Thalia Therapeutics (LSE:THAT) — Investor Presentation

0:00 Good afternoon, and welcome to the THALIA THERAPEUTICS PLC Investor Presentation. Throughout this recorded presentation, investors will be in listen only mode. Questions are encouraged and could be submitted at any time via the Q and A tab situated on the right hand corner of your screen. Simply type in your questions and press send. The company may not 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. I'd now like to hand you over to David Solomon, CEO. Good afternoon, sir. Thank you so much for the introduction, and thank you all for your attendance today. I'm David Solomon. I'm the relatively new CEO of THALIA THERAPEUTICS, and I'm delighted to be here today to tell you about our innovative RNA therapeutics, programs.

0:46 This is our usual, safe harbor disclosure. So THALIA, as you might know, in Greek means to flourish or to bloom or to blossom. And really at THALIA, we are, building now a new therapeutics RNA therapeutics, leader and champion. Our our goal is to have a diversified portfolio of innovative RNA therapeutics to treat both, cancer and cardiovascular disease, and I'm joined by an extremely talented management team with proven track records in RNA therapeutics. And in due course, I'm I'm glad to, introduce them and how we will work together to add significant value. We announced this morning, as you saw, through an RNS at 7AM, an acquisition that transforms THALIA into a clinical stage company and an emerging RNA therapeutics champion, And that acquisition was the purchase of Sanmirna Therapeutics, a US Delaware privately held c corp c corporation.

1:50 And by doing that, we brought on a new asset called Meresten that is in the clinic at City of Hope in California in Los Angeles for the treatment of acute myeloid leukemia, a very aggressive adult leukemia. I'll come back to tell you more. As you might know from the company, from its earlier inception as N four Pharma, the company was focused on delivery system on the left side of the slide called Nuvec, which is a silica nanoparticle that can actually deliver RNA therapeutics. As I joined the company, we laid down some new IP and new assets of, in the middle panel, an siRNA or gene silencing medicine to treat, the risk of cardiovascular disease, specifically stroke and heart attack. I'll come back on that.

2:36 But today's acquisition and financing to go along with it was really to bring on board a microRNA asset called Meresten, as I said, for the treatment of acute myeloid leukemia or abbreviated as AML. This acquisition, we believe, is is transformational. It has the possibility of significant value creation for shareholders, but also to bring this medicine to patients, their caregivers, and their families, And also adds another modality in RNA therapeutics. We already had a gene silencing double stranded s iRNA. And by bringing on this asset, we now have a microRNA, which is an emerging type of RNA therapeutic that is getting a lot of attention now.

3:23 The acquisition of Mirasen as a clinical stage therapeutic is is very differentiated. It's in phase one. The company we acquired, Sanmirna Therapeutics, has a a exclusive license from the City of Hope, a leading or the leading cancer research center and treatment center in the state of California, 14,000 people. That license is to use Mirasen to treat the root cause of AML, and we believe that this clinical asset is the key value driver now for the company going forward. And important, and we'll discuss this further, is this acquisition and the milestone structure of the earnout of the acquisition minimizes dilution to existing shareholders. So we believe that both new investors but existing shareholders will be able to enjoy, I think, a significant accretive opportunity as we advance Miriston in the clinic to results, but also our other assets as well.

4:24 The fundraise that went along with this acquisition raised £2,750,000 sterling in an oversubscribed fundraise, and it really strengthens our balance sheet. The important thing to note here is this fundraise fully, fully funds the development of Mirastin through the completion of this phase one trial in AML patients with readout in in h one twenty twenty seven. We will not need to raise further money until the results are in in h one twenty seven, and the money that we have on board will also enable all the other activities in the company, our IND enabling studies of our cardiovascular asset that I'll tell you more about, and clearly allow shareholders then at this stage to participate in long term value creation as we advance the company.

5:12 The key steps in this transition is to really transform THALIA into a clinical stage RNA company. When I joined the company in February and renamed the company together with the board THALIA THERAPEUTICS, the goal was bold, and the and the strategy was bold. It was to become a therapeutic RNA company, and we did that in the first step by creating our own new asset, a dual acting therapy against key targets that cause cardiovascular risk of both stroke and and and and heart attack. But by adding the second asset that is differentiated, it's already in the clinic, already treating an aggressive leukemia cancer that has a huge amount of unmet need, and that is already bringing us to a a clinical stage asset.

