Thanks for standing by, and welcome to the Syntara Investor webinar, following the company's announcement today of top-line data from its phase 2A clinical trial of amsulastat to treat myelofibrosis, as well as strategic advisors appointed to further the development of this program going forward. All participants are in a listen-only mode. There'll be an initial comment provided by a presentation from management, after which we'll 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, and we'll be focusing on questions regarding today's announcements. On the webinar from Syntara, we have the CEO, Gary Phillips, and I'll hand it over to him now.
Thanks, Matt. Thank you all for joining this morning. So we put out a couple of interim data sets from this study. So while I realize some of this may feel a bit déjà vu, it is the final data from the study. It's obviously still analysis to go through that would be put into regulatory submissions, but this is the final top-line data that we get from the study. And it gives us a chance to really look at the totality of the data, the context of it, and what it means for both the drug and the company. So I'm delighted to have this opportunity to talk to you this morning.
I'm going to skip through the usual introduction of the company and whatever the slides are there for those of you that are not as familiar with the company to go into, and I'm happy to answer any questions on it at the end. Just a note though, before we go into the clinical trial itself on cash, so we put out an announcement last week for AUD 5.6 million in R&D tax credit. So the pro forma cash balance as at the end of June was nearly AUD 21 million. That amount of cash takes the company through to the beginning of 2027. And I'd ask you to remember that when we get to look at the pipeline of assets that this company has developed over the last few years and the number of news flow items that are coming within that runway.
Also point you towards the research coverage that the company has from four separate organizations: Canaccord, Bells, Euroz, and Evolution. Myelofibrosis, just to remind you, is a bone marrow cancer that disrupts the body's normal production of blood cells. Patients have about five years of life expectancy from onset and typically get very large spleens, lowering blood counts and lots of symptoms that go along with it. Standard of care at the moment is a drug called a JAK inhibitor. Sales of JAK inhibitors are between one and two billion a year, despite only really treating the symptoms of the disease. That level of unmet need has meant that there's a large commercial opportunity in this disease area, which is largely unserved by new drugs coming through.
And the last three exits in this area have been north of AUD1.7 billion. So for drugs with phase 3 data, so an attractive commercial area, one with a high unmet clinical need with patients that are really in need of new treatments. Our drug works through inhibiting an enzyme called lysyl oxidase. Lysyl oxidase is involved in two things. One is the cross-linking of collagen fibers and stiffening of the bone marrow, which causes aberrant cell production, but also by upregulating a channel called PDGFR, which also boosts growth factor-induced cell division and yet proliferation of fibroblasts and activated immune cells. This is a bypass mechanism for the JAK-STAT pathway, which the JAK inhibitors go through.
So if you can inhibit lysyl oxidase and have an impact both on the bone microenvironment and on this PDGFR route, then you stand a good chance of having something which works well in combination with the current standard of care. The study we engaged in was an open label study with 16 patients recruited. I think notably here, I mean, we had nine patients discontinue during the study. So we had seven patients who completed 52 weeks. The dropout rate in this study is what you would expect to see in patients with this level of disease severity. On the right-hand side, you see the characteristics of the patients that we've recruited. These patients had, on average, more than three years of treatment with ruxolitinib before entering the study. They were symptomatic and they had enlarged spleens.
This was a patient group with a high disease burden where you would expect to see this level of dropouts going through. So the withdrawal rate was consistent with what has been seen in other studies with patients of similar disease severity. Of note though, of those nine patients that discontinued, just to reassure you, six of them did have efficacy data before they exited the study. So there were three that exited before the first data was taken. Six that did have efficacy data. Half of those had a TSS 50, so a complete symptom response of more than 50% reduction in their symptoms. And there were three patients in there who were evaluable from a spleen size perspective. All of them had a spleen volume reduction, and one of them actually had a spleen volume reduction of 61%. None of those withdrawals were due to drug-related adverse effects.
A really reassuring patient group, a severe group, and one which asks a lot of the drug going into it. Given that background, I was looking at this data last night, just trying to round up the final steps of the press release and thinking about the journey we've been on. Frankly, I don't think we could have asked the drug to do any more than it did. We have a drug which, in this severe group of patients, for patients that were on the drug for six months or more, we saw 73% of them get a TSS 50. That's quite an astonishing rate, and it's almost double the rate we've seen in other competitor drugs in development in similar patient groups, which typically would see TSS 50 of between 30%-40%. To see a TSS 50 of 73% is an outstanding result.
