Good morning, everyone. The clock has now ticked past 11:00 A.M., we're gonna get started with today's very special investor briefing with Syntara CEO, Gary Phillips, who has some exciting clinical data just analyzed from the Phase 2 clinical trials to treat myelofibrosis. My name is Alfred, and I'm part of the Syntara Investor Relations team, and I'll just assist with Gary to run the session. Just a quick formality. After the presentation, Gary will take questions from those in attendance, and a few that have been emailed through already. If you do have a question for Gary, there is a sidebar at the bottom of your screen which says Q&A. Just hit that, and type your questions in, and we'll read them out towards the end.
If you're on a smart device, same deal, Q&A button. With the data just finalized and released about an hour ago, it's been a very busy few days at Pharmaxis, and I'm sure Gary is very excited to present this data. Gary, I won't take over any more of your time. Let me hand over to you.
Thanks, Alfred. Let's crack on and get this slide to go. I'm just trying to move my slides on here. There we go. Too far. I'll go back. Just before I get into the data, just a reminder, you know, Pharmaxis is a global leader in this particular kind of chemistry and biology that surrounds lysyl oxidase enzymes. We're the first-in-class drugs in two areas, and we've come with a long-term development program around these particular enzymes that are involved in fibrosis. The chart on the left just summarizes the way in which these drugs work. All of us have these fibroblasts in our bodies. You find them in organs, skin, and they can become activated by a number of different mechanisms: mechanical injury, metabolism, genetics, chemicals, injury.
Once they become activated, they release collagen and lysyl oxidase enzymes. Those two things together cause cross-linking of the collagen, which gives the stiffness in the tissue, and if you have a scar on your skin, you can actually see and feel the stiffness in the scar. That happens in our organs and in our bones as well when this process gets going. That stiffness leads to a feedback mechanism, which then causes release of more collagen and more LOX. This vicious circle is something which is at the very final stage of fibrosis. There are lots of things upstream, including inflammation and a very other mechanisms that other companies are working on. We are the only company that are here with drugs which inhibit all of these lysyl oxidase enzymes, the final stage in fibrosis.
Because it's the final stage of fibrosis, it makes these drugs very good at adding on to other drugs which work upstream as well, something which I'll come back to later that's really important. Both of these programs, they're both PXS-5505, which is our oral drug, and PXS-6302, which is our topical drug, are inventions of our own labs, and they're very recent patents. PXS-5505 is a patent priority date of 2018, PXS-6302, 2019. These kind of drugs have got a lot of life left in them, a lot of runway to go to commercialization and revenue. We've got for PXS-5505, it's been through the FDA and an IND approval, and it's got potential in a number of different cancer indications.
Both these drugs have already shown in both healthy volunteers and in patients, that when you give them, we fully inhibit, or more than 90% inhibit, these lysyl oxidase enzymes. We know that these drugs block the target that they're going after. The question was, in the clinical studies, do they then have an effect on fibrosis? I'm really delighted to be here today to give you an update on that. Myelofibrosis is the disease that we're going to be talking about today. This is the trial with the patients that have come from this group. This is an orphan disease. It affects about 15 in 1 million people worldwide.
The patients that have this have about a 5-year median survival from diagnosis. They typically get diagnosed at the age of 50 and onwards. A lot of them transform into leukemia along the way. The symptoms that these patients get are caused by the cytopenia that's caused by their bone marrow no longer working. The bone marrow becomes fibrotic, it stops producing red cells, white cells and platelets. This gives to a host of symptoms that these patients have, including tiredness, shortness of breath, fatigue, increased infections, bleeding, bruising, and enlarged spleen, fever, night sweats, and bone pain. The current standard of care for these patients are drugs called JAK inhibitors.
JAK inhibitors, there are now three which are approved, another one which is coming up to the latest one from GSK, which is in the late stages of approval with the FDA. Quite a lot of JAK inhibitors available. The market in myelofibrosis is more than $1 billion a year. These drugs don't cause disease modification. They are very good at treating some of the symptoms, particularly the spleen size in these patients, which they do quite quickly. They also come, all of them, with tolerability issues as well. One of the main issues being that they cause some of the, in some patients, cytopenia.
You know, up to a third of patients can actually get reductions in platelets and red cells because of using a JAK inhibitor. The very thing that they're trying to correct also can become a problem. This obviously leads to discontinuation, and at five years, 75% of patients have dropped off. Once you've come off of a JAK inhibitor, you've only got about 1 year, 16 months to live. There is a desperate need for new drugs which can be added onto these JAK inhibitors so that you get some disease modification and start treating the underlying disease which is here, and give these patients some extended life. You know, that's where we're coming from with our drug.
