If you'd like to submit a question still, please do so using the Q&A option within Zoom. On the webinar from Syntara today, we have the CEO, Gary Phillips. I'll hand it over to Gary for the presentation.
Thanks Matt. Good morning to everybody, i t's a busy period and thank you for sparing us some time to listen to what we have to say this morning. I'm just going to pick out a few of the things which have happened in the last quarter and really look ahead to the news flow that's coming, because I guess that's really the point of interest for most people on the call, what comes next. We were really pleased to be able to announce yesterday that we have had our poster accepted for presentation at the European Hematology Association meeting. I'll talk a little bit about 5505, recap on the data that we showed at ASH in December, and just talk about the things to look for in the data that's coming up in June at this meeting. It is great.
I mean, the Hematology Association meeting in Europe is a gathering of some of the world's leading hematologists, allows us the opportunity for the data that we're showing to be reviewed, peer-reviewed by them, and live commentary coming out about the data at the same time as we're sharing it with the market. I think that's hopefully a really helpful thing to do for everybody. During the last quarter, we also announced the progression of the Skin Scarring Program. That's been going ahead with independent investigator studies with Professor Fiona Wood in Perth and UWA, Fiona Wood Foundation, for a number of years.
The recent analysis of the last study showing just how fundamentally we were changing scar structure has really emboldened us to move forward and bring that program fully in-house with going into a next-generation compound, a topical compound 9465, which we announced earlier in the quarter and which I'm happy to talk about after this presentation as well. We are very much excited about that and getting it into the clinic and getting that study underway and getting that new drug through phase I. I guess we can't really talk at the moment about biotechs and the markets without considering the global markets at the moment and the high level, high degree of uncertainty that exists for future funds and funding of companies like Syntara. It is really pleasing to sit here actually and to be able to talk about a really strong cash position that we have.
We ended the quarter with $ 18 million. In fact, I'll just delve into that just a little bit further. We've seen obviously the drop in valuation that's mirrored what's gone on elsewhere. Market cap now sitting at just under $ 100 million. The cash balance at the end of March was $ 18 million. Within that, I'm also pleased to tell you that the money that was owed to the company from the company that bought the mannitol business at the end of 2023, all but about $ 1 million of that has now been paid to the company and is now sitting within our cash. The cash balance looks actually healthier than it perhaps even did at the end of the previous quarter. $ 18 million worth of cash gives the company a runway of around about 18 months.
We have historically been spending about $1 million a month unless we kick off a much, much bigger study on 5505, then that cash takes us out through to the second half of 2026 and through the many milestones which I'll talk about when we get to the news flow. It is really reassuring, and I think for us as well as shareholders to see a strong cash position, particularly at this moment in the market where we see such a lot of uncertainty and difficulty in funding, probably for the next foreseeable period, I think. Just to focus on that 5505 and myelofibrosis, because that's the key event coming up. I'm sure that many of you listening to me this morning have heard me talk about myelofibrosis before. The study that's ongoing at the moment is one that's on top of standard of care, a JAK inhibitor, ruxolitinib.
JAK inhibitors sell around about $1.9 billion per year. Despite that, they really are still only symptomatic treatments of myelofibrosis for which the progression for these patients, the outlook for these patients is quite poor, with a life expectancy of about five years. JAK inhibitors generally being pretty poorly tolerated and causing cytopenias, drops in platelets and red cells. When they come off of these drugs they only have about 12 months to live. Huge opportunity here for a drug that can work on top of a JAK inhibitor, that can do something about the underlying disease and improve the results for many of those patients. I think we estimate that there's a half to three quarters of those myelofibrosis patients on JAK inhibitors which are not getting an optimum response. They're a suboptimal response to the drug.
Out of that 1.9 billion patients that are on drug, there's about $1 billion of that at least, which is the addressable market for a drug like SNT-5505. At ASH, in the American Society of Hematology meeting back in December last year, we presented the first set of interim data from this study. That was patients that had achieved, some of them, up to nine months worth of therapy. I think we had five patients that were out to nine months worth of therapy. The rest were at six months or three months worth of therapy. If you remember, this trial is running for 12 months. All these patients will eventually run for 12 months worth of therapy.
