Sareum Holdings (LSE:SAR) — Annual General Meeting

0:01 Good morning, ladies and gentlemen, and welcome to the SAREUM HOLDINGS PLC Annual General Meeting. Throughout this recorded meeting, attendees online will be in listen only mode. Questions are encouraged and could be submitted at any time using the Q and A session.

0:18 Company may not be in a position to answer every question submitted today given the attendance on today's call. All questions will be reviewed with responses published on the Investor Meet company platform where it is appropriate to do so. It gives me great pleasure to hand over to Non Executive Chairman, Doctor. Stephen Parker. Good morning. Thank you. Good morning, ladies and gentlemen, and welcome to the Annual General Meeting of SAREUM HOLDINGS PLC. I'm Stephen Parker, Chairman of the Board. A quorum, being two members, is present, and therefore, we may now proceed with the business of the meeting. Because of the train strike today, we have also opened a link through the investor meet company sites in addition to the conventional meeting. I'm particularly grateful to those of you who have overcome the transfer problems today to attend in person. We will take questions from the floor in the usual manner of our Annual General Meetings and try to cover some or all of the questions posed via the IMC site.

1:10 I will therefore read through the resolutions together with the votes received. I should actually say not with the votes received, I'll explain in a second, and then provide the opportunity to remote shareholders to post questions, which the directors will endeavor to answer during the meeting. Any answers which we have been unable to provide immediately will be posted on the company's website within the next few days. I would now like to introduce the board. Starting from my extreme right, Clive Birch, the senior independent director, doctor Tim Mitchell, CEO. Morning. On my left, doctor John Reeder, CSO, and doctor Mike Owen, who are non exec director and chair of the remuneration committee.

1:55 I would now like to start the formal proceedings of this Annual General Meeting. The notice of Annual General Meeting was posted to shareholders on the 11/24/2022. Accordingly, the requisite notice of the annual general meeting has been given. I propose, therefore, that with your consent, the notice of annual general meeting should be taken as read. Do you agree to that? Thank you. Before proceeding with the formal business of the meeting, I will now read a statement which was issued to the market this morning. The company made good progress in the financial year to the 06/30/2022 and remains confident in its future despite some recent set backs. SDC eighteen oh one is SAREUM's TYK2 JAK1 inhibitor being developed as a potential new therapeutic for a range of autoimmune diseases with an initial focus on psoriasis, an autoimmune condition affecting the skin.

2:47 As announced on the 11/08/2022, the UK Medicines and Healthcare Products Regulatory Authority informed SAREUM that it has not been able to approve the clinical trial authorization to evaluate safety and tolerability of SDC eighteen o one. The company can confirm that it provided a robust preclinical data package to support the CTA application in collaboration with several world leading internationally recognized contract research organizations. The MHRA has indicated that it requires an additional review by the UK Good Laboratory Practice Monitoring Authority as part of the preclinical data included in the application to approve the clinical study. SAREUM and its advisers have sought additional clarification for MHRA and The UK GLP on the next steps.

3:35 In parallel, we're seeking clarification with the MHRA. The company is also assessing regulatory opportunities in other countries. SAREUM remains committed to SEC to SDC1801 and is focused on finding the quickest and clearest pathway to obtaining authorization to commence clinical studies for the asset. TYK2 JAK1 inhibition has demonstrated benefits in maintaining a healthy immune system and has strong clinical validation in psoriasis and psoriatic arthritis. And we believe this asset has great potential. This week, we have seen evidence of the continued commercial interest in the TYK2 class following the announcement by Takeda of plans to acquire Nimbus' Laxmi, Inc, a unit of Nimbus Therapeutics for an upfront consideration of 4,000,000,000 US dollars.

4:22 We believe this underscores the great potential of this class. STC 18 o two, SAREUM continues to work on the translational studies for '18 o '2 needed to define the optimal cancer application prior to completing toxicology and manufacturing studies. Planning for such studies will incorporate what we have learned from our experience with eighteen oh one. The license program s SARE seven thirty seven, which is the selective check inhibitor. As announced on the 10/12/2022, SAREUM has been informed by Sync SAREUM HOLDINGS now a subsidiary of GSK PLC, but it intends to return the rights of SAREUM, the selective checkpoint one kinase inhibitor to SAREUM's co development partner, the CRT pioneer fund.

5:11 The SRA seven thirty seven license agreement has a ninety day notice period for termination, and therefore, the company expects the rights to be formally returned in January 2023. SAREUM is evaluating the potential development opportunities for this asset with CPF and will provide further updates as appropriate. SRA seven thirty seven was discovered and initially developed by scientists at the Institute of Cancer Research in collaboration with SAREUM, with funding from SAREUM and Cancer Research UK. In conclusion, the board believes SAREUM has a strong pipeline of kinase inhibitors, which have the potential to provide great benefit to patients. The company is committed to advancing SDC 18 o one into clinical development and is focused on finding the quickest and clearest pathway to obtaining authorization to commence clinical studies for the asset, whether it be in The UK or via the MHRA or other countries.

6:05 The company also remains confident for the potential of SRA-seven 37 and now has the opportunity to be more closely involved in planning its future development. We would like to thank our shareholders, suppliers, contractors and other stakeholders for their continued support and look forward to providing further updates on progress in due course.

