Sareum Holdings (LSE:SAR) — Investor Presentation

0:00 Good morning, ladies and gentlemen. Welcome to the SAREUM HOLDINGS PLC Investor Presentation. Throughout this recorded presentation, investors will be in listen only mode. Questions are encouraged and could be submitted at any time using the Q and A tab situated on the right hand corner of your screen. Just please simply type in your questions at any time and press send. Company may not be in a position to answer every question received during the meeting itself. However, the company review all questions submitted today and publish responses where it is appropriate to do so. Before we begin, we'd like to submit the following poll. And if you give that your kind attention, I'm sure the company would be most grateful. And I'd now

0:31 like to hand over to Non Executive Chairman, Doctor. Stephen Parker. Good morning, sir. Good morning. Good morning to everybody on the line. Great. Welcome to join us for this update as a result of the recent CTA submission and our period ends at the end of June.

0:52 Tim Mitchell, our CEO, will take you through the headlines. And then John Reeder, our CSO, will talk in a little bit more depth about the science side. And then we'll be further over to questions at the end of that. So if you've already submitted questions, we will try and get through as many as we can. If you haven't, there is the opportunity to do so. Although at short notice, we may have to hold questions on the day and submit them back as written answers via the website and the IRS at a later stage. So with that, I'll hand over to Tim Mitchell. Thank you, Steven. Yes. Good morning, everybody. Thank you for for joining our presentation today.

1:41 As as Steven said, you may have noticed last week, we announced by RNS that we've submitted the CTA, that's the clinical trials authorization application for our SDC eighteen o one autoimmune disease candidate. And and, really, the the purpose of this meeting is to give a little bit more details around that program and and answer any questions you have.

2:08 So so as Steven said, presenting today is is is myself, Tim Mitchell, the chief executive and one of the cofounders, and John Reeder, chief scientific officer, and the other cofounder of the company. For those of you who are new to the company, then I'll start with a quick overview. We're a clinical stage small molecule drug development company developing next generation kinase inhibitors. So kinases are a class of cellular machinery that regulate many biological processes, and we have a particular focus on autoimmune diseases and cancers. So we're led by a highly experienced team with particular expertise in kinase inhibition, decades of experience in general r and d, and also in public company management. Our current drug development pipeline is focused on the JAK cell signaling family, and we'll talk in a bit more detail about that later.

3:01 It comprises four members, tick two, JAK one, JAK two, JAK three, and they're all important in maintaining healthy immune systems. So our strategy is to develop these programs into the late preclinical or early early clinic clinical stages before we license or part them with a pharmaceutical major. And while we do that, we maintain a lean cost base. We have a small executive team, and we use trusted third party providers to maximize our return on investment. So some of our recent highlights are are shown here. As I said, well, the the main focus is on SDC 18 o one. This is the the TYK2 JAK1 inhibitor for autoimmune diseases.

3:47 We have

3:49 we've we've noted in the RNS that we've got a particular focus now on psoriasis, which is a skin disease. So the the CTA application for a phase one a b clinical trial was submitted last week. So the the plan is to initiate clinical trials, firstly, in healthy volunteers so that we can understand the dose levels and and any safety issues with the compound and then in psoriasis patients. And we're looking to start this trial by the end of this year. So we'll look to dose up to a 120 volunteers and patients in total, and we'll recruit these at a site in Manchester in in England. Earlier in the year, we we announced that the toxicology studies to start these trials had been completed.

4:36 We were we were waiting on the the drug products and the drug substance. So the drug substance, that's the sort of the raw material, a 18 o one material, that's now complete. The capsule formulation that the volunteers and patients will actually take, that's also been completed and is currently undergoing quality control. So we're on track for this year end start. And then just a couple of points on on SDC 18 o two. So so this is a separate molecule that also targets TIC two and JAK one. This is our cancer and cancer immunotherapy program. We're continuing to undertake our translational studies just to work out in in which particular cancers we should best use this compound. And then we also noted that the the the IP portfolio has been strengthened with the granting of a patent in the European Union.

