Transcript
Speaker: Hello and welcome to Edison TV. We are joined today by Mats Birgat, Chief Business Officer of Synact Pharma. The company has reported some interesting findings from additional analysis of its phase two advanced data. And Mats is here to help us understand what they mean for Resume Lagoon and the path ahead.
Speaker: Welcome Mats. Thank you very much. that's The incremental analysis suggests that around 20% of the advanced patients entered during temporary inflammatory flares.
Speaker: Why did this have such a huge impact on the placebo response? What you do when you do trials in in in this patient type, in the newly diagnosed patient type, you really reach patients at ah at a moment where their inflammation really is at at maybe at the highest. and And that's the reason why they are in this situation in the first place.
Speaker: and And one of those reasons is this um kind of temporary flare-up or or temporary increase or hill of of inflammation, so to speak.
Speaker: And what will happen there is that it's a very natural progression for high inflammation, but also a natural regression to a kind of a baseline state out of inflammation.
Speaker: And if you measure change from baseline on an artificial high, you will automatically have a a very high response to whatever ah both treatment or placebo that that you give.
Speaker: ah In the approximately one out of five patients that was included in the advanced study, we saw an increase in inflammation above a certain level from kind of two weeks before baseline and to baseline, suggesting that they, in fact, are on this kind of up uphill curve um and and thus were in this flare situation. um And what you saw when you isolated those patients, you really saw a a markedly different response to methotrexate and and a placebo, as well as also methotrexate and and
Speaker: resomaligon, but in the placebo arm, you really saw this tremendous and change from in in in those particular patients, which were out of scope compared to what we've seen when in previous trials.
Speaker: So this is quite interesting, Mads. um So now that you have this observation and ah this analysis in place, does this change how you think about the patient selection for phase three? And how do you plan to adapt the phase three design to address the issues seen with advance?
Speaker: Yeah. So what what this analysis has provided us is is really insights to um what what happens when you recruit in this treatment IU patient population.
Speaker: And of course, some will have these will be in this flare-up situation. You can ah you could do a couple of things. And I think with the learning series, is the we added to the toolbox of what to do about this. And you can do a couple of things. One is that you can you can recruit in a much bigger trial. So that evens out some of this variability.
Speaker: This is what we've seen with um phase three trials conducted in this patient population with patients. basically serving much more patients and thus even out the variability, that will happen to phase-free program as well for us.
Speaker: I also think that there is reason to account for baseline variations um and basically have it as a part of the recruitment in making sure that you actually have a somewhat stable baseline inflammation score so you see the true treatment effect of, you both the placebo and obviously the active arm.
Speaker: And I think that that can be that can be, that's obviously a discussion with FDA and you know moving forward, but I think that's a reasonable solution and learning from this. And just continuing with the phase three plans, you're also considering the phase three plan duration to be around 26 weeks versus 12 weeks for the advanced study. How important do you think is the longer duration in demonstrating deeper responses, particularly when we talk about ACR 50 and ACR responses?
Speaker: but So first of all, and the 26-week study duration is ah is a fairly standard way of looking at phage-free programs. In addition to that, you likely have up to 52 weeks of of therapy as and as an addition to that. really should demonstrate um sustainable effects for resomelagon. And the what we saw from the advanced study was that resomelagon really, ah because of the cell modulation effects, we see a somewhat slower um effect compared to what you expect from JAK inhibitors or TNF alpha inhibitors and so forth. um
Speaker: And what we see from from the advanced data is that around week eight or from week eight up to week 12, you see this markedly difference in in how resumellagon active groups are are differentiating from placebo.
Speaker: um suggesting that on ACR 20, we may have an and possibility to expand the the um the effects somewhat compared to what we've seen. ah But really on the ACR 50, that requires more time to get the full ah the full value out of that. And that will come after the 12th week of of studies that we've done so far. which basically favors and the face-free design to unique it to Resumeligon, which is a plus, I guess.
Speaker: So obviously, very important period upcoming for SYNAC and Resumeligon. You plan to discuss the face-free design and the supporting toxicology report with the FDA during the last quarter of this year.
Speaker: What are some of the areas where you are seeking regulatory alignment? And what, according to you, would constitute a successful outcome from the type C meeting? So the kind of the purpose of the meeting is to um is to make sure that there is a consensus around um a you know the the principles of the study design, the doses that we are going to be using, and the supportive evidence that we are suggesting to meet that. That all goes into a final protocol or a final package that then will be submitted once you you have that cleared. So right now, it's all about the certainty of presenting the results that we have from our Phase 2A begin, the EXPAND study, and the ADVANCE study that all points in the same direction of how of an active therapy in the newly treatment diagnosed will present our statistical analysis. and suggesting of the number of patients that is needed based on effect sizes and the side effect profile of the compound.
Speaker: ah So that's a very important um feedback or consensus that that that that we can reach with agency on on on things like that, because that tells you about risk and timeline.
Speaker: In addition, the supportive evidence is also very important that we have a consensus of you know the the various toxicology studies that is needed to to make sure that a drug like this can be safe-lipped and is sturdy-than-the-phase-free trial is also you know adequate for for the agency.
Speaker: um So getting clarity and and on on those parameters that will reduce the risk and really gain certainty around the timeline of the program of the program in totality.
Speaker: Right. So um a very important question to ask him as now with the upcoming type C meeting, based on what you've observed so far with the advanced data, as well as the subsequent analysis, which you've recently presented, how confident are you that Rizemilugan can move directly into phase three without requiring any sort of further phase two work?
Speaker: we are very certain that we will be able to ah take the data that we have and present a case that can go into phase three. um That's what we're going into the meetings with. And we believe that with free clinical studies in the appropriate patient population and the last two studies you know, phase 2b setups, we have the data that we need to argue that for that design. So that's clearly what we're going into the meeting with.
Speaker: I can't say, you know, what what kind of certainty is that and so forth. Obviously, there are many questions that needs to be aligned on in terms of getting consensus on that. we are ah fairly certain that that what we have is strong enough to to meet kind of the requirements for going into phase three. And that's obviously what we're seeking alignment on.
Speaker: that's That's great, Matt, and sounds good. We look forward to the results of the Type-C meeting. And I just want to close this conversation with with a question of partnering, because this is an important strategic goal for Synact. um How does this latest analysis impact your ongoing discussions?
Speaker: And we also saw in the release that you mentioned the potential for an outright sale for Reza Millagon or potentially even Synact itself.
Speaker: What has driven this broader strategic thinking from the company? So maybe maybe the last question first. and and we We remain open to your for fairly broad dialogue with potential strategic partners, and which could include you know a a a a strategic move of of basically selling the entire company or the entire product and so forth. So what we retain the kind of the the optionality is to focus on what creates the most value for a compound like this and for a company like this, whether that is being a mix of regional deals and moving that forward, whether it's a global one or it's it's a direct sale of of you know the
Speaker: of the company. um that is you know Everything is on the table. ah We are focused on getting the most value out of out of the the compound. We strongly believe in in what this compound can do for for many, many patients with rheumatoid arthritis. But so many other indications beyond that.
Speaker: um And we strongly believe in in in the value upside to that scenario. How to get there, that is the question that we basically remain an open book, so to speak, or open an open, what's called a blank page. So we'll remain focused on the value instead of the kind of the format of getting there.
Speaker: That's excellent. Mats, thank you for joining us today and providing further insight into the advanced analysis and the next steps for Resume Lagoon. For our audience keen to learn more about Synact Pharma, please visit edisongroup.com for our on ongoing coverage of the company.
Speaker: Thanks again, Mats. Thank you very much.
