All right. Well, thank you folks for showing up. Today is obviously the first day of the Cantor Healthcare Conference, and my name is Yanni Souroutzidis. I am a Biotech Analyst here with the research team. Today I have with me Satellos, Liz Williams, the CFO, and Dr. Wildon Farwell, CMO. Before we jump into Q&A, would love to just hand it over to you guys for a few opening remarks just on the history of the company, what has been going on over the last six months or so, and what do we have to look forward to over the next 12 months.
Sure. Thanks, Yanni, for having us here today. We have had a fantastic day of meetings, so appreciate it, and the opportunity to share, a little bit about the exciting things we have got going on at Satellos. So a little bit of background on the history of the company. Satellos was founded around a discovery that Dr. Michael Rudnicki made about dystrophin and the role it plays in muscle stem cells. The company was founded by Frank Gleeson, our CEO, and Michael, our Chief Discovery Officer. Michael is a Stem Cell Biologist. He is a well-known expert in the field, and he spent his career studying stem cells, particularly muscle stem cells. Duchenne was a mystery to him because he understood the accepted hypothesis that dystrophin is missing in boys with Duchenne, and dystrophin is a structural protein in the muscle fiber.
What Michael could not understand is why. We understand that the muscle is missing dystrophin, so therefore more susceptible to damage and breakage. But why do these boys lose their muscle over time? When he started to dig into this a little bit more, and just to back up a little bit, the reason this was confusing to him is because muscle is the most regenerative organ in the human body. A healthy individual has muscle damage, like all of us here. We can repair that damage. The body repairs it. So why in boys with Duchenne, if their regenerative capacity is working properly, could they not repair their muscle that is more susceptible to damage? What he discovered in digging into this is that dystrophin has a secondary role.
Yes, it is in the muscle fiber, but it is also in the muscle stem cells, where it has a signaling role, and it tells the stem cells how to divide properly to create muscle progenitor cells, which go on to repair and regenerate muscle. This is a seminal discovery that he made. A little bit controversial because it went against the accepted understanding of what the problem in Duchenne was. Frank and Michael set about founding Satellos with the goal of finding a way to address this problem. Through that work, they identified an alternative pathway, which is called AAK1, to replace the signaling role of dystrophin in the muscle stem cells, which repairs the polarization problem, allowing the stem cells to polarize properly and create new progenitor cells and go on to repair and regenerate the muscle. It is very exciting.
Our drug is just today we announced it's been named forazapadin, formerly known as SAT-3247. It's in phase II clinical trials, and we'll talk a little bit more about the data we have so far. We are on the precipice of a very exciting couple quarters for the company. Been at this for a long time, but right now we've got two phase II clinical trials ongoing, both of which will have data before the end of this year. When we look at our BASECAMP study, we are on track to complete enrollment this month. That's 51 patients in a phase II clinical study in a global study, which is pretty remarkable to have been able to enroll 51 patients in nine months. Kudos to Wildon and his team for being able to do that..
We will have some initial data from that study before the end of the year and a complete data set early next year. That's a placebo-controlled, randomized proof-of-concept clinical study. Very important milestone for the company. We also have our TRAILHEAD study, which is an open-label study in adults with Duchenne. We anticipate additional data from that before the end of the year, and also enrolling the first patients in the Part B of that study. Finally, we are also planning to initiate a phase II clinical trial in FSHD as our next follow-on indication and expect that trial to get started before the end of this year as well.
Understood.
Exciting.
Quite a lot going on obviously. Will be some fireworks here at year-end, I imagine.
Absolutely. We are excited.
I think that was an excellent review in terms of the mechanism and the mode of action here. I guess maybe dovetailing that a little bit into what we have seen clinically because I think that really starts to validate this notion that by increasing the progenitor formation, we are seeing early signals of function. I think that is really unique here in DMD, where we are not so focused on dystrophin anymore, but actual functional improvements that are improving patient lives. Yeah, maybe just walk us through how that data evolved with the initial phase II data and now with the ongoing TRAILHEAD study.
Yeah. Over to the doctor.
Sure. Satellos conducted a phase I study that really had two parts. One part was in healthy volunteers. So 72 healthy volunteers where they explored the single ascending dose up to 400 mg, a multiple ascending dose up to 240 mg over seven days.
In the phase I study that Satellos conducted, there really were two parts. A part in 72 healthy volunteers, and then there was a five DMD participants. These were adults with Duchenne to evaluate safety, tolerability, PK, and then to begin to evaluate efficacy, looking at different functional assessments. In both the healthy volunteers and in the DMD participants, safety profile was very reasonable. No concerning safety signals were identified. The PK was as predicted based upon the preclinical data. What we began to see in the adults with Duchenne is, first of all, very reasonable safety profile. Again, no concerning safety signals. We saw a near doubling in hand grip strength in 28 days. This was observed in the participants who had higher drug concentration, and then in participants who had more muscle mass as measured by baseline creatinine.
