Q2 2025 Skye Bioscience Inc Earnings Call
This 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.
I would now like to turn the conference over to Bernie Hertel head of Investor Relations. Please go ahead, 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 <unk>.
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.
Speaker #1: Ladies and gentlemen, thank you for standing by. My name is Joel, and I will be your conference operator today. At this time, I would like to welcome everyone to the Skye Bioscience second quarter 2025 financial results and business update call.
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.
Speaker #1: All lines have been ced on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. I would now like to the conference over to Bernie Hertel, Head of Investor Relations.
Marriage, you to review all the company's filings with the Securities and Exchange Commission concerning these and other matters.
Speaker #1: Please go head.
I'll now turn the call over to Puneet Dillon, Sky's President and CEO. Good afternoon, everyone. Today, we have most of our executive team participating in our financial results and operations update through prepared comments or they are available to address questions. During the Q&A.
Speaker #2: 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.
Speaker #2: Including statements about Skye'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.
As we often say we've managed of course with discipline and we're now approaching the point where preparation that comes through.
This quarter marks a notable prelude to a reporting of our phase Iia data for the mass about sky's differentiated peripheral CB one inhibitor in terms of execution as well as the clarity arising from the convergence of key activities, including the progress of our phase Iia study understanding of the mechanism of the mathematics and planning for next steps.
Speaker #2: 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.
Relating to our clinical development thesis.
Speaker #2: I'll turn the call over to Punit Dhillon, Skye's President and CEO.
On today's call will walk through the progress we've made the data that we've generated and the path. We're charging forward will cover three key areas.
Speaker #3: Good afternoon, everyone. Today, we have most of our executive team participating in our financial results and operations update, through prepared comments or their available to address questions during the Q&A.
One clinical progress, where we stand on our phase III program and the topline timing.
Speaker #3: 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 2A data for the mass map.
Two R&D Foundation, how we believe our antibody approach to <unk> inhibition is mechanistically distinct and supported by reproducible preclinical data.
And three we're in a mass market positioning our assets within the evolving obesity treatment landscape, including gaps, we believe our overlook and not readily fulfill a bowl with other mechanisms.
Speaker #3: Skye's differentiated peripheral CB1 inhibitor in terms of execution, as well as the clarity arising from the convergence of key activities, including the progress of our Phase 2A study, understanding of mechanism of the mass map, and planning for next steps relating to our clinical development thesis.
Begin with the clinical progress.
The phase III <unk> trial is advancing as planned on budget and ahead of schedule enrollment was completed in February ahead of schedule and the 26 week visit for the last patient is projected to occur very shortly the 26 week extension study is also now underway with both the monotherapy and combination arms enrolling.
Speaker #3: On today's call, we'll walk through the progress we've made, the data that we've generated, and the path we're arting forward. We'll cover three key areas: one, clinical progress, where we stand on our Phase 2A program, and the top line timing.
Approximately 50% of the patients from the original study are eligible for enrollment and we are optimistic that a majority of the eligible patients will choose to participate in the extension study.
Speaker #3: Two, R&D foundation: how we believe our antibody approach to CB1 inhibition is mechanistically distinct and supported by reproducible preclinical data. And three, where the mass map fits, positioning our asset within the evolving obesity treatment landscape, including gaps we believe are overlooked and not readily fulfillable with other mechanisms.
The data safety monitoring Committee has now reviewed the study four times and issued no recommendations for changes.
This is Ben and 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 26 week extension.
Speaker #3: Let's begin with the clinical progress. The Phase 2A CB1 trial is advancing as planned on budget and ahead of schedule. Enrollment was completed in February, ahead schedule, and the 26-week visit for the last patient is projected to occur very shortly.
We look forward to completing treatment of our final enrolled patients for this first segment of CVR and dense stepping into the data analysis, we remain on track to deliver topline results by late Q3 early Q4.
Speaker #3: The 26-week extension study is also now underway with both the monotherapy and combination arms enrolling. Approximately 50% 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.
Next let's discuss R&D.
As a reminder, the massive mab is a fully humanized peripherally restricted CB, one antibody designed to target a well established metabolic pathway to do so without the central toxicity that is historically limited CB one inhibitors.
Speaker #3: The data safety monitoring committee has now reviewed the study four times and issued no recommendations for changes. This has been an effectively managed program from timeline management and data capture on various endpoints, to regulatory coordination from the initial I&D to the recent protocol updates to facilitate the 26-week extension.
We differentiate from non antibody CB one inhibitors in two fundamental ways, one from a distribution standpoint and two mechanism.
<unk> advantages that support our broader therapeutic window.
And target engagement in the periphery.
Speaker #3: We look forward to completing treatment of our final enrolled patient for this first segment of CB1 and then stepping into the data analysis. We remain on track to deliver top-line results by late Q3/early Q4.
Let's focus in on peripheral restriction.
<unk> shows negligible brain penetration across many different species its confirmed through pet imaging cerebral spinal fluid analysis, and postmortem tissue assessments, even at high and repeated doses the molecule remains peripherally compartmentalize.
Speaker #3: Next, let's discuss R&D. As a reminder, the mass map is a fully humanized, peripherally restricted CB1 antibody designed to target a well-established metabolic pathway.
Next let's talk about mechanism.
Allosteric noncompetitive inhibition no massive mab binds at the allosteric site of CB, one retaining potency even the presence of elevated endocrinology noise, which is commonly associated with the Ob state. This is in contrast to small molecules that bind to the ortho steric site of the <unk> receptor, which may face increasing.
Speaker #3: But to do so, without the central toxicity that has historically limited CB1 inhibitors. We differentiate from non-antibody CB1 inhibitors in two fundamental ways. One, from a distribution standpoint, and two, mechanism.
Speaker #3: Both advantages that support a broader therapeutic window and target engagement in the periphery. Let's focus in on peripheral restriction. The mass map shows negligible brain penetration across many different species.
Competition to bind to the receptor and can lose efficacy and the presence of high concentration of <unk> noise.
We've evaluated this molecule through multiple preclinical studies using our human CB one knock in DIR. Most model based on these DIR. Most studies. We believe there are at least four distinct yet converging mechanisms that define the mass <unk> action and form our platforms Scientific Corp.
Speaker #3: It's confirmed through PET imaging, cerebrospinal fluid analysis, and post-mortem tissue assessments. Even at high and repeated doses, the molecule remains peripherally compartmentalized. Next, let's talk about the mechanism.
