Leap Therapeutics to Present Preclinical Data of FL-501, a Novel GDF-15 Neutralizing Antibody, at the AACR 2025 Annual Meeting
Leap Therapeutics (NASDAQ:LPTX) announced preclinical data presentation for FL-501, their novel GDF-15 neutralizing antibody, at the AACR 2025 Annual Meeting in Chicago. FL-501 shows promise in treating cancer cachexia, a life-threatening condition characterized by weight loss and muscle wasting.
Key findings demonstrate that FL-501 exhibited a 2-3-fold longer half-life and 50% reduced clearance compared to its wild-type precursor and ponsegromab in humanized FcRn mouse studies. The antibody successfully restored body composition in mouse cachexia models and effectively countered cisplatin-induced weight loss in non-small cell lung cancer patient-derived xenograft models.
The company plans to advance FL-501 into clinical trials in 2026, positioning it as a potential best-in-class treatment option for cancer cachexia, a condition currently lacking effective treatments.
Leap Therapeutics (NASDAQ:LPTX) ha annunciato la presentazione di dati preclinici per FL-501, il loro nuovo anticorpo neutralizzante GDF-15, al Congresso Annuale AACR 2025 di Chicago. FL-501 mostra potenzialità nel trattamento della cachessia tumorale, una condizione pericolosa per la vita caratterizzata da perdita di peso e atrofia muscolare.
I risultati chiave evidenziano che FL-501 ha mostrato un tempo di emivita 2-3 volte più lungo e una clearance ridotta del 50% rispetto al suo precursore selvatico e al ponsegromab negli studi su topi umanizzati FcRn. L’anticorpo ha efficacemente ripristinato la composizione corporea nei modelli murini di cachessia e ha contrastato con successo la perdita di peso indotta da cisplatino in modelli xenotrapianto derivati da pazienti con carcinoma polmonare non a piccole cellule.
L’azienda prevede di avviare le sperimentazioni cliniche di FL-501 nel 2026, posizionandolo come possibile trattamento di riferimento per la cachessia tumorale, una condizione attualmente priva di terapie efficaci.
Leap Therapeutics (NASDAQ:LPTX) anunció la presentación de datos preclínicos de FL-501, su nuevo anticuerpo neutralizante de GDF-15, en la Reunión Anual AACR 2025 en Chicago. FL-501 muestra potencial para tratar la caquexia cancerosa, una condición mortal caracterizada por pérdida de peso y desgaste muscular.
Los hallazgos clave demuestran que FL-501 presentó una vida media 2-3 veces más larga y una reducción del 50% en la depuración en comparación con su precursor silvestre y ponsegromab en estudios con ratones humanizados FcRn. El anticuerpo restauró con éxito la composición corporal en modelos de caquexia en ratones y contrarrestó eficazmente la pérdida de peso inducida por cisplatino en modelos de xenoinjerto derivados de pacientes con cáncer de pulmón no microcítico.
La compañía planea avanzar con FL-501 hacia ensayos clínicos en 2026, posicionándolo como una posible opción terapéutica líder para la caquexia cancerosa, una condición que actualmente carece de tratamientos efectivos.
Leap Therapeutics (NASDAQ:LPTX)는 시카고에서 열리는 AACR 2025 연례회의에서 새로운 GDF-15 중화 항체인 FL-501의 전임상 데이터 발표를 했습니다. FL-501은 체중 감소와 근육 소모를 특징으로 하는 생명을 위협하는 암 악액질 치료에 유망한 후보입니다.
주요 결과에 따르면, FL-501은 인간화 FcRn 마우스 연구에서 야생형 전구체 및 폰세그로맙 대비 반감기가 2-3배 더 길고 클리어런스가 50% 감소하는 것으로 나타났습니다. 이 항체는 마우스 악액질 모델에서 체성분을 성공적으로 회복시켰으며, 비소세포폐암 환자 유래 이식 모델에서 시스플라틴 유도 체중 감소를 효과적으로 억제했습니다.
