Skye Bioscience (SKYE) Q1 2025 earnings call transcript

Joining me today is Benite Dillon, Skye's president and CEO, Chris Twitty, CSO, and Caitlin Arsenault, Skye's CFO. Before we begin, I'd like to caution that comments made during this conference call will contain forward-looking statements under the safe harbor provisions of the U. S. private securities litigation reform act of 1995, including statements about Skye's expectations regarding its development activities, timelines, timelines, and milestones.

Forward-looking statements are subject to risk and have certain needs that could cause actual results to differ materially and adversely, and reported results should not be considered as an indication of future performance.

These forward-looking statements speak only as of today's date and the company undertakes no obligation to revise your update any statements made today. I encourage you to review all the companies filings with the Securities and Exchange Commission concerning these and other matters.

I'll now turn the call over to Benite Dillon. Good afternoon, and thank you for joining us. I'm here with members of our management team to review Skye's first-quarter 2025 performance. I'll briefly recap our key upcoming clinical milestones and highlight our operational roadmap for the rest of 2025, before turning it over to our CSO and CFO to share more details around our preclinical data and financials.

We delivered meaningful scientific, clinical, and operational progress this quarter. Most notably, we completed enrollment in our phase 2A, CBON trial ahead of schedule. We've now moved forward with an amendment to extend the study to 52 weeks. This positions us to collect longer-term data on safety, tolerability, and efficacy, both as monotherapy and in combination with GLP1.

Lastly, we generated compelling new preclinical data that further validates the potential of the Massumab as a weight loss therapy.

The Massumab continues to stand out with a differentiated mechanism that is distinct from both perfully restricted small molecule CB1 inhibitors and GLP1 agonists. Importantly, our recent preclinical studies demonstrated a truly perfully restricted antibody like the Massumab can potentially result in significant weight loss similar to a less restricted small molecule. And the Massumab has the potential to provide additive weight loss to an incredent, memetic, light, trizepitite.

Later, our CSO, Dr. Chris Twitty, will discuss this new data in more detail. These findings reinforce our belief that the Massumab has the potential to deliver durable weight loss with fewer safety concerns.

We'll present additional data, including mechanistic and combination findings at key scientific and investor events this year, starting with eco-next-week and ADA engines.

Clinically, we are on track. Patients continue to receive treatment. The Data Safety Monitoring Committee has completed three reviews with no safety concerns. Site engagement remains high. Based on this progress, we expect to report top-line weight loss data from the 26-week primary analysis of CBON in late Q3 or early Q4.

Before I pass it on, I want to address one topic proactively, the evolving policy environment. While our focus remains on disciplined execution, we're operating in a period of regulatory uncertainty, marked by potential shifts in drug-picing policy and a lack of clear direction from federal health care leadership. Ongoing transitions at the FDA and NIH raise important questions about how innovation will be balanced with regulatory oversight in the years ahead.

At Sky, we've assessed our exposure and believe it's limited in the near term as we prioritize our clinical development milestones. We're on track and we're tracking developments carefully and we have preserved flexibility in our supply chain and capital deployment planning.

Kate will speak more to how we've accounted for these variables in our financial outlook. Overall, we feel that we're in a solid position to move forward through the next stages of the mass and mass development lifecycle and that we're uniquely positioned to help address the chronic nature of obesity and the need for sustainable long-term solutions.

Chris, over to you.

Thank you, Penny. I'm pleased to share our thoughts on a few recent preclinical studies with the mass map, a novel antibody-based periphery restricted CB1 inhibitor. These studies were designed to not only address the hypothesis that a truly peripherally restricted CB1 inhibitor, such as the mass and mass, can effectively redraw have weight loss, but to also generate mechanistic data to support Sky's differentiate approach to CB1 inhibition.

Recent biomarker analysis from our initial mouse DIO study has further extended the impact of the dose-dependent weight loss observed with the mass and mass treatment. Specifically, now we can report the mass and mass dependent reduction in fasting insulin levels that complement significant glycemic control as well as productive modulation of key appetite-regarding hormones, including GLP1 and leptin.

Additional data sets also highlight significant reduction of inflammation in adipose tissue, as well as liver steatosis. We are also happy to report that the initial study has now been repeated by an independent lab with very reproducible results, not only in terms of the magnitude of weight loss and body composition, that is, preservation of lean mass with significant reduction of fat mass, but also with positive changes in glycemic control.