5:30 And then for the SRA seven three seven check one program, so this is a program that was licensed to Sierra Oncology. The news here is that Sierra have been acquired by GSK, and that was in April this year. So we're waiting to hear from GSK as to what their plans are for any future development of SRA seven thirty seven. And, obviously, we'll update you as soon as we hear anything from them. And then also in the RNS of last week, we noted our year end financial position. So it's a cash of 4,300,000. Okay. So let's move on to our JAK programs, the TYK2JAK1 programs where we have our particular kinase inhibition expertise.

6:15 And I'll hand over to John to take you through that.

6:20 Thank you, Tim. So JAK family, as Tim has alluded to, is very important in the signaling of immunoregulatory cytokines, so helps to maintain this healthy balanced immune system. The two members of the family of particular interest to us, TYK2 and JAK1, they are involved in a signaling pathway frequently deregulated in multiple autoimmune diseases, one of which is psoriasis and will be the focus of our phase one b trial. The inhibition of both TYK2 and JAK1 has the potential to get superior efficacy compared with agents that block just one of the two kinases.

7:11 If you look at cartoon, the cartoon, you'll see, for example, that interferon alpha, the third cytokine from the left there, uses both TIC two and JAK one. And by inhibiting both of those, we think we can have a really profound inhibition of that interferon alpha signaling pathway. Tick two and JAK one are therefore optimal targets for autoimmune diseases, targeting the two other members of the JAK family, two and JAK three, has led to some unwanted side effects in in patients. So from the beginning, we've been keen to avoid inhibition of those two kinases and SDC 18 o one. That's the right balance balance of of potency and selectivity amongst the JAK channel that we were looking for.

8:05 The inhibition of these two kinases is of great interest in the industry and increasing interest. There's a lot of activity, a large amount of commercial focus on on the the JAK family as a whole

8:20 and strong clinical validation from big players such as BMS and Pfizer for TYK2 selected and dual TYK2 JAK1 molecules in both psoriasis and psoriatic arthritis. There's a number of mid and late stage clinical trials of the TYK2 and dual inhibitors from BMS, the Pfizer molecule, which has been picked up by a new company called Cryovant. And they have trials ongoing in lupus, ulcerative colitis, Crohn's disease, vitiligo, and dermatomyositis. So a range of dermal and other autoimmune and inflammatory diseases.

9:06 Readouts are expected over the next two or three years. There's also scientific evidence for a role in the modulation of the severe inflammatory responses and respiratory symptoms arising from viral infections such as COVID nineteen. And two JAK family inhibitors are already approved for certain COVID nineteen patients.

9:34 And I mentioned the growing commercial focus. BMS are forecasting sales in excess of $4,000,000,000 of their TYK2 inhibitor, dupravacitinib, in 2029.

9:56 So as you know, we are focused on selective and potent TYK2 JAK1 inhibitors. There are significant opportunities available to us in this area. Currently, no marketed products with selectivity for TYK2. So that's a recent target for therapeutic intervention. There are very few dual TYK2 JAK1 inhibitors in clinical trials, we have a nicely differentiated product. And there are no selective TYK2 inhibitors in clinical trials for cancer, which gives us a first in class opportunity for SDC1802. So both of our molecules SDC1801 and SDC1802 are potent and selective inhibitors of both TYK2 and JAK1.

10:47 A favorable selectivity profile against JAK2 and JAK3 in contrast with some of the early first generation JAK inhibitors such as topositinib and baricitinib. The molecules have a potential for once daily oral dosing in humans, and we should start to get early on in the phase one a process for SCC eighteen o one. We'll get to see exactly how the pharmacokinetic profile of eighteen oh one is looking, and that will inform us on the dosing schedule. And we also have a strong IP portfolio, protecting both candidates in all of the key territories and markets.

