Revolution Medicines Announces Publication of a Peer-Reviewed Research Paper in Science on the Discovery and Development of Zoldonrasib, a RAS(ON) G12D-Selective Inhibitor
Revolution Medicines (NASDAQ:RVMD) announced the publication of a peer-reviewed paper in Science detailing the discovery and development of zoldonrasib, their RAS(ON) G12D-selective covalent inhibitor. The drug targets RAS G12D mutations, which are present in 92% of pancreatic cancer, 50% of colorectal cancer, and 30% of non-small cell lung cancer cases.
The paper highlights zoldonrasib's novel tri-complex inhibitor mechanism, which creates a neomorphic protein-protein interface between cyclophilin A and activated RAS to selectively target RAS(ON) G12D proteins. Preclinical data showed significant tumor regression in multiple tumor types with KRAS G12D mutations.
The drug is currently being evaluated in clinical trials, including the RMC-9805-001 Phase 1 study for patients with advanced solid tumors harboring KRAS G12D mutations.
Revolution Medicines (NASDAQ:RVMD) ha annunciato la pubblicazione di un articolo peer-reviewed su Science che descrive la scoperta e lo sviluppo di zoldonrasib, il loro inibitore covalente selettivo per RAS(ON) G12D. Il farmaco mira alle mutazioni RAS G12D, presenti nel 92% dei casi di cancro al pancreas, nel 50% dei tumori del colon-retto e nel 30% dei casi di carcinoma polmonare non a piccole cellule.
L'articolo mette in evidenza il nuovo meccanismo di inibizione tri-complesso di zoldonrasib, che crea un'interfaccia neomorfica tra proteine tra la ciclophilina A e RAS attivato per colpire selettivamente le proteine RAS(ON) G12D. I dati preclinici hanno mostrato una regressione tumorale significativa in diversi tipi di tumore con mutazioni KRAS G12D.
Il farmaco 猫 attualmente in fase di valutazione clinica, incluso lo studio di Fase 1 RMC-9805-001 per pazienti con tumori solidi avanzati che presentano mutazioni KRAS G12D.
Revolution Medicines (NASDAQ:RVMD) anunci贸 la publicaci贸n de un art铆culo revisado por pares en Science que detalla el descubrimiento y desarrollo de zoldonrasib, su inhibidor covalente selectivo para RAS(ON) G12D. El f谩rmaco se dirige a las mutaciones RAS G12D, presentes en el 92% del c谩ncer de p谩ncreas, el 50% del c谩ncer colorrectal y el 30% del c谩ncer de pulm贸n no microc铆tico.
El art铆culo destaca el novedoso mecanismo inhibidor de tri-complejo de zoldonrasib, que crea una interfaz neom贸rfica prote铆na-prote铆na entre la ciclofilina A y RAS activado para atacar selectivamente las prote铆nas RAS(ON) G12D. Los datos precl铆nicos mostraron una regresi贸n tumoral significativa en m煤ltiples tipos de tumores con mutaciones KRAS G12D.
El f谩rmaco se est谩 evaluando actualmente en ensayos cl铆nicos, incluyendo el estudio de Fase 1 RMC-9805-001 para pacientes con tumores s贸lidos avanzados que presentan mutaciones KRAS G12D.
Revolution Medicines (NASDAQ:RVMD)電� RAS(ON) G12D 靹犿儩鞝� 瓿奠湢 瓴绊暕 鞏奠牅鞝滌澑 臁鸽弰雮橂澕鞁�(锄辞濒诲辞苍谤补蝉颈产)鞚� 氚滉铂 氚� 臧滊皽鞐� 甏�頃� 霃欕 鞁偓 雲茧鞚� Science鞐� 瓴岇灛霅橃棃雼り碃 氚滍憸頄堨姷雼堧嫟. 鞚� 鞎诫鞚� 旆岇灔鞎旍潣 92%, 雽�鞛レ晹鞚� 50%, 牍勳唽靹疙彫韽愳晹鞚� 30%鞐� 臁挫灛頃橂姅 RAS G12D 霃岇棸氤�鞚措ゼ 響滌爜鞙茧 頃╇媹雼�.
