PepGen said that a phase 1 trial of PGN-EDO51 in healthy adult males met its main goal by showing that the drug was safe and generally well tolerated at pharmacologically relevant doses.
PGN-EDO51 is PepGen's lead product candidate being developed to treat patients with Duchenne muscular dystrophy (DMD) whose mutations are amenable to an exon 51 skipping approach. PGN-EDO51 uses the company's proprietary Enhanced Delivery Oligonucleotide (EDO) technology to deliver a therapeutic oligonucleotide which is aimed to target the root cause of the disease, the company said in a Sept. 28 press release.
In the study the 32 healthy normal volunteers (HNV) received either 1, 5, 10 or 15 mg/kg of PGN-EDO51 or placebo.
The company said PGN-EDO51 exhibited the highest levels of oligonucleotide delivery and exon skipping in a clinical study following a single dose when compared to publicly available clinical data for other exon 51 skipping approaches.
PepGen added that a dose dependent increase in PGN-EDO51 tissue concentration and exon skipping was seen in biceps.
The company said that the majority of treatment-emergent adverse events (TEAEs) were assessed as mild and resolved without any intervention. At 10 mg/kg, there were only Grade 1 (mild) adverse events.
At 15 mg/kg, there were mild, transient, reversible changes in kidney biomarkers which resolved without intervention in all but one HNV who received IV hydration, the company noted.
In addition, PepGen said transient mild (Grade 1) to moderate (Grade 2) hypomagnesemia ( low levels of magnesium) was seen in two people at the 15 mg/kg dose and did not require any intervention.
The company noted that Serum cystatin C, the recommended biomarker to evaluate kidney function in DMD, showed minimal change at the highest dose.
All participants completed the trial and there were no discontinuations, according to the company.
"We are thrilled to announce that we have observed very high levels of oligonucleotide delivery and exon skipping in muscle in our Phase 1 HNV trial. The EDO technology performed above our expectations," said PepGen President and CEO James McArthur.
PepGen said it remains on track to start a phase 2a multiple ascending dose trial of PGN-EDO51 in patients with DMD in H1 2023.
DMD is genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations in a protein called dystrophin.
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PepGen's Duchenne muscular dystrophy drug shows promise in phase 1 trial in healthy people