Sareum Holdings plc (SAR) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and welcome to the Sareum Holdings plc Annual General Meeting. [Operator Instructions] The company may not be in a position to answer every question submitted today given the attendance on today's call. However, all questions will be reviewed with the 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, Dr. 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 2 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 transport 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 posted via the IMC site. I will, therefore, read through the resolutions together with the votes received. I should actually say not to the votes received, I'll explain in a second, and then first 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; Dr. Tim Mitchell, CEO; on my left is Dr. John Reader, CSO; and Dr. Mike Owen, who Non-executive Director and Chair of the Remuneration Committee. 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 24th of November 2022. Accordingly, the requisite notice of the Annual General Meeting has been given. I propose, therefore, that with your consent, the notice on Annual General Meeting should be taken as read. Do you read 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 30th of June 2022 and remains confident in its future despite some recent setbacks. SDC-1801 with Sareum's TYK2/JAK1 inhibitor being developed as a potential new therapeutic for the range of autoimmune diseases with an initial focus on psoriasis, autoimmune condition affecting the skin. As announced on the 8th of November 2022, the U.K. Medicines and Healthcare Products Regulatory Authority informed Sareum that it has not been able to approve the Clinical Trial Authorization to evaluate the safety and tolerability of SDC-1801. 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 pre-clinical data included in the application to approve the clinical study. Sareum and its advisers have sought additional clarification from the MHRA and the UK GLP on the next steps. In parallel with seeking clarification with the MHRA, the Company is also assessing regulatory opportunities in other countries. Sareum remains committed to SDC-1801 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' Lakshmi Inc., a unit of Nimbus Therapeutics for an upfront consideration of USD 4 billion. We believe this underscores the great potential of this class. SDC-1802, Sareum continues to work on the translational studies for SDC-1802 needed to define the optimal cancer application prior to completing toxicology and manufacturing studies. Planning for such studies will incorporate what we have learnt from our experience with SDC-1801. So, Licensed Programme SRA737, which is the Selective Chk inhibitor. As announced on 12th of October 2022, Sareum has been informed by Sierra Oncology, Inc., now a subsidiary of GSK plc, that it intends to return the rights for SRA737, a selective Checkpoint 1 kinase inhibitor, to Sareum’s co-development partner, the CRT Pioneer Fund. The SRA737 licence agreement has a 90-day notice period for termination and therefore the company expects the rights before we returned in January 2023. Sareum is evaluating the potential development opportunities for this asset with CPF and will provide further updates as appropriate. SRA737 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-1801 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. The company also remains confident in to the potential for SRA737 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. 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 non-ascending shareholders previously. Any shareholder listening through the IMC platform can only vote through the submission of proxies and I hope that you've already done so. I will propose each resolution in turn, having briefly summarize the concepts. I will then not read the results until the end of the meeting, because we need to collect your proxies from those in the room and to make the quick calculations. I hope to do that before the meeting finally closes. The directors will not answer questions relating to the individual rights of shareholders. Any shareholder who wishes to raise such questions, we will communicate with me or Dr. Mitchell by e-mail following the meeting. I shall move on to the formal 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. Resolutions 1 to 5 are proposed as ordinary resolutions, each requiring a simple majority of the votes cast to be in favor in order to be passed. Resolution 6 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 -- an order to be passed. Resolution 1, I propose Resolution 1 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 30th June 2022. Resolution 2, I propose Resolution 2 in the Notice of Annual General Meeting as an ordinary resolution, to receive and adopt the Remuneration Commission report for the year ending 30th of June 2022. Resolution 3 on Notice of Annual General Meeting is for the reelection of Dr. John Reader, who retires by rotation under Section 76 and 77 of the Articles of Association and who, being eligible, offers himself for re-election as a director. Resolution 4 in the Notice of Annual General Meeting is to confirm the appointment of Shipleys 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. Resolution 5, I propose Resolution 5 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 551 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 GBP 850,867 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 allot shares and grants 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 of that Resolution 5 is approved or passed, Resolution 6, I propose Resolution 6 in the Notice of Annual General Meeting as a special resolution, as the directors 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 resolution as if Section 561 of the Act did not apply to any such allotment, provided that this power shall be limited to the allotment of equity securities: a, in connection with an offer of such securities by way of rights, open offer or preemptive offer of holders' 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 of any territory, or the requirements of any regulatory body or stock exchange. And, b, otherwise than pursuant to sub-paragraph (a) above up to an aggregate nominal amount of GBP 850,867 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 just to be allotted after such expiry and the directors may allot equity securities of any such offer or agreement notwithstanding that the power conferred by this resolution has expired. Now, as everybody in the room has a chance to complete their proxy forms. If you haven't, I'd be grateful if you could do so at this stage, and then we've got those collected, so they can be summed together with the proxies already received in advance of the meeting. So that will -- that concludes 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 online questions that have been posted.