雲茧鞚� 臁鸽弰雮橂澕鞁潣 靸堧鞖� 靷检 氤淀暕 鞏奠牅 氅旍护雼堨鞚� 臧曥“頃橂姅雿�, 鞚措姅 鞁胳澊韥措頃勲Π A鞕� 頇滌劚頇旊悳 RAS 靷澊鞐� 靸堧鞖� 雼氨歆�-雼氨歆� 鞚疙劙韼橃澊鞀るゼ 順曥劚頃橃棳 RAS(ON) G12D 雼氨歆堨潉 靹犿儩鞝侅溂搿� 響滌爜頇旐暕雼堧嫟. 鞝勳瀯靸� 雿办澊韯半姅 KRAS G12D 霃岇棸氤�鞚措ゼ 臧�歆� 鞐煬 膦呾枒 鞙犿槙鞐愳劀 鞙犾潣氙疙暅 膦呾枒 韲挫稌鞚� 氤挫棳欤检棃鞀惦媹雼�.
鞚� 鞎诫鞚� 順勳灛 KRAS G12D 霃岇棸氤�鞚措ゼ 臧�歆� 歆勴枆靹� 瓿犿槙鞎� 頇橃瀽毳� 雽�靸侅溂搿� 頃� RMC-9805-001 1靸� 鞐瓣惮毳� 韽暔頃� 鞛勳儊 鞁滍棙鞐愳劀 韽夑皜 欷戩瀰雼堧嫟.
Revolution Medicines (NASDAQ:RVMD) a annonc茅 la publication d'un article 茅valu茅 par des pairs dans Science d茅taillant la d茅couverte et le d茅veloppement de zoldonrasib, leur inhibiteur covalent s茅lectif RAS(ON) G12D. Le m茅dicament cible les mutations RAS G12D, pr茅sentes dans 92 % des cancers du pancr茅as, 50 % des cancers colorectaux et 30 % des cancers du poumon non 脿 petites cellules.
L'article met en avant le m茅canisme novateur d'inhibition par tri-complexe de zoldonrasib, qui cr茅e une interface prot茅ine-prot茅ine n茅omorphique entre la cyclophiline A et le RAS activ茅 pour cibler s茅lectivement les prot茅ines RAS(ON) G12D. Les donn茅es pr茅cliniques ont montr茅 une r茅gression tumorale significative dans plusieurs types de tumeurs avec des mutations KRAS G12D.
Le m茅dicament est actuellement 茅valu茅 dans des essais cliniques, notamment l'茅tude de phase 1 RMC-9805-001 pour les patients atteints de tumeurs solides avanc茅es portant des mutations KRAS G12D.
Revolution Medicines (NASDAQ:RVMD) gab die Ver枚ffentlichung eines peer-reviewten Artikels in Science bekannt, der die Entdeckung und Entwicklung von zoldonrasib, ihrem RAS(ON) G12D-selektiven kovalenten Inhibitor, beschreibt. Das Medikament zielt auf RAS G12D-Mutationen ab, die in 92 % der Bauchspeicheldr眉senkrebsf盲lle, 50 % der kolorektalen Krebsf盲lle und 30 % der nicht-kleinzelligen Lungenkrebsf盲lle vorkommen.
Der Artikel hebt den neuartigen Tri-Komplex-Inhibitor-Mechanismus von zoldonrasib hervor, der eine neomorphe Protein-Protein-Schnittstelle zwischen Cyclophilin A und aktiviertem RAS schafft, um selektiv RAS(ON) G12D-Proteine zu targetieren. Pr盲klinische Daten zeigten eine signifikante Tumorr眉ckbildung bei mehreren Tumorarten mit KRAS G12D-Mutationen.
Das Medikament wird derzeit in klinischen Studien evaluiert, darunter die RMC-9805-001 Phase-1-Studie f眉r Patienten mit fortgeschrittenen soliden Tumoren mit KRAS G12D-Mutationen.
