Skye Bioscience (SKYE) Q3 2025 earnings call transcript

Hello, and thank you all for participating in today's call. 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 US private securities litigation reform act of 1995, including statements of the sky's expectations regarding its development activities, timelines and milestones. Forward-looking statements are subject to risk and uncertainty 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 or update any statements made today. I encourage you to review all of the company's filings with the Securities and Exchange Commission concerning these and other matters. I'll now turn the call over to Caitlin Arsenault, Sky's CFO.

Thanks Bernie. After the market closed today, we issued a press release and filed Sky's quarantined queue with the Securities and Exchange Commission outlining our quarterly financial results. We encourage you to reference our filings for the details of our financials and the risk factors described therein.

I will now provide a brief overview of our key financial results for the third quarter ended September 30th, 2025. We ended the third quarter with cash and cash equivalents and short-term investments totaling $35.3 million. We expect our current working capital to fund operations and key clinical milestones into 2027. This includes the completion of the extension of our Phase 2A study for NAMASMAB and certain manufacturing and preparatory clinical activities needed to initiate an extent.

In addition, our runway continues to include a modest discovery R&D budget and the dose concentration and processing intensification were required to support our expected TPP and scale and support later stage studies for NAMASMAB. R&D expenses for the three months ended September 30th, 2025 or 9.4 million as compared to 4.9 million for the same period in 2024. The increase was primarily due to contract manufacturing, clinical trial costs associated with our obesity study for NAMASMAB, discovery R&D expenses, salary and stock-based compensation expense and consulting advisory and professional fees.

General and administrative expenses for the three months ended September 30th, 2025 for 3.9 million as compared to 4.6 million for the same period in 2024.

The decrease was primarily related to decreases in consulting, advisory and professional fees, recruitment fees, salaries and stock-based compensation expense.

Our net loss for the three months ended September 30th, 2025 totaled 12.8 million including non-cash share-based compensation expense of 1.9 million compared to 3.9 million for the same period in 2024 with non-cash share-based compensation expense of 1.9 million.

Now I'll turn the call over to our president and CEO, neat Dylan.

Thanks, Kate. So today and during this quarter and the subsequent quarters, we're really focused on what matters most, turning the answers from our CBON study into the logical next steps. We're gonna walk you through what we've learned from our Phase 2A CBON study so far and how that data has really sharpened our focus, maintained our focus on our clinical path and strengthened our conviction in an MS-MAB opportunity.

From the start, we said that the next step for the MS-MAB would be to determine an optimal dose for an MS-MAB. And to that end, the top line data from the Phase 2A study provided us with a wealth of information that we continued in mind for further insights. Most importantly, it gave us evidence in the biological activity of the MS-MAB and the clarity on the PK to move forward confidently on our combination development pathway while simultaneously planning to further understand the MS-MAB's benefit in a monotherapy setting.

On today's call, we'll walk you through the progress that we've made over the past 90 days, the data that we've generated, and the path that we're really focused on in terms of charting forward. We're gonna cover four key areas today. One is clinical development, specifically what we've learned from the CBON study, how those insights are shaping the potential for future next studies.

Number two is CMC and product economics, how we're designing the MS-MAB for scalability and long-term market penetration. Number three is R&D, and the work we're doing there, the science that continues to validate that peripheral CBON antibody and, sorry, the MS-MAB or a peripheral CBON antibody is differentiated and it's a durable mechanism. And four, the continued emphasis on just really strong accountability and consistency. How are actions this quarter measure against what we said that we would deliver?

And I'm gonna conclude with an outline of what's next. I look ahead at the key milestones and the catalysts over the coming 90 days. So first, let's get into the clinical development.

We'll start with what we said last quarter and where we are now. In Q2, we committed to three different things. One was deliver top line data in Q4 from CBON. Two was the use that data set to inform the dose ranging strategy for the next clinical phase. And three, maintain operational and regulatory milestones and readiness to move efficiently into the next study. And we've delivered on each one of those commitments.