We were interested in two main endpoints, the two endpoints that both the clinicians and the regulators focus on, which is the symptom score, the TSS 50. That says how many patients get a 50% reduction in their symptom score, which is a patient-reported outcome within the period, and then compared to baseline, and also their spleen volumes as well. On symptom score, we had at that point in December 62% had reached a TSS 50 up to the nine months worth of therapy. That was some patients that had only completed three months worth of therapy that had gotten TSS 50, some at six months, TSS 50. What we were seeing was a gradual improvement in that as time went on. This is for patients who had been on ruxolitinib for a long time.
These are patients on standard of care if the average was about three years. It was a really impressive result to see 60% of them actually getting a TSS5 0. There is some marker of comparator in first-line therapy with a JAK inhibitor. They see something like 40% of patients getting a TSS 50. Adding another drug on top of that and lifting those patients who were all suboptimally controlled to a TSS 50 is really impressive. The patient numbers are small, but the size of the result, I think, makes it stand out. The consistency that we were seeing at that point going through to nine months was also quite impressive. The other side of that was the spleen volume, where we measure the reduction in spleen volume as a percentage. Many of these patients have a spleen that is over three L in size.
It is a very large spleen. A healthy patient would have a spleen of around about 250 to 300 mL That is 10 times the size of a normal patient's spleen. Again, we saw patients improving over time, getting better the longer they were on drug, which is a novel finding. We have not seen any other drugs where patients out beyond six months also can still continue to improve in their symptom score and their spleen volume. That was really encouraging. A spleen volume response of 25% is deemed to be both clinically significant for this group of suboptimal patients, but also from a regulatory point of view, we believe the FDA will probably look at SVR25 as one of the endpoints in the study coming forward.
We were seeing at this point that we had three patients out at nine months that had achieved an SVR25. We are now waiting to see what the results look like when we get more patients getting through to these kind of endpoints. Overall, we were seeing a very consistent result with the monotherapy when we used the drug on its own in an earlier study in that it was very safe and very well tolerated. There' s a fairly mixed patient population we had here. We are very confident now that the safety result we are seeing is going to be reproducible in larger patient numbers. The safety of the drug stands out as being one of its key features and one that really differentiates it from the competition. I think despite the small sample size that we saw, the improvement in symptom score was very encouraging.
Although it's a small number of patients, it's certainly a best-in-class result that we're seeing there in terms of the number of patients getting to that level of improvement, particularly given their history and long time on ruxolitinib before coming into the study. The fact that both the improvement in symptoms and spleen continue to improve over time, again is a very novel finding. We are now coming up to the next data point, which is going to be at the European Hematology Association meeting in June. That data will contain all the patients in the study completing nine months' worth of therapy and the majority of patients getting to 12 months worth of therapy as well. It is a considerable additional data point from what we declared, what we showed at the American Society of Hematology in December.
We think that that data set will help inform our discussions with regulatory bodies like the FDA and the European Medicines Agency in the second half of 2025. We expect to get guidance back from the FDA in quarter three on how we progress the study, what they think of the data, and how we progress the study to the next clinical trial. Our pipeline now looks, I think, quite healthy. 5505, the lead drug is in two different diseases. The myelofibrosis one, which is obviously the lead that we've talked about with that interim 12-month data coming out in June. Myelodysplastic syndrome, two studies funded by grant money from the Australian government and the German Cancer Fund, where we expect both of those studies to kick off around the middle of the year. We're getting interim data in the first half of next year.
The Skin Scarring Program with 9465, that's a new drug going into phase I for the first time. The first part of that study is looking at healthy volunteers and checking safety and the PKPD of the drug. How much is getting into the skin? Is it inhibiting the enzymes in the skin that we're seeing? The second part of that study is where we're looking at patients with hypertrophic scars, where we expect to see the impact of the treatment over three months. We'll get data back again in the first half of next year from that. Meanwhile, Professor Wood and her group will be looking at keloid scarring with another independent investigator study that we'll be supporting her with. Last but not least, 4728 is a drug which is in a fully funded study by Parkinson's UK.