This was nice correlation with objective ability to explain this increase in hand grip. What we then saw was an improvement in different biomarkers. Proteomic assay showed even within 15 days, we were able to see a decline in several proteins that are known to be associated with Duchenne. What we reported most recently at ICNMD is we saw also an improvement in fat fraction. This is another objective endpoint. We know in people living with Duchenne that they have an increase in fat fraction over time. What we saw is in all four participants that were enrolled now in the TRAILHEAD study, which is the follow-on to the CL-101 study, that each of those four participants had a decrease in fat fraction. The mean improvement in fat fraction was 3.7%.
That is compared to the natural history where you typically see an increase in fat fraction of around 6% in the muscle, which was the bicep muscle. We also saw an improvement in total effort, the 99th percentile. This is an assessment of upper arm movement, looking at the force generated over time. In each of the four participants, again, we saw an improvement in total effort. We saw the greater improvement in those participants who had more muscle mass at the baseline assessment. Again, suggesting that in patients with more muscle, we would be able to see a greater improvement in function.
This is all giving us encouragement that in our ongoing study in BASECAMP, which is the phase II study in boys between seven and 10 years of age, we will have the opportunity to potentially see improvement because we will evaluate the 60 mg dose and 120 mg dose. We know the boys have more muscle mass than do the adults. There will be the opportunity to evaluate these same assessments plus many more that we can get into as well.
Understood. Yeah, I think the consistency is what stood out to me. For MRI in particular, just looking up the variability there measure to measure, it is generally I think within 1% or 2%. So to see the changes that you are seeing in aggregate here, I think to me at least, were encouraging. Maybe talk a little bit about the BASECAMP study design then. It is the first time you are dosing in pediatrics, so obviously it is nice to see two dose levels. But walk us through some of the endpoints that are different versus the adults and what to expect there based on typical natural history data.
Sure. So BASECAMP, again, is a placebo-controlled study in 51 boys between the ages of seven and 10 years. It is randomized one-to-one-to-one placebo, 60 mg, 120 mg for three months, followed by a nine-month long-term extension. So the participants who are on drug in those first three months will stay on their drug for the long-term extension. Those participants who are on placebo will receive either 60 mg or 120 mg in that nine-month long-term extension. So in BASECAMP, we will obviously be evaluating safety tolerability. We will look at PK in this pediatric population. But we will also begin to be able to look at different assessments of biology as well as function. So we will be doing biopsy of the bicep. So we had not done the biopsy in the adults with Duchenne. But in the boys, we will be able to do a biopsy.
Dr. Rudnicki published a paper earlier this year on what is called the Regenerative Index. This is an evaluation of muscle biopsies. What he showed was that the Regenerative Index declines precipitously in these boys over this age range. What the Regenerative Index is looking at are the levels of embryonic myosin heavy chain to IgG. Embryonic myosin heavy chain represents regenerative capacity of the muscle. IgG represents necrosis of the muscle. One would expect that as people living with Duchenne age, they have more necrosis, so the levels of IgG increase, the levels of embryonic myosin heavy chain decrease. What was seen in the dog that Satellos evaluated with SAT-3247 at the time, what we are now calling forazapadin, is an increase in that Regenerative Index. So we would be looking to see if in these boys we are able to increase the Regenerative Index at that muscle biopsy.
We will also be evaluating dynamometry, so strength across several different muscle groups. In TRAILHEAD, we looked at grip strength and upper arm. We will look at those same muscles in BASECAMP, as well as lower extremity muscle groups as well. There is clear natural history showing, for example, knee extensor strength with vastus lateralis fat fraction with NSAA ambulation. So we know that changes in strength in the lower extremities are very much correlated with function, as is change in hand grip and upper extremities correlated with function. Fat fraction, we will have the opportunity to evaluate with a muscle MRI in BASECAMP. We will be looking at the vastus lateralis, so the quadricep muscle. Here too, there is a lot of established natural history for this muscle in people living with Duchenne. So we know that other sponsors have presented data on fat fraction to the regulators.
They've been evaluating this for a long time. We knew that it's very much a key part of the givinostat approval package. The regulators are clearly very familiar with this endpoint. What's known in the natural history is, in a population consistent with BASECAMP, you typically see a fat fraction between 10% and 20%. When the fat fraction gets to 50%, the risk of losing ambulation increases about tenfold. Between 10% and 50%, it usually increases about 10% per year. What's also known is the MCID for fat fraction is described as anywhere between 1% and 5%. In TRAILHEAD, what we saw over the five months of observation, we saw a 3.7% decline in fat fraction in the adults. If we could stabilize or perhaps improve fat fraction similar to what we saw in TRAILHEAD, that would be a quite meaningful response.
