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 can be submitted at any time using the Q&A tab situated on the right-hand corner of your screen. Just please simply type in your questions at any time and press send. 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 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 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 site 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 posed via the IMC site. 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 pose questions which the directors will endeavor to answer during the meeting. Any answers which we've 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.
Morning. Yes.
On my left, Dr. John Reader, CSO, and Dr. Michael Owen, who Non-Executive Director and Chair of the Remuneration Committee .
Morning.
I would now like to start the formal proceedings for this annual general meeting. The notice of annual general meeting was posted to shareholders on November 24th 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 till of June 30th 2022, and remains confident in its future despite some recent setbacks. SDC-1801 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.
Announced on the November 8th 2022, the U.K. Medicines and Healthcare products Regulatory Agency 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 pre-clinical 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 U.K. Good Laboratory Practice Monitoring Authority as part of the pre-clinical data included in the application to approve the clinical study. Sareum and its advisors have sought additional clarification for MHRA and the U.K. GLPMA on the next steps. Parallel with seeking clarification with the MHRA, the company is also assessing regulatory opportunities in other countries.
Sareum remains committed to SDC-1801, is focused on finding the quickest and clearest pathway to obtaining authorization to commence clinical studies for the asset. TYK2/JAK1 inhibitions has demonstrated benefits in maintaining a healthy immune system and has strong clinical validation in psoriasis and psoriatic arthritis. 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 $4 billion. We believe this underscores the great potential of this class. SDC-1802, Sareum continues to work on the translational studies for 1802, 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 1801. The license program SRA737, which is the selective Chk1 inhibitor. As announced on the twelfth of October 2022, Sareum has been informed by Sierra Oncology, Inc., now a subsidiary of GSK plc, that it intends to return the rights of SRA737, the selective checkpoint 1 kinase inhibitor to Sareum's co-development partner, the CRT Pioneer Fund. The SRA737 license agreement has a 90-day notice period for termination. 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.
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 U.K. or via the MHRA or other countries. The company also remains confident for the potential of 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-attending 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 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.
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 a question should communicate with me or Dr. Mitchell by email following the meeting. I shall move on to the full business of the meeting and 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 one to five were proposed as ordinary re-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 order to be passed.
Resolution one. I propose resolution one in the notice of annual general meeting as an ordinary resolution to receive and adopt the report to the directors and financial statements for the financial year ending June 30th, 2022. 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 ending June 30th, 2022. Resolution three in the notice of annual general meeting is for the re-election 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 four 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 five.
I propose resolution five in the notice of annual general meeting as an ordinary resolution that the directors B, 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 850,000 867, provided that this authority is for a period expiring at the conclusion of the company's next annual general meeting.
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 grant of such offer or agreement, 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 directors B, 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 allotments, provided that this power shall be limited to the allotment of equity securities.
In connection with an offer of such securities by way of rights, open offer or preemptive 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.
B, otherwise in pursuant to subparagraph 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 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. Has everybody in the room had the 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.
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. Just collect the forms.
Should we just kick it off?
Yes.
Could we have a little bit more clarity if that's possible around the issues regarding the CTA? Which I think is probably the hot topic for the majority of investors. In terms of is the board confident that plans are in place to provide us with the necessary progress to get 1801 into the clinic?
I would say we're absolutely confident.
Yes.
Yes.
Good. Fantastic. I won't ask you to disclose any plans in that respect. Okay. I mean, there has been some comment, as you stated in the RNS, in terms of looking at other countries. As one possibility. Obviously the investors will 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 we've already put in?
John, do you want to-
Sure.
Yes, yeah.
There's an element of rollover in respect to the fact that the documentation that we've already prepared and submitted to MHRA, to a large extent, is ready to roll over directly to any other regulatory authority that we choose to approach. If there could, for example, be some foreign language translation requirements, like patient-facing documents.
Right.
We are talking to an authority in Europe. There would need to be some translation. That'd be very rapid. 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 alongside that clinical research organization. We have a protocol that was ready to go with our Manchester group. It would need some change to it just to accommodate their working practices. it...