11:40 So this slide gives a snapshot of our pipeline as it stands at the moment. You'll see our proprietary programs, STC1801 and eighteen oh two. Eighteen oh one is at the end of its preclinical phase. And

11:56 hopefully, with a favorable response from MHRA, we'll be entering clinical Phase one before the end of this year. SPC 18 o two is a little further behind, and we continue our translational studies. And then below, you'll see SRA seven thirty seven now in the hands of GSK, but important to remember that it's completed two clinical phase two studies in solid tumors as a monotherapy and combination and showed a very good safety profile and some signs of efficacy, which we're hoping will encourage GSK to take this molecule further.

12:52 In terms of our development time line then, the internal focus, as mentioned, is on progressing SDC 18 o one into our first in human phase one AB clinical trial.

13:04 Initial focus is on psoriasis, and the clinical studies will be conducted at a single specialist center in Manchester. Can see in the timeline, q three twenty twenty two, we were able to file our CTA. And as Tim mentioned, we've completed the manufacture of the capsules for the clinical trial, and they're just going through their final QC process before they are released to the clinical unit. In q four twenty twenty two, then the big objective is to initiate that phase 1a clinical trial subject to approval from MHRA and the ethics committee. And then that trial is scheduled to go through 2023. We'd aim to complete the phase one a during 2023 and initiate the phase one b clinical trial in patients.

13:56 And then we're hoping we'll have all of the data and completion of that clinical trial

14:02 hopefully early in 2024. But that's very much subject to successful recruitment and progress and funding.

14:15 Just briefly on STC eighteen oh two then, targeting multiple cancers here. It's demonstrated good efficacy in immunotherapy disease models against many cancers. The antitumor effects have been seen in models of, for example, kidney, colorectal, skin cancers, B cell lymphoma. Got strong evidence that SDC eighteen o two acts through a novel immunotherapeutic mechanism. And, again, we're dosing orally here, seeing positive results using SDC eighteen o two as a monotherapy and in combination with a number of chemotherapeutic agents. Our recent patent grants strengthen the IP portfolio in the major territories.

15:02 And as we've mentioned, translational studies are ongoing to define the optimal cancer application. These involve additional biomarker studies to better understand the mechanism of action, and that will help us to identify the ideal patient population for the Phase one studies of the population with the best chance of responding to our molecule.

15:24 And once we have this in place, we'll be completing our toxicology and manufacturing studies. And I think the experience we have in developing SDC1801 will greatly aid the the development of eighteen oh two. They have a very similar chemical structure. A lot of the synthetic steps are identical, so we already have optimized process chemistry for those steps. I think we'll be able to move eighteen oh two more rapidly through these toxicology and manufacturing studies in the future. And just a reminder of 737, where it stood before the GSK acquisition of Sierra, this is from one of Sierra's presentations from March earlier this year.

16:15 You can see lots of opportunities for

16:19 SRA737. Sierra, we're talking about combinations with a BET inhibitor that they in licensed called SRA515, also opportunities for combinations with immuno oncology agents

16:34 gemcitabine. So we're just waiting to hear what GSK will do about this. Obviously, as soon as we know something, we'll pass that on to our shareholders. But But there's a $550,000 approximately, well, dollars 550,000 milestone payment to us upon first patient placed in the next clinical trial and and still a total of nearly $80,000,000 in total milestone payments. And additionally, there are royalties due if SRA737 gets on the market.

17:14 So I'll hand back to Tim at this point to just conclude the presentation before we move on to the Q and A. Thank you, John. Yes. So to remind everyone of then the potential value inflection points that we can look forward to over the next three months through this year. So we we we talked about a a midyear date for the CTA submission. And and as you'll have noticed, we we did that in at the end of July. We've selected the initial indication for the phase one b clinical trial. That's psoriasis. So the next event we're looking for is the approval of the the CTA by MHRA.