6:01 We think this now completes the beginning of our our our strategic journey for THALIA to become an RNA therapeutics champion. In fact, when we think about this asset, Meresten, it's already receiving an enormous amount of attention. The asset, Meresten, was discovered by a leading oncologist in The United States called doctor Guido Marcucci. He's vice chair of oncology at the City of Hope Medical Center in Los Angeles. And in March, of this year, he published in the journal Blood, which is the leading journal in hematology oncology globally, a a key key paper, that shows that, Miriston inhibiting miR one twenty six, a microRNA, really, enhances the activity of the key of the key chemotherapy medicine called venetoclax in AML.

6:53 And not only was this a significant paper, but the editors of this journal, realizing its significance, decided to put this this this publication and this discovery on the cover of blood on the left side and commissioned a commentary or editorial on the right side about the importance of this finding in the treatment paradigm for AML. So we're very pleased now through the acquisition of Sanmirna that holds the license to this asset from City of Hope to be able to now advance this. And we're really pleased to tell you that the study is recruiting plate patients, not not healthy subjects to test only safety and tolerability, but to really show that this medicine may have an efficacy signal in AML patients proper. And that's the study that's ongoing, and we will be able, as it's a open label study, we'll be able to tell you more about the data as we continue.

7:46 But, again, top line data from this study will be published in h one twenty seven using existing funds to complete the study. No additional fundraise is anticipated. So this is a real transformational step to drive further value creation. It adds, again, as I mentioned, a key value driver for the public markets, Meresten, a a a a innovative asset that's in the clinic in patients with AML. It's a very differentiated approach because it really treats the root cause of this rare and aggressive blood cancer. The market opportunity is enormous because, unfortunately, there are twenty two thousand new patients annually diagnosed with this disease, and the five year survival is only thirty three percent. And that is exactly the five year survival, sadly, of pancreatic cancer, one of the most aggressive malignancies that that is known today. So we believe that treating AML patients with Meresten may be a real paradigm shift, in, in the treatment of this, very aggressive adult leukemia.

8:52 Again, this, this program accelerates our strategy to create an RNA therapeutics champion. And as I, have earlier mentioned, the funding required, to conclude this study is all now on board with this fundraise, and so we can, charge forward. What is evident in the chart on this slide is that companies that do a transition, as we've just done, from preclinical to all of a sudden, phase one asset, have a significant amount in the middle column of accretive growth. When Avidity, Dine, and Wave, all public companies in different spaces, added a phase one asset, their share price over a reasonable period of time jumped between 3570%.

9:37 And when the data came up, there was a significant lift from over a 100% to even six fold. So we're hopeful that if we continue this journey cautiously and with discipline, that we'll be able to show accretion for our shareholders. The acquisition of Sanmirna brings this asset in in a in a very important way also financially. When we think about the the actual key terms of the acquisition, they're as follows. There was a consideration to the vendors, the the owners of Sanmirna. And I must be very clear with everyone on the call that I was also a founder and sole board director of San Marina. So this is in fact a related party transaction. But the San Marina shareholders will receive over the course of time up to £16,675,000 sterling, but 13,000,000 of that is in a deferred consideration only upon success of both advancing the medicine into phase two and getting it approved at the FDA and commercialized, etcetera. The upfront consideration is £3,675,000 sterling, but that all comes not in cash, but in shares. So the owners of Sanmirna that are vent are the sellers of this of this opportunity will receive approximately 485,000,000 shares, and some of that is in a convertible loan note. And the reason for this to be, clear and to sort of dig into the