We've also seen in recent past trial results presented in other ways for a symptom score. And often when the trials maybe haven't shown statistical significance in TSS 50, the numbers of responders, the trial publications have resorted to showing the absolute reduction in symptom score as opposed to the number of patients that get beyond a certain point. And again, very reassuring that the symptom reduction from baseline to week 38 or nine months was 56%. And we saw that increase out to week 52 to 68%. So that's the average symptom score improvement in that time. So really, really positive. And of the patients that reached 52 weeks, we had three patients after the last data update in June, and two of those three completed the 52 weeks, and both of them had 100% resolution of their symptoms from baseline.
So from a symptom score perspective, really, really excellent results, very reassuring. And added together with even the patients that dropped out, with half of them getting a TSS 50 as well, I think is a really encouraging profile for the drug. Obviously, also backed up by spleen volume reduction. And here we're looking for a 25% reduction in spleen volume. And week 24 and beyond, 44% of patients got a spleen volume reduction of 25% or more. So that, again, is an outstanding result.
It's competitive with what we've seen other drugs do at this stage, and not what you would expect to see in a patient group that's been this long on ruxolitinib, with no changes in ruxolitinib dose and still seeing those kind of improvements is a great feature of the drug and one that's very reassuring that this is really going to make a difference to patients when it gets into the clinic. So overall then, those improvements of 50% or more, they were observed quickly. They were sustained with that picture looking the same out to 52 weeks. Spleen volume reduction is the same. And those patients that did complete 52 weeks of treatment, I think looking at beyond the trial and what it meant to those patients, of the seven patients who completed 52 weeks, six of them have chosen to stay on drugs.
They've made applications through their clinicians to continue to receive the drug after the end of the study. And of those six patients, three of them had a minor anemia response. And two of them, as I mentioned before, had a complete resolution of symptoms from baseline. So this is a really reassuring picture. It's nice to see patients doing well in the study, but it's really nice to see patients feeling that well that they want to continue on the drug at the end of it. So that positive outcome from the study now allows us to think very clearly about the next stage of amsulastat clinical development and engaging with partners.
To that sense, today we also put out a press release strengthening the company with a series of appointments of advisors to the leadership team and to the board to help us navigate the next steps in this process. The two people taken on as strategic advisors to the board, specifically for their experience in hematology. First one being Adam Craig. Adam was the former CEO of CTI BioPharma. CTI BioPharma had developed a JAK inhibitor called pacritinib. They took that through development, FDA approval, and subsequent commercialization. And in 2022, CTI, under the leadership of Adam, was acquired by a company called Sobi in a deal worth more than AUD1.7 billion. Adam stands out as an experienced executive in the myelofibrosis space who not only has taken a drug through late-stage development into commercialization, but also managed an exit as well.
So we're really pleased to have him on board to give us advice as we go through the next steps. Dr. Kevin Lynch had a senior medic with appointments at Celgene and Antengene, both companies where they had oncology/ hematology drugs, so very relevant for the portfolio that we have. So we're delighted to see Kevin come along. And again, that experience in managing late-stage clinical development will be invaluable for the company going forward. So those two strategic advisors coming to look at the board and the management team. We've also formally identified our clinical advisory board, which is the steering committee for the next clinical study that we go into and helping us develop the protocol to go back to the FDA for approval later this year. Professor Claire Harrison, Dr. Gaby Hobbs, and Professor John Mascarenhas.
All of them global, well-recognized opinion leaders who were really welcomed their involvement in the team and listening very carefully to their advice and looking at the data that we have and the next stage of clinical development. So that leads us to next stages. So one of those is continued partner engagement. I've shown this slide before. It shows the level of commercial interest in myelofibrosis from several different deals. The one on the left, Keros exit to Takeda, was for a drug at the end of phase 2 with data in myelodysplastic syndrome and myelofibrosis. I'll talk to you in a minute about our myelodysplastic syndrome program, but that went for AUD200 million upfront and a deal worth more than AUD1.1 billion in milestones. So there is strong commercial interest, that that deal was done in December last year. So it's current, it's active.
