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249. Bull, Bear & Beyond – Sareum: executive interview
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In this interview, Dr John Reader, co-founder and CSO of Sareum, discusses the publication of the Phase I data for lead candidate SDC-1801 in the British Journal of Clinical Pharmacology and explains why the results strengthen confidence in the programme as it advances towards Phase II. He highlights the drug’s favourable safety profile, once-daily dosing potential and evidence of selective TYK2/JAK1 inhibition, while outlining its potential advantages over competing dual TYK2/JAK1 inhibitor, brepocitinib. John also provides an update on Phase II preparations, including ongoing toxicology studies and formulation optimisation, before discussing the broad commercial opportunity for SDC-1801 across autoimmune diseases, Sareum’s partnering strategy and the key catalysts investors should watch over the next 12–18 months.
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Transcript
Introduction and Interview with Dr. John Reader
00:00:06
Speaker
Hello and welcome to this Edison TV interview with Dr John Reader, founder and chief scientific officer of Sarium, a UK-based drug development company focused on novel small molecule kinase inhibitors.
00:00:18
Speaker
Welcome. Thank you, Aaron. It's great to be
Publication of SDC 1801 Phase One Data
00:00:21
Speaker
here. So first of all, congratulations on the phase one data publication for SDC 1801 in the British Journal of Clinical Pharmacology. To kick off, could you start by maybe summarising some of the key takeaways from that and then help us understand if there was sort of any other insights into that beyond the initial top line readouts?
Key Findings from SDC 1801 Phase One Study
00:00:40
Speaker
Yeah, sure. um I mean, first of all, it was great to get the paper published in ah in a peer-reviewed journal, so it's really giving that sort of seal of validation to the um so of data that we've put out there.
00:00:50
Speaker
um The findings were really directed in four different areas, and it's fairly standard for a phase one, first in human study. So we're looking at safety, pharmacokinetics of a molecule, pharmacodynamic effects, or is it interacting with the targets we want it to. And we also added a food effects study into the um interval project, so that's to see if the absorption of the drug is affected ah by whether you're eating prior to taking the pills or whether you've fasted when you take the when you take the capsules so yeah those four different parts um i mean really just to take them in order the safety signal was excellent we couldn't really hope for much better um'm no serious adverse events no deaths
00:01:32
Speaker
um No real um safety signals of concern at
Discussion on SDC 1801 Safety and Pharmacokinetics
00:01:36
Speaker
all. and We look at ECGs, we look at um ah a wide range of different um ah levels in the laboratory, and but we didn't really see any clinically significant changes in any of those, so an excellent safety signal. We did see some mild, moderate, um what are called treatment emergent adverse events, but no real difference between the treated groups and the placebo groups, just kind of things like headaches.
00:02:02
Speaker
mild myalgia, and so muscle ache. um But again, you know no real difference between the the treatment um groups and the and the placebo, so that's that's great. So yeah, from a safety point of view, really, really happy. The pharmacokinetics point of view, so we were getting good levels of the drug into the subjects.
00:02:20
Speaker
We had a really good half-life. It's quoted between 15 to 27 hours, I think, which is quite a wide range, but typically we're seeing half-life around about 18 I mean, the point is that's suitable for once daily dosing, and that's quite important. um So yeah, very happy with the pharmacokinetics. We also see ah a sort of quite a mild curve, not ah not a big spiky curve.
00:02:43
Speaker
um What that means is that the maximum concentration is not getting up into the area where it might affect off targets, for
Target Interaction and Biomarkers of SDC 1801
00:02:51
Speaker
example. So um yeah, good good to see that.
00:02:54
Speaker
And then from a phonico-dynamic point view, are we actually interacting with the targets TIC2 and JAK1 that we want to affect? Well, yeah, we generated some good evidence to suggest that we are. So we looked at, um I suppose, four biomarkers.
00:03:08
Speaker
um One's called interferon gamma-induced protein 10, IP10. Okay, it's a um a marker that's it's considered biomarker of autoimmune disorders.
00:03:19
Speaker
um It's primarily driven by a JAK1 effect. So we were able to show that our molecule reduced these levels of a JAK1 driven a biomarker.
00:03:30
Speaker
Likewise, with another one called high sensitivity C reactive protein, That's a general marker of inflammation. You see that rise in diseases such as cancer, um autoimmune diseases, diabetes, etc. And again, we were able to show a good reduction in levels of IP10 when people were treated with our drug.
00:03:51
Speaker
And then we looked at a couple of ex vivo markers. So we took blood from the um volunteers on the trial. challenged it with an inflammatory cytokine called interferon alpha.