11:08 trenches on this is that the owners of Sanmirna coming into THALIA can only own less than 30%. So this was not a not a reverse takeover, but rather an acquisition. So although the shares are are being conveyed now to the sellers, approximately £764,000 to sterling reside in a loan note that bears no interest and will convert as soon as the share price goes up, and therefore, that ownership structure of equity will be less than the 30% threshold as guided by the stock exchange rules. The asset, Mirosten, is coming from a global, exclusive license that Sanmirna has and, as well as a global patent portfolio that SenMirna has and now comes into, into THALIA that allows, composition of matter method of use patents through between 2040 and 2045, allowing for, think, a significant runway to have exclusive rights to this medicine as we go forward. And under the license, to Sanmirna, City of Hope will be reimbursed for up to 1,200,000 US dollars of clinical costs, certainly by the end of five years since the inception of this deal. So Sanmirna is now a wholly owned subsidiary of THALIA and will stay extant. We'll hold the license, but THALIA and its board will determine the direction of how we progress

12:39 MIRIEST and the clinical trials, discussions with regulators, etcetera. The transaction that we announced this morning in the RNS press release also showed that we strengthened our balance sheet. We had a 2,750,000 oversubscribed fundraise, and this again, as I mentioned earlier, finances the completion fully of the phase one study in patients and also IND enabling studies of our other assets, including our bispecific gene silencing medicine. In terms of the timing, this transaction has now been approved by both the THALIA and the CEMRINA boards, and the transaction is expected to close on the 07/17/2026 at the time of the THALIA, annual general meeting.

13:26 Let me continue and, tell you a bit more about our pipeline as we go. So the pipeline is as it now stands, our ticker symbol, by the way, is t h a t or that. And so our new asset, MiraStim, is now called THAT ONE. And THAT ONE, a treatment, as I mentioned, for AML or acute myeloid leukemia, is well into the clinic in phase one and advancing well with patients currently being recruited as we speak. That two and that three are, in fact, the dual acting cardiovascular medicine. I'll tell you more about that. But they're getting ready for IND enabling studies where we hope to have preclinical proof of concept by the end of h one twenty seven and then, approach regulators like the FDA to open an IND to begin clinical studies on that set of assets. The difference between that two and that three is that that three allows the medicine to be packaged into Nuvec, the preexisting, delivery system at, the former ENFORA and now THALIA that I'll tell you, of course, more about.

14:28 So we are now joining, no pun intended, THALIA's name, a blossoming RNA therapeutics landscape. Today, there are six gene silencing or s iRNA medicines approved, generating over 3,000,000,000, US dollars of sales. And it's estimated by, analysts looking at this space carefully that by 2035, there'll be, more than 15 gene silencing medicines approved with over 10,000,000,000 of of sales. Most of these medicines are siRNA medicines, as I mentioned, that actually are targeting liver cells or hepatocytes where certain genes need to be silenced that are resulting in disease. But the brave new world in the RNA therapeutic space is also to add microRNA assets as as as is Meresten and other approaches, including targeting other cells and tissues and organs so that there's more opportunity for RNA therapeutics to be a really key and important class of medicine to target a range of different diseases, cardiovascular oncology, as well as immune and chronic, disorders.

15:35 Joining me on the management team are a group of, very experienced domain experts. To the right of my, of my profile is Fiona McLaughlin, who's been at Avacta, Big Pharma, Algeta, companies that have risen up and some have had, like, Algeta exits. And Fiona is an acknowledged oncology expert and will be leading the charge on Mirosyn. Next to Fiona is Mark Edbrooke, who, is our head of strategy and has worked, both at GSK and AstraZeneca, really advancing and championing their, RNA therapeutics programs. And so brings a wealth of experience to us, and he's really, one of the key people, on the, on the dual acting or bispecific cardiovascular medicine. As we'd like to address lots of lots of large pharma companies for perhaps licenses and raising nondilutive capital, Simon Bennett, an experienced BD officer, is joining us. Margaret Courtney, leads the charge on manufacturing and and, and pharmaceutical development. And Rachel Schiller, as our head of operations, also will be working on the bispecific cardiovascular asset. And Rachel is a key role to assure that the trains, in fact, run on time.

