Skye Bioscience

We @skyebio are back on the road this week at Citi, Evercore and Piper - been nice to get back in front of folks with a clear plan ahead for $SKYE. One of the key updates is from slide 13 of the corp deck which represents a development and dosing blueprint based on *new* and existing preclinical data. It confirms three fundamental pieces about nimacimab that are driving our current strategy: 1) Efficacy is linear and dose-dependent; 2) Combination synergy continues to be unlocked especially after reaching an active dose threshold; and 3) The mechanism offers a unique durability advantage over incretins alone. 1. Higher Dose Drives Efficacy (monotherapy data) (top Left + top right *new*): This DIO model demonstrates a clean, linear dose-response curve. Crucially, when dosed adequately, nimacimab outperforms a small-molecule CB1 inhibitor (green line) that is a known brain penetrant and where nimacimab has a safety advantage with ample headroom for dosing. When we provide sufficient exposure of a peripherally restricted antibody, we improve efficacy (similar to what was shown in the clinical data). This is the preclinical validation for our decision to step up to higher human doses in subsequent studies. 2. Combination efficacy continues to improve (top right *new*): This panel illustrates why dose optimization is the key to our strategy. When we combined a suboptimal, 'CBeyond' dose of nimacimab with semaglutide, we saw only a modest benefit. However, when we increased to closer to our expected active clinical dose (75mg/kg in mice), driving significantly deeper and more sustained weight loss. This confirms that nimacimab delivered with the right exposure, may meaningfully upgrade the entire combination profile, despite the already competitive clinical data we are seeing at 26-weeks with the suboptimal dose. We look forward to seeing what the 52-week combination data reveals. 3. Durability Advantage and Solving the Rebound (bottom left): Finally, this data highlights our most significant commercial differentiator: durability post-treatment. You can see the sharp initial weight loss with incretin therapy (gold line), followed by a rapid rebound the moment treatment stops. In contrast, nimacimab (blue line) produces meaningful weight loss with significantly less rebound after discontinuation. This reflects a fundamental difference in mechanism, peripheral metabolic re-wiring versus central appetite suppression. At higher doses, we aim to amplify this effect, positioning nimacimab as the essential 'maintenance engine' to lock in weight loss and solve the industry-wide challenge of GLP-1 rebound. So far, you can see early evidence of this being translated in the clinic with the combo 12-week follow-up period data we shared at OW, where +nimacimab demonstrated lower post-treatment rebound (~18% combo vs. ~50% sema-alone) and a favorable body-composition profile. More new clinical and pre-clinical data to follow during Q1.

$SKYE . Appreciate catching up with investors at Jefferies. @skyebioscience latest deck is now live, outlining how nimacimab, the first peripherally-restricted CB1 antibody, can reshape the obesity market: 1. Differentiated MOA: Dual inverse-agonist and antagonist / negative-allosteric modulator with >600× CNS safety window. 2. Robust Data: Dose-dependent fat loss, lean-mass preservation and hepatic steatosis reversal in hCB1 DIO models. 3. Clinical Momentum: Phase 2a (CBeyond™) fully enrolled; 26-week topline read-out in H2-25, 52-week extension data to follow. 4. Capital: Funded into 2027 with multiple inflection points ahead. Dive into the full story and our roadmap here: bit.ly/4mN8zwH

$SKYE Does CB1 Inhibition in the Brain Drive Weight Loss? No. The data presented at ECO this week strongly suggest that peripheral CB1 inhibition alone is sufficient for effective weight loss - central (brain) inhibition only adds neuropsychiatric risk without boosting efficacy. - Nimacimab is the only CB1-targeting monoclonal antibody in development. - It works through allosteric modulation, not orthosteric binding, which contributes to a broader and safer therapeutic window Link to poster: bit.ly/4jST7gF

$SKYE Clear strategy. Strong execution. Well-funded. Read our latest shareholder letter for a full update on @skyebioscience ’s progress and path forward as we build a leading metabolic health company. // bit.ly/4d26OHx

$SKYE Last year, we @skyebioscience had a bold hypothesis. This year, we have data - and more coming. Mechanism, monotherapy, combination, potency, dose-response, and a clinical path forward. Every slide in the linked deck reflects the work of a team that refused to cut corners and refused to be boxed in by outdated assumptions. Here’s the deck. Let the data speak for itself. | d1io3yog0oux5.cloudfront.net…

$SKYE shareholders, The news cycle is flooded with noise - rumors, sensational headlines, and a growing chorus of economic “experts” weighing in on trade wars and market swings. In contrast, biotech is driven by long-term conviction: grounded in science, propelled by innovation, and ultimately judged by scientific/data outcomes - not clickbait. Since our March @skyebioscience earnings update, we’ve engaged with stakeholders around the world - external collaborators, clinical partners, regulators (incl. FDA), our institutional shareholders, and the sell side. Our fundamentals remain intact and we continue to prioritize the objectives that build long-term value. We beat our Q1 milestones, accelerated the timeline for top-line data, expanded our Phase 2a CBeyond study to provide a 52-week data point, and set expectations for preclinical updates during our ADA Analyst Day in late June. Our focus hasn’t shifted: execute on the science, support our clinical sites, hit meaningful milestones, and allocate capital with discipline. Appreciate your continued support - just thought I’d drop a note given the current backdrop in biotech. 💪🏽

$SKYE Today’s update reinforced what we’ve believed all along: CB1 inhibition - done right - is a major therapeutic frontier. Investors have been whipsawed trying to pick obesity winners - chasing the arbitrage, obsessing over absolute weight loss. But the narrative is shifting. There’s growing recognition that obesity isn’t just about how much weight you lose - it’s about how you lose it, how safely, and how sustainably. The market is big, but the real opportunity lies in understanding its fault lines: the cracks where current therapies fall short. That’s where differentiated mechanisms like nimacimab are not just relevant - they’re essential.

