Thank you for standing by and welcome to the Syntara Investor Webinar today, following the company's earlier announcement of FDA guidance on the clinical development of amsulostat. All participants are in a listen-only mode. There will be an initial comment provided by management, after which we will focus on Q&A based on questions submitted via email and live during the session. If you'd like to submit a question, please do so using the Q&A function within Zoom. On the webinar from Syntara, we have the CEO, Gary Phillips. I'll hand it over to Gary first. Please go ahead.
Thanks, Matt. Good morning, everybody. Thank you for your time this morning. I'll keep my commentary relatively brief to allow enough time for any questions that you have. I want to cover off three different aspects. The first one is the actual FDA guidance itself and talk about what they've given us as feedback on the proposal that we gave them and the implications for the clinical development of amsulostat going forward. I want to talk a little bit about the impact of this on potential funding and partnering. What are the implications of the FDA guidance on that? Finally, I'll end up with a little bit on the cash position of the company and the news flow that's yet to come. If we start on the FDA guidance, we received the guidance on Saturday, actually after end of close of business in Washington on their Friday, our Saturday.
We haven't had that long to digest the information they've given us. What I'm going to talk about here is our impressions of what we've been given. There is still quite a bit of work inside the company to do in terms of understanding the exact implications for the clinical development and the costs in the sector that we're incurring. With that, I think we're comfortable that we can give you a good understanding and insight into where we sit. First of all, that FDA guidance. We had given them the data package that was more or less the same that we issued in June at the European Hematology Association for amsulostat in that phase II study in combination with ruxolitinib. We proposed that we would go to a phase III study looking at the suboptimal patient group in myelofibrosis.
The FDA has come back and has taken, I think, a more conservative approach to the process that we would go through to get approval for the drug. I think it's reassuring that they have given us a pathway forward. It's not exactly the fast track that we were looking for to get through there quickly by going straight to a pivotal study. Nevertheless, their guidance is extremely helpful. What their, I think, concern is that the lack of any control data in the phase II study, which we're currently undertaking, makes it really difficult for them to judge the safety and efficacy of our drug in a manner which gives them enough confidence to agree on the trial design for phase III. I think that's the fundamental thing here, that lack of control data and how do we characterize these suboptimal patients.
What they're suggesting is a better way forward is to undertake, rather than a phase II/III study. What we were planning here was to, you know, patients would be enrolled. We would take a look after the first sort of 80 patients or so were through the study and look at whether they met certain criteria and then spill them all over into a phase III. A so-called adaptive design with a phase II patient running into phase III. The cost of that study would have been in the order of around about AUD 80 million and undertaken about 300 patients. The FDA's guidance suggests that a better way of approaching this would be to do first, to split that one study into two. You start with a phase II-B study. In that study, we would have a control group on placebo.
We would look to really have a study design which helps us fully characterize the patients coming into the study and make sure we really understand the baseline of suboptimal patients. What does characterize what is a suboptimal patient and what is their baseline data coming in? That way, the results of the II-B give us absolute clarity on safety and efficacy and allow us to design a phase III study, which is, I guess, more powerful and reduces clinical risk going into phase III. A good phase II-B study with a good result would mean that the phase III study we need to run is potentially smaller than the one we would need to run if we were doing it the way we were opposed to doing it.
The endpoints would be much clearer and would have less risk around them because we would have the results of the phase II-B to lean upon. I think it's not that there's anything in the FDA guidance about this, but it's our own interpretation from talking to our regulatory advisors. Good phase II-B data can also generate you in a position where you can get breakthrough status and therefore get a faster approval as well. This is undeniably a slowdown in the development pathway. This will take us longer to go through a II-B and then a III than it would have done to that phase II/III adaptive design. There may be some additional costs incurred in that in time, but it may not be as big as we first think about when you think about the potential impact of doing a positive phase II-B study.
I think the next thing I wanted to just talk about was the funding of this study and the partnering of this study. We had talked previously about running two things in parallel, and that was to run a partnering process for the drug at the same time as looking at the possibility of raising money to do that phase III study. That really hasn't changed. We will still be now putting forward at the end of this whole process a further engagement with the FDA once we have the final study report of the ongoing study at the moment. We have clear guidance on the next clinical development path, which is what we wanted to get and what potential partners will value.
