Sareum Holdings (LSE:SAR) — Annual General Meeting

0:01 Good morning, ladies and gentlemen, and welcome to the Q and A session. I'd now like to hand over to Executive Chairman, Doctor. Stephen Parker. Good morning. The The quorum being two members is present, and therefore, we may not proceed with this meeting. In common with recent senate general meetings, we've also opened a link through the investor meeting site in addition to the conventional meeting. I'm particularly grateful to those of you who have chosen to attend in person. We will deal with formal business meeting first, and there will be a presentation from doctor John Greene, our chief scientific officer, to provide an update on their research progress.

0:55 We will then take questions to the floor in the usual manner around general meetings. Following following these questions, we will try to cut some or all of the questions posted via the IMC site Tim Mitchell, chief operating officer, Mike Owen, who chairs the moderation committee, and our finance manager, Chris Neil, who is over our side.

1:50 Right now, I'd start the formal proceedings of this Annual General Meeting. The notice of Annual General Meeting was posted to shareholders on the 11/17/2025. Accordingly, the requisite notice of Annual General Meeting has been given. I propose, therefore, that with your consent, the notice at the general meeting should be taken as of late. Thank you. Before proceeding with all business of this meeting, I would now read a statement which was issued to the market this morning. The company has continued to advance its lead program, MSTC 18 o one, following the successful completion of its phase one clinical trial in 2024. Despite the temporary setback of the discontinuation of toxicology study, the company has made significant operational progress, including the appointment of a leading global contract research organization that is now well positioned to restart these important studies SCC eighteen o one, SAREUM selective JAK1 inhibitor, remains positioned as a potential for a range of autoimmune diseases, with an initial focus on psoriasis, but also immune condition affecting the skin.

3:03 As previously announced, STC eighteen Phase one clinical development. A randomized placebo controlled trial demonstrated that STC eighteen oh one achieved blood plasma levels significantly exceeding the predicted therapeutic exposure with a half life of seventeen to twenty hours, supporting once daily dosing and with smooth delivery of drug over the dosing period. Importantly, no deaths or serious adverse events due to a t SDC eighteen o one were reported, And the frequency of adverse events, all mild or moderate, was similar in the active and placebo groups. Notably, SDC1801 has not exhibited any of the potentially dose limiting side effects that have been observed leading dual TYK2 JAK1 inhibitors in clinical development, reinforcing the molecule's differentiated profile and best in class potential.

3:56 Following successful completion of the clinical trial, two large scale batches of STC1801 have been manufactured, one under GMP conditions for future planned clinical studies, and a non GMP batch for the phase two enabling toxicology studies. Process chemistry improvements have enhanced the purity profile of SDC eighteen oh one while maintaining good manufacturing yield. A program of work to optimize the capsule formulation of SDC-eighteen oh one is underway, aimed at enhancing drug release at higher doses and reducing the number of capsules required per dose in future clinical trials. Considerable progress has been made and the company expects this project to conclude in Q1 twenty twenty six. As announced on December 10 sorry, think the 10/10/2025, the company discontinued its sixteen week GLP preclinical toxicology study for SDC eighteen oh one following unexpected safety findings observed by a third party provider of the study.

4:55 These findings occurred at a higher incidence in control group animals that received an inactive dosing solution compared to those dosed with SDC1801. The company has now appointed a different lead global CRO with extensive experience in long term toxicology studies to restart the phase two enabling toxicology program. Prior to commencing the full sixteen week toxicology study, the company will conduct a separate pharmacokinetic study to evaluate four different formulations, three liquid formulations for Gavage dosing, and one capsule formulation. This five day study will provide valuable data on both tolerability and exposure levels, helping to optimize the formulation selection for the full toxicology study.

5:42 The carrier formulation is specific to the animal toxicology studies only and will not form part of any human dosing regimen. The PK study is expected to commence imminently with the full toxicology study expected to restart as early as possible in Q1 twenty twenty six. Both studies will be completed using the company's existing cash resources and the existing toxicology patch of SDC1801. Translational studies with SDC1802 have been completed, providing a solid dose data package to support potential further development. The strongest cancer response was seen in hematological cancers with significant unmet medical need, including T ALL and B cell lymphoma.

6:27 The company is reviewing how best to progress SDC1802 into clinical development and notes that partnering may be the preferred route at this stage. SRA seven thirty seven is a clinical stage oral selective inhibitor of checkpoint kinase one, check one, that targets cancer cell replication and DNA damage repair mechanisms. In March 2025, the former US license arrangement for SRA seven thirty seven was terminated and the asset reverted to the CRT Pioneer Fund. SAREUM successfully acquired the license for SRA seven thirty seven following this termination, renegotiating significantly improved economic terms. The company now received 63.3% of all future revenues compared with 27.5% under the formal agreement at no cost to the company.

7:18 The company continues to explore partnering opportunities for SRA737 building on positive Phase onetwo data that demonstrated good tolerability as monotherapy and promising activity in combination with low dose gemcitabine in anogenital cancers, an area of significant unmet medical need. Furthermore, SAREUM has maintained an investigational new drug application with the United States Food and Drug Administration opened by the previous license holder to conduct a Phase I trial in patients with acute myeloid leukemia and myodysplastic syndromes. The company retained sufficient stock of SRA-seven thirty seven capsules to conduct such a trial. The company remains confident in the potential of SRA-seven thirty seven and is assessing the most effective routes to progress and create value from this asset.