There's a group of companies out there that are looking for assets in hematology and oncology in particular, which we will be updating with the data and next stages in regulatory development. Our pipeline, I asked you to think about this when I was talking about the cash that we have. So amsulastat, our pan-LOX inhibitor, myelofibrosis, next stages for that is to engage with the FDA in getting an approval for our development plan and engaging with potential partners in there. That's all going to happen in the first half of next year. We have two MDS studies, one in Australia and one in Germany, both funded with non-dilutive cash. We're expecting interim data from those by the middle of next year. We have two ongoing studies in scarring with a topical pan-lox inhibitor.
One of those is likely to produce some safety data before the end of this year. Both of them hopefully getting efficacy data during the course of next year from the middle of next year onwards. And then finally, not last but not least, last but not least is our Parkinson's disease patient group study, which we expect top-line data from in quarter two next year. So a pipeline of drugs, multiple shots on goal, one clear lead asset in amsulastat, which has completed now phase 2A and looking to the next stage with a strong group of experts behind it.
So in terms of news flow, you can expect more news flow coming out of the MDS studies as we continue to recruit towards the end of this year, as well as completing the recruitment for the Parkinson's IRBD study and that safety data coming out of our hypertrophic scarring trial. First half of next year, the next stage of the amsulastat clinical development and partnership engagement coming on the back of the study results today. On top of that, MDS studies, we hope due to report some interim data in the first half of the next year, and then the IRBD study and the hypertrophic scar and keloid scarring coming in the second half of the year, so a strong set of news flow from a company with a strong pipeline and cash through to the beginning of 2027, and with that, I will stop.
Matt, I'm happy to hand it back to you and take any questions.
Thanks, Gary. Just again, as a reminder to the audience, if you have a question, please type it in using the Q&A panel within Zoom, and we'll jump into those now. The first question is, can you please explain the rationale behind the phase 2A trial design?
It's a classic way of approaching, particularly oncology development. The first thing you need to do with a drug is take it through phase one in healthy volunteers, where you demonstrate the safety of the drug in increasing doses, and you pick your dose, which is going to go into patients. We then took two doses into this phase 2A study. This phase 2A study incorporated, first off, a group of patients who were at the severe end, so had failed on ruxolitinib, a JAK inhibitor, so failed standard of care. That's classic. You start with patients who have no other treatment options with a drug because you don't know how safe it's going to be.
Once we demonstrated that the drug was both safe and effective in that group of patients who had no other treatment options, you then move to the next stage, which is in patients who are on a JAK inhibitor but are still suboptimally controlled. At this stage, it's normal also that the study stays open label, and because it's unethical at this point to be treating patients with a placebo when you don't know whether the drug is going to work in that group of patients or not, it's generally a small group of patients as well, and then so that's what we've just completed.
The next stage after that can be to go either into a, in both cases, a controlled study where you're using a placebo in one group of patients so you can measure more exactly the efficacy and safety of the drug. In some cases, you can go straight to phase 3 in that, and that's been quite common in oncology drugs as well. With good data coming out of phase 2, you can sometimes leap into phase 3, or you can go into a phase 2B, which then jumps into a phase 3 after that. So we're probably going to go down the phase 2B route on the basis of the advice from the FDA, but that's something that we'll be discussing with our advisors and the FDA in the next few months.
Thank you. The next question is, how are the experts that were announced today being remunerated? Is it via cash or issue of shares?
Mainly remunerated by cash.
Thank you. And then the next question is, does the company see any need to reduce staff numbers over the coming months?
Okay, well, as I've said, the company has pro forma end of June AUD 20.7 million in cash. The team of staff that we have are responsible for generating, I think, a leading pipeline of drugs. They've been extremely effective and efficient at getting that and the number of opportunities for Syntara shareholders to benefit from with news flow and milestones coming thick and fast in the next 12 months. And that cash runway takes us through to the beginning of 2027. Clearly, we are making sure that that cash runway lasts as long as possible, and we have undertaken a stringent review of the expenses and where we go, but there is no plan to reduce staff numbers at this time.
Thank you. So regarding the appointments announced today, one of them being Dr. Adam Craig, which is a real coup for the company to get someone with his experience and success in the field. How did you manage that, and what's the relationship there?
