Entrada Therapeutics Announces Positive Results from the First Cohort of Participants with Duchenne Muscular Dystrophy (DMD) in the Phase 1/2 ELEVATE-45-201 Study of ENTR-601-45
The initial-dose results showed increased dystrophin production but no observable functional benefit after three doses.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Summary
Entrada Therapeutics (TRDA) reported that ENTR-601-45 met safety and tolerability objectives in the first cohort of its Phase 1/2 DMD study. Eight participants received three doses of 5 mg/kg or placebo in ELEVATE-45-201. Treated participants had a 0.10% mean increase in dystrophin, a muscle-supporting protein, versus a 0.02% mean decrease with placebo. Exon skipping increased by a mean 0.15% versus a 0.04% mean decrease with placebo.
One participant experienced two serious adverse events, vomiting and fever, which resolved. No participants discontinued, and all entered the open-label phase. No functional benefit was observed after three doses, consistent with company expectations. Cohort 2 enrollment is complete and dosing at 10 mg/kg is ongoing; Entrada expects data in the first half of 2027, followed by Cohort 3 data at up to 15 mg/kg. The company expects higher doses to increase dystrophin production and provide functional benefit.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Hollow bars mark forward-looking points. How the balance works
Positive
- Moderate point5 mg/kg ENTR-601-45 met Cohort 1 primary safety and tolerability objectives.
- Moderate pointDystrophin increased 0.10% from baseline in treated participants (n = 6, nominal p = 0.03), versus placebo’s 0.02% decrease.
- Moderate point. Forward-looking: it has not happened yet and may not happen.Cohort 2 enrollment is complete; 10 mg/kg dosing is ongoing, with data expected in the first half of 2027.
- Minor pointExon skipping increased 0.15% from baseline (n = 5, no p-value calculated), versus placebo’s 0.04% decrease.
- Minor pointNo hypomagnesemia or renal safety concerns were noted; magnesium and treated participants’ renal markers remained within normal ranges.
5 minor points
- Minor pointPlasma exposures were consistent with predictions based on juvenile non-human primate data.
- Minor point. Forward-looking: it has not happened yet and may not happen.No study discontinuations occurred; all Cohort 1 participants entered the open-label phase for six 5 mg/kg doses.
- Minor point. Forward-looking: it has not happened yet and may not happen.Higher-dose cohorts are expected by Entrada to increase dystrophin production and provide functional benefit.
- Minor point. Forward-looking: it has not happened yet and may not happen.Cohort 3 dosing up to 15 mg/kg is planned, with data to follow Cohort 2.
- Minor pointELEVATE-44-201 Cohort 3 received an independent monitoring committee recommendation to proceed to the highest dose of 18 mg/kg.
Negative
- Minor pointTwo serious treatment-emergent adverse events, vomiting and fever, occurred in one participant and subsequently resolved.
- Minor pointHeadache was the most common treatment-emergent adverse event: five events in two participants.
- Minor pointNo observable functional benefit was expected or observed after three doses, given participants’ ages and baseline function.
Details
Market Reaction – TRDA
On Oct 14, the day this news came out, the latest delayed price for TRDA is 2.67% below the previous close. The latest delayed price is $4.73.
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Key Figures
- Dystrophin change
- 0.10% mean increase (n=6; nominal p=0.03)
- Treated participants versus baseline
- Exon-skipping change
- 0.15% mean increase (n=5; no p-value calculated)
- Treated participants versus baseline
- Placebo dystrophin change
- 0.02% mean decrease
- Placebo participants versus baseline
- Placebo exon-skipping change
- 0.04% mean decrease
- Placebo participants versus baseline
- Cohort 1 enrollment
- 8 participants
- ELEVATE-45-201 Cohort 1
- Initial dose
- 5 mg/kg
- Cohort 1
- Cohort 2 dose
- 10 mg/kg
- Cohort 2 dosing is ongoing
- Cohort 2 data timing
- First half of 2027
- Company-reported expected timing
Previous Clinical trial Reports
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EU authorization advanced the same ELEVATE-45-201 study toward its Cohort 1 results.
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UK authorization advanced the same ELEVATE-45-201 study toward its Cohort 1 results.
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Key Terms
dmd medical
pharmacokinetics medical
pharmacodynamics medical
teae medical
lloq technical
AI-generated analysis. How Rhea-AI works. Not financial advice.
-- Cohort 1 met the primary objectives of favorable safety and tolerability at the initial dose of 5 mg/kg --
-- ENTR-601-45 plasma exposures were consistent with those predicted based on juvenile non-human primate exposure data --
-- In line with expectations, the secondary objectives demonstrated a
-- Company expects a significant increase in dystrophin production and functional benefit in future cohorts while maintaining a convenient Q6W dosing schedule --
-- ELEVATE-45-201 Cohort 2 enrollment is complete and the Company is on track to report data at the increased dose of 10 mg/kg in the first half of 2027 --
BOSTON, Oct. 14, 2026 (GLOBE NEWSWIRE) -- Entrada Therapeutics, Inc. (Nasdaq: TRDA) today announced positive topline data from Cohort 1 of the double-blind, placebo-controlled, multiple ascending dose (MAD) portion of the Phase 1/2 ELEVATE-45-201 clinical study of ENTR-601-45 in ambulatory participants with a confirmed mutation in the DMD gene amenable to exon 45 skipping.
