Edward Tenthoff

George Farmer

Jay Olson

Jonathan Wolleben

Kristen Kluska

Albert Lowe

Gum-Ming Lowe

Andy Hsieh

Jon Wolleben

Matthew Hershenhorn

Tsan-Yu Hsieh

- **Nimacimab monotherapy (200 mg weekly) did not achieve its primary endpoint for weight loss**, showing -1.52% weight loss compared to -0.26% for placebo, with preliminary analysis suggesting lower than expected drug exposure.  **[1516551_0001628280-25-044223_a251006_skyexnrxp2topline.htm:0]** **[1516551_0001628280-25-044223_a251006_skyexnrxp2topline.htm:2]** 
- The combination of **nimacimab (200 mg weekly) and semaglutide demonstrated a clinically meaningful additional weight loss of -2.95%** compared to semaglutide alone (-13.2% vs -10.25%, p=0.0372).  **[1516551_0001628280-25-044223_a251006_skyexnrxp2topline.htm:0]** **[1516551_0001628280-25-044223_a251006_skyexnrxp2topline.htm:2]** 
- Nimacimab, both as monotherapy and in combination, exhibited a **favorable safety profile with no added gastrointestinal or neuropsychiatric adverse events**.  **[1516551_0001628280-25-044223_a251006_skyexnrxp2topline.htm:0]** **[1516551_0001628280-25-044223_a251006_skyexnrxp2topline.htm:2]**

Skye Bioscience Reports Topline Phase 2a Nimacimab Data

- Skye Bioscience's nimacimab monotherapy (200 mg QW) **did not meet its primary endpoint** for weight loss in the CBeyond Phase 2a trial, showing a placebo-adjusted weight loss of **-1.26% (p=0.2699)** at 26 weeks.  **[1516551_2168536:10]** **[1516551_2168536:20]** 
- In combination with semaglutide, nimacimab achieved a **clinically meaningful placebo-subtracted weight loss** of **-12.9% (p=0.0372)** compared to semaglutide alone in the mITT analysis.  **[1516551_2168536:10]** **[1516551_2168536:20]** 
- The combination treatment also demonstrated an **improved lean mass to fat mass ratio** at Week 26 compared to semaglutide alone (**0.26 vs. 0.13, p = 0.0126**).  **[1516551_2168536:10]** **[1516551_2168536:15]** **[1516551_2168536:20]** 
- Nimacimab maintained a **clean safety profile** with **no neuropsychiatric adverse events** and no added gastrointestinal burden when combined with GLP-1.  **[1516551_2168536:10]** **[1516551_2168536:20]** 
- The company attributes the monotherapy's limited efficacy to **underexposure** and plans to focus on the combination strategy while evaluating higher-dose monotherapy and optimal exposure.  **[1516551_2168536:15]** **[1516551_2168536:20]**

Skye Bioscience Reports CBeyond Phase 2a Trial Data

- The **200 mg nimasumab monotherapy arm** did not meet its primary endpoint for weight loss compared to placebo, showing a least square mean change from baseline of **-1.5%** for nimasumab versus **-0.3%** for placebo.  **[1516551_2169003_1]**  This outcome was attributed to lower than expected drug exposure.  **[1516551_2169003_1]** 
- In contrast, the combination arm of nimasumab with semaglutide demonstrated a clinically meaningful additional weight loss, achieving approximately **-14.3%** at 26 weeks in the per protocol population, compared to **-10.8%** for semaglutide alone.  **[1516551_2169003_2]**  This represents a **3.51%** incremental weight loss over semaglutide only in the per protocol subset (p-value **0.01**).  **[1516551_2169003_6]** 
- Nimasumab exhibited a favorable safety and tolerability profile, with its adverse event profile similar to placebo as monotherapy and no increase in GI side effects when combined with semaglutide.  **[1516551_2169003_2]** **[1516551_2169003_11]**  Notably, no nimasumab-associated neuropsychiatric adverse events were reported.  **[1516551_2169003_2]** **[1516551_2169003_11]** 
- Skye Bioscience plans to evaluate higher doses of nimasumab in future studies, with an ongoing extension study already testing a **300 mg** dose.  **[1516551_2169003_12]**  Potential future doses could range from **600 mg** to **1000 mg** once weekly, supported by preclinical data and safety margins.  **[1516551_2169003_10]** **[1516551_2169003_14]** 
- The company's cash runway remains unchanged into **Q1 2027**, which excludes the cost of any additional Phase 2 clinical studies.  **[1516551_2169003_13]**

Skye Bioscience Announces Phase 2a CBON Clinical Trial Top-Line Results

- Skye Bioscience's nimacimab monotherapy (200 mg) **did not meet its primary endpoint for weight loss** in the 26-week Phase 2a CBeyond™ study, with preliminary pharmacokinetic analysis suggesting lower than expected drug exposure and a potential need for higher dosing.  **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_0]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_1]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_2]** 
- The combination of nimacimab (200 mg) with semaglutide demonstrated **clinically meaningful additional weight loss** of **-13.2%** compared to **-10.25%** for semaglutide alone at Week 26, with no plateau observed.  **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_0]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_1]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_2]** 
- Nimacimab, both as monotherapy and in combination with semaglutide, showed a **favorable safety profile**, reporting no added gastrointestinal adverse events and no nimacimab-associated neuropsychiatric adverse events.  **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_0]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_1]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_3]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_4]** 
- Skye Bioscience is evaluating the data to determine next steps, including a potential follow-on Phase 2 study to optimize dosing, and expects to report data from the ongoing 26-week extension study in **Q1 2026**.  **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_1]** **[1516551_10995b9720864f67ac3aedb9ff1e3ef2_5]**

Skye Bioscience (SKYE)