We'll also be collecting different time function tests, such as stride velocity 95th centile, which is very similar assessment to total effort that was collected in the TRAILHEAD study. Time to rise, 10 m walk, NSAA, quality of life assessments. It'll be a very robust data set that we'll be able to generate with the BASECAMP data that we believe could then potentially, depending upon the data, be the basis of accelerated approval with the FDA.
I guess on that note, starting to connect the dots a bit further because, as you mentioned, you also have this open label extension as well. It seems like there's lots of ways to win. Obviously, if you're stat sig across the board, very little debate to be had. At the same time, first time in pediatrics, it's a relatively short period over the course of the overall disease. What are you looking to to really define success, if you will, or sufficient enough to continue to engage with regulators and to see how things evolve in the open label extension?
Yeah. I believe that just as you said, there are multiple paths to success with the program that we have at Satellos. Obviously, we're expecting to see improvement in the muscle biopsy. I believe if we can see that early, that that then could translate into clinical function at a later time point. I have experience from ALS. I was part of the team that designed the QALSODY program. If you think about how that program evolved, they saw early change in neurofilament that was then translated into improvement in ALSFRS-R at a later time point. It could be that we see early change in the muscle biopsy results, or early change in fat fraction, or early change in dynamometry, but it takes longer period of time to play through to the time function test or to play through to NSAA.
But we have the long-term extension, the nine-month long-term extension, to be able to see just are those early points of on-target biology, are they able to play through within the three-month placebo control period of time, or do we need to wait for time within that long-term extension to see the full effect play out? What we are seeing in TRAILHEAD so far is that the early gains in strength are being maintained over a longer period of time. We will have the opportunity this year to provide a 12-month data update on those TRAILHEAD participants to again see whether the early change in fat fraction, the early change in TE99c are able to be further improved or be maintained with time on drug there. So I think the total data set between BASECAMP and TRAILHEAD give us lots of opportunities to engage with regulators.
Understood. Maybe also just to expectation set a little bit, because the mechanism here is more about regeneration, I know we saw some declines in creatine kinase from the adult population. But at the same time, I think one could argue that is not necessarily something that we would necessarily see in the pediatrics. Maybe just call out some of those differences where, again, it is not akin to the exon skipping where we are looking for the exact same fingerprint.
Right. So, first and foremost, dystrophin is not our surrogate biomarker. We are not evaluating dystrophin. We do not have any reason to believe that we would be increasing dystrophin or changing dystrophin expression. So we are not evaluating dystrophin in this program. We do believe that we are going to improve the healing of muscle, improve the regeneration of muscle. As we do that, what we have seen so far in TRAILHEAD is initially we did not see a decline in CK, but with longer time on drug, we have seen some decline on CK. But we could also expect that with increase in production of muscle that one might see an increase in CK. As more muscle is generated, one then has more opportunity to release enzymes like CK, which are known to be present in the muscle.
So we will have to see how this plays out over time, especially in a young pediatric population where they may be more active. They may be having more functional gains, and so therefore, some of the biomarker trajectories that we have become accustomed to with dystrophin replacement therapies may not be the same biomarker trajectories that we will see with this mechanism. We just do not have the experience yet to know for sure how that plays out.
Understood. Maybe coming a little bit back to the dose levels. You are testing 60 mg and 120 mg. Can you walk us through the rationale there in terms of why those doses, and just give us a reminder as well. It is a little bit of a unique dosing schedule. It is not continuous, and I think that is supported by the preclinical studies. Yeah, just walk us through the work there and how you arrived at those two dose levels.
Sure. What was seen consistently preclinically was that a 10 mg/ kg dose level demonstrated efficacy. When that is translated into the human, that turns into a 50 mg, 60 mg dose. When we did the tox work, we had a very wide safety margin. Again, in the SAD, we tested doses up to 400 mg. In the MAD, we tested doses to 240 mg. Did not have any concerning safety signal. When we looked at the PK, what we saw was that the concentration that we were achieving at 60 mg was the concentration that we were aiming for from a therapeutic level. We do believe that 120 mg dose also allows us to achieve concentration within that therapeutic range. Again, we have a very wide safety margin even at that level.
What we saw consistently in our non-clinical studies was that when we introduced a break into the treatment regimen, that we saw optimized efficacy. Whether it was two days, three days, as long as there was a break in that regimen, the efficacy was greater than if we had less of a break. So we have brought that same approach into the clinic. We believe that this is related to the biology of AAK1 within the stem cell pool and within the progenitor cells. Again, we are not looking to completely knock down AAK1 expression. We are not looking to turn off AAK1. What we are looking to do is to inhibit it for a short period of time to allow the stem cell to polarize appropriately to then lead to asymmetric division. With a short half-life, which is what we have seen with forza?
forazapadin.
forazapadin. Thank you, Liz. We believe we have that opportunity to hit AAK1, but then allow the natural biology to occur within progenitor cells and elsewhere.