8:08 SAREUM has initiated a collaboration with Receptor AI to accelerate discovery of blood brain barrier penetrant isoform selective TYK2 JAK1 inhibitors for potential use in neuroinflammatory indications such as multiple sclerosis and Parkinson's disease. This program builds on earlier preclinical work from the company's Skill platform, which demonstrated broad brain barrier permeability of selected TYK2 JAK1 molecules. The collaboration extends the relevance of SAREUM's TYK2 JAK1 expertise into central nervous system diseases, areas of increasing scientific and commercial interest. The first batch of compounds have been designed and synthesized and are currently undergoing testing in biochemical assays to assess their potency against the JAK kinases and in early stage absorption, distribution, metabolism and excretion assays to assess their potential to cross the propane barrier and give sufficient exposure to the target site.

9:07 As part of a broader value realization strategy, SAREUM has engaged specialist U. S.-based business development consultants to actively broaden and accelerate ongoing partnering discussions for SDC eighteen oh one and SRA seven thirty seven. The Board continues to prioritize non dilutive funding routes to advance the pipeline and protect shareholder value with current core activities funded from existing cash resources. SAREUM continues to review the optimum level of staffing for the company, including Chief Medical Officer and Chief Executive Officer roles. SAREUM has made substantial progress across its pipeline during 2025. The positive Phase I data for SDC1801, together with the competitive profile versus other TYK2 JAK1 inhibitors in development continues to support SDC1801's potential as a best in class once daily oral therapy for autoimmune diseases.

10:04 Despite the frustrating delay to the toxicology study, the company's confidence in the molecule remains strong and the study is now on track to restart in Q1 twenty twenty six. The significantly improved economic terms for SRA-seven thirty seven, coupled with active partnering discussions for this asset and STC eighteen oh two, position the company to create value across its portfolio. The new TYK2 neuroscience collaboration adds further long term potential. The company has engaged specialist business development consultants to support partnering efforts across key programs. With strengthened intellectual property, a clear operational road map, active business development initiatives and sufficient financial resources, the company enters the new period with confidence and a clear set of value creating milestones ahead.

10:51 We would like to thank our shareholders and other stakeholders for their continued support. Before we turn to the resolutions, I would like to say a few words about the procedure and remind you that only physical attendees or shareholders are able to vote today. I will propose each resolution in turn having briefly summarized its content. I will then read the results of the votes received through proxies. 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 Mr. Birch by email following the meeting. I shall move on to the formal 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 was posted to shareholders or their nominee holders and is on the company's website.

11:44 Resolutions one to six were proposed as ordinary resolutions, each requiring a simple majority of the votes cast to be in favor in order to be passed. Resolutions seven and eight were proposed as special resolutions requiring the majority of 75% of votes cast to be in favor of laws passed. Each resolution received a total of between 11,838,576, which represents 8.6%, and 11,456,534, which represents 8.3% of the the total votes outstanding. Resolution one. I proposed Resolution one in the notice of Annual General Meeting as an ordinary resolution to receive the company's annual report and audited financial statements for the financial year ended 06/30/2025, together with the directors' reports and the auditors' report obtained in the annual report.

12:43 Proxy votes have been received as follows: in favor 11,000,000 39,690 6 against 283,614 withheld 472,289. I will now put the resolution to the meeting on a show of hands. All those in favor, please raise your hands. You. Those against, please raise your hands. Thank you. That resolution is carried with the necessary majority. Resolution two. I proposed resolution two in the notice of annual general meeting as an ordinary resolution to receive and adopt the director's remuneration report for the year ended 06/30/2025.

13:36 Proxy votes have been received as follows: in favor, 10,021,984 against 1,544,196 withheld two hundred and twenty nine thousand four hundred and nineteen. I will now put the resolution to the meeting on a show of hands. Will all those in favor please raise your hands. Thank you. Those against, please raise your hands. Thank you. That's carried by the necessary majority. Resolution three. Resolution three in the notice of general meeting is for the reelection of doctor John Reeder, who retires by rotation under section 93 of the articles of association and who, being eligible, offers himself reelection as a director.

14:27 Proxy votes have been received as follows: In favor, 10,329,982 against 1,000,383 withheld 465,234. I will now put the resolution to the meeting on a show of hands. All those in favor, please raise your hands. Thank you. All those against, please raise your hands. Thank you. I declare the resolution carried by the necessary majority. Resolution four in the Annual Legislative Annual General Meeting is to reappoint Moore King ston Smith LLP as auditor of the company and to hold office from the conclusion of this Annual General Meeting until the conclusion of the next general meeting at which financial statements are laid before the company.

15:20 Proxy votes have been received as follows: in favor, 11,342,993 against 325,897 withheld 126,709. I will now put the resolution to the meeting on a show of hands. All those in favor, please raise your hands. Thank you. All those against, please raise your hands. Thank you. I declare the meeting of this resolution carried with the necessary majority. Resolution five, notice to item general meeting, is to authorize the audit committee to determine the remuneration of the auditors of the company for the ensuing year.

16:06 Proxy votes have been received as follows: in favor 10 million 7 and 27,590 6 against 977,756 withheld 89,977. I will now put the resolution to the meeting on a show of hands. All those in favor, please raise your hands. Thank you. Those against, please raise your hands. Thank you. I declare this resolution carried by the necessary majority. Resolution six. I propose resolution six to notice of any general meeting as an ordinary resolution to generally and unconditionally authorize the directors pursuant to and in accordance with section five fifty one of the Companies Act 2006 to exercise all the powers of the company to allot shares or grant rights to subscribe for or to convert any security into shares of the company: a, up to an aggregate nominal amount of GBP 1,725,815 and b) comprising equity securities as defined in Section five and sixty one point one of 2006 Act up to a further annual nominal amount of 1,725,008 and £15 in connection with an offer by way of a rights issue.