Yeah, I mean, I'm delighted that all of the appointments that we've announced today, I think that they're a very strong group of global experts, which is appropriate for the company to be engaging with at this time. Our relationship with Adam Craig goes back actually quite a long time. So I first talked to Adam when he was the CEO of CTI BioPharma a number of years ago, back in 2021, 2022. And even at that point, he was interested in amsulastat, or 5505, as it was known at that time. We both felt that there was a strong strategic fit between CTI BioPharma and Syntara, given that their JAK inhibitor had a fairly limited label for patients with a very low platelet count. And amsulastat had the potential to, in combination with that, widen the treatment label.
So CTI BioPharma were bought before then, but Adam had already at that point taken on a, I think, what was quite a complicated picture with the data they'd had out of their phase three studies with pacritinib. And he'd shown himself to be really effective at mining that data set, navigating away through the regulatory authorities, commercializing that drug, and then exiting a sale exit for the company as well. So he was a natural person for me to pick up the phone and talk to as we were starting to get data out of our study a year ago. And I think he, as has been shown by his willingness to be now publicly appointed and associated with the company, is that he's attracted by the novelty of the mechanism that we have and the way that we're treating. He understands myelofibrosis very, very well.
He understands the regulatory process and the clinical development really well, so I'm delighted to have him on board and able to give us advice and talk to us about the next steps that the company could take.
Thank you. Another question that's come through is, during the presentation, when you say 100% reduction from baseline, what does that mean? They are cured, or exactly what does 100% reduce?
Yes, it means that they're no longer registering any symptoms. So the symptom score goes from 0 to 70. There's seven different domains. So it means on each of those domains, the patient is no longer registering themselves as experiencing any symptoms. They feel normal and healthy.
Thank you. The next question is, is your expectation that phase 2B will have an SVR25 or SVR35 as a co-primary endpoint, noting that the IWG-ELN guidelines require this? And is your expectation for a 24 or 52, or there might be 26 or 52 weeks trial?
Both good questions. Yeah, I think based on the precedent that we believe exists for patients that are suboptimally controlled on a JAK inhibitor, we believe SVR25 will be the endpoint, but it's ongoing. It will be a point of discussion with the FDA, and in terms of the length of the study, this study has been really interesting and valuable in going out to the 52 weeks. It's really given us a feel for the length of time that the drug not only takes to work at the beginning. We saw symptom control starting to emerge within three months. The spleen volume gets stronger around six months and beyond, so there really is a balance to be struck here between how long you want to run the study for and how quickly you could also bring it to a close with a positive endpoint.
So that will be the subject of more analysis and going forward. So we haven't yet decided on the length of the study, but the data we have is extremely valuable in that regard.
Thank you. And just following on from that, the same person asked, does the phase 2A data stack up on SVR35?
Yes, I think even at SVR35, there's enough of a response there. When you look at competitor sort of drugs in development and you look at SVR35, we're in the realm of sort of 20%, 25% of SVR35 that these drugs are seeing on top of a JAK inhibitor in patients who are suboptimally controlled. So our drug would be around that. That's why I say my choice of words is quite deliberate. I think that in symptom control, our drug has an outstanding profile, and it's probably the best in class in terms of the data that we've seen at this particular stage, comparing apples with apples. And when it comes to spleen volume reduction, I would call our data set competitive with other drugs in this space.
Thank you. Another question that's come through is just what options the company has with regards to funding of the phase 2B trial through to the completion?
So this is, I think, I put up a slide there showing the amount of commercial interest there is in this disease. It's clearly very strong. So we will be engaging with both investors who would be interested in funding a study which has such a strong commercial rationale behind it and exit values at the end of a phase 2B or a phase 3 study. But also, we'll be engaging with potential partners who would be likely collaborators with us at this point in either cornerstoning or funding the money required to do a phase 2B or whatever design of study we end up deciding to do.
The next question is, is the 100% reduction in symptom score in suboptimal patients unique to this drug?
It will pass. I'm not sure it's unique. We have to be careful not to overextrapolate these things, but it was just striking that the two patients who could get to 52 weeks in the last data set did reach that point. So it's really good to see. It's a patient-reported outcome. I think it demonstrates the fact that the drug works on things that are important for patients. But I think even more than those patients that had a complete zero symptoms at the end of it, I take even more heart from the fact that six out of the seven patients who got to 52 weeks wanted to stay on the drug and carry on. You don't do that at the end of a trial unless you're really feeling the benefit from it.
