WALTHAM, Mass. — Dyne Therapeutics, Inc., a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, today announced positive initial clinical data from its ACHIEVE trial of DYNE-101 in patients with myotonic dystrophy type 1 (DM1) and its DELIVER trial of DYNE-251 in patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.
“We are excited that Dyne’s first clinical data in two programs have demonstrated proof-of-concept and validated the promise of the FORCE™ platform in developing targeted therapeutics for rare muscle diseases. In addition to the opportunity with our co-lead programs, this clinical validation reinforces the potential of FORCE to deliver for patients in other areas, including building a global DMD franchise, addressing FSHD and exploring diseases involving the CNS,” said Joshua Brumm, Dyne’s president and chief executive officer. “The safety profiles for both DYNE-101 and DYNE-251 have supported dose escalation to a combined 10 cohorts and the administration of nearly 600 doses across both the ACHIEVE and DELIVER trials. This positions us to optimize dose and dose regimen in both trials with the goal of initiating registrational cohorts as we end 2024. We anticipate reporting data for multiple, higher dose cohorts from both trials in the second half of 2024, while continuing to pursue expedited regulatory pathways and working to help address the urgent need for therapeutics for people living with DM1 and Duchenne.”
“These compelling initial data from our ACHIEVE and DELIVER trials highlight the exciting opportunity we have to advance our investigational therapeutics for devastating diseases with no or limited treatment options. DYNE-101 demonstrated early dose-dependent results, including in correction of splicing, the key biomarker for DM1, as well as meaningful improvement in myotonia at the lowest dose. Treatment with DYNE-251 surpassed the level of dystrophin production reported for the standard of care for DMD exon 51 with a fraction of the dose. Underpinning these results are favorable safety profiles, which are critical in the development of therapies for chronic diseases,” said Wildon Farwell, M.D., MPH, Dyne’s chief medical officer. “We are grateful to the participants, clinicians and the community for their ongoing partnership as we collectively strive to transform the treatment of rare muscle diseases.”
Phase 1/2 ACHIEVE Trial of DYNE-101 in Myotonic Dystrophy Type 1
The initial efficacy assessment of the DYNE-101 ACHIEVE trial is based on data from 32 adult DM1 patients enrolled in the randomized, placebo-controlled multiple ascending dose (MAD) portion of the trial, including 6-month data from the 1.8 mg/kg (approximate ASO dose) cohort (n=16) and 3-month data from the 3.4 mg/kg Q4W cohort (n=16). In each of these cohorts, participants were randomized to receive either DYNE-101 (n=6) or placebo (n=4) once every four weeks or participants in the recovery arm (n=6) received two doses of DYNE-101 followed by placebo for the remainder of the MAD portion of the trial.
In the ACHIEVE trial, DYNE-101 demonstrated a dose-dependent splicing correction and increase in muscle delivery and DMPK knockdown while also showing functional improvement in myotonia. Key initial findings from ACHIEVE include:
- Muscle Delivery: Administration of 3.4 mg/kg of DYNE-101 Q4W demonstrated a mean ASO muscle concentration of 21.5 ng/g at 3 months, while administration of 1.8 mg/kg Q4W showed a mean ASO muscle concentration of 10.0 ng/g at 3 months.
- DMPK Knockdown: Evaluable patients in the 3.4 mg/kg Q4W group had a 40% mean DMPK knockdown from baseline compared to 25% in patients in the 1.8 mg/kg Q4W group at 3 months.
- Splicing: Evaluable patients treated with 3.4 mg/kg Q4W of DYNE-101 had a 19% mean splicing correction from baseline across a broad, 22-gene panel at 3 months, with all evaluable participants experiencing an improvement. Patients in the 1.8 mg/kg Q4W group at 3 months had a 13% mean splicing correction.
- Function: Patients treated with 1.8 mg/kg of DYNE-101 Q4W had a mean 3.8 second benefit in myotonia at 6 months as measured by video hand opening time (vHOT). Myotonia, which is difficulty in relaxing muscles, is a common symptom of DM1 patients.
