Entrada Therapeutics Receives Authorization in the United Kingdom to Initiate ELEVATE-45-201, a Phase 1/2 Multiple Ascending Dose Clinical Study of ENTR-601-45 in People Living with Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping
Entrada Therapeutics (NASDAQ: TRDA) has received authorization from the UK's MHRA to initiate ELEVATE-45-201, a Phase 1/2 multiple ascending dose clinical study for ENTR-601-45 in Duchenne muscular dystrophy (DMD) patients amenable to exon 45 skipping.
The study is structured in two parts: Part A will evaluate safety, pharmacokinetics, and pharmacodynamics in approximately 24 patients across three cohorts, with doses ranging from 5 mg/kg to 15 mg/kg administered every six weeks. Part B will further assess the optimal dose established in Part A. Study participants may be eligible for an open-label extension study.
The company plans to initiate the study in Q3 2025. ELEVATE-45 represents the second of three Duchenne programs Entrada expects to advance into global clinical development in 2025, with regulatory filings already submitted in the EU.
Entrada Therapeutics (NASDAQ: TRDA) ha ricevuto l'autorizzazione dalla MHRA del Regno Unito per avviare ELEVATE-45-201, uno studio clinico di Fase 1/2 a dosi ascendenti multiple per ENTR-601-45 in pazienti affetti da distrofia muscolare di Duchenne (DMD) suscettibili al skipping dell'esone 45.
Lo studio è strutturato in due parti: la Parte A valuterà la sicurezza, la farmacocinetica e la farmacodinamica in circa 24 pazienti suddivisi in tre coorti, con dosi che vanno da 5 mg/kg a 15 mg/kg somministrate ogni sei settimane. La Parte B valuterà ulteriormente la dose ottimale stabilita nella Parte A. I partecipanti allo studio potrebbero essere idonei a uno studio di estensione in aperto.
L'azienda prevede di avviare lo studio nel terzo trimestre del 2025. ELEVATE-45 rappresenta il secondo dei tre programmi su Duchenne che Entrada prevede di sviluppare nella clinica globale nel 2025, con le domande di autorizzazione già presentate nell'UE.
Entrada Therapeutics (NASDAQ: TRDA) ha recibido autorización de la MHRA del Reino Unido para iniciar ELEVATE-45-201, un estudio clínico de Fase 1/2 de dosis múltiples ascendentes para ENTR-601-45 en pacientes con distrofia muscular de Duchenne (DMD) susceptibles a la omisión del exón 45.
El estudio está estructurado en dos partes: la Parte A evaluará la seguridad, la farmacocinética y la farmacodinamia en aproximadamente 24 pacientes en tres cohortes, con dosis que varían de 5 mg/kg a 15 mg/kg administradas cada seis semanas. La Parte B evaluará más a fondo la dosis óptima establecida en la Parte A. Los participantes del estudio pueden ser elegibles para un estudio de extensión abierto.
La compañía planea iniciar el estudio en el tercer trimestre de 2025. ELEVATE-45 representa el segundo de tres programas sobre Duchenne que Entrada espera avanzar en el desarrollo clínico global en 2025, con solicitudes regulatorias ya presentadas en la UE.
Entrada Therapeutics (NASDAQ: TRDA)는 영국의 MHRA로부터 ENTR-601-45의 두 번째 단계 1/2 다중 용량 상승 임상 연구인 ELEVATE-45-201을 시작할 수 있는 승인을 받았습니다. 이 연구는 45번 엑손 스킵이 가능한 듀셴 근육 위축증(DMD) 환자를 대상으로 합니다.
연구는 두 부분으로 구성됩니다: A 부분은 약 24명의 환자를 세 개의 집단으로 나누어 5mg/kg에서 15mg/kg까지의 용량을 6주마다 투여하여 안전성, 약동학 및 약리작용을 평가합니다. B 부분은 A 부분에서 설정된 최적 용량을 추가로 평가합니다. 연구 참가자는 오픈 라벨 연장 연구에 참여할 수 있는 자격이 있을 수 있습니다.
회사는 2025년 3분기에 연구를 시작할 계획입니다. ELEVATE-45는 Entrada가 2025년에 글로벌 임상 개발로 진행할 것으로 예상하는 세 가지 듀셴 프로그램 중 두 번째를 나타내며, 이미 EU에 규제 신청이 제출되었습니다.
Entrada Therapeutics (NASDAQ: TRDA) a reçu l'autorisation de la MHRA du Royaume-Uni pour lancer ELEVATE-45-201, une étude clinique de Phase 1/2 à doses multiples ascendantes pour ENTR-601-45 chez des patients atteints de dystrophie musculaire de Duchenne (DMD) susceptibles de bénéficier d'un skipping de l'exon 45.
L'étude est structurée en deux parties : la Partie A évaluera la sécurité, la pharmacocinétique et la pharmacodynamie chez environ 24 patients répartis en trois cohortes, avec des doses allant de 5 mg/kg à 15 mg/kg administrées toutes les six semaines. La Partie B évaluera plus avant la dose optimale établie dans la Partie A. Les participants à l'étude pourraient être éligibles à une étude d'extension en ouvert.
