Skye Bioscience Q2 2025 Earnings Report

Skye Bioscience EPS Results

• Actual EPS: -$0.44
• Consensus EPS: -$0.34
• Beat/Miss: Missed by -$0.10
• One Year Ago EPS: N/A

Skye Bioscience Revenue Results

• Actual Revenue: N/A
• Expected Revenue: N/A
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Skye Bioscience Announcement Details

• Quarter: Q2 2025
• Date: 8/7/2025
• Time: After Market Closes
• Conference Call Date: Thursday, August 7, 2025
• Conference Call Time: 4:30PM ET

Skye Bioscience (NASDAQ:SKYE), a clinical stage pharmaceutical company, discovers, develops, and commercializes cannabinoid-based molecules for the treatment of infectious diseases. The company's lead product candidate is SBI-100 used in the treatment of glaucoma and ocular hypertension. It is also developing SBI-200 to treat and manage various eye diseases, including uveitis, dry eye syndrome, macular degeneration and diabetic retinopathy. It has license agreement with university of Mississippi. The company was formerly known as Emerald Bioscience, Inc. and changed its name to Skye Bioscience, Inc. in January 2021. The company is headquartered in San Diego, California.

Skye Bioscience Q2 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: The Phase 2a CBEYOND trial is ahead of schedule with enrollment completed in February and top-line results expected by late Q3/early Q4, supported by four DMC reviews with no safety changes.
• Positive Sentiment: In preclinical DIO studies, Nimasumab combined with a suboptimal dose of tirzepatide achieved 44% placebo-adjusted weight loss, outperforming optimal-dose tirzepatide alone.
• Positive Sentiment: Nimasumab demonstrated durable weight loss post-treatment, with only 7.4% weight regain by day 24 versus 29.7% for tirzepatide, highlighting its maintenance potential.
• Positive Sentiment: With $48.6 million in cash and short-term investments, Sky is funded through at least Q1 2027 to complete Phase 2a, initiate Phase 2b, and support key CMC and R&D activities.
• Negative Sentiment: R&D expenses rose to $14.3 million in Q2 2025 (up from $4.1 million) driven by contract manufacturing and clinical costs, contributing to a net loss of $17.6 million.

Presentation

[Operator]

Ladies and gentlemen, thank you for standing by. My name is Joe, and I will be your conference operator today. At this time, would like to welcome everyone to the Sky Bioscience Second Quarter twenty twenty five Financial Results and Business Update Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session.

[Operator]

I would now like to turn the conference over to Bernie Hertel, Head of Investor Relations. Please go ahead.

[Bernie Hertel, Head of IR & Communications at Skye Bioscience]

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 U. S. Private Securities Litigation Reform Act of 1995, including statements about Sky's expectations regarding its development activities, timelines and milestones. Forward looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely and reported results should not be considered as an indication of future performance.

[Bernie Hertel, Head of IR & Communications at Skye Bioscience]

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 the company's filings with the Securities and Exchange Commission concerning these and other matters. I'll now turn the call over to Puneet Dillon, Sky's President and CEO.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Good afternoon, everyone. Today, we have most of our executive team participating in our financial results and operations update through prepared comments, or they're available to address questions during the q and a. As we often say, we've managed the course with discipline, and we're now approaching the point where preparation becomes proof. This quarter marks a notable prelude to our reporting of our phase two a data for Nimazumab, Sky's differentiated peripheral c b one inhibitor in terms of execution as well as the clarity arising from the convergence of key activities, including the progress of our phase two a study, understanding of the mechanism of Nimasumab, and planning for next steps relating to our clinical development thesis. On today's call, we'll walk through the progress we've made, the data that we've generated, and the path we're charting forward.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

We'll cover three key areas. One, clinical progress, where we stand on our phase two a program and the top line timing. Two, r and d foundation, how we believe our antibody approach to c b one inhibition is mechanistically distinct and supported by reproducible preclinical data. And three, where Nimasumab fits, positioning our asset within the evolving obesity treatment landscape, including gaps we believe are overlooked and not readily fulfillable with other mechanisms. Let's begin with the clinical progress.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