Okay.
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. That would be short period of time to get those documents ready.
Okay. The issues that we're encountering in the U.K. with the MHRA are potentially not issues that we would encounter, hopefully, if we were to go to Europe, for instance?
We believe that's the case.
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. not 100%, but a high degree of confidence that we would actually get the CTA through?
A high degree of confidence. I'm not gonna say 100%.
No. Yeah.
Given our experience with MHRA, which, came as a surprise, so let's put it that way.
Okay. In terms of the impact on 1802, presumably if we resolve the CTA issues for 1801, then that would clear the way for 1802 in exactly the same way? Are we anticipating that we'll have to make changes to the CTA application for 1802?
No.
No.
There'll be no changes to the CTA application.
No changes. Okay. This is like a once process issue that needs to be resolved.
Yes.
Yeah.
Yeah. Okay. In a similar vein, in that case, 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 seven three seven back into the clinic?
Shall I-
Yes.
Shall I take that one? 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. I don't think we'll be in a position to make that call until we've seen the, you know, the minutiae of the details from the clinical study report, which we haven't had returned to us yet.
Okay. Subject to encouraging data in that case, the intention would be to try and get it back into the clinic, presumably as a combo?
If, if we were to progress into the clinic, yes, it would almost certainly be as a co-combination. Well, I think the prudent thing for us to do 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. In that case, we have to wait and see what the data reveals before we can-.
Yeah. Yeah.
Right. Okay. We should be getting that data back in January.
Yes. T he process, I mean, it's sort of as soon as possible as well, without delay after that formal return date is. I mean, you know, it's an unwritten time, but it's, you know, it should be fairly prompt. You know, it should be fairly quick that we get that data back.
Going back to TYK2 in that case.
That Takeda
news this week was obviously high profile. Does that give you confidence with TYK2, AT0018?
Absolutely. Yeah, yeah. Yeah. I mean, it was. Yeah. For those who didn't see the announcement yesterday, Takeda... Well, we actually mentioned it in the call. Yes. 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. That was a product that had reached the end of Phase 2b. I suppose mid-stage clinical. Yeah, I mean, I think from our point of view, that shows the importance of TYK2 as a product area. I suppose the increase in value on venturing into the clinic before doing a license deal. I think, you know, that we're very encouraged by that. You know, by the size of that deal and the interest amongst the big pharma companies.
Interesting point you made that that was a Phase 2b.
Yeah. Mm-hmm.
Evaluation, which obviously we're a long way from.
Yeah.
You have mentioned in previous statements, looking at the different valuations placed upon the TYK2 molecule. Sareum's business model's always been to license preclinical.
Yes. Preclinical or early clinical.
Early clinical.
Yeah.
Okay. We certainly shouldn't be looking at changing the business model to take us into phase 2 or something like that.
Not at this stage, I would say.
Okay.
Yeah.
The reason for designing the phase II study as a phase 1a and phase 1b, so that the phase 1b is actually carried out in patients, is that we would hope to see, not a statistical significance, but perhaps a signal of efficacy...
Right.
which may be enough to open conversations with at that stage. Okay. Interesting. Just may be enough to open conversations. At the moment, I think you've been talking to potential licensees, partners, whatever. Presumably they're saying, "Show us me more before-
Yeah.
-looking at it.
I think it's, "Show us some clinical data.
Yeah.
Yeah.
Not gonna hold you on that.
Okay. Yes.
Yes.
Simple line. Yeah.
Yes. Just, just going back to your colleague, Piers, mentioned about the MHRA.
Yes.
Something you've mentioned that obviously tied up Manchester at the moment. Are we gonna run parallel with that with a bit of consideration? Obviously I know there's obviously gonna be GMP view.
Mm-hmm.
Are we still gearing that if that was to get concluded and positive, that we're not just spat backwards on the timelines again?