- None.
- Still in early clinical development phase
- Efficacy in humans yet to be fully demonstrated
Insights
Revolution Medicines' Science publication validates zoldonrasib's novel mechanism for targeting historically undruggable RAS G12D mutations in multiple cancers.
This Science publication represents a significant scientific breakthrough in the RAS inhibitor space. Targeting RAS mutations鈥攅specially non-G12C variants like G12D鈥攈as been one of oncology's most persistent challenges. The described tri-complex inhibitor approach is particularly innovative, creating a neomorphic protein-protein interface between cyclophilin A and activated RAS to facilitate selective covalent bond formation with the G12D variant.
What makes this approach remarkable is overcoming the specific technical hurdle of targeting aspartic acid residues with covalent inhibitors. Previous generation RAS inhibitors like sotorasib and adagrasib successfully targeted G12C mutations through cysteine's nucleophilicity, but the G12D variant had remained elusive due to aspartic acid's chemical properties.
The clinical significance is substantial given that KRAS G12D mutations appear in approximately
The company's progression into clinical trials with already presented data at major conferences (AACR for NSCLC and EORTC-NCI-AACR for PDAC) indicates they're advancing rapidly through development. This publication serves as scientific validation for their approach and strengthens their position in the competitive landscape of RAS-targeting therapeutics.
REDWOOD CITY, Calif., July 24, 2025 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced the publication of a peer-reviewed research paper in Science. The scientific paper details the discovery and development of zoldonrasib (RMC-9805), a RAS(ON) G12D-selective covalent inhibitor.
Oncogenic RAS mutations are observed in approximately
鈥淭he tri-complex inhibitor modality has proven to be a productive approach to solving the challenge of developing mutant-selective inhibitors for RAS variants beyond the G12C substitution, as demonstrated by zoldonrasib that targets the G12D variant,鈥� said Jan Smith, Ph.D., chief scientific officer of Revolution Medicines. 鈥淭his report demonstrates the novel features of zoldonrasib that enable it to bind to the active or RAS(ON) state, including a highly novel covalent bond formed selectively with the substituted aspartic acid in this oncogenic variant.聽The preclinical profile combined with recent clinical data presentations provide an encouraging picture of the therapeutic potential for zoldonrasib in cancers caused by RAS G12D and further validate the broad utility of this drug discovery approach.鈥澛�
The full manuscript, titled 鈥淎 neomorphic protein interface catalyzes covalent inhibition of RAS G12D aspartic acid in tumors,鈥� is available online at .
Zoldonrasib is currently undergoing evaluation in several clinical trials, including RMC-9805-001 (NCT06040541), a multicenter, open-label, dose escalation and dose-expansion Phase 1 study designed to evaluate zoldonrasib in patients with advanced solid tumors harboring a KRAS G12D mutation. NSCLC results from this study were presented in April 2025 at the and PDAC results from this study were presented in October 2024 at the .
About Revolution Medicines, Inc.
Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company鈥檚 R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company鈥檚 RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter clinical development. Additional development opportunities in the company鈥檚 pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit聽聽and follow us on聽.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding progression of clinical studies and findings from these studies, including the safety, tolerability and antitumor activity of the company鈥檚 candidates being studied and the durability of these results; dosing and enrollment in the company鈥檚 clinical trials; and the potential of zoldonrasib as a therapeutic option for pancreatic ductal adenocarcinoma or non small cell lung cancer. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause the company鈥檚 development programs, future results, performance or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including the company鈥檚 programs鈥� current stage of development, the process of designing and conducting preclinical and clinical trials, risks that the results of prior clinical trials may not be predictive of future clinical trials, clinical efficacy, or other future results, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company鈥檚 ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company鈥檚 capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company鈥檚 business of the global events, such as international conflicts or global pandemics. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines鈥� Annual Report on Form 10-K filed with the Securities and Exchange Commission (the 鈥淪EC鈥�) on May 7, 2025, and its future periodic reports to be filed with the SEC. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events.
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