The phase two a CBEYOND trial is advancing as planned, on budget and ahead of schedule. Enrollment was completed in February ahead of schedule, and a twenty six week visit for the last patient is projected to occur very shortly. The twenty six week extension study is also now underway with both the monotherapy and combination arms enrolling. Approximately fifty percent of the patients from the original study are eligible for enrollment, and we're optimistic that a majority of the eligible patients will choose to participate in the extension study. The data safety monitoring committee has now reviewed the study four times and issued no recommendations for changes.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

This has been an effectively managed program from timeline management and data capture on various endpoints to regulatory coordination from the initial IND to the recent protocol updates to facilitate the twenty six week extension. We look forward to completing treatment of our final enrolled patient for this first segment of CBEYOND and then stepping into the data analysis. We remain on track to deliver top line results by late q three, early q four. Next, let's discuss r and d. As a reminder, Nimasumab is a fully humanized, peripherally restricted CB1 antibody designed to target a well established metabolic pathway, but to do so without the central toxicity that has historically limited CB1 inhibitors.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

We differentiate from nonantibody CB one inhibitors in two fundamental ways. One, from a distribution standpoint and, two, mechanism, both advantages that support a broader therapeutic window and target engagement in the periphery. Let's focus in on peripheral restriction. Nimasumab shows negligible brain penetration across many different species. It's confirmed through PET imaging, cerebral spinal fluid analysis, and postmortem tissue assessments.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Even at high and repeated doses, the molecule remains peripherally compartmentalized. Next, let's talk about mechanism. Allosteric noncompetitive inhibition. Nimasumab binds at the allosteric site of CB1 retaining potency, even the presence of elevated endocannabinoids, which is commonly associated with the obese state. This is in contrast to small molecules that bind to the orthosteric site of the CB1 receptor, which may face increasing competition to bind to the receptor and can lose efficacy in the presence of high concentration of endocannabinoids.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

We've evaluated this molecule through multiple preclinical studies using our human CB one knock in DIO mouse model. Based on these DIO mouse studies, we believe there are at least four distinct yet converging mechanisms that define Nimasumab's action and form our platform's scientific core. One, caloric restriction via peripheral hormonal coordination. Nimasumab reduces food intake by acting on adipose and gastrointestinal tissues to modulate appetite regulating hormones such as GLP one, leptin, and resistant. This enables a peripherally mediated reduction in central appetite signaling without requiring brain exposure.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Two, improvement and restoration of glycemic control. We see consistent improvements in fasting glucose and insulin with significant improvements in glucose tolerance in DIO models, supporting Nimasumab's relevance for patients with prediabetes or insulin resistance. Three, enhancement of lipid metabolism. Nimasumab reduces steatosis and circulating cholesterol levels, a direct benefit for patients with obesity linked metabolic comorbidities like MAFLD or dyslipidemia. Four, reduction of obesity induced inflammation.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Nemasumab reduces the level of key serum inflammatory mediators and macrophage infiltration in liver and adipose tissue, pointing to a disease modifying role of Nimasumab related to comorbidities of obesity. These effects seen in our DIO models are robust, reproducible, and mechanistically distinct from, though complementary to, incretin based agents. That gives us potential optionality across monotherapy, combination, and maintenance strategies. Okay. Let's dive into that last point and touch on the new preclinical data that was shared today.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

To test how Nimasumab could perform in real world settings, we recently conducted a preclinical DIO study asking three key questions. One, can Nimasumab enhance the efficacy of a suboptimal dose of tirzepatide? This is highlighted by the yellow part of the study schematic. Two, does Nimasumab offer a more durable weight loss profile post treatment? This is highlighted by comparing the yellow to the blue part of the study schematic.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Three, can nolasumab act as a maintenance or rescue therapy after incurred and discontinuation. This is comparing the yellow to the pink color as a clear control. Here's what we found. First, the combination efficacy. The preclinical DIO study findings demonstrated that at day twenty five, the combination of namazumab and a suboptimal tirzepatide dose of three nanomoles per kilogram daily yielded 44% vehicle adjusted weight loss.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