6:30 Before we turn to the resolutions, I would like to say a few words about the procedure as this will again necessarily differ from previous years in that only physical attendees are able to vote today, having received proxies from nonattending shareholders previously. Any shareholder listening through the IMC platform can only vote through the submission of proxies, and I hope you've already done so. I will propose each resolution in turn, having briefly summarized the content. I will then not read the results until the end of the meeting because we will need to collect your proxies from those in the room and to make the quick calculations. But I hope to do that before the meeting finally closes. The directors will not answer questions relating to the individual rights of shareholders.

7:21 Any shareholder who wishes to raise such a question should communicate with me or doctor Mitchell by email following the meeting. I shall move on to the full business of the meeting. I will now recite the resolutions. The full text of each of the resolutions is set out in the notice of annual general meeting, a copy of which is on the company's website.

7:41 Resolutions one to five were proposed as ordinary resolutions, each requiring a simple majority of the votes cast to be in favor in order to be passed. Resolution six was proposed as a special resolution requiring a majority of 75% of the votes cast to be in favor in the order to be passed in order to be passed. Resolution one. I proposed resolution one in the notice of annual general meeting as an ordinary resolution to receive and adopt the report of the directors and financial statements for the financial year ended 06/30/2022.

8:19 Resolution two, I propose resolution two in the notice of annual general meeting as an ordinary resolution to receive and adopt the remuneration committee report for the year ended 06/30/2022. Resolution three in the latest final general meeting is for the reelection of doctor John Reeder, who retires by rotation under section seventy six and seventy seven of the articles of association and who, being eligible, offers himself for reelection as a director. Resolution four in the notice of annual general meeting is to confirm the appointment of Shipley's l l LLP as auditor of the company to hold office until the conclusion of the next AGM at which accounts are laid before the company and to authorize the directors to fix its remuneration.

9:08 Resolution five. I proposed resolution five in the notice of annual general meeting as an ordinary resolution that the directors be, and they are generally and unconditionally authorized for the purposes of Section five fifty one of the Companies Act 2006, the act, to exercise all the powers of the company to allot shares in the company and to grant rights to subscribe for or convert any security into shares in the capital of the company up to an aggregate nominal amount of £850,000.167, provided that this authority is for a period expiring at the conclusion of the company's next Annual General Meeting. But the company may, before such expiry, make an offer or agreement which would or might require shares to be allotted or such rights to be granted after such expiry, and the directors may

10:04 of such offer or agreements, notwithstanding that the authority conferred by this resolution has expired. This authority is in substitution of all earlier authorities to the extent unused. On the assumption that resolution five is approved and passed, resolution six, I propose resolution six in the notice of annual general meeting as a special resolution that the directions be and they are empowered in accordance with section 570 of the act to allot equity securities as defined in section 560 of the act wholly for cash pursuant to the authority conferred by the previous as if section five six one of the act did not apply to any such allotments provided that this power shall be limited to the allotment of equity securities.

10:54 A, in connection with an offer of such securities by way of rights, open offer, preemptive or offer, or holders of ordinary rights in proportion as nearly as may be practical to their respective holdings of such shares, but subject to such exclusions or other arrangements as the directors may deem necessary or expedient in relation to fractional entitlements or any legal or practical problems under the laws or any territory or the requirements of any regulatory body or stock exchange. And b, otherwise, in pursuant to subparagraph a above, up to an aggregate nominal amount of 850 thou thousand £867 and shall expire on the conclusion of the next annual general meeting of the company after the passing of this resolution, save that the company may, before such expiry, make an offer or agreement, which would or might require equity securities to be allotted after such expiry, and the directors may allot equity securities of any such offer or agreements, notwithstanding that the power conferred by

11:56 this resolution has expired. Now has everybody in the room had the chance to complete their property forms? If you haven't, I'd be grateful if you could do so at this stage, and then we'll get those collected so they can be summed together with the the properties already received in in advance of the meeting.

12:22 So that will that concludes the the the formal resolutions. I'd like to throw the meeting open to any questions that you may have in the room. Once we have answered your the questions in the room, we will then go to the the online questions that that have been posted. Yep. We should have gotta kick it off. Yes. All good. Could we have a little bit more clarity, if that's possible, around the issues regarding the CTA?

13:07 Which I think is probably a hot topic for the majority of investors Yep. In terms of are are the board is the board confident that plans are in place to provide us with the necessary progress to get 18 o one into the clinic? I would say we're absolutely confident. Yes. Yes. Good. Okay. I won't ask for disclosure. Okay. Because, I mean, there there has been some comment as you stated in r and s in terms of looking at other countries. Mhmm. It's not a possibility. Yep. Obviously, the investors would be concerned if other countries are involved. Does that mean we start from square one in submitting an application for CTA, or is there an element of rollover from the application of what you've got in? John, do you want to Sure. Yes.

13:59 Yeah. There's an element of rollover in respect to the fact that the documentation that we've

14:04 already prepared and submitted to MHRA to a large extent is ready to over directly to any other regulatory authority that we choose to approach. If there there could, for example, be some foreign language translation requirements, so patient facing documents Right. If we don't so so we are talking to in Europe. There would need to be some translation. That would be very rapid and quite quite short documents. The clinical trial protocol, if we were to change clinical research organization, which we would need to if we go overseas, that would need to be developed with the alongside that clinical research organization.

14:49 So we have a protocol that was ready to go with our Manchester Group.

14:55 It would need some Right. Change to to just to accommodate their working practices, but it Yeah. We have Actually, what we're proposing to do with healthy subjects and the patients would not change, but there'd be some, you know, administrative changes to that documentation that would need to be made. But that would be short period of time to get those documents ready. Okay. So the issues that we're encountering in The UK with the MHRA are potentially not issues that we would encounter, hopefully, if we go to Europe, for instance. We believe that's We we believe so. The country that we've got in mind in in particular, we have a very strong reason to believe we would not encounter those difficulties that we've encountered with an HRA.

