Skye’s CB1 Inhibitor, Nimacimab, Demonstrates Superior Weight Loss and Differentiated Mechanisms from Monlunabant, and Continues to Show Enhanced Combination with Tirzepatide with Durable Post-Treatment Weight Maintenance in DIO Model
Skye Bioscience (NASDAQ:SKYE) reported promising preclinical data for its CB1 inhibitor nimacimab in diet-induced obesity (DIO) mouse studies. The drug demonstrated superior weight loss efficacy compared to monlunabant and enhanced results when combined with tirzepatide, achieving over 40% weight loss.
Key findings show nimacimab's differentiation as a peripherally-restricted CB1 inhibitor with potential superior safety profile, ability to reduce post-treatment weight rebound by over 50%, and enhanced efficacy when combined with both low and high-dose tirzepatide. The company expects to report top-line Phase 2 CBeyond™ study data in late Q3/early Q4 2025.
Skye Bioscience (NASDAQ:SKYE) ha comunicato dati preclinici promettenti sul suo inibitore CB1 nimacimab in studi su topi con obesità indotta dalla dieta (DIO). Il farmaco ha mostrato una maggiore efficacia nella perdita di peso rispetto al monlunabant e risultati ulteriormente migliorati se combinato con tirzepatide, raggiungendo una perdita di peso superiore al 40%.
I risultati principali evidenziano che nimacimab si distingue come inibitore CB1 a azione periferica con un potenziale profilo di sicurezza migliore, la capacità di ridurre il rimbalzo di peso dopo il trattamento di oltre il 50% e un aumento dell’efficacia se associato a tirzepatide a basse e alte dosi. L’azienda prevede di riportare i dati principali dello studio di Fase 2 CBeyond™ tra la fine del terzo trimestre e l’inizio del quarto trimestre 2025.
Skye Bioscience (NASDAQ:SKYE) informó datos preclínicos prometedores de su inhibidor CB1 nimacimab en estudios con ratones con obesidad inducida por dieta (DIO). El fármaco demostró mayor eficacia en la pérdida de peso frente a monlunabant y resultados mejorados al combinarse con tirzepatida, logrando una pérdida de peso superior al 40%.
Los hallazgos clave muestran que nimacimab se diferencia como un inhibidor CB1 de acción periférica con un potencial perfil de seguridad superior, la capacidad de reducir la recuperación de peso tras el tratamiento en más del 50% y una eficacia potenciada cuando se combina con tirzepatida en dosis bajas y altas. La compañía espera publicar los datos principales del estudio de Fase 2 CBeyond™ a finales del tercer trimestre o principios del cuarto trimestre de 2025.
Skye Bioscience (NASDAQ:SKYE)는 식이 유도 비만(DIO) 생쥐 연구에서 자사의 CB1 억제제 니마시맙(nimacimab)에 대한 유망한 전임상 데이터를 보고했습니다. 이 약물은 몬루나반트(monlunabant)보다 우수한 체중 감소 효과를 보였으며, 티르제파티드(tirzepatide)와 병용했을 때 효과가 더욱 향상되어 40%를 넘는 체중 감소를 달성했습니다.
주요 결과는 니마시맙이 말초 제한형 CB1 억제제로서 잠재적으로 우수한 안전성 프로파일을 가지며, 치료 후 체중 반등을 50% 이상 줄일 수 있는 능력과 저·고용량 티르제파티드와 병용 시 효과가 강화된다는 점을 보여줍니다. 회사는 2025년 3분기 말~4분기 초에 CBeyond™ 2상 주요 결과를 발표할 것으로 예상하고 있습니다.
Skye Bioscience (NASDAQ:SKYE) a publié des données précliniques prometteuses pour son inhibiteur CB1 nimacimab dans des études chez des souris obèses induites par l’alimentation (DIO). Le médicament a montré une efficacité supérieure de perte de poids par rapport au monlunabant et des résultats améliorés en association avec la tirzepatide, atteignant une perte de poids supérieure à 40%.
Les conclusions clés indiquent que nimacimab se distingue en tant qu’inhibiteur CB1 à action périphérique avec un profil de sécurité potentiellement supérieur, la capacité de réduire la reprise de poids après traitement de plus de 50%, et une efficacité accrue lorsqu’il est associé à la tirzepatide à faibles et fortes doses. La société prévoit de communiquer les données principales de l’étude de phase 2 CBeyond™ fin T3/début T4 2025.
Skye Bioscience (NASDAQ:SKYE) meldete vielversprechende präklinische Daten zu seinem CB1-Inhibitor nimacimab in diätinduzierten Adipositas-(DIO-)Mausstudien. Das Medikament zeigte eine überlegene Gewichtsverlustwirksamkeit gegenüber Monlunabant und verbesserte Ergebnisse in Kombination mit Tirzepatid, wobei >40% Gewichtsverlust erzielt wurden.