It's in a sleep disorder where patients progress to Parkinson's disease in a high number of them. That study is recruiting in Australia for some months now. In this last quarter, we announced that the U.K. site, which had been delayed, has overcome the technical problems they had with the PET scanner that they were using in the study to scan these patients' brains. That's overcome. The patients are now starting to be recruited. We expect full recruitment by the end of the year and data in the first half of next year. Finishing on the all-important news flow and what's going to drive value in the upcoming months. Clearly, the key thing here is that data coming out at the European Hematology Association meeting. It's going to be on the 12th to the 15th of June.
We're in a poster session, which is taking place on Saturday, the 14th of June, which is early morning on the Sunday, the 15th here in Australia. We will make sure that we disclose that data in an appropriate fashion alongside what's going on at the Hematology Association meeting in Milan. After that, we're still on track to submit our briefing book to the FDA, which is proposing the next stage pivotal study, phase II, III study for myelofibrosis alongside the interim data from this study to the FDA. We expect to get an answer back from the FDA in quarter three. I've mentioned already those two myelodysplastic syndrome studies starting around the middle of the year, as well as that hypertrophic skin scarring study as well starting.
It's a busy time for the team here at Syntara with a number of trials kicking off and a number of trials producing data and quite a lot of interaction with regulatory authorities at the same time. If we look forward to the first half of next year, which is 12 to 18 months down the road, we've got three studies due to, in fact we've got the IRBD study due to report in the first half. We've got the two myelodysplastic studies due to produce interim data coming out at that time period. Also the skin scarring study as well. In a biotech company, we've cash through the next 18 months with data from studies that are fully funded coming through in that time and a really key data drop coming up in the very near future in the middle of June.
With that, I'll hand back to Matt and happy to take any questions from the audience at this point.
Thanks, Gary. Just a reminder to everyone again, if you have a question you'd like to submit please feel free to do so using the option within Zoom, and we'll go from there. Gary you've touched on it a bit there around EHA in June. All going well with that. Can you just speak again to what investors can expect from there with 5505 and the next milestones they should be looking for?
I think the things to look for are primarily the endpoints which are going to be drivers for that agreement with the FDA on the next clinical study. I mean, that's we're looking for some degree of confidence that we've got a drug which can hit endpoints which the regulators value.
Those two are the TSS 50 and the spleen volume reduction. I think those are the two things that we will certainly be looking at very, very closely when we are putting the data package together for that poster presentation. Clearly, safety as well is an ongoing thing you never take your eye off that. We have got, I think, increasingly comfortable with the safety profile of the drug and that we really have not seen anything to date which causes any concern. It is the thing that opinion leaders, hematologists globally have all remarked on, that this is a key asset going forward.
Just as a reminder, the drugs that are on the market now, the JAK inhibitors, and also the drugs that are in development, most of them have a tolerability profile which includes quite a lot of hematological toxicity and cytopenias that they cause in a number of the patients that are taking the drugs. That being absent in our drug means that this is a clean drug which could be added on to the current standard of care without making these patients feel worse. That is a key aspect of it. Yes, looking at what you should be keeping your eye on, I think it is those two things. In December, we showed a very encouraging symptom score improvement and one that looked like it was improving over time.
And also an emerging story around spleen volume where we were seeing patients who, after three years on ruxolitinib and not being well treated, and their symptom scores going up and getting worse, to see both symptom score and some response in the spleens from those patients after that length of time on ruxolitinib, I think was really encouraging. We are hoping when we take these patients out to 12 months, but also the additional patient data we are going to get at nine months and concluding the six-month data as well is going to be important. Those are the things to look for.
Thank you.
You touched on it there, but just to maybe be slightly more specific, the question that's come through is, given we are still waiting data release from myelofibrosis, can you confirm whether or not engagement with the FDA commenced before then based on preliminary results?
Yeah. The FDA work on a very sort of specific timeframe. I know that there's been lots of noise in the media around what's happening with the FDA and redundancies and things. I was encouraged to hear the new head of the FDA talking about still the importance of rare diseases, which myelofibrosis fits into. We are not anticipating at this point in time any change in their timetable. The data set that we are presenting in Milan in June will form the basis for the briefing book that goes into the FDA in June.