Mitchell, you got to kick it off.

Could we have a little bit more clarity and the possibles of around the issue regarding the CTA, is probably a hot topic the majority of investors. In terms of all the board looking forward confident that some plans are in place to provide us with the necessary progress to get SDC-1801 into the clinic.

I will say, we're absolutely confident.

Yes. Yes. Good. I won't ask a disclosure. Okay. Because I mean there has been some comment as you stated in the RNS in terms of looking at other countries, it's about possibility. Yes. Obviously, the investors will be concerned if the other countries are involved, does that mean we start from square one in submitting an application to the CTA? Or is there an element of rollover from the application of where you protest?

John, do you want to take?

It's Reader. It's known as a rollover in respect to the fact of the documentation that we've already prepared and submitted to MHRA. It's when large extent is ready to rollover directly to any other regulatory authority that we choose to approach. If there could, for example, be some foreign language translation requirements, so patient-facing documents, if we go -- so we are talking to authority in Europe, there would need to be some translation probably very rapid and 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 of that clinical research organization. So we have a protocol that was ready to go with our Manchester group. It would need some change just to accommodate their work in practices, but actually, what we're proposing to do with healthy subjects and the patients would not change, but there will be some administrative changes to that documentation that would need to be made. But that would be a short period of time to get those documents ready.

Okay. So, the issues that we're encountering in the U.K. with the MHRA are potentially up issues that we would encounter hopefully with Europe?

We believe that.

Which we believe so, the country that we've got in mind in particular, we have a very strong reason to believe we would not encounter those difficulties that we've encountered with MHRA.

Okay. So not 100% a high degree of confidence that we will actually get the CTA?

A high degree of confidence. I'm not going to say 100% given our experience with MHRA which came as a surprise, so that's really at.

Okay. In terms of the impact of SDC-1802, presumably, if we resolve the CTA issues for SDC-1801, then that would clear the way for SDC-1802, are exactly the same way or are we anticipating that we'll have to make changes with the CTA application for SDC-1802?

No. There will be no changes to the CTA application.

So, this is SDC-1801 process, this year that needs to be resolved?

Yes.

Okay. And in the similar way, in that case, I'm not asking you to reveal plans, but with SRA737 due to come back into circulation in January. Is it encouraging that we will have plans in place to actually get SRA737 back into the clinic?

So much. Shall I take that? So part of the review process will be to go through the data pack that Sierra generated, I suppose with a fine-tooth comb for us to assess the pros and cons of looking for a new license partner immediately versus doing a little bit more clinical work with it to progress it. But I don't think we'll be in a position to make that call until we've seen the minutia of the details from the clinical study report, which we haven't had returned to us yet.

Got you. Okay. But subject to encouraging data in that case, the intention would be to try and get a [indiscernible]

So if we were to progress into the clinic, yes, it would almost certainly be as a combination. I think the prudent thing for us to do would be to progress both looking for a partner and consideration of clinical studies in parallel to still one of those options becomes apparent, is the best way forward.

So, I think in that case, you have sort of wait and see what the data reveals before return. I think I get that. We should be getting our data back in January.