Well. No. We're still committed to the process that we're in. We're also very focused on the need to waste as little time and as little shareholder value as we can. Therefore, if it appears that the MHRA is not going to be the most effective route through, then we're looking at a plan A, plan B scenario so that we can very rapidly switch and go down an alternative track.
As you can imagine, there's already been chat, as always happens. One of the things that I have picked up is that you're looking for the clearest and quickest way. There will come a time when we need to make a decision.
Yeah.
Could I ask that if the decision is that you're gonna go to another country, wherever that may be.
Mm-hmm.
that there is also some clear guidance on what you expect timelines to be? Because that's probably one of the biggest risks that's come out
Yeah. Mm.
amongst investors is that things are stated, to use my term there, gray and woolly.
Mm-hmm.
Can we be a little bit nicer, clearer, and sell ourselves a little bit better?
Well, we certainly want to do that. I mean, the one, I think it's widely recognized at the moment that MHRA in particular has been through quite a period of employment attrition. They've lost a lot of people in the last year. We've heard from many quarters that pretty much all applications are taking longer than the stated timeline. When we announce what happens next in terms of the approach, either continuing where we are or applying under a new system, we will set out at least the stated timeline, shall we say.
Yeah.
as to what we expect. Obviously we're Otherwise, we're second guessing what happens internally in a regulator.
Yes.
which we don't want to do.
We're being honest here is that the second guessing has caused a lot of share price over the last 5 weeks, and dare I say it in this morning, while we sit drinking coffee. I'm just looking for, dare I say, a clearer picture on the facts that we do know.
Mm-hmm.
If I can use, by way of an example, is the RMS came out regarding the Let's say delay would. You, you yourself tweeted earlier in the week, and if you actually look at the two points of information, I could actually ask was your tweet a fact because it was different to the RNS. There's a case of the RNS saying we're in delay, you say we're going. Can we just bring them together?
Well, yeah.
Much clearer picture.
The purpose of the tweet, of course, was to recognize the deal that Nimbus had done with Takeda, and it is unquestionable that we are on a process to the clinic. That tweet was not seeking to put any kind of a timeline on the process. I actually don't think that I said anything which was at variance from the company position.
It was at variance. I'm just saying that it apparently just seems to muddy the water in the fact that one is not giving any information other than delay. One is saying we are proceeding, continuing. All I'm saying is can we get a clearer statement from Sareum when they announce things? That's really my main point.
Okay.
I think that's a main point for a lot of investors.
Mm-hmm.
Well, I mean, one of the difficulties, of course, for us is that the timelines are out of our hands to a large extent. Once we've made our submission to the regulatory authorities, there is a statutory time by which they're meant to respond. Actually MHRA exceeded that statutory time frame.
I appreciate that.
Not our fault. Very frustrating to us and to our shareholders, I'm sure. There are, you know, there are plans. There are estimated timelines, but they are unfortunately by definition woolly because it's out of our control. We're relying on other people.
I appreciate that. All I'm asking is for a little bit more thorough statement announcing how we announce things.
Okay.
I mean, I'm in building planning applications.
Mm-hmm.
You literally get eight weeks regulated to pass plans. They literally say, "If you don't accept an extension, we refuse it." I know how it all works, which is why I'm asking is for us to sell ourself a little bit better and be a little bit clearer on our statements and the stories.
We'll do our best.
Okay.
Sorry. Back right.
Yeah. Atopic seems clearly quite a hot space, particularly given as you said at the beginning of the screen-
Mm-hmm
which is up from the
Mm-hmm.
I wonder, though, are we out here being outcompeted, I recognize it's probably a very large space.
Mm-hmm.
Correct me to even comment on that? Are we? I just recognize the progress that's been made by Ventyx . Investors in Ventyx as well, which have been making huge progress. They've raised a vast amount in VC. It's moving fast. I just worry, are we being outcompeted?
Mm-hmm.
Particularly given the delay and given that others now are making quite significant progress into the clinic as well?
Sure.
Shall I take it?
Mm-hmm.