17:30 Such authority is to apply in substitution for all previous authorities pursuant to Section five fifty one of the 2006 Act and to expire at the end of the next Annual General Meeting or, if earlier, at the close of business fifteen months after the passing of this resolution. But in each case, so that the company may make offers and enter into agreements during the relevant period, which would or might require shares to be allotted or rights to subscribe for or to convert any security into shares to be granted after the authority ends. For the purposes of this resolution, rights issue means an offer to ordinary shareholders in proportion as nearly as may be practical to their existing holdings and holders of other equity securities if this is required by the rights of those securities or if the directors consider it necessary as permitted by the rights of those securities, to subscribe for further securities by means of a renounceable letter or other negotiable document, which may be traded for a period before payment of the securities is due, but subject in both cases to exclusions or other arrangements as a director's meeting necessary or expedient in relation to treasury shares, fractional entitlements, record dates or legal, regulatory or practical problems in or under the laws of any territory.

18:57 Proxy votes have been received as follows: in favor 10,291,950 eight against 1,000,300 and 30 3 thousand one hundred and sixty two withheld 170,479. I now put the resolution to the meeting on a show of hands. Will all those in favor, please raise their hands. Thank you. Will all those against, please raise your hands. Thank you. I declare the resolution carried by the necessary majority. Resolution seven. Given the passing of Resolution six, I propose Resolution seven in the notice of Annual General Meeting as a special resolution, again substitution for any existing authority, but without prejudice to the exercise of any such authority prior to the date of passing this resolution, the Board of Directors be, and they are, generally empowered to secure the Sections five seventy and five seventy three of the 2006 Act to allot equity securities within the meaning of Section five sixty of the Act, including the grant of rights subscribed for or to convert any securities into ordinary shares of GBP 0.125 each in the capital of the company for cash either pursuant or to the authority conferred on it by Resolution seven or by way of the sale of Treasury shares within the meaning of Section

20:29 560.3 of the Act as if Section five sixty one of the Act did not apply to any such allotment or sale, provided that this power should be limited to: a, the allotment of equity securities or sale of treasury shares for cash in connection with the rights issue, open offer or other preemptive offer in favor of the holders of ordinary shares on the register of members or that they fixed by the Board, where the equity securities respectively attributable to the interest of such holders of ordinary shares are proportionate as nearly as may be practical to the respective numbers of ordinary shares held by them on that date, subject to such exclusions or other arrangements in connection with the rights issue, open offer or other preemptive offer as the Board deems necessary or expedient to deal with shares held in treasury, fractional entitlements to equity securities and to deal with any legal or practical problems or issues arising in any overseas territory or under the requirements of any regulatory body or stock exchange to or to deal with any other matter whatsoever and b, the allotment of equity securities or sale of treasury shares otherwise pursuant to subparagraph a of this resolution up to an aggregate nominal amount of GBP £1,725,815 and provided that this power shall expire at the conclusion of the Annual General Meeting of the company to be held on or before the

21:59 03/13/2027, say that the company may, before such expiry, make an offer to enter into an agreement which would or might require equity securities to be allotted or treasury shares to be sold after such expiry and the Board may allot equity securities and sell equity treasury shares in pursuant to such an offer or agreement as if the authority conferred hereby had not expired. Proxy votes have been received as follows: in favor, million 165,325 against 1,312,924 withheld 317,330. I will now put the resolution to the meeting on a show of hands.

22:46 All those in favor, please raise your hands. Thank you. All those against, please raise your hands. Thank you. I would now declare that the resolution carried by the appropriate majority. Steve, would you go to speak a bit? Sorry. I might I might I'm sorry. Why can't I be just shaking on over the front? Okay. Let me have a quick first. My apologies. Be pleased to know we're at the end of the road. I proposed Resolution eight in the notice of Annual General Meeting as a special resolution that a general meeting, other than an Annual General Meeting, may be called on not less than fourteen clear days notice. Proxy votes have been received as follows: in favor 10,941,745 against 391,565 withheld 462,289.

23:42 I will now put the resolution to the meeting on a show of hands. All those in favor, please raise your hands. Thank you. All those against, please raise your hands. Thank you. I declare the resolution carried by the necessary majority. Ladies and gentlemen, that concludes all of today's formal business. On behalf of the Board, I'd like to thank you all for your attendance, and I declare that formal business of the Annual General Meeting is closed. In closing, may I thank you for all your ongoing support during this year, which has continued to present challenges to the sector generally, despite your company's significant achievement in completing the Phase I study for SDC1801. I will now ask Doctor. John Reed to present an update on the SDC1801 and CNS projects as well as other projects in portfolio.

24:32 Following that, we'll be happy to try and answer questions from attendees and, if time permits, from the IMC platform. Thank you. Okay. Thank you, Steven. Be happy to give you an overview of the pipeline as it currently stands. It's the usual disclaimer slide. Please familiarize yourselves with this. This will be online after the meeting. I'm not posing to read through all of this.

25:20 Okay, so company overview. SAREUM is a clinical stage drug development company. We deal with small molecule drugs. We're developing next generation kinase inhibitors for autoimmune diseases and cancer. The strategy is to take programs to the late preclinical or early clinical stages and then look to license or partner. We have deep expertise in kinase inhibition, including the JAK signaling family, which is an area of growing commercial focus with good scientific validation. Our lead program is a dual TYK2JAK1 inhibitor for autoimmune diseases and has successfully completed a Phase one clinical trial. And as mentioned, we recently regained control of the oncology asset SRA737 with improved economic interest.