Yes, the process -- I mean the -- it's sort of as soon as possible as well without delay after that formal return date is. But I mean, that it's an unwritten time, but it should be fairly -- should be fairly quick that we get that data back.

Going back to TYK2, in that case that Takeda, this which was obviously high profile. Does that give you confidence with TYK2?

Absolutely. Yes. Yes. I mean it's -- yes, so for those who didn't see an announcement yesterday, Takeda, where we actually -- we mentioned it and before them -- so yes, so they bought essentially the TYK2 program from one of our competitors, Nimbus Therapeutics for an enormous $4 billion, plus another $2 billion in sales milestones. So that was a product at that reached the end of Phase IIb. So I suppose, mid-stage clinical. So yes, I mean, I think from our point of view, that shows the importance of TYK2 as a product area. And I suppose the increase in value on venturing into the clinic before doing a license deal. So I think that we're very encouraged by that -- by the size of that deal and the interest amongst the big pharma companies.

Interesting point, you noted that, that was a Phase IIb innovation which obviously we're a long way from that you have mentioned in previous statements, looking at the different valuations placed on the TYK2 molecule. Sareum's business model has always been to licensed preclinical?

Yes, preclinical or early clinical. Yes.

So we certainly shouldn't be looking at change in the business model precise such as poster or something like that?

Not at this stage, I'd say, yes. And the reason for designing the Phase I study as a Phase Ia or Phase Ib, so that Phase Ib is actually carried out in patients, is that we would hope to see not a statistical significance, but perhaps a signal of efficacy, which may be enough to open conversations with at that stage.

Okay. So interesting, just may be 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 internet.

I think, show us some clinical data. Yes.

[indiscernible] Just assume, just going back to, probably as you mentioned about, make sure that [indiscernible] at the moment. Are we going to run parallel with that in consideration. Obviously, I know there's [indiscernible] I wish you'll hearing that, that was to include your positive that we are not just fragments on timelines again?

No, we're still committed to the process that we're in, but we're also very focused on the need to waste a little time and as a 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 looking at Plan A, Plan B scenario so that we can very rapidly switch and go down an alternative track.

As you can imagine, [indiscernible] is already been charted [indiscernible] one of the things that I have to be clear is the quickest way, but there will come a time that needs to make decision and -- could I ask that if the decision is that the [indiscernible] encouraged not only the country, but over [indiscernible] but there is also some clear guidance on what you expect timeline, because it's actually probably one of the biggest [indiscernible] coming from most [indiscernible] and sell ourselves a little bit better?

Well, we certainly want to do that. I think it's widely recognized at the moment that MHRA in particular, has been through a period 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. But -- or we can and when we announce what happens next in terms of the approach of continuing where we are or applying under new system, then we will set out at least the stated time line, shall we say, as we expect obviously, otherwise, we're second-guessing what happens internally in a regulator if we don't know what to do.

We're being honest here is the second-guessing has caused a lot of share price over the last 5 weeks time [indiscernible]. So I'm just looking to [indiscernible] You yourself tweeted earlier in the week, if you actually look at the 2 points of inflation, I could actually ask [indiscernible] as fact, because it was different to the RNS. So there's a case of the RNS, let's say, we're in delay, you say we go in, can you just bring them together?

The purpose of the tweet was to recognize the deal that Nimbus have done with Takeda and it is unquestionable that we are in a process to the clinic, that tweet was not seeking to put any kind of time line on the process. So I actually don't think that I said anything which was variance sort of from the company was issued.

There's just saying that just seeing some [indiscernible] in fact one is not giving any [indiscernible] we are receiving, [indiscernible] we get a clearer state from Sareum when they announce things. That's clear, from my point. You guys have made point for a lot of the investors.

I mean one of the difficulties, of course, for us is that the time lines 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 to our shareholders, I'm sure. So there are -- our plans are estimated time lines. But they are, unfortunately, by definition, will be because it's out of our control. We're relying on [indiscernible]

I appreciate that [indiscernible] annoucements. I mean building planning applications [indiscernible] 8 weeks regulating surpass plans, did you say, [indiscernible] refuse it. So I know how it all works, and for us -- tell us a little bit clearer on our statements on the studies.