It's not the final pathway to the final approval that we were hoping to get, but it still is the clinical pathway to success and approval from the FDA that gives us certainty for a partner to be able to value the asset and engage in a potential partner discussion. That timetable and the approach to this remains the same as it was before.
I guess you should also think about that, although for us as a company, moving quickly through to phase III was the right thing to do, a larger company, which doesn't have the same restrictions on capital raising and time to market as we do, for them, probably the sense that another way of looking at this would be that from where we are now, they may well have chosen to do a phase II-B study followed by a phase III rather than the phase II/III that we were proposing to do. In actual fact, the guidance coming out of the FDA is extremely important and valuable for that partnering process, which I would still expect to run to the same kind of timetables that we had before. I guess lastly, to talk about those differences in cost and timeline and whatever.
We previously guided that we had cash until the middle of next year. There is a considerable investment in additional materials and trials that need to be done before you start phase III. We were anticipating that we would have to, for example, there's an additional study that you need to start before phase III called a human mass balance study. That's in the order of AUD 4 million or AUD 5 million. We no longer need to do that because we're not proposing to go straight to phase III. We're now guiding that the cash that we have on hand, so we were at AUD 15 million at the end of June. There's obviously the R&D tax credit that you'd need to take into account in both this year and the following year. The cash we have will now take us through to 2027.
I would just point you to the strength of the business model of Syntara in that, you know, we are not a one shot on goal. Whilst we still have the possibility of developing amsulostat in myelofibrosis and partnering that drug in that indication with what has been and is still acknowledged to be impressive data that came out of that phase II study, it's still a competitive drug now with a pathway forward approved by the FDA. We also have a number of other studies that will read out within the runway that the company has. They include, in no particular order, the two studies on myelodysplastic syndrome, which I would remind you are largely funded by non-dilutive cash that comes from that side. That doesn't take away from our cash runway. Both of those studies are extremely important.
Both give us a chance at increasing the value of the asset, also providing additional safety and efficacy data that will be useful for the FDA in their review of our drug in the future as well. Secondly, the skin scarring program, there's two studies that are active, one in keloid scars run by Professor Fiona Wood and another one in hypertrophic scars that we're running ourselves. Both of those studies should read out during calendar year 2026. Finally, but not least, the study that's fully funded by Parkinson’s UK in that sleep disorder where patients are liable to progress to Parkinson’s on the back of that disease. That study is more than 50% recruited now. We expect it to be fully recruited by the end of the year. It's a double-blind placebo-controlled study, three months in duration.
If it recruits by the end of the year, that study will give us an outcome in the second quarter of 2026 calendar year. On that note, I think I'll pause there and I'm happy to take any questions that the audience has that Matt's gathered over the email as well.
Thanks, Gary. Just a reminder again, if anyone has a question, please type it in using the Q&A function within Zoom and we'll get through as many as we can now. Gary, the first question is, how much will phase II-B trial cost?
I'll just preface this by saying, you know, we are digesting what the FDA have told us and trying to work that out. A phase II-B study was one of the options that we had going forward as a clinical development path. In our planning process, we came up with a study that was around about 90 patients in size to do a phase II-B. That would entail probably 60 patients on active and 30 patients on placebo. That study would be in the order of $25 million. Comparing that with the AUD 80+ million for the phase III study, you can see that the cash need to run that study is much lower. From a time perspective, I think that study would take 12 - 18 months to recruit.
You're looking at a two-year process for the phase II-B versus a probable three-year or a bit more process for the phase III. You then have to do the phase III on the back of that. As I said, it won't be the same phase III that we were talking about before. The additional cost is around about $25 million.
Thank you. On that note, how will you fund the phase II-B and what are your options to fund it in other ways or non-dilutive ways?
The options are the same as we had before. This is the FDA has given us a different clinical path, but everything else around this asset stays the same. We still have positive phase II data, which shows the drug to have a very interesting and exciting commercial profile and clinical profile for the market in suboptimal patients with myelofibrosis. As far as the, you've got two ways of funding this. One is to partner the drug. Again, the timeline and the process will stay the same. We now have got FDA guidance on what the next stage in the clinical pathway is, which gives certainty to potential partners about how to think about the drug stage and what stage they'd be taking it over at. This is not a drug with no clinical data, with no efficacy or safety data that they can evaluate.