We're trying to treat the fibrosis in the bone marrow. Our first trial was designed to do that in patients who were not on a JAK inhibitor. Just to review the study that we're talking about. This was a phase 1/2a study. It started off with patients who were given an escalating series of doses of our drug, to see which was to be the right one. We've already reported on that, and we treat these patients with a 200 milligram dose twice a day. It's an oral tablet. It's not injected, it's an oral dosage form. The patients in the study were all patients who are unsuitable for a JAK inhibitor.
These are all patients who've been on mainly, most of them have been on a JAK inhibitor and then have come off because they're failing to tolerate it, or the JAK inhibitor is no longer working. These patients are actually quite sick. They're in that group of patients which have about a year left in their life expectancy. Many of them are very sick, as we'll see, and we'll talk a little bit about those patients as we go through the data. These patients were gonna be treated for 26 weeks. It's an open-label study. We've already reported on the first six patients that completed six months therapy, and we're gonna talk about the others that have completed since then in a moment.
The endpoints were primarily the FDA wanted us to look at safety and tolerability in this group of patients without background therapy from a JAK inhibitor, so they could really understand what was the safety profile of our drug when there were no other confounding factors around. We also wanted to see some of the efficacy readouts, and this would be understanding the inhibition of the enzyme, the PK/PD, that we got with the drug dosed over 6 months. What we saw with the bone marrow fibrosis, what we saw with the symptom scores, spleen volumes and hematology. These are the things we're doing. We've, you know, this has been a multinational study following the FDA at IND approval.
We're active in 20 sites across four countries, Australia, South Korea, Taiwan, and the U.S. This is the latest update from that. In terms of status, where are we? We've recruited 21 out of the targeted 24 patients to be enrolled, and 10 of those patients have completed 24 weeks of treatment. We have had 10 patients drop out of the study. None of those were treatment-related. Overall, 5505 has been really well tolerated.
I think it's a standout feature of the drug relative to other drugs which are in the development pipeline at the moment and those that are marketed, as we've had no serious treatment-related adverse events reported on drug in this that were related to the treatment in any of these 21 patients that have been on the study. In fact, the majority of adverse events have been mild and have not been related to treatment. I think more than 90% of the adverse events were not down to the treatment itself. This is a drug which is really well tolerated, has a safe profile.
you know, when we think about what comes next and adding it on to drugs like JAK inhibitors, which do have a problematic safety profile, this cannot be underestimated. The importance of this can't be underestimated. Lastly, efficacy. What we reported this morning, and this is all for those 10 patients, who have completed six months of treatment. I guess the really standout new thing in this data, compared with the data we reported before, the end of last year, and it was a poster at the American Society of Hematology, is the number of patients where we've measured an improvement in bone marrow fibrosis. This is something we expected to see with the drug. We weren't sure how much we'd see in six months of treatment.
This is the first time we've had these patients in there, and all of these patients have had their bone marrows now looked at by a central laboratory. One, one central body that's looked at the data and evaluated it to see what's happened with the grades. Bone marrow fibrosis is graded from 0, 1, 2, and 3. 3 being the most severe. We had out of those 10 patients, we had 9 that were evaluable. Now, what I mean by that is that 1 of those 10 patients didn't have enough tissue at baseline for the fibrosis grade to be measured. So they weren't...
Although we can see what happened to them over the other period of time in the study, we can't count them as a responder because we can't see what they were at baseline. That leaves us with 9 patients, and 5 out of those 9, almost 60% of patients, had improved bone marrow fibrosis scores of at least 1 grade. They've gone from a 3 to a 2 or a 2 to a 1. I think really excitingly, out of those 9 patients as well and the 5 responders, 4 out of those 5 fibrosis responders had stable blood parameters, so platelets, white cells, red cells. In those 5, 3 of those patients started out this study, they had it, having sort of improved, symptomatic improvement.
There is appearing to be a link between the fibrosis improvements we're seeing and the symptomatic and the hematological improvements we're seeing with these patients. That's a nice link and a really important one. I think demonstrating this amount of patients showing an improved fibrosis score in six months is an outstanding result, and it's one that's really exciting us. As you'll see, is also impressing the clinicians that work in this area. Four of the patients had an improvement in symptom score of more than 20%, seven of them having a stable or improved hemoglobin counts, eight had stable or improved platelet counts. Now, I think it's worth also pointing out here that when we look at these patients and their platelet counts.