The combination outperformed either agent alone with nimasumab demonstrating 21.5% vehicle adjusted weight loss and tirzepatide demonstrating 29.7% vehicle adjusted weight loss. The combination efficacy also exceeded an optimal dose of tirzepatide of ten nanomoles per kilogram daily, which resulted in thirty eight point nine percent vehicle adjusted weight loss. This highlights a meaningful opportunity to develop combination strategies that achieve greater efficacy at lower doses, potentially improving tolerability, reducing cost, and expanding treatment accessibility. Now point number two. Nimasumab demonstrated durable post treatment weight loss compared to incretin therapy after the therapy stopped.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

In comparison of namazumab and tirzepatide following cessation of treatment in the preclinical DIO mouse model, namazumab demonstrated superior durability of weight loss. Specifically, the low dose tirzepatide group regained most of their original weight back eight days after coming off therapy, regaining 29.7% of weight by day twenty four post treatment. In comparison, the nimasumab treated group maintained their posttreatment weight for approximately twenty days, regaining only 7.4% by day twenty four. This, quote, rebound effect has been well documented in animal models and clinical data and represents a major issue for patients who come off incretin based therapies. Nimaxumab's durability after cessation of therapy represents a potentially clinically beneficial and distinct outcome relative to incretin based therapies.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Let's move to the third point and now add back namazumab. Here, we're looking at maintenance of weight loss using namazumab alone post incretin treatment. When namazumab alone was used after an initial tirzepatide or combination treatment in the preclinical DIOMOs model, it greatly reduced rebound weight gain in these bottom three groups of mice, the suboptimal TRZ anemia combo in purple, the optimal TRZ dose in red, and the one we're gonna zoom into is the suboptimal TRZ following Nimasumab, which is in pink. The key takeaway, no matter which of these line graphs you're looking at, is that the data show Nimasumab reinforcing its potential role as a postincident weight loss maintenance therapy. And specifically, when Nimasumab was added following treatment with low dose tirzepatide, the pink line, Nimasumab reduced rebound weight gain from 29.7% to twelve point eight percent.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Taken together, these data suggest Nimazumab has utility across a broad continuum of care, not just initiating weight loss, but also sustaining it. This continues to strengthen our thesis and bring us to the real world setting and answering where Nimasumab fits and understanding the real world therapeutic gap. Again, we're not trying to displace GLP ones. We believe they are foundational and they're a backbone, but they also have well recognized limitations. Fifty eight percent of patients discontinue before twelve weeks, eighty percent by year two, up to forty percent of weight loss can come from lean mass, and GI side effects remain a major driver of treatment discontinuation and patient dissatisfaction.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

This ultimately creates a significant therapeutic gap and one that Nimasumab is designed to address. There's three market opportunities. One, as a monotherapy for patients who can't tolerate or don't respond to incretin therapeutics. Two, as a combination partner to amplify efficacy or reduce incretin dose burden. And three, as a maintenance therapy to sustain weight loss after a desired weight is achieved with better tolerability.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

As developers are racing to optimize potency, dosing, and formulation, the field is now bumping up against a real world ceiling, tolerability. And despite their clinical efficacy, incretin based drugs are facing significant discontinuation rates up to fifty percent within the first year, and nausea is the most frequently cited reason. As illustrated here, many of the late stage programs cluster in the high nausea, high dropout zone, trading gastrointestinal burden for marginal weight loss gains. This has created a therapeutic paradox. There are actually stronger agents, but they have a weaker persistence.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

We believe that this is not just a side effect problem. We believe it's a structural vulnerability in the current obesity treatment paradigm, and it's leaving a growing population of patients without sustainable options. That's where Nimasumab comes in. Rather than replicate what's already been done, Nimasumab is designed to potentially expand the therapeutic options in obesity treatment not only as a well tolerated and effective monotherapy, but as a differentiated and essential combination where the current incretin saturated market does not provide such options. Its mechanism offers alignment to GLP ones, unlocking the combination potential without compounding the GI burden.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