15:40 Okay. So not 100%, but high degree of confidence that we will actually get the CTA through. High degree of confidence. I mean, I'm not gonna say a 100% given our experience with MHRA, which came as a surprise. So let's put it that way. Okay.

15:59 In terms of the impact on eighteen o two, presumably, if we resolve the CTA issues for eighteen o one, then that would clear the way for eighteen o two in exactly the same way, or are we anticipating that we'll have to make changes CTA application for eighteen o two? No. There'll be no no changes to the CTA application. Okay. So this is, like, a once in process issue that needs to be resolved. Yeah. Okay. Okay. In a similar vein in that case, I'm not asking you to reveal plans, but with seven three seven due to come back into circulation in in January Mhmm. Is it encouraging that we will have plans in place to actually get seven thirty seven back into the clinic?

16:50 Shall I take that?

16:53 So so part of the review process will be to go through the data pack that Sierra generated. Yeah. I suppose with the fine tooth comb for us to assess the pros and cons of looking for a a new license partner immediately versus doing doing a little bit more clinical work with it to progress it. But I I don't think we'll be in a position to make that call until we've seen the, you know, the the minutiae of the details from the the clinical study report, which we haven't we haven't had returned to us yet. Right. Okay. But subject to encouraging data in that case, the intention would be be to to try try and get it back into the clinic.

17:42 If if we were to progress into the clinic, yes, it would almost certainly be as a combination. I think I well, I think the prudent thing for us to do would would would be to progress, you know, both looking for a partner and consideration of clinical studies in parallel till I suppose till one of those options becomes apparent as the best way forward. Right. Okay. So in in that case, we have to wait and see what the data reveals before we can Yeah. Get the operation. Right. Okay. But we should be getting that data back January. Yes. The the process I mean, the it it it's sort of as soon as possible as as well without delay after that formal return date is but, I mean, you know, that's so that's a it's it's an unwritten time, but it's, you know, it it it should be fairly prompt yeah. It should be fairly quick that we get that data back.

18:35 Going back to tip two in that case, the tequila Mhmm. Used this week was obviously high profile. Does that give you confidence with TIC two h a o one h? Oh, absolutely. Yeah. Yeah. Yeah. Yeah. I mean, it was yeah. So so so for those who who didn't see the announcement yesterday, Takeda well, we actually mentioned it in in the report in in so yes. So so so they bought essentially the the program from one of our competitors, Nimbus Therapeutics, for an enormous $4,000,000,000 plus another 2,000,000,000 in sales milestones. So so that was a product at that had reached the end of phase two b. So so I suppose mid stage clinical. So, yeah, I I mean, I think from our point of view, that shows the importance of tick two as as a product area.

19:29 And and I suppose the the increase in value on venturing into the clinic before doing a license deal. So I think, you know, that that we we're very encouraged by by that, you know, by the size of that deal and and the interest amongst the big pharma companies. Interesting point you made that that was a phase two b Yeah. Evaluation, which obviously we're a long way from. Yeah. But you have mentioned in previous statements looking at the different valuations valuations placed on the TYK2 molecule. SAREUM's business model has always been to license preclinical. Yes. Preclinical or early clinic or early clinical.

20:09 Yeah. Okay. So we we certainly shouldn't be looking at changing business model to phase two or something like that. I not at this stage, I would say. Yeah. And and the the reason for designing the Phase one study is a Phase 1a and Phase 1b so that Phase 1b is actually carried out in patients that we would hope to see not a statistical significance, perhaps a signal of efficacy, which which may be enough to to open conversations with

20:46 at that stage. Okay. So interesting just maybe enough to open conversations. At the moment, I think you've been talking to potential licensees, partners, whatever. So presumably, they're saying, show us some more for Yep. Commit. I think show us some clinical data. Yeah. Not the whole show. Okay. Great. Little line. Yeah. Yes. Just so just going back to comment here. Yes. Are we gonna run parallel with that with that consideration?

21:36 We're no. We have we're we're still committed to the process that we're in, but we're also very focused on the needs to waste as little time and as little shareholder value as we can. And therefore, if it appears that the MHRA is not going to be the most effective route through, then we're we're we're we're we're looking at a plan a, plan b scenario so that we can very rapidly switch and go down an alternative track. Whatever that might be. Mhmm. But there is also some clear guidance on what you expect

22:39 time on actually be. Because that's probably one of the biggest criticisms coming out amongst investors is that things are stating to use my term, their gray and bully, and we'd be a little bit more price clearer and sell ourselves a little bit better. Oh, we certainly we certainly want to do that. I mean, the the one I think it's it's it's it's widely recognized at the moment that MHRA in particular has been through quite a period of of of employment attrition. They've lost a lot of people in the last year, and we've heard from many quarters that pretty much all applications are taking longer than the stated timeline.

23:26 But all all we can when we when we announce what happens next in terms of the the the the approach either either continuing where we are or applying under a new system, then we will set out at least the stated timeline, shall we say, as what we expect. Obviously, we're we're otherwise, we're say we're second guessing what happens internally in a regulator, which we don't want to do. We're being honest here is the second guessing of facts that we do know. Mhmm.

