Lexicon to Present Preclinical IN VIVO Efficacy Data Demonstrating Ability of New Investigational Compound to Enhance and Maintain Semaglutide-Promoted Weight Loss
Lexicon Pharmaceuticals (Nasdaq: LXRX) presents data on LX9851, a novel anti-obesity compound, at Obesity Week 2024. Two preclinical studies demonstrate significant findings: First, LX9851 showed substantial reductions in weight, food intake, and fat mass in diet-induced obese mice, particularly when combined with semaglutide. The combination therapy prevented weight regain after semaglutide discontinuation and improved liver-related endpoints.
Second study revealed LX9851's mechanism of action through ACSL5 inhibition, which activates the ileal brake - a natural satiety pathway. The company plans to file an Investigational New Drug (IND) application in 2025 for this first-in-class, orally bioavailable molecule.
Lexicon Pharmaceuticals (Nasdaq: LXRX) presenta dati su LX9851, un nuovo composto anti-obesità, durante l'Obesity Week 2024. Due studi preclinici dimostrano risultati significativi: in primo luogo, LX9851 ha mostrato notevoli riduzioni del peso, dell'assunzione di cibo e della massa grassa in topi obesi indotti da dieta, in particolare quando combinato con semaglutide. La terapia combinata ha prevenuto il recupero di peso dopo l'interruzione di semaglutide e ha migliorato gli endpoint legati al fegato.
Il secondo studio ha rivelato il meccanismo d'azione di LX9851 attraverso l'inibizione dell'ACSL5, che attiva il freno ileale - una via naturale di sazietà. L'azienda prevede di presentare una domanda di nuova droga sperimentale (IND) nel 2025 per questa molecola di prima classe, bio-disponibile per via orale.
Lexicon Pharmaceuticals (Nasdaq: LXRX) presenta datos sobre LX9851, un nuevo compuesto antiobesidad, en la Obesity Week 2024. Dos estudios preclínicos demuestran hallazgos significativos: primero, LX9851 mostró reducciones sustanciales en peso, ingesta de alimentos y masa grasa en ratones obesos inducidos por dieta, especialmente al combinarse con semaglutide. La terapia combinada previno la recuperación de peso tras la discontinuación de semaglutide y mejoró los resultados relacionados con el hígado.
El segundo estudio reveló el mecanismo de acción de LX9851 a través de la inhibición de ACSL5, que activa el freno ileal - una vía natural de saciedad. La compañía planea presentar una solicitud de nueva droga en investigación (IND) en 2025 para esta molécula de primera clase, bio-disponible por vía oral.
Lexicon Pharmaceuticals (Nasdaq: LXRX)는 LX9851이라는 새로운 비만 치료제를 Obesity Week 2024에서 발표합니다. 두 개의 전임상 연구에서 중요한 결과가 나타났습니다: 첫째, LX9851은 식이요법으로 유도된 비만 쥐에서 체중, 음식 섭취량 및 지방량을 크게 줄였습니다. 특히 세마글루타이드와 병용했을 때 효과가 두드러졌습니다. 병용 요법은 세마글루타이드 중단 후 체중 회복을 예방하고 간 관련 지표를 개선하였습니다.
두 번째 연구에서는 LX9851의 작용 메커니즘이 ACSL5 억제를 통해 발견되었으며, 이는 장내 포만감을 유도하는 자연적인 경로인 일레알 브레이크를 활성화합니다. 회사는 이 최초의 클래스에 해당하는 경구용 생체이용 가능 분자의 임상 시험용 신약 신청서 (IND)를 2025년에 제출할 계획입니다.
Lexicon Pharmaceuticals (Nasdaq: LXRX) présente des données sur LX9851, un nouveau composé anti-obésité, lors de l'Obesity Week 2024. Deux études précliniques démontrent des résultats significatifs : premièrement, LX9851 a montré des réductions substantielles du poids, de l'apport alimentaire et de la masse graisseuse chez des souris obèses induites par le régime, en particulier lorsqu'il est combiné avec de la sémaglutide. La thérapie combinée a permis d'éviter la reprise de poids après l'arrêt de la sémaglutide et a amélioré les résultats liés au foie.
La deuxième étude a révélé le mécanisme d'action de LX9851 par l'inhibition de l'ACSL5, ce qui active le frein iléal - une voie naturelle de satiété. L'entreprise prévoit de soumettre une demande de médicament expérimental (IND) en 2025 pour cette molécule de première classe, bio-disponible par voie orale.
Lexicon Pharmaceuticals (Nasdaq: LXRX) präsentiert Daten zu LX9851, einer neuartigen Anti-Adipositas-Verbindung, während der Obesity Week 2024. Zwei präklinische Studien zeigen bedeutende Ergebnisse: Erstens zeigte LX9851 erhebliche Reduzierungen des Gewichts, der Nahrungsaufnahme und der Fettmasse bei durch Diät induzierten fettleibigen Mäusen, insbesondere in Kombination mit Semaglutid. Die Kombinationsbehandlung verhinderte eine Gewichtszunahme nach Abbruch von Semaglutid und verbesserte leberbezogene Endpunkte.