This repeat study also looked carefully at food consumption and noted a significant reduction in cumulative caloric intake, lightly left but in line with semi-glutide. Collectively, these studies highlight that namazimap-dependent efficacy is driven by multiple peripheral pathways coordinated through different organ systems. Building on our monotherapy studies, we compared namazimap, monlunabant, a small molecule CB1 inhibitor, and the dual GLP1-GIP agonist to zepitide, both alone and in combination with the namazimap, using our DIO model.

We chose to use higher yet clinically translatable doses of CB1 inhibitors with the namazimap having a simple level of exposure of the current phase two dose, and monlunabant being slightly higher than its 28 daily phase two dose. Both CB1 inhibitors demonstrated significant weight loss over 23%, given by reduced fat mass with lean mass preservation. We encourage that skies highly restricted in the namazimap drove similar efficacy compared to less peripherally restricted CB1 inhibitor monlunabant in a DIO model at clinically relevant doses. This study further highlighted that why on active yet sub-optimal dose of zepitide could yield a similar level of weight loss as namazimap, the combination with namazimap produced 31.5% weight loss. These results combine with our mechanistic data strongly support the potential from the namazimap to be affected as both a monotherapy and as part of a combination approach to address the growing obesity epidemic.

These medieval studies continue to support our belief that our differentiated antibody approach can provide meaningful efficacy without the challenge that current small molecule inhibitors face, which is brain exposure that can cause unwanted neuropsychiatric side effects. To address this potential advantage, we ran a series of a vitro potency experiment designed to leverage a critical mechanistic difference between the namazimap and small molecule inhibitors.

Unlike small molecules, CB1 inhibitors, such as monlunabant, the bind to the CB1 receptor at the orthostaric site, that is, the same site as the endogenous agonist, primarily dendocannabinoids, AEA and 2AG. The namazimap binds with the allosteric site and inhibits CB1 in a non-competitive manner. We modeled a low concentration of CB1 agonist at 50 nanomolar, representing potential physiological conditions, where both drugs showed similar potency.

However, when challenged with an elevated concentration at 2,000 animals, mimicking a pathological state, such as obesity, in which endocannabinoids become upper regulated, the namazimap potency remained remarkably stable while monlunabant activity was significantly compromised. This differentiated mechanism has significant clinical implications. In obesity, where endocannabinoids can be greatly upregulated, small molecules, CB1 inhibitors, such as monlunabant, may face increasing competition to bind to the receptor.

This circumstance may potentially require higher doses of the small molecule inhibitor, which will increase brain exposure and the potential for neuropsychic risk. Conversely, namazimap's allosteric binding avoids this competition, maintaining relatively similar potency, regardless of endocannabinoid concentration.

These data suggest that namazimap may offer the widest possible therapeutic window among CB1 inhibitors, potentially delivering significant metabolic benefits without having to navigate around the hurdle of neuropsychiatric side effects associated with achieving an appropriate peripheral exposure.

We look forward to continuing our preclinical research efforts, focus on further characterizing the namazimap's differentiated and clinically relevant mechanism of action and having more data to share over the next month.

Now I'll turn the call over to our chief financial officer, Kaitlyn Arsenal. Thanks, Chris. After the market closed today, we issued a press release and filed Skye's Form 10 queue with the Securities and Exchange Commission outlining our quarterly financial results. We encourage you to reference the filing for details of our financials and the risk factors described in our other filings with the FCC.

I will now provide a brief overview of key financial results for the first quarter ended March 31st, 2025. Cash and cash equivalents and short-term investments told 59.2 million as of March 31st, 2025. Our cash load guidance remains intact with the expectation that our current capital will fund operations and key clinical milestones through at least Q1, 2027, allowing us to achieve completion of the CAA study for namazimap and CAA to be manufacturing activities in anticipation of our future dose-ranging study.

Research and development expenses for the three month ended March 31st, 2025 were 7.2 million as compared to 1.9 million for the same period in 2024.

The increase was primarily due to contract manufacturing and clinical trial costs associated with our phase QA clinical study for namazimap. Salaries and stock-based compensation consulting and depreciation expense.

Our general administrative expenses for the three month ended March 31st, 2025 for 4.6 million as compared to 4.2 million for the same period in 2024. The increase was primarily related to investor relations, marketing and communication costs and consulting and advisory fees.

Our net loss for the three month ended March 31st, 2025 totaled 11.1 million with non-cash share-based compensation expense of 2.2 million compared to 5 million for the same period in 2024 with non-cash share-based compensation expense of 2.5 million.