회사는 FL-501을 2026년 임상시험으로 진전시킬 계획이며, 현재 효과적인 치료법이 없는 암 악액질에 대해 잠재적인 최고 수준의 치료 옵션으로 자리매김할 전망입니다.
Leap Therapeutics (NASDAQ:LPTX) a annoncé la présentation de données précliniques concernant FL-501, leur nouvel anticorps neutralisant GDF-15, lors de la réunion annuelle AACR 2025 à Chicago. FL-501 semble prometteur pour le traitement de la cachexie cancéreuse, une condition potentiellement mortelle caractérisée par une perte de poids et une fonte musculaire.
Les résultats clés montrent que FL-501 a présenté une demi-vie 2 à 3 fois plus longue et une clairance réduite de 50% par rapport à son précurseur sauvage et au ponsegromab dans des études chez des souris humanisées FcRn. L’anticorps a restauré avec succès la composition corporelle dans des modèles murins de cachexie et a efficacement contré la perte de poids induite par le cisplatine dans des modèles xénogreffes dérivés de patients atteints de cancer du poumon non à petites cellules.
L’entreprise prévoit de faire progresser FL-501 vers des essais cliniques en 2026, le positionnant comme une option thérapeutique potentielle de référence pour la cachexie cancéreuse, une condition actuellement dépourvue de traitements efficaces.
Leap Therapeutics (NASDAQ:LPTX) gab die Präsentation präklinischer Daten zu FL-501, ihrem neuartigen GDF-15-neutralisierenden Antikörper, auf dem AACR 2025 Jahreskongress in Chicago bekannt. FL-501 zeigt vielversprechende Ansätze zur Behandlung der Krebskachexie, einer lebensbedrohlichen Erkrankung, die durch Gewichtsverlust und Muskelabbau gekennzeichnet ist.
Wesentliche Ergebnisse zeigen, dass FL-501 in Studien mit humanisierten FcRn-Mäusen eine 2-3-fach längere Halbwertszeit und eine um 50 % verringerte Clearance im Vergleich zu seinem Wildtyp-Vorläufer und Ponsegromab aufwies. Der Antikörper stellte erfolgreich die Körperzusammensetzung in Mausmodellen der Kachexie wieder her und konnte den durch Cisplatin induzierten Gewichtsverlust in patientenabgeleiteten Xenotransplantat-Modellen des nicht-kleinzelligen Lungenkarzinoms wirksam bekämpfen.
Das Unternehmen plant, FL-501 im Jahr 2026 in klinische Studien zu überführen und positioniert es als potenzielle Best-in-Class-Behandlungsoption für die Krebskachexie, eine Erkrankung, für die es derzeit keine wirksamen Therapien gibt.
- Demonstrated 2-3x longer half-life and 50% reduced clearance compared to competitors
- Successfully restored body composition in preclinical models
- Effective against cisplatin-induced weight loss in cancer models
- Addresses unmet medical need in cancer cachexia treatment
- Clinical trials not starting until 2026
- Currently only preclinical data available
- No proven efficacy in humans yet
Insights
Leap's FL-501 shows promising preclinical efficacy against cancer cachexia with potential advantages over competing antibodies, representing positive pipeline advancement.
Leap Therapeutics' preclinical data for FL-501 represents a significant development in addressing cancer cachexia - a devastating condition characterized by severe weight loss and muscle wasting that affects up to 80% of advanced cancer patients and currently has no FDA-approved treatments. The data presented at AACR demonstrates considerable potential for this novel GDF-15 neutralizing antibody.
The pharmacokinetic profile shows meaningful advantages, with a
The GDF-15 pathway represents a biologically validated target for cachexia, and FL-501's performance suggests potential best-in-class characteristics if these results translate to humans. However, investors should recognize that preclinical success doesn't guarantee clinical efficacy, and the planned clinical entry in 2026 indicates a multi-year development timeline before potential commercialization.