As you would expect, some of these patients are very sick on entry to the study. Three of these 8 patients who go on to get stable or improved platelet counts, entered with life-threatening thrombocytopenia. Their platelets were so low that they had what would be categorized as a life-threatening, low level of platelets at that point. That's, again, a really nice thing to see, that we're stabilizing or improving these patients, even if they're really in a really poor state when they enter. We haven't seen any spleen volume response yet. I think that's something that we anticipated, we thought would happen.
There is a question mark over, you know, how much improvement you need to see in fibrosis in the bone marrow before you see the improvement in bloods that you want, and then that has then a knock-on effect on the spleens. We don't have Unlike the JAK inhibitor, which have a direct impact on spleen volume, with our drug, we will have an impact on spleen volume as it works through the reduction in bone marrow fibrosis, and then the improvement in the blood parameters, which will then lead to an improvement in the spleen. We'd expect to see that some way down the track. Overall, a really pleasing set of data.
Given that we've recruited 21 and, you know, 10 of those patients have dropped out of the study, and we reported on 10, we've labeled this as the final interim data that we will be putting. There will be another final report from this study, which we will be presenting at ASH in December later this year, with the final patients in. This is the final bit of interim data we'll have, and I think one that rounds up the picture that we're seeing from this. We were also quite keen at this point to see, you know, from the clinicians and Dr. Lucia Masarova is an assistant professor at MD Anderson. She's an investigator in the study. She's reviewed the data in detail.
She's gone through all the individual patient data, and we asked her to look at that and give us an opinion on what she thought about where PXS-5505 fitted within the, you know, the environment at the moment, the clinical development environment, and the other drugs that she sees being used in myelofibrosis. She pointed, like I just have, to the excellent safety profile, and a promising clinical activity. She was particularly taken by the effect on bone marrow fibrosis, and she describes the effect on this as exciting in a disease like this, because at the moment, we don't have any effective anti-fibrotic drugs.
To have this one coming through with Phase 2 data like this, where we're seeing more than half the patients at six months showing an improved level of fibrosis, and we suspect that more will be responders if we treated for longer, is a really important point to draw your attention to. She was also, you know, identified that the majority of these ten patients showing improvements in symptoms and stable or improved blood counts, again, pointed to those patients that had severe thrombocytopenia at baseline as being very valuable from a clinical perspective. She was very supportive of our plan to continue clinical investigation of the agent in monotherapy, but also looking ahead to the combinations with a JAK inhibitor.
And again, pointing out here that the lack of overlapping hematological toxicity, so the fact that we don't make the blood counts and the cytopenias worse, makes 5505 an ideal add-on candidate for the future. That was really nice to have her comments and thoughts on that, and it certainly mirrors our own in terms of where we think they'll go next with this. In the meantime, we've also had feedback from the FDA on our program. We announced this a couple of months back, but just to recap where we are with the FDA. We held a Type C meeting in Q 2. The FDA gave us extensive feedback on a set of questions we asked them.
Having reviewed all of the safety and efficacy data we had available at that time, which was the majority of what we've now reported here as well. This is all subject to a protocol review by the FDA, so we have to submit, based on their feedback, a protocol to them. They supported the progression for us, for PXS-5505 to go into a study in combination with a JAK inhibitor as the next step. They also provided guidance on the number of patients, the treatment dosage, study duration, and the endpoints. The study we have proposed to the FDA, we've put the protocol in. We did that a few weeks ago, so we'd be expecting feedback on the protocol later this month.
We're using existing trial sites for this next cohort, where we're gonna be recruiting patients that are on a JAK inhibitor. The advantage of this is it gives us very fast startup. One of the biggest factors that slows down clinical trials is negotiating contracts with each of the clinical trial centers and getting them started up at the beginning of the study. That can often take 6-12 months to do. The fact that we can use our existing 20 clinical trial sites to immediately start recruiting patients on a JAK inhibitor, gives us a really fast startup and minimal initiation costs. That's a really important thing for us to be able to have achieved.
The other one, which really speeds up the whole process to getting data out of this next phase, is that the FDA have not required us at this stage to do a dose escalation step. The protocol we've gone back with goes straight in with the 200 milligram dose twice a day. It doesn't step us through lower doses first to see what effect we have on that.
That was because they were, you know, impressed and felt that the safety data that we had supported that, and that the PK that they were seeing and the inhibition of LOX that they were seeing meant that, you know, going at the highest dose was the most sensible thing to do, with no safety data, to have us have a proportion of going in at lower doses either. It's the fastest route to meaningful data. And we'll be giving feedback to the market on that, in towards the end of the month, when we get the feedback from the FDA, which we expect, in a few weeks' time. In summary, you know, that leaves Pharmaxis with still a, a pipeline, with multiple opportunities in high-value markets.