Yeah. The two leading TYK2 products are deucravacitinib from BMS and the Nimbus compound we've just been talking about. They are both pure TYK2 inhibitors targeting the allosteric site. We've adopted a slightly different approach with our dual TYK2 JAK1 product. We've got a slightly different TYK inhibition or JAK inhibition profile. I think that, you know, there'll be autoimmune disease areas where this dual profile is more suitable and that there'll be some others where, you know, the single TYK2 activity is good or if not preferable. I think, you know, there is this space for us on that basis.
I think really the, you know, the early clinical data will indicate, you know, how competitive we are going to be. Well, certainly in psoriasis and, and potentially give a lead into other indications as well. I think there's, you know, the... There's a long list of autoimmune indications that, where, where a TYK or TYK/JAK inhibitor would work very well. I think that there is plenty of space. We're not too concerned about being overcompeted.
I think, you know, the leading products are doing a great job in validating the target 'cause certainly when we first started looking at TYK2, you know, we had trouble getting traction amongst the big pharma companies because it was an area that nobody was working on and hadn't been validated. I'm perhaps grateful is too strong a word, but certainly, you know, the likes of BMS have done a lot in validating TYK2 as a good target area.
Stephen, if I could just interject. If I could just ask you to repeat.
Sorry. It's just taken. Sorry.
If I could just ask you to repeat, the question. It's just, it's quite faint picking the people up...
Okay. Yep.
At the back of the room. Just in brief, if you'd be so kind, sir. Thank you.
Okay, sure.
The question was, given the increasing competitive activity in the TYK2 space, are we being outcompeted? Did you have another question to follow up or?
Yeah. Yeah. I really agree with the joint vision. The TYK2 with the JAK as has been spoke.
Mm-hmm.
Is there any clinical validation for that particular dual inhibition?
Yes.
Where would you see that positioned in terms of.
Yeah. so Pfizer have-
Sorry. Before you answer.
Oh, sorry. Sorry, yes.
Apologies for this. The question was, is there any clinical support for the joint TYK2 JAK1 approach that we're taking, which Stephen's about to answer?
Yeah. Thank you. Yes. Pfizer have or had actually. They've moved it on. I'll come onto that in a bit. A molecule called brepocitinib, which has a dual TYK2 JAK1 profile, very similar to ours. They've done phase II in psoriasis and psoriatic arthritis. They're looking at. Dermatomyositis.
Yeah
and lupus. They've put the molecule out into a single asset company that they've part-funded called Priovant. They sort of own it, but they've sort of put it off to one side at the moment. Yeah, there's clinical validation for that, your TYK2/JAK1 approach.
All right.
Yeah. I go a little bit back, timeline wise with my question because I believe we don't know, and if you don't learn from history, we won't necessarily be sure of the future. We haven't heard what are the reasons behind that the authorities have not approved our file.
Mm-hmm
here in the U.K. So it is important to hear from Sareum what are the reasons that you got to know about not approving the file. Have Sareum been an exception in that, or have been other cases, and are there any similarities?
Mm-hmm.
I'll take it.
Jerome.
The question.
Yeah. yes. Steve, yes. Do you want to-
Oh, yes. Sorry. Yes. The question was, what was the basis for the MHRA refusing the CTA?
Yeah. I suppose, you know, the level of detail we're going into at present is that they seek some additional review of part of the pre-clinical package. We, you know, 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. That's the stage we're at at the moment in working out the path to get the U.K. GLP to prove that data.
Mm-hmm.
I think that that's really. That's the level of detail that. Yeah, we obviously know chapter and verse of what's going on.
How does it come at this stage? I mean, after.
Well-
They normally run out conditions, requirements, restatements.
In-indeed.
all that.
Yeah. This... I mean, this came as a surprise to us. You know, we really weren't expecting it. Yeah. I mean, we... Yeah. We were kind of...
Yeah. That was my question. Are we an exception here? I mean surprise.