16:49 This whole operation is really guided by our very experienced board of directors led by chairman Chris Britton, pictured on the left side of the slide, but also members of the board that include Luke Cairns with wealth of experience in corporate finance, Alastair Smith in oncology and company operations as the successful CEO of Avakta, Ed Wardle as a leading shareholder from Northern Standard, and Mike Palfreman on RNA therapeutics in general and also delivery systems. So we have a very experienced and mature board in terms of corporate government governance and domain expertise. Now I wanna dig in a little bit to the actual assets, and the first one is MIRASIN, of course, which is now called THAT ONE. Again, a novel approach to treat, AML.

17:35 The targets, in fact, a very specific microRNA I'll talk about. But first, I wanna tell you a bit about AML itself. This is an extremely rare and aggressive blood cancer that unfortunately hits, young adults from age about 25 to 55, and is extremely aggressive. Eighty three thousand people in The US have this disease at present. Twenty two thousand new cases annually. Eleven thousand five hundred deaths annually. That's one point eight percent of all nonaccidental deaths annually in The US. And the survival, as I mentioned, is is very poor. Approximately thirty three percent of all comers are still alive at five years. So, unfortunately, these patients are treated largely with venetoclax, which is a a a b c l two inhibitor from AbbVie selling about 3,400,000,000.

18:24 They all become resistant to this medicine, and we think that one way that this, Mirastin asset could work is allow patients not to become resistant to venetoclax. And so, you know, in this field, it will be Mirastin together with other medicines in combination as combination therapy is the, gold standard of therapy in AML today. And, analysts believe that, you know, as there are more good medicines like Mirastin, the market size will grow from approximately 4,000,000,000 to near 10,000,000,000 by 2035. There's no treatment that targets the leukemia stem cells, the root cause of AML, and we believe that, in fact, Meresten does do that. So, I'll tell you more about that. Meresten actually, downregulates or inhibits miR one twenty six, and microRNAs, by definition, are short noncoding single stranded RNA molecules.

19:17 And what they do in the nucleus of a cell is they regulate genes either up or down. This is an important new modality. In fact, in 2024, Victor Ambrose and Gary Rufkin won the Nobel Prize in medicine and physiology to for the discovery of microRNAs, and now large pharma companies are realizing the importance of this. Just last year in 2025, Novartis purchased Regulus, a competitor of ours now, for 1,700,000,000 US dollars when their asset was just beginning in phase two. So there's precedent for big pharma interest in microRNAs now and for buying them at early stages. And so we're hopeful that our foray into a a microRNA will be important for us and for our shareholder shareholders in value creation.

20:04 Mirastin, in fact, mounts a triple attack on AML, and that's why I think it's such an important medicine. When you inhibit miR one twenty six using Mirastin, you essentially eliminate the source of leukemia leukemic blasts and therefore stop the spread of this very aggressive leukemia. It shifts the leukemia stem cells out of quiescence or their hibernation, making these leukemia stem cells vulnerable to kill by medicines like venetoclax or other tyrosine kinase inhibitors. And so we can both overcome resistance and make the right population of stem cells amenable to kill by appropriate chemotherapy or other agents. In fact, the early experiments done by Guido Marcucci, the discoverer of Meresten, in his lab at City of Hope in Los Angeles shows the following. The the graphs you see are called Kaplan Meier survival curves.

21:02 They show on the, x axis going up the percent of animals that are still alive. And in black, you can see, animals that have, AML, mouse AML, if you will. And you can see that by around a hundred days, a hundred percent of the animals are DED dead. On the other hand, if you treat them at around day sixty with Meresten, you can see that many of the animals keep surviving all the way through, over two hundred days. And so you see a significant shift to the right of survival, and then that's exactly what you wanna try to achieve with a, novel important medicine like Meresten. In fact, even if you transplant on the right hand side of the slide human AML into these mice, you can also, show that you can get a significant amount of extra survival in these animals. And so this was the basis of City of Hope going to the FDA and getting permission under an IND to begin a phase one study, and that's what's ongoing now. So this is the this is the phase one study that is now ongoing.

22:01 It's a study that you can see at clinicaltrials.gov. It hopes to achieve 12 patients treated, but this study actually is designed to treat up to 20 patients. The primary objective, as is normal in a phase one study, is to evaluate the safety and tolerability of Meresten and determine the ultimate dose for a phase two and maybe even a pivotal study by increasing the dose in patients. But in fact, because this is done in relapsing recurring patients with aggressive AML, we're also looking at sec secondary objectives that will evaluate the overall survival of these patients, their progression free survival, and the duration of their response at six months following their initial therapy.