Speaker #3: Allosteric, non-competitive inhibition. The mass map binds at the allosteric site of CB1, retaining potency even in the presence elevated endocannabinoids, which is commonly associated with the obese state.
One caloric restriction by a peripheral hormonal coordination no massive mab reduces food intake by acting on adipose and gastrointestinal tissues to modulate appetite regulating hormones such as GOP, one leptin and resistance. This enables a peripherally mediated reduction in central.
Speaker #3: 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.
Signaling without requiring brain exposure.
Two improvement and restoration of glycemic control, we see consistent improvements in fasting glucose and insulin with significant improvements in glucose tolerance in DIR models supporting the mathematics relevance for patients with pre diabetes or insulin resistance.
Speaker #3: We've evaluated this molecule through multiple preclinical studies using our human CB1 knock-in DIO mouse model. Based on these DIO mouse studies, we believe there are at least four distinct yet converging mechanisms that define the mass map's action and form our platform's scientific core.
Three enhancement.
Enhancement of lipid metabolism, no massive reduces steatosis and circulating cholesterol levels, a direct benefit for patients with obesity linked metabolic comorbidities like <unk> or dyslipidemia.
Speaker #3: One, caloric restriction via peripheral hormonal coordination. The mass map reduces food intake by acting on adipose and gastrointestinal tissues to modulate appetite-regulating hormones such as GLP-1, leptin, and resistin.
For reduction of obesity induced inflammation no massive mab reduces the level of key serum inflammatory mediators and macrophage infiltration and liver and adipose tissue pointing to a disease modifying role of no mass map related to comorbidities of obesity.
Speaker #3: This enables a peripherally mediated reduction in central appetite signaling without requiring brain exposure. 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 the mass map's relevance for patients with prediabetes or insulin resistance.
These effects seen in our Dio models are robust reproducible and mechanistically distinct from though complementary to incurred based agents that gives us potential optionality across monotherapy combination and maintenance strategies.
Speaker #3: Three, enhancement of lipid metabolism. The mass map reduces steatosis and circulating cholesterol levels, a direct benefit for patients with obesity-linked metabolic comorbidities like MAFLD or dyslipidemia.
Okay, let's dive into that last point and touch on the new preclinical data that was shared today.
To test how no massive mab could perform in real world settings. We recently conducted a preclinical tio study asking three key questions.
Speaker #3: Four, reduction of obesity-induced inflammation. The mass map reduces the level of key serum inflammatory mediators and macrophage infiltration in liver and adipose tissue, pointing to a disease-modifying role of the mass map related to comorbidities of obesity.
One can the mass about enhanced the efficacy of a suboptimal dose of tours appetite. This is highlighted by the yellow part of the study schematic.
Two no masimov offer a more durable weight loss profile post treatment. This is highlighted by comparing the yellow to the blue part of the study schematic.
Speaker #3: These effects seen in our DIO models are robust. Reproducible and mechanistically distinct from, though complementary to, incredin-based agents. That gives us potential optionality across monotherapy, combination, and maintenance strategies.
Three can the mass amount of act as a maintenance or rescue therapy. After incurred in discontinuation. This is comparing the yellow to the pink color is it clear control.
Speaker #3: Okay, let's dive into that last point and touch on the new preclinical data that was shared ay. To test how the mass map could perform in real-world settings, we recently conducted a preclinical DIO study asking three key questions.
Here's what we found first the combination efficacy the preclinical DIR study findings demonstrated that at day 25, the combination of the massive mab and a suboptimal trees appetite dose of 300 animals per kilogram daily.
Speaker #3: One, can the mass map enhance the efficacy a suboptimal dose tirzepatide, this is highlighted by the yellow part of this study's schematic? Two, does the mass map offer a more durable weight loss profile post-treatment?
Did 44% vehicle adjusted weight loss.
The combination outperformed either agent alone with the mass amount demonstrating 21, 5% vehicle adjusted weight loss.
Speaker #3: This is highlighted by comparing the yellow to the blue part of the study's ematic. And three, can the mass map act as a maintenance or rescue therapy after incredin discontinuation?
And tours appetite, demonstrating 29, 7% vehicle adjusted weight loss.
The combination efficacy also exceeded an optimal dose of <unk> appetite of 10 nanometer per kilogram daily which resulted in 38, 9% vehicle adjusted weight loss.
Speaker #3: 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 25, the combination of the mass map and a suboptimal tirzepatide dose of three nanomoles per kilogram daily yielded 44% vehicle-adjusted weight loss.
This highlights a meaningful opportunity to develop combination strategies that achieved greater efficacy at lower doses potentially improving tolerability, reducing cost and expanding treatment accessibility.
Now point number two.
The massive mab demonstrated durable post treatment weight loss compared to incurred in therapy. After the therapy stopped.
Speaker #3: The combination outperformed either agent alone, with the mass map 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 10 nanomoles per kilogram daily, which resulted in 38.9% vehicle-adjusted weight loss.
In comparison.
Of note <unk> and trees appetite following cessation of treatment in the preclinical DIR mouse model no massive mab demonstrated superior durability of weight loss, specifically, the low dose to as uptight group regained most of their original weight back eight days after coming off therapy, regaining 29, 7% of weight by day.
Speaker #3: 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.
24 post treatment in comparison, the mass map treated group maintained their post treatment weight for approximately 20 days regaining only seven 4% by day 24.
This quote rebound effect has been well documented in animal models and clinical data and represents a major issue for patients who come off increment based therapies.
Speaker #3: Now, point number two, the mass map demonstrated durable post-treatment weight loss compared to incredin therapy after the therapy stopped. In comparison of the mass map and tirzepatide following cessation of treatment in the preclinical DIO mouse model, the mass map 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 24 post-treatment.
<unk> ability after cessation of therapy represents a potentially clinically beneficial and distinct outcome relative to increase <unk> based therapies.
Let's move to the third point and now add back the mass map here, we're looking at maintenance of weight loss using the mass Mab alone post increment treatment.
When no mass Mab alone was used after initial trees appetite or a combination treatment in the preclinical D. I almost model it greatly reduced rebound weight gain in these bottom three groups of mice.