Well, anecdotally, we have no firm evidences. Anecdotally, we understand that there have been other companies that had the same situation. I think that there's a degree to which the MHRA is effectively being reborn and reinvented as a self-standing U.K. regulator. There are certainly some people in the U.K. that would like to 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 pharmaceuticals is above all a 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. That's, you know, that's straying into politics and I don't want to do that. I think that there is a degree to which this is part of the MHRA's process of working out how it handles things.
Yeah
in its new guise.
Unless you communicate to the market and to us who are the others, then we ought to believe that there has been no others. We see in the market, we hear about the acquisitions, we hear about the transactions. You mentioned them already in your RNS. On the other side, we need also to hear from saying who has been the others, if any others. That's why.
Well, if that information is.
In the public domain.
Exactly.
Yeah. They may well be private companies who wouldn't have to announce those. Yeah. Yeah.
MHRA doesn't put out a list of who succeeded in.
No. You know, companies as special as we do publish.
Well, not the private ones. Yeah. Mm-hmm.
If any would be private then.
Well, we think so. Yeah. I mean, we haven't seen any announcements from listed companies.
Yeah, that's what...
I mean, we You know, we don't know what the names of these companies are. You know, I suppose our sources probably aren't at liberty to divulge the names anyway. I mean, Because we've not seen anything in the market, our inference is that these are private companies.
Mm-hmm.
As I said, these are anecdotal reports. Roger.
Yeah. I mean, little knowledge is a dangerous thing, yeah. Did I understand you, Tim, to say that we're going head to head with Pfizer on a combined TYK, never know how you pronounce it?
Yes. Yes. TYK2/JAK1. Yeah.
Did I hear you right saying we're going head to head with Pfizer?
Well, I suppose in terms of the profile of the molecule, ours is closer to the well, now ex-Pfizer molecule than it is to the BMS or the Nimbus molecules. Yeah.
Would I be right in picking up that given these unexpected delays in getting approval, management time's obviously been focused on that, and that there will therefore naturally be a delay in SDC-1802? Am I right in assuming that?
No. No. No, I wouldn't think that.
I'll address that. No. 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. We still have time to progress SDC-1802. That's still going ahead on the schedule we've been working to.
Jim, can we just explore? Tim was referring to us when we were talking about 737, and could we just tease out, is us, the Pioneer Fund, or is.
Yes.
-Sareum and just how you anticipate-
Yeah. Yes. Yeah.
As you play it going.
Sorry, can I just check, are you hearing that question better?
Yeah, that question was fine, sir. Thank you.
Excellent.
No need to repeat. Thank you.
Just as I spoke about at the back. Just to remind you, of course, that the ownership of SRA737 is the CRT Pioneer Fund has 72.5%, and we have 37.5%. Of course, the license agreement was directly between CPF and what is now Sierra Oncology. Our interest in that came through a side agreement direct with CPF to cover the economics. 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. 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. As Tim rightly said before, until we get the documents and the data back, which will not be before January, there's nothing that any of us can do in that regard other than to create an orderly queue.
Okay. I mean, presumably there is a kind of a formal agreement between Sareum and CPF, kind of a joint venture type agreement.
Co-covering, covering the economic interests, yes.
Could I just say, in fact, I think it was a question I asked your predecessor 10 years ago. When you ask Peel Hunt as to why there are no institutional shareholders on the register, what is the answer you get from Peel Hunt?
Well, I think that they would probably start by showing you the entire sector performance of the last 12 months.
Yeah.
Which has been absolutely dismal. I mean, there's no beating about the bush here. I mean, any pharmaceutical biotech investment that you have is almost certainly got red ink all over it. Sadly, we are absolutely in the midst of that. There seems to be, well, control, shall we say, appetite by the institutions to look at development stage companies at the moment. 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 Hunt and indeed Privateer and institutions.
If I could ask a more philosophical question. I mean, you highlight in the annual report the principal risks of the company.
Yes.
I mean, a risk that I probably recognized in the 15 years I've been as a shareholder is what I'll call not a single man risk, double man risk.