22:47 So we're starting with groups of patients individually, testing at low doses for safety, and then treating groups of three patients with higher and higher doses until we see response, and we'll be able to see that these patients respond or live longer or make normal blood cells because, as you might know, the problem in AML is that they have all these blast cells, but no mature immune cells that can fight infections, including opportunistic infections that often kill the patient. And so we'll be able to get a lot of data in this open open label study done at City of Hope, where we have now close relationships owing our purchase of Sanmirna, the owner of the license of the of these assets and now shortly this clinical trial.

23:34 I wanna change gears now and talk about a topic that I've already addressed on podcasts and with investors over time since I've been CEO in February, and that is the two other assets, that two and that three, that are gene silencing medicines to reduce cardiovascular risk. One of the key targets, there's two of them, for this medicine is called l p little a or lipoprotein a. And lipoprotein a levels are set at birth genetically. They don't change. You can run all you want and eat the best diet and do everything properly. If your l p little a levels are high, sadly, you are at enormous risk, up to fourfold risk of a heart attack or stroke. Notice on the right side image, patients or individuals with high LP, and they could be thin and marathon runners, high LP correlates highly with occlusions of vessels, like coronary, vessels in the heart. It can be occluded with cholesterol plaque, as you see on the right side of the slide, or, valves like an aortic valve that can be snosed when there's buildup of, cholesterol plaque that will damage the heart valve itself.

24:41 And so by reducing LP, it's already known that you can reduce the occlusion of these vessels and therefore reduce the risk. In fact, there's already other companies that are reducing LP, and you can see my former company, Silence Therapeutics, is doing so. Amgen is doing so. Novartis is doing so, and, their experiments look as follows on the graph. You can see that a single injection of an LP little a lowering gene silencing medicine, a single injection over three months will lower by fourteen days, in the dark line, at the bottom, the level of Lp compared to in red, a placebo or essentially saline or water injection. And you can see that that response is durable all the way through sixty days or two months.

25:26 In fact, Novartis is carrying out a global study called Horizon where they're lowering Lp in patients, and they are looking at number of events. And if in fact the readout turns out to be positive in that study that low LP little a means less events, then this will be a halcyon moment, if you will, to prove that lowering LP benefits reducing cardiovascular risk through less heart attacks and less strokes, and therefore will make these medicines important and are dual acting the next generation of this approach. Not only are we inhibiting Lp, but we're also inhibiting PCSK nine. PCSK nine levels go up when you don't exercise, when you eat a poor diet, when you're obese, or have type two diabetes. And so we believe that actually making a dual acting that is a combination blocking both Lp and PCSK nine, not in the once every three months, but once every six months or once every year, will allow the the the cardiovascular risk in global patients both from bad behavior and genetic reasons to be reduced. And so in countries like India, China, where there's less physicians but lots of patients at risk, including patients then in The Americas and in in developed countries in Europe, a single injection that may last up to a year will arguably reduce the risk of both genetic causes, LP and behavioral causes, PCSK nine, and bring down the number of heart attacks and strokes that despite statins, despite all good advice about diet and exercise, are still a leading cause of sudden death

26:58 today. You can see in the panel in the middle that too, that's the medicine the double the the the bispecific double stranded gene silencing medicine against both PCSK nine and Lp with a linker between them. We can also package that inside Nuvec where you can then load even more of the medicine or different ratios. And you notice the little balloons on the surface that decorate Nuvec. That's a molecule that targets liver cells. And so we're actually studying, as we speak, whether Nuvec can get into liver cells and deliver RNA therapeutics, and that would add yet more IP and new avenues to use both Nuvec and also this bispecific gene silencing medicine and methodology.