L'entreprise prévoit de commencer l'étude au troisième trimestre de 2025. ELEVATE-45 représente le deuxième des trois programmes sur Duchenne qu'Entrada prévoit de faire avancer dans le développement clinique mondial en 2025, avec des dépôts réglementaires déjà soumis dans l'UE.
Entrada Therapeutics (NASDAQ: TRDA) hat die Genehmigung der MHRA im Vereinigten Königreich erhalten, um ELEVATE-45-201 zu starten, eine klinische Studie der Phase 1/2 mit mehrfachen aufsteigenden Dosen für ENTR-601-45 bei Patienten mit Duchenne-Muskeldystrophie (DMD), die für das Exon-45-Skipping geeignet sind.
Die Studie ist in zwei Teile gegliedert: Teil A wird die Sicherheit, Pharmakokinetik und Pharmakodynamik bei etwa 24 Patienten in drei Kohorten bewerten, mit Dosen von 5 mg/kg bis 15 mg/kg, die alle sechs Wochen verabreicht werden. Teil B wird die in Teil A festgelegte optimale Dosis weiter bewerten. Die Studienteilnehmer könnten für eine offene Verlängerungsstudie in Frage kommen.
Das Unternehmen plant, die Studie im dritten Quartal 2025 zu starten. ELEVATE-45 stellt das zweite von drei Duchenne-Programmen dar, die Entrada voraussichtlich im Jahr 2025 in die globale klinische Entwicklung vorantreiben wird, wobei bereits regulatorische Anträge in der EU eingereicht wurden.
- Received UK regulatory authorization for Phase 1/2 trial
- On track for Q3 2025 trial initiation
- Part of expanding pipeline with three Duchenne programs planned for 2025
- EU regulatory review in progress
- No U.S. FDA approval yet for clinical trials
- Clinical trial results not expected until after Q3 2025
Insights
Entrada Therapeutics has received UK regulatory clearance to begin ELEVATE-45-201, a Phase 1/2 clinical trial for ENTR-601-45 in Duchenne muscular dystrophy (DMD) patients amenable to exon 45 skipping. This marks important pipeline progress as the company's second DMD program advances to human testing.
The trial design is comprehensive, featuring a multiple ascending dose study to evaluate safety, pharmacokinetics, and pharmacodynamics, including the critical biomarkers of exon skipping and dystrophin production. The company plans to test doses from 5 mg/kg to 15 mg/kg administered every six weeks, followed by an extension phase to assess longer-term outcomes.
Entrada's strategic approach of initiating trials in the UK and EU before FDA engagement helps accelerate development timelines while building a global data package. This authorization reinforces management's execution on their stated goal of having three DMD programs in clinical development by year-end.
While this represents positive progress, investors should recognize that Phase 1/2 trials are early-stage, with results likely 12+ months away and potential commercialization still years off. Nevertheless, expanding the clinical pipeline in a high-need indication like DMD is a significant milestone that validates Entrada's platform technology and development strategy.
This clinical trial authorization for ENTR-601-45 represents meaningful progress for Duchenne muscular dystrophy patients with exon 45 skippable mutations, who constitute approximately 8% of the DMD population. DMD is a devastating progressive muscle-wasting disease that typically leads to loss of ambulation in early adolescence and premature death due to respiratory or cardiac failure.
Entrada's oligonucleotide approach utilizing their proprietary Endosomal Escape Vehicle (EEV) technology aims to enhance cellular delivery - a critical limitation of current approved exon-skipping therapies. If successful, improved delivery could potentially translate to better dystrophin production and meaningful clinical outcomes.
The trial design is scientifically sound, evaluating both biochemical markers (exon skipping, dystrophin production) and functional outcomes. The dose range exploration is particularly important as finding the optimal therapeutic window is crucial in oligonucleotide therapeutics.
The company's parallel development of multiple exon-skipping candidates (44, 45, and a third program) demonstrates a comprehensive approach to addressing different genetic subtypes of DMD. While clinical validation remains pending, this authorization enables critical human testing of a potential treatment for a patient population with significant unmet medical need.
– Company on track to initiate ELEVATE-45-201 study in Q3 2025 –
– ELEVATE-45 regulatory filings submitted in the EU, with regulatory review ongoing –
– ELEVATE-45 is the second of three novel exon skipping Duchenne programs the Company expects to progress into global clinical development in 2025 –
BOSTON, March 24, 2025 (GLOBE NEWSWIRE) -- Entrada Therapeutics, Inc. (Nasdaq: TRDA) today announced it has received authorization from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) and Research Ethics Committee to initiate ELEVATE-45-201. ELEVATE-45-201 is a Phase 1/2 multiple ascending dose (MAD) clinical study to evaluate Entrada’s investigational medicinal product ENTR-601-45 for the potential treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation in the DMD gene amenable to exon 45 skipping.
“We are pleased to receive U.K. clearance for the second clinical program in our growing Duchenne franchise. Building on the momentum of our ELEVATE-44 program, this authorization brings us closer to having three Duchenne programs in clinical development by the end of this year,” said Dipal Doshi, Chief Executive Officer of Entrada Therapeutics. “For people living with progressive diseases, every moment counts. To meet this urgency in Duchenne, we will continue our strategy of initiating and running studies in the U.K. and EU before sharing these study results with the FDA to potentially enable registrational studies in the U.S."