This positions Nimazemab to potentially meet the needs of patients who discontinue using the drug due to side effects, who fail to sustain weight loss, or who require multi pathway intervention for broader metabolic impact. For us at Sky, the opportunity's clear. Nimazumab is not just an alternative. We believe it's a next generation backbone candidate for durable, combinable, and more accessible obesity care, and it's a platform that can potentially extend beyond monotherapy to life cycle expansion across lines of therapy and patient segments that are currently underserved by today's options. And this is a key area to zoom in on, and we've been working on how best to frame it within the broader obesity treatment landscape.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

We believe we're entering the fourth wave of obesity pharmacotherapy, a new phase that's driven by scientific innovation still, but the needs to address real world complexity in patient care. The FDA has now approved six drugs for long term obesity treatment, each marking a step forward in the standard of care from short term stimulants to safer agents like orlistat to the rise of GLP one based therapies such as semaglutide and tirzepatide, which have brought us closer to disease resolution. But a new chapter is unfolding. Today's obesity market is evolving beyond the singular goal of caloric restriction. The next generation of anti obesity medications such as the peripheral approach is being shaped by the need for broader metabolic impact, targeting pathways related to insulin sensitivity, lipid regulation, inflammation, and central reward signaling.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

This reflects a shift from weight loss alone to true disease modification, sustainable weight loss, and even addressing the other related comorbidities. With the top line data ahead, we're preparing to potentially demonstrate how Nimazumab delivers on the core needs of the evolving obesity treatment paradigm that, in our opinion, fit the definition of the fourth wave by improving quality and durability of weight loss through alternative metabolic pathways, better tolerability, and strategic combinability. Thank you again for listening to our update, and I'll wrap by emphasizing that the next ninety days will be busy, and Kate's gonna walk you through a few of our upcoming milestones in her remarks. Overall, for us finishing q two and heading into q three isn't just a checkpoint. It's a culmination of disciplined execution, scientific clarity, and focused investment in a differentiated mechanism.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

We appreciate your continued support. And now I'll turn the call to Kate, our CFO.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

Thanks, Puneet. After the market closed today, we issued a press release and filed Sky's Form 10 Q 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 key financial results for the second quarter ended 06/30/2025. We ended the second quarter with cash and cash equivalents and short term investments totaling $48,600,000 Our cash flow guidance remains intact with the expectation that our current capital is projected to fund operations and key clinical milestones through at least Q1 twenty twenty seven.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

This includes the completion of our Phase 2a study for Nimasumab and certain Phase 2b manufacturing and preparatory clinical activities, including the initial manufacturing runs needed to start the phase two b dose ranging study and clinical feasibility activities. In addition, our runway also includes a modest discovery research and development budget and the formulation and development work expected to support later stage studies for venosumab. Research and development expenses for the three months ended 06/30/2025 were $14,300,000 as compared to $4,100,000 for the same period in 2024. The increase was primarily due to contract manufacturing, clinical trial costs associated with our clinical study for damasumab, discovery research and development expenses, and salaries and stock based compensation expense. General and administrative expenses for the three months ended 06/30/2025 were 3,900,000.0 as compared to 4,300,000.0 for the same period in 2024.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

The decrease was primarily related to decreases in general business expenses and legal and professional fees, offset by increases in salaries and stock based compensation expenses, consulting and advisory fees along with investor relation costs. Our net loss for the three months ended 06/30/2025 totaled 17,600,000.0, including noncash share based compensation expense of 4,200,000.0. This compared to 7,900,000.0 for the same period in 2024 with noncash share based compensation expense of 4,300,000.0. In q two, we maintained our track record of execution, hitting clinical milestones while managing capital with precision. We continue to build internal cadence and operational rigor, including the strategic expansion of our team to 20 employees.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

We made key hires in regulatory affairs, quality, clinical operations, and CMC. Notably, we welcomed a vice president of CMC to directly support our advancing development activities. This deliberate scaling is intended to allow us to minimize downtime between clinical trials and stay positioned to move quickly following upcoming data readouts. As we enter the 2025, we remain focused on disciplined execution and are well positioned to advance the Imasimod through its next development phase. We are entering what is arguably the most crucial execution period in Sky's history.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