Study participants in Cohort 1 received three doses of 5 mg/kg of ENTR-601-45 or placebo. Topline results met the primary objectives of favorable safety and tolerability. The secondary objectives also met Company expectations and demonstrated a
“Establishing a favorable safety profile in Cohort 1 was our main objective and we are pleased with the outcome. These positive safety results, combined with an increase in dystrophin across treated participants at the initial low dose of 5 mg/kg, are promising. Importantly, ENTR-601-45 is designed to be dosed once every six weeks. For families currently managing a weekly infusion schedule, ENTR-601-45’s current dosing schedule translates to a potential therapy built around approximately nine administrations per year instead of more than fifty,” said Natarajan Sethuraman, PhD, President of Research and Development at Entrada Therapeutics. “Additionally, an Independent Data Monitoring Committee’s recent recommendation to proceed to the highest dose of 18 mg/kg in Cohort 3 of the ELEVATE-44-201 clinical study supports our confidence in the opportunity to escalate the dose up to 15 mg/kg in Cohort 3 of ELEVATE-45-201, where we expect to see meaningfully higher exposure, dystrophin production and functional benefit.”
“People with a confirmed mutation in the DMD gene who are amenable to exon 45 skipping represent a significant portion of the DMD patient population. As one of the most advanced next-generation exon skipping conjugate PMOs in clinical trials, ENTR-601-45 has the potential to offer a well-tolerated, low-frequency of dosing option for a large Duchenne subpopulation with a clear and increasing unmet need,” said Professor Giovanni Baranello, MD, PhD, Professor of Paediatric Neuromuscular Disorders at UCL and Honorary Consultant in Paediatric Neuromuscular Diseases at the Great Ormond Street Hospital, London, and principal investigator in the ELEVATE-45-201 clinical study. “Importantly, establishing a favorable safety profile at this initial dose in a three dose MAD study is the essential foundation for escalating to higher doses, and seeing any dystrophin produced in participants this young, with such low baseline levels, is an encouraging early signal.”
Highlights from the topline results of Cohort 1 of ELEVATE-45-201 include:
Dystrophin measured by western blot and normalized to MHC; Dystrophin values are actual observed values, including values <LLOQ; Two participants in the ENTR-601-45 group had baseline dystrophin levels <LLOQ and >LOD; LLOQ for dystrophin was
Safety, Tolerability and Pharmacokinetics
- Favorable safety and tolerability with ENTR-601-45 at the 5 mg/kg dose
- Headache (5 events in 2 participants) was the most common treatment-emergent adverse event (TEAE)
- One participant experienced 2 serious TEAEs (vomiting and pyrexia) which subsequently resolved
- There were no study discontinuations due to any cause, and all participants enrolled in the open-label extension
- No hypomagnesemia or renal safety concerns were noted
- Renal markers, including eGFR and cystatin C, were within normal ranges in treated participants
- Magnesium levels were also within the normal range
- Plasma ENTR-601-45 exposures were consistent with those predicted by juvenile non-human primate (NHP) data
- Modeled plasma exposures provide confidence in a significant increase in dystrophin expression at higher doses in Cohort 2 (10 mg/kg) and Cohort 3 (up to 15 mg/kg)
- Modeled plasma exposures provide confidence in a significant increase in dystrophin expression at higher doses in Cohort 2 (10 mg/kg) and Cohort 3 (up to 15 mg/kg)
Dystrophin Production, Exon Skipping and Functional Benefit
- A mean increase of
0.10% (n = 6, nominal p = 0.03) from baseline in dystrophin production was observed in study participants who received ENTR-601-45 versus a0.02% mean decrease from baseline in study participants who received placebo - A mean increase of
0.15% (n = 5, no p-value calculated) from baseline in exon skipping was observed in study participants who received ENTR-601-45 versus a0.04% mean decrease from baseline in study participants who received placebo - Based on the age of Cohort 1 participants and baseline levels of function, no observable functional benefit was expected or observed after three doses of ENTR-601-45
- Functional impact will be assessed with higher doses and over longer dosing periods via future cohorts and the open-label studies
About the ELEVATE-45-201 Phase 1/2 Study
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 participants aged four to 20 with Duchenne who are amenable to exon 45 skipping. The multiple ascending dose (MAD) Part A portion of the study is evaluating the safety, pharmacokinetics, pharmacodynamics and functional parameters following intravenous administration of ENTR-601-45 to study participants in three cohorts at sites in the U.K. and EU. Cohort 1 of the MAD portion of the study enrolled eight participants with Duchenne. They were randomized 3:1 to receive ENTR-601-45 at a dose of 5 mg/kg or placebo, administered intravenously. During this double-blind period, doses were administered on days one, 43 and 85, and muscle biopsies were performed at the time of screening and at six weeks after the last dose. Following the initial three doses administered in Part A, all participants continued into the Phase 2, open-label portion in which the safety and efficacy of ENTR-601-45 are evaluated over a longer period of time. Cohort 2 enrollment is complete and dosing at 10 mg/kg is ongoing. The Company is on track to report data from Cohort 2 (10 mg/kg) in the first half of 2027, with data from Cohort 3 (up to 15 mg/kg) to follow.