- Patient Reported Outcome (PRO): Patients in the DYNE-101 1.8 mg/kg Q4W group experienced an overall improvement at 6 months in the Myotonic Dystrophy Health Index (MDHI), including the fatigue subscale, suggesting potential benefit of DYNE-101 in the CNS.
Safety and tolerability data in this initial assessment of the ACHIEVE trial are based on 45 patients enrolled through the 5.4 mg/kg Q8W cohort of the MAD portion. As of the data cutoff date2, DYNE-101 has demonstrated a favorable safety profile. The majority of treatment-emergent adverse events were mild or moderate and no related serious treatment-emergent adverse events have been identified. In addition, no participants demonstrated treatment-emergent anemia, and no clinically meaningful changes were observed in kidney or liver parameters. All participants who have completed the MAD portion of ACHIEVE have enrolled in the 24-week open-label extension (OLE).
Enrollment is complete through the 5.4 mg/kg Q8W cohort of the ACHIEVE trial (48 total patients enrolled), and approximately 300 doses have been administered to date, supporting dose escalation up to 6.8 mg/kg. Dyne anticipates providing its next clinical data update from the ACHIEVE trial in the second half of 2024.
Phase 1/2 DELIVER Trial of DYNE-251 in Duchenne Muscular Dystrophy
The initial efficacy assessment of the DYNE-251 DELIVER trial is based on 6-month data from 6 male patients with DMD amenable to exon 51 skipping enrolled in the 5 mg/kg (approximate PMO dose) cohort of the randomized, placebo-controlled MAD portion of the trial. Patients were randomized to receive either DYNE-251 (n=4) or placebo (n=2) once every four weeks. Once every 4-week administration of DYNE-251 reached levels of dystrophin expression, exon skipping and percent dystrophin positive fibers that exceeded levels reported in a clinical trial for the current weekly standard of care for DMD exon 51, eteplirsen, at 6 months1 with a 24-fold lower total PMO dose. Key initial findings from DELIVER include:
- Muscle delivery: DYNE-251 showed a mean 657 ng/g PMO muscle drug concentration at 6 months.
- Exon 51 skipping: DYNE-251 demonstrated a mean absolute exon skipping level of 0.90% and a 0.80% change from baseline at 6 months. The current standard of care, eteplirsen, which is administered weekly, showed a 0.59% mean absolute exon skipping level and a 0.40% change from baseline at 6 months. 1
- Dystrophin expression measured by Western blot: Patients treated with DYNE-251 had a mean absolute dystrophin level of 0.88% of normal and a 0.28% change from baseline at 6 months. Eteplirsen reached a mean absolute dystrophin level of 0.30% of normal and a 0.06% change from baseline at 6 months.1
- Percent dystrophin positive fibers: DYNE-251 demonstrated 22.2% mean level of dystrophin positive fibers (PDPF) and a 19.8% change from baseline at 6 months. Eteplirsen showed a 19.6% mean level of PDPF and a 10.7% change from baseline at 6 months.1
Safety and tolerability data in the DELIVER trial are based on 37 patients enrolled through the 20 mg/kg cohort of the MAD portion. As of the data cutoff date2, DYNE-251 has demonstrated a favorable safety profile. The majority of treatment-emergent adverse events were mild or moderate and no related serious adverse events have been identified. In addition, no participants demonstrated treatment-emergent anemia, and no clinically meaningful changes were observed in kidney parameters or electrolytes, including magnesium. All participants who have completed the MAD portion of DELIVER have enrolled in the 24-week OLE.
Enrollment is complete through the 20 mg/kg cohort of the DELIVER trial (40 total patients enrolled) and approximately 275 doses have been administered to date, supporting dose escalation up to 40 mg/kg. Dyne anticipates providing its next clinical data update from the DELIVER trial in the second half of 2024.
About Dyne Therapeutics
Dyne Therapeutics is a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases. With its proprietary FORCE™ platform, Dyne is developing modern oligonucleotide therapeutics that are designed to overcome limitations in delivery to muscle tissue. Dyne has a broad pipeline for serious muscle diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and a preclinical program for facioscapulohumeral muscular dystrophy (FSHD).
Contacts
Investors
Amy Reilly
[email protected]
857-341-1203
Media
Stacy Nartker
[email protected]
781-317-1938