24:12 And if I can use it by way of example is the RMS came out regarding the, you know, the, you second you yourself tweeted earlier in the week. If you actually look at the two points of information, I could actually ask what's your sweet effect because it was different to the RNS. So there's a case of the RNS saying we're in delay. You say

24:40 we're going. Can we just bring them together? Well, yeah, the the the picture. The the the of the tweet, of course, was to recognize the deal that that Nimbus had done with Takeda, and it is unquestionable that we are on a process to the clinic. That that tweet was not seeking to put any kind of a timeline on on the process. So I actually I actually don't think that I said anything which was a variance from the company position. Just saying that he just sent some money from water. In fact, one is not giving any. One is

25:35 I mean, one of the difficulties, of course, for us is that the timelines are out of our hands to a large extent. So once we've made our submission to the regulatory authorities, there is a statutory time by which they're meant to respond. And actually MHRA exceeded that statutory time. Not our fault. But very frustrating to us and and and to our shareholders, I'm sure. There are, you know, there are plans or estimated timelines, but they are unfortunately by definition woolly because it's out of our control. We're we're we're reliant on other people. That. All I'm asking is for a little bit more. There are some announcing how we announce Okay. I'm I'm in building planning applications.

26:21 You literally get eight weeks regulating to pass plans. They literally say, if you don't accept an extension, we'll we'll refuse it. So I know how it all works,

26:32 for us to tell ourselves a little bit better, be a little bit clearer on our statements on the stories. We'll do our best. Okay. Sorry. Is back right? Yeah. I think it seems clearly quite a hot space, particularly given as you said Uh-huh. Which is up from the. I wonder, though, are we out here of being outcompeted into I recommend it for you very much, based on that. Are we and I just really recognize the progress of the as well, which is making huge progress in price, you know, fast enough to be seen. It's moving fast. So I'm just worried, are we being outcompeted? Given the delay and given the others now, I'm making quite significant progress into the clinic as well. Sure.

27:23 So shall I take it? Mhmm. So so so the two leading tick two products are duprebisis from BMS and the Nimbus compound we've just been talking about. So they are both pure TIC two inhibitors targeting the allosteric site. So we've adopted a slightly different approach with our dual TIC two JAK one product. We've got a slightly different tick inhibition pro or JAK inhibition profile. So I think that, you know, there'll be autoimmune disease areas where where this dual profile is more suitable, and that there'll be some others where, you know, the single tick two activities is is is good or or if not preferable. So I think, you know, that there there is there's space for us on that basis.

28:10 So and and then I I think, think really, you know, the early clinical data will will indicate how competitive we are going to be. Well, certainly in psoriasis and and potentially give a lead into other indications as well. But I think there's, you know, there's a long list of autoimmune indications that where where a tick or tick track inhibitor would work very well. So I think that there is plenty of space. We're not we're not too concerned about being overcompeted.

28:40 And I think, you know, the the leading products are are doing a great job in validating the targets because certainly when we when we first started looking at TIC two, yeah, we we had trouble getting traction amongst the big pharma companies because it was an area that nobody was working on and and hadn't been validated. So I I mean, perhaps grateful is is too strong a word, but but certainly, you know, the likes of BMS have have done a lot in in validating tick two as a as a good target area. Steven, if I could just interject. If I

29:11 could just ask you to repeat Sorry. It's just a second. Sorry. If I could just ask you to repeat the questions, just it's quite faint picking the people up Okay. Back to the room. Just just in brief, if you'd be so kind, sir. Thank you. Okay. Sure. The The the the the quest the question was given the increasing competitive activity in the tick two space, are we being out competed? So did you have another question to follow-up? Yeah. The I was you know, I really agree with vision. The tick tube with with the.

29:42 Mhmm. Is there any clinical validation for that particular tumor vision?

29:47 Yes. So And where would you see that as where would you see that?

29:51 Yeah. So so if I have So before you answer Oh, sorry. Sorry. Apologies for this. The the the question was is is there any clinical support for the joint tick two, JAK one approach that we're taking in terms of about to answer. Yes. Thank you. Yes. So Pfizer have or had had actually they've they've moved on. I'll come into that in a bit. A molecule called brepocitinib, which has a dual tick two, JAK one profile, very similar to ours. So they've they've done phase twos in psoriasis and psoriatic arthritis, and they're looking at dermatomyositis and and lupus. So so they they've put the the molecule out into a into a single asset company that they've part funded called Proivant. So it they they they sort of own it, but they've sort of put it off to to one side at the moment. But, yeah, there there's there's clinical clinical validation for that that tick two JAK one approach.

30:54 Yeah. So I go a little bit back timeline wise with my question because I believe we don't know and If if we you don't don't hear learn from history, we won't necessarily be sure of the future. If it's we haven't heard what are the reasons behind that the authorities have not approved our our file Mhmm. Here in UK. And so it is important to hear from SAREUM what are the reasons that we got to know you got to know about not approving the file. And have SAREUM been an exception in that or have been other cases? And are there any similarities?

31:33 I'll take it. I have question. Yes. So so, Steve, yes, John. Oh, yes. Sorry. Yes. The the question was, what was the basis for the MHRA refusing the CTA? Yeah. So so the I suppose, you know, the level of detail we're we're we're going into at present is that they they seek an additional review part of the preclinical package. Now we, you know, we're we're confident that there's a good solid package behind that submission. MHRA have requested that their their GLP monitoring authority also examine the data. And and that's the that's the stage we are at the moment in working out the path to get The UK GLP to to to prove that data. Mhmm.