For a small-cap biotech company with approximately
FL-501 fully restored body composition and reversed key indicators of cachexia in preclinical models
Findings confirm GDF-15's role in cachexia and support advancing FL-501 into the clinic
FL-501 is a potential best-in-class monoclonal antibody targeting growth differentiation factor 15 (GDF-15), a cytokine that is implicated in multiple diseases and therapeutic areas, including cancer cachexia.
"Cancer cachexia is a devasting and potentially life-threatening condition characterized by significant weight loss, muscle wasting, fatigue, and severely reduced quality of life. It is a major contributor to cancer-related mortality, and unfortunately there are no effective treatment options available to patients," said Jason Baum, PhD, Chief Scientific Officer of Leap. "These data not only demonstrate that FL-501 is a novel and potential best-in-class anti-GDF-15 antibody, but also capable of fully restoring body composition in preclinical models that is comparable or better than other, clinical-stage antibodies. We look forward to progressing the development of FL-501 and bringing the asset into the clinic in 2026."
Key Findings:
- In humanized FcRn mouse studies, FL-501 demonstrated a 2-3-fold longer half-life and
50% reduced clearance compared to its wild-type precursor and ponsegromab - In mouse cachexia models using GDF-15-overexpressing colorectal cancer cells, FL-501 fully restored body composition, comparably or better than clinical-stage antibodies visugromab and ponsegromab
- In a non-small cell lung cancer patient-derived xenograft model, FL-501 effectively countered cisplatin-induced weight loss, restoring body weight, composition, and condition scores
- These findings confirm GDF-15's role in cachexia and support FL-501's advancement in development
Poster Details:
Title: FL-501 is a potential best in class GDF-15 inhibitor with extended half-life and potent anti-cachexia activity in preclinical models
Presenter: Roma Kaul, PhD, Leap Therapeutics
Session Category: Experimental and Molecular Therapeutics
Session Title: New and Emerging Cancer Drug Targets
Date and Time: Tuesday, April 29, 2025, 9:00 a.m. – 12:00 p.m. CT
Poster Board Number: 15
Published Abstract Number: 4258
About FL-501
FL-501 is a potential best-in-class monoclonal antibody in preclinical development that targets growth differentiation factor-15 (GDF-15), a cytokine that is produced at elevated levels in response to various stresses, including chronic inflammation, obesity, cardiovascular diseases, cancers, and chemotherapy treatment. High GDF-15 expression is associated with cancer cachexia including loss of appetite, nausea and weight loss. FL-501 was engineered for higher affinity to GDF-15 and longer plasma half-life compared to competing therapies. In addition to cachexia, FL-501 may be able to reverse immunosuppression in cancers where elevated GDF-15 is correlated with poor survival, as well as play a role in treating other GDF-15-related diseases. FL-501 is being developed through a collaboration agreement with Adimab.
About Leap
Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, sirexatamab (DKN-01), is a humanized monoclonal antibody targeting the Dickkopf-1 (
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All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; the anticipated timing for initiation or completion of clinical trials and release of clinical trial data and the expectations surrounding the outcomes thereof; Leap's future clinical or preclinical product development plans for any of Leap's product candidates; Leap's estimations of projected cash runway; and any assumptions underlying any of the foregoing, are forward-looking statements. Important factors that could cause actual results to differ materially from Leap's plans, estimates or expectations could include, but are not limited to: (i) the results of Leap's clinical trials and pre-clinical studies, including the final data from Part B of the DeFianCe study and additional preclinical data for FL-501, (ii) Leap's ability to successfully finance or enter into new strategic partnerships for sirexatamab or FL-501; (iii) any regulatory feedback that Leap may receive from
CONTACT:
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Leap Therapeutics, Inc.
617-714-0360
donsi@leaptx.com
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FAQ
What are the key preclinical results of Leap Therapeutics' FL-501 for cancer cachexia treatment?
When will Leap Therapeutics (LPTX) begin clinical trials for FL-501?
How does FL-501 compare to existing GDF-15 inhibitors in development?
What specific cancer conditions did LPTX's FL-501 show effectiveness against in preclinical studies?