26:06 And we're based in Cambridge in The UK. Here's an overview of our pipeline then in a picture. So you'll see that SDC1801, the dual TYK2 JAK1 inhibitor, has completed a Phase one in healthy volunteers. Behind that we have eighteen oh two and the recently announced neuroscience project. Then in the field of CHECK-one, former license holder Sierra Oncology completed two phase one two trials, one as a monotherapy and one in combination with low dose gemcitabine, chemotherapeutic. And then there is a lot of preclinical work that has been done around this molecule and other checkpoint inhibitors to find other potential combinations which would have utility in the clinic.

27:01 To give you a summary of the STC1801 program then, we believe it's well positioned for further development as a potentially a best in class TYK2JAK1 inhibitor in multiple high value indications. There's a validated mechanism of action and a strong rationale, dual inhibition of TYK2 and JAK1 can deliver superior efficacy across a large number of autoimmune diseases. We think it's better than single inhibition of each target, but avoids the liabilities tied to JAK2 and JAK3 inhibition. The high cell activity for TYK2 and JAK1 supports a stronger safety profile and positions the molecule to be potentially best in class. I'll show you some data where we've seen a very favorable pharmacokinetic profile for JAK inhibition, driven by the extended human half life of the drug.

27:54 18 o one showed no effect on neutrophils or reticulocytes at doses equivalent to one hundred mg of brepacitinib. Brepacitinib is the leading asset, in the clinic, a molecule developed by Pfizer. And I'll show you some data comparing eighteen o one to brepacitinib, we believe very favorably. Brefacitinib shows some side effects, which we avoid. Principally, this OCT two mediated kidney liability and the effect on neutrophils and reticulocytes. These are components of blood. Our molecule has a greater human half life, so about seventeen to twenty hours versus the epacetinib six to eight hours. We believe that, dual TYK2 JAK1 inhibition has the potential to target multiple autoimmune disorders, so there's a broad therapeutic reach within a single molecule.

28:48 And strong evidence to support efficacy in diseases such as psoriasis, lupus, inflammatory bowel disease, rheumatoid arthritis, other autoimmune diseases. Our phase one data was very favorable. We had a great safety profile, excellent pharmacokinetic characteristics, and we believe they provide meaningful advantages over competing agents. And currently we're aiming to get STC1801 ready for phase two by the end of Q2 twenty twenty six. Why do we believe dual inhibition is better than single inhibition? Well, I'm not going to go through this slide in great detail, but what it's showing is for a number of diseases, autoimmune diseases, the key pathogenic cytokines. These are signaling molecules that drive the development and the duration of the disease.

29:44 And what we're showing on this slide is that inhibiting TYK2 and JAK1 really gives you much broader coverage than the single agents. The main difference, I would say, between our molecule and, selective TYK2 inhibitors is the effect on interferon gamma. And you'll see interferon gamma is a key pathogenic cytokine for all of these molecules. The selective TYK2 agents do not touch that cytokine. Dual inhibition of TYK2 inject one does. And I would say that's the single most important thing, but I'd be happy afterwards to go through this slide in more detail with anyone who's interested. What I'm showing you here is some data from the MAD phase of our phase one clinical trial. So this is multiple ascending dose, ten days dosing of SDC eighteen o one in healthy volunteers, and I'm showing you the levels of drug in in in the blood of the volunteers.

30:41 And, again, so we're looking at four cohorts here. I'll just draw your attention to the top two cohorts, really. Cohort, c and d, and we're comparing the levels in the blood to the, IC50 or EC50. This is 50% inhibition of these target cytokines. And you can see that, cohort d, we exceed the human whole blood interferon alpha and IL 12 y c fifties throughout the entire dosing period. Cohort c, we're very nearly there, exceeding interferon alpha throughout the period and IL 12 for a significant period of time. Our plasma exposure is equivalent to brepacitinib at a 100.

31:29 Okay? Brepacitinib cannot be used in the clinic at a hundred mgs. There's too many toxic side effects. We saw no hematology or serum creatinine changes with our molecule during ten days dosing. Repo at a hundred mgs causes increased serum sorry, reductions in reticulocytes and neutrophils after ten days dosing in their MAD study. This is showing, cohort d in more detail. Now, It may not be obvious, but what we're seeing here is we're doing twice daily dosing for cohort d. Okay? And this was to do with maximizing the levels of compound that we got. So we couldn't achieve those high levels with a single dose. Even though the half life is set up ideally for single dose. And this is really why we're working to improve the formulation of the molecule so that we can give a higher dose of the of SDC eighteen o one with a smaller number of capsules.

32:35 But what we're seeing is, in the table below, cohort d, we're greater than the IC fifties, we're greater than the IC eighties, so 80% knockdown of these cytokines for the entire period of time that we're we're dosing. In contrast, prepacitinib at thirty mgs. So that's the dose that prepacitinib is typically used in the clinic. They have gone as high as forty five mgs. They can't use a hundred mgs. Okay? You'll You'll see at thirty mgs, they're getting five and eight hours excess of the EC eighty, fourteen and twelve hours in excess of the EC 50. So we believe eighteen oh one has potential for best in class efficacy. What we're looking at here is a number of agents on the market or close to the market for psoriasis and talking about this PASI ninety, so that's a psoriasis area and severity index. It's the score that dermatologists use to say how severe a psoriasis, symptoms are to the patient.

