA 6207 announcement, will you have a development ready candidate or further optimisation still to complete? What safety and efficacy criteria must it meet and which steps towards IND submission and first patient dosing are funded today?

59:44 Yes, definitely. So we will have a development-ready candidate. There are multiple steps before we get to sort of those more expensive places, but the year of IND-enabling studies, we have to manufacture the drug. Once we start the manufacturing, that drug actually goes into the preclinical models, the toxicology models. We really have to be convinced at both a TK and an efficacy level as we move and that we have a patient population that is relevant for. So a lot of data coming. This program is really our first one that's designed to attack those key resistance mechanisms. So the clinical planning here is critical and is going to be ongoing in the months of the IND enabling studies in parallel with that.

1:00:30 We have to find the right patient populations. We have to find the right centers. but the beautiful part of this one is it is a true precision medicine approach and so we know who are the patients that are likely to respond here. Perfect. Thank you. There are a number of additional questions on business development and one has been asked multiple times. Are you in formal diligence with any potential partners even if unnamed and what milestones would trigger a deal? We very much understand the intense interest around updates on our partnering discussions, but as I'm sure everyone can understand, keeping the status and the details of ongoing discussions confidential is just as important to successful partnering as it is waiting for clinical data to mature for a successful trial.

1:01:29 and we have multiple conversations that are ongoing under confidentiality so we can't disclose anything there until there is something to be announced. I can say that we continue to have productive conversations both under CDA but also with multiple partners not yet ready to sign a CDA with us. It's important that we do the right deal at the right time. We know that One of these deals could bring in quite a bit of non-dilutive funding, but it's important to note that these deals always give away key pieces of our IP estate. So again, back to doing the right deal at the right time.

1:02:16 What I can also add here is that we're very fortunate to have a highly experienced and strategic board who are very supportive of the management team in this aspect. of the business. And we will keep everyone updated as we move forward. Some of the new data coming are really important to some of these conversations. So I'll stop there. That's great. Thank you, Chris. Brian, that is a long list of questions for today. Chris, would you like to sum up with a few words on where Evacta is now and what's next for the company? Sure. Thanks, Lily. Appreciate it. and indeed thank you to everyone here on the call for your continuing interest and supporting Abacta. This is an incredibly exciting time for our company.

1:03:03 We have made huge progress in advancing the pipeline. It's centered around our unique precision technology. We've made some big advances We're very well positioned. We have a solid financial basis, two programs in clinical development, many upcoming milestones, and a truly innovative preclinical program in our dual payload. That program is designed to go after some of the toughest to treat cancers by attacking one of the key resistance mechanisms. Look, we have a very busy eight weeks in front of us. Five key Thank you so much for joining us. I can say we are so excited, really looking forward to delivering these data sets, which will deliver value through this. You know, we have a potentially transformative period coming up for Avacta and our patients.

1:04:26 And we're looking forward to a number of these updates. And the company continues to make just remarkable progress and thrilled with where we are. Thank you for updating investors today. Please ask investors not to close this session as you will now be automatically redirected to provide your feedback in order that the management team can better understand your views and expectations. This will only take a few moments to complete and I'm sure will be greatly valued by the company. On behalf of the management team, we'd like to thank you for attending today's presentation and good afternoon to you all.