At obesity week, last week, Dr. Lewaroni presented the late breaking results from CBON and the findings are both clear and very encouraging. We showed synergistic efficacy with the MS-MAB plus semi-glutide and achieved an additional approximately 3% weight loss at 26 weeks compared with semi-glutide alone. This was with a p-value of 0.0372 on a modified intent to treat population.

That's nearly a 30% improvement with this combination with no observed plateau at 26 weeks. We also showed quality of weight loss that the combination of the combination of the MS-MAB and semi-glutide improved lean to fat mass ratio of 0.26 versus 0.13 with a p-value of 0.0126.

And reduced waist circumference by an additional 3.17 centimeters with a p-value of 0.0492. We also showed durability in the 12-week post-treatment follow-up, the MS-MAB plus semi-glutide blunted weight regain with an only an 18% regain or 2.3 kilograms versus 50% regain or 4.7 kilograms on the semi-glutide alone are, then that's with a p-value of 0.006 versus placebo.

The safety signal has also been very positive. There's been no neuropsychiatric signal and no additive GI burden. And so this overall data really confirms that the MS-MAB is biologically active, clinically meaningful in combination and exceptionally well tolerated. They validate our long held view that the mechanism is sound and that the value now lies in rerefining really the dose to unlock the MS-MAB true efficacy window and fully capture the therapeutic potential of a peripheral CB1 antibody.

Additionally, in September, we completed enrollment of the 26-week extension study. A total of 43 patients were enrolled with 19 and 24 patients in the combination and monotherapy cohorts respectively.

Retention in the extension study has been very strong and the data from the 26-week extension study is expected in late Q1, early Q2 of 2026 and will provide information on the potential for full treatment duration of 52 weeks followed by a 12-week follow-up period.

This long-term follow-up from the extension will be a new inflection point with a richer data set and a more complete understanding of the MS-MAB's clinical potential.

In parallel, we're gonna continue moving up the dose. So the monotherapy extension study is evaluating a slightly higher dose where we've stepped it up from 200 milligrams to 300 milligrams weekly, but our current plan is to even go higher. Analysis of our preliminary PKPD model showed that patients achieving higher systemic levels than the MS-MAB corresponded with a greater weight loss and that aligns with the range where we expect to show clinically significant results.

Our PKPD model based on the clinical data and the pre-clinical dose ranging really gives us confidence that the higher dose, a higher dose of the MS-MAB can potentially achieve better model therapy efficacy and drive even further weight loss when combined with some agglutide. The parallel approach that we're taking with further clinical data from the extension study for the durability and then evaluating a higher dose ranging in a well-powered phase to focused combination study with understanding a better characterization of the monotherapy dose will really keep the development of the MS-MAB on track and we're really focused on that. And we think that that's the next logical step for understanding our next important decision points.

Next, I'll move to CMC. So another area that we've continued to make progress in has been all of our manufacturing and CMC work that includes our high concentration formulation strategy. And that remains on track and we believe a path to achieving the formulations that really align with our clinical protocols and expectations for our TPP as well as patient convenience remain on track. This isn't simply like a technical milestone for us. It's really rooted in a commercial TPP and our focus is on reducing overall injection volume, lowering costs, program and ensuring we can compete as pricing pressures on ingredients continues to continue to intensify.

This aligns, we believe perfectly with our titration free target product profile. And that's a key advantage over the included based injectables that require a step up dosing for tolerability.

To clarify, the MS-MAB has shown no additive GI burden at the 200 milligram once weekly dose. And we expect to evaluate any higher dose without the need for titration, making it easier for both prescribers and patients. Equally important, we're continuing to evaluate and manage and execute on measures that can significantly impact our cost of goods. This process includes optimization of the upstream and downstream manufacturing steps for the MS-MAB and scaling up into high fermentation volumes.

And we're continuing to evaluate multiple delivery devices, including auto injectors that will improve the patient experience. Together, these activities will have a significant impact on reducing our cost of goods to support an eventual pricing model that aligns with Medicare and is rapidly influencing the obesity market.

