Sareum Holdings plc

and welcome to the salarian peel holdings plc investor presentation throughout this recorded presentation investors will be in listen only mode questions are encouraged and they can be submitted at any time using the q a tab situated on our hand corner of your screen simply type in your questions and press send the company may not be in a position to answer every question receives during the meeting itself however the company can review all questions submitted today and publish responses which is appropriate to do so before we begin i would like to submit the following poll And I would now like to hand you over to Executive Chairman Dr Stephen Parker. Good afternoon to you.

Good afternoon everyone, thank you for joining us. It's a pleasure to be here to present SARIEM's results for the year ended 30th of June 2025. I'm joined today by Dr Tim Mitchell, our co-founder and chief operating officer, and Dr John Reeder, the scientific officer and indeed co-founder. Together we'll take you through our progress over the past year and importantly how we're positioning SARIEM next phase of growth going forwards. but obviously we will be paying your attention to the recent news around the toxicology study with 1801. Before we begin I'd like to draw your attention to the usual forward-looking statements As always, this presentation will include forward-looking statements relating to future events and performance. These statements involve risks and uncertainties, and actual results may differ materially. We therefore encourage investors not to place undue reliance on them. Now, before we move into the main part of the presentation, I'd like to take a moment to address the recent issues on everyone's minds. Let me start by saying that SARIO has made good progress across its pipeline and is entering the new financial year with confidence and momentum. We are of course frustrated by the unexpected and disappointing discontinuation of the GLP toxicology study for SDC1801 and I know that many of you shared that reaction. However, the adverse findings occurred predominantly in control animals and are unrelated to SDC1801. That outcome has reinforced, not diminished, our confidence in the molecule and the platform behind it. are already in advanced discussions with several CROs to restart the study as quickly as possible using existing cash resources. Our focus remains firmly on completing the phase two enabling package and progressing towards patient studies whether that be with a licensing partner or indeed less likely but possibly ourselves. The strong phase one results during this period, together with positive clinical readouts across the broader TIK2 field, continue to strengthen our conviction SCC1801 has the potential to become a best-in-class, once daily oral therapy for autoimmune diseases. In parallel, we secured full rights to SRA737 on substantially improved terms, and we're actively assessing the best routes to progress and create value from this asset. Beyond these programmes, a new collaboration with Receptors.ai is extending the relevance of our TIK2JAK1 science into neuroinflammation, applying AI-driven discovery to identify brain penetrant molecules. While the past year has brought its challenges, it has also strengthened the foundations for growth. Marion today is a focused clinical stage biotechnology company with a clear path ahead, strong conviction in its science and a set of tangible milestones to deliver. Let's just summarise this in the pipeline chart. As you can see how the programmes line up, 1801 leading the way in autoimmune disease, STC 1802 advancing in oncology and SRA 737 and the CMS collaboration broadening our reach. The message here is focus and depth, one scientific backbone, the TIK-2 Check-1 pathway applied across several high value indications. With that overview in mind, let me hand over to John, who will take you through the opportunity behind SDC 1801 in more detail, how it works, how it compares across the field, and why we're so confident in its potential.

Thank you Stephen and welcome everybody. So I'll tell you about the TIK2 JAK1 inhibitor program principally focusing on STC1801. We see this as a very exciting area. The science is well validated, the significant commercial potential and a broad potential to help patients in a number of different disease areas. So the validated science is proven by the approval of BMS is TIK2 inhibitor, so TIK2. This was approved without the black box warnings that were given to the earlier generation of JAK inhibitors. And this boosts confidence in TIK2. AbbVie's JAK1 inhibitor RINVOC, a selective JAK1 inhibitor, has been found to be extremely well tolerated in long-term safety studies and ongoing now that it's been marketed. And most recently, Priovant's TIK2-JAK1 inhibitor, brepacitinib, is the first targeted therapy to achieve a positive registrational trial in the skin disease dermatomyositis. Moving on to the commercial potential then, there have been some very big deals in this area. Just on the field of psoriasis, it affects more than 125 million patients worldwide. has an approximate market size of $29 billion in 23. And so TIK2 has got forecast peak sales of $3 billion. A couple of recent deals, $4 billion upfront acquisition of Nimbus' phase two TIK2 inhibitor by Takeda and a phase three deal by Kaken Pharmaceutical to develop Illumis' clinical stage TIK2 inhibitor in Japan only, $140 million. And then the broad applicability and how we can help patients in numerous disease areas. So TIK2, for example, has been approved not only for psoriasis, but also for psoriatic arthritis. RINVOC approved in rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis and TIK2. JAK inhibitors have successfully completed or are undergoing clinical