Entrada Therapeutics Presents New Data Supporting its Expanding Duchenne Franchise at the 29th Annual Congress of the World Muscle Society

Rhea-AI Summary

Entrada Therapeutics (Nasdaq: TRDA) presented new data supporting its Duchenne franchise at the 29th Annual Congress of the World Muscle Society. The company shared additional positive data from its completed Phase 1 trial of ENTR-601-44, reinforcing its safety profile and supporting planned Q4 2024 global regulatory filings for a Phase 2 trial. Preclinical data for ENTR-601-45 showed exon skipping and dystrophin production, supporting planned Q4 2024 regulatory filings for a global direct-to-patient Phase 2 trial.

Key highlights include:

• No adverse findings or clinically relevant changes to renal toxicity biomarkers at the highest dose tested for ENTR-601-44
• Statistically significant differences in exon skipping between 6 mg/kg and placebo administrations
• ENTR-601-45 produced robust dose-dependent exon skipping and dystrophin restoration in preclinical models
• Improved skeletal muscle function in an exon 45 skip-amenable DMD mouse model

Positive

• Phase 1 trial of ENTR-601-44 met all study objectives with no adverse events related to administration
• Statistically significant differences in exon skipping observed between 6 mg/kg and placebo administrations
• ENTR-601-45 showed robust dose-dependent exon skipping and dystrophin restoration in preclinical models
• Improved skeletal muscle function observed in exon 45 skip-amenable DMD mouse model
• Company on track to submit regulatory applications for Phase 2 trials of ENTR-601-44 and ENTR-601-45 in Q4 2024

Negative

• None.

Insights

Medical Research Analyst

The presentation of new data for Entrada Therapeutics' Duchenne muscular dystrophy (DMD) franchise is highly significant for the company's clinical development pipeline. Key points include:

• Additional safety data from the Phase 1 trial of ENTR-601-44 showed no adverse findings or clinically relevant changes in renal toxicity biomarkers at the highest dose tested.
• Preclinical data for ENTR-601-45 demonstrated robust exon skipping and dystrophin production, supporting planned regulatory filings for a Phase 2 trial.
• The company is on track to submit regulatory applications for Phase 2 trials of both ENTR-601-44 and ENTR-601-45 in Q4 2024.

These results validate Entrada's Endosomal Escape Vehicle (EEV) platform for delivering oligonucleotide therapeutics to skeletal muscle. The positive data across multiple candidates strengthens the company's position in the competitive DMD treatment landscape and could potentially lead to breakthrough therapies for patients with different genetic mutations causing DMD.

Biotechnology Industry Expert

Entrada's progress with its DMD franchise represents a significant advancement in the field of oligonucleotide therapeutics. The key implications are:

• The safety profile and efficacy signals from the ENTR-601-44 Phase 1 trial provide a strong foundation for moving into Phase 2, potentially accelerating the development timeline.
• Preclinical data for ENTR-601-45 showing functional improvement in animal models suggests a higher likelihood of clinical success, which could differentiate Entrada's approach from competitors.
• The planned expansion to include ENTR-601-50 in 2025 demonstrates the scalability of Entrada's platform to address multiple genetic subtypes of DMD.

For investors, this news indicates that Entrada is executing well on its clinical development strategy and has a growing pipeline of potentially valuable assets. The company's ability to target multiple exon-skipping mutations could lead to a broader market opportunity and reduced risk compared to single-product companies in the rare disease space.

– Additional positive data from the Company’s completed Phase 1 clinical trial evaluating ENTR-601-44 reinforces its safety profile and supports the planned Q4 2024 global regulatory filings for a Phase 2 clinical trial –

– Preclinical data presented for the first time, showing exon skipping and dystrophin production for ENTR-601-45, supports the planned Q4 2024 regulatory filings for a global direct-to-patient Phase 2 clinical trial –

BOSTON, Oct. 09, 2024 (GLOBE NEWSWIRE) -- Entrada Therapeutics, Inc. (Nasdaq: TRDA) is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets long considered inaccessible. Today the Company announced the presentation of clinical and preclinical data in support of its expanding Duchenne clinical franchise at the 29^th Annual Congress of the World Muscle Society in Prague, Czechia from October 8-12, 2024.

“We are excited to present these data which support the advancement of our Duchenne franchise. Adding to our previously reported positive data from our Phase 1 ENTR-601-44-101 trial, we are presenting further safety data demonstrating that there were no adverse findings or clinically relevant changes to any biomarkers of renal toxicity measured at the highest dose tested during the study. We are also pleased to present new data from preclinical studies of ENTR-601-45, showing compelling in vivo dystrophin production and functional improvement,” said Natarajan Sethuraman, PhD, President of R&D at Entrada Therapeutics.

