Sareum Holdings plc

Hello and good afternoon to everybody on the call. Thank you for joining us. Today we announced, as you know, the unaudited interim results for the six months to the 31st of December last year. And we will take the opportunity, as well as looking at those numbers, to give you an update on the progress that we're making. uh there is of course the usual disclaimer do please um remember that we will be talking about forward-looking events which may or may not happen or may or may not happen to the extent that we're describing so uh that's very usual but it's as well to remind you just then to remind you about the company um we uh we have the three programs uh tick to um tick to jack one 1801 and 1802 and the uh check one inhibitor sra 737 and we will be talking at greater or lesser length about all of those today during the period or since the period i should say we have restarted the phase 2 enabling tox program for 1801 with a a new leading global cro as we were able to say this morning all subjects have commenced dosing in that study uh as you know we were unfortunately had to discontinue the previous study with a with a different cro um after the unexpected findings uh that uh that came up came about there um we have uh so so that unfortunately set us back about six months Then the phase one data of course just to remind you gave a very favorable safety and tolerability profile in human patients and the pharmacokinetics support one dose daily dosing which is very good. um so we're working to optimize the formulation the capsule formulation of 1801 and that is nearly completion uh 1802 as we indicated at the end of uh 2025 um we think we've got as far as we can in scoping out the the opportunities with 1802 but it's it's probably better carried out by a third party with expertise in blood cancers so we will be we're putting together a package to support a licensing program for that Then we continue to look for partnering opportunities for SRA 737 That exercise is moving forwards I'm pleased to say and of course One of the things that is appealing to that program now is the extension of the IP which we announced this morning and the fact that there is now an active IND in the US. So anybody who takes on that program will be able to move forward in a very rapid manner. Lastly, the CNS collaboration with Receptor.ai is progressing well. There's a second batch of compounds in synthesis after the second round of predictions. So with that, we'll just give you a quick reminder of what the pipeline is looking like. so coming towards towards the end of phase one for 1801 getting phase two ready uh coming towards the clinic for 1802 and obviously the earlier program in the new neuroscience area so with that i'm going to pass you over to uh our cso dr john reader uh who will take you through those programs in in a little more detail john thank you stephen

So to talk about the TIK2 JAK1 space first of all and in particular SDC1801 we see this as a very supportive commercial environment with really well validated science we talk about science first of all there's a TIK2 inhibitor selective TIK2 inhibitor from BNMAS called so TIK2 has no black box warnings and that gives us great confidence in the TIK2 class earlier first generation jack inhibitors do carry black box warnings it should be said then AbbVie's jack one inhibitor rinvoc does have a black box warning but has been extremely well tolerated in long-term safety studies and they're not really seeing any of those effects that are warned about in the black box labeling extremely good safety profile And then more recently, Preovant's dual TIK2-JAK1 inhibitor brepacitinib is the first targeted therapy that's achieved a positive registrational trial in a skin disease dermatomyositis and believe Preovant are moving forward to NDA with that molecule in the near future. so good precedent there there's wide commercial potential i mean psoriasis is a disease that affects over 125 million people worldwide there was an approximate market size of 29 billion dollars back in 2023 bms are forecasting peak sales of 3 billion for so tick to a cicada of paid four billion dollars for Nimbus Therapeutics TIK2 inhibitor which was in phase two at the time and just for Japanese rights in the Illumis TIK2 inhibitor Kaken Pharmaceutical paid 140 million dollars so you can see there are some some big deals in the area And I think that's reflected in the broad potential applicability of these molecules so not only is so tick to approve for psoriasis but also for psoriatic arthritis likewise ring box approved for rheumatoid arthritis psoriatic arthritis atopic dermatitis and inflammatory bowel diseases. And there are TIK2JAK inhibitors that have successfully completed or currently undergoing clinical trials in a whole range of different autoimmune disorders. You can see the list there. I don't propose to go through them all, but many opportunities in a wide variety of autoimmune diseases where these molecules could find applicability. So why do we think SDC1801 has the potential to be better? Well, we have this differentiated mechanism and a