Foghorn Therapeutics Announces First Patient Dosed with First-in-Class Oral SMARCA2 Selective Inhibitor FHD-909 in a Phase 1 Trial for SMARCA4 Mutated Solid Tumors
Foghorn Therapeutics (Nasdaq: FHTX) has announced the dosing of the first patient with FHD-909, a first-in-class oral SMARCA2 selective inhibitor, in a Phase 1 trial for SMARCA4 mutated solid tumors. The primary target population is non-small cell lung cancer (NSCLC). This trial is part of a U.S. 50/50 co-development and co-commercialization collaboration with Lilly, who leads the clinical development.
FHD-909 is a highly potent and selective compound targeting SMARCA2 over SMARCA4. The Phase 1 open-label, multicenter trial will assess safety, tolerability, and initial efficacy in patients with locally advanced or metastatic solid tumors harboring SMARCA4 alterations. Preclinical studies have shown promising results, including robust anti-tumor activity and favorable tolerability.
Foghorn Therapeutics (Nasdaq: FHTX) ha annunciato la somministrazione del primo paziente con FHD-909, un inibitore selettivo di SMARCA2 di prima classe per via orale, in una fase 1 dello studio per tumori solidi mutati da SMARCA4. La popolazione target primaria è il carcinoma polmonare non a piccole cellule (NSCLC). Questo studio è parte di una collaborazione di co-sviluppo e co-commercializzazione 50/50 negli Stati Uniti con Lilly, che guida lo sviluppo clinico.
FHD-909 è un composto altamente potente e selettivo che colpisce SMARCA2 rispetto a SMARCA4. La fase 1 dello studio è un trial multicentrico, in aperto, che valuterà la sicurezza, la tollerabilità e l'efficacia iniziale nei pazienti con tumori solidi localmente avanzati o metastatici che presentano alterazioni di SMARCA4. Gli studi preclinici hanno mostrato risultati promettenti, inclusa una robusta attività anti-tumorale e una tollerabilità favorevole.
Foghorn Therapeutics (Nasdaq: FHTX) ha anunciado la dosificación del primer paciente con FHD-909, un inhibidor selectivo de SMARCA2 de primera clase por vía oral, en un ensayo de fase 1 para tumores sólidos mutados por SMARCA4. La población objetivo principal es cáncer de pulmón no microcítico (NSCLC). Este ensayo es parte de una colaboración de co-desarrollo y co-comercialización 50/50 en EE. UU. con Lilly, que lidera el desarrollo clínico.
FHD-909 es un compuesto altamente potente y selectivo, que se dirige a SMARCA2 sobre SMARCA4. El ensayo de fase 1, abierto y multicéntrico, evaluará la seguridad, tolerabilidad y eficacia inicial en pacientes con tumores sólidos localmente avanzados o metastásicos que contienen alteraciones en SMARCA4. Los estudios preclínicos han mostrado resultados prometedores, incluyendo una robusta actividad anti-tumoral y una tolerabilidad favorable.
포그혼 테라퓨틱스(Foghorn Therapeutics, Nasdaq: FHTX)는 SMARCA4 변이 고형 종양을 위한 1상 시험에서 최초의 환자에게 FHD-909, 첫 번째 클래스의 경구용 SMARCA2 선택적 억제제를 투여했다고 발표했습니다. 주요 목표 인구는 비소세포 폐암 (NSCLC)입니다. 이 시험은 릴리와의 50/50 공동 개발 및 상업화 협력의 일환으로, 릴리가 임상 개발을 주도하고 있습니다.
FHD-909는 SMARCA4보다 SMARCA2를 선택적으로 표적으로 하는 매우 강력한 화합물입니다. 1상 개방 라벨 다기관 시험은 SMARCA4 변이가 있는 국소 진행 또는 전이성 고형 종양 환자에서 안전성, 내약성 및 초기 효능을 평가합니다. 전임상 연구는 강력한 항종양 활성과 유리한 내약성을 포함하여 유망한 결과를 보여주었습니다.