Oh.
I mean, you know, what happens if Tim and his motorbike have an unfortunate event? You know, John has a size travel around the world. I mean, seriously, I mean, as far as I'm concerned, this is a risk that we accept, or at least I accept.
Mm-hmm.
I don't want to think about the consequences. Isn't it a risk that should be highlighted in the annual report?
Well, for you, Clive.
I mean, it's a good point.
It's a point, yes.
We do ensure our key men. We certainly recognize that, and hopefully we mitigate against a catastrophic impact on the business. You're right, it is, it's a good point, isn't it? You know, and John and Tim in particular are absolutely crucial to the future of our products 'cause their knowledge is extraordinary.
I think short term, I can stand in for John, yeah, or John and Stephen can stand in for me. You know, if the worst were to happen, you know, we can cover the eventuality short term while we look for any replacements.
Yeah. 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 than it has before. With none of us getting younger.
Well, yeah.
You're getting wiser.
Well, let's hope so. Let's hope so. Was there another question at the back?
Yes. Yeah. We got the CRO partner.
Yes.
Is it fair to assume you're using the same partner for 1802 as you had 1801? Are you worried given what happened with 1801 or something similar? Yeah, it's regards to the partner.
Well, SDC-1802 is still pre-clinical.
You haven't yet...
No.
At all.
No. No. I mean.
They may be listening, so I don't want to speak too kindly about them 'cause I'll put their prices up. I would anticipate we would certainly consider the same partner. They did nothing wrong. You know, I think that's quite important to state.
Yeah. Yeah, the secret to success is never tripping over the same rock twice. Let's hope people will be wiser with SDC-1801. So
Sorry.
Sorry.
Just go back to the SRA737.
Yes.
I'm probably incorrect, but did Sierra take out any patents on the data that they have sent back to you?
Yes, Well, they haven't sent data back yet, just to be clear.
Yeah.
Did you get the question?
If you could repeat that'd be great. Thank you.
Yep. Did Sierra take out any patents in its own right, covering SRA737? The answer is yes. They returned to us as part of that package.
You take that back.
Yes.
I believe they had patterns applications as well. I'm not sure anything's granted yet.
Yeah. Well, and the clinical data that won't get patented.
No, the clinical data.
Yeah.
Yeah.
That's not subject to that.
It has adjustable restriction on something. We cannot know.
No, no, we get absolutely everything back.
Yeah. Yeah.
Yeah.
Richard, can I just continue on SRA737 thread. With Pioneer Fund owning 72.5%, that's obviously controlling majority. If we wanted to do something with SRA737, could they stop us?
I would imagine that would be a negotiation with them.
Yeah. Unlikely.
They need a solution as much as we need a solution. I think that 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? Yes, sir.
Regarding 1801.
Yes.
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.
Yeah.
I mean, at the moment, we are pursuing in parallel several courses of action. We're continuing with MHRA, of course. We're looking at a European authority and we're looking at an overseas, I'll just say overseas for now, authority, non-European. You know, until a compelling reason comes to drop one of those strands, we'll continue with the three. If there are no other questions in the room. Yes, sir.
One final question. Was it consolidated?
We did.
In hindsight, looking at the performance this year, was that a wise decision?
Well, timing is everything. 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. It is our fault. It's a mathematical treatment, and not much more than that. I don't, I mean it would be lovely to say if only we hadn't done that, but I think that, as I say, we would be in a similar performance boat, irrespective, is my view. 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 you have a poll result, Chris?
Yes, we do.
In that case, if I could have that and I'll just read the results out, and then we'll go to the online-.
Send it to the email, sorry.
Technology is wonderful. The online questions from there.
I've got the latest there today.
Thank you. Thank you. 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. If you can hopefully remember what they were. This was the annual report. Votes for 8,297,025, which represents 99.87% of the vote. Against 11,023. Withheld 4,533. The second resolution, which was the appointment of auditors from memory. No, sorry.