This is a drug which is ready to go to the next stage of clinical development. That next stage is a phase II-B study as opposed to a phase II/III adaptive design. The appetite for companies to pick up drugs in phase II-B is still strong. It's still an asset that's got clinical data sitting there. It's not an unknown. It's not just a phase I asset or even a preclinical asset. We as a company have sold an asset previously in the middle of phase I with no clinical data that had AUD 83 million in upfront payments and a deal size of AUD 750 million. There is another company out there which was bought by Takeda at the end of last year, which had phase II data and maybe it was a little bit more advanced than we've got.
They had some data in MDS as well as myelofibrosis, which we will have next year. They had $200 million upfront and a deal value of more than $1 billion. There are two comparators there to say that partnering a drug with phase II data that's ready to go into a II-B is absolutely still on the cards and that's still a very, very strong option in terms of funding the next study going forward. Timetable for that will be in the first half of next year, probably once we've got probably a further bit of guidance from the FDA on what that II-B study exactly looks like. They've given us high-level guidance, but the next step would be a protocol for them to review.
We will be discussing this with potential partners and taking their suggestions also on the design of the study as well into account before we go back to the FDA again. That is certainly one way. The other way is clearly still to raise money to do this. That's why I talk about the runway that we have and the other assets that are still to produce clinical trial news flow coming in the next half of the year. We are in the same stage as many biotechs are approaching the next stage of clinical development, but with the benefit that we have additional assets that can still produce a news flow, which generates capital appreciation in the share price and the possibilities of funding money. This is by no means a situation where the company is in a much worse state than it was before.
We have had a delay, which maybe affects the asset value because it's seen as being phase II-B ready rather than phase III ready. Other than that, it's still very much the same options apply as did before.
Thanks, Gary. The next question, I know you touched on it, but if there's any color to add, was how many patients are needed for the trial?
Yeah, so our first, as I said, a pre-existing plan suggested that the II-B would be around 90 patients. You need to think of that in the way as well, the impact on phase III. The phase III study, you know, the FDA requires a minimum number of patients with safety data in order to get to approval. That was part of the reason why the phase III study had to be around the 300 + patient mark. The fact that we would undertake a II-B and put those 90 patients counts towards that overall safety database. That's why I say the consequent phase III after that might not be as large. We think the relevant number is subject to looking at the stats and everything else, but it's around about the 90 patient mark for the II-B.
Thank you. The next question is, how do you see the design of the trial capturing safety and efficacy in an efficient manner?
It's going back to the key element of the guidance from the FDA. We need to put in patients on a placebo within the study. We also need to make sure that we understand the baseline of those patients going in. There's a possibility here to have recruiting patients that are suboptimally controlled and then monitoring them for, say, two to three months to make sure we collect enough data on where they sit before randomizing them to drug. When we talk about efficiency, it's about clearly understanding the entry criteria for the patients coming in, making sure, and the FDA have also, I think, given us some helpful thoughts here on how to characterize these patients in terms of their symptom score or their spleen size.
They've left a number of questions open, which we can, under the fast track designation, we're in a position to dialogue with them over narrowing that down and coming up with a trial protocol, which gives us definitive data in this patient group to make sure that the subsequent phase III is designed as optimized and as efficient as possible so it can be as small as possible and as quick as possible with as few patients as possible.
Thank you. What sort of endpoints are being considered for the phase II-B?
The phase II-B would again be the endpoints of symptom score and spleen volume.
Following on from that, someone's asked, are there precedent clinical trials that have been run in suboptimally dosed myelofibrosis patients to understand the patient population?
There have been a number, but I think there's quite a few of them that there have been still some differences, I would say. The way that different trials, we've done quite a good scan of the universe here in terms of trials that have been run, and there's not a universal sort of set of parameters that guide what is a suboptimal patient. I think that goes somewhat to the heart of the FDA's guidance as well, that needs to be really hammered down before we project into certainly a phase III study. That's partly the reason why you do the phase II-B, right? You could be in a situation where the II-B, we set this II-B criteria, but then we narrow it even further when we get to the phase III based on the results that we see.
