Entrada Therapeutics, a company developing treatments for rare diseases, reports encouraging preliminary data from a Phase 1 clinical trial (ENTR-601-44-101) of their drug ENTR-601-44 for Duchenne muscular dystrophy (DMD). Their data will be presented at the 29th Annual conference of the World Muscle Society in Prague, Czechia in October 2024.
ENTR-601-44 is an investigational therapy for the potential treatment of people living with Duchenne who are exon 44 skipping amenable. The treatment 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.
The Entrada Therapeutics Phase 1 clinical trial (ENTR-601-44-101) had two main objectives:
- Safety and tolerability: This was the primary objective. The trial assessed if a single dose of ENTR-601-44 was safe and well-tolerated by healthy volunteers. This involved monitoring for any serious adverse events or side effects.
- Pharmacokinetics & Target engagement: This objective evaluated whether the drug reached its target (muscle tissue) and triggered the desired response. In DMD, the desired response is exon skipping, a cellular process that could potentially improve muscle function in patients with specific genetic mutations. The trial measured both muscle concentration of the drug (0.75mg/kg, 1.5mg/kg, 3mg/kg and 6mg/kg) and the extent of exon skipping (on a ng/g of tissue adjusted basis).
We are excited to present the first clinical data from our Duchenne franchise, led by ENTR-601-44. ENTR-601-44 was well tolerated in healthy volunteers and we are pleased to see significant plasma concentration, muscle concentration and exon skipping. We achieved the goals of the ENTR-601-44-101 trial, including the identification of a clinically relevant starting dose for the planned Phase 2 global patient study. Based on the cumulative data to date, we expect to see a significant accumulation of exon skipping and dystrophin production in patients, which we believe will lead to an improvement in functional outcomes after multiple doses. Patients are at the core of our mission at Entrada. We believe that the flexibility of our EEV-based approach will allow the therapeutic to be tailored to meet the changing needs of growing paediatric and young adult patients via dosing and other important parameters. Today’s update represents a clear validation and differentiation of Entrada’s approach and brings us one step closer to providing a potential treatment for this relentlessly progressive neuromuscular disease.
Dipal Doshi, Chief Executive Officer at Entrada Therapeutics.
Phase 1 Clinical Trial Key Points:
- Positive Safety Profile: No serious adverse events or drug-related side effects were observed in healthy volunteers.
- Target Engagement: The drug reached muscle tissue and induced exon skipping, a cellular process potentially leading to improved muscle function in DMD patients with specific genetic mutations (in this case exon 44).
- Promising Initial Results: Exon skipping was statistically significant compared to a placebo group at the highest dose tested (6mg/kg).
- Next Steps: Entrada plans regulatory filings in Q4 2024 to initiate separate Phase 2 trials for ENTR-601-44 in DMD patients amenable to exon 44 skipping and for another drug (ENTR-601-45) targeting exon 45 skipping. A Phase 2 trial for a third drug (ENTR-601-50) targeting exon 50 skipping is planned for 2025.
I am encouraged to see the preliminary results of Entrada’s Phase 1 clinical trial of ENTR-601-44. These data in healthy volunteers represent a potentially transformative treatment option for boys and young men living with Duchenne who are exon 44 skipping amenable, a population for which there are currently no exon skipping options. The data on safety generated so far are very encouraging. This, coupled with the possibility for Entrada’s EEV-therapeutics to allow for dosing intervals of at least six weeks, would significantly reduce the burden of the administration of this novel therapeutic compound and I am sure this information will be positively received by the patient community.
Francesco Muntoni, MD, Professor of Paediatric Neurology
These early findings are encouraging and represent a positive step towards a potential new treatment for DMD being developed. However, further research is necessary to confirm the drug’s efficacy and safety in DMD patients.
Would you like to know more about Duchenne muscular dystrophy? Increase your knowledge and understanding of Duchenne with our bite-sized science video series.
Section 1 – Facts about Duchenne muscular dystrophy
Section 2 – Signs and Symptoms of Duchenne muscular dystrophy
Section 3 – Diagnosis of Duchenne muscular dystrophy
Section 4 – Crucial Genetic Terminology
Section 5 – Genetics – Blueprint of Duchenne muscular dystrophy
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