The Remcom.
The Remcom. I beg your pardon. For 7,274,693, which is 88.96% of the vote. Against 902,951. Withheld 134,937. Resolution 3, which was I think the auditors.
That's the election.
Is that you?
Myself
Right. 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. Withheld 133,673. Resolution 5, which was the allotment ordinary resolution for 700,387.72 votes, which represents 89.52%. Against 864,630. Withheld 60,879.
Resolution 6, which was a special resolution, for 7,357,884, which represents 89.17% against 893,858. 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.
Mr. Chairman, can I just make a comment? I was very pleased to see that you had a turnout, voter turnout of 12%. For me, I think in previous AGMs, it's been 3%-4%.
Indeed.
I think, anyway, congratulations.
Moving.
I mean, Tim and John used to control the company.
Moving in the right direction.
Moving in the right direction.
Exactly. Exactly. Thank you for that. Much appreciated. With that, I'm gonna pass the baton to our newly appointed head of IR, Alex Harrison, who is going to act as the quizmaster for the online questions. Alex, over to you.
Thank you, Stephen, I hope everybody can hear me. 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. You know, I alluded to it earlier, we're reliant on other people to do that. The processes at MHRA have to request for that review to take place from the U.K. GLP Monitoring Authority. Then the review needs to occur. All I can say is at the moment that has not begun.
Good. next one is, has the MHRA acted outside of normal guidelines so far as refusal of the CTA? If not, how has the additional requirements been missed by yourselves and the so-called internationally recognized CROs?
It's to do with a portion of the data, they're querying the process by which that data was generated. They're not querying the data itself, they're querying the process. I think the fact that they're asking the U.K 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, 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 or no. Hopefully yes.
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, it's to do with the process by which that data was gathered.
Thank you. Also on SDC-1801, if you're confident of CTA approval, why would you consider at cost overseas applications?
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. We're not. We want to be quick, but we're gonna still do a thoroughly excellent job of the clinical study. At the moment, while the timelines are wooly or indistinct, we're looking at alternatives to MHRA because MHRA might take a long time. They took their, I've said already they took slightly over their statutory time limits to consider our application. That could happen again, we just want to hedge against that, in essence, by looking at other territories.
Great. This one's on seven three seven. When do you expect to receive the clinical study report, data pack for seven three seven? 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 seven three seven from any other company or interested party? I know, Stephen, you've alluded to that.
Yep.
Um.
I mean, the process as we understand it 'cause you know, we haven't really been down this path before is that, as soon as the formal termination date comes up, which is early January, Sierra stroke GSK return the packages, you know, quote, "Without delay," unquote. We'd expect, you know, I suppose soon after, you know, low number of weeks, hopefully. I think it's difficult to second-guess that. Really the review period is
I mean, it's kind of difficult. Again, yeah, I mean, I think, you know, it may take more than a day. It shouldn't take more than a month, I think. Is that about right? Yeah.
I think so.
Yeah. I mean, they're pretty solid documents, aren't they?
Yeah.
There's quite a lot to wade through, but obviously, you know, that'll be a priority for us. Yes, I think those are, you know, the, the timelines are roughly, I just think there's some low number of weeks to get the data, 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. You know, there could be a correlation between the genetic background of patients and their response to treatment. At this moment, we don't have a good feeling for how much Sierra 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. 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 who didn't respond, that's a very key piece of information that will help us to develop a project or whoever takes the project on, will be looking through that data. It's hard to say until we actually see what's coming back to CPF. I think a guide of between a day I think it could 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. The compound that Tim mentioned, brepocitinib, that Pfizer had and are now working in partnership with Priovant can be improved. I think our molecule has some potential to improve upon that molecule. I, you know, 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, you know, the safety profile and the efficacy profile. Until we get our phase 1a, which will give us the safety data, and phase 1b, which will hopefully give us some efficacy signal, that might be biomarker, it might be disease modification.
We'll be able to compare to Pfizer's report on brepocitinib from their phase I 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 very much linked. 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 TYK2/JAK1 affinity?