32:29 So I think that that's really that that's the level of detail that we're yeah. We we obviously know chapter and verse of of what's going on. How does it come at this stage? I mean, after submitted Well yes, requirements, restatement Indeed. All that. So Yeah. So so this I mean, this came as a surprise to us. You know, we we we we really weren't expecting it. So, yeah, yeah, I mean, we yeah. We we were kind of Yeah. I I my question was it's are we an exception here? I mean, I didn't tell you one surprise. Well, anecdotally anecdotally, I mean, we we have no firm evidence of this. But anecdotally, we we understand that there have been other companies that had the same situation.

33:16 I think that there's a degree to which I mean, the the MHRA is effectively being reborn and reinvented as a self standing UK regulator. And there are certainly some people in The UK that would like to see a whole new book of rules adopted for for the the new way that UK is doing things. My personal view, of course, is that health pharmaceuticals is is above all the global industry. And if we put ourselves too far away from the mainstream, then the future may not be as as rosy as as as it would like to be. But that's, you know, that's strange politics, and and I don't wanna do that.

34:02 But I think that there is a there is a degree to which this is part of the the MHRE's process of working out how it it handles things Yeah. In in its new guise. But but unless you communicate to the market and to us who are the others, then we ought to believe that there has been no others because we we we see in the market. We hear about the acquisitions. We hear about the transactions. You mentioned them already in your RNS. So on the other side, we need also to hear from SAREUM who has been the others any other chance why it's Well, but that information is not in the public domain. Exactly. Yeah. So they they may all be private companies who wouldn't necessarily have to announce those. Yeah. Yeah. And HRA doesn't put out a a list of who's succeeded in who hasn't succeeded. Companies, past specialists we do publish.

34:53 Well, not the private ones. Yeah.

34:56 Unfortunately not. Not. So if any would be private? Well, we think so. Yeah. I mean, we we haven't seen we haven't seen any announcements from listed companies. That's what I haven't seen. So, yeah, I mean, we, you know, so so we don't we don't know what the names of these companies companies are. Are. You know, the I suppose our our sources probably aren't at liberty to divulge the names anyway.

35:18 But yeah. So, I mean, that that because we've not seen anything in the market, our inference is that these are private companies. Mhmm. As as I said, these are these are these are anecdotal reports. So Roger. Yeah. I I mean, mean, little knowledge is the thing. Yeah. But I understand you, Tim, to say that we're going head to head with Pfizer on a combined t y c. Let me know how you pronounce it. Yes. Yes. Tick two Jack one. Yeah. Jack, Did I hear did I hear you right? We're going It's a. Well, I suppose in terms of the profile of the molecule, ours is closer to the the, well, now ex Pfizer molecule than it is to the BMS or the Nimbus molecules. Yeah. Okay.

36:09 Would I be right in picking up that given these unexpected delays in getting approval, management time has obviously been focused on that. And that there will therefore naturally be a delay in 18 o two. Am I right in assuming that? No. No. No. I'm gonna think no. I'll address that. No. I mean, we are absolutely focused on getting regulatory approval for SDC 18 o one. We're working with a development company to to get us through that process. So we still have time to progress 18 o two, but that's still going ahead on the schedule we've been working to. So can we just explore Tim was referring to us when we're talking to you about seven three seven. And could we just tease out? Is us the the pioneer fund, or it's us Yes.

37:02 SAREUM and just how you anticipate Yeah. Yes. Yep. That is the way you're going. Sorry. Can I just check? Are are you hearing that question better? Yeah. That question was fine, sir. Thank you. No need to repeat. Just just a soft spoken about at the back. Just just to remind you, of course, that the ownership of seven thirty seven is is the Cancer Pioneer Fund has 30 72.5%. We have 37 and a half percent. So and and, of course, the the license agreement was directly between CPF and what is now SAREUM HOLDINGS And our interest in that came through a signed agreement direct with CPF to cover the economics.

37:49 So in terms of the the legal flows, it's to and to and from with with with CPF, and any future deal that is done will be with CPF. They have engaged with us, however, to discuss the situation, and we are talking actively about future directions. And we have been approached both I mean, I personally have been approached on a couple of occasions. I know that some approaches have gone into CPF as well. But as Tim rightly said before, until we get the the documents and the data back, which will not be before January, then there's nothing that any of us can do in that regard other than to create an orderly queue.

38:38 Okay. I mean, I'm presumably there is a kind of a a formal agreement between SAREUM and CPF, kind of a joint venture type agreement. Covering covering covering the economic interests. Yes. Could I just think it was a question I asked your predecessor ten years ago. When when you when you ask Fuel Hunt as to why there are no institutional shareholders on the register, What is the answer you get from Pure Hunt? I I I think I think that they will probably start by by showing you the the entire sector performance in the last twelve months Yeah. Which has been absolutely dismal. I mean, there's no there's no beating about the bush here. I mean, any any any pharmaceutical biotech investment that you have is is is almost certainly got red ink all over it.

39:35 And sadly, we are absolutely in the midst of that. There seems to be control, shall we say, appetite by the institutions to look at development stage companies at the moment. But we also know that these windows open as well as shut. And that next time around, when the window opens, hopefully, we will be in a much better position to take advantage of that because of the increasing communications that there are between Peel Hunts and indeed hybrid and and institutions. If I could ask a more philosophical question, I mean, you highlight in the annual reports the principal risks of the company. Yes.

40:27 I mean, a risk that I fully recognized in the fifteen years I've been as a shareholder is what I call we're not a single man risk, double man risk. You know? I mean, you know, what happens if Tim and his smoke bike have an unfortunate or or you know, John has a size of trouble around the world. I mean but seriously, I mean, as far as I'm concerned, this is a risk that we accept, or at least I accept. Mhmm. And I I don't want to think about the consequences. But isn't it a risk that should be highlighted in the annual report? Well, if you could. I mean, it's it's it's a good point. We we do ensure our key met.