Wesentliche Erkenntnisse zeigen, dass nimacimab sich als peripher wirkender CB1-Inhibitor mit potenziell besserem Sicherheitsprofil abhebt, die Fähigkeit besitzt, das Gewichtsnachsteigen nach der Behandlung um über 50% zu reduzieren, und eine gesteigerte Wirksamkeit in Kombination mit niedrig- und hochdosiertem Tirzepatid aufweist. Das Unternehmen erwartet, die Topline-Daten der Phase-2-Studie CBeyond™ Ende Q3/Anfang Q4 2025 zu berichten.
- None.
- Results are only from preclinical studies, requiring validation in human trials
- Phase 2 clinical trial results still pending
Insights
Skye's nimacimab shows promising preclinical obesity data with 40%+ weight loss when combined with tirzepatide and better post-treatment weight maintenance than competitors.
Skye Bioscience's new preclinical data for nimacimab, their peripherally-acting CB1 inhibitor antibody, represents a potential triple threat in the competitive obesity treatment landscape. The data shows nimacimab achieved comparable or superior weight loss versus monlunabant (another CB1 inhibitor) while demonstrating significantly better post-treatment weight maintenance. This suggests nimacimab's mechanism extends beyond simply reducing caloric intake.
Most impressively, when combined with tirzepatide (Eli Lilly's GLP-1/GIP drug), nimacimab demonstrated over 40% weight loss in diet-induced obesity mouse models. This combination efficacy worked with both optimal and sub-optimal tirzepatide doses, suggesting potential for dose-sparing approaches that could improve tolerability.
The drug's ability to reduce weight rebound by over 50% after stopping tirzepatide treatment is particularly noteworthy, as post-treatment weight regain remains a significant challenge with current obesity medications. This maintenance benefit could position nimacimab as a sequential therapy after GLP-1 treatment or as part of a combination approach.
With these results suggesting potential as monotherapy, combination agent, and maintenance treatment, Skye is strategically positioning nimacimab to address multiple unmet needs in obesity management. The peripheral-only mechanism suggests a potentially improved safety profile compared to earlier small molecule CB1 inhibitors, which faced safety issues affecting the central nervous system. Investors should watch for the upcoming Phase 2 CBeyond™ study results expected in late Q3/early Q4 2025, which will be crucial in validating these preclinical findings in humans.
- Skye shares new preclinical DIO data at virtual KOL event
- Nimacimab + tirzepatide demonstrates over
40% weight loss in multiple preclinical DIO studies - Nimacimab demonstrates durable post-treatment weight loss compared to tirzepatide
- Nimacimab reduced rebound weight gain following treatment with tirzepatide or nimacimab + tirzepatide
- Nimacimab outperformed monlunabant head-to-head, and is uniquely positioned as a well-tolerated therapeutic to potentially induce healthier and sustained weight loss, both as a monotherapy, combination and maintenance therapy
- Top-line data from Phase 2 CBeyondTM study expected to be reported in late Q3/early Q4 2025
SAN DIEGO, Sept. 04, 2025 (GLOBE NEWSWIRE) -- Skye Bioscience, Inc. (Nasdaq: SKYE) (“Skye”), a clinical-stage biotechnology company focused on unlocking new therapeutic pathways for obesity and other metabolic health disorders, today reported results from two new preclinical diet induced obesity mouse (DIO) studies evaluating nimacimab, a peripherally-acting CB1-inhibiting monoclonal antibody. The first study measured the efficacy and weight regain dynamics (“rebound”) of monlunabant, a small molecule CB1 inhibitor, versus nimacimab, and demonstrated similar or better weight loss than monlunabant, while showing a superior post-treatment maintenance of weight loss, reinforcing a potentially differentiated mechanism. The second study re-evaluated the combination of nimacimab, this time with both optimal and sub-optimal doses of tirzepatide, and continued to show enhanced weight loss effects compared to tirzepatide alone, while also limiting rebound after treatment with tirzepatide is stopped. Importantly, these studies position nimacimab as a potential stand alone, combination and maintenance therapy in the obesity drug development landscape.
Key takeaways from Skye’s preclinical DIO data readouts:
- Nimacimab is differentiated from monlunabant: As a truly peripherally restricted CB1 inhibitor which has potential to have a superior safety and tolerability profile compared to the small molecules like monlunabant, these preclinical DIO studies have shown that nimacimab can potentially not only drive weight loss similar to, if not better than, monlunabant, but also shows a differentiated post-treatment weight maintenance profile that suggests potential broader metabolic effects beyond reduced calorie intake.