Yes. I mean, the key thing is, are the shades of JAK selectivity and then any off-target activity that might be in the molecule. We believe that brepocitinib has some JAK2 inhibition, that some sponsors are to define or measure exactly, but some JAK2 activity which may be causing some of the side effects that they see. Reduction in reticulocyte s is the main one. These are red blood vessel, early red blood vessel, sorry, red blood cells. Progenitors of red blood cells are called reticulocyte s. Pfizer do see some reduction in reticulocyte s at the higher doses, and that's dose-limiting. They went up to, I think they went up to certainly beyond a 100 mg dose in their phase I trials.
I believe they're currently using a 30 mg dose in their phase III and phase II trials. You know, we may see a reduced effect on reticulocyte s . Again, yeah, until we get in the clinic, it's very difficult to be precise about these things. We have less JAK, JAK2 activity, so we may see less effect on reticulocyte s , which would allow us to dose higher, which would allow us to increase or improve on the efficacy that Pfizer have demonstrated. There's absolutely potential. You know, off-target effects, Pfizer reported on brepocitinib that there is some activity on a transporter called OCT2. Okay. It's a renal transporter.
It affects the transport of creatinine, and they did see some increases in creatinine levels in some of the subjects in their phase I, which may be due to that. We have less effect on that particular renal transporter from in vitro studies. There's a potential benefit to our molecule there. Conversely, there may be something that we haven't seen about our molecule that could cause a side effect. That's why it's, 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 and not seen anything. Until you get it in the clinic, you know, you might miss something.
That's what needs to happen.
Thank you. Back to SDC-1801. What is the commercial reason you don't disclose the CROs? These obviously play a large part in the progress of Sareum. MHRA has now questioned their progress. Sorry, that's for assistance. Sorry.
Yeah. 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 wanna be tainted by that brush. Similarly, 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 we really can't be doing is giving our competitors any snippets of information or, you know, to try and to talk our molecules down when they're having discussions with their potential partners.
We are, I suppose, deliberately vague about who we're working with and where they operate. Except that they're world-leading CROs in fully inspected laboratories. You know, this is. These are high-class operators. 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 at well-funded U.S. VC companies, what do you consider to be the best way to create a differentiated target product profile for SDC-1801 and make this attractive prospect to a potential partner?
Do you want.
I think sort of 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. There's an awful lot of treatments coming through for psoriasis at the moment. We'll be looking to position SDC-1801 against a different disease. However, that said, our plan is to do the Phase 1b trial in psoriasis patients. The reason being, patients are available, so you can recruit to your trial quite readily. Psoriasis is biologically driven by the kinds of pathways that we're going to be impacting on. We would expect to see some certainly biomarker-driven signal of efficacy.
It's a very good proof of concept disease for our molecule. Bearing in mind that our business model is to partner at late preclinical or early clinical stage, we want to provide 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 market. 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 patient population. 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.
Okay. Great. Just a follow-up. Just to be clear, have Sareum or CRUK received any interest from any parties addressing SRA737?
We already addressed that. The answer is yes.
Yes.
Can't hear any. One more question which was submitted in advance. What would the board say to potential investors to convert interest into real investment?
Well, 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, and perhaps in that context, more importantly, in terms of the financial future of the company. That, we remain, and we have always been, but we absolutely remain very confident that, despite, say, the 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. There are some very meaningful commercial discussions to be had with them as part of that process.
I think that the product portfolio at the moment, is attractive and hopefully will become more so as we succeed in getting into the clinic.
Great. Thank you. I think that, obviously, there's quite a lot of duplication of some of the questions and from the floor live today, so hopefully that represents most of the questions. Any others we will respond to through the portal.
Very good. Well, thank you. 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. 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 and the active role that you take here 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. Do please keep up your support of the company and of the team here.
We look forward to seeing you, if not before, at next year's AGM. 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. Could I please ask attendees online not to close this session, as we'll 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 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.