trials in many diseases, psoriasis, psoriatic arthritis, rheumatoid arthritis, Parkinson's disease, dermatomyositis, alopecia, noninfectious uveitis, hydrogenitis, suppurativa. So we're seeing very positive effects from JAK inhibition in many different disease areas. sdc 1801 we believe has a differentiated mechanism and a demonstrated strong safety profile it's a selective tick 2 jack 1 inhibitor which we're developing for autoimmune diseases with an initial focus on psoriasis we have positive top line data from a phase 1 clinical trial with very favorable safety and tolerability profile pharmacokinetics supportive of once daily dosing and dose responsive pharmacodynamic biomarker reductions toxicology studies obviously we've put out the disappointing news recently about the 16 week glp tox study that has been discontinued following unexpected findings which we observed more frequently in the control group animals that did not receive 1801 we've recently had additional data that has confirmed that the control group were not dosed with 1801 so we can say that the findings are considered unrelated to 1801. We will restart this study as soon as possible and we'll be able to complete it with the existing cash resources. So the next steps in the program, obviously to resume the TOC studies, the phase two enabling work continues. We have completed drug remanufacture and formulation optimization is in progress to support the initiation of phase two clinical trials. And the combined package of manufacture formulation and toxicology will inform the study design of any future phase two trial. So how does SDC1801 stand apart from brepacitinib we talked about brepacitinib a couple of slides ago it's priovant's dual tick 2 jack 1 inhibitor if you look at the clinical data for brepacitinib we believe these are dose limiting side effects principally blood cell effects so clinically significant or relevant reductions in key blood cells were observed at higher doses of brepacitinib In contrast, 1801 showed no effect on blood cells at equivalent doses. Kidney function. Brepacitinib increases a marker of kidney function called creatinine. Again, seen at higher doses. In contrast, 1801 shows no changes in kidney markers, even at similar or higher doses. The half-life of a molecule for brepacitinib is six to eight hours. for 1801, 17 to 20 hours. That's the time it takes for a body to reduce the concentration of drug in the blood by a half. And the dosing profile for brepacitinib, once daily dosing, but they get a very spiky PK profile. So that's to say they get a high maximum concentration and then it drops down to a low minimum concentration. And this is a factor of the absorption of a molecule and it's relatively short half-life in contrast with 1801 we get once daily dosing with a smooth pharmacokinetic profile that means a lower Cmax but we drop off to a higher Cmin and this is ideal for JAK inhibitor where a sustained concentration throughout the dosing period is advantageous so we think SGC1801 may offer a safer alternative to brepacitinib We've seen no clinically relevant effects on blood cells or kidney function and a potentially advantageous PK profile. A bit of evidence on this slide to support our idea that dual inhibition of TIK2 and JAK1 is more effective than inhibiting those kinases individually. so we're comparing across clinical trials here okay so some caveats around that the different patients different centers different principal investigators etc but i think you know broadly speaking considering this data we're looking at the effects of these drugs on psoriasis patients after 12 weeks of dosing and psoriasis trials are usually scored using this PASI scale that's the psoriasis area and severity index and a PASI 75 score means that a 75% improvement in most psoriasis symptoms has been shown and that's a very common clinical goal in psoriasis trials so what the graph is showing is the percentage of patients on trial that achieved PASI 75 after 12 weeks and if you look at the um bars to the right of the diagram, that's prepacitinib. You can see that placebo-adjusted response of about 65% of patients achieving that PASI 75 score after 12 weeks. And that's outdoing both TAC279, that's the Nimbus molecule acquired by Tocada, Ducravacitinib, also TIC2, and a dual JAK1-2 inhibitor, baracitinib. Furthermore, Prepacitinib has shown meaningful efficacy in other clinical trials in patients with numerous diseases, including psoriatic arthritis, dermatomyositis, uveitis, atopic dermatitis, alopecia, hydrodinitis, suppurativa and ulcerative colitis. So again, just proving the potential for a dual inhibitor in these multiple different autoimmune diseases. Moving on to SDC 1802 then in oncology, we've concluded our translational and preclinical studies on SDC 1802. Our experience in the development of 1801 has been helpful, supports the process development of 1802, particularly in the chemistry field. We've increased the strength of our patent position, now cover several disease targets with 1802. The strongest validation for 1802 has been seen in hematological cancers such as T, ALL and B cell lymphomas. And so we're reviewing our options for further clinical or for initiating clinical development of SDC 1802. And I think we're noting at this stage, it may be preferable to partner this program. And then in August, we announced that we were expanding into CNS, that's central nervous system diseases, so targeting neuroinflammatory diseases. This is in response to some strong scientific rationale that has emerged in the literature recently. There's growing evidence that TIK2 inhibition plays a key role in neuroinflammatory diseases, multiple sclerosis, Parkinson's disease, Alzheimer's disease and others all represent areas of high unmet