Verastem Oncology Exercises Option Early to License VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, from GenFleet Therapeutics and Provides Preliminary Clinical Update on Phase 1 Study in China
Verastem Oncology (VSTM) has exercised its early option to license VS-7375, a potential best-in-class oral KRAS G12D inhibitor, from GenFleet Therapeutics. The preliminary clinical data from the ongoing Phase 1 study in China shows promising results, with both confirmed and unconfirmed partial responses observed in patients with metastatic pancreatic cancer and advanced non-small cell lung cancer.
The study has cleared six dose cohorts with no dose-limiting toxicities, demonstrating oral bioavailability and plasma levels correlating with efficacious exposures that induced deep tumor regressions in preclinical models. Verastem plans to file a U.S. IND application in Q1 2025 and initiate a Phase 1/2a study by mid-2025.
The license grants Verastem global development and commercialization rights outside China, Hong Kong, Macau, and Taiwan. This agreement stems from an August 2023 collaboration with GenFleet targeting RAS pathway-driven cancers.
Verastem Oncology (VSTM) ha esercitato la sua opzione anticipata per licenziare VS-7375, un inibitore orale potenzialmente di prim'ordine del KRAS G12D, da GenFleet Therapeutics. I dati clinici preliminari dello studio di Fase 1 in corso in Cina mostrano risultati promettenti, con risposte parziali sia confermate che non confermate osservate in pazienti con cancro pancreatico metastatico e carcinoma polmonare non a piccole cellule avanzato.
E' stata completata l'analisi di sei coorti di dosaggio senza tossicità limitanti, dimostrando la biodisponibilità orale e livelli plasmatici che nei modelli preclinici hanno indotto regressioni tumorali notevoli. Verastem prevede di presentare una domanda IND negli Stati Uniti nel primo trimestre del 2025 e di avviare uno studio di Fase 1/2a entro metà del 2025.
La licenza concede a Verastem diritti globali di sviluppo e commercializzazione al di fuori di Cina, Hong Kong, Macao e Taiwan. Questo accordo deriva da una collaborazione di agosto 2023 con GenFleet mirata a combattere i tumori guidati dalla via RAS.
Verastem Oncology (VSTM) ha ejercido su opción anticipada para licenciar VS-7375, un potencial inhibidor oral KRAS G12D de primera clase, de GenFleet Therapeutics. Los datos clínicos preliminares del estudio de Fase 1 en curso en China muestran resultados prometedores, con respuestas parciales tanto confirmadas como no confirmadas observadas en pacientes con cáncer de páncreas metastásico y cáncer de pulmón no microcítico avanzado.
El estudio ha superado seis cohortes de dosis sin toxicidades limitantes, demostrando bioflexibilidad oral y niveles plasmáticos que corresponden a exposiciones eficaces que inducen regresiones tumorales profundas en modelos preclínicos. Verastem planea presentar una solicitud IND en EE. UU. en el primer trimestre de 2025 e iniciar un estudio de Fase 1/2a a mediados de 2025.
La licencia otorga a Verastem derechos globales de desarrollo y comercialización fuera de China, Hong Kong, Macao y Taiwán. Este acuerdo se origina de una colaboración de agosto de 2023 con GenFleet que apunta a los cánceres impulsados por la vía RAS.
Verastem Oncology (VSTM)는 GenFleet Therapeutics로부터 잠재적인 최고급 경구 KRAS G12D 억제제인 VS-7375에 대한 조기 라이센스 옵션을 행사했습니다. 진행 중인 중국의 1상 연구에서 확보된 초기 임상 데이터는 전이성 췌장암 및 비소세포 폐암 환자에서 확인된 응답과 확인되지 않은 부분 응답 모두에서 유망한 결과를 보여줍니다.
이 연구는 용량 제한 독성 없이 여섯 개의 투여 그룹을 완료했으며, 이는 경구 생체이용률과 효능 노출과 관련된 혈장 수치를 입증하여 전임상 모델에서 깊은 종양 퇴행을 유도한 결과입니다. Verastem은 2025년 1분기에 미국에서 IND 신청서를 제출할 예정입니다 그리고 2025년 중반까지 1/2a 단계 연구를 시작할 계획입니다.
이 라이센스는 Verastem에게 중국, 홍콩, 마카오, 대만 이외의 지역에서 전 세계 개발 및 상용화 권한을 부여합니다. 이 협정은 RAS 경로에 의해 유도된 암을 목표로 하는 GenFleet과의 2023년 8월 협력에서 비롯됩니다.
Verastem Oncology (VSTM) a exercé son option anticipée pour licencier VS-7375, un inhibiteur oral KRAS G12D potentiel de premier plan, de GenFleet Therapeutics. Les données cliniques préliminaires de l'étude de phase 1 en cours en Chine montrent des résultats prometteurs, avec des réponses partielles confirmées et non confirmées observées chez des patients atteints de cancer du pancréas métastatique et de cancer du poumon non à petites cellules avancé.