So I think that for me in this last round of analysis was the thing that really struck. And those six patients who wanted to stay on drug, three of them had an anemia response, which again speaks strongly about the effectiveness of the drug and the fact that it does work over a long period of time. I keep on going back to the sort of the previous question was talking about the length of the study and should it be six months or nine months or 12 months. And we believe that a lot of the myelofibrosis studies are for drugs which do have quite severe tolerability issues, many of them called cytopenia. And there's a problem in keeping patients on drug for longer periods of time because they start to drop off. So our drug has a unique profile.
It does have a tolerability profile, which means that patients can stay on drug for a long period of time, and after all, these patients do live for five years from the point when they're first given a JAK inhibitor, so they do have appreciable life expectancy, and it's important that during that period of time they can take a drug which doesn't make them feel any worse and doesn't actually cause them cytopenia, which is what eventually kills them, so if you put that together with a drug which is continuing to develop and both their symptoms and spleen volumes are improving over time, and maybe some of them having a hematological response as well, then that points to a drug which has quite a different profile than other drugs which are in development or on the market at the moment.
I think that's why we chose deliberately, again, the headline for the media release today was that this data underlines what's a really competitive and differentiated profile for this drug. I think that's why we've got interest from the advisors that we've appointed as well. They also see something here which is a bit different and potentially holds out a lot of promise for the future.
Thank you. And with this next question, there's some sort of ethical considerations on this, Gary. But is it possible to have some testimonials published on the ASX or interviews with the 100% news you just provided?
Testimonials from patients?
Yes.
You think you do interpret that as? Yeah, under the sort of privacy because we would be yeah, we probably wouldn't want to go there. But certainly, it's things that we can look at and bring out, I think, probably through potentially some selective interviews maybe with clinicians who've had patients in the study reporting about their overall impressions of it in a de-identified sense is something that we can look into. Yes.
Other question is, do you have an estimate of when phase 2B trial might begin and what needs to happen between now and then?
So what happens between now and then is we have a dialogue with the FDA and EMA. So we're in touch with the European authorities as well. We'd expect to get feedback from them on the sort of detailed protocol design in the first half of next year. And then we would start the next study shortly after that. So study start in the second half of next year, finalization of the protocol, and engagement with investors and potential partners in the first half.
Were the six patients allowed to continue on amsulastat? And if so, when will they come off?
They stay on as long as they want or we continue to supply them. So the named patient supply, so these are not patients all from one country either. We have patients from Australia, Korea, and Taiwan, I believe, that have chosen to stay on. Each of those countries has a different regulatory pathway for accessing drugs which are not approved by the regulatory authority for commercialization. So it's a process that we engage with the clinician and their regulatory authority to make sure it can happen. So again, it's very reassuring. It's not a simple process for patients to access drugs after a trial like this. It takes quite a lot of paperwork and administration on behalf of the hospital and the clinicians that are involved in this.
So again, this is not patients saying, "Oh, well, I'll keep trying it for a bit longer." They've made a very deliberate choice, and then there's been considerable effort on behalf of quite a number of people to make it happen. So that's why we're really pleased. But yeah, the supply continues on.
Related to that, someone's asked: Will you report on ongoing endpoints with patients that remain on drug?
They're no longer part of the study. So any information we collect will be much more in a sort of an informal sense. So it's unlikely that we would make announcements on the back of data we collect from the patients going forward.
Gary, I'll just throw it back to you to provide a closing comment.
Yeah, well, thank you very much for your time this morning. I realize that when we were writing the press release, the amount of new data in this was relatively limited after the last update in June. However, I think it has been valuable in looking at the totality of the trial as a whole, what's been achieved, and I'll finish with what I said at the beginning. We could not have asked more from this drug. It's emerged with a very competitive profile. I think a really interesting one, not only for the company, but for patients as well, that can potentially access a drug which is going to not make them feel worse. It's well tolerated and makes them feel better over time.
I'm delighted to see the outcome of this and really looking forward to the next steps along with the advisors, who I'm very grateful for their willingness to join us publicly and be named in the press release today.
Thanks, Gary, and thanks to everyone for joining today.
Thank you.