In closing, I'd like to briefly address how we view the uncertainty and implications of the proposed tariffs by the current US administration and any potential impact we anticipate as it relates to our manufacturing activities. Our drug substance is currently being manufactured in Germany with no expected impact from tariffs on raw materials or amphibians as they are shipped directly to our European partner from sources outside the US.

Our final drug substance is shipped to the US and is currently unaffected due to its classification under the applicable customs codes. Our final drug product is finished in the US and we currently foresee no significant impact on the stage of the supply chain, though we are closely monitoring development. We anticipate that tariff pressures will affect pharmaceutical products that are manufactured and finished outside of the US and sold into the US market, but that US-based manufacturing could also face increased costs due to imported raw materials from other regions.

We are actively tracking these changes and engaging with multiple global manufacturing partners domestically and abroad to maintain an agile long-term strategy. Our goal is to de-risk future supply planning as the CBON program advances.

This concludes our prepared comments for today. Thank you very much for joining us and we'll now open the call for questions from our covering self-fighting analysts. Operator, over to you.

Hey, Chloe, this is Penny here. I'm gonna defer the ADA versus the EECO presentation and what to expect there to Chris, because him and his team have been working really hard on that data package. But I appreciate the little bit of a layup on the other question regarding Monlonobant and the full data set. Yeah, we were carefully paying attention to what guidance Nova has been giving regarding that. And on the same note, I think what's been very important to us as a management team and overall, in terms of differentiation is being very clear in terms of our mechanism. And we've, as you've seen multiple times, we've really tried to differentiate ourselves from the small molecule space.

We've now demonstrated the mass amounts weight loss efficacy in these preclinical models. And it's not only comparable to Monlonobant, but it's also shown additive effect to trizetitide in combination. And that's the last data set that was just publicly made available where we achieved over 30% weight loss in DIO models. So I think we, it's just hard to predict at this point. We do think that the street is better equipped with that background.

We've been receiving, sorry, we've been received well from the information that we've laid out, even received well from our counterparts because we've had a chance to have dialogue there as well. That combination potential is also, I think, really evident in terms of now with preclinical data and everyone wants to see that read through with our clinical data with some blue-type compost. So I hope that your prediction's right and there's gonna be a better and a separation from that.

But that is why the rest of the work that we're doing on the preclinical side continues to be very data-intensive and we're making an effort to be at these scientific conferences. So I'll turn it over to Chris and he can tell you the expectations on that side.

Thanks, Danique. Regarding ECO, we've developed and sort of put together a pretty cohesive model based on published clinical data that looks at the peripheral versus the central activity of different CB1 inhibitors and it overlays our own phase two. Those really looking at this from the lens of PK and PD activity. And so we went into some depths and really focused on really presenting that model.

So you can look forward to that at ECO and not to give away the punch on. There's actually a lot of interesting pieces that come out of this work, but ultimately I think it makes a really convincing case or the necessity peripheral CB1 inhibition and speaks to the central, the brain activity that unfortunately is a hurdle that the small molecules are content with. It really presents that as driving the neuropsychiatric AE. So a bunch of strong data that helps really bring that to focus. And so that'll be the driver there at ECO.

In terms of 88, we'll be showing more in-depth and additional preclinical data. So we have a bunch of very interesting biomarker data, some of which came out in a press release and is up on our current deck, you can find online. There's more of that. So really looking at mechanistic data that helps really support this concept of coordinated organ systems driving peripheral mechanisms that allow weight loss to occur, not just from antirexogenic drivers, but really a few different pathways.

We think it's quite compelling. In addition to that in our initial DIO setting, we have combination data, which will also be highlighted there along with some very interesting biomarker data and support of that. So that'll be the thrust of ADA. And I think we mentioned this last time, we have now multiple colonies, with multiple collaborators and labs running in parallel. So our cadence of research is just increasing.

There's a lot of interesting questions and data sets on the horizon. We look forward to sharing that beyond ADA.

Yeah, that's a great question. So I can kick it off and I know Dr. Roar is on the line, I see him on the portal. So I'm gonna let him talk about the regulatory interactions. But there's been two kind of key activities at Chloe that's important for us. One is being very clear, crystal clear, in terms of what's that roadmap for approval. And the approval regulatory development strategy in obesity or anti-OPC medications hasn't shifted. So even with the new guidance, we're sticking to that overall strategy in terms of obtaining approval as a monotherapy.