L'étude a franchi six cohortes de dose sans toxicités limitantes, démontrant une biodisponibilité orale et des niveaux plasmatiques correspondant à des expositions efficaces qui ont induit des régressions tumorales profondes dans des modèles précliniques. Verastem prévoit de déposer une demande IND aux États-Unis au premier trimestre 2025 et de commencer une étude de phase 1/2a d'ici la mi-2025.
La licence accorde à Verastem des droits de développement et de commercialisation mondiaux en dehors de la Chine, de Hong Kong, de Macao et de Taïwan. Cet accord découle d'une collaboration d'août 2023 avec GenFleet visant les cancers induits par la voie RAS.
Verastem Oncology (VSTM) hat seine vorzeitige Option zur Lizenzierung von VS-7375, einem potenziellen besten oralen KRAS G12D-Inhibitor, von GenFleet Therapeutics genutzt. Die vorläufigen klinischen Daten aus der laufenden Phase-1-Studie in China zeigen vielversprechende Ergebnisse, mit sowohl bestätigten als auch unbestätigten partiellen Reaktionen bei Patienten mit metastasierendem Pankreaskrebs und fortgeschrittenem nicht-kleinzelligen Lungenkrebs.
Die Studie hat sechs Dosisgruppen ohne dosislimitierende Toxizitäten abgeschlossen und zeigt orale Bioverfügbarkeit sowie Plasmaspiegel, die mit wirksamen Expositionen korrelieren und in präklinischen Modellen tiefe Tumorrückgänge induzierten. Verastem plant, im ersten Quartal 2025 einen IND-Antrag in den USA einzureichen und bis Mitte 2025 eine Phase-1/2a-Studie zu starten.
Die Lizenz gewährt Verastem globale Entwicklungs- und Vermarktungsrechte außerhalb von China, Hongkong, Macau und Taiwan. Diese Vereinbarung stammt aus einer Zusammenarbeit mit GenFleet im August 2023, die sich auf durch den RAS-Weg bedingte Krebserkrankungen konzentriert.
- Partial responses observed in pancreatic and lung cancer patients
- No dose-limiting toxicities across six dose levels
- Successful oral bioavailability achievement
- Plasma levels correlate with efficacious exposures in preclinical models
- Secured global rights for VS-7375 outside Asian markets
- Clinical trials to China currently
- U.S. clinical trials won't begin until mid-2025
- geographical rights excluding key Asian markets
Insights
The early exercise of VS-7375 license represents a strategic advancement in targeting KRAS G12D mutations, which are present in approximately 30% of pancreatic cancers and 13% of colorectal cancers. The preliminary Phase 1 data is particularly encouraging, showing both confirmed and unconfirmed partial responses in pancreatic and lung cancer patients - historically challenging indications. The absence of dose-limiting toxicities across six dose levels suggests a favorable safety profile, which is important for potential combination therapies.
The pharmacokinetic data indicating plasma levels correlating with preclinical efficacy is a critical technical validation. For comparison, many early KRAS inhibitors struggled with bioavailability issues. The oral administration route and demonstrated bioavailability significantly enhance the commercial potential compared to injectable alternatives.
Think of KRAS G12D as a stuck accelerator in a car - VS-7375's ON/OFF mechanism aims to restore normal cellular "speed control". This approach could prove more effective than permanent inhibition strategies.
The early option exercise indicates strong confidence in VS-7375's potential, strategically expanding Verastem's RAS/MAPK portfolio. The deal structure is particularly noteworthy - securing global rights while leaving the Chinese market to GenFleet creates a capital-efficient development pathway. This approach allows Verastem to leverage GenFleet's existing Phase 1 data, potentially accelerating the U.S. development timeline.