Speaker #3: In comparison, the mass map-treated group maintained their post-treatment weight for approximately 20 days, regaining only 7.4% by day 24. This quote rebound effect has been well documented in animal models and clinical data and represents a major issue for patients who come off incredin-based therapies.
Optimal Trc and NEMA combo in purple, the optimal trc dose and red and the one we're going to zoom into is the suboptimal PRC following the mass amount which is in pink.
The key takeaway no matter, which of these line graphs youre looking at is that the data show no mass mab reinforcing its potential role as a post including weight loss maintenance therapy, and specifically when <unk> was added following treatment with low dose <unk> appetite the pink line the massive map reduced rebound weight gain from <unk>.
Speaker #3: The mass map's durability after cessation of therapy represents a potentially clinically beneficial and distinct outcome relative to incredin-based therapies. Let's move to the third point, and now add back the mass map.
Speaker #3: Here, we're looking at maintenance of weight loss using the mass map alone, post-incredin treatment. When the mass map alone was used after an initial tirzepatide or combination treatment in the preclinical DIO mouse model, it greatly reduced rebound weight gain in these bottom three groups of mice.
Nine 7% to 12, 8%.
Taken together these data suggest <unk> has utility across a broad continuum of care not just initiating weight loss, but also sustaining it.
Speaker #3: The suboptimal TRZ and NEMA combo in purple, the optimal TRZ dose in red, and the one we're going to zoom into is the suboptimal TRZ following the mass map, which is in pink.
This continues to strengthen our thesis and bring us the real world setting and answering.
There no masonite fits and understanding the real world therapeutic gap.
Speaker #3: The key takeaway, no matter which of these line graphs you're looking , is that the data show the mass map reinforcing its potential role as a post-incredin weight loss maintenance therapy.
Again, we're not trying to displace <unk>.
<unk> once we believe they are foundational and they are a backbone, but they also have well recognized limitations, 58% of patients discontinue before 12 weeks, 80% by year to up to 40% of weight loss can come from lean mass.
Speaker #3: And specifically, when the mass map was added following treatment with low-dose tirzepatide, the pink line, the mass map reduced rebound weight gain from 29.7% to 12.8%.
And Gi side effects remain a major driver of treatment discontinuation and patient dissatisfaction.
Speaker #3: Taken together, these data suggest the mass map has utility across a broad continuum of care, not just initiating weight loss, but also sustaining it.
This ultimately creates a significant therapeutic gap and one that in the mass map is designed to address.
Speaker #3: This continues to strengthen our thesis and bring us the real-world setting and answering where the mass map fits. And understanding the real-world therapeutic gap.
There's three market opportunities.
One as a monotherapy for patients who can't tolerate or don't respond to incurred in therapeutics.
Two as a combination partner to amplify efficacy or reduce incurred in dose burdens and.
Speaker #3: Again, we're not trying to displace GLP-1s. We believe they are foundational and they're a backbone, but they also have well-recognized limitations. 58% of patients discontinue before 12 weeks, 80% by year two, up to 40% of weight loss can come from lean mass, and GI side effects remain a major driver of treatment discontinuation and patient dissatisfaction.
And three as a maintenance therapy to sustained weight loss. After a desired weight is achieved with better tolerability.
As developers are racing to optimize potency.
Dosing and formulation the field is now bumping up against a real world ceiling.
All of our ability.
And despite their clinical efficacy increment based drugs are facing significant discontinuation rates up to 50% within the first year and nausea as the most frequently cited reason.
Speaker #3: This ultimately creates a significant therapeutic gap, and one that the mass map is designed to address. There's three market opportunities. One, as a monotherapy for patients who can't tolerate or don't respond to incredin therapeutics.
As illustrated here many of the late stage programs cluster in the high nausea high dropout zone.
Speaker #3: Two, as a combination partner to amplify efficacy or reduce incredin dose burden. And three, as a maintenance therapy to sustain weight loss after a desired weight is achieved with better tolerability.
Trading gastrointestinal burden for marginal weight loss games. This has created a therapeutic paradox, there are actually stronger agents, but they have a weaker persistence.
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.
Speaker #3: 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, incredin-based drugs are facing significant discontinuation rates, up to 50% within the first year, and nausea is the most frequently cited reason.
That's where <unk> comes in.
Rather than replicate what's already been done <unk> 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 incurred in saturated market does not provide such options.
Speaker #3: 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.
Its mechanism offers alignment to <unk> unlocking the combination potential without compounding the Gi burden.
Speaker #3: There are actually stronger agents but they have a weaker persistence. 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.
Dispositions to mass map to potentially meet the needs of patients who discontinue using the drug due to side effects, who failed to sustained weight loss or who require multi pathway intervention for broader metabolic impact.
For us at Sky the opportunities clear the mathematics 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 lifecycle expansion across lines of therapy and patient segments that are.
Speaker #3: That's where the mass map comes in. Rather than replicate what's already been done, the mass map 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 incredin saturated market does not provide such options.
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.
Speaker #3: Its mechanism offers alignment to GLP-1s, unlocking the combination potential without compounding the GI burden. This positions the mass map 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 multipathway intervention for broader metabolic impact.
We believe we're entering the fourth wave of obesity pharmacotherapy, a new phase thats, driven by scientific innovation still but needs to address real world complexity in patient care.
The FDA has now approved six drugs for long term obesity treatment.
Speaker #3: For us at Skye, the opportunities are clear. The mass map 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 lifecycle expansion across lines of therapy and patient segments that are currently underserved by today's options.
Each marketing a step forward in the standard of care from short term stimulants to safer agents like Orlistat too the rise of <unk> based therapies, such as <unk>, and <unk> appetite, 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.
Speaker #3: 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.
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 signal.
Speaker #3: We believe we're ering 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.
This reflects a shift from weight loss alone to true disease modification sustainable weight loss and even addressing the other related comorbidities.
Speaker #3: The FDA has now approved six drugs for long-term obesity treatment. Each marketing a step forward in the standard of care, from short-term stimulants to safer agents like Orlistat, to the rise of GLP-1-based therapies such as semaglutide and tirzepatide, which have brought us closer to disease resolution.
With the topline data ahead, we're preparing to potentially demonstrate how no masimov 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.
Speaker #3: 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.
<unk> and strategic Combinability.
Thank you again for listening to our update and I'll wrap by emphasizing that the next 90 days will be busy and Kate is going to walk you through a few of our upcoming milestones in her remarks OS.