The Truth About Biotech's So-Called Zombies: A Call for Consolidation Biotech investing has never been for the faint of heart. It requires patience, conviction, and a deep understanding of the science and business fundamentals. Yet, in the latest wave of market pessimism, the industry is being painted with a broad brush—labeling struggling companies as "zombies" that should simply be shuttered. This narrative is not just accurate—it’s necessary - thanks @adamfeuerstein for shedding light on this again in last weeks @statnews article (statnews.com/2025/02/20/why-…). The market needs efficiency, and if we want to get out of this five-year biotech slump, we need to take action. // @TimOpler @bradloncar Reading the Room: Consolidation is the Path Forward The argument that hundreds of public biotechs with negative enterprise values should close their doors is not just fair - it’s overdue. We've been talking about this for years and I can speak for some that we've embraced it but there is still lots to do. Instead of prolonging the inevitable, the industry - especially bankers and sell-side analysts - must become more activist in pushing for consolidation (and specialist buyside is already leading this effort behind the scenes). The capital markets have made it clear where money wants to flow, and it’s not into inefficient, cash-burning entities with no real prospects. It’s time to catalyze where the value is. There are multiple levers at play but here are four levers I recommend to fix biotech’s stagnation 1. Improve Cash Runway - For Those Who Deserve It A stronger balance sheet is critical, but let’s be clear: not every company deserves to survive. Cash runways need to be at least 2+ years. The focus should be on ensuring capital flows to high-potential assets while cutting off those that have no real future. Strong and smart capital allocation should prioritize investments that improve downtime (active programs), ensuring that resources are directed toward companies with a clear path to value creation (and derisking assets). Smart financial management is about making sure the right companies get funded - not just any company that can stretch its runway. 2. Embrace Aggressive Consolidation Enough hesitation. The industry needs bold moves, and that means M&A needs to be at the forefront for every sellside firm. The strongest players should be absorbing viable assets from weaker firms instead of allowing "zombie companies" to meander along, wasting investor dollars and wasting bandwidth in the broader biotech supply chain. Investment bankers and sell-side analysts know how to follow the money - they have the relationships to understand where consolidation makes the most sense. They need to serve their clients by identifying valuable assets and bringing forward actionable ideas. Management teams and boards are increasingly open-minded about value-add opportunities, and it’s time for dealmakers to step up. 3. Focus on Bigger and Sooner Catalysts Companies that can’t demonstrate tangible milestones that lead to a clear derisking or inflection in the near future shouldn’t be in business. Investors want proof points, and leadership teams must focus on delivering data and progress that matter. This means prioritizing clinical catalysts and accelerating timelines wherever possible. Consolidation should not just be about financial efficiency - it must also be leveraged to demonstrate how to de-risk assets and create synergies that make success more likely. Operators need to concentrate on proving that milestones are within reach and that progress isn’t just speculative but actively happening. 4. Shut the Zombies Down - Regardless of Pipeline Size The worst thing biotech can do is let these companies linger. Whether a company has a single product, a double product, or a larger pipeline, what matters is the ability to deliver proof points. If a lead asset fails, companies should not be burning through remaining cash under the guise of exploring new directions. That money needs to be returned to investors or redirected into consolidation efforts that strengthen the industry incentivise management with equity and payout so it's win-win (I like @TimOpler made this point on @BiotechCH). Buyside/investors and sellside should be demanding this kind of efficiency, not letting management teams coast along without a viable strategy. A Smarter, Stronger Biotech Industry This isn’t just about frustration - it’s actually in many cases about survival and the best science leading to the innovation and broader success of the industry. If we want biotech to emerge from this cycle, we need to act decisively. The industry needs real leadership from the investment community, not passive observers. Consolidation, efficiency, and smarter capital allocation are the only ways forward. It’s time to stop propping up companies with no future and focus on those that can truly drive innovation and returns.

BIO CEO 2025: Exciting new directions for obesity drug research bio.news/latest-news/bio-ceo… #BIOevents @skyebioscience $SKYE

Reflecting on 2024: Gratitude and Momentum for What’s Ahead As the year comes to a close, I find it essential to pause, reflect, and express gratitude—for the milestones we’ve achieved, the lessons we’ve learned, and, most importantly, the people who’ve made it all possible. To the @skyebioscience team: Your resilience, focus, and commitment continue to drive our progress. From advancing the CBeyond™ Phase 2 trial to strengthening our strategy and operations, every step we’ve taken this year is a testament to your hard work and collaboration. To our partners and stakeholders: Your trust and support fuel our momentum. Together, we’re breaking new ground in metabolic health and shaping a future where innovative therapies address critical unmet needs. 2024 was a year of building and executing, and 2025 promises to be one of validation and growth. I’m proud of what we’ve accomplished and energized by what lies ahead. Wishing everyone a joyful holiday season and a fulfilling year ahead! Link to our 2024 YIR and Look Ahead: vimeo.com/1041806439