17:59 So that's that's the medicines and health care regulation or regulatory authority. And, I mean, the the that so that's that's slightly out of our control, but we are hoping that we'll have that in time for the the the start of the phase one a clinical trial by the end of this year. So we'll have the the trial start to announce and then any updates on preclinical progress with SDC 18 o two. And then for for check one, as as John has alluded to, then we we've we've seen that the the acquisition offer has been approved by SAREUM shareholders. We're now looking to see any news from SRA seven thirty seven. Obviously, we can't divulge anything that GSK haven't put into the public domain, so we're waiting for public announcements on that. And then any milestone payments should GSK choose to progress seven three seven. We we look forward to the milestone payments on on the first patient's dose in any new clinical trials.

19:01 So looking for plenty of important preclinical and clinical progress from the three programs here, so eighteen o one, 1802, and 737. Okay. So that's the formal part of the presentation concluded. If I hand back to Mark for a minute Yes. To That's great, Tim. Tim, John, Stephen, thank you very much indeed for updating investors this morning. Ladies and gentlemen, please do continue to submit your questions using the Q and A tab situated on the right hand corner of the screen. So while the company take a few moments to prepare for the questions submitted today, I'd like to remind you that a recording of this presentation along with a copy of the slides and the published Q and A can be accessed via your Investor Meet company dashboard. Jessica, if I may just hand back to you. As you can see, you've received a number of questions ahead of today's event along with a number throughout today's meeting. And if I may just hand back to you to read out the questions for the team to respond to, then I'll pick up from you at the end. Thanks very much Mark and thanks everyone for joining for your interest today.

19:59 So I'm going to read some of the questions which have been submitted and then I'll invite Tim and the team to respond. And just to say we'll try to to ask as many questions as possible, but you'll appreciate there's a lot. If we're not able to respond live, we'll do so after the meeting in written form, so please bear with us on this. So question one, question regarding SDC 18 o one clinical trials. How long until the CTA is approved? And then beyond the approval, what's the lead times before the first patient is dosed? So, Tim, if I could hand over to you on that, please. Yeah. Thanks, Jessica. Yes. So I I think we've we've covered some of this in today's presentation then. So we're so say the CTA approval, know, we're we can't really give a firm date on because it it's it's dependent on the the MHRA.

20:57 But based on previous experience, particularly with the consulting company we're using, we're expecting to get that approval in time for a a clinical trial start. So we'll we'll we'll put them we'll put it we're putting everything in place to start recruiting patients pretty much as soon as we've got that approval, and and we're hoping that that will all be done by the end of the year. In terms of how long the trial will take, again, that's that's slightly dependent on on how quickly the the Manchester unit can recruit patients. But but as John noted, the the the phase one a part, we're hoping to conclude during next year. Thanks, Tim.

21:44 Second question, excellent news on the CTA submission. For many years now, the company has been stating an objective to find licensing partners. Are you able to share the number of potential interested parties in the last twelve months who've shown an interest? So so I can't really talk speculate on the the number of of, you know, of of interested parties we're talking to, but we we talk to potential partners all the time as as part of our normal course of business. So so we have an an ongoing dialogue that that continues with a number of interested parties. And I think that's really all I can say about it for now. Thanks.

22:32 So the next question is about consolidation. When previously asked on the reasoning behind consolidation, the response was that at a higher consolidation price, there would be more likelihood of institutional interest. How has this strategy played out since consolidation? Shall I pick that one up? This is Steven. The answer quite simply is that you don't flick a switch on the markets and everything immediately runs as you would like them to. Over time, I'm quite convinced that the decision to consolidate the shares will prove to be the right one. But of course, you have to remember that we are we're not isolated. We're part of the sector and we're part of the market.