To outline what you can expect in the coming months, on September 4, we will host a KOL event at Nasdaq, which will be webcast live focused on the mechanism, CVION phase two a clinical data expectations, and market positioning. In addition, in the fall, we are participating in multiple investor conferences where we look forward to engaging directly with many of you. Finally, ahead of our top line data, we are presenting the phase one SADMAD MAFLD data at EASD on September 19, reinforcing hepatic and metabolic benefits. In late q three, early q four, we expect our top line clinical readout from c beyond. As we have previously stated, this will be data from both the monotherapy and combo arms with placebo adjusted weight loss, safety, body composition, and mechanistic biomarkers.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

With the top line data in hand in q four, we expect to finalize the phase two b protocol, further advance CMC, initiate regulatory engagement, and external planning for next phase studies. 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 sell side analysts. Operator, over to you.

[Operator]

Thank you. The floor is now open for questions. Your first question comes from the line of Tenthoff of Piper Sandler. Your line is open.

[Edward Tenthoff, MD & Senior Research Analyst at Piper Sandler Companies]

Great. Thank you very much and thanks for the update. Getting excited for data. I have just a little bit of a housekeeping question, but with a specific angle on it. So R and D was higher.

[Edward Tenthoff, MD & Senior Research Analyst at Piper Sandler Companies]

I saw that you've made some progress on the manufacturing ones. Did that account for a big part of it? And in the press release, you mentioned this Airecor, A R E C O R, and a potentially higher concentration Nimazumab formulation. Can you tell us a little bit about what the goal is from that and when you may be able to use that higher concentration on Nimazumab? Thanks.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Hey, Ted. Thanks for joining the call. I'll take the first. This is Puneet here. I'll take the first or I'll let Kate take the financial questions relating to R and D.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

I can jump in and just explain the Evercore relationship. So at the moment, we have a concentration of two hundred mgs per two mil or one hundred mgs per mil is our is our is our current concentration, and that's what we're using in the clinic. Our goal here from a target product profile is to increase that concentration to to allow for a longer dosing period or or less frequent dosing. And ideally, would mean even considering two hundred mgs per mil. So we're basically looking to increase our concentration to go higher than one hundred mgs per mil, and EraCore is is supporting that effort.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

And just just so we are clear about that, that's a separate kinda r and d track. It doesn't interfere with our clinical development strategy. So as you know, our clinical development strategy and CMC efforts continue on track to support the advancement of Nimazumab. But as we consider additional lifecycle management, that's where we are looking for ways that we can improve concentration. Kate, do you wanna answer the financial piece?

[Edward Tenthoff, MD & Senior Research Analyst at Piper Sandler Companies]

Hi, Kate. I'm pretty on mute. And the question really is just with the step up in R and D to $14,000,000 in the second quarter, was that largely due to this manufacturing one or more clinical trial expense? Thanks.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

Yeah. Sure. So there was approximately $9,100,000 that we spent during the six months ended on contract manufacturing costs, and that related primarily to the phase two a resupply for the extension study and the supply for the phase 2b trial as well.

[Edward Tenthoff, MD & Senior Research Analyst at Piper Sandler Companies]

Great. Thanks. Excited for more data and seeing you this fall.

[Kaitlyn Arsenault, CFO at Skye Bioscience]

Thanks, Ted.

[Operator]

Your next question comes from the line of Jay Olson of Oppenheimer. Your line is open.

[Matthew Hershenhorn, Equity Research Associate at Oppenheimer & Co. Inc.]

Hey, guys. This is Matt on for Jay. Thanks so much for taking our questions and congrats on all the progress. So as we near CBEYOND data, just curious, I guess, what you're thinking for Nimasumab's weight loss efficacy potential at week twenty six. Should we expect to see something around eight percent?

[Matthew Hershenhorn, Equity Research Associate at Oppenheimer & Co. Inc.]