Foghorn Therapeutics (Nasdaq: FHTX) a annoncé l'administration du premier patient avec FHD-909, un inhibiteur sélectif de SMARCA2 de première classe par voie orale, dans un essai de phase 1 pour des tumeurs solides mutées par SMARCA4. La population cible principale est le cancer du poumon non à petites cellules (NSCLC). Cet essai fait partie d'une collaboration de co-développement et de co-commercialisation 50/50 avec Lilly, qui dirige le développement clinique.
FHD-909 est un composé hautement puissant et sélectif ciblant SMARCA2 au détriment de SMARCA4. L'essai de phase 1, en ouvert et multicentrique, évaluera la sécurité, la tolérance et l'efficacité initiale chez des patients atteints de tumeurs solides localement avancées ou métastatiques présentant des altérations de SMARCA4. Des études précliniques ont montré des résultats prometteurs, y compris une activité anti-tumorale robuste et une tolérance favorable.
Foghorn Therapeutics (Nasdaq: FHTX) hat die Dosierung des ersten Patienten mit FHD-909 angekündigt, einem erstklassigen oralen selektiven SMARCA2-Hemmer, in einer Phase-1-Studie für SMARCA4-mutierte solide Tumoren. Die primäre Zielpopulation ist nicht-kleinzelliges Lungenkarzinom (NSCLC). Diese Studie ist Teil einer 50/50 Co-Entwicklungs- und Co-Kommerzialisierungs-Kooperation mit Lilly, die die klinische Entwicklung leitet.
FHD-909 ist eine hochpotente und selektive Verbindung, die SMARCA2 über SMARCA4 zielt. Die Phase-1- offene, multizentrische Studie wird Sicherheit, Verträglichkeit und erste Wirksamkeit bei Patienten mit lokal fortgeschrittenen oder metastasierten soliden Tumoren, die SMARCA4-Alternationen aufweisen, bewerten. Vorklinische Studien haben vielversprechende Ergebnisse gezeigt, einschließlich robuster Anti-Tumor-Aktivität und guter Verträglichkeit.
- First-in-class SMARCA2 selective inhibitor entering clinical trials
- Collaboration with Lilly for co-development and co-commercialization
- Promising preclinical results showing anti-tumor activity and favorable tolerability
- Potential application in NSCLC and other SMARCA4 mutated solid tumors
- None.
Insights
The initiation of the Phase 1 trial for FHD-909 marks a significant milestone in the field of targeted cancer therapies. As the first SMARCA2 selective inhibitor to enter clinical trials, this compound represents a novel approach to treating SMARCA4 mutated cancers, particularly non-small cell lung cancer (NSCLC).
The synthetic lethality strategy employed here is particularly promising. By selectively inhibiting SMARCA2 in tumors with SMARCA4 mutations, FHD-909 aims to exploit a vulnerability specific to cancer cells while potentially sparing normal tissues. This approach could lead to more effective and less toxic treatments for patients with NSCLC and other solid tumors harboring SMARCA4 alterations.
Preclinical data showing robust anti-tumor activity and favorable tolerability provide a strong rationale for clinical development. The demonstration of dose-dependent modulation of SMARCA2 target genes and tumor regression in xenograft models suggests potential for meaningful clinical efficacy.
The collaboration with Lilly adds significant value, bringing additional resources and expertise to accelerate development. The 50/50 co-development and co-commercialization agreement for the U.S. market indicates shared confidence in the program's potential.
This news represents a positive development for Foghorn Therapeutics and potentially for patients with SMARCA4 mutated cancers. The advancement of FHD-909 into clinical trials validates Foghorn's Gene Traffic Control® platform and strengthens their position in the competitive oncology drug development landscape.
The collaboration with Lilly is a key factor to consider. It provides Foghorn with significant financial and developmental support, mitigating some of the risks associated with clinical trials. The 50/50 profit-sharing agreement for the U.S. market could lead to substantial returns if FHD-909 proves successful.
Investors should note that while this is an important milestone, it's still early in the clinical development process. Phase 1 trials primarily focus on safety and dosing and efficacy signals, while hoped for, are secondary endpoints. The timeline to potential commercialization is likely several years away, assuming successful trial progression.
The broader implications of Foghorn's platform technology and pipeline should also be considered. Success with FHD-909 could validate their approach and potentially increase the value of their other programs, including the additional undisclosed oncology target and three discovery programs mentioned in the Lilly collaboration.