They work on a specific timetable, which means that we expect to get an answer back in quarter three. I think we can be more specific about that as time goes on. We are working more or less on schedule. We've maybe lost a couple of weeks while we're waiting for data from digging into certain aspects of the database that we've got and waiting on third-party companies to produce analysis of the data we've got. We've got the full package together to give to the FDA, but still expecting to get that into the FDA in the near term and get a response back in quarter three.
Thank you. Another question that's come through is, is there the possibility of commercialization of 5505 upon delivery of positive phase II data without the requirement for a full phase III study?
It depends what you mean by commercialization. I think that there is obviously an opportunity to partner the drug at this stage. We will be working these things in parallel. At the same time, and I should say that whether we go ahead and do the phase II, study that would enable us to get a registration package together, an approval for the drug and commercialization in the sense of actually selling it globally as a product to patients with myelofibrosis, or whether we look to attract a partner and license the drug at this earlier stage, both of those outcomes depend on us getting a positive readout from the FDA, which says, "Yes, we think your data is enough to support you going into the next clinical study. Yes, we think the safety profile is okay.
You need to get this number of patients more to convince us that it's okay to approve. These are the endpoints that we are looking for. I think we can go one of two ways here, either down the partnering route or down the route of doing the next study. Both of them depend on the data that comes out in June and then the subsequent response from the FDA in terms of the outcome of the meeting that we have with them.
Thanks, Gary. The next question is, how are you thinking about including additional JAK inhibitors in the phase II, III trial, particularly testing my pronunciation here ?
Yeah, momelotinib. Yeah, yeah. That's pretty good.
Given its growing share, particularly in the anaemic population.
Yeah. It's good to see I think, that momelotinib, I think has made a good start in the market.
It is being used in myelofibrosis patients, as the question suggests with anemia. It's interesting to see that it's growing the market rather than cannibalizing the market. It does not appear to be taking patients away from ruxolitinib. If you look at their scripts, their quarterly scripts, they look pretty stable. What we're seeing is a group of patients who are not on ruxolitinib that are suddenly being made available for momelotinib. It will be interesting to see how that develops over time. Ruxolitinib, though, is still by far the largest drug in the market by units. I also note that it's going to be coming off patent in 2028, at which point there will be a price differential between ruxolitinib and momelotinib. I think market share of ruxolitinib will remain high, and the number of patients taking it will remain high for a long time.
It will be one of the questions that we discuss with the FDA, will be whether this next study coming up should be including just one JAK inhibitor, whether there needs to be whether that would give us a label for then treating our drug on top of any JAK inhibitor that's in the market, or whether it would be specific to ruxolitinib. What kind of data will we need to generate in order to get our drug approved for use on top of other JAK inhibitors as well as RUX? It is a good question and one that we'll be discussing with the FDA in some detail, I imagine.
Thank you. The next question is, have any other competitor trials had SVR25 rather than 35 as an endpoint?
Yes.
The most recent studies, we believe from reading FDA minutes and talking with consultants, would appear that in the suboptimal population, SVR25 is an acceptable endpoint. It will be a discussion point with the FDA when we get there. From what we're seeing, there is enough precedent to suggest that SVR25 is a, in this patient population, I should just add that the clinicians believe that SVR10 is actually significant for their patients. Given the length of time the patients in our study have been on RUX, they certainly think that any improvement in spleen volume is clinically significant. From a regulatory perspective, we believe that a 25% reduction in SVR would be acceptable. One of those things that will be a question for the FDA.
Thanks, Gary.
Today, as we discussed earlier, we've seen another company in the sector, Dimerix, announce a licensing deal. Can you just speak to your view and a sort of approach to a potential licensing deal for Syntara and the potential to do that with 5505?
Yeah, I guess these deals done with drugs like 5505 at this stage. If we talk about a deal that's done after phase III, then we've got plenty of comparators out there. The last three deals have been north of $1.7 billion. The last one was actually $2.9 billion for a drug which was going to be added on top of a JAK inhibitor, which has subsequently had a safety problem. The comparators there for a deal that's done after that stage are there and very clear.
If we look at comparator deals that are done for drugs in phase II, I think there are a limited number of comparators. We've got our own internal ones where we've licensed a drug in the past. At the end of phase I, upfronts or before starting phase II, we had revenues of above $80 million taken in and a total deal value of around about $750 million. That was for a phase II
asset. This drug is in phase II It's a large market and an attractive one. We think a sizable upfront followed by development milestones is also certainly possible for a drug at an earlier stage. Again, there's different ways of looking at value and different strategies of getting to those points.