Dr. Sethuraman continued, “We are on track to submit regulatory applications this quarter to initiate separate global Phase 2 clinical trials for ENTR-601-44 and ENTR-601-45 in patients with Duchenne who are exon 44 skipping and exon 45 skipping amenable, respectively. In addition, we plan to submit regulatory applications in 2025 to initiate a global Phase 2 clinical trial for our third Duchenne candidate, ENTR-601-50, in patients who are exon 50 skipping amenable.”

The posters will be presented during Poster Session 2 (DMD Treatments, 5:15-6:15 pm CET) and will be available on the Scientific Presentations page of the Company’s website.

Poster presented by Natarajan Sethuraman, PhD, President of R&D of Entrada Therapeutics: Therapeutic Potential of ENTR-601-44, an Endosomal Escape Vehicle (EEV™)–Oligonucleotide Conjugate for the Treatment of Exon 44 Skip-Amenable Duchenne Muscular Dystrophy

Highlights of the poster presentation include:

• Study ENTR-601-44-101 met all study objectives in healthy male volunteers with no adverse events related to ENTR-601-44 administration.
• Newly presented data include urine PK data, kidney function assessments and additional safety details. The data demonstrate that there were no adverse findings or clinically relevant changes to any biomarkers of renal toxicity at the highest dose tested (6 mg/kg) during the study.
• Dose dependent increases of the final metabolite were observed.
• Statistically significant differences in exon skipping between the 6 mg/kg and placebo administrations were also observed.

These results demonstrate, for the first time, that the EEV platform can safely and effectively deliver oligonucleotide therapeutics to skeletal muscle with significant target engagement in human volunteers.

Poster presented by Sweta Girgenrath, PhD, Vice President, Head of Cardiovascular and Neuromuscular Therapeutic Areas of Entrada Therapeutics: Exon 45 Skipping and Dystrophin Production with ENTR-601-45 in Preclinical Models of Duchenne Muscular Dystrophy

Highlights of the poster presentation include data presented for the first time:

• ENTR-601-45 produced robust dose-dependent exon skipping and dystrophin restoration in both in vitro and in vivo models of exon 45 skip–amenable DMD.
• Improved skeletal muscle function in an exon 45 skip-amenable DMD mouse model suggests that ENTR-601-45 is capable of producing functional dystrophin protein in vivo.
• At the highest dose of ENTR-601-45 examined, dystrophin production and muscle function were similar to healthy control mice.
  

These results show the therapeutic potential of ENTR-601-45 and support further study in patients with DMD amenable to exon 45 skipping.

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 and 50 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 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 its ability to provide a potential treatment for patients, expectations regarding significant accumulation of exon skipping and dystrophin production in patients, expectations regarding improvement in functional outcomes for patients after multiple doses of ENTR-601-44, expectations regarding the importance of endosomal escape to therapeutic index optimization, expectations regarding the timing of regulatory filings for the planned Phase 2 clinical trials for ENTR-601-44 and ENTR-601-45 in the fourth quarter of 2024, and ENTR-601-50 in 2025, the ability to recruit for and complete a global Phase 2 trial for ENTR-601-44, ENTR-601-45 and ENTR-601-50, the potential of Entrada’s EEV product candidates, including the potential for ENTR-601-44 to be a transformative treatment option, and EEV platform, and the continued development and advancement of ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the treatment of Duchenne and the partnered product VX-670 for the treatment of myotonic dystrophy type 1, 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 will be predictive of the results of later preclinical studies and clinical trials; whether preliminary clinical data will be predictive of final clinical data; 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 and Media Contact
Caileigh Dougherty
Head of Investor Relations & Corporate Communications
cdougherty@entradatx.com

FAQ

What new data did Entrada Therapeutics (TRDA) present at the World Muscle Society Congress?

Entrada Therapeutics presented additional positive data from its Phase 1 trial of ENTR-601-44 and preclinical data for ENTR-601-45, showing exon skipping and dystrophin production in Duchenne muscular dystrophy models.

When does Entrada Therapeutics (TRDA) plan to submit regulatory filings for Phase 2 trials of ENTR-601-44 and ENTR-601-45?

Entrada Therapeutics plans to submit global regulatory filings for Phase 2 trials of both ENTR-601-44 and ENTR-601-45 in Q4 2024.

What were the key safety findings for ENTR-601-44 in Entrada Therapeutics' (TRDA) Phase 1 trial?

The Phase 1 trial of ENTR-601-44 showed no adverse findings or clinically relevant changes to any biomarkers of renal toxicity at the highest dose tested (6 mg/kg).

What preclinical results did Entrada Therapeutics (TRDA) report for ENTR-601-45?

Preclinical studies of ENTR-601-45 showed robust dose-dependent exon skipping, dystrophin restoration, and improved skeletal muscle function in models of exon 45 skip-amenable Duchenne muscular dystrophy.