- Nimacimab enhances weight loss when combined with tirzepatide: when combined with both low-dose and high-dose tirzepatide, nimacimab has demonstrated in multiple preclinical DIO studies that it can result in
40% + weight loss. - Nimacimab blunts rebound following treatment with tirzepatide: There is significant weight regain when treatment with tirzepatide is ended. Nimacimab has demonstrated an ability to blunt this “rebound” effect by over
50% in preclinical DIO models.
“These two new in vivo studies advance a clear story: nimacimab can potentially both amplify and sustain weight loss, amplify in combination with GLP‑1 therapy, and potentially sustain by limiting rebound when treatment is ended,” said Punit Dhillon, Chief Executive Officer of Skye. “We believe the ability to switch to or maintain nimacimab after GLP‑1 treatment aligns with real‑world needs where durability and adherence remain critical due to a variety of factors including GI tolerability of the incretin-based anti-obesity medicines.”
“Mechanistically, we see what peripheral CB1 inhibition should deliver - improved metabolic homeostasis with less compensatory rebound with treatment withdrawal,” said Chris Twitty, Ph.D., Chief Scientific Officer. “Notably, nimacimab compared favorably to monlunabant promoting more durable weight loss upon treatment discontinuation, reinforcing our differentiation versus small‑molecule CB1 approaches.”
Skye will review these findings during its KOL event today, September 4, 2025 (webcast), where academic and clinical experts will discuss how combining and sequencing peripherally‑acting CB1 antagonism with GLP‑1s could improve the magnitude, tolerability, and maintenance of weight loss.
Detailed slide decks and figure sets for the two new pre‑clinical studies, the repeat DIO combination/maintenance study of nimacimab with tirzepatide and the in vivo nimacimab dose‑titration study versus monlunabant, along with additional nimacimab pre‑clinical data with voiceover are available on Skye’s website under the Spotlight page.
About Skye Bioscience
Skye is focused on unlocking new therapeutic pathways for metabolic health through the development of next-generation molecules that modulate G-protein coupled receptors. Skye's strategy leverages biologic targets with substantial human proof of mechanism for the development of first-in-class therapeutics with clinical and commercial differentiation. Skye is conducting a Phase 2a clinical trial (ClinicalTrials.gov: NCT06577090) in obesity for nimacimab, a negative allosteric modulating antibody that peripherally inhibits CB1. This study is also assessing the combination of nimacimab and a GLP-1R agonist (Wegovy®). For more information, please visit: www.skyebioscience.com. Connect with us on X and LinkedIn.
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FORWARD LOOKING STATEMENTS
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, forward-looking statements can be identified by terminology including “anticipated,” “plans,” “goal,” “focus,” “aims,” “intends,” “believes,” “can,” “could,” “challenge,” “predictable,” “will,” “would,” “may,” “potential” or the negative of these terms or other comparable terminology. These forward looking statements include, but are not limited to: statements relating to any expectations regarding the efficacy and therapeutic potential of nimacimab as a monotherapy or in combination with a GLP-1 targeted drug or other incretin drugs, statements regarding the potential of CB1 inhibition to address certain unmet needs of patients on GLP-1 weight loss drugs, statements regarding the timing of receipt of data from Skye’s Phase 2a obesity study, including its extension study, statements regarding the ability of nimacimab to perform in humans in a manner consistent with preclinical DIO data, statements regarding the potential market opportunities of nimacimab and statements regarding nimacimab’s potential to have a superior safety and tolerability profile compared to the small molecules like monlunabant,. Such statements and other statements in this press release that are not descriptions of historical facts are forward-looking statements that are based on management’s current expectations and assumptions and are subject to risks and uncertainties that could cause our actual results to differ materially from those expressed or implied by such forward-looking statements. We operate in a rapidly changing environment, and new risks emerge from time to time. As a result, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Risks and uncertainties that may cause actual results to differ materially include, among others: that preclinical data are not predictive of, may be inconsistent with, or more favorable than, data generated from future or ongoing clinical trial of nimacimab, including the Phase 2a study of nimacimab, competition from third parties that are developing products for similar uses, Skye’s ability to obtain, maintain and protect its intellectual property, Skye’s dependence on third parties for development and manufacture of product candidates, Skye’s ability to manage expenses and to obtain additional funding when needed to support its business activities, as well as those risks more fully described in the section entitled “Risk Factors” of Skye’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q. Except as expressly required by law, Skye disclaims any intent or obligation to update these forward-looking statements.
FAQ
What were the key results of Skye Bioscience's (SKYE) nimacimab preclinical studies?
How does Skye's nimacimab differ from monlunabant in weight loss treatment?
When will Skye Bioscience (SKYE) report Phase 2 CBeyond study results?
What advantages does nimacimab show when combined with tirzepatide?
How does nimacimab affect weight rebound after treatment discontinuation?