We want to keep both our options open at this point and certainly go ahead and plan for conducting the next study because that's the, as I mentioned during the presentation, getting that approval from the FDA is a key marker of value both for potential partners now and for people that are going to invest in the follow-up study as well.
Thank you. The next question, just someone's emailed through asking, can you provide an updated status on the skin scarring studies?
Yes, we've announced a couple of months back, 9465, going into phase I.
I think this is a really nice way of illustrating the strength of this entire business model in that having an internal drug discovery group and with all the compounds we've produced come from our own team meant that once we saw the benefits of that first-generation drug, SIG-302, in the studies that Fiona Wood and her team conducted over in Perth, we were able to quickly analyze the improvements that we could make both in study design and also in the actual drug itself to make sure that we were maximizing both the tolerability profile of the drug and its ability to inhibit those key lysolocasase enzymes in the skin at a high level for 24 hours with a daily application. And 9465 was brought through really, really quickly. I'm really proud of the effort the team made there to get that through.
It's gone through all the preclinical testing in a very short period of time. In the next couple of months, we will initiate that phase I study. The first part of that study will be looking at healthy volunteer patients using a gradually increasing dose of the topical cream just to make sure that we have seen an improvement in tolerability that we expect from the design of the drug.
Once that's done, we will go into patients probably in two or maybe three centers, all of them in Australia, looking for patients with hypertrophic scars and looking at them over a period of three months and comparing the scars at the end of three months with the baseline at the beginning to see whether we're seeing also, as well as the changes in structure that we saw in the previous study with SIG-302, also looking to see if we can get a change in the appearance and the physical properties of the scar as well.
Thank you. Another one on skin scarring was, are the trials for hypertrophic and keloid scars being conducted together or separately in Perth, and are you looking at other sites?
They're very much separate studies.
The one in hypertrophic scars with 9465 is a Syntara-sponsored study where we will be working directly with the CRO in a number of centers across Australia to conduct and recruit those patients. The keloid scarring one is very much under the management of the Fiona Wood Foundation and UWA and the work that they do together. That will be a study that is probably done in centers around Perth.
Thank you. One final one was, are you proposing to use AI tools to expedite trial analysis and results in skin scarring again?
Not just in skin scarring, also in looking at the bone marrow fibrosis samples that we take within the myelofibrosis study as well, whether it is machine learning or AI. We are using the latest technology to analyze the cell makeup of tissue samples that we take both from the skin and from bone marrow.
Also, in the imaging that we take of the scars, we're using the latest technology we can to measure and look at three-dimensional images, for example, of the scars to check on volume as well as appearance, pigmentation, a number of different parameters. Yeah, we stay abreast of the latest techniques in this area and try to utilize them wherever appropriate to make sure that we have the best assessment of the clinical samples that we have from patients to make sure that we reach the clearest conclusions that we can w e're not missing anything.
Another question is, is there any particular reason for the slight delay in MDS trials?
These are independent investigator studies, so they're not something that we have direct control over at the start of. There were some small hiccups in the drug supply.
There was another company supplying drug to the Australian study. Those have been ironed out now. Both studies now are in the final stages before kicking off. Yeah, it's almost inevitable when these are the most important things for us. Clearly, some of the centers which are involved in these studies, they've got several other things going on at the same time. Their priorities change slightly. We believe both studies now are in the final stages before starting. There's a lot of enthusiasm in the multiple centers that are involved, both in Australia and Germany, to look at this drug. Yeah, both of them got a very high ranking within the hematology community of both countries to go ahead and progress. Once we've got some of the admin and bureaucracy out of the way, I think they'll both recruit well.
We look forward to seeing results of that in the first half next year.
Thanks, Gary. That's all the questions. I'll just throw it back to you to provide a closing comment.
Thanks. Thanks all for your time. Obviously, we're looking forward to this quarter that we're in now. It's only a matter of weeks, really, before we get a chance to review that next lot of data from the myelofibrosis study. It's going to be an exciting time. I look forward to talking to you again at that point when we've got that data out there again. Thanks very much.