33:39 PASI 90 has become the gold standard for psoriasis patients and that's really been driven by advances in biologics and antibodies such as SKYRIZI. It's an inhibitor of IL-twenty three. And then recently announced oral IL-twenty three inhibitors such as icotrokinra achieve significant PASI 90s after four to sixteen to twenty four weeks. Now prapacitinib was taken into a short four week study at a hundred mgs, and they achieved PASI 90 for four weeks. That is much better than any of these other agents. Now just a reminder, brepacitinib cannot be used at a hundred mgs in the clinic.

34:26 Side effects are too great. But we believe we can, without cohort d, we can achieve a similar exposure to brepacitinib without the side effects. So we would expect that we can achieve similar PASI scores to breplacitinib. What we're doing at the moment then is preparing for phase two readiness. We've resynthesized the drug substance, that's that's the molecule, the powder that goes into the into the capsules. That's complete, two batches for TOPS and for a future clinical study. We've improved process chemistry around that. We're working on improving formulation. We're expecting to complete that next quarter with the objective of improving absorption particularly for higher dosage capsules.

35:21 And then we'll prepare the capsule sizes consistent with the predicted phase two doses. And then sixteen week toxicology, which will restart early in the New Year, and we're expecting to complete by the end of q two. Let's just talk a little bit about what happened in the toxicology studies as far as I'm able. So eighteen o one has been very well tolerated in our previous preclinical and and short term toxicology studies. The data from those and the human data from a clinical trial supports a longer duration, high exposure studies to really define a safety margin. Because we're trying to get a higher exposure of the drug in the preclinical species than we do in humans, we use specialist formulations, usually unsuitable for human use, frequently used in the industry to enable the sustained high exposure that you won't get in a toxicology study.

36:24 So we used formulation a in our previous all of our previous tox studies, but including the four week study, and there were no adverse effects reported. Unfortunately, in the recent sixteen week study, we used the same formulation, and at around the four week time period, we had to discontinue the study on animal welfare grounds. The effects were observed with greater frequency in the control groups receiving formulation only, so we are very, very confident that these effects are not due to SDC 18 o one. They're vehicle related. So as Steven mentioned in the report that came out this morning, we have a five day PK study, which starts today, actually, which will look at four additional formulations.

37:18 They three of them have a track record of use in long duration studies. The fourth is a capsule formulation, which we have developed ourselves. And the objective is to evaluate the tolerability of these formulations, to look at the exposure, and obviously to select the best one to take forward into the sixteen week studies. That's that study has been commissioned as an alternative CRO and will commence as soon as possible in q one after we have the data from the PK study. Just briefly on '18 o two. The translational studies are finished. The chemistry is closely related to eighteen o one, so we'll be able to use our learnings from the development of eighteen o one to transfer onto eighteen o two.

38:09 We have a strong patent position covering several disease targets both in oncology and autoimmune disease. Again, eighteen oh two is a dual TYK2 JAK1 inhibitor. As well validated in hematological cancers such as T ALL, B cell lymphomas, and we're reviewing our options for further development of eighteen oh two to get it into the clinic. Partnering is likely to be preferred. Let's talk about the new CNS project. So there's been a lot of evidence recently in the literature concerning TYK2 inhibition in neuroinflammatory diseases and linking the two closely together in diseases such as multiple sclerosis, Parkinson's, and Alzheimer's disease, all areas of high unmet medical need.

39:00 TYK2 has been demonstrated to be a key neuroimmune modulator in most settings. So we have a collection of TYK2 JAK1 inhibitors, and we thought we ought to look at the potential for brain penetrance amongst those molecules. We selected six compounds and got them screened, and we were able to demonstrate that three of them showed meaningful blood brain barrier penetration, and one in particular had high levels of free drug in the brain. And importantly, it was not on this slide, but we were able to use an in vitro assay that would give us a really high level of confidence and correlated very nicely with blood brain barrier penetration. So we can use that going forward. The big market opportunities in neuroinflammation, millions of people affected with limited treatment options.

39:55 So we partnered with Receptor AI, announced this collaboration in August 25, an initial four month partnership to optimize brain penetrant TYK2 JAK1 inhibitors. We own a 100% of the IP. Receptor AI do their virtual screening and PK predictive models. We've done the compound synthesis and testing, and we'll take any molecules that show merit into disease models downstream. Progress to date, Receptor AI developed their model of blood brain barrier permeation. They've done docking. So this is modeling how our molecules sit in the active site of TYK2 and the other JAKs to look at selectivity. Our first round of compound design and synthesis is complete.

40:44 We've got our in vitro ADME profiling back, and actually biochemical screening data came back last night, so I've had a good look through that. Very briefly, so we've got molecules that pass our in vitro assessment for blood brain barrier penetration, and we've got some really potent molecules inhibiting TIC two from that. Now we almost certainly don't have a clinical candidate. Right? There's more work to do, but I think it represents a very good starting point for that. And the objective of that collaboration was to really get us started down this route to some developed candidate for taking into CNS disease models. And then just finally, I'll talk about SRA seven thirty seven. It's a small molecule checkpoint kinase inhibitor.

41:37 It's completed phase one, two trials. Its history was originally developed by us from CR UK. It's completed two phase one, two trials as monotherapy and in in combination with gemcitabine sponsored by Sierra Oncology. When Sierra was acquired by GSK, they handed back the assets other than maimolitinib. SRA seven thirty seven was relicensed for about a year to a US biotech. They returned it in December 24, and we took a program over in March 25 with improved economics. And so we're currently evaluating the potential licensing and development opportunities for seven thirty seven.