Primary target patient population for the FHD-909 Phase 1 trial is non-small cell lung cancer (NSCLC)
Lilly leads the clinical development of the Phase 1 trial
Foghorn’s selective SMARCA2 oncology program is part of a U.S. 50/50 co-development and co-commercialization collaboration with Lilly
CAMBRIDGE, Mass., Oct. 10, 2024 (GLOBE NEWSWIRE) -- October 10, 2024 -- Foghorn® Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, today announced that the first patient has been dosed with FHD-909 (LY4050784) in the Phase 1 trial for SMARCA4 (BRG1) mutated cancers, with non-small cell lung cancer (NSCLC) as the primary target patient population. FHD-909 is a first-in-class oral, highly potent compound that demonstrates high selectivity for SMARCA2 (BRM) over SMARCA4, a closely related protein.
“FHD-909 is the first SMARCA2 selective inhibitor to enter the clinic. Dosing the first patient marks an important milestone for the program and our collaboration with Lilly,” said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. “FHD-909 has high selectivity over closely related SMARCA4, offering a promising synthetic lethality strategy for prevalent SMARCA4 mutations and their sensitivity to SMARCA2 inhibition in NSCLC and other solid tumors. We look forward to continued advancement of FHD-909 in partnership with Lilly.”
A Phase 1 open-label, multicenter trial will assess the safety, tolerability and initial efficacy of FHD-909 in patients with locally advanced or metastatic solid tumors harboring a SMARCA4 alteration.
Preclinical studies support that FHD-909 is a potent and selective SMARCA2 inhibitor with robust anti-tumor monotherapy activity. In vivo, FHD-909 has demonstrated favorable tolerability with dose-dependent modulation of SMARCA2 target genes, as well as robust and dose-dependent tumor growth inhibition and regression as a monotherapy in SMARCA2 mutant xenograft mouse models.
In December 2021, Foghorn announced a strategic collaboration with Lilly to create novel oncology medicines. The collaboration includes a U.S. 50/50 co-development and co-commercialization agreement for Foghorn’s Selective SMARCA2 oncology program and an additional undisclosed oncology target. The collaboration also includes three discovery programs using Foghorn’s proprietary Gene Traffic Control® platform.
To learn more about the Phase 1 trial of FHD-909, please visit ClinicalTrials.gov.
About FHD-909
FHD-909 (LY4050784) is a potent, first-in-class, allosteric and orally available small molecule that selectively inhibits the ATPase activity of SMARCA2 (BRM) over its closely related paralog SMARCA4 (BRG1), two proteins that are the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, tumors with mutations in SMARCA4 rely on SMARCA2 for BAF function. FHD-909 has shown significant anti-tumor activity across multiple SMARCA4 mutant lung tumor models.
About Foghorn Therapeutics
Foghorn® Therapeutics is discovering and developing a novel class of medicines targeting genetically determined dependencies within the chromatin regulatory system. Through its proprietary scalable Gene Traffic Control® platform, Foghorn is systematically studying, identifying and validating potential drug targets within the chromatin regulatory system. The Company is developing multiple product candidates in oncology. Visit our website at www.foghorntx.com for more information on the Company, and follow us on X (formerly Twitter) and LinkedIn.
Forward-Looking Statements
This press release contains “forward-looking statements.” Forward-looking statements include statements regarding the Company’s clinical trials, product candidates and research efforts, including statements relating to FHD-909, and other statements identified by words such as “could,” “may,” “might,” “will,” “likely,” “anticipates,” “intends,” “plans,” “seeks,” “believes,” “estimates,” “expects,” “continues,” “projects” and similar references to future periods. Forward-looking statements are based on our current expectations and assumptions regarding capital market conditions, our business, the economy and other future conditions. Because forward-looking statements relate to the future, by their nature, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. As a result, actual results may differ materially from those contemplated by the forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include regional, national or global political, economic, business, competitive, market and regulatory conditions, including risks relating to our clinical trials and other factors set forth 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. Any forward-looking statement made in this press release speaks only as of the date on which it is made.
Contacts:
Karin Hellsvik, Foghorn Therapeutics Inc. (Investors & Media)
khellsvik@foghorntx.com
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