The planned Q1 2025 IND filing positions Verastem to enter the competitive KRAS inhibitor market with differentiated technology. The timing aligns well with market dynamics, as first-generation KRAS inhibitors have validated the target while leaving room for improved approaches. The "best-in-class" potential, if realized, could capture significant market share in what's projected to be a
VS-7375 is a potential best-in-class oral and selective KRAS G12D (ON/OFF) inhibitor currently in Phase 1 development in
License establishes global development and commercialization rights for Verastem for VS-7375 outside of
VS-7375 demonstrated oral bioavailability, no dose-limiting toxicities across six dose levels, and partial responses, including patients with pancreatic and lung cancers in preliminary clinical data from the Phase 1 dose-escalation study in
As previously announced by GenFleet, 26 patients have been treated with VS-7375 in a Phase 1 dose-escalation study being conducted in
Enrollment in the Phase 1 dose-escalation study in
“Bringing VS-7375 formally into our pipeline allows us to leverage our scientific and development expertise in the RAS/MAPK-pathway to target KRAS G12D - the most prevalent KRAS mutation in human cancers,” said Dan Paterson, chief executive officer at Verastem Oncology. “Our decision to exercise the option early for VS-7375 was based on the safety, pharmacokinetics and efficacy data to date in the Phase 1 study in
In August of 2023, Verastem entered into a discovery and collaboration agreement with GenFleet to advance three oncology discovery programs targeting RAS pathway-driven cancers. The collaboration was designed with a risk-sharing structure and flexibility for Verastem to exclusively license up to three compounds selected for collaboration after the successful completion of pre-determined milestones in Phase 1 trials. Under the terms of the license for VS-7375, Verastem receives an exclusive global license to VS-7375 outside of the GenFleet markets of mainland
About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor
VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet’s IND for VS-7375 (known as GFH375 in
The Phase 1 portion of the study is being conducted in approximately 20 hospitals in
Preclinical data presented at the American Association for Cancer Research (AACR) Annual Meeting in April 2024 demonstrated oral bioavailability across preclinical species, strong anti-tumor activity as a single agent, and potent efficacy in an intracranial tumor model suggesting the potential to treat brain metastases.
KRAS G12D represents
About the GenFleet Therapeutics Collaboration
The collaboration with GenFleet Therapeutics aims to advance three oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase 1 trial. Verastem selected VS-7375 (also known as GFH375), an oral KRAS G12D (ON/OFF) inhibitor, as its lead program in December 2023 and the license for VS-7375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of the GenFleet markets of mainland
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition and KRAS G12D inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn.
Forward-Looking Statements
This press release includes forward-looking statements about, among other things, Verastem Oncology’s programs and product candidates, strategy, future plans and prospects, including statements related to the anticipated timing for the IND application for VS-7375/GFH375, the expected outcome and benefits of its collaboration with GenFleet Therapeutics (
Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements we make. Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the development and potential commercialization of our product candidates, including VS-7375, avutometinib in combination with other compounds, including defactinib, LUMAKRAS™ and others; the uncertainties inherent in research and development, such as negative or unexpected results of clinical trials, the occurrence or timing of applications for our product candidates that may be filed with regulatory authorities in any jurisdiction; whether and when regulatory authorities in any jurisdiction may approve any such applications that may be filed for our product candidates, and, if approved, whether our product candidates will be commercially successful in such jurisdictions; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding trial design, labeling and other matters that could affect the timing, availability or commercial potential of our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from clinical trials will be predictive of the results or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is uncertain; that the market opportunities of our drug candidates are based on internal and third-party estimates which may prove to be incorrect; that third-party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that enrollment of clinical trials may take longer than expected, which may delay our development programs, including delays in review by the FDA of our NDA submission in recurrent KRAS mutant; risks associated with preliminary and interim data, which may not be representative of more mature data, including with respect to interim duration of therapy data; that our product candidates may cause adverse safety events and/or unexpected concerns may arise from additional data or analysis, or result in unmanageable safety profiles as compared to their levels of efficacy; that we may be unable to successfully validate, develop and obtain regulatory approval for companion diagnostic tests for our product candidates that require or would commercially benefit from such tests, or experience significant delays in doing so; that the mature RAMP 201 data and associated discussions with the FDA may not support the scope of our NDA submission for the avutometinib and defactinib combination in LGSOC, including with respect to KRAS wild type LGSOC; that our product candidates may experience manufacturing or supply interruptions or failures; that any of our third party contract research organizations, contract manufacturing organizations, clinical sites, or contractors, among others, who we rely on fail to fully perform; that we face substantial competition, which may result in others developing or commercializing products before or more successfully than we do which could result in reduced market share or market potential for our product candidates; that we may be unable to successfully initiate or complete the clinical development and eventual commercialization of our product candidates; that the development and commercialization of our product candidates may take longer or cost more than planned, including as a result of conducting additional studies or our decisions regarding execution of such commercialization; that we may not have sufficient cash to fund our contemplated operations, including certain of our product development programs; that we may not attract and retain high quality personnel; that we or Chugai Pharmaceutical Co., Ltd. may fail to fully perform under the avutometinib license agreement; that the total addressable and target markets for our product candidates might be smaller than we are presently estimating; that we or Secura Bio, Inc. (Secura) may fail to fully perform under the asset purchase agreement with Secura, including in relation to milestone payments; that we may not see a return on investment on the payments we have and may continue to make pursuant to the collaboration and option agreement with GenFleet Therapeutics (
Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (SEC) on March 14, 2024 and in any subsequent filings with the SEC, which are available at www.sec.gov. The forward-looking statements contained in this press release reflect Verastem Oncology’s views as of the date hereof, and the Company does not assume and specifically disclaims any obligation to update any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law.
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Source: Verastem Oncology
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