00:04:05
Speaker
And then we looked at how um certain proteins in the blood were affected in the presence of our drugs. So um we're looking particularly at phosphorylation of um proteins called STAT1 and STAT3, and we were able to show that phosphorylation was reduced in a dose-responsive manner when our drug was there. So Some really good evidence to show that we're inhibiting JAK1 and TIK2 with our molecule, but the kinds of effects we saw were not caused by off-target um interactions with the drug.
00:04:34
Speaker
So yeah, great um to get that phonico-dynamic validation of the avili molecule.
Impact of Food on Drug Absorption
00:04:39
Speaker
And then the fourth thing was the food effect study. We did that so you you you treat patients who have just eaten a meal.
00:04:45
Speaker
ah Sorry, not patients, volunteers. These are healthy volunteers, and that's something i you know I need to stress. These are not patients, healthy volunteers, but they have a meal, you treat them with a drug, ah or they're fasted, you treat them with a drug, and you're looking for any differences in the exposure of the drug in those different um conditions.
00:05:03
Speaker
and We didn't really see anything. There was a marginal increase of exposure in the people who'd had ah had a breakfast, um but it was not really significant. and so um That's great. so That gives you maximum flexibility in a dosing schedule for for people when we move into clinical trials and patients start to take this. We're not saying you've got to take this with you and with with a meal. You take it at your convenience, really. Yeah, good results all round. And also, I think the other thing we found was we we used three different capsule formats and the top dose, which was a 50 mid capsule, didn't really release as much drug as we'd hoped it would.
00:05:43
Speaker
So we've needed to, since we got this data, we've we've been working on improving the formulation so that we can deliver the high doses of of SDC 1801, which from a safety point of view, we could deliver, but we need to do that with a sensible number of capsules. So yeah, that's um that's just something we've been working on since we got the data.
Comparison with Brepacitinib
00:06:05
Speaker
Excellent. So sounds like a highly comprehensive publication. ah We saw as well there were some comparisons between 1801 and other TIK2 JAK inhibitors. So be great to hear in your own words what you think differentiates your your lead candidates.
00:06:19
Speaker
Yeah, um so I mean, I think the the lead molecule in this space is a ah molecule called brepacitinib. It was developed at Pfizer, but it's being developed currently by a company called PreAdvent.
00:06:31
Speaker
And um i mean, they've recently completed a phase three trial in dermatomyositis. It's likely that they'll be um applying for marketing authorization later this year or early next year.
00:06:42
Speaker
um So that's real you know really the trailblazer in this area. And what we found with our molecule was, so we could compare it very nicely with some data that Pfizer, as it was at the time, published around brepositinib in their phase one trial.
00:06:58
Speaker
um where they did a it's so it's called the ah multiple ascending dose, the MADD phase of the clinical trial. They did a 10-day study just as we did, and they were able to dose um at 100 milligrams, and they started to see some really serious adverse effects. So these were ah reductions in certain blood components, reticulocytes and um neutrophils.
00:07:26
Speaker
and they also see an increase in ah in a protein called serum creatinine, or creatinine is found in the serum, okay and that's a marker of um kidney damage.
00:07:36
Speaker
Now, I don't think brepositinib causes kidney damage, but what it does is inhibit a transporter in the kidneys, and and Pfizer put out some good evidence to support that. But it's a problem because it is a marker of kidney damage, and if you take that forward, um you know primary care physicians, for example, might see this and start to worry. okay so it's it's just Something to avoid if you can. So we were really happy to see that at an equivalent exposure in our MAD study, we did not see any of these effects. We didn't see effects on hematology.
00:08:08
Speaker
And we didn't certainly didn't see the serum creatinine effect that we think is dose limiting for brepositinib.
Progress Toward Phase Two Trials
00:08:14
Speaker
Sarium recommenced phase two enabling TOC studies earlier this year. be great to hear a little bit more about how the program has progressed since then as you move towards phase two.
00:08:24
Speaker
I mean, i can I can't really go into details on that, but just to say that those studies are ongoing. I mean, I think I can probably say they're nearing completion. Okay. Okay. So um yeah, we're optimistic about the outcome of those studies, and but it's something that really we're going to have to talk about in the future, whereas you know as as the results become available, the data becomes available and and and we will update our shareholders accordingly. So that's that's one to watch out for really.
Efforts to Optimize SDC 1801 Formulation
00:08:51
Speaker
um I think the other thing we've been doing that i i sort of alluded to is this formulation optimization. ah In order to get the highest exposure in in cohort D of a MAD study, we had to dose the for subjects with 140 milligrams, but we had to give that as 10 milligram capsule, so that was 14 capsules.
00:09:12
Speaker
We went to a twice daily um dosing, so they were having seven capsules on each dosing event. um That's not really sustainable. It's not something you could take forward into ah um into a phase two clinical trials, certainly. So the other thing we've really been focusing on is improving that formulation so that we can deliver the necessary dose of SDC 1801 in a sensible number of capsules. okay and And we've made really good progress on that.