Speaker #3: Targeting pathways related to insulin sensitivity, lipid regulation, inflammation, and central reward signaling. This reflects a shift from weight loss alone to true disease modification sustainable weight loss and even addressing the other related comorbidities.
Overall for US, finishing Q2 and heading into Q3 isn't just the checkpoint. It's a culmination of disciplined execution scientific clarity and focus investment and a differentiated mechanism.
We appreciate your continued support and now I will turn the call to Kate our CFO.
Speaker #3: With the top-line data ahead, we're preparing to potentially demonstrate how the mass map delivers on the core needs of the evolving obesity treatment paradigm that, in our opinion, fit the definition of the fourth wave.
Thanks, Anthony after the market close today, we issued a press release and filed Form 10-Q, with the Securities and Exchange Commission.
Outlining our quarterly financial results.
Speaker #3: By improving the 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 up by emphasizing that the next 90 days will be busy, and Kait is going to walk you through a few of our upcoming milestones in her remarks.
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 June 32025.
We ended the second quarter with cash and cash equivalents and short term investments totaling $48 6 million.
Speaker #3: Overall, for us, finishing Q2 and heading into Q3 isn't just a checkpoint. It's a culmination of disciplined execution, scientific clarity, and focused investment in a differentiated mechanism.
Our cash flow guidance remains intact with the expectation that our current capital is projected to fund operations and key clinical milestones throughout Q1 2027.
Speaker #3: We appreciate your continued support, and now I'll turn the call to Kait our CFO.
This includes the completion of our phase Iia study for <unk> and for <unk> manufacturing and preparatory clinical activities.
Speaker #4: Thanks, Punit. After the market closed today, we issued a press release and filed Skye's 4 and 10 Q with the Securities and Exchange Commission.
Including the initial manufacturing ramp needed to start a phase <unk> dose ranging study and clinical feasibility activated.
Speaker #4: 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 June 30th, 2025.
In addition, our runway also includes a modest discovery research and development projects and the formulation and development are expected to support later stage studies for international.
Research and development expenses for the three months ended June 30 of 2025 or $14 3 million as compared to $4 1 million for the same period in 2024.
Speaker #4: We ended the second quarter with cash and cash equivalents and short-term investments totaling $48.6 million dollars. 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 2027.
The increase was primarily due to contract manufacturing and clinical trial costs associated with our clinical study for <unk> discovery research and development expenses and salaries and stock based compensation expense.
Speaker #4: This includes the completion of our Phase 2A study for the mass map and certain Phase 2B manufacturing and preparatory clinical activities. Including the initial manufacturing runs needed to start the Phase 2B dose-ranging study and clinical feasibility activities.
General and administrative expenses for the three months ended June 32025, or $3 9 million as compared to $4 3 million for the same period in 2024. The decrease was primarily related to decreases in general business expenses.
Speaker #4: 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 the mass map.
Legal and professional fees offset by increases in salaries and stock based compensation expenses consulting and advisory fees, along with Investor Relations.
Speaker #4: Research and development expenses for the three-month ended June 30th, 2025, were $14.3 million as compared to $4.1 million for the same period in 2024.
Our net loss for the three months ended June 32025 totaled $17 6 million, including noncash share based compensation expense of $4 2 million <unk>.
Speaker #4: The increase was primarily due to contract manufacturing clinical trial costs associated with our clinical study for the mass map, discovery research and development expenses, and salaries and ware compensation expenses.
This compared to $7 9 million for the same period in 2024 with noncash share based compensation expense of $4 3 million.
In Q2, we maintained our track record of execution hitting clinical milestones, while managing capital with precision we continue to build internal heater and operational rigor, including the strategic expansion of our team to 20 employees.
Speaker #4: General and administrative expenses for the three-month ended June 30th, 2025, were $3.9 million as compared to $4.3 million for the same period in 2024.
Speaker #4: 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.
We made key hires in regulatory affairs quality clinical operations and TMT, notably we welcomed a vice president at CMC to directly support our advancing development activity.
Speaker #4: Our net loss for the three-month ended June 30th, 2025, totaled $17.6 million, including non-cash share-based compensation expense of $4.2 million. This compared to $7.9 million for the same period in 2024, with non-cash share-based compensation expense of $4.3 million.
This deliberate scaling is intended to allow us to minimize downtime between clinical trial and state position to move quickly following upcoming data readouts.
As we enter the second half of 2025, we remain focused on disciplined execution.
And are well positioned to advance <unk> for its next development.
We are entering what is arguably the most crucial execution period in <unk> history to outline what you can expect in the coming months.
Speaker #4: In Q2, we maintained our track record of execution. Hitting clinical milestones while managing capital with precision. We continued to build internal cadence and operational rigor, including the strategic expansion of our team to 20 employees.
September 4th we will host the Kols event at NASDAQ, which will be webcast live focus on the mechanism CVR phase Iia clinical data expectation and market positioning.
Speaker #4: 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.
In addition in the fall we are participating in multiple investor conferences, where we look forward to engaging directly with many of you.
Speaker #4: This deliberate scaling is intended to allow us to minimize downtime between clinical trials and stay positioned move quickly following upcoming data readouts. As we enter the second half of 2025, we remain focused on disciplined execution, and our well-positioned to advance the mass map through its next development phase.
Finally head of our topline data we are presenting the phase one sad mad and <unk> data.
On September 19, reinforcing.
<unk> and metabolic benefits.
In late Q3 early Q4, we expect our topline clinical readout from <unk> as we have previously stated this will be data from both the monotherapy and combo arm with placebo adjusted weight safety body composition and mechanistic biomarkers.
Speaker #4: We are entering what is arguably the most crucial execution period in Skye's history. To outline what you can expect in the coming months, on September 4th, we will host a KOL event at NASDAQ, which will be webcast live focused on the mechanisms, CB1 Phase 2A clinical data expectations, and market positioning.
With the topline data in hand in Q4, we expect to finalize the phase <unk> protocol further advance TMT initiate regulatory engagement and external planning for next face value.
Speaker #4: 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 1 SADMAD MAFLD data at EAFD on September 19th, reinforcing hepatic and metabolic benefits.
This concludes our prepared comments for today. Thank you very much for joining us and we will now open the call for questions from our covering sell side analysts operator over to you.
Thank you.