We're ultimately designing a product that is potentially not only clinically differentiated, but commercially durable, from a manufacturability and real world affordability.

Next, we'll move into R&D. So beneath all the clinical data sits an increasingly powerful scientific base. The preclinical and translational work continue to show that the MS-MAB reduces fat mass while preserving lean mass, improves insulin sensitivity and glucose control, lowers leptin and increases GLP1, reduces hepatic steotosis and inflammatory markers and maintains weight loss durability after treatment stops.

And this is consistent with what we're seeing clinically. Combination studies in DIO models with triseptide and semaglutide show greater than additive weight loss and minimal rebound, confirming peripheral CB-1 inhibition, complements increased in biology mechanistically. And collectively, these results reinforce why the MS-MAB is really the right molecule, the right mechanism and the right program to move forward.

Our message to investors ever since we began development on the MS-MAB program has been about discipline and delivery and that remains true to today. In Q2, we said we'll complete the top line readout by late Q3 or late Q4 and we did that and we presented late breaking data at obesity week last week. We also said we're gonna continue with the current data set to guide our dose ranging and that's what we're doing.

We're gonna continue advancing our CMC readiness in parallel and we continue to improve manufacturing capability as well as process improvements are gonna continue to be ongoing that we're focused on the higher concentration formulation path and that's on track and synchronized with our clinical development planning.

We ultimately expect our monoclonal antibody to be the best way to target CB-1 inhibition to enable confidence in the safety and this pathway will ultimately show the clearest mechanism validation in terms of targeting this particular pathway. With our Phase 2A data, we have now provided an important initial demonstration of the MS-MAB's utility that does offer the validation of the mechanism and notably we did that by showing that there is no neuropsychiatric adverse events or other unexpected adverse signals across the different cohorts that received the MS-MAB and we've just completed the fifth DMC meeting this past week with no concerns.

So every commitment that we've made, we made it on time, we made it with precision and we're gonna continue doing that. Over the next 90 days and into 2026, our focus is on converting what we've learned from the clinical data into further execution. We're gonna generate a more complete picture of the MS-MAB's potential using insights from our PK and PD modeling and the ongoing extension study.

We're finalizing the next Phase 2 design that we're concentrating on combination and also in maintenance indications where the data already point towards a really strong direction and we're continuing to advance the formulation and manufacturing work so that the MS-MAB can be delivered practically at scale and with the cost discipline that the market demands.

We'll also be presenting at several investor conferences beginning next week and into December and gearing up for sharing new preclinical and clinical data at all the major scientific conferences and meetings in 2026. Across each of these fronts, the through line is really about consistency. We've said what we would do and we've delivered on the data and then on the timelines and on the execution.

Our next steps are an extension of that same discipline and we're interested in continuing to focus on translating all of this into momentum and the momentum into value. So this concludes the prepared remarks and comments today. We thank you everyone for joining the call and we'll now open the call for questions from our covering Southside analysts. Operator, over to you.

Hey, Michael, thanks for dialing in and asking the questions. We'll take the first question and kind of hand it over to Chris because you can further elaborate. But as you kind of indicated there, obviously we showed a really strong validation of the mechanism in the combo efficacy. The monotherapy dosing I think has been evident in terms of issue with dose, not the biology.

The exposure response really has demonstrated that the observed concentrations at the 200 milligram dose didn't achieve the efficacy that we would expect because they were patients were under dose. But Chris can further elaborate in terms of what we've seen now based on the 26 week data set as well as any thing he wants to point to from the preclinical data.

Thanks, Benite. Yeah, so to that point we have in fact looked at a more complete PK data set. I would just note that the final PKPD analysis which is still underway likely won't be available and probably for another few more weeks to a month. But we do have a more robust build out and we looked at a mixed effects model, both controlling for the placebo effect as well as doing a similar type of modeling where we controlled for the semi-glute head effect and looked at that in a combo setting.