27:48 So the current status here, we filed IP in 2026. We are getting ready to do IND enabling studies, including in monkeys. And when once we do that, we'll go to the FDA and get permission to submit an IND in the second half of next year to begin studies in earnest in patients. And by doing that, we'll be able to also bring attention to global pharmaceutical companies of this asset and maybe develop partnerships and validation that comes from partnerships with large pharmaceutical companies in the space. I wanna touch on Nuvec for a second. You probably know a bit about Nuvec from the earlier exposure to n four pharma, the predecessor of now THALIA. And this is a silica nanoparticle that can be decorated with specific molecules that allow it to penetrate specific cells, organs, and tissues.

28:41 We are now studying Nuvec to see if it can actually get into liver cells and deliver that to into liver cells specifically, and we'll be able to tell you more about our results in this in this manner in the coming weeks and months. And so in terms of next steps, there's an awful lot of news flow coming now that we, on the left side of the slide, have completed the acquisition of bringing on Mirastin, and we've completed the first steps of our dual acting cardiovascular medicine. And we're we'll be able to tell you through a lot of news flow, press releases, and, podcasts, and other ways of, of informing the markets of all of our activities and news flow, hopefully meaningful news flow that we believe will, be able to be value creating as we, advance the company going forward.

29:30 When we look overall then at the investment case, we now have a differentiated RNA therapeutics platform that addresses significant unmet need in both cancer, here AML, and cardiovascular disease, heart attack, and stroke by having two key assets, that two that one, which is Meresten, in the clinic with data to follow over time, and then top line readout within h one twenty seven, and also advancing our cardiovascular bispecific medicine, as I mentioned. The upcoming milestones beyond the acquisition is that we can tell you that this is fully funded through all the value inflection milestones, including the phase one data in AML, and, our, bispecific, is funded with the existing fundraise through submitting an IND in 2027.

30:20 The underpinnings of this whole operation, to be clear for you as potential investors or shareholders now in the company, is that we have an experienced management team with expertise in our RNA therapeutics to lead the charge and build significant value. We're supported now by long term investors and the sellers of of Sanmirna who are participating in this journey with us. And most importantly, we are applying a very strict capital discipline in executing this strategic transformation. The money raised now will take us through the key transformations of data from the the MERESTIN trial and advancing the bispecific to get approval to begin the journey in humans as well. And so we think that by holding the rudder straight, doing things on time and on budget, we'll be able for shareholders to add significant value over time.

31:11 So I'm gonna stop there. Thank you for your attention, but I look forward to taking any questions you may have. And I'll pass it back to the moderator to move to our next, part of the session. Thank you very much. That's great. Thank you very much for your presentation this afternoon. Ladies and gentlemen, please do continue to submit your questions just by using the q and a tab situated on the right hand corner of your screen. Just while the company take a few moments to review those questions submitted today, I'd like to remind you that recording of this presentation along with a copy of the slides and the published q and a can be accessed via investor dashboard. As you can see, we have received number of questions throughout today's presentation. And, Marianne, if I could just hand back to you just to share the q and a, and I'll pick up from you at the end. Great. Thanks for that. So we'll start with a high level one on microRNA.

31:59 Cardior, acquired by Novo Nordisk for over $1,000,000,000, was developing a heart failure drug candidate, also a microRNA, I believe. So there are some recent validations however, many older MIR, however, were discontinued after entering development. What can we learn about that, and has anything changed? Yeah. It's a very good question. I mean, there was an a lot of early interest, in microRNAs. There were companies like like you allude to and and Mirna, another microRNA company. But what has changed is really thinking about how you do studies to address the safety profile and targeting the right microRNAs. And I think the experience of Regulus just purchased by Novartis for 1,700,000,000 is sort of leading the charge.

32:45 Oncology is a great place to use microRNAs because it's clear that in certain, malignancies, unlike treating cardiovascular disease, certain malignancies, microRNA levels are specifically very, very elevated. And these patients are so ill that by assuring first the safety and tolerability as we are doing in our study, that you can then lower the microRNA level that you're trying to address and then come in with with a multiple level of combination chemotherapeutic agents and others to address their their cancer, their malignancy. So I think a lot of people agree that, a a key approach in microRNA is in fact in oncology, and that's why we're excited to carry out this program where we think after our phase one, we may be able to, and, again, it'll depend on feedback from the FDA, enter a a pivotal study, that will allow us to get a label and early approval of our medicine. But, again, stay posted on this channel, but it's a very good question. There's been, like in a lot of fields, like in gene therapy, a lot of early adopter companies that had bumps in the road. But I think now the microRNA space is getting more mature, and the approach taken by Guido Marcucci and the City of Hope is, I believe, like Regulus, a very mature approach.