<unk> is now open for questions. If you have dialed in and we'd like to ask a question. Please press star one on your telephone keypad to raise your hand and joined the queue.
Speaker #4: In late Q3, early Q4, we expect our top-line clinical readout from CB1. As we had previously stated, this will be data from both the monotherapy and combo arms, with placebo-adjusted weight loss, safety, body composition, and mechanistic biomarkers.
I'd like to withdraw your question simply press Star one again.
If you are called upon to ask a question or listening via a loudspeaker on your device. Please pick up your handset and ensure that your phone is not on mute when asking your question.
Your first question comes from the line of Ken <unk> Piper Sandler Your line is open.
Speaker #4: With the top-line data in hand, in Q4, we expect to finalize the Phase 2B protocol, further advance CMC, initiate regulatory engagement, and external planning for next phase studies.
Great. Thank you very much and thanks for it up together inside of our data.
Just a little bit of a housekeeping question, but was there a specific angle on it. So R&D was higher I saw that you've made some progress on the manufacturing ones.
Speaker #4: This concludes our pared 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.
Speaker #4: Operator, over to ou.
The other come for a big part of it.
So as you mentioned those are core they are <unk>.
Speaker #1: Thank you. The floor is now open for questions. If you have dialed in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue.
Potentially higher concentration the mass amount formulation can you talk a little bit about what the goal was from that and when you may be able to use a higher concentration on the mass months Greg.
Speaker #1: If ou would like to withdraw your question, simply press star one again. If ou're called upon to ask a question and are listening via a loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking our question.
Hey, Chad Thanks for joining the call I'll take the first this is Tony here I'll take the first.
Speaker #1: Your first question comes from a line of 10th off of Piper Sandler. Your line is open.
Can you take the financial question is relating to R&D I can jump in and just explain the air core relationships.
Speaker #5: Great. Thank you very much and thanks for the update. I'm getting excited for the data. I had just a little bit of a housekeeping question, but with a specific angle on it.
Our relationship so.
At the moment, we have a concentration of 200 mix.
Speaker #5: So R&D was higher I saw that you made some progress on the manufacturing lines. Did that account for a big part of it? And in the press release, you mentioned this air core, A-R-E-C-O-R, and a potentially higher concentration in the mass map formulation.
Kurt to mill.
Our 100 <unk> per 1000, as our as our as.
Our current concentration and.
And that's what we're using in the clinic our goal here from a target product profile is to increase that concentration.
Two to allow for.
A longer dosing period or less frequent dosing and ideally.
Speaker #5: 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 the mass map?
It would mean, even considering 200 megs per mill. So we're basically looking to increase our concentration to go higher than 100, Megs per 1000, and Eric or is supporting that effort.
Speaker #5: Thanks.
Speaker #6: Hey, Ted. Thanks for joining the call. I'll take the first this is Punit here. I'll take the first or I'll let Kait take the financial questions relating to R&D.
And just just so we are clear about that that's a separate kind of R&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.
Speaker #6: I can jump in and just explain the air core relationship. So at the moment, we have a concentration of 200 megs per 2 mil.
Speaker #6: Or 100 megs per mil is our 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 allow for a longer dosing period or less frequent dosing.
The advancement of the mass amount, but as we consider additional lifecycle management, that's where we are looking for.
Ways that we can improve concentration.
Keith do you want to answer the financial piece.
Speaker #6: And ideally, it would mean even considering 200 megs per mil. So we're basically looking to increase our concentration to go higher than 100 megs per mil.
Yes.
Hi, Andrew.
And the question will.
Speaker #6: And air core is supporting that effort. And just so we are clear about that, that's a separate kind of R&D track. It doesn't interfere with our clinical development strategy.
The step up in R&D.
$14 million in the second quarter was largely due to this manufacturer one or more clinical trials.
Speaker #6: So as you ow, our clinical development strategy in CMC efforts continue on track to support the advancement of the mass map. But as we consider additional lifecycle management, that's where we are looking for ways that we can improve concentration.
Yeah sure.
So there was approximately $9 1 million.
And then on contract manufacturing cost and that related primarily to the ASU a resupply for the expansion study.
And the supply for the <unk> trial as well.
Great. Thanks.
Speaker #6: Kait, do you want to answer the other financial piece?
Our data and our seniors this fall.
Yes.
Your next question comes from the line of Jay Olson of Oppenheimer. Your line is open.
Speaker #5: Hi, Kait Evans. Are you on mute? And the question really is just with the step up in R&D, the $14 million in the second quarter, was that largely due to this manufacturing line or more clinical trial?
Oh, Hey, guys. This is Matt on for Jay. Thanks, So much for taking the questions and congrats on all the progress.
As we mirror <unk> data just curious I guess, what youre thinking for new mass Bob's weight loss efficacy potential at week 26.
Speaker #5: Thanks.
Speaker #4: Yeah, sure. So there was approximately $9.1 million that we spent during the six months ended on contract manufacturing costs. And that related primarily to the Phase 2A resupply for the extension study.
Should we expect to see something around 8% or slightly below that.
The range of around 5% to 8% be potentially compelling.
And then I guess additionally, beyond weight loss and obviously safety what are their key metrics will you be being will you be paying attention to.
Speaker #4: And the supply for the Phase 2B trial as well.
Speaker #5: Great. Thanks. Excited for more data and seeing you this fall.
What Biomarkers do you believe could be informative as well really appreciate it.
Speaker #4: Thanks, Ted.
Hey, Matt Thanks for joining in and taken a call on behalf of Jay Yes.
Speaker #1: Your next question comes from a line of Jay Olson of Oppenheimer. Your line is open.
We are looking at phase two.
Beyond trial the phase III.
Speaker #7: Oh, hey, guys. This is Matt Long for Jay. Thanks so much for taking our questions and congrats on all the progress. So as we near CB1 data, just curious to guess what you're inking for new mass maps weight loss efficacy potential at week 26.
It really is a proof of mechanism study it.
It was originally designed to detect an 8% placebo adjusted difference in weight loss with 80% power over 26 weeks. So our goal here is to demonstrate.
Speaker #7: Should we expect to see something around 8%, or if it's slightly below that, would the range of around 5% to 8% be potentially compelling?
A really clear.
Clinically meaningful weight loss separation from placebo and as you alluded to we believe that if we're seeing 5% to 8% range placebo adjusted that's really a strong signal of biological activity of the massive map.