But the big bug there is that there's obviously an advancing kind of landscape with the incurred in class continuing to demonstrate success. But at the same time, there's this opportunity of patients coming off drugs, discontinuation rates, tolerability issues, maintenance opportunities, and there lies a significant opportunity. So one activity that we've been really active in is active in, not active in as the target, but is the discussion with KLLs and how that defines the target product profile and how that refined target product profile goes after a very clear market.

And we probably have some of that information become available in Q2. But in the second strategy is the regulatory strategy, which a lot of it gets defined after the data readout on the 2A. But if Dr. Aurora wants to elaborate, I'm gonna turn it over to him.

Yeah, sure, thank you. Chloe, we in the not so distant future, I'd say, in the near future, we are going to have an opportunity to have these regulatory interactions. As Pudding pointed out, we're going to have data from the phase 2A, which will be available in Q4 this year. And we're going to take that data and take that opportunity to have discussions with the FDA and possibly with other regulatory properties, both in terms of seeking their advice and also proposing definitive or dole-ranging phase 2B study to this. And that will be an opportunity for us also to discuss populations of we can study and how we can define them. So I think that with data and plans.

And there, Jay, I'm acting as operator right now. So I'm going to let Chris take that first question and then maybe that's teed up really well for two who's been handling all the commercial assessments. And so after Chris can give you a response in the second part of your question.

Thanks, Green, and thanks for the question, Jay. So we actually need to clarify the combination data was around tresapatide. So in combination and alone with tresapatide. So in terms of body composition, we did see when we look at NEMACIMAB model therapy, similar to what we saw in the previous repeated studies, which by the way, those were done with independent labs and we saw very reproducible data.

We see body composition where significant reduction in fat mass with preservation of lean mass. And we see that to a lesser extent with tresapatide, chisaptide alone, still significant, but it's trending up towards less fat mass. And in combination with NEMACIMAB, we see the greatest amount of reduction. They're all fairly notable. And so there's not like a huge shift, but we do see that in fact in combination, it looks like there's even more fat mass there. So it really sets the stage for combination. If we look at the weight loss, we see this nice out of effect, partially out of effect. And this again gets back to some of the mechanism where there is some overlap in the entergetic driver compartment, if you will.

So the clerk in case both can impact that pathway, but there's additional pathways that CB1 in addition with the mass in that touch on. And we feel that's where we get this additive nature of the weight loss.

And two, do you wanna take the next piece?

Yeah, we've been, thanks for that question, Jay. We've been modeling sort of our commercial opportunity. As Penny said, we've been doing a lot of sort of a commercial assessment of the mass in that in terms of what the target populations really are. And as being highlighted, we think we do have that opportunity both as a monotherapy and in combination.

Monotherapy, most likely in the area where patients are intolerable or unresponsive, or have a contraindication to GLP1s, which we think is probably a much larger opportunity that some people may have originally thought. In terms of the combination opportunity, again, I think this is a potentially large opportunity where you have a class of patients who do require some significant weight loss, again, looking at that 20, 25% plus weight loss, likely in that class three obese population, where maybe again, they're not tolerable to the higher doses of, let's say, a tereseptide and can achieve those higher weight losses, or they need just additional weight loss on top of the tereseptide or other GLP1 class. When we look at sort of what those commercial opportunities are between the monotherapy and combo, they're relatively equal, I think, at least at this point in terms of how we're seeing the market.

They both are quite large and they, billions dollar size markets, and one hasn't necessarily differentiated itself at least at this point as we've been going through the analysis.

Okay, great, thank you, that's super helpful. And if I could squeeze in one last follow-on question, have you guys done any work on the co-formulation of the Massumab with GLP1 or GLP1GIP, and is a fixed dose combination technically feasible? And can you comment on any potential IP advantages or lifecycle management advantages of doing a fixed dose combination?

Yeah, that's a great question there, Jay. So the opportunity for us in terms of co-formulation obviously exists, but that hasn't been something that we've explored yet. The first proof of concept is gonna be just in terms of the dosing happening at the same time in the current trial. Instead, there has been interests from a fixed dose perspective. We definitely see an advantage of being a biologic being an antibody that there's really a future where you can be a CB1 plus story.