strong safety profile. Just the overview of 1801, it's a selective TIK2 JAK1 inhibitor, which is being developed for autoimmune diseases with an initial focus on psoriasis. positive data from the phase one clinical trial, which we carried out in Australia. We did a single ascending dose, a multiple ascending dose, a fairly standard design of phase one trial. And we saw really favorable safety and tolerability profile for the molecule and the pharmacokinetic profile supportive of once daily dosing. And we also saw some dose responsive pharmacodynamic biomarker reduction. So although these were healthy volunteers, we were able to show an effect on the immune system and a reduction in inflammatory proteins in the blood of these patients. So since for phase one, we've been working on these phase two enabling activities. And as Steven mentioned a moment ago, post period, we restarted the GLP toxicology program for SDC1801 and dosing is ongoing. This followed the discontinuation of a previous study where unexpected findings were observed in more frequently in the control group. So we were able to confirm through subsequent analysis that the findings were unrelated to SDC 1801. They were driven by the vehicle that we were using to deliver SDC 1801. Current dosing is expected to complete mid-2026 and the full phase 2 enabling regulatory package is anticipated to be complete by year end. We have been manufacturing and have completed manufacture of a GMP batch of SDC1801 that's complete and in storage ready to move into a clinical trial. and formulation optimization is nearing completion so this is getting capsules which are able to dose the required amount of compound for the phase two trial with a sensible number of capsules per day so we're looking to dose one two maybe three capsules per day to achieve the exposures that we want to in a subsequent phase two trial Now, I mentioned brepacitinib two slides ago. That's the preovant molecule that's moving forward. I have a successful phase three study in dermatomyositis. How do we stand apart from brepacitinib? Well, I think the main side effects caused by brepacitinib at high doses, so up to 100 mg per day, are these effects on key blood cells, so in particular neutrophils and reticulocytes. These are clinically relevant reductions. It means brepacitinib can't move forward at 100 mg per day. But in contrast, our molecule at equivalent doses 140 mg per day which gave us the same kind of exposure as brepacitinib at 100 we don't see any of those changes to blood cell count. Brepacitinib also causes an increase in a kidney function marker creatinine and that's seen at doses just above 30 milligrams in contrast we don't see any effect on those kidney markers even at 140 mg per day our top dose And then the pharmacokinetic profile of the molecules are different. We believe we have an advantage. We certainly have a longer half-life. So 17 to 20 hours gives us coverage of the target over a longer period compared to brepacitinib. and although both are suitable for once daily dosing repositinib because of its shorter half-life to get the exposure they need this higher c-max so they get a spiky pk profile a high maximum concentration and a low minimum concentration whereas we get a nice smooth pk profile which is ideal for JAK inhibitors so we believe that 1801 may offer a safer alternative to prepositinib had none of the clinically relevant effects on blood cells or kidney function and a advantageous pk profile which should allow us to move forward with a higher dose of sdc-1801 compared to Now we think Repositiv has demonstrated that dual TIK2-JAK1 inhibition can be more effective than single TIK2 or dual JAK1-2 inhibition in clinical studies. And what I'm showing you here is data from several clinical studies. Just a word of caution, it's difficult to compare between studies. These are different patients, different protocols, different timings, et cetera. But I think the data does support the fact that dual TIK2JAK1 inhibition is more effective. we're looking at here the PASI 75 so this is a 75% reduction in psoriasis symptoms that's for PASI the psoriasis area and severity index a score of psoriasis symptoms and it's it's a common clinical goal to achieve a 75% reduction and you can see that brepacitinib does better after 12 weeks dosing at a 30 mg dose than Ducrevacitinib or the the selective TIK2 inhibitors Ducrevacitinib and TAK279 and is better than the first generation JAK1-2 inhibitor varicitinib brevacitinib additionally has shown meaningful symptom improvements in patients with a whole range of diseases you can see the list at the bottom there um and so you know i think it's really demonstrating the potential of dual tic-2-jac-1 inhibition and uh if we have a better molecule in prepositinib we would hope to achieve even better results uh in subsequent clinical trials why we think there's a good chance for that for for 1801 to have potential best in class efficacy we're comparing molecules now in different psoriasis clinical trials and we're looking at PASI 90 so 90% improvements in PASI scores in psoriasis symptoms. And that's really become