Or if it's slightly below that, would the range of around five percent to eight percent be potentially compelling? And then I guess additionally beyond weight loss and obviously safety, what other key metrics will you be paying attention to? And what biomarkers do you believe could be informative as well? Really appreciate it.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Hey, Matt. Thanks for joining and and taking the call on behalf of Jay. Yeah. So, you know, we we are looking at phase two, the CBON trial, the phase two a, really as a proof of mechanism study.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

It it was originally designed to detect an 8% placebo adjusted difference in weight loss with 80% power over twenty six weeks. So our goal here is to demonstrate a really clear clinically meaningful weight loss separation from placebo. And as you alluded to, you know, we believe that if we're seeing five to 8% range placebo adjusted, that's really a strong signal of biological activity of Nimasumab. Importantly, the study would was not powered really to detect a smaller difference with with any statistical significance. So that's an intentional component because otherwise, we would have required a a way larger study.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

So the objective here is to validate the mechanism, establish a really strong safety and tolerability profile, and really proceed to a definitive dose ranging study to identify the optimal dose and then then the the the ultimate reg regimen for nimasumab in a in a phase three setting. And our goal here is to deliver, obviously, consistent weight loss, improved GI tolerability profile. I think, you know, we alluded to that today in terms of where there's a lot of white space in the market, and that's where we feel we have really the upper hand and, obviously, a clear safety signal without any neuropsychiatric side effects. So so all of those those three parameters we would consider consider CBON as fast, and it really puts a strong foundation to move forward with phase two b for us.

[Matthew Hershenhorn, Equity Research Associate at Oppenheimer & Co. Inc.]

Okay. Got it. That makes sense to me. Really appreciate it. And just a quick follow-up.

[Matthew Hershenhorn, Equity Research Associate at Oppenheimer & Co. Inc.]

If you have any expectations on the potential discontinuation rate within twenty six weeks? And also how based on your expectations, you believe that could translate into an advantage versus GLP-one in the real world setting? And also just to clarify, as you previously said you expect about fifty percent of patients from the original study to be eligible for the extension study. If you could just walk us through your thinking there, that'd be great. Thank you so much again.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Yeah. So, doctor Lora, you can take the take the the fifty percent approximate on the extension study. I'll let me walk you through the other pieces of your question question. So in terms of discontinuation, we we we're we're expecting the similar kind of trends that we're seeing in most of these studies. Now keep in mind in the last two years, I think overall in across all obesity studies, we've seen probably about twenty five to thirty percent discontinuation.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

And I don't think that's a factor of always the drugs. It's also a factor of a very competitive landscape and the accessibility of just commercial drugs and access to to new modalities. And a lot of patients are looking for, you know, that access. So we haven't seen any unusual trend in terms of discontinuation of in our study and and and definitely, you know, not not seeing anything related to safety. But in terms of the real world situation, as as I alluded to in the presentation, there's there's a really large opportunity here where, you know, we're seeing fifty percent of patients not continuing incretin therapy after after a year.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Right? And that's that's it. That's where this maintenance data really showcases. And and here, we can essentially capture those patients and and continue on with with drug and allowing patients to have that long term sustainable weight loss. So I think there's a really clear market opportunity there where Nimasumab's not really competing for that initial weight loss that incretins do, but it's designed to really lock in those losses that once the incretin therapies do their do their work, then we we can see that there's an there's an application there in a really large market.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

And and then, obviously, there's still an opportunity there in the monotherapy setting too because there's patients that don't respond. I I hope I answered those two questions. I'll turn it over to doctor Arora to to just talk about extension study and those expectations.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

Yeah. So hi. Thank you. The extension study enrollment has started. Think I'll just start with the good news.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

We have we've been enrolling for the last month or so patients in the combination arms and we are also now enrolling patients in monotherapy. Just between the logistics of starting the extension and allowing patients to roll in. As you know, you know, we didn't we didn't initially plan for an extension, but we've been able to, execute on it. Between that and, you know, the natural early termination that you'll get in an obesity study, we still believe that about approximately fifty percent of our original, patient target will be eligible to grow low into extension. And it's it's just started, so I can't give you any precise numbers.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

But, you know, just based on the enthusiasm of the sites and from what we hear, they're they're very optimistic that, a majority of these patients are going to roll over because we see a lot of interest in it.