Speaker #7: 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?
Importantly, the study was not powered.
Speaker #7: Really appreciate it.
Speaker #6: Hey, Matt. Thanks for joining. And taking the call on behalf of Jay. Yeah, so you know we are looking at Phase 2 the CB1 trial, the Phase 2A really as a proof of mechanism study.
Really to detect a smaller difference.
With any statistical significance. So that's an intentional component because otherwise we would have required.
Way larger study 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 the.
Speaker #6: It was originally designed to detect an 8% placebo-adjusted difference in weight loss with 80% power over 26 weeks. So our goal here is to demonstrate a really clear clinically meaningful weight loss separation from placebo.
Ultimate regimen for <unk> in a phase III setting and.
Speaker #6: And, as you alluded to, you know we believe that if we're seeing a 5% to 8% range, placebo-adjusted, that's really a strong signal of biological activity of the mass map.
Our goal here is to deliver obviously consistent weight loss.
Improved Gi Tolerability profile I think we alluded to that today in terms of where there is a lot of white space in the market.
And that's where we have really the upper hand.
Speaker #6: Importantly, the study was not power really to detect a smaller difference with any statistical significance. So that's an intentional component because otherwise we would have required a way larger study.
And obviously, a clear safety signal without neuropsychiatric.
I'd effects. So so all of those are those three parameters we would consider.
Consider CVR honest.
And it really puts a strong foundation to move forward in phase III for us.
Speaker #6: 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 the ultimate regimen for the mass map in a Phase 3 setting.
Okay got it that makes sense to me it really appreciate it and just a quick follow up if you have any expectations on the potential discontinuation rate from 2016, and also how you're going to be.
Okay.
That could translate into an advantage versus Q1 in the real world setting and also just to clarify as you previously could you expect about 50% of patients from the original study to be eligible for the extension study. If you could just walk us through your thinking there great. Thank you so much again.
Speaker #6: And our goal here is to deliver obviously consistent weight loss, improve GI tolerability profile. I think 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.
Speaker #6: And obviously a lear safety signal without any neuropsychiatric side effects. So all of those three parameters we would consider CB1 best and it really puts a strong foundation to move forward with Phase 2B for us.
Yes.
You can take to take there.
The 50%.
Approximate on the extension study, let me walk you through the other piece of this question.
So.
In terms of discontinuation.
Speaker #5: Okay, got it. That makes sense, Punit. Really reciate it. And just a quick follow-up. Do you have any expectations on the potential discontinuation rate within 26 weeks and also how you know based on your expectations you ieve that could translate into an advantage versus GLP-1s in the real-world setting?
Where were expecting.
Similar kind of trends Youre seeing.
In most of these studies now keep in mind in the last two years.
I think overall.
All of these studies we've seen.
Speaker #5: And also just to clarify, as ou previously said, you expect about 50% of patients from the original study to be eligible for the extension study.
Probably about 25% to 30% discontinuation and I don't think Thats a factor of always the drugs Thats also a factor of a very competitive landscape and the accessibility of just commercial drugs and access to two new modalities and a lot of patients are looking for.
Speaker #5: If you could just walk us through your thinking there, that'd be great. Thank you so much again.
Speaker #6: Yeah. So Dr. Laura, you can take the the 50% approximate on the extension study. Let me walk you through the other pieces of your question.
That access so we haven't seen any unusual trend in terms of discontinuation.
Our study and and definitely.
Speaker #6: So in terms of discontinuation, we're expecting the similar kind of trends that ou're seeing in most of these studies. Now, keep in mind in the last two years, I ink overall in across all obesity studies, we've seen probably about 25 to 30% discontinuation.
Not not seeing anything related to safety.
But in terms of the real world situation.
As I alluded to in the presentation.
There's a really large opportunity here, where we're seeing 50% of patients.
<unk>.
Claim incurred in therapy after after a year and that's that's that's where this maintenance data really showcases and and here we can.
Speaker #6: 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 new modalities.
Essentially capture those patients and continue on.
With with drug and allowing patients to have that.
Speaker #6: And a lot of patients are looking for that access. So we haven't seen any unusual trend in terms of discontinuation in our study. And definitely, you know not seeing anything related to safety.
Long term sustainable weight loss. So I think there's a really clear kind of market opportunity there were no mass maps.
Not really competing.
For that initial weight loss of increments do budgets designed to really lock in those losses.
Speaker #6: But in terms of the real-world situation, as I alluded to in the presentation, there's a really large opportunity here where we're eing 50% of patients not continuing incredin therapy after a year, right?
Once the increment therapies do their work and we can see that there is an application there and a really large market and then obviously there is still an opportunity there in the monotherapy setting to work because there are patients that don't respond.
Speaker #6: And that's where this maintenance data really showcases. And here we can essentially capture those patients and continue on with drug and allowing patients to have that long-term sustainable weight loss.
I hope I answered those two questions.
I'll turn it over to Dr. <unk> to just talk about extra extensive study on those expectations.
Yeah. So thank you.
So study enrollment has started I think I'll just start with the good deals we have.
Speaker #6: So I think there's a really clear kind market opportunity there where the mass maps not really competing for that initial weight loss, that incredins do, but it's designed to really lock in those losses that once the incredin therapies do their work, then we can see that there's an application there in a really large market.
In enrolling for the last month or so patients in the combination arms and we are also now enrolling.
<unk> monotherapy just between the logistics.
Starting the extension and allowing patients to enrollment as you know we didn't we didn't initially planned for an extension, but we have been able to execute on it between that and the natural.
Speaker #6: And obviously there's still an opportunity there in the monotherapy setting too because there's patients that don't respond. I hope I answered those two questions.
Early termination can you get it in obesity study, we still believe that about approximately 50% of our original patients.
Speaker #6: I'll turn it over to Dr. Aurora to just talk about extension study and those expectations.
<unk> will be eligible to grow low end to extension and it is just start until I can give you any precise numbers, but just based on the pool you have some of the sites and from what we hear there may have any optimistic that a majority of these patients are going to rollover, because we see a lot of interest in it.
Speaker #8: Yeah. The extension study involvement has started, I think, at the start with the good news 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.
Okay got it that all make sense really appreciate the questions again. Thank you so much.
Thanks, Matt.
Yeah.