You know, I think with the data that we've released today, we can really now be claiming to see that we have a safe and from a clinical efficacy point of view, a very promising drug with Phase 2 data. We're now taking the next step in terms of the clinical application, but also a really big step in terms of the commercial opportunity for 5505 in myelofibrosis. Given that the standard of care in myelofibrosis is a JAK inhibitor, generating data when we add our drug onto that, opens up a really wide and significantly big market for 5505 to go into. It's also the area where we have the most interest from potential partners.
Other companies that either have a JAK inhibitor already in their pipeline on the market, or ones which are interested in finding add-on drugs that can go into this area. The data that we get from the add-on study will be extremely valuable to the overall potential of the drug. Again, because we're able to use the existing centers, the first patient in this will be recruited in the H2 of this year. We'll be giving an update on that when we get the feedback on the protocol from the FDA on the size, number of patients, trial costs, et cetera. Last month, we reported 6302 data, our topical uncertain inhibitor in skin scarring.
Again, showing a true anti-fibrotic effect like we've seen with PXS-5505. We saw a 30% reduction in collagen in patients with established scars after 3 months' worth of treatment. Again, a really breakthrough result for both these drugs in showing the true anti-fibrotic effect in 2 different diseases. I think it really underlines the development work that the company has done in the last few years and really underlines the commercial potential of our pipeline going forward. We're looking at scar prevention as a next step in the development of a pan-LOX in scarring, and we'll have more to say about that later on in the year as well.
There's our drug, PXS-4728, which is in a sleep disorder and related to Parkinson's. We are expecting our first patient to be recruited and dosed in this quarter we're in now. News flow. I've got here all of the news flow for the year. Obviously, we're already through a busy part of the year for the company with reporting on data from two different studies now in two different indications with large commercial opportunities. H2 of the year is gonna be equally busy. We'll be starting our recruitment of that phase 2 myelofibrosis study, where we're adding on to standard of care, the JAK inhibitor, in the next few months.
We'll be talking more about the clinical development of the pan-LOX scar treatment and initiating trials later on in the year as well. We'll have more to say about that later on in this quarter. There's the initiation of the PXS-4728 study in neuroinflammation and Parkinson's. And then finally, the reporting of the myelofibrosis study with the interim data we've given today, the final report given at a poster and presentation at the American Society of Hematology later in the year. With that, I'll finish up at that point and hand it back to Alfred for questions.
Excellent. Thank you, Gary, for the very informative presentation, and congratulations on the clinical trial data. We've had a few questions come in already, which I'll get you to start answering in a moment. If anyone does have any, please pop them into your Q&A box. A few have come in a few times and are quite similar, I'm gonna group a couple together. Gary, first one comes from Michael and Derrick. "Curious why nearly 50% of patients dropped out of the study, and do you expect the FDA to have any issue with this?
No, the patient dropouts were similar in percentage terms when we talked to the FDA. These patients have all dropped out from events which are not related to the drug treatment. It's roughly what you would expect, given that these patients only have a life expectancy of about a year when they come in, on average. Some of them are obviously in a worse state when they enter. The clinicians are very aware of this and often have to switch them to other treatments, because of worsening state of the patient, and those then become contraindications to carrying on in the study. They're kind of exclusions, so those patients have to drop out.
No, we're not concerned at all that the FDA will think of that as a thing, because all of those dropouts were due to disease progression and not related to the drug treatment.
Thanks, Gary. A follow-up from Derrick: "Given the lack of dose escalation in the proposed trial protocol with the FDA, how confident are you that the dose and schedule are optimized?
We are very confident. We've got a One of the things that the company has developed alongside these treatment drugs is a set of assays, which allow us to measure the inhibition that we achieve of these enzymes in the body, in tissue and in the blood. We know from, the samples that we've taken from these patients, that when we get to 200 milligrams twice a day, we have maximized the inhibition. We're at over 90% inhibition of these enzymes over a full 24 hours. The 90% inhibition is at trough, so at the lowest point between the 2 doses. We believe there is nothing left on the table, from increasing the dose.
We've gone with the highest dose because it's not associated with any safety problems. If we had the highest dose giving us the highest inhibition, but also an increasing tolerability issues, then we might be saying, "Okay, we'll scale it back, and we'll do a lower dose where the safety profile is better." What we have here is a perfect situation. We have a dose which gives full inhibition of the enzymes, and at that same dose, we don't see tolerability issues which restrict the use of the drug at all. No, we're really confident we got the best drug.
That was a question that we had with the FDA and debated at length with them, showing them all the PK data we had, and the profile of the drug and the level of inhibition and the activity of the enzyme in these patients. One where I think we got them very comfortable with this. Clearly, we still need to wait for the their comments on the final protocol, but I think we're very confident that this will be the way that we go forward.