41:15 So we certainly recognize that and and hopefully we we we mitigate against a catastrophic impact on the business. Business. But you're right. It it is it's a good point, isn't it? You know? And and John and Tim in particular are are absolutely crucial to the future of our products because their knowledge is is extraordinary. I think I think short term, yeah, I can stand in for John, yeah, or John and Stephen can stand in for me. So, you know, if if the worst to happen, you know, we we can cover the eventuality short term while we look for any replacements. Yeah. I think it's probably also worth worth adding that over the course of the last year, the board has started discussing succession planning rather more actively than than it has before.

42:03 We're we're not always getting younger. Don't say. Well But yeah. You're getting wiser. Well, let let's let's hope so. Let's hope so. So was there another question at the back? Yeah. Yeah. So we got the CRO partner. Yes. Is it better to see you're the same partner? Partner? And are you worried? Disregard the partner. Well, 18 o two is still preclinical. So you haven't No. No. I mean, I I may be listening, so I don't want to speak too clunky about it because I'll put the prices up, but I would anticipate we would certainly consider the same problem. Okay. I they did nothing wrong. Yeah. I I think think that's quite important to study. So Yeah. And, yeah, the the the secret to success is never tripping over the same rock twice.

43:00 So let's hope people will be wiser with with $18.82. So it's special now. So just about that to the $73.07. Yes. Probably incorrect, but it's sort of taken out and patents on the data that they've sent back to you. Yes. Yes. They well, they haven't sent data back yet, just to be clear. Yeah. But do want yes. Did you get the question? If you could repeat that, that'd be great. Thank you. Did did Sierra take out any patents in his own rights covering seven three seven? And the answer is yes. And they but they returned to to us as part of that package. Yes. And we've got patents applications as well. I'm not sure anything's granted yet. Well, then and and and the clinical data, that's that won't get active. No. The clinical data. Yeah.

43:47 That's not subject to It hasn't just put restriction on something. No. No. No. We get we get absolutely everything back. Yeah. Yeah. Yeah. Richard? Just go and continue on seven three seven thread. With Pioneer Fund owning 72 and a half percent, that's obviously obviously a majority. If we wanted to do something with seven three seven, could they stop us? I would imagine that would be a negotiation with them. Yeah. Unlikely. They need a solution Mhmm. As much as we need a solution. So I I I think that all of these conversation all the all the conversations so far have been constructive, and I'm quite sure that will continue to be so. So were there any other questions? Yes, sir.

44:35 Regarding eighteen o one Yes. What is the possibility of trying to get the CTA approval not just in The UK, but in other countries at the same time? Why not do that? It's possible. Yeah. I mean and at the moment, we are pursuing in parallel several several courses of action. So we're continuing with MHRA, of course. We're looking at the European authority, and we're looking at overseas I'll just say overseas for now, authority, non European. And, you know, until a compelling reason comes to drop one of those strands, we'll continue with the three. And if there are no other questions in the room yes, sir?

45:22 Final question. Was it consolidated? We did. In hindsight, Is that a wise decision? Well, timing is everything. And but having said that, I I don't think there is anything particularly to suggest that our performance would have been any better if we hadn't consolidated. It's our fault. It's a it's a mathematical treatment and and not much more than that. So I don't I don't I mean, it'll it'll be lovely to say if only we hadn't done that, but I think that, as I say, we would we would be in a similar performance boat irrespective is my view. So if there are no more questions in the room, and I thank you all for for your your your questions and your contributions, I'm going to pass the baton over to do we have a a full result, Chris?

46:26 Yes. So in that case, if if I could have that, I'll just read the read the results out, and then we'll go to the the online Technology is wonderful. The online questions from there. Well, I've got the votes. Those are there. Thank you. Thank you. So I can start by telling you that all six resolutions have been carried. Resolution one, forgive me, I don't intend to read them out again, but if you can hopefully remember what they were. This was this was the the annual report. Votes for 8,297,025, which represents 99.87 of the votes against 11,023, withheld 4,533.

47:29 The second resolution, which was the appointment of auditors from memory sorry, RIMCOM. RIMCOM, I beg your pardon, for 7,274,693, which is 88.96% of the vote against 902,951, withheld 134,937. Resolution three, which was, I think, the auditor's reelection. Was that you? Myself. Oh, that's right. Well, John got away with it. $48,127,306, which represents 99.15% against 69,338, withheld 115,937.

48:20 Resolution four, which is finally at the auditors, for $7,660,150.55, which represents 93.66% against 518,753 and withheld 133,673. Resolution five, which was the allotment ordinary resolution for 700, three hundred and eighty seven and seventy two votes, which represents 89.52% against 864,630 withheld 60,879. And Resolution six, which was a special resolution for eight sorry, 7,357,844, which represents 89.17% against 893,858 and withheld 60,879.

49:26 Those results will, of course, be posted on an RNS later in the day so you can you can see the the numbers from there. Mister Sheldon, it's very common. I was very pleased to see that you had a turnout first turnout of 12%. I mean, I think in previous AGMs, it's been three to 4%. Indeed. I think, anyway, congratulations. Good. I mean, Tim and Tim and John used to control the company. Moving moving in the right direction. Yes. In the right direction. Exactly. Exactly. Thank you for that. Much appreciated. So with with that, I'm gonna pass the baton to our newly appointed head of IR, Alex Harrison, who is going to as the quiz master for the online questions.