[Matthew Hershenhorn, Equity Research Associate at Oppenheimer & Co. Inc.]

Okay, got it. That all makes sense. Really appreciate the questions again. Thank you so much.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Thanks, Matt.

[Operator]

Your next question comes from the line of John Woolaban of Citizens. Your line is open.

[Jon Wolleben, Managing Director at Citizen JMP]

Hey, thanks for the update and taking the questions. Puneet, you kind of laid out a nice optionality between maintenance monotherapy combo. How do you think about what we'll see in CBEYOND and how that might guide development and the different utility in those three different modalities for nolasiban?

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Yeah. So it's a great question. Thanks, John. The look. I think there's a there's a significant opportunity for a broader maintenance franchise really taking place, and that's probably really underappreciated in the market because, let's face it, we're dealing with a a very rapidly moving market.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

And, you know, just this week, we've seen some highlights from other other obesity developers drug developers, and and everyone's, you know, kind of adjusting to to what what what where does everything shake out. I think that there's an a clear opportunity for Nimasumab in all three settings in the monotherapy. You know, we've we've we've quoted about ten to fifteen percent of patients based on our primary research that don't respond to GLP one therapy. So there there's a pretty large capture rate of those patients. In the maintenance setting, we've pointed to some really important stats there, about fifty percent discontinuing after one year, eighty percent discontinuing after two years.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

So there's really a clear need for a drug that can kinda cap capture that patient population with minimal GI side effects, and we're not expecting to add on to any of the tolerability concerns that we're seeing with the incretins. And then the third opportunity, you know, is is in terms of combination, I think that's really gonna come down to evidence based data. So far, you know, this data that we pointed to today really is is is an is another important development, because now we've shown with a suboptimal dose of tirzepatide in combination with namasumab that we actually get a deeper weight loss. So apply that to the real world, then we expect that you a patient may be able to take a more tolerable dose of an incretin therapy, and we can make up that delta in terms of weight loss with another modality. And it really points to a separation of the different biology here and pathway that c b one is acting on versus g l p one.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Two has been doing a lot of the market access research, so I I wanna give him a few minutes here to just maybe elaborate on anything I've said.

[Tu Diep, Chief Operating Officer at Skye Bioscience]

No, I think thanks Puneet. I think you've hit all the highlights. I think what's important is when we speak to KOLs, they make it pretty clear that they are very excited at the prospects of new modalities that are beyond just incretins. I think they want the option to be able to provide their patients with additional mechanism of action that may be more tolerable, may provide different benefit and may provide different options for patients that may not need to lose significant amounts of weight but may need to manage other areas of their health. So these are important things that I think the market needs to understand and is beginning to understand that weight loss as a bottom line number is no longer going to be the most important endpoint as these new drugs, new therapies in particular, these drugs are are, you know, new data is coming coming to the fore, and that these these other complementary mechanisms and other other endpoints are going to be important.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Yeah. And and just to add to that, you know, looking at the orfogriptan data today, I mean, there's still a clear, opportunity here that orals, are not necessarily gonna save the day in a in a maintenance setting. They don't necessarily add any more substantial weight loss. But here, we've now pointed to a completely different biology, a peripheral mechanism, maybe enhancing that weight loss. So I think from a competitive positioning snapshot perspective, there's clearly room from an efficacy standpoint.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

We'll see what that data looks like in in the clinical setting now. There's a maintenance franchise, which we're starting to, I think, understand better, and there's a really clear safety mode, right, with the the peripheral exclusion on the on the neuropsychiatric side as well as the tolerability profile to date. So those those three things, I think, really stand out from a competitive positioning perspective.

[Jon Wolleben, Managing Director at Citizen JMP]

That's really helpful color, guys. I appreciate it. And looking forward to, the event in September.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Thanks, John.

[Operator]

Your next question comes from the line of Kristen Kluska of Cantor Fitzgerald. Your line is open.