And in both instances we see that there's really no bias in the residual so the model fit well. They align with the observed weight change that we saw in the trial. And importantly, they point to the point you're making that is we're seeing a nice slope, a very believable credible slope that demonstrates this response related to exposure. We feel very comfortable that the PK data's holding will again have a final PKPD model but we feel very confident that in fact there is a dose response.

And as we get to better and better exposures we will see better and better weight loss as both monotherapy and in combination. And the other thing I've just pointed briefly since we've last talked, Michael, the translation of the DIO data has been further validated. We've done some important bio distribution studies looking at the where or the compartments and how those fill relative to what's in the serum and using that along with some other approaches to really get a good fit in terms of how the DIO data which demonstrates very clean dose response as well and how that translates to the clinical doses. So both those pieces are really supporting this concept of higher dosing in the clinic to see better weight loss.

Michael, would you mind just repeating your second question or did we answer it?

Yeah, so the good news on the extension is that enrollment has been, obviously that was good that we saw a good interest in the study and then retention has continued to stay really strong. It is a smaller number of patients relative to the core study, the first part, but we do believe that there will be a clear separation that we would be able to see, especially as if you recall, in the 26 week time point, the first 26 week time point in the combination, we did see a really strong difference and then the slope wasn't plateauing, it continued. So we hope that we're gonna continue to see that separation between semaglutide alone.

On the monotherapy, as we've indicated, we believe that there's still room to go higher in terms of dose, so we'll see what the data reveals, but at this point, it's a little tough to comment on that because we don't have that separation that we expected on the first 26 weeks.

Yeah, these are both great questions and interrelated. I can pass it over to Dr. Aurora to take those and then I might come back with some additional commentary on the maintenance setting.

Yeah, Andy, to address your first question, yes, if we were to do maintenance therapy with the math lab as a monotherapy that would require monotherapy approval, although if that is the strongest food for the drug, then the approval could be as maintenance as well. And we are as part of our plan as we go forward is to continue looking at the monotherapy to find that up to those and frequency on how to those monotherapy for varying indications, including maintenance.

That's a question that we will be discussing with the agency and I think that will be part of our continuing interaction with them as to how to push both monotherapy and combination forward and what differential part each one may need.

So I'm sorry, what was your second question?

Oh yeah, so, you know, if you look across, if you look at weight rebound data across a bunch of studies, there was a step one withdrawal study, I think it's one of the ones your core had some and then to zip it, I did some randomized withdrawals. In one year, the whole weight regain is about, and it does tend to be somewhat accelerated in the first half because the weight regain faster initially and then tends to plateau a little. We do see a somewhat faster regain in this study. We don't know why. We don't know of particular characteristics of wasting in the demographics in the study of frankly the same as you see in most other studies.

So we don't know why these patients regain their weight this quickly, but they did and being a randomized trial, we figure the both the cohorts are effectively similar.

Yeah, I think just to elaborate on one thing, Andy, so you look, the durability data that we've showed last week with the only 18% regain versus 50% for semaglutite alone is I believe a real cornerstone of our strategy and it really validates what we saw from an R&D preclinical perspective. It shows that peripheral CB1 inhibition can provide a durable effect after treatment stops, which is a significant issue for the Ingrid and only therapies. And I noticed, you know, coming from obesity week, there's been a growing emphasis of the Incredence or companies that have Ingrid and pipelines focusing on the maintenance market as well.

We believe that this comment we made at the last earnings call and we stand by it as we do believe that we really have an interesting opportunity for the Massumab to aggressively pursue a maintenance indication, which we can formally kind of look at once we finalize our dosing strategy, but we see a massive commercial opportunity that's differentiated because it's more likely and doctors will confirm this, that they would treat with a differentiated mechanism rather than maintenance with another Ingrid and after induction of Ingrid and is completed.

And no twos investigated that from a commercial standpoint from the survey that we've done and that's been confirmed too. Do you want to just expand on that?