a gold standard score for psoriasis patients now in clinical trials. You can see on the slide that biologics such as Skyrizi or Binzelx, these are IL-23 antibodies. So Skyrizi, you get an 18% of patients achieve PASI 90 after four weeks, and then that improves to 75% after 16 weeks. the newer oral il-23 inhibitors so these are oral peptides that inhibit il-23 uh such as icotrokinra uh 56 percent pazzy 90 score after 16 weeks and that improves as time goes by up to 65 The TIK2 single inhibitors, so TIK2 and zazacitinib TAK279, are less effective. So TIK2 27%, Casi90 improving to 33% after 24 weeks. Zazer a bit better. Now if you look on that slide, the week 4 top left, you're seeing brepacitinib at 100 mg once daily. Pfizer carried out a phase one trial in psoriasis patients where they dosed for four weeks and they saw really spectacular results at this 100 mg once daily dose about 90 percent of patients were achieving PASI 90 and just a reminder though that's great but this 100 mg once daily dose is not tolerated it can't be taken forward if you see the exposure that I've put on the slide the this is AUC the area under the curve it's a measure of how much compound is in the blood during the dosing period, 7,600 nanogram hours per milliliter for brepacitinib. Our molecule in the MADD cohort, that's the top dose, 140 mgs per day, achieved a similar area under the curve, 7,000 nanogram hours per mil. However, we didn't see any of those side effects that brepacitinib demonstrates at that level of exposure. Importantly for this analysis to make any sense, I have to point out that 1801 has a similar potency to brepacitinib in human whole blood cytokine assays. So we're getting the same exposure as top dose brepacitinib without the side effects. That's why we believe 1801 has the potential to achieve the same PASI 90 scores as brepo at 100 mgs per day, but without those dose limiting toxicities. And that's why we are prioritizing SDC1801 in our portfolio. Moving on to SDC1802, it's another member of our TIK2 JAK1 inhibitor family being developed for cancer and cancer immunotherapy applications. We've completed a number of translational studies now in different preclinical models of cancer. to support potential further development of a molecule. The strongest cancer response we've seen are in indications of significant unmet medical need and primarily in hematological cancers such as T-cell acute lymphoblastic leukemia, TALL and B-cell lymphoma. We've looked at 1802 both as a monotherapy as a single agent and also in combination with existing therapies and we've seen some interesting efficacy results using both paradigms but really as our priority must be SDC1801 we've taken the decision to press forward with 1802 in collaboration with a partner we think that's the best way to progress this molecule and so we're putting the data pack together to initiate that process very shortly And then we also want to expand our knowledge, our experience with TIK2 and JAK1 inhibition into central nervous system diseases targeting neuroinflammatory diseases in particular. Again, there's a strong scientific rationale for inhibiting these two kinases in the CNS. A lot of evidence coming out in the literature supporting in particular the role of TIK2 in these diseases. diseases that really represent areas of high unmet medical need multiple sclerosis parkinson's disease alzheimer's disease for example there are many others and lots of published research implicating tic2 as a key neuro immune modulator in these diseases so we wanted to make use of our experience and our existing data sets uh went back and looked at our existing collection and screened some of the molecules in models to look at how well they got into brain and into the cns and we found three that passed the blood brain barrier. One in particular showed real promise of good high levels of free drug in the brain. And so we've been working with Receptor AI from that starting point. They designed the first batch of compounds which were synthesized and have completed their early stage testing in both biochemical anatomy assays and then worked with Receptor again for a further batch of compounds which has been designed and is currently undergoing synthesis again there's a wide market opportunity I mean these are big diseases many millions of patients affected with really limited treatment options and brain penetrant kinase inhibitors in particular to address these inflammatory diseases in the CNS are an emerging prospect just to talk a little more about this collaboration with receptor.ai then we announced it in august the initial four-month partnership was designed to complete two phases of chemistry which we're well into the second phase of now so we were able to complete the first design test sorry design synthesize and test cycle well within the four-month period and then receptor designed the second round of chemistry which is what we're doing at the moment. They've done that using their virtual screening and predictive PK modeling. We've been responsible for compound synthesis, testing and admet profiling, et cetera. Importantly, we own all