Speaker #8: As you ow, we didn't initially plan for an extension, but we've been le to execute on it between that. And you know the natural early terminations that ou get in an obesity study, we still believe that about approximately 50% of our original patient target will be eligible to roll over into extension.
Your next question comes from the line of John <unk> of citizens. Your line is open.
Hey, thanks for taking the questions.
Can you kind of laid out a nice.
Optionality between.
Maintenance monotherapy combo.
How do you think about what we'll see in <unk> and how that might guide development and the different utility in those three different modalities for asthma.
Speaker #8: And it's just started. So I can't give you any precise numbers, but you know just based on the enthusiasm at the sites and from what we hear, we're very optimistic that a majority of these patients are going to roll over because we see a lot of interest in it.
Yes, so it's a great question. Thanks John.
<unk>.
Look I think there is there is a significant opportunity for a broader maintenance franchise really taking place and that's probably really underappreciated in the market.
Speaker #5: Okay, got it. That all makes sense. Really appreciate the questions again. Thank you so much.
Speaker #6: Thanks, Matt.
Because let's face it we're dealing.
Speaker #1: Your next question comes from a line of John Wolloben of Citizens. Your line is open.
With.
Very rapidly moving market and just this week, we've seen some highlights from other other.
Speaker #7: Hey, thanks for your update and taking the estions. Punit, you kind of laid a nice optionality between you know maintenance, monotherapy, combo, how do you think what we'll see in CB1 and how that might guide development and the different utility in those three different modalities for the mass map?
<unk>.
Developers drug developers and <unk>.
And everyone's kind of adjusting to what.
Where does everything shake out I think that.
There is a clear opportunity for <unk> in all three settings in the monotherapy.
We've quoted.
Speaker #6: Yeah. So it's a great estion. Thanks, John. The look, I think there's a significant opportunity for a broader maintenance franchise really taking place and that's probably really underappreciated in the market.
10% to 15% of patients based on our primary research that.
Don't respond to <unk> one therapy. So there is a pretty large capture rate of those patients in the maintenance setting we've appointed to have some really important stats there about 50% discontinuing after one year, 80% discontinuing after two years. So there is really.
Speaker #6: Because let's face it, we're dealing with a very rapidly moving market and you ow just this week we've seen some highlights from other obesity developers and drug developers and everyone's kind of adjusting to what where does ything shake out.
A clear need for a drug that can kind of cap.
The 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 increments and then the third opportunity.
Speaker #6: I think that there's a clear opportunity for the mass map in all three settings in the monotherapy, we've quoted about 10 to 15% of patients based on our primary research that don't respond to GLP-1 therapy.
And in terms of combination I think that's really going to come down to evidenced based.
Data so far this data that we pointed to today really is is.
<unk> is another important development.
Speaker #6: So there's a pretty large capture rate of those patients in the maintenance setting. We've pointed to some really important stats there, about 50% discontinuing after one year, 80% discontinuing after two years.
Because now we've shown with a suboptimal dose of <unk>.
Combination with the mass of Mab that we actually get a deeper weight loss, so apply that to the real world.
Speaker #6: So there's really a clear need for a drug that can kind of 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 eing with incredins.
And we expect that.
A patient may be able to take.
More tolerable dose of an incurred in 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.
Speaker #6: And then the third opportunity you know is in terms of combination, I think that's really going to come down to evidence-based data so far you know this data that we pointed to today really is another important development.
Pathway.
CB, one is acting on versus <unk>.
<unk> has been doing a lot of the market access research. So I want to give him a few minutes here to just.
Maybe elaborate on anything I've said.
Speaker #6: Because now we've shown with a suboptimal dose of tirzepatide, in combination with the mass map, 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 more tolerable dose of an incredin therapy and we can make up that delta in terms of weight loss with another modality.
Yeah, No I think thanks, Puneet I think.
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 prospect of new modalities that are beyond just anchor tenants I think they want the option to be able to provide their patients.
With additional mechanisms of action.
Speaker #6: And it really points to a separation of the different biology here and pathway that CB1 is acting on versus GLP-1. Two has been doing a lot of the market access research.
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 that may need to manage other other areas of their health. So.
Speaker #6: So I want to give him a few minutes here to just maybe elaborate on anything I've said.
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.
Speaker #8: Yeah, no, I think thanks, Punit. I ink you've hit all the highlights. I think what's important is when we speak to KOLs, you know they make it pretty clear that they are very excited at the prospects of new modalities that are beyond just incredins.
The most important endpoint.
These these new drugs new therapies in particular, these non incretin drugs or new data is coming coming to the fore.
And that these other complementary mechanisms and other other endpoints are going to be important.
Speaker #8: I ink they want the option to be able to provide their patients with additional mechanisms 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.
Yes, and just to add to that.
Looking at the orphan grip on data today, I mean, there's still.
Clear opportunity here that <unk> are not necessarily going to save the day in a maintenance setting they don't necessarily add any more substantial weight loss, but here. We have now pointed to a completely different biology of peripheral mechanism, maybe enhancing that weight loss. So I think from a competitive.
Speaker #8: So you ow 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 non-incredin drugs are new data is coming to the fore.
Positioning snapshot perspective, there's clearly room from an efficacy standpoint, we'll see what that data looks like in the clinical setting now.
As a maintenance franchise, which we're starting to I think understand better.
There's a really clear safety mode right with the peripheral.
Speaker #8: And that these other complementary mechanisms, another endpoint are going to be important.
<unk> on the on the neuropsychiatric side as well as the Tolerability profile to date.
Speaker #6: Yeah. And just to add to that, you ow looking at the ORFL gripper on data today, I mean, there's still a clear opportunity here that orals are not necessarily going to save the day in a maintenance setting.
So those those three things I think really standout from a competitive positioning perspective.
That's really helpful color guys I appreciate it and looking forward to September.
Speaker #6: They don't necessarily add any more substantial weight loss. But here, we've now pointed to a completely different biology, a ipheral mechanism maybe enhancing that weight loss.
Thanks, John.
Your next question comes from the line of Kristen Cusco of Cantor Fitzgerald. Your line is open.
Hi, This is Ian on Christian Klein, Congrats on the progress and thanks for taking our questions first regarding the independent bondholders the trial for safety.
Speaker #6: So I think from a competitive positioning snapshot perspective, there's clearly room from an efficacy standpoint. We'll see what that data looks like in the clinical setting now.