We'll do our best. Sorry, [indiscernible]?

Yes. I typically seems clearly quite a hot space, particularly given as [indiscernible] I wonder that are we [indiscernible] being completed into a correct probably very long base [indiscernible] comment on that, but -- are you just recognize the progress [indiscernible] moving fast. So I'm just worried are we being out committed given the delay and given the obvious now are making quite significant progress into the clinic as well?

Shall I take it? So the two leading TYK2 products, the deucravacitinib BMS and the Nimbus compound we've just been talking about. Since they are both pure TYK2 inhibitors targeting the allosteric site, so we've adopted just a slightly different approach with our dual TYK2/JAK1 products. So we've got a slightly different TYK inhibition -- JAK inhibition profile. So I think there will be also new disease areas where this dual profile is more suitable. And there'll be some others where the single TYK2 activities is good or if not preferable. So I think there is this space for us on that basis. So -- and then I think really the early clinical data will indicate how competitive we are going to be. Well, certainly in psoriasis and potentially give allegiance into other indications as well. But I think there's a long list of autoimmune indications that where a TYK2/JAK1 inhibitor we've worked very well. So I think that there is plenty of space. We're not too concerned about being over competed. And I think the leading products are doing a great job in validating the target because certainly, when we first started looking at TYK2, we had trouble getting traction amongst the big pharma companies because it was an area that nobody is working on and hadn't been validated. So perhaps grateful, it's too strong a word, but certainly, the likes of BMS have done a lot in validating TYK2 as a good target area.

Stephen, If could just interject, if I could just ask you to repeat the question, just it's quite [indiscernible] picking the people up back of the room. Just in brief, if you'd be so kind, sir.

Sure. There's a question -- the question was, given the increasing competitive activity in the TYK2 space, are we being outcompeted? So did you have another question to follow up?

Yes, the [indiscernible]. Is there any clinical validation for that particularly the [indiscernible] inhibition and where would you see that in [indiscernible].

So before you answer. Apologies for this. The question was, is there any clinical support for the joint TYK2/JAK1 approach that we're taking and Tim's about to answer.

Yes. So Pfizer have -- or had actually they've moved on or to comment that in a bit, a molecule called brepocitinib, which has a dual TYK2/JAK1 profile, very similar to ours. So they've done Phase II in psoriasis and psoriatic arthritis, and they're looking at dermatomyositis and lupus. So they've put the monitor out into a single asset company that they're part funding called Priovant. They sort of own it, but they've sort of put it also to one side at the moment. But yes, there's clinical validation for that dual TYK2/JAK1 approach.

Yes. So I'll go a little bit back time line-wise with my question because I think we don't know -- and if we don't [indiscernible] from history [indiscernible] the future. We haven't heard what are the reasons behind that the authorities have not [indiscernible] our file in U.K. 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 -- are there any similarities?

I'll take it. Yes. Sorry. The question was what was the basis for the MHRA refusing CTA.

Yes. So I suppose, the level of detail we're going into at present is that they see the additional review of part of the preclinical package. Now we're confident that there's a good solid package behind that submission. MHRA have requested that their GLP monitoring authority also examine the data. And that's the stage we are at the moment in working out the path to get the U.K. GLP to prove that data. So I think that's really -- that's the level of detail that we obviously no chapter and verse of what's going on.

Does it come up at this stage, I mean after submitters [indiscernible] conditions, requirements, restatements and all that?

Yes. So this -- I mean this came as surprise for us. We really weren't expecting it. So Yes. I mean, yes, we will kind of.

My question was, are there exception here?

Well, anecdotally. Anecdotally, and we have no firm evidence is, but anecdotally, we understand that there have been other companies that had the same situation. I think there's a degree to which -- I mean the MHRA is effectively being reborn and reinvented as a self-standing U.K. regulator. And there are certainly some people in the U.K. that would like to sort of see a whole new book of rules adopted for the new way that the U.K. is doing things. My personal view, of course, is that health of pharmaceuticals is above all the global industry. And if we put ourselves too far away from the mainstream, then the future may not be as rosy as it would like to be, but that's strain politics, and I don't want to do that. But I think that there is a degree to which this is part of the MHRA's process of working out how it handles things in this new guys.