of the intellectual property and the compounds arising from the collaboration. And the objective is obviously to use these results to inform selection of a lead candidate or candidates for CNS diseases for future development. So moving finally on to SRA737, our selective CHECK1 kinase inhibitor. Again, there's a well validated scientific principles underlying this program. CHECK1 is a part of the DNA damage response pathway, which is well validated pathway for cancer therapeutics. The molecule itself is very well tolerated in clinical studies. And there are synergies between CHECK1 inhibitors, including 737, and many different types of chemotherapy, targeted therapies, immunotherapies, a huge array of literature reporting interesting findings and synergies with CHECK1 with other agents. There are currently no approved CHECK1 inhibitors, so that creates a first in class opportunity for 4SRA737. There have been earlier generation CHECK1 inhibitors which have failed in clinical trials. mainly due to their selectivity profile leading to dose limiting toxicities frequently that off-target effect has been an inhibition of checkpoint kinase 2 which our molecule is well clear of we have very good selectivity profile against checkpoint kinase 2 and we think that creates a great opportunity for a selective check one inhibitor such as sra737 again there's broad potential applicability in a wide range of diseases clinical and preclinical data to support selective check one a selective check one inhibitor in multiple settings in combination with chemotherapies other DDR inhibitors immunotherapies and targeted therapies so 737 is a clinical stage oral selective inhibitor it's completed two phase two trials as monotherapy and in combination we hold the license for 737 on improved economic terms currently 63 and a half percent of all future revenues compared with our previous 27 and a half percent share positive data shows excellent tolerability as a monotherapy with limited efficacy but very promising activity when combined with low-dose gemcitabine particularly in anogenital cancers where there is significant unmet medical need we have an active ind with the usfda that's an investigational new drug application to conduct a phase one trial in patients with acute myeloid leukemia and myelodysplastic syndromes and we have sufficient stock of SRA 73 capsules to conduct that trial and a stock of active pharmaceutical ingredient API that's the stuff that goes in the capsules to make many more capsules so as Stephen mentioned earlier a company picking up this project could could hit the road very quickly get get this trial running very rapidly that's attractive We're looking and continuing to explore the partnering opportunities, including relicensing, partnering, or potentially internal development to maximize the value of the 737 asset. Okay, I'm going to hand over to Tim now to take you through the preliminary financial results.

Thank you, John, and good afternoon, everybody. So if we first look at the income statement, we can see expenses have remained pretty similar to what they were last year. So the half year figures are within an approximation of about half they were for the full year. um the share of loss of associates that that is the uh the income or expenses with the partnership with um the crt pioneer fund for the 737 project uh now now that we are the full owners of the um uh the 737 program and the cpf are out of the picture uh that line will soon disappear once all the historical numbers are aren't reported um and so uh say yeah um lost well a tax credit of of 200 000 uh so lost for the year of uh 1652 uh as it was in cash terms of say approximately half what it was uh last year actually you'll you'll notice on for the four-year figures um there's a finance charge uh associated with the warrants that this is just an accounting factor I'll go on to in more details because it appears on the balance sheet as well but it's no cash is moving out of the company due to this charge it's just an accounting factor um so looking at the balance sheet um yeah so two and a half million uh pounds in cash um trade and other receivables i'll i'll just touch on that because i i've seen a question posted on that so so around 750 000 uh 200 000 of that uh is is due to the tax credit uh noted in the income statement um um uh yeah uh so so that that's answers one of the questions that's been posted Again, we see the warrant charge on the balance sheet. It's an accounting factor to do with the warrants. Many of these warrants were four year warrants from nearly four years ago, and they will expire throughout the year. So that sort of accounting anomaly, if you like, will disappear off the figures soon. so yeah so so leaving net assets but that's sort of of of uh around 1.2 million but there's the the as the one liability goes goes away uh that that that 1.6 million will will come back onto the the net assets okay uh so that's a a quick tour around the numbers uh there's obviously a fuller description of everything in the statement released uh this morning uh with that i will hand back to Stephen to sum up