23:23 And as everybody knows, the last twelve months in this market and in this sector has been pretty damn bloody. Interestingly, we're actually running at about halfway down the scale of performance in the sector at the moment. So whilst clearly, I'd like it to be better, I'm conscious that it certainly could be worse. Thanks, Steven. The next is a question about, 737, and we've had a number of questions on this topic, so I'll I'll try and consolidate these as far as possible. And the question essentially is, has the board requested any information from GSK on its intentions and obligations under the original SAREUM under SAREUM HOLDINGS PLC does not have an agreement either with SAREUM The agreements for licensing the drug was done through Cancer Research.

24:38 And we have an agreement with Cancer Research, which gives us the 37.5% economics of the agreement. So we are simply not in a position to or we have no status to go to GSK and ask these questions. Those questions have to come from the licensing partner, which is Cancer Research. We are in active conversations with Cancer Research to make sure that those that is happening. But we are simply not in a position to pick up the phone or any other means to GSK and ask those questions. Thank you. So the next question is about what activities have been carried out prior to any response on the CTA from MHRA?

25:34 Possibly, Tim, a question for you. Yeah. John, do you want to pick that up? Yeah, can do. Yeah. I mean, it's really a case of with respect to 1801, it's all of the final details in for the clinical plans with the unit in Manchester. So as part of the CTA application, we've drawn up the protocol that will be used in the clinical It's a very detailed document, extends to over a 100 pages. But once that's in place, you then have to break down every single activity within that clinical plan to make sure that the clinical unit know exactly what it is that we're asking them to do. And so it's really that's the ongoing task there.

26:23 We're gonna make sure that all of our internal procedures are absolutely, you know, 100%. It's conceivable that MHRA will come and inspect us. And so, obviously, we want to make sure that we're prepared for that event. And I think the other one is the with finalizing the quality control checks on the capsules. That's all going ahead of schedule and looking good so far, but that needs to complete before the capsules are sent off to the clinical unit. So it's really that. And then eighteen o o two, two, we've talked about the ongoing translational study. Thanks, John. So we have a few questions about cash and cash runway.

27:13 What runway does the current approximately 4,000,000 provide, and how is this expected to be used over the next two years is the first question. So I might ask Tim to take that one now. Yeah. Okay. Thanks, Jessica. Yeah. So the main focus is still the clinical trials on SDC 18 o one. So as we said in the RNS and and as we've alluded to in today's presentation then that we well, we're we're funded for the phase one a part, but we would require additional funding to complete the psoriasis phase one b trial. So, yeah, so I think that's the the answer there. And and then I think there were some further questions about clinical development of eighteen o two, and that would all to take s d c eighteen o two into the clinic, that would also require further funding.

28:09 Thank you. And I think there was a further question on the the current estimates of the cost of phase one b as well, Tim. Yeah. I think we will can we just make sure we got that one right and provide a written answer to that, if that's okay? Of course. So the next question, the results from the CTA have been received, what are the intentions in relation to progressing the COVID potential of 18 o '1? And what would be what would the steps be to progress this? Okay. So so the phase one a part of the trial will provide safety and dosing information that will be applicable for for any trial.

28:56 So with the the the the first part in healthy volunteers will look out for any safety issues, and we'll we'll get a a feel for how often we have to dose for and and what dose levels can be maintained at the various dosing schedules that we'll try. So that would be that that information can be applied to any trials in in any disease where eighteen o one is taken as as an oral capsule, so in including COVID nineteen. But I think yeah. So the we know that TYK2 JAK1 inhibition is is demonstrated very, very good benefits in in psoriasis and psoriatic arthritis. So we think there's a strong rationale for the initial focus on psoriasis there. And then once we have that data, we'll consider any other diseases which may or may not include COVID.

29:53 Thanks, Tim. Next question is around impacts of the current geopolitical and economic situation on SAREUM. I'll take this one. I suppose it's an operational one, really, isn't it? I mean, nothing really. We're we're yeah. We're just focused on our drug development. Most of our work's with CROs. The clinical trial, as we've said, will take place in The UK. Much of our recent work on drug substance and drug product has also been done in The UK. So, you know, we're sheltered from currency issues, if any. So nothing really that I can think of.