But unless you communicate to the market and to us, who are the others then we want to believe that there has been no others because we see in the market, we hear about the acquisitions, we hear about the transactions. You mentioned them already in your RMS. So -- on the other side, we need to also hear from Sareum who has been the others -- that's why [indiscernible]

It's not in the public -- so they may want to be private companies who wouldn't necessarily -- we wouldn't have to announce that.

MHRA doesn't put out a list of who succeeded in a [indiscernible] as we do publish.

No, not the private ones.

So if any would be private?

Well, we think so, yes. I mean we haven't seen any announcements from listed companies as well. Yes. So yes, I mean, so we don't know what the names that these companies are, I suppose, our sources probably aren't at liberty to divulge the names anyway. But yes, so I mean that's because we've not seen anything in the market our inference is that these are private companies.

As I said, these are anecdotal reports.

Yes. I mean little knowledge of to be interesting. [indiscernible] to say that we're going head-to-head with [indiscernible] on a combined TYK2/JAK1 -- I don't know how to pronounce it.

Yes, TYK2/JAK1.

Did I hear you right to win head-to-head with [indiscernible]

Well, I suppose in terms of the profile of the molecule, ours is closer to the -- well, now [indiscernible] molecule than it is to the BMS or the Nimbus molecules, yes.

Okay. Would I be right to picking up given these unexpected delays in getting approval, management times obviously been focused on that. And that there will, therefore, naturally be a delay in 1802, am I right in assuming that?

No, I'll address that. I mean, we are absolutely focused on getting regulatory approval for SDC-1801. We're working with a development company to get us through that process. So we still have time to progress SDC-1802, but that's still going ahead on the schedule we've been working to.

Mitchell, can you just explore [indiscernible] referring to us when we were talking about 737, and do we just tease out is us the pioneer fund or it's us Sareum and just how you anticipate?

Sorry, can I just check, are you hearing that question better?

Yes, that question was fine, sir. Do not need to repeat.

Just to remind you, of course, so the ownership of 737 is the Cancer Pioneer Fund has 72.5% and we have 27.5%. So -- and of course, the license agreement was directly between CPF and what is now CRO oncology. And our interest in that came through a site agreement direct with CPF to cover the economics. So in terms of the legal flows, it's to and from 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 documents of 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.

I mean, presumably, there is a kind of a formal agreement between Sareum and CPF, kind of the joint venture type of agreement.

Covering the economic interests, yes.

Could I just add -- I think it was a question I asked you predecessor 10 years ago. When you ask for your hunt as to why they're no institutional shareholders on the register, what is the answer you had [indiscernible]?

I think that they will probably start by showing you the entire sector performance in the last 12 months which has been absolutely dismal. I mean there's no beating around the bush here. I mean any pharmaceutical biotech investment that you have is almost certainly got ready in all over it. And sadly, we are absolutely in the midst of that. There seems to be well controlled, 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 and there are between Peel Hunt and indeed [indiscernible] and institutions.

Just can I ask a more philosophical question. I mean, you highlighted in the annual report, the principal risks of the company. I mean a risk that I fully recognize in the 15 years I've been as a shareholder is what I recall we're not a single man risk, double man risk. What happens if Tim and his [indiscernible] have an unfortunate [indiscernible] or John has a size of travel around the world. I mean seriously, I mean, as far as I'm concerned, this is a risk that we accept [indiscernible]. And I don't want to think about the consequences. But isn't there a risk which should be highlighted in the annual report?

I mean it is a good point. We do ensure [indiscernible] So we certainly recognize that and hopefully, we mitigate against a catastrophic impact on the business. But you're right, it's a good point. And John and Tim, in particular, are absolutely crucial to feature of our products because their knowledge is extraordinary.