34:05 Great. Thank you. Then one on the trial. What what should we expect in terms of timing of dosing and up upcoming news flow for Miriston from the clinical trial? Yeah. A good question because the trial is open label, so it will be at our election to be able to report results as we go as appropriate. And right now, the trial is recruiting patients and dosing in groups of three. The recruitment period ends at the end of December, and we have disclosed that the top line data will be presented before the end of h one twenty twenty seven. So it is a reasonable expectation that we'll have in the course of the study some clinical updates on the safety, tolerability, and a modicum of efficacy of Merestim in these patients.

34:53 But, again, leave it to the company to actually make the appropriate disclosures over time. But I think what's important is it will allow people transparently to see the progress of the trial also well ahead of of the final top line results within h one twenty seven. Great. Okay. Next one thinks about those results themselves. So recognizing the primary endpoints are safety related, what measures should we focus on when clinical results are available to build confidence in the efficacy potential of Mirasthen? Well, of course, the trial will be determined as successful based on the primary endpoints, which as you say, Mary Anne, are safety and tolerability. And so the goal of the trial is to increase the dose of Meresten and evaluate that safety and tolerability. But at the same time, because all these patients are in fact AML patients and they have relapsing recurring disease, one of the hallmarks of this disease is that patients don't have mature white blood cells. And so one of the things that, you know, people can look for as we disclose results ahead of top line results is do these patients start to recover making mature white blood cells?

36:06 And over time, you know and that'll only be known much later. Will will they have, you know, longer progression free, survival periods or overall survival? The endpoints that we're looking at are not survival based, to be a 100% clear. So when people are looking towards whether the dog hunts here, I think it's more about whether, new new white blood cells are being generated. And so that is a hint as to what may be, perceived as we, start to discuss patient data, but that will come over time between now and the end of h one twenty twenty seven. Yep. Thank you. Right. What do we know about the potential side effects profile from Meresten's preclinical work and also from its mechanism of action?

36:52 No. It's a very good question. You know, luckily, because of the specific nature of the way the molecule is designed in animals, including in nonhuman primates that are closer to humans than, obviously, rodents, there was not a significant safety signal even at doses that are approaching a thousand fold more than are being anticipated to use in humans in this study. So that gave a lot of confidence already to the investigators and to the markets. In general, when you do this kind of study, then Meresten will be a safe and well tolerated medicine. But, again, we'll only know that when we see the results proper. But I I I can feel comfortable that we're advancing a medicine that has had a good safety profile thus far in animals, as has already been published in the literature, and, prospective investors and shareholders can look at that literature by, going to Medline and looking at the Meresten literature in animal models.

37:54 Great. Thank you. Are there other types of cancer that Meresten might be applicable to? And if so, why did City of Hope select AML as the lead indication? Yeah. So meresten targets miR one twenty six, and miR one twenty six is dysregulated, if you will, in a range of other diseases, like, solid tumors, like, colorectal cancer and non small cell lung cancer. But the reason the reason that Meresten was chosen by City of Hope is actually a fairly simple one, for two reasons. One, City of Hope is one of, the world's leading cancer treatment and research centers. 14,000 employees in Los Angeles area and one of the most important comprehensive cancer centers in The United States, where they are a leader in treating leukemias and lymphomas. And Guido Marcucci, the vice chair of oncology there, is one of the recognized leaders globally in AML.

38:52 So it made sense to treat this rare and aggressive, leukemia. Number two is that solid tumors are much harder to address. They're harder to gain access of of therapeutic medicines. Leukemias are a lot easier. They are nonsolid tumors. They are liquid tumors, and the cells are readily, as we all know, floating about in the blood to be pedantic. And, therefore, when Merestin is in the bloodstream, comixing with these cells, it's a lot easier for the leukemia stem cells in the bone marrow and the leukemia blasts in the circulating, blood to be addressed by Mirastin. And so it makes logical sense between the expertise of City of Hope, of Guido Marcucci, and of, treating a non solid tumor is the best and first approach.