Gary, a question from Dennis. "Why do you see bone marrow fibrosis reduction, but no spleen volume reduction?
The sequence of events for a patient of this kind. Once their bone marrow becomes fibrotic, the bone marrow is the body's production unit for red cells, white cells, platelets. As it becomes fibrotic, the body sees reduced levels of red cells and white cells and platelets. The spleen is an organ in the body which can also produce blood cells. In response to the bone marrow becoming less productive, the spleen starts to produce and upscale its production of blood cells, and in doing so, it becomes enlarged. This is the enlargement of the spleen is as a consequence of the fibrosis.
The only drugs that are currently approved in myelofibrosis are the JAK inhibitors. The JAK inhibitors work by a very different mechanism. They work directly on the spleen. You see significant reductions in spleen size. As I said before, often, because they're reducing the spleen, they're also reducing the amount of production of blood cells, so you see cytopenia with these JAK inhibitors as well. Our drug works in a very different way. It's working from the bottom up. It's disease-modifying, so you're reducing the fibrosis in the bone marrow. You're then seeing a consequently, an improvement in cell production from the bone marrow, and eventually, that feedback loop will lead to the spleen then reducing in size.
We're working in a different way to the JAK inhibitors, which is why we expect to see spleen volume reduction at the other end. It's important from a regulatory endpoint review, and we're very interested to see what happens when you add it on to a JAK inhibitor. What we expect to see is the JAK inhibitor damping down the spleen volume, but at the same time, our drug starting to help the body produce more blood cells, so they're able to stay on the JAK inhibitor for longer and get the benefits from that, but also get the benefits of the disease-modifying drug as well. You know, you'd hope to see disease modification and life improvement in life expectancy from that combination going forward.
Thanks, Gary. We are starting to get tight on time, so I'll probably just go through another two or three. If anyone does have any questions, please type them into your Q&A box. A follow-up from that, Elise is asking: "Did you see a delayed response in spleen volume reduction in the preclinical models after bone marrow and fibrosis improvements?
Yes, I'm not sure that the animal models are sensitive enough to be able to pick that apart. Yeah. Thanks for the question, Elise. I'd have to come back to you on that and have, maybe have a chat with the investigators on that point. Our drug does have other effects other than just the inhibition of the cross-linking. There are some intracellular effects of LOX as well, which we're working through and trying to understand. It may be in the animal models that you saw spleen size changing a little bit earlier, but yeah, I'll come back to you on that one.
Just one more from Derek: "Curious on your thoughts as to why you think 80% of patients showed stable blood counts, yet 56% of patients showed improved fibrosis scores. Is a 6-month duration long enough to see a reversal of fibrosis?
Yes, good question. When we talk to the opinion leaders about fibrosis scores, they all point out that what they're starting to learn. The way that we measure fibrosis in the clinical study is through bone biopsies. That's a wide needle that's put through the skin and into the bone to take an aspirate from the middle of the bone. When we've now got a lot more information coming back from some of the more well-equipped centers that scan their patients quite regularly. It's not in this study, but we're seeing in other publications that the bone marrow fibrosis, which we see in these patients, is somewhat patchy.
You not only have you got to measure the fibrosis level in the bone marrow biopsy, but you've also got it's a bit hit and miss as to whether you've got a needle that goes into an area whether you have fibrosis or not. We're confident with the result that we have, but it may be that a different mechanism would reveal more widespread bone marrow fibrosis reduction if we had it another way. You know, at the moment, from a regulatory perspective, the bone marrow biopsy is the one that we have to do. Does it need longer to get there? I think we'll report more on this at ASH later in the year.
We do see some signs that we get an improvement as we go through the six months. I think that there is a time-dependent part of this. As you might expect, you're reducing the cross-links in the collagen that's forming, the body is naturally chewing through the existing fibrotic tissue as well. Our drug changes the balance between formation and destruction of the fibrotic material in the bone. We're stopping the production of new fibrotic material, the body is naturally degrading the old fibrotic material itself, in doing so, we change the balance. You know, it will be time-dependent. I think the answer to your question is yes, we will see.
The longer we treat these patients, the more anti-fibrotic effect we'll see.
Excellent. We are now out of time, so I'm gonna wrap up the questions here. If anyone does have any further questions, please feel free to email them through. Gary and David are very open with their time, and their contact details are available on the final slide of the deck that was released to the ASX. A recording of this webcast will also be made available shortly on the Pharmaxis website. Gary, on behalf of all the investors in attendance, thank you very much for your time today.
Pleasure. Thank you. Thank you for your time. Appreciate it.