Yeah, I know, I think you kind of covered it pretty well. I think it is important to understand that the maintenance approach therapy is something that's being looked at a lot, not just by sky, but from investigators and clinicians as well as obviously, you know, other companies. And then as Finite said, you know, right now there's not a lot of options other than another GOP one for patients to go on.

And so physicians are generally either reluctant or in fact, at least the ones I've spoken to and generally actually put them on something else other than a GOP one, like a Fenterine or something like that, that that makes more sense because of the different mechanism of action, even though Fenterine may have some other comorbidity issues as well as maybe not be as effective.

So I think again, in that space, I think there's a real market for drug like the MassMap that we think we can, where we think we can win.

Yeah.

Yeah, I think it's a great, thanks Ananda. I'll turn it over to Panita Rora. He can take both those questions.

Yes, Ananda, thanks for that question. You've seen that a lot of the effective weight loss mitigations that we've out there cluster in around the 20, 22% range. In fact, if you, you know, if you speak to most of these decisions, they'll tell you that a lot of patients don't even need for the weight loss, frankly, once you start exceeding about 10% weight loss, you can reverse a lot of comorbidities. But, you know, in so far as the benchmark today is about 20% semi-glutide or a generic GLP one, usually it's about 15% and then we start seeing the other combinations adding up to another 5%, 6% like you see with this appetite.

That's a differential that we would hope for. We're already seeing in our protocol set here a 14 point something percent weight loss at 26 weeks, which is three and a half percent more than semi-glutide alone, so it's about a 35% increase. And we think that when we do a full 52, actually a 68 week treatment, which is where all these are measured, we will have a combination treatment effect that will be in the range or better than what we are seeing with all these other current combinations.

We are actually seeing improvement in body composition along with this 30% weight loss, so we had printed this at obesity week as well. What we're showing is that if you just look at the crude numbers, semi-glutide alone has about a 72% fat loss and 28% clean mass. And when you add the mass map to it, this actually becomes a 76% fat loss and only 24% lean mass loss. So there is a transition towards fat mass loss. And when we break this down, we see that as you know, there is 30% extra weight loss, right? But the fat loss goes from 15% for semi-glutide to more than 20% when we look at the combination.

Whereas the lean mass loss almost doesn't change. It goes from about 5.5% to 6%. And that is what is the effect that we are seeing in the lean to fat mass ratios and why the body composition is improving. So all of the additional weight loss existing is almost all fat mass loss. Our secondary endpoint to be specific was lean to fat mass ratio. And that ratio should increase with weight loss. And the more the increase, the better your body composition is. And in our trial, semi-glutide increased that lean to fat mass ratio by 0.13.

And the combination improved by 0.26, which is twice the improvement. And this number was actually significant. The P value was 0.01.

Yeah, thanks, Jay. Thanks for joining the call today. That's a key question. We are certainly focused on the induction side. When we're seeing this improvement that we've showed over the course of this early data set with no observed plateau at 26 weeks, it really demonstrates a synergistic activity. And it's been very encouraging. We were looking forward to seeing what the 52 week data reveals, but the current focus for the phase 2B is on evaluating the right and optimal dose in combination with SEMA.

And I think there's a little bit of other supportive data that we've seen from a preclinical perspective that Chris might be able to point to in terms of why we feel confident of dosing higher can lead to a better, deeper weight loss in SEMA, because of the data that we've seen so far, which was appetite in SEMA in combination.

Chris, do you want to discuss that?

Sure. Yeah, to that point, we directly asked that question in light of our recent clinical data. It was important to understand as we get better exposure, moving from what we've modeled to be, something very similar to our CV on the MassNAM dose, which we're calling sort of a sub-optimal dose in this DIO preclinical model. And then a more active dose, an active dose representing something that we're looking towards potentially using in future trials. So comparing the difference between the active and the sub-optimal, you can of course see that as a model therapy in terms of weight loss, importantly, when we look at this in the setting of combination, we see while the added effect is there, we really see a large improvement beyond the magnitude you might expect with the model therapy.