So stay tuned, I think first things first is we wanna demonstrate the Massumab's advantage as a monotherapy and highlight this data and it's been well supported by the preclinical evidence. And we expect that later this year, once we get through the clinical data, we can start highlighting what does that pipeline look like as a CB1 plus story that includes fixed dose.

Okay, great. Thank you so much for taking all the questions. Thank you.

Dr. Roy, you wanna take that question?

Sure. So we are actually holding these online reviews on a quarterly basis, but the independent DMC meets every quarter and they are provided with unblinded data on safety in order to review. Now, what we have told you, and as you were mentioning was that they've reviewed that data and told us that there were no concerns moving forward with the study. They are provided with a list of all the adverse events that are reported in the study and the previous adverse events.

We also report any neuropsychiatric events that may occur in the study as adverse events or special interests. So those are also channeled into the DMC. So they get to review all of this and they are doing it on a quarterly basis and no concerns have been raised so far. The next review is scheduled for July the 18th and they will be ongoing from there on until the study ends.

Yes, they, I mean, they get all of the data that's available for the study and they are, we have on that review board two psychiatrists, actually, and we have people who have experienced both with CD1 and with obviously studies in general. So, it's a very experienced set of people who understand exactly how these studies run, what this data looks like and what they're looking for.

Yeah, Albert, that's an excellent question. So the primary endpoint is for 8%. At 26 weeks, based on what has been kind of shared, now, when we put that number out, we had the, we didn't have the benefit of 16 week data from Monunabant, which showed 5.7% to placebo adjusted to five recall. So, for us, we are expecting to see separation between placebo and active and obviously we're targeting over 5%. The study has a design based on 8%.

Yeah, there is a, there is a rollover period that we've had to account for because naturally there's an operational kind of updates that come along with adding an extension that wasn't previously a part of the protocol. But we don't, I mean, the data will be collected based on weight and other parameters at the start of the extension as well. So it, it's, you know, we don't know if there's going to be variability, but if there is variability, it'll be collected in terms of the data and we can discuss that once we have all that information.

Hey Ted, thanks. That's, you know, it's a pretty important question. Like as we talked about in the last earnings call, what we really wanted to try to do is maximize what we could from the current trial. So having one, having the trial up the phase two way up and running with the primary endpoint based on 26 weeks, it did allow us the flexibility to leverage a study that's already there, patients already enrolled and then generate another data point that allows us to have broader efficacy, safety data, other information that we're collecting from the trial.

So that's been one of the key factors and it's always been important for us to eliminate any white space between any of our development objectives. So at the moment, this extension actually slots in really well before the phase two B starts and allows us to take the phase two A data, able to have a productive discussion with the agency about what a phase two B would look like. And at the same time, continue collecting information based on this extension before that phase two B begins. And perhaps even inform the phase two B to some extent. But at the moment, it hasn't created any extra time. In fact, it's slotted really well operationally and we have to drug product to be able to be able to get that additional data point.

The last thing I would say is that the 52 week data point is another important thing to continue to build confidence on the broader safety that we wanna see with this mechanism. So I think that's been another important factor and as well as the tolerability information. Dr. Roy, do you wanna expand on anything I missed?

Yeah, I just, I think you've covered a lot of it. I just want to add a couple of small things. It's so in the vulnerability on this because it's an open label arm, we are able to continue to refine our PKPD models as the study goes on beyond 26 weeks and that will help us in picking the correct dose range for the phase two B study. So that data will be helpful.

And of course, as Pudid pointed out, the safety data is invaluable because we are treating longer and being able to show that the mask lab is safe and tolerable. There is also a second arm to the study. So we're also extending the combination dose. And the combination dose isn't currently being tested in the proposed phase two B which will be a dose ranging for the model therapy. So for the combination dose, we're getting this additional 52 week data which just adds to what happens when you dose these drugs together and what happens to the perfs and the trajectories of weight loss. So we think that data will be really useful both for safety and for efficacy.

Well, at the moment the phase two B is planned and proposed as a monotherapy study because what we need to do is to do a proper dose ranging, right? We need to understand what the optimal dose for the mask map is. It doesn't preclude the idea that we could do a study with the combination or do other work but it is necessary to find that optimal dose in order to go to phase three.

Yeah, Kristin, that's a really great and important question that you've raised. The data generated so far preclinical wasn't something that we had when we launched the program. So, this demonstrating that we've now, I think there's three important, kind of important takeaways here. We've demonstrated this robust inhibition of CB1 across multiple assays, data information's available in the deck and that shows the potency relative to, or the differentiation relative to small molecules.