30:40 Thanks. There's another question about a sale of shares by directors. And the question specifically is does this activity not run contrary to the board's expectations of SAREUM and its potential? Possibly a question there for Steven. Yes. You're referring to a recent sale, which was carried out by Tim and by John, which was linked to options which were running out of date. Now the previous year, both gentlemen had actually lost options because there wasn't an opportunity to trade them within an unlocked period.

31:32 And so on this particular occasion, it was felt that it was fair to allow them to trade because otherwise, they would simply have lost these options they've been holding over the lifetime of them. We don't expect that to be a frequent occurrence. But on that instance, that was why the board felt it was appropriate to let them do so. Thank you, Steven. Next question is thank you to everyone involved with SAREUM. At what stage in the development of 18 o one and eighteen o two would be the preferred point to consider a license agreement?

32:25 Okay. So we've talked previously about our ongoing dialogue with with interested partners, and and we continue to assess the potential value of an earlier stage transaction versus the risks and the time and the funding required for a later stage deal. So it it's all the time, it's a balance of the the further down the the the development track you go, the the higher the the value of the potential deal is, and also that there there's more companies out there looking for later stage deal deals generally than earlier stage deals. So it's really a a judgment call by the board on on how far we think we want to take the programs before we do license them on. But I think that there's pretty much a hard stop that that we we'd never take a program into the market. So we'd at at some stage during the late at the latest at the sort of mid to late clinical stage, we would be looking to license these on.

33:25 But if, yeah, if the right deal comes along at an earlier stage, then, of course, we'll take it. Great. Thank you. Next question is about f l t three. Will there be any attempt to fix solubility issues on f l t three? Shall I take it, John, or do you want to chip in? Go ahead, and I'll add anything if I resent it. Okay. Great. So our current priorities are SDC 18 o one and eighteen o two. That that's the two tick two JAK one programs. So we've had several attempts to find ways of progressing FLT three in Aurora with with various partners, particularly in China. So I think where we are at the moment is that it's the program's deprioritized.

34:15 If we will be become aware of any new methodologies that would address the the formulation issues that we have with FLT three, then we would we we'd continue the program based on on that. But I think at the moment, we're we're just waiting to see waiting to find a way to address these formulation issues before we progress any further. Great. Thank you. Next question. Now that eighteen o one is heading to the clinic, what's the time frame for 18 o two to do the same? So I guess really too early to give a definite frame for 18 o or time frame for 18 o two to commence its clinical studies.

35:00 We really need to complete the translational studies to determine these cancer indications for the molecule, and then we can plan to complete the the studies the clinicals no. The preclinical studies to get it into the clinic. But I think as as John noted in the presentation, eighteen o two is similar in structure, molecular structure to eighteen o one. So the experience that we we gain from the preclinical studies on eighteen o one should be very much transferable and will facilitate the preclinical work on eighteen o two. Great. Thank you. And then a a further question on eighteen o two. Will it be administered in the same capsule form as eighteen o one? So I think we'll we'll just assess both capsule and powder and bottle.

35:50 And again, we can use the experience from our preclinical formulation studies on eighteen oh one to guide us on this. As as we said, these molecules are quite similar. So, John, were you mean, I think the only other thing is we may have some of the clinical data on the capsule formulation of eighteen o one by the time we get to the stage of eighteen o two, which obviously will will use to guide our I think that field would be preferable. So, you know, that's that's where my preference lies at the moment, but we'll we'll assess it once we have all of the data on eighteen o two and go with the most appropriate formulation. Great. Thanks.

36:37 Thank you. Next question is about patents. And do you have plans to extend the life of any of the older patents? John, do you wanna take that? Yes. I will do. I mean, we have a strategy in place that maximizes the lifetime of all of our patents as far as we can. So I think just on the older patents, a lot of them, some of them have served their purpose very well. So, you know, which was to carve out an area of chemical space in which we could operate. The strategy then was to file selection patents on the actual molecules of interest, and that's that's what we've done. So we've got, I think, good lifetime remaining on our patents for eighteen o one and eighteen o two.