42:23 Just want to show you this data. This is quite old data from the clinical trial, I think it really shows why seven thirty seven is potentially the resting class check one inhibitor. And what we're looking at, if you look at the monotherapy data, you'll see low grade, mainly side effects on the gastrointestinal tract, so nausea, vomiting, diarrhea, fatigue. Very little effect on hematology. Some anemia was seen, but very low anemia of high grade. No neutropenia, that's effects on neutrophils. No thrombocytopenia, that's effects on platelets. If you look at the phase one clinical data for other Check one inhibitors, you very often see hematological toxicities.

43:13 And we believe that is because they are not selective enough particularly against Check two. So inhibiting Check two, which as the name suggests is closely related structurally, that brings in hematological toxicities, which we don't see with SRA seven thirty seven. And that means that you can combine it with chemotherapeutics, and you'll see in this one even with low dose gemcitabine, you do start to bring in hematological toxicities as you'd expect from a chemotherapy. But because of the, I suppose, benign nature of SRA seven thirty seven, we're able to combine with these chemotherapies and still have very low incidence of high grade hematological toxicities. So we think that is a real distinguishing feature of seven thirty seven. Just this is against some old data from the clinical trial at SARE sponsored showing the meaningful tumor response amongst some patients when combined with low dose gemcitabine.

44:17 And, you know, this is really significant obviously to the patients who received this, but in taking this program forward that we've shown meaningful tumor responses amongst patients. I'm not going to go into this slide in any great detail, but the company who had the asset for a year did quite a lot of work and they've really validated the potential of SRA737 in acute myeloid leukemia myelodysplastic syndromes, AML and MDS. So these are blood cancers. And they were able to open an IND, so the right the ability to start a clinical trial in The US in AML and MDS patients with SRA seven thirty seven. We've taken that on board now.

45:06 And I just draw your attention to the third bullet point. I'm not gonna get into this in any great detail, but these mutations to SRSF two and and U2AF one, these are splicing factors, they're essentially actionable predictive biomarkers. So you can screen patients for these mutations in advance, give them SRA seven thirty seven with a high expectation that they could respond to seven thirty seven. And these are really the first predictive biomarkers for check one inhibition that have emerged in the literature recently. So we're getting excited about AML. So with this open IND with the US FDA to conduct a phase one clinical study in combination with the standard of care, the previous license holder demonstrated profound profound synergy in preclinical studies between the standard of care and SRA seven thirty seven at concentrations which are readily achievable in clinic.

46:08 A potential subgroup of patients who can be selected with a high expectation of sensitivity to the agents. We've got enough capsules to conduct this planned study, and there's also a lot of the active pharmaceutical ingredient, powder. We've got lots of that in store and advanced intermediates to generate more of that molecule. So we think it's a really great package of IP data assets, physical assets, that a licensed partner could get into the clinic extremely rapidly. So this is the final slide just to summarize. SAREUM has demonstrated demonstrated promising clinical activity.

46:56 It's very well tolerated as a single agent, which means it can be combined with chemotherapy. Strong clinical validation for this class of molecules with DNA damage response class. The molecule has excellent trivial like properties, low drug drug interaction potential, a strong preclinical dataset, and this open IND to conduct a study in AML MDS patients. There's also a lot of other preclinical data to support potential use and clinical data, I should say, in anogenital cancer combined with low dose gemcitabine or in other tumors when combined with immuno oncology agents such as anti PD L1 or other inhibitors of DVR pathways such as POP inhibitors.

47:44 Okay. That's the final slide. Can move on to Thank John. Thank you. So let's throw it open to the floor. Would anyone like to kick off and ask a question? Yes, sir. This point, probably not far off. I guess if you want an accurate answer, we can, you know, we can double check it and post it on as as an answer to an IMC question.

49:10 But I'm just trying to think. So the the company. Yes. The company is. What? The company is eligible. Yes. So you could Yeah. So that cost is eligible. Yeah. Yes. So, I mean, the company in general is I don't know whether cost gets split out. I don't I'm pretty sure they don't. No. I mean, it's it's it's it's company generally, yeah, rather than what what we're trying to do with it.

49:57 Does that mean that this kind of preface my comments that I'm a very active member of There was no mention of what I see.

50:48 It was a key a key man risk at film. Mhmm. What happens if he has the because he had an argument with the with the London only. We we never did this image. Am I am I right? So so we have I mean, we have insurance. So if I were to have an argument with a bus, this would be financial compensation. I think I work with consultants, so particularly with toxicology and for the chemistry. There consultants who are very involved in the project.

51:34 Have all of the records that I have would be able to pick up if I was to have this accident with the bus. And and I think the other thing is just just to say that, you know, everything everything is now the data is stored. The data is available. It could be picked up by somebody. So I think we have good, you know, contingency plans if should the worst happen. Okay. I mean, I have to say, my perspective, the CEO at this stage seems seems an unnecessary. Mhmm. A CMO seems to be a you know, seems to be something very worthwhile too. Yes. Well, and and that is exactly where the priorities are.

52:21 Are Please sorry, sir. If I may just ask you if you to repeat questions because we can't hear the attendees in the room just moving forward. Thank you, sir. Thank you. Okay. Thank you. Sorry to interrupt. Yes. Well, we'll carry on and finish this one. I mean, yes, CMO is the higher priority of the two roles, absolutely. And broadly speaking, so in terms of the the skill set that we brought, I mean, John, of course, is absolutely fantastic on discovery and has got us to where we currently are Development as going forwards and, indeed, planning for development is an entirely different set of skills. And whilst Joel has done a fantastic job thus far, probably, if if you're looking to plan an efficacy study, then you want somebody who's actually been there and done it thoroughly.