medical need. And plenty of research has been published by academic groups and by other companies confirming that TIK2 is a key neuroimmune modulator. So given our experience with development of TIK2 and JAK1 inhibitors, we thought we would go back to our compound collection and have a look if any of ours were brain penetrant. I should say actually that STC1801 is not brain penetrant, and it was partially selected on that basis. But looking at other compounds in the collection, we selected six that we thought had a good chance of getting into the brain, got them tested, and we're pleased that three of the compounds did demonstrate meaningful blood brain barrier penetration. one compound in particular showed strong levels of free drug in the brain so the drug not only has to get into the brain but it has to be not bound up by some of the proteins that are just naturally present in the brain and can stop a drug interacting with its intended target so that's equally important to getting into the brain so a really good starting point uh for a new program and the market opportunity is there neuroinflammatory diseases affect millions globally. There are limited treatment options for many of them. And brain penetrant kinase inhibitors are representing a new frontier in CNS therapeutics. So we think the time and the evidence is right for us to make further use of our TIK2-JAK1 compound collection to press forward with this program. And we announced a partnership with Receptor dot ai back in august they use their ai platform to power discovery acceleration they've lots of potential for the use of ai and machine learning in drug discovery where you're trying to solve multi-parametric problems at the same time so about the collaboration men an initial four-month partnership to optimize brain penetrant tick-2 jack-1 inhibitors Receptor AI will support the work by using their virtual screening and pharmacokinetic predictive models. Obviously, absolutely key that these molecules get into the brain in meaningful quantities. And then we're overseeing the compound synthesis, the biological testing and the ADMET profiling and taking candidate molecules on into proof of efficacy or proof of concept in disease models. The terms are such that we own 100% of all of the intellectual property and rights to compounds from the collaboration. And the results will inform selection of lead CNS candidates for preclinical development. Moving on to our Check 1 kinase inhibitor then, SRA737. Again, a target with validated science behind it. Broad commercial potential and potential applicability to numerous oncology diseases and and some non oncology indications potentially. So check one forms part of the DNA damage response pathway. It's a well validated pathway for cancer therapeutics. SRA 737 has proven to be well tolerated in clinical studies. And synergies between check one inhibitors such as 737 and many types of different chemotherapies targeted therapies and immunotherapies have been reported in preclinical studies the commercial potential then there are currently no approved check one inhibitors which creates a first in class opportunity earlier generation less selective check one inhibitors have not succeeded in clinical trials And this has mainly been due to dose limiting toxicity. And this creates an opportunity for SRA 737, which has much greater selectivity and has proven to be better tolerated in the clinic. The selectivity is really important. I think the selectivity over the related kinase check two really sets SRA 737 aside, certainly from the early generation check one inhibitors. and potentially from some of the more recent and current CHK1 inhibitors. Clinical and preclinical studies support the use of a selective CHK1 inhibitor in many different clinical settings. I think because of the clean safety profile of 737 as a monotherapy and in the combination therapy trial that was run, we've seen that it's suitable for combining with other chemotherapies. So particularly in solid tumor types with defective G1 cell cycle checkpoints, for example. And then other DNA damage response inhibitors, for example, PARP inhibitors in ovarian cancer. We've seen some very interesting preclinical data when combined with immunotherapy in lung and colon cancers. And again, combinations with chemotherapy in blood cancers such as AML have all been seen in preclinical experiments. So 737 is a clinical stage oncology asset with broad combination potential, a selective check one inhibitor, two phase one, two trials completed. They were funded by Sierra Oncology and showed excellent tolerability as a monotherapy and in combination with chemotherapy. During the period, we have gained control of the program and increased our economic interest up to 63.5%. and the clinical safety data supports the use of 737 in combination with other anti-cancer agents. For example, with immunotherapies in certain lung cancers and with PARP inhibitors or WE-1 inhibitors in, for example, ovarian cancer. The program was licensed to a unnamed US biotech for a period of about a year. during that time the biotech was able to open an ind with the usfda also synthesized enough drug product that's capsules to give to patients and also drug substance that's that's the powder that goes into the capsules to conduct a planned trial in aml and mds patients there's a couple of blood cancers and this ind has now transferred over to sarium so this would give potentially us or a partner rapid access to a clinical trial if we chose to go down that route so at the moment we're reviewing the options we're evaluating relicensing partnering with the project or developing it internally to maximize the asset value I'm going to hand over to Tim Mitchell now to take you through the preliminary financial results.