So it seems to really unlock the combo potential as well. It may be even beyond what we see as a model therapy. So it's important, we think, to really get the dose right as we look towards sort of that induction combination approach in the clinic.

And I think it's just important for us to emphasize that it's really relevant in terms of being a truly differentiated alternative or orthogonal approach to what's out there in terms of current combinations. So although the data is early in the 26 week data is very encouraging, when you do stack it up across these other combinations, it's really interesting to see how deep that response is initially. So we're all excited to see how that reveals in a longer 52 week data point.

But it makes, at the moment, it makes a very compelling case for us to evaluate this in a phase two B combo.

Hey Jay, this is too, I just wanna sort of also add in the relevance of this sort of this rebound data and what I think that also means potentially for a market opportunity, not just in the maintenance setting, but also more in the combination setting where you can get that induction of weight loss.

And if in the real world locations need to go on a dosing holiday for whatever reason, maybe they're actually going on holiday, they just don't wanna bring their drug with them, or maybe they have other things, maybe there's access issues, things like that.

What our data suggests is that that's not gonna be as big of a problem as it has been when patients do either lose access to their GLP1 or lose, or have to go on vacation to have other reasons, that they're not gonna have a significant rebound like we're seeing and that like the step one data has shown in that you can have this sort of holiday without sort of losing the gains that you've achieved through the treatment. So I think that's really meaningful, I think a lot of the positions are looking at that and what that means is how you can manage patients' weight over a much longer period of time than just sort of these sort of compressed times you're seeing in clinical trials and what that really means in the real world for patients.

Okay, great, thank you, that's super helpful. And if I could ask a second question, can you please talk about any KOLC back you've received following your top line CBON phase two-way data and also any feedback you may have received over a few weeks?

Yeah, I think Chris is, sorry, two, probably verse two and Dr. Roy, you guys can take those questions.

Yeah, thanks for the question, Jay. I'll say that I think the reaction was positive. I think they see the combination data as very intriguing. They think that the responses that they're seeing are different and they definitely look forward to looking at sort of this dose-ranging study. They obviously see that that's a key and that's gonna be really important for us to establish. That's sort of baseline with that optimal dose. Dose is gonna be, in terms of the blunting of the rebound data that also has kind of resonated with the number of physicians and KOLs that we've spoken to to the point that I actually just just brought up earlier, one specific physician actually brought that up and said this is really cool data.

And if this means that a patient can go on a dosing holiday and not have to worry about gaining their way back, then this can be really meaningful for their practice. So yeah, I think ultimately positive.

And again, from a monotherapy side, I think they recognize our need to dose higher. But they don't see that as necessary a deterrent for the future of the program.

And I think that- Some of the leading physicians out there had experience with CD1 before. So that's why they've had interest in for a long time and the psychiatric events have been a force of probably really, I think they're really enthusiastic about the idea that you can get these effects and get them in a safe and tolerable manner. So there's a rekindled interest now that we are showing with this biological activity. And you can do that with an antibody without crossing the blood brain barrier and getting these zero psychiatric effects.

Yeah, that's great that you emphasize that, Dr. Roy. I mean, I think that was the biggest immediate takeaway once the data hit the tape that we saw when we spoke to our clinical advisory board and other investigators that a lot of folks had just recognized that this was a big leap forward for the class. This is the first time that any data set has been shared with no neuropsychiatric adverse events.

So that's a really important kind of step for us in being able to give us the comfort to be able to dose higher and we feel confident that there's gonna be biological activity.

Thanks, Jay.

Hey, Catherine, thanks for joining the call and stepping in for John. We, yeah, so from the next 26-week data that the differences here is that we've added, increased the dose from 200 milligram to 300 milligram. What we have emphasized, obviously to our clinical sites is really making sure that there's strong follow through in terms of the, not only from a patient retention standpoint but ensuring that if there's any noise here regarding compliance, we rectify that. So at the end of the day, what we're really looking for is a better understanding for our PK model at this dose. In terms of efficacy, it's really hard to predict at this point in terms of what that's gonna be relative to what we've seen so far in the first, based on the 26-week data, we're obviously encouraged by the PKPD modeling that we've done at higher doses that we should be able to reach the 5% or higher bar but we need to see that data and we want to make sure that we have improvement in terms of our sensitivity around the PKPD understanding.