Speaker #6: There's a maintenance franchise which we're starting to, I think, stand better. And there's a really clear safety mode, right, with the peripheral exclusion on the neuropsychiatric side as well as the tolerability profile to date.
Just remind us what the protocol is here what types of adverse events with taking apart 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.
Speaker #6: So those three things, I think, really stand out from a competitive positioning perspective.
About 50% of the patients sometimes regional study made the cut.
Sure Thanks for joining us today.
Speaker #5: That's really helpful call, guys. I appreciate it and looking forward to the event in September.
I'm going to let Dr Rohrer, Chief Medical officer take both those questions.
Speaker #6: Thanks, John.
Speaker #1: Your next question comes a line of Kristen Kluska of Cantor Fitzgerald. Your line is open.
Yes, thank you and the.
As far as the DMC is concerned on a routine basis Sedney quad.
Speaker #9: Hi, this is Ayan and Kristen's line. Congrats on the progress here and thanks for taking our questions. First, regarding the independent ward that oversees the trial for safety, could you just remind us what the protocol is here?
Quarterly and we actually provide them all of the data safety data on the studies. So we we give them the complete lifting of all adverse events all see fabulous events.
Speaker #9: What types 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 50% of the patients from the original study made the cut.
<unk> that are reported and they also have.
Fleet information on all of those patients any narrative all the labs. So so actually they have the complete.
They have a complete store off.
Blinded information, which they work and their review of the data for the study.
Speaker #6: Sure. Thanks for joining today. And I'm going let Dr. Aurora, Chief Medical Officer, take both of ose questions.
Are they are in a position to come back and ask us for clarification. So asked us if they want us to monitor anything but they want to know about an individual patient at this point frankly, we've had four.
Speaker #8: Yes, thank you, Ayan. As far as the DMC is concerned, on a routine basis, they meet quarterly, and we actually provide them all of the safety data for the study.
Paul reviews completed the last bundles on July 18th barring some minor classifications and some questions whether they wanted to know about an individual patient and I'm curious about certain things there really hasnt been anything too significant and each of the each meeting they've indicated that they are comfortable with the study continuing exactly as it is.
Speaker #8: So we give them the complete listing of all adverse events, all serious adverse events, and any AESIs that are reported. And they also have a complete information on all of those patients, any narratives, all the labs.
Speaker #8: So actually, they have the complete they have a complete store of unblinded information with which they work when they review the data for the study.
Thank you for that and then the second question on Justice clarification enrollment intelligence LTE in the extension study.
Yes, so the.
Speaker #8: 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 or they want to know about an individual patient.
The enrollment eligibility and we've been talking about this earlier, so patients who complete the dosing for 26 weeks are eligible for enrollment into the extension study so anyone.
Speaker #8: At this point, frankly, we've had four reviews completed the last one was on July the 18th. Barring some minor clarifications and some questions where they wanted to know about an individual patient and were curious about certain things they really haven't been anything too significant.
It's not complete 26 weeks of dosing is not but.
Primarily what's happened here is that because we designed the extension study.
Somewhat belatedly. After the original study was started its taken us awhile to get it going to get all the approvals, but again all of the site setup. So we did lose a certain number of patients who would be otherwise eligible to roll over into the study. So when we say, 50%. It doesn't mean that 50% the remaining 50% would not necessarily have been eligible.
Speaker #8: And each after each meeting, they've indicated that they are comfortable with the study continuing exactly as it is.
Speaker #9: Thank you for that. And then the second question on just clarification around the enrollment eligibility in the extension study.
A lot of those patients are not eligible simply because they had already completed the study before the time far rollover came.
Speaker #8: Yes. So the enrollment eligibility, and we were talking about this earlier, so patients who complete their dosing for 26 weeks are eligible for enrollment into the extension study.
And.
Yes, there is a certain amount of drop outs as well as you know <unk> been seeing them at all of these feed studies.
Speaker #8: So anyone who does not complete 26 weeks of dosing is not. But you know, primarily what's appened 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.
Seem to be in line with what you see when you combine those two things what we are looking at not only so we can get about 50% about 50% of eligible.
Got it thank you for that.
Yes.
Your last question comes from the line of Albert LOE of Craig Hallum. Your line is open.
Speaker #8: So we did lose a certain number of patients who would be otherwise eligible to roll over into the study. So when we say 50%, it doesn't mean that 50% would not the remaining 50% would not necessarily have been eligible.
Hi, Thanks for taking my question.
Just a quick one from me I know the original study design had the 13 week follow up period to track for durability of weight loss and.
Speaker #8: A lot of those patients are not eligible simply because they had already completed the study before the time for rollover came. And of course, there is a certain amount of yeah, there is a tain amount of dropouts as well as you know if you've even seen them at all obesity studies.
Yes, I was wondering if the follow up period. After the extension study still has.
Follow up period to look for durability and rebound weight gain and in either case when might we see data from either portion of CPR.
Speaker #8: And you know, as seen to be in line with what you see 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.
Hey, Albert Thanks for joining the call today, yes, that's a great question, we're going to continue to have that 13 week follow up.
Speaker #9: Got it. Thank ou for that.
That probably won't be available until the first half of 2026 in terms of that part of the data readout. So.
Speaker #1: Your last question comes from a line of Albert Lowe of Craig Hallam. Your line is open.
Now with the extension.
Speaker #10: Hi. Thanks for taking my estion. Just a quick one from me. I know the original study design had this 13-week follow-up period to track for durability of weight loss and so yeah, 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.
We will finish the 52 weeks and then all of those patients will be tracked for follow up 13 weeks and then that data would be available. So that's more of a 2026 of them now.
Alright got it thank you.
Okay.
Yes.
There are no further questions at this time.
Speaker #10: And in either case, when might we see this data from either portion of CB1?
This concludes today's conference call. We thank you for your participation.
You may now disconnect.
Speaker #6: Hey, Albert. Thanks joining the call today. Yeah, that's a great question. We're going to continue to have that 13-week follow-up. But that probably won't be available until the first half of 2026 in terms of that part of the data readout.
Yeah.
Speaker #6: So now with the extension, we will finish the 52 weeks and then all those patients will be tracked for a follow-up 13 weeks and then that data would be ailable.
Speaker #6: So that's more of a 2026 event now. All right. Got it. Thank ou.