37:34 And, obviously, yeah, there are little tricks to extend the lifetime as much as possible. I mean, an example of that would be the crystallization or the the solid form pattern that you've seen for 18 o one, or you may have seen it's a it's a patent that seeks to protect particular crystal forms of SDC 18 o one. It starts for patent clock ticking again when we file that application. So, yeah, with we have have a a strategy in place to extend the the lifetime of patents as as far as as possible. Great. Thank you. Next question is about whether there are plans for anyone to attend the JAK inhibitors development summit summit in Boston.

38:21 If you've already apologies. The question was if you have attended. Right. Yeah. Well, yes. Except except that it became an online event, but I was this is John speaking. I I I was at the event online, and it was very good at it. Some very interesting discussion about therapeutic areas, the JAK inhibitors, and discussion from physicians, but the people who actually prescribed the medicines concerning the black box warnings around some of the earlier JAK inhibitors, which is very interesting. That was interesting. Great.

39:15 Thank you. I think that we have a few additional questions coming in on the chat. One was related to plans to carry out research on new molecules on the SKIL platform. And the question is how many roughly are you looking at? Yes. So I'll I'll pick it up. It's Tim. So as as we said, it's it's eighteen o one is our top priority followed by eighteen o two. So we're we're doing we're we're we're we're really concentrating on the the progression of those molecules. But if if if the the funding were available or we we had some particular ideas about how to recruit new molecules coming out of the skill platform that then we would pick that up. But at the moment, it's 18 o one and eighteen o two are top priorities.

40:10 Great. Then as an additional question on the chat, what are John's thoughts on the allosteric mechanism of inhibition versus eighteen oh one? Well, it's interesting. I mean, the duclavacitinib molecule from BMS looks to be working well in the clinics, giving good safety data. It's obviously a very selective method for inhibiting TYK2 only. I think where we're hoping there will be an advantage with our molecule is that we get the JAK1 inhibition as well alongside TYK2. And as I mentioned in the presentation, you know, we think that could be very important in, for example, the interferon alpha signaling pathway, which relies on both TYK2 and JAK1 to inhibit that signal fully.

41:05 And there are other opportunities where JAK1 plays a very important role in many inflammatory cytokines. So I think Alistair, it's a nice approach for pure TYK2. Several other companies going down that route of Nimbus, Arcutis. You know, it's hard to it's hard to know how they are gonna differentiate their molecules from cucravacitinib. But, anyway, that's their problem. But I think, know, we're nicely nicely differentiated with the additional JAK1 activity, which we believe will give us some has the potential to give us some efficacy efficacy advantages. Great. Thank you. I think that's the bulk of the questions asked already.

41:56 So it might be a good time to hand back to Tim to wrap up now. Yes. Thanks very much. Yes. So I think I think some of the questions posted live, I think we've covered off in in the presubmitted ones. The there there's others there that I think we need we need a more considered written answer to, which we will provide that during the next week or so. So, really, it it remains me to thank everybody for attending today. Thank you for your questions. And we we we certainly got a lot to look forward to here at SAREUM as we work through the the the CTA approval of SDC 18 o one and start its clinical journey. So, again, thank you very much for joining us. That's great. Tim, John, Steve, and Jessica, thank you ever so much for your time this morning and for updating investors.

42:47 Can I please ask investors not to close this session as you'll now be automatically redirected for the opportunity to provide your feedback in order the management team can better understand your views and expectations? May take a few moments to complete, but I'm sure it'll be greatly valued by the company. On behalf of the management team of SAREUM HOLDINGS PLC, we'd like to thank you for attending today's presentation. That now concludes today's session. May I wish you all a very pleasant morning?