50:17 Alex, over to you. Thank you, Steven. And I hope you can everybody can hear me. So the first question that I will put to you is how long is the review by GLP likely to take? The short answer is we don't know. And, you know, I alluded to it earlier. We're reliant on other people to do So the processes at MHRA have to request for that review to take place from The UK GLP monitoring authority, and and then the review needs to occur. And all I can say is at the moment, that has not begun. Next one is, has the MHRA acted outside of normal guidelines so far as refusal of the CTA?

51:07 If not, how has the additional requirements been missed by yourselves and the so called internationally recognized CROs? So it's to do with a a portion of the data. They're querying the process by which that data was generated. And so they're not querying the data itself. They're querying the process. And I think the fact that they're asking the UK GLP monitoring authority to review suggests that they have some concerns about the you know, whether the studies were done under GLP conditions. We believe they were. There were inspection certificates in place current at the time that the experiments took place.

51:57 But MHRA have have clearly got got some some issues with that, and they would like the UK GOP authority to review that data, to look at the processes that were in place when that data was collected, and to to say say yes or no. Hopefully, yes. But so I think it's important to say, you know, it's not the data itself that they have any issues with. They're not querying the results of any experiments. They're not questioning the data we presented, but it's to do with the process by which that data was gathered. Thank you. So also on eighteen o one, if you're confident of CTA approval, why would you consider at cost overseas applications? So we're looking for the quickest route to the clinic. I I I mean, it's important to say, but we're also looking we're we're only talking to good high quality clinical units and high quality regulatory authorities. Okay? So we're not we want to be quick, but we're gonna still do a thoroughly excellent job of the of the clinical study.

53:05 And at the moment, while the timelines are are woolly or indistinct, we're looking at alternatives to NHRA because NHRA might take a long time. They they took their I've said already, they took slightly over their statutory time limits to consider our application. That could happen again, and we just want to hedge hedge against that in essence while looking at other other territories. Great. So this one's on seven three seven. When do you expect to receive the clinical study report data pack versus seven three seven? And how long do you expect expect your evaluation of these reports to take before going forward with the project?

53:52 Have you or Cancer Research UK received any interest for seven three seven from any other company or interested party? I know, Steven, you've alluded to that. But Yep. And And so so, I mean, the I I the the process as we understand it, because because, you know, we haven't we haven't really been around this this path before, is that as soon as the formal termination date comes up, which is is early January, then Sarah stroke GSK return the packages, you know, quote without delay, unquote. So we'd expect, you know, I suppose soon after, you know, low number of weeks hopefully, but I think it's difficult to second guess that.

54:43 And then really, the review period is I mean, it's it's it's kind of difficult. Again, yeah, I mean, I think, you know, it it it may take more than a day. It shouldn't take more than a month, think. Is that about right? Yeah. Yeah. Mean, mean, they're they're they're pretty solid documents, aren't they? Yeah. There's quite a lot to wade through, but, obviously, you know, that's a that'll be a priority for us. Yes. I I think those are, you know, the the timelines are roughly I should think there's a low low number of weeks to get the data, a number of a low number of weeks to review it. Great. It will depend to some extent on how much SAREUM have trawled through that data as well because there's quite a lot of genetic information taken for each of the patients in that study.

55:32 And so, you know, there could be a correlation between the genetic background of patients and their response to treatment. And at this moment, we don't have a good feeling for how much SARE have dug into that. Yeah. If they provide us with a nice report correlating genetic background of patients with the outcomes, fabulous. We can read that through quickly. But if they haven't done that, we'll want to do that ourselves because I think that's important, you know, if we can see a clear signal for patients who responded or or who didn't respond, that's a very key piece of information that will help us to develop that project. Well, you know, whoever takes the project on, we'll be looking through that data. So it's hard to say until till we actually see what's coming back to to CPF.

56:20 But I think a guide of between a day to I I I think it probably take more than a day, but between a day and a month is yeah. Thank you. In terms of our JAK kinase, do we still have best in class potential as mentioned in the final results, or are there now competitors with a better product? I think I mean, we have best in class potential. So the compound that Tim mentioned, brepacitinib, that Pfizer had and are now working in partnership with Prevent has can be improved. And I think our molecule has some potential to improve upon that upon that molecule. You know, it's absolutely key that we get it into the clinic because the preclinical studies are not going to differentiate the molecules.

57:12 It's all about the, you know, the safety profile and the efficacy profile. And until we get phase one a, which will give us a safety data, phase one b, which will hopefully give us some efficacy signal. That might be biomarker. It might be disease modification. But then we'll be able to compare to Pfizer's report on brepocitinib from their phase one studies, and we'll be able to look for differences and hope that we're gonna see some benefits from our molecule. I mean, the next question is is very much linked. So do you believe there are likely to be any potential points of differentiation of SDC 18 o one versus brepasipinib, I e, a molecule with the same mechanism tick to JAK one affinity?

57:59 Yes. I I mean, the the key thing is are the shades of JAK selectivity and then any off target activity that might be in the molecule. So we believe that brepasitinib has some JAK two inhibition that some hard to hard to define or measure exactly, but some JAK two activity, which may be causing some of the side effects that they see. So reduction in reticular sites is the main one. These are red blood vessel, early red blood vessel sorry, red blood cells. So progenitors of red blood cells are called reticulocytes, and Pfizer do see some reduction in reticulocytes at the higher doses, and that's dose limiting. So they went up to I think they went up to certainly beyond a hundred mg dose in their phase one trials, and I believe they're currently using a thirty mg dose in their phase three and phase two trials.