39:37 And we are hopeful, therefore, that this will be, therefore, valuable. But again, data will speak, we will disclose it to you in due course. Very good. Thank you. Looking ahead, at what stage would THALIA look to outlicense or partner assets? Well, that's a great question. And, you know, the reason we have this strategy is the lessons I learned from being the CEO of of Silence Therapeutics. For those that follow, RNA therapeutics and gene science and companies and companies that were earlier on, London Stock Exchange or on AIM, it's clear that Silence, by redefining its platform and its pipeline, started licensing some assets and keeping other assets in in house as proprietary.

40:23 By doing so, by licensing our assets to AstraZeneca for near 25,000,000 upfront and 2,000,000,000 of milestone payments, and the same upfront payments, 25,000,000 to Mallinckrodt, and another 1,900,000,000 of milestone payments that we brought in nondilutive capital that didn't dilute shareholders, brought validation, and caused the market cap in my time as CEO to go from 40,000,000 to about £600,000,000 sterling. And so consequently, we're gonna follow a very similar strategy. It may be that our cardiovascular assets are very attractive to companies, for example, like the the Lilies and the Pfizers of the world. And therefore, we would continue discussions with companies, big pharma like that, to see interest and and develop partnership opportunities together with the board and our management team.

41:13 And if that happens and brings on more nondilutive capital to the benefit of the company and shareholders and also validation, and so we will follow that strategy. We'll look at our assets and see which ones could be partnered, which ones should remain in house. But we are most excited and most proud to try to take Meresten right now as far as we can as it's already advancing in patients. And in a way, if you look at it from 30,000 feet or 10,000 meters, bringing on a clinical stage asset jumpstarts us about seven years. It would take seven years in the £30,000,000 sterling to in house make a, clinical stage asset like Meresten. Or if we have to go buy it in the open market from a large pharma, they're now asking for double digit millions upfront just owing transactional costs. So doing the merger this way in a share based deal that is fair, dilutively, for our existing shareholders, we think is the best way to jump start THALIA and follow our strategy to be a leading clinical stage RNA therapeutics company.

42:16 That's really clear. Thank you. One last question. THALIA's stated goal is to build a diversified RNA therapeutics pipeline. Should we expect more acquisitions or in licensing? Well, look. To be clear, we just raised money to carry out full on all the programs that we now have under the tent, under the umbrella. So in the beginning, what we're gonna do is focus and focus and focus on on time and on money on completing the phase one study in in AML patients of Meresten, report that out on time within h one twenty seven, and use the balance of the money to advance our cardiovascular assets all the way towards the clinic. So I do not anticipate doing further, acquisitions or further in licensing.

43:01 Right now, we have to focus on our knitting, and the knitting is clear. It's very exciting. There are not many companies in the RNA therapeutic space that have the luxury of having an advanced clinical stage asset like we do or having very important assets like our dual acting or bispecific cardiovascular asset. And so we're gonna focus, focus, focus with a a very disciplined management team, a very able board in governance mode to extract victories and shareholder value, and that's the name of the game in the next full calendar year. Very good. Thank you. So, David, we've come to the end of the questions. I will hand back to you for a few a few closing remarks, please. Thank you. Yes. Thank you, Mary Anne, and and thanks to all of you for spending your time this afternoon on a very hot day to listen to our our new advances at THALIA, the acquisition of Sanmirna, the financing to fully fund our our pipeline now, and to begin the journey as a new RNA therapeutics champion.

43:59 I'm grateful to our board, as well for, assuring that we had the right structures to do this, and I look forward to many of you joining as new shareholders into this journey as I think it's a worthwhile journey and a valuable journey for all of us and ultimately for patients, their families, and their caregivers. So, again, thank you for your time. That's great. Thank you for updating investors today. Can I please ask investors not to close this session as you'll 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 it'll 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.