53:18 Could I just Please. You're quite right about about the CMO. CMOs become very expensive. I mean, a full time CMO, Bruno certainly can have a very savvy CEO. However, are a lot of CEO consultants CMO consultants around the globe who come out of industry and follow-up. One can utilize their services at a level that the company can afford. And the very best ones can make a huge difference in value in the sense of being able to if you do a phase two, can. I could figure things. I'm not going to qualify. I could figure things. But the the disease, the type of disease, the patient population with the source of measurements that one does and the intrinsic knowledge of where the patients are because of phase two trials in multiple centers, networks with with the clinical PIs.

54:29 Absolutely essential. One can use consultancy. One can regulate the cost of. So I, at least, do not think unless the world changes in terms of investment, we will be getting a full time FTE even to say three days a week sooner because they are super expensive. There's a lot of top notch concerns there that we can use. Yeah. And so I absolutely take your point of view. We need to add we need to decompress John. We need to add expertise. And we need to be able to factor that in the way we can. Yes, sir. First of all, was glad to see you got mean, in votes against you, John.

55:17 I know that they were just the the company's policy going forward is obviously non dilutive funding. Even what we've heard so far toxicity once we repeat that, I'm assuming that the cash funds will be running out. And that's in six months' time according to the sort of showers. Mhmm. So are there any proposals to the agenda that you can put to the floor and we'll wait for as far as funds are concerned?

56:04 Yeah. This is a question regarding future funding for the company. And the answer, obviously, this is these these are forward looking statements, of course. But the answer is this is exactly why we have such a high priority for getting seven thirty seven and ideally 18 o two partnered because those are each of them potentially sources of non dilutive funding, coming into the company. And, obviously, you know, all all thing all things have to come together. And but in terms of our priorities, it's very, very firmly fixed on getting those over the line. Yes, sir.

57:59 Lack of their confidence in their company. And it just to me, questions the way investors should continue to fund a business which is singularly failed to turn scientific progress, don't know about that, into measurable financial progress. Certainly, with regard to the share purchases, I'm quite a stare. I do appreciate that, obviously, there are periods when we come to regulatory restrictions. Which should be granted over many years. And as I understand it, those those those share options are all out to the money. But when our share options were issued at a price of 30p, I think I rightly say in December of last year, Well, shit price sits on the whole fact.

58:57 So does that not encourage you to to want to invest and show confidence at least in the company? Well, you've raised a whole a whole host of issues, many many of which are unfortunately a lot to do with the the sector, not necessarily just the company. But I would gently point out to you that I have repeatedly bought shares in this company. So I, frankly, I'm not impressed by the criticism. I have got and and moving on from that, there isn't as you rightly say, there isn't always an opportunity to buy shares. There is a very fine line that we have advisers in the room who will be very quick to tell me that there is a very fine line between investing in the company and and seeking to manipulate the share price, which is not something, of course, which we can do or will do.

59:58 So we are we believe we are working extremely hard for all shareholders, not least ourselves, but as you rightly say, we also, being shareholders, are not wildly excited about where the share price is at the moment. So we are, you know, we're things forward. And we are very committed, or might argue overly committed in terms of share portfolio, to this company and to holding shares in it. And speaking personally, all I could say is that the the the quality of my old age would be materially affected by the the exits that SAREUM achieves. So we are entirely incentivized to to to make that as as positive as possible.

1:01:01 Well, some of them are, but I've I have gone into the market repeatedly and and hold shares. Push the share price in the other direction.

1:01:48 Well, as I say, you must be very, very careful in the way that you describe that because we are not able that we would be fitted for a very nice, arrogant suit if we start manipulating the share price through share purchase or otherwise. And before anybody on the board can buy a single share, it has to be cleared through all the advisers. So this is this is not a sort of this is not a trivial matter. You know, we and and I well, I have been able to. I have bought shares. You know, we we can't just go sort of dancing into the market. You know, we're we're not employed as fund managers. The the value the value in this company will come from getting the fundamentals of the drugs right and move move move them forwards so that that value is is is recognized in the external market and help hence, I hope, in the share price.

1:02:54 The that happens after the year has ended, which it hasn't ended yet. Oh. Could I So Please. You mentioned the remuneration directors. So this really Brian and I are the two members of the remuneration committee. We look every year at the benchmarking data for for AIM companies of of of the appropriate size and of similar size. The two non executive directors remuneration is well within the first quarter. So so the two non execs I myself would like would certainly not be higher than this of well paid non execs in paid companies of as of an approvates of this subsidy.

1:03:45 The two execs are a roundabout the median, but actually a little on the left of the median. So again, not in terms of pace sound. They're not in the in the upper quarters. So we deliberately look, we look from a shareholder perspective, I. E. Your mind, and we try to give remuneration down. Now to the previous question, we could say, fine, okay, we'll take them like that. You lose job maybe. And we've just actually said how important job is to the company. So we try to strike a balance between retention, which is important, and keeping the salary cost down.