Got it. Understood. Relating that a little bit back to TRAILHEAD as well, it seems like there's another chapter to be had there with recruiting additional adult patients outside of the current four that are on. Maybe walk us through that plan there as it relates to dose as well and what we're hoping to see. Lastly, maybe tying that into the fact that DMD is a bit of a spectrum in terms of severity. I think we've previously discussed Becker as well and how you're thinking about patient selection in the adult population to prove out potentially a broader efficacy profile.
Yeah. So with TRAILHEAD, what we're planning to do is to initiate new sites within the U.S. and Australia to be able to enroll 25 additional participants. So have total of up to 30 participants within TRAILHEAD. These new participants would be between the ages of 16 and 25. We're very close to having those sites activated to be able to then start enrolling these new participants. We would hope that in these new participants, we're able to see results similar to what we've already demonstrated in TRAILHEAD, to be able to see early benefit in strength and to see benefit across multiple functional assessments. Again, by the end of the year, we'll have update on 12 month assessments for the four participants that are currently within TRAILHEAD. We'll be able to see additional MRI data, additional TE99C data, additional strength, safety tolerability.
That'll provide longer term follow-up for those participants. The DMD population is really a very heterogeneous population. The Becker and Duchenne, it's really the same foundational biology. All these people are missing dystrophin. The degree to which they're missing dystrophin, the quality of the dystrophin that they're producing, then determines their phenotype, whether their phenotype is more consistent with a Duchenne population or whether their phenotype is more consistent with a Becker population. What we've seen already in TRAILHEAD is we know these four participants have different degrees of their phenotype. Two of the participants at the baseline of CL-101 were still ambulatory. Two participants were not ambulatory. Those participants, all four participants have shown benefit on the muscle MRI, on the TE99c. To us, this is consistent with forazapadin being able to demonstrate benefit across the dystrophinopathy phenotype.
As we increase the population in TRAILHEAD, as we're able to demonstrate population within BASECAMP, we think that this may allow us to have conversation with the agency beyond just DMD, but perhaps even a Becker type phenotype.
Understood. Okay. I know we're coming up on time. I did want to maybe come back to FSHD since I know that's coming into the clinic. Any last messaging on DMD and BASECAMP that we haven't touched on? I think we covered it.
I think we've hit most all of the key points.
Understood. Yeah, why don't we spend then just a couple of minutes on FSHD. What data do we have out there currently? What is the mechanistic rationale, given that it's a bit different than DMD, and how are you hoping to prove that out in the clinic?
As Liz laid out, the way that Michael came to forazapadin was through the lens of Duchenne. However, the mechanism by which forazapadin is working is independent of dystrophin. It is a mechanism that is present in all of us. Even in non-disease models, when the muscle is injured, what is seen is improvement in function after forazapadin is administered. In people living with FSHD, it's a disease due to the abnormal expression of a DUX4 protein. The current therapies that are in development are primarily targeting knockdown of the DUX4 protein expression. There has been some encouraging data, first generated by Avidity, now under the control of Novartis, showing potential improvement in biomarkers and there was a lot of work done by other sponsors in the field to understand the natural history and phenotype.
What is also known is that in people living with FSHD, they have abnormal satellite cell biology. We know that they have a lot of inflammation that is impacting the ability of these satellite cells to regenerate. Satellos evaluated forazapadin in the FLEX DUX4 model of FSHD, and they did it in the model without induction with tamoxifen. In that model then, the disease is more similar to the human features of FSHD. What was seen was improvement in the force generated by the muscles after forazapadin was administered. Building upon all of the phase I work that we've done as part of the DMD program, we now believe that we can quickly initiate a phase II program for FSHD. We're on track to being able to do that this year.
We believe that could then provide us with the opportunity to perhaps see data the end of next year or early in the 2028 period.
Understood. Well, I think we're up on time, but a very exciting year ahead of you with the BASECAMP study, the TRAILHEAD updates, getting to the clinic with FSHD. I think definitely a story worth keeping a close eye on. If you guys have any other messages that you want to broadcast to the conference, now's the time. Otherwise, thank you so much for today.
If we could just say that we're excited about the next couple of quarters. For those of you who follow the space know that Satellos is currently valued at a fraction of others working in the space. As momentum builds into the BASECAMP data later this year and early next year, we think it's a very compelling investment to consider.
Yeah.
Thank you so much.
I would agree. All right. Thank you.