59:09 So, you know, we may see a reduced effect on reticular sites. Again, yeah, until we get in the clinic, it's very difficult to be precise about these things, but we have less JAK JAK two activity. So we may see less effect on reticulocytes, which would allow us to dose higher, which would allow us to increase or improve on the efficacy that Pfizer demonstrated. So there's absolutely potential. Then, you know, off target effects, Pfizer reported on repositinib, but there is some activity on a transporter called DOCT two. Okay? So a renal transporter. It affects the transport of creatinine, and they did see some increases in creatinine levels in in some of the subjects in their phase one, which may be due to that. So we have less effect on that particular renal transporter in in from in vitro studies.

1:00:06 And so there's a potential benefit of our molecule there. Yep. Conversely, there may be something that we haven't seen about our molecule that could cause a side effect. And and that's why it's you know, we've just got to get it in the clinic and try it and see what happens. We've done all the preclinical studies to show the safety. We're not expecting that we hit anything off target. We've looked, screened against other targets, not seen anything. But until you get it in the clinic, you you might you might miss something. So that's what needs to happen. Thank you. Back to eighteen o one, what is the commercial reason you don't disclose the CROs? These obviously play a large part in the progress of SAREUM and MHRA has now questioned their progress.

1:00:55 Sorry. Their processes. Sorry. So yeah. I mean, so we are deliberately coy about which CROs we use, which countries they operate in for for a number of commercial reasons. I suppose I suppose one is if there's a a problem with a particular CRO unrelated to what we're doing, but maybe with some other work they're doing, we don't wanna be tainted by that brush. Similarly, if if there's sort of issues arising from the countries they operate in, you know, again unrelated to us, but we can still get tainted by that brush. And what what we really can't be doing is is giving our competitors any snippets of information or, you know, to try and to to talk our our molecules down when they're having discussions with with their potential partners. So we we we are, I suppose, deliberately vague about who we're working with and and and where they operate.

1:01:52 Except that they're world, yeah, they're world leading CROs in fully fully inspected laboratories. So, you know, the the this is these are high class operators. We just, for for commercial reasons, don't disclose who and where. Thank you. Given there are at least five TYK2 inhibitors in clinical development and two others in late preclinical at well funded US VC companies, what do you consider to be the best way to create a differentiated target product profile for SDC 18 o one and make this attractive prospect to a potential partner? Yeah. I think so it leads to a question from a from a gentleman in the room here about outcompeted.

1:02:41 I mean, my my feeling is that we're not being outcompeted in terms of molecule profile, but we perhaps are in terms of psoriasis, for example. So there's an awful lot of treatments coming through for psoriasis at the moment. So we'll be looking to position STC 18 o one against a different disease. However, that said, our plan is to do the phase one b trial in psoriasis patients. The reason being patients are available, so you can recruit to your trial quite readily. And psoriasis is biologically driven by the kinds of pathways that we're going to be impacting on. So we would expect to see some certainly biomarker driven signal of efficacy.

1:03:27 And it's a very good proof of concept disease for our molecule. Bearing in mind that our business model is to partner at late at at late preclinical or early clinical stage, we want to provide a, you know, a package of data with patient data in there to a partner who's going to develop a molecule and take it into to market. And, you know, my suspicion is they will look at different diseases to psoriasis. Yeah. We may get an absolutely fabulous result in these psoriasis patients, and it becomes compelling to take it forward in that in that patient population. But my suspicion is at the moment that they'll be looking for different therapeutic areas which respond best to the inhibition of TYK2 and JAK1, and there are several that might be considered for that.

1:04:24 Okay. Great. Just to follow-up. Just to be clear, have SAREUM or CR UK received any interest from any parties when you're expressing seven three seven? Well, we we already addressed that, so the answer is yes. Yeah. Yeah. We can't give any. One more question which was submitted in advance. What would the board say to potential investors to convert interest into real investment? I I would say that there's a combination here of several products, any one of which coming through will be absolutely transformative both in terms of patient benefit, but also perhaps in that context, more importantly, in terms of the financial future of the company.

1:05:25 And that we are we remain, and we have always been, but we absolutely remain very confident that despite, say, a few rocks in the road we've seen in this latter part of the year, that we are well positioned to move products forward to a point where they can be taken up and by major pharma companies. And there are some very meaningful commercial discussions to be had with them as part of that process. So I think that the product portfolio at the moment is is is attractive, but hopefully will become more so as we succeed in getting into the clinic.

1:06:12 Great. Thank you. So I think that I've tried. Obviously, there's quite a lot of duplication in some of the questions and from the the floor live today. So, hopefully, that represents most of the questions and any others we will respond to through the portal. Very good. Well, thank you, and thank you, everybody, for your contributions. I would just, as I say, remind you that there will be an RNS posted with the formal results of the votes today. But thank I'd like to thank all of you, whether you're online or you've managed to overcome the transport difficulties actually come here today. We really do appreciate your active view and the active role that you take in this company.

1:07:04 We are always pleased to hear from you, especially when the criticism is constructive, but we are always pleased to hear from you. And do please keep up your support of the company and of the team here, and we look forward to seeing you, if not before, at year's AGM. So with that, I'll formally close the business of the meeting. Thank you. That's great. Thank you to the Board of SAREUM for updating attendees this morning. This will only take a few moments to complete, but I'm sure it will be greatly appreciated by the company. On behalf of the board of SAREUM HOLDINGS PLC, we'd like to thank you for attending today's Annual General Meeting. Good morning to you all.