Okay, I'm sorry, just to clarify, we did use a slightly higher dose in the extension but as we need to say, primarily to help us refine our PK models, we will be, when we do a face-to-study, we will look at meaningfully higher doses and different exposures and we'll take that with a more positive result.

Yeah, we're still working through that, Catherine. For monotherapy, we expect basically to unlock efficacy at higher doses. So we've, like we said, it's in line with our exposure and response modeling and it hasn't necessarily ruled out that the 200 and 300 are effective doses as well. I think we had some lack of consistency in terms of what we saw in the face in the first 26 weeks and in our slides that we shared during the top line data review.

I think we showed some indication of what the optimal dosing would have revealed and those patients that had increased exposure response, they tended to do really well versus the patients that were suboptimally dose or that had lower exposure response. So I think what we need to see is if that is kind of course correcting in what we're evaluating and then we have confidence that dosing higher is definitely going to show a higher likelihood of efficacy signal that we expect to see and we expect that to be over 5% at 26 weeks at these higher doses that we want to evaluate.

Hey, thanks, Ted. Yeah, I think we feel really confident about the safety signal and allowing us the room to go higher in terms of dose, especially from the standpoint of any concern of neuropsychiatric adverse events. So even in this study based on our phase one data, based on our talks data, there's a substantial amount of room relative to where we're at in terms of dosing. In terms of other safety concerns, I think we have to see. So we don't have the data to get at higher doses over the longer period of time, whether that's a change in terms of GI tolerability.

But we feel at this point, based on the data that we've seen in the phase two, that there wasn't any concerns to be able to go higher. But across the class, it seems to be a little bit different. Some small molecules have had only about 30% GI issues. And then the Monluna Band data recently showed about 60% GI issues.

And we don't know if that's linked to CB1 yet or if it's, you know, or if it's like, if it's molecule specific. At the moment though, there still seems to be substantial room for us to be able to evaluate that. And mechanistically, it's not the same. It doesn't, the mechanism is different than what the GLP1 drugs are doing.

So we feel that we shouldn't have any exacerbated GI burden. But Dr. Roy, sorry, you might wanna take that further.

Yeah, you know, it's been my sense that even with the data, I should go back to Ramonabant, that even though they showed 30% GI effects, there was a certain placebo effect as well, that's worth comparing to, which seemed to suggest that the GI effects that you see with the CB1 pathway are not that significant. And of course, with Namaste, we are showing even better results at this dose where a country is no difference between placebo and what we are seeing with the drug.

With the GLP1s, which is where all the attention comes from, I believe that a lot of the GI effects tend to come because of the central action on places near the hypothalamus like the area of streamer, which whose job is to see what's going on in your blood and cause you to have nausea or vomiting if they think that there is something that's deleterious. And stimulating receptors that is causing that, and it's very possible that the CB1 mechanism doesn't actually do that. And that's why you see GI effects being so much more muted with this mechanism, and especially with the antibody, NEMASMA. We will test this, as Pune said, with higher doses, but we're pleased to see that, at least with the dose that we've tested, we are seeing really neutral effects.

Thanks, Ted.

Yes.

Go ahead, Pune. Go ahead.

So, you know, in a phase two study, I mean, we would, we wanted those people all the way out to a year of 52 weeks, but, you know, we're still looking at what the primary structure of the study should be. What we'd like is to design a study that will move us meaningfully towards doing pivotal studies. So we may still read out data at, say, 26 weeks where, you know, you can get a substantial indication of how individual doses are working and get a lot of safety information.

But, you know, we do, we do want to design studies in the end where the patients that we recruit get longer term treatment and can be treated for a year or even longer.

Thanks, Ted.