1:04:37 That's base salary. In terms of bonuses, we are, to be honest with you, Clive and I get continual pushback I guess in terms of how stingy we are in recommended bonuses before. So we do not pay every year large bonuses. And if you look at the bonus levels again by the benchmarking data for AIM companies, the bonuses that we pay are actually not in comparison. We chose to pay a bonus for 2024 because in fact the effort required to run a clinical trial, a Phase one trial successfully, on time, within budget in Australia which was the major value driver at the time in our view for the company. You might argue it hasn't given it that much, but sure as hell it would have failed in the trial that it would have been much less.

1:05:34 We felt that that merited a bonus. And the bonus given for 2024 was it when we served 25% of the base salary. That is a low bonus for this industry. Whether we pay a bonus for 2025, we will look at the same criteria. It will have to be something truly exceptional or an executive to get a bonus because that's how we look at it. So you raised an important point, we do need to keep salary costs down. The remuneration committee tries hard as possible and I do not think that if you look to other companies, you would say that we're paying ourselves wherever we are. I don't know whether that helps or whether you're convinced have an issue with the SAREUM.

1:06:20 Well, you mentioned the remuneration of the directors. I was gonna say, don't think that's the question. No. But I think the question was more the lack of buying shares in the market. So after the report, we asked him, came to the room and asked him to invest, and if we did, got our our money into business. I think what we're asking here is that for you guys to pass through the same if you're currently able to. Well, just to point out, so did so did we. So did we at that stage. A. Oh, Lumos. Yeah. Yeah. They they I mean, they're certainly more advanced, and they've got a a a program.

1:07:15 But I think just to give you context, their directors have bought in substantially over the last few months and that's actually a significant increase in share. So I think the point remains that if you have commitment and you have belief in companies, the founders, the founders, that's exactly what we did. It's exactly what I would do in your position. So it doesn't show a lot of confidence. I think that's the point that they've made here. If you're not willing to put that money in, know, asking everyone else to do the same thing. Sort of Do do do But it's is there is is Yeah. So point point taken, Matt, but do be careful with correlation versus causation. You're you're describing a company that you you yourself said is is is further along than we are. So that that would suggest that there is an intrinsic reason for there being greater value in the company.

1:08:05 So rather than, you know, the the so yes. We'll If we can move on. Yes. For clarity, John, on the the slides with the where we are with 18 o one, I know that, obviously, seeing start of four weeks. So, obviously, quite early impact. You're saying that we're going we started as of today, the five day study side of things. We're looking at, in q one, finalizing the formulation and the view of completing the actual toxicity by the end of q two. They're all very fine timelines given the festive period coming up. Yeah.

1:08:55 And if we work on the worst case scenario, we don't get formulation right to the end of q one. We get up to the end of q That's '2. True. Do you see that as the worst case scenario? So I think one of the things for shareholders was the lack of communication on where we were. We were imminently starting. Actually starts with toxicity. Just for my own piece of mind, I'd like to think that the human one will be completed before the end of this year and move forward. Do you expect the formulation to take three months before you actually start the toxicity study? Sorry. You said the human the human one? You know, the five day, I'm expecting the data from that to be fairly imminent, so they get into the reformulation immediately in the New Year. Right. So the PK study that starts today is not in humans. Sorry, John, do want to repeat the questions? So for the benefit of people online, was a question about the timelines of the ongoing PK and tox studies.

1:09:56 Yeah. Yeah. So the PK study that started today is in the preclinical species that will be used in the toxicology study. I would say it's very realistic timelines. Okay? And this is I know I every year, we have comments about communication and and lack of communication. I I personally struggle a great deal with the amount of detail that we do give out. Things Things like that. So a five day PK study does not take five days. It takes considerably longer. Right? I mean A sixteen week toxicology study does not take sixteen weeks. It takes considerably longer. And I I I personally find the level of detail that we give in communications sometimes problematic.

1:10:42 Okay? However, we hear you. Communication is I would like you to put across is because, you know, sort of our only communications on the lovely billboard that we have from LSE, which gets quite childish sometimes. And it would be good that the the board actually feed that information out generally so it's understood where we we are. Because the way I'm seeing it at the moment is that there's lots of things that are ambiguous, and it is good that as you complete those phases, provided you can up with the market conditions, put that out to the market so we know where we are rather than just sitting there waiting. And I think that alone would encourage the SP without you guys having to invest or whatever. Think the lack of communication does have an effect on the SP.

1:11:37 Yeah. Okay. I understand. That's all I'm asking. I understand. Mean, the danger the danger of that is is exactly what happened. Okay? We we make announcements about we started the toxicology study. Yeah. It went wrong. Yeah. We'd have to announce that. Yeah. Of course, sure. And those things happen. And and when you make the announcements of starting a toxicology study, the share price goes up 3%. Yeah. And when you make the announcement that you have to stop us, bloody, share price goes down Yeah. 20%. Yeah. Okay. I just feel good. You could be a little bit more clearer and more informative as these things progress. Okay. Right. Well, as as John said, as we've said various times before, we we we we hear we are in fact, we have them in the room, of course, but we are surrounded by advisers as to what should or shouldn't be said as we go. And the the only thing worse paying money for to to have advisers around you is not to listen to them when they advise.

1:12:49 So so we do we do pay attention to to their advice as well. Time is well away with us, I'm afraid. We haven't had a chance to get on to pre submitted questions. So I apologize to people online. We will, as we said previously, produce answers and post them on the on the website in the next few days. I would just like to wrap by thanking you all for making the effort to come. It's always good to have a have a full room in person. I hope that you feel happier post the announcements in the AGM than you than you were yesterday. And let's all have a a very good Christmas and look forward to 2026. Thank you all. Thank you to the board of SAREUM. Thank you very much indeed. We'll now redirect those online to provide their