I think short term, I can stand in for John or John or Stephen can stand in for me. So if worst to happen, we can cover the eventuality short term, while we look for any replacements.

Yes, I think it's probably also worth adding that over the course of the last year, the Board has started discussing succession planning rather more actively. But I mean it has before -- we're none of us getting younger.

So you're getting more wiser.

So is there other question on the back?

Yes. [indiscernible] CRI Partner. Is it interesting to the same partner as you have at [indiscernible] and are you worrying [indiscernible] Yes, it's because of the partner.

[indiscernible] is still preclinical. So when you think you haven't yet noted out [indiscernible]

No. I mean -- may be listening because I don't want to speak to about, because I put the prices up, but I would anticipate we would certainly consider the same part. They did nothing wrong. I think that's quite important to say. And the secret to success is never tripping over same rock twice. So let's hope we will be wiser with SDC-1802.

So touch on that, so just [indiscernible] 737 probably correct, but to take [indiscernible].

Yes. Well, I haven't seen data back yet. Did you get the question?

If you could repeat that, that would be great.

Did Sierra taken out any patents in its own rights covering 737. And the answer is yes, and but they return to us as part of that package.

Probably that patents applications, so I'm not sure anything is granted.

And the clinical data that we'll get back to.

Clinical data, yes.

[indiscernible]

Just to continue on 737, Fred, with Pioneer Fund owning 72.5% as obviously control majority, if we want to do something with 737, could they stop us?

I would imagine there will be a negotiation with that. Yes. Unlikely. They need a solution as much as we need a solution. So I think that all of these conversations -- all the conversations so far have been constructive. And I'm quite sure that will continue to be so. Sorry, were there any other questions?

Regarding 1801. What is the possibility of trying to get the CTA approval not just in the U.K. but in other countries at the same time? Why not do that?

It's possible. Yes. I mean at the moment, we are pursuing in parallel to several quarters of actual. So we're continuing with MHRA, of course. We're looking at the European authority, and we're looking at overseas to say overseas for now or for the non-European. And until a compelling reason comes to drop one of those strands will continue through.

There are no other questions in the room.

My question, was it consolidated?

We did.

Hindsight, performance this year, is that a right question?

Well, timing is everything. And -- but having said that, I don't think there is anything particularly to suggest that our performance would have been any better if we hadn't consolidated. I think these are for -- it's a mathematical treatment and not much more than that. So I don't -- it will be lovely to say if only we hadn't done that. But I think that, as I say, we will be a similar performance both irrespective is my view. So if there are no more questions in the room, and I thank you all for your questions and your contributions. I'm going to pass the baton over to -- do we have a full result?

Yes.

In that case, if I could have as I'll just read the results out. And then we'll go to the online. Technology is wonderful. The online questions from there.

Look at the votes. [indiscernible]

Thank you. Thank you. So I can start by telling you that all 6 resolutions have been carried. Resolution 1 -- forgive me, I don't intend to read the note again if you can hope you remember what they were. This was the annual report. Votes for 8,297,025 which represents 99.87% of the votes against 11,023 withheld 4,533. The second resolution, which was the appointment of auditors on memory, sorry resolution on income, [indiscernible] for 7,274,693, which is 88.96% of the votes, against 902,951 withheld 134,937. Resolution 3, which was, I think, the order the re-election myself [indiscernible] Well John got away with it, for 8,127,306, which represents 99.15%, against 69,338, withheld 115,937. Resolution 4, which is finally at the auditors, for 7,660,155, which represents 93.66%, against 518,753 and withheld 133,673. Resolution 5, which was the allotment ordinary resolution for 7,387,072 votes which represents 89.52% against 864,630, withheld 60,879. And resolution 6, which is a special resolution for 7,357,844 which represents 89.17%, against 893,858, and withheld 60,879. Those results will, of course, be posted on an RNS later in the day. So you can see the numbers from there.

[indiscernible] pleased to see you had a turnout of 12% rate. I think in previous AGMs has been 3% to 4%. I think anyone question if you're doing Chairman John used to control the [indiscernible].