We've continued to benefit from a really strong safety profile. We had this previous work of multiple distribution studies done in NHP, she didn't show any CNS penetration. We've achieved now monotherapy of like 16 to 23 and a half percent weight loss in several studies and repeat studies as monotherapy and now shown over 30% in a combo model.

So, across the board, it checks a lot of boxes. How does that translate to human? Of course, it gives you this aspect of, well, we feel more confident around the mechanism and there's this component that comes along with it that we expected to translate into the clinic. But to be at the same time, transparent, that these are my studies. So, we have to put that in one aspect and the only other confident thing that we can leverage is that the DIO models across the landscape have been interestingly a very good tool, a very good tool in the therapeutic area, a therapeutic area across different mechanisms. So, the DIO models have translated to some degree in the clinical setting.

So, that's kind of our broad take. Chris, do you want to take any different approach on entering Kristin?

No, I think you touched it really all the key points. I might just add a very small detail and that relates to, and this is sort of the translatability and how well in terms of confidence, do we feel the DIO models will predict what we see in the clinic and you catch on from the key areas. But what other aspect is, we're dosing, when we look at our DIO dosage, it looks relatively high and it's worth noting that we have a very different behavior in terms of the GAP profile in the mouth than we do in the human.

And so, we're very mindful looking at exposures, not necessarily a C-max. It's really when you understand the whole area of the curve analysis and what the exposure and engagement looks like in these DIO models and keep in mind that these are obviously very short duration relative to what we're doing in the clinic. So, when you look at that all together, you really start to appreciate how we're matching exposure and we're looking at doses that are, we feel very translatable.

And we've seen some success with predicting efficacy in the in-grin space and arguably looking at the CB1 space with no-boo dataset which we feel is actually a pretty significant dataset. This is actually a very, I think very strong dataset and they too had DIO data that looked pretty strongly reproduced that in our own lab. So, coming back to this idea of translating, we do feel pretty confident that we're going to have an active target in the clinic. So, I'll just add that piece, that's all.

Thanks, Chris.

Yeah, thanks, Andy. So, we haven't disclosed any new data today. What we expect is updates to these datasets that we've shared recently in upcoming scientific meetings. And we'll keep some of these in from that information close to our vast until we get there. But there'll be an update at those meetings. And what we're committed to, as Chris kind of pointed to earlier, is we now have multiple efforts underway, domestic and international, where we are going to continue to build on the understanding of the mechanism and support our clinical activities and biomarker activities and other stuff.

So, because of that workflow that is allowing us a much larger data set to work with and continue to support our clinical activities.

I'll turn that over to Dr. Aurora, and then Chris, you can elaborate on anything after Dr. Aurora.

Yes, so your question was about regulatory interaction. So, as you know, with protocol amendments, the FDA doesn't ask for and doesn't grant actual meetings. So, we have submitted the protocol amendment to the FDA. They have asked us for some minor clarification at this point. And we have already sent them the responses for that. It's our expectation that we will be able to, we will be able to sort out the minor issues that have been raised, and we will be able to start rolling patients into our extension.

It's very unlikely that they will ask for any kind of actual meeting around the protocol amendment.

So, Jonathan, we're still blinded to the data, so we don't really have access to anything, but Dr. Roy, do you want to take staff at anything that you want to provide context from your experience?

Yeah, so we have, I think we managed to get a pretty good representative population recruited for this trial. We do have some Hispanic representation, and we also have a pretty good weight range to my mind, so once we unblind, we, to the extent that some analysis is actually possible based on these parameters, we will be able to do that, but at the moment, as Tony pointed out, we have blinded, so it's hard to know right now whether or not there's any correlation or whether any of these individual parameters are making a difference.

And so that's one of the reasons that we've kept the rollover gap small, is that we don't want patients off some of the diet for any extended period. They are limited to being off their drug for only four weeks, and this will only, this will only account for the few initial patients who will be able to join the rollover extension when we are able to begin it and have recently finished. After that, everyone who rolls over will rollover directly, so there will be no gap, and we won't need to do any nose adjustments for the semi-glutide, because they're already on effective doses of semi-glutide. For the few patients who will have this small gap, we have made some allowance to be able to go back a little bit on those and be able to, if they're required to, and to be able to re-adjust to the semi-glutide, we know that these people can tolerate the effective dose of semi-glutide, because they will all have completed 26 weeks of treatment on it.