ELEVATE-45-201 is a global, two-part, randomized, double-blind placebo-controlled Phase 1/2 study evaluating the safety, tolerability and effectiveness of ENTR-601-45 in ambulatory patients with Duchenne who are exon 45 skipping amenable. Part A is a multiple ascending dose study designed to evaluate the safety, pharmacokinetics and pharmacodynamics, including exon skipping and dystrophin production in approximately 24 patients. Dosing will be administered every six weeks, with the planned doses across three cohorts anticipated to range from 5 mg/kg up to 15 mg/kg. Part B of the study is designed to further evaluate the optimal dose established in Part A for safety and efficacy, including functional outcomes and patient reported quality of life measures. Study participants may be eligible to enter an open label extension study (OLE), in which the safety, efficacy and tolerability of ENTR-601-45 will be evaluated over a longer period of time. The Company is on track to initiate ELEVATE-45-201 in Q3 2025.
About ENTR-601-45
ENTR-601-45, a proprietary Endosomal Escape Vehicle (EEV™)-conjugated phosphorodiamidate morpholino oligomer (PMO), is the second product candidate within Entrada’s Duchenne muscular dystrophy franchise from its growing pipeline of EEV-therapeutics. Each EEV-PMO therapeutic candidate has an oligonucleotide sequence designed and optimized for the specific subpopulation of interest. ENTR-601-45 is designed to address the underlying cause of Duchenne due to mutated or missing exons in the DMD gene. ENTR-601-45, an investigational therapy for the potential treatment of people living with Duchenne who are exon 45 skipping amenable, is being evaluated for its potential to restore the mRNA reading frame and allow for the translation of dystrophin protein that is slightly shortened but still functional.
About Duchenne Muscular Dystrophy (DMD)
Duchenne muscular dystrophy (DMD) is a rare disease caused by mutations in the DMD gene, which encodes for the dystrophin protein. These mutations lead to inadequate dystrophin production. Dystrophin is essential to maintaining the structural integrity and function of muscle cells. Lack of functional dystrophin leads to progressive loss of muscle strength, impacting mobility and causing heart or respiratory complications that contribute to high mortality rates. An estimated 41,000 people in the U.S. and Europe have Duchenne.
About Entrada Therapeutics
Entrada Therapeutics is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets that have long been considered inaccessible. The Company’s Endosomal Escape Vehicle (EEV™)-therapeutics are designed to enable the efficient intracellular delivery of a wide range of therapeutics into a variety of organs and tissues, resulting in an improved therapeutic index. Through this proprietary, versatile and modular approach, Entrada is advancing a robust development portfolio of RNA-, antibody- and enzyme-based programs for the potential treatment of neuromuscular, ocular, metabolic and immunological diseases, among others. The Company’s lead oligonucleotide programs are in development for the potential treatment of people living with Duchenne who are exon 44, 45, 50 and 51 skipping amenable. Entrada has partnered to develop a clinical-stage program, VX-670, for myotonic dystrophy type 1.
For more information about Entrada, please visit our website, www.entradatx.com, and follow us on LinkedIn.
Forward-Looking Statements
This press release contains express and implied forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Entrada’s strategy, future operations, prospects and plans, objectives of management, the validation and differentiation of Entrada’s approach and EEV platform and its ability to provide a potential treatment for patients, expectations regarding Entrada’s planned Phase 1/2 MAD clinical study of ENTR-601-45, including its initiation in the United Kingdom in Q3 2025, the expectations about the planned dosing levels of the planned Phase 1/2 trial for ENTR-601-45 and their efficacy, the ability to recruit for and complete a global Phase 1/2 trial for ENTR-601-45 and the anticipated number of patients to be enrolled, the potential of Entrada’s EEV product candidates, including the potential for ENTR-601-45 to be a transformative treatment option, and the continued development and advancement of ENTR-601-45 for the potential treatment of DMD, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Entrada may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities and the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical and clinical studies; the timing of and Entrada’s ability to submit and obtain regulatory clearance and initiate clinical trials; whether results from preclinical studies or clinical trials will be predictive of the results of later preclinical studies and clinical trials; whether Entrada’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Entrada’s filings with the Securities and Exchange Commission (SEC), including the Company’s Annual Report on Form 10-K for the fiscal year and quarter ended December 31, 2024 and in subsequent filings Entrada may make with the SEC. In addition, the forward-looking statements included in this press release represent Entrada’s views as of the date of this press release. Entrada anticipates that subsequent events and developments will cause its views to change. However, while Entrada may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Entrada’s views as of any date subsequent to the date of this press release.
Investor and Media Contact
Caileigh Dougherty
Head of Investor Relations & Corporate Communications
cdougherty@entradatx.com
FAQ
When will Entrada Therapeutics (TRDA) begin the ELEVATE-45-201 clinical trial?
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What regulatory approvals has TRDA received for the ELEVATE-45-201 study?
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