We're moving in the right direction.

Moving in the right direction. Exactly. Exactly. Thank you for that, much appreciated. So with that, I'm going to pass the baton to a newly appointed Head of IR, Alex Harrison, who is going to as the quiz master for the online questions. Alex, over to you.

Thank you, Stephen. 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 I alluded to it earlier, we're reliant on other people to do that. So the process is at MHRA have to request for that review to take place from the U.K. GLP monitoring authority. And then the review needs to occur. And all I can say is at the moment, that has not begun.

Next one is, how's the MHRA acted outside of normal guidelines so far as refusers of the CTA. If not, how has the additional requirements be missed by yourselves in the so-called internationally recognized CROs?

So it's to do with a portion of the data they're querying the process by which that data was generated. So we're not querying the data itself, they're clearing the process. And I think the fact that they're asking the U.K. GLP monitoring authority to review suggest that they have some concerns about the -- whether the studies were done under GLP conditions. So we believe there were -- there were inspection certificates in place current at the time that the experiments took place. But MHRA have clearly got some issues with that, and they would like the U.K. GLP authority to review that data to look at the processes that were in place when that data was collected. And to say, yes -- well, no, hopefully, yes. But so I think it's important to say it's not the data itself that they have any issues with. They're not querying the results of any experiments, and not questionings the data we presented, but it's a process by which that data was covered.

So also on 1801, 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 mean it's important to say, but we're also looking -- 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 going to still do a thoroughly excellent job of the clinical study. And at the moment, while the time lines are wholly are in distinct. We're looking at alternatives to MHRA because MHRA might take a long time they took the I've said already, they took slightly over their statutory time limits to consider our application. That could happen again, and we just wanted to hedge against that in essence when looking at other territories.

Great. So this one is on the 737. When do you expect to receive the clinical study report, data pack versus 737? And how long do you expect your evaluation of these reports to take before going forward with the project. Have you or Cancer Research U.K. received any interest for 737 from any other company or interested party? I know Stephen, you've alluded to that.

So I mean -- the process, as we understand it because we have really been around this path before is that as soon as the formal termination date comes up, which is early January, then Sierra GSK returned the packages "without delay". So we'd expect I suppose soon after a low number of weeks, hopefully. But I think it's difficult to second guess that. And then really, the review period I mean it's kind of difficult. Again, yes, I mean, I think it may take more than a day, it shouldn't take more than a month, I think, is that about right? Yes. Yes. I mean they're pretty solid documents, something so there's quite a lot of way through, but obviously, that will be a priority for us. Yes. I think those are -- the time lines are roughly -- actually have some low number of weeks to get the data a number of -- a low number of weeks to review it.

It will depend to some extent on how much Sierra 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. And so 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 Sierra have gone into that. They provide us with a nice report correlating genetic background of patients with the outcomes having that 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 if we can see a clear signal for patients who responded or who didn't respond, that's a very key piece of information that will help us to develop a project or take a project on when we're looking through that data. So it's hard to say until we actually see what's coming back to CPF. But I think the guide between a day to -- I think we'd probably take more in a day, but between the day and a month.

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 brepocitinib that Pfizer had and we're now working in partnership with Priovant has -- can be improved. And I think our molecule has some potential to improve upon that molecule. It's absolutely key that we get it into the clinic because the preclinical studies are not going to differentiate the molecules. It's all about the safety profile and the efficacy profile. And until we get Phase Ia, which will give us some safety data; and Phase Ib, 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 representing a premier Phase I studies, and we'll be able to look the differences and I hope that we're going to see some benefits from our molecule.

I mean the next question is very much linked. So do you believe there are likely to be any potential points of differentiation of SDC-1801 versus brepocitinib i.e., a molecule with the same mechanism to TYK2/JAK1 affinity?