00:09:38
Speaker
I think we're very close to what is called locking the formulation, so basically saying, this is what we're going to work with in the future. We're very close to to that. And then we have to get those capsules on on a stability study this is to make sure that you know they've got a ah reasonable shelf life. um And those studies will sort of go on over the over the latter half of this calendar the year. so Yeah, that's that's where we're at at the moment. And this is really to deliver this phase two a ready package, which we've ah said we will we'll have the data for by the end of calendar the year
Potential of TIC2 and JAK Inhibitors in Autoimmune Diseases
00:10:14
Speaker
26. Yeah, well, we we certainly look forward to following the progress. ah Taking a step back now, TIC2, JAK inhibitors, they've shown potential across a whole host of autoimmune indications. So
00:10:26
Speaker
For psorium, does psoriasis remain the lead sort of target indication or you know, it'd be great to hear if there's any other sort of opportunities you think could be applicable to the candidate. Yeah, well, I think one of the arguments we make about a dual TIK2-JAK1 inhibitor is its potential in a wide variety of autoimmune diseases.
00:10:45
Speaker
So, and I mean, we're a selective TIK2 molecules on the market and soon to be on the market. They've shown some good efficacy in psoriasis. um I think the thing with psoriasis is it's an extremely crowded space, ah very competitive. There are um biological therapies that are available and show really good results.
00:11:05
Speaker
There's the selective TIK2 molecules which showing good results and and's there are newer ones coming along um behind SO-TIK2 that ah are improvements on SO-TIK2. um And then there are some um other oral peptide therapeutics. There's a molecule called icotide, which has really shown um pretty good results in psoriasis. So it's great. The outcome for psoriasis patients over the last few years has has really moved on. um It's a very crowded space. I think um SDC 1801 could be competitive in that area.
00:11:35
Speaker
And I think certainly if SARIUM were to take the project forward, there's a lot of advantages in doing a psoriasis trial. okay You can access for patients relatively easily, and for a lot of them. show um you can um the There are really well-established protocols in place and and endpoints, so you know you know you know what you're looking for. um There's a very low placebo effect. That's that's important because sometimes some of the autoimmune diseases do suffer from the high placebo effect and can really confound your data. So um there are some definite positives. And then I think the other thing is that, you brepacitium, as I mentioned, has been studied in psoriasis. So there's comparative data that we could directly compare STC-1801
00:12:18
Speaker
to the result. yeah It's a caveat, you have different patients, different centers, you know, so it is you have to be careful comparing across clinical trials, but there's some data we can directly compare to. So and psoriasis is great. However, yeah, um I mean, prepositinib has shown good efficacy in a number of diseases now. um Alopecia areata, I mentioned dermatomyositis earlier. and There's ah an eye disorder called uveitis. It's demonstrated good efficacy in that.
00:12:46
Speaker
um So that's really sort of um enabling us to look at other areas and see where the strengths of this dual Tick2 Jack1 approach lie. I think, you know, we're looking for partners for the project.
00:13:01
Speaker
um And we're really looking, hoping to identify someone who can explore these different therapeutic areas. But if we can't, you know, if we can't find ah a partner or strike a deal that's beneficial to us, I think, you know, psoriasis is a place we we could move forward
Upcoming Milestones and Future Developments
00:13:17
Speaker
in yet. Just before we wrap up today, could you summarize for our audience the key milestones and potential catalysts to watch out for across the next, say, 12 to 18 months? Yeah. um So, I mean, we've just completed our financial year end. So obviously we'll be getting our um our numbers of our annual report out. They're usually late September, early October sort of time. So that's that sort of business as as usual, I suppose. Then it's really the ah the outcome of the...
00:13:45
Speaker
um ah ongoing toxicology and trials that I've i've i've mentioned. um It'll be progress in the formulation and the stability studies. and I'm not saying we'll specifically announce results from these via RNS, but we'll keep our shareholders informed as much as we're able to. um And then um obviously we have ongoing partnering discussions not just around SDC1801 but also our other leading candidacy SRA737, the CHK1 inhibitor, and SDC1802, another dual TIC2-JAK1 kinase but positioned more in the oncology space.
Sarium's Collaborations and Future Announcements
00:14:21
Speaker
And then we've got the um collaboration with Receptor AI that we announced late or mid last year where we're looking for CNS penetrant, brain penetrant, TIC2, JAK1 inhibitors as well. So we're making some interesting progress in that area and we'll hope to be announcing some some data around around that program as well over the course of the next a year or so.
00:14:45
Speaker
Fantastic. Lots lots to to look forward to then. Indeed. Well, hopefully. Fantastic. it John, thanks very much for joining us today. been pleasure. Thank you.