[Analyst]

Hi, this is Ayn on Kristen's line. Congrats on the progress here and thanks for taking our questions. First, regarding the independent board that oversees the trial for safety, could you just remind us what the protocol is here? What types of adverse events would they report? And then second, I know you touched on this already, but I just wanted to get some clarification around the enrollment eligibility in the extension study and how about fifty percent of the patients from the original study made the cut.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Sure. Thanks for joining today. And I'm I'm gonna let doctor Arora, chief medical officer, take take both of those questions.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

Yes. Thank you, Ayan. The, as far as the DMC is concerned, on a routine basis, they meet, quarterly and we actually provide them all of the data, safety data of the studies. So we we give them the complete listing of all adverse events, all serious adverse events, and any AESIs that are reported. And they they also have, complete information on all of those patients, any narratives, all the labs.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

So so actually, have the complete, they have a complete store of, unblinded information with which they work when they review the data for the study. They are they are in a position to come back and ask us for clarifications to ask us, you know, if they want us to monitor anything, but they want to know about an individual patient. At this point, frankly, we've had four four reviews completed. The last one was on July 18, barring some minor clarifications and some questions where they wanted to know about an individual patient and were curious about certain things. There really hasn't been anything too significant and each after each meeting, they've indicated that they are comfortable with the study continuing exactly

[Analyst]

Thank you for that. And then the second question on just the clarification around the enrollment eligibility in the extension study.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

Yes. So, so the enrollment eligibility, and we were talking about this earlier. So patients who complete their dosing for twenty six weeks are eligible for enrollment into the extension study. So anyone who does not complete twenty six weeks of dosing is not. But, you know, primarily what's happened here is that because we designed the extension study, somewhat belatedly after the original study was started, it's taken us a while to get it going, to get all the approvals, to get all the sites set up.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

So we did lose a certain number of patients who would be otherwise eligible to roll over into the study. So when we say fifty percent, it doesn't mean that fifty percent would not the remaining 50% would not necessarily have been eligible. A lot of those patients are not eligible simply because they had already completed the study before the time for rollover came. Of course, there is a certain amount of yeah. There's a certain amount of dropouts as well as you know, as we've been seeing them at all of these three studies and, know, I've seem to be in line with what you see.

[Puneet Arora, Chief Medical Officer at Skye Bioscience]

When you combine those two things, what we are looking at now is that we think it'll be about 50% about 50% are eligible.

[Analyst]

Got it. Thank you for that.

[Operator]

Your last question comes from the line of Albert Lowe of Craig Hallum. Your line is open.

[Albert Lowe, Senior Research Analyst at Craig-Hallum Capital Group LLC]

Hi, thanks for taking my question.

[Albert Lowe, Senior Research Analyst at Craig-Hallum Capital Group LLC]

Just a quick one from me. I know the original study design had the thirteen week follow-up period to track for durability of weight loss. I was wondering if the follow-up period after the extension study still has this follow-up period to look for durability and rebound weight gain? And in either case, when might we see data from, either portion of CBEYOND?

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

Hey, Albert. Thanks for joining the call today. Yeah. That's great question. We we're gonna continue to have that thirteen week follow-up, but that probably won't be available until the 2026 in terms of that that part of the data readout.

[Punit Dhillon, President, CEO & Director at Skye Bioscience]

So now with the extension, we will finish the fifty two weeks, and then all those patients will be tracked for a follow-up thirteen weeks, and then then that data would be available. So that's more of a 2026 event now.

[Albert Lowe, Senior Research Analyst at Craig-Hallum Capital Group LLC]

Alright. Got it. Thank you.

[Operator]

There are no further questions at this time. This concludes today's conference call. We thank you for your participation. You may now

Participants

Executives

• Bernie Hertel, Head of IR & Communications
• Punit Dhillon, President, CEO & Director
• Kaitlyn Arsenault, CFO
• Puneet Arora, Chief Medical Officer
• Tu Diep, Chief Operating Officer

Analysts

• Edward Tenthoff, MD & Senior Research Analyst at Piper Sandler Companies
• Matthew Hershenhorn, Equity Research Associate at Oppenheimer & Co. Inc.
• Jon Wolleben, Managing Director at Citizen JMP
• Analyst
• Albert Lowe, Senior Research Analyst at Craig-Hallum Capital Group LLC