Yes. I mean the key thing is of the shapes of JAK selectivity and then any off-target activity that might be in the molecule. So we believe that brepocitinib has some JAK2 inhibition, it's hard to define or measure exactly, but some JAK2 activity, which may be causing some of the side effects that they see. So reduction in reticulocytes is the main one subsidy is a red blood vessel, early red blood vessel -- sorry, red blood cells sort of progenitors of red blood cells of reticulocytes and Pfizer do see some reduction in reticulocytes at the higher doses, and that's dose limited. So they went up to -- I think they went up to certainly beyond the 100 mg dose in the Phase I trials. And I believe they're currently using a 30 mg dose in their Phase III and Phase II trials. So we may see a reduced effect on reticulocytes again, until we get in the clinic, it's very difficult to be precise about these things, but we have less JAK2 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 have demonstrated. So there's absolutely potential. But then off-target effects, Pfizer reported on brepocitinib, but there is some activity on a transporter called OCT2. So, it's a renal transport, it affects the transport of creatinine and they did see some increases in creatinine levels in some of the subjects in their Phase 1, which may be due to that. So we have less effect on that particular renal transporter and in from in vitro studies. And so there's a potential benefit of our molecule there. Conversely, something may be something that we haven't seen about our molecule that could cause a side effect. And that's why we just got to get it in the clinic and try it and see what happens. We've done all the preclinical studies to show safety. We're not expecting that we hit anything off target. We've looked screened against other targets and not seeing anything. But until you get it in the clinic, you might miss something. That's what needs to happen.

Back to 1801. 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. Sorry.

So yes, I mean, so we are deliberately coy about which CROs we use, which countries they operate in for a number of commercial reasons. I suppose, one is, if there's a problem with a particular CRO unrelated to what we're doing, but maybe with some other work they're doing, we don't want to be tainted by that brush. Similarly, if there are sort of issues arising from the countries they operate in, again, unrelated to us, but we can still get tainted by that brush. And what we really can't be doing is giving our competitors any snippets of information or you have to try and to talk our molecules down when they're having discussions with their potential partners. So we are as we deliberately vague about who we're working with and where they operate except that they're world-leading CROs in fully inspected laboratories. So this is -- these are high-class operators as we just -- for commercial reasons, don't disclose who and where.

Thank you. Given there are at least 5 TYK2 inhibitors in clinical development and 2 others in late preclinical, a well-funded USBC companies, what do you consider to be the best way to create a differentiated target product profile for SDC-1801 and make this attractive prospects to a potential partner?

Yes, I think -- so alludes to a question from a gentleman in the room here about outcompeted. I mean 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 SDC-1801 against a different disease. However, that said, our plan is to do the Phase Ib trial in psoriasis patients. The reason being patients are available so you can recruit 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 on efficacy. 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 -- the late preclinical or early clinical stage, we want to provide a package of data with patients data in there to have a partner who's going to develop a molecule and take it to market. And my suspicion is they will look at different diseases to psoriasis. We may get an absolutely fabulous result in these psoriasis patients, and it becomes compelling to take it forward in that patient population. But my suspicion is at the moment that they will 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.

Great. Just a follow-up. Just to be clear, have Sareum or CRUK received any interest from any parties expressing 737?

We already addressed that, and the answer is yes.

Yes. One more question, which was submitted in advance. What would the Board say to potential investors to convert interest into real investment?

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 and also perhaps in that context, more importantly, in terms of the financial future of the company. And that we are -- we remain -- 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 hence 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 attractive, but hopefully, it will become more so as we succeed in getting into the clinic.

Great. Thank you. So I think that I've tried -- obviously, there's quite a lot of duplication on some of the questions from 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 I'd like to thank all of you, whether you're online or you've managed to overcome the transport difficulties and actually come here today. We really do appreciate your active view on the active role that you take in this company. 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 next year's AGM. So with that, I'll formally close the business of the meeting.

That's great. Thank you to the Board of Sareum for updating attendees this morning. Can I please ask attendees online, not to close this session as we're now automatically redirect you for the opportunity to provide your feedback in order that the Board can better understand your views and expectations. This will only to take a few moments to complete, but I'm sure it'll 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.