About ENTR-601-45
ENTR-601-45 is a proprietary Endosomal Escape Vehicle (EEV™)-conjugated oligonucleotide that has a sequence designed and optimized for people with a confirmed mutation in the DMD gene who are amenable to exon 45 skipping. This population comprises approximately nine percent of the Duchenne patient population globally. These patients face an aggressive disease course, with a median age at loss of ambulation of between 11 and 14 years among those receiving standard-of-care treatment. ENTR-601-45 is an investigational therapy 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.
Patients and Their Care Partners
Patients and their care partners are a critical part of our community, and we are committed to keeping them informed and connected. To receive community updates in real time and read today’s update, please visit Community Updates on our corporate website.
About Duchenne Muscular Dystrophy (DMD)
Duchenne muscular dystrophy (DMD) is a rare disease caused by mutations in the DMD gene, which encodes 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 are living with DMD. Of those, approximately 11,500 are amenable to skipping of exon 44, 45, 50, or 51.
About Entrada Therapeutics
Entrada Therapeutics is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of genetic medicines that engage intracellular targets that have long been considered inaccessible. Through proprietary, versatile and modular approaches, Entrada is advancing a robust development portfolio of genetic medicines for the potential treatment of neuromuscular and inherited retinal diseases, among others. The Company’s lead oligonucleotide programs are in development for the potential treatment of people living with Duchenne muscular dystrophy 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 Phase 1/2 MAD clinical study of ENTR-601-45, including the timing of data from Cohort 2 in the first half of 2027 with data from Cohort 3 to follow, a significant increase in dystrophin production and functional benefit in future cohorts, the potential for dosing up to 15 mg/kg in Cohort 3 to lead to meaningfully higher exposure, dystrophin production and functional benefit and the ability of the MAD Part A portion of the study to evaluate the safety, pharmacokinetics, pharmacodynamics and functional parameters of ENTR-601-45, expectations regarding ENTR-601-45, including the potential to restore the mRNA reading frame and allow for the translation of dystrophin protein that is slightly shortened but still functional and the potential for a dosing schedule built around approximately nine administrations a year, the potential therapeutic benefits of Entrada’s EEV product candidates, including the potential for ENTR-601-45 to be a transformative treatment option, the continued development and advancement of ENTR-601-44, ENTR-601-45, ENTR-601-50, and ENTR-601-51 for the treatment of DMD and the partnered product candidate VX-670 for the potential treatment of DM1, the ability to continue to expand and develop additional therapeutic programs and modalities, including the potential treatment of neuromuscular and inherited retinal diseases, 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 studies; 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 studies; whether results from preclinical studies or clinical studies will be predictive of the results of later preclinical studies and clinical studies; 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 most recent Form 10-K 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 Contact
Doug Snow
Head of Investor Relations
dsnow@entradatx.com
Patient Advocacy Contact
Sarah Friedhoff
Head of Patient Advocacy
patientadvocacy@entradatx.com
Media Contact
Megan Prock McGrath
CTD Comms, LLC
megan@ctdcomms.com
A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/cde575bd-e9e5-4471-840f-8ba5b119bd32
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What did Entrada’s ENTR-601-45 trial show about dystrophin production?
Participants receiving ENTR-601-45 had a 0.10% mean increase from baseline in dystrophin production, compared with a 0.02% mean decrease among placebo recipients. The treated-group result included six participants and had a nominal p-value of 0.03. No observable functional benefit was seen after three doses.
When will Entrada report the next ELEVATE-45-201 results?
Entrada expects to report Cohort 2 data in the first half of 2027. Enrollment is complete and dosing at 10 mg/kg is ongoing. Data from Cohort 3, using doses up to 15 mg/kg, are expected to follow.
How was Entrada’s first ELEVATE-45-201 cohort studied?
The eight participants were randomized 3:1 to ENTR-601-45 at 5 mg/kg or placebo in a double-blind study. Intravenous doses were given on days one, 43 and 85. Muscle biopsies were performed at screening and six weeks after the last dose.
What measurement limits applied to dystrophin results in Entrada’s ENTR-601-45 study?
The dystrophin assay’s lower limit of quantification was 0.25%, and its limit of detection was 0.1%. Two treated participants had baseline levels below the quantification limit but above the detection limit. Reported dystrophin values included actual observed values below the quantification limit.
How will Entrada assess functional benefit in the ENTR-601-45 study?
Functional impact will be assessed at higher doses and over longer dosing periods in future cohorts and open-label studies. Cohort 1 participants entered the Phase 2 open-label portion, where they will receive six doses of 5 mg/kg ENTR-601-45.