Thank you. Just a couple of questions with regards to partnering. Does the outcome announced this morning hurt your chances of partnering the drug?
Hopefully, I've addressed that a bit, but just to reiterate the point, there are many, many drugs which are partnered when they finish phase II-A studies and they're about to go into a phase II-B study. The valuation might be less than the study that's ready to go straight into phase III, but the number and frequency and also the value of those deals that are done for drugs that go, that are, you know, II-B ready, one study away from a pivotal, are still very significant. Whilst the outcome from the FDA does represent a slowdown in the clinical development path that we had proposed, it doesn't remove the value of the asset and it also still acknowledges that we do have sufficient safety and efficacy data to move on with this drug and into II-B.
In my view, this is still very much a drug which is in the market and will be attractive for a number of people, a number of companies to look at.
Does the longer path to approval expedite the desire to find a partner with a larger resource base to conduct the phase II-B trial quickly?
I don't think so. I think the phase II-B is a smaller undertaking than the phase III. If anything, it would be the other way around, that the phase III study would have demanded that you picked up a company that had hematological experience in running hematological trials globally, because that study would have been probably north of 100 clinical trial sites run in many countries. The II-B is a smaller undertaking. The cash that you require to run it is also smaller. I think that opens up the field actually to more companies that might want to do that, that wouldn't have the capacity or the bandwidth to start running at those big phase III studies that would see a II-B as being quite an attractive proposition.
The next question is, does this alter your view on the portfolio within the company and the potential need to add new assets?
We certainly don't need to add new assets. We have a number of assets that are being progressed, mainly under non-dilutive funding that the company has got because of the quality of those programs underway already. We haven't been standing still and just doing one thing. We found a way, you know, that the team here has been extremely good at developing drugs which make it through from preclinical and into the clinic, which is a huge, a very positive thing in its own right. We have also found ways of identifying sources of non-dilutive funding to move those drugs into clinical trials where you will see efficacy and safety. You do see proof of clinical concept with those studies with non-dilutive funding, which is, I think, really good value for shareholders.
They haven't been asked to put their hands in their pocket to do that, but we get the benefit of those trials reading out within the cash runway that the company has.
Will the additional phase II trial potentially reduce the patient number for the eventual phase III trial provided the efficacy remains the same?
Potentially, yes. I think, as I mentioned, one of the drivers of the size of the phase III is that when you go for approval, you have to have a minimum number of patients that are exposed on the drug from a safety perspective for the FDA to be confident to give it an approval. That includes the patients within that safety database, includes all the patients in previous studies. At the moment, we've had more than 40 patients exposed to amsulostat for more than a month in the trials, up to 12 months in the data from the two studies, the monotherapy and the combination study we run already.
The phase II-B study would also contribute to that database so that the final number in the phase III will be driven more by the powering that you need to show efficacy in symptom score and spleen volume, and not by the need for the numbers of patients in the safety database, which is what drove our estimate for the phase III of 300 or more patients.
Could amsulostat be sold to the interested parties that Gary has mentioned previously, and is this something that you would potentially explore?
Yes, we will be re-approaching the companies that we've talked to already this year with the update from the FDA, with the guidance on the phase II-B, and with a timeline which takes us through to a phase II-B further discussion with the FDA at the beginning of next year.
The next question is, have all the phase II-A patients completed dosing?
We are currently evaluating the last few patients to come through, so we don't have all the data yet. Data cutoff is approaching, and we still estimate that we will have the top line data from the study from all the patients at 12 months by the end of this quarter.
The announcement mentions the cash runway for the company reaching first half 2027. What's changed from the previous target that was within 2026?
That guidance on the runway taking us into 2027 is due to the postponing of activities that would have been necessary to do the phase III. As you can imagine, this news is fresh for us, so we have to do a more detailed look. What I'm giving you there in terms of guidance on the cash runway is just a first high-level look at removing the things that we knew we had to do to gear up for a phase III. That is still subject to change, but as I say, we will take a very close look at all the activities in the company and the expenses to see what we now need to do to make sure that we've got the cash to deliver on the milestones that are still standing out there from studies underway.
Also, you know, go into the position of potential partner discussions with strength.
Given the lack of definition for suboptimal patients, what are the inclusion/exclusion criteria being proposed for recruitment?