Die zweite Studie offenbarte den Wirkmechanismus von LX9851 durch Hemmung von ACSL5, die den ilealen Bremsmechanismus aktiviert - einen natürlichen Sättigungsweg. Das Unternehmen plant, 2025 einen Investigational New Drug (IND) Antrag für dieses erstklassige, oral bioverfügbare Molekül einzureichen.
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Investigational New Drug (IND) application planned in 2025 for LX9851, a first-in-class, potent, selective, orally bioavailable molecule, as an anti-obesity agent
Data from Lexicon’s Obesity Week presentations summarize the preclinical efficacy and mechanism of action of LX9851
THE WOODLANDS, Texas, Nov. 04, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced it will present data from two studies related to LX9851, its investigational compound for obesity and weight loss, at Obesity Week 2024, November 3-5, 2024, at the Henry B. Gonzalez Convention Center in San Antonio, Texas.
Preclinical in vivo efficacy data from the first study showed that treatment with LX9851 resulted in significant reductions in weight, food intake and fat mass in diet-induced obese (DIO) mice. Among other important findings, LX9851 mitigated weight regain following discontinuation of the GLP-1 analogue semaglutide. This study (“First-in-Class ACSL5i LX9851 Enhances and Maintains Semaglutide-Promoted Weight Loss in DIO Mice”) investigated the body-weight reduction and weight maintenance effects of Lexicon’s first-in-class small molecule ACSL5 inhibitor, as a monotherapy and in combination with semaglutide, in a DIO mouse model. On Day 28, fat and lean body mass were measured by DEXA (OsteoSys body analyzer). All treatments with LX9851 resulted in a reduction in fat mass compared to vehicle control. The greatest weight reduction with no significant effect on lean body mass was observed when LX9851 was combined with semaglutide. The combination therapy also resulted in additive positive effects on liver steatosis and related study end points.
Preclinical in vivo efficacy data from the second study characterized the novel mechanism of action of LX9851. Previous research demonstrated that free fatty acids in the small intestine drive the release of GLP-1 and other gut hormones, which delays gastric emptying and ultimately lowers the desire for additional food consumption. This series of neural relays creates satiety, the feeling of fullness after consuming food, and is known as the ileal brake. This study (“Acsl5 KO and an Oral ACSL5 Inhibitor Lower High Fat Diet Intake in Mice by Activating the Ileal Brake”) demonstrated that inhibition of ACSL5, either through genetic knockout of the gene or pharmacological inhibition of the enzyme in wildtype mice, activates the ileal brake.
“Data presented during Obesity Week reinforces our optimism for LX9851. We believe that these promising findings, along with other ongoing research, will provide robust evidence to support our planned Investigational New Drug Application (IND) filing with FDA for LX9851 in 2025,” said Alan Main, Ph.D., Executive Vice President, Innovation and Chemical Sciences.
Details for the presentations are as follows:
- First-in-Class ACSL5i LX9851 Enhances and Maintains Semaglutide-Promoted Weight Loss in DIO Mice -- a moderated poster presentation (Poster # 634), Tuesday, November 5, 2:30-3:30p.m. CT Exhibit Hall 4, presented by Patricia McDonald, Ph.D., Senior Director, Biology, Lexicon Pharmaceuticals Inc.
- Acsl5 KO and an Oral ACSL5 Inhibitor Lower High Fat Diet Intake in Mice by Activating the Ileal Brake – a moderated poster presentation (Poster #006), Sunday, November 3, 7:30-8:30 p.m. CT, Exhibit Hall 4 presented by David Powell, Scientific Advisor, Lexicon Pharmaceuticals
About LX9851
LX9851 is an orally delivered small molecule drug candidate for the treatment of obesity and associated cardiometabolic disorders. We are investigating the pharmacology of LX9851 as a stand-alone therapy and in combination with GLP-1 agonists such as semaglutide. We anticipate filing an Investigational New Drug application with the U.S. Food and Drug Administration (FDA) in 2025, followed by the initiation of clinical development. Our scientists identified ACSL5, the target of LX9851, based on their discovery that knockout mice lacking the target enzyme exhibited favorable phenotypes across multiple measures of metabolic syndrome in preclinical models, including resistance to diet-induced obesity and improved body composition.
About Lexicon Pharmaceuticals
Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has commercially launched one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com.
Safe Harbor Statement
This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, conduct preclinical and clinical development and obtain necessary regulatory approvals of LX9851 and its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2023 and other subsequent disclosure documents filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.
For Investor and Media Inquiries:
Lisa DeFrancesco
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com
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