I think the ones that we have in our mind is really the minimum level of symptom score and the minimum spleen size are the two criteria. I think the discussion with the FDA is around making sure that we fully understand that and the variability in those potential endpoints for the patients going into the study and what their history is going in. There may be other factors which come into play here and other things, but that's something that we'll take up with our clinician advisors as well in terms of how they define suboptimal, which are the patients on JAK inhibitors and ruxolitinib in particular that they feel need further treatments and warrant access to a drug like amsulostat.
Would Syntara potentially change tech and focus on 9465 seeing as dermal treatments have a lower regulatory bar?
I think we're in a good position here in that we have those two studies running. They are funded and they will deliver results which I believe will be pivotal in valuing that program and taking it forward. There's nothing more that we need to do with those two programs to get to the point where we do have data that tells us whether those drugs have a real value to shareholders. There's nothing new that we need to do there. At the same time, the cost expenditure on the amsulostat and myelofibrosis is actually coming to that study, the existing study is coming to a close. We don't need to spend anything more on that drug at the moment until we evaluate and decide on a pathway forward.
Next question is, why the delay in the phase II-B study being in 2026? Why could it not be sooner?
In terms of starting the phase II-B study?
That's my read on it, Gary, yes.
Yeah, the process we would now go through is similar to the start of the phase III in that, you know, we would, if we decide to go ahead with a II-B, then we would be submitting probably a type C meeting application. Once we have the full study report from the existing study, we would then go through a period of three to four months with the FDA of discussing that, and it would include a protocol design for the phase II-B study. Once you have that, you can commission obviously the contract research organizations and go ahead with it. A phase II-B could potentially start in the second half of 2026 if you wanted it to.
Thank you. When will data from the 9465 trial be available?
We expect data coming out of the existing hypertrophic scar study. That's got two parts to it. The first part is the safety data and PK/PD data that tells us that the drug is well tolerated and is achieving the right level of enzyme inhibition in the skin. That data will come probably end of the year, beginning of next year. Once that's in, it kicks over into a study for a three-month study with patients with hypertrophic scars, and we think the results from that study will be around the middle of next year. The keloid scarring study, which Professor Fiona Wood is running, is an independent investigator study that she's running. I don't have a clear insight into the timing of that study, but they're recruiting patients already. We would expect results from that study around the middle or right towards the end of next year.
Maybe a bit hard to speculate on, but do you think there was a change in the FDA's approach compared to Syntara's expectations given the U.S. government's shift in attitude to supporting more American pharmaceutical development and manufacturing?
No, I don't think so. No, I think this is, they're purely reacting to the ongoing development in myelofibrosis and other drug trials which are ongoing and seeing the difficulty that some companies have had in characterizing suboptimal patients and measuring baselines. There have been some notable drugs in phase III where they haven't seen the expected symptom score improvements in patients when they get to the end of the study, and where the placebo arm has done better than expected. I think that's just probably given them pause for thought in making sure that the companies going into this space better characterize what is a suboptimal patient and what is their baseline going into the study.
Thanks, Gary. I don't have any more questions in the queue, so I'll throw it back to you just to provide a closing comment.
Thank you, Matt, and thanks everybody for their attention today. It's disappointing. I can see from the reaction of the market that this has been a surprise. It wasn't something that we wanted to see coming back from the FDA. I would like to leave on a note of giving context to this in that the study, the clinical development pathway that's proposed by the FDA is still a solid one forward that recognizes the value of the asset and its potential benefit for myelofibrosis patients that were not well controlled on a JAK inhibitor. That value and the fact that we've seen the number of inpatients we've seen improve in their symptom score by 50% or more who've been on ruxolitinib for four or five years still stands there.
The reduction we've seen in spleen size in those patients as well still stands there as a testament to that this drug has value and can go forward. What we are saying here today is that the pathway forward is slightly slower than the one that we had hoped for, but it still gives a clear pathway to value, a clear pathway to potential partnering. Along with the other assets in the Syntara pipeline, this is a company which is going to deliver a lot of potential news flow which can positively impact valuation of the company within the runway of cash that we have. Thank you very much for your time, and I'm happy to answer follow-up questions as well if anybody has them after the podcast is finished.
Thanks, Gary, and thanks again to everyone for joining today.