Pipeline
Expanding therapeutic possibilities
Using our novel Enhanced Delivery Oligonucleotide (EDO) platform, we are developing a broad pipeline of disease-modifying peptide-conjugated oligonucleotide candidates to treat a variety of degenerative neuromuscular diseases.
People with serious neuromuscular diseases including Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1) have limited therapeutic options. In spite of approved therapies for DMD, there are no treatments that have clinically demonstrated a meaningful impact on disease progression.
| PROGRAM | TARGET | DISCOVERY | PRECLINICAL | FIH/FIP | ESTIMATED PATIENTS |
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| Exon 51 |
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H1 2022 | US: >10,000 with DMD, PepGen will address 35%+ |
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| Other Exons |
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| DMPK |
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H1 2023 | US: ~40,000 | ||
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Indication
Discovery
Preclinical
Phase 1
Phase 2
DMD is a rare genetic disease affecting approximately 15,000 patients in the U.S. It results from genetic mutations that prevent the body from producing dystrophin, a protein that muscles need to work properly. Without dystrophin, muscle cells become damaged and weaken. Over time, children with DMD will develop problems walking and breathing, and eventually the muscles that help them breathe and help their hearts beat will stop working, with few patients surviving into their 30s. DMD is an irreversible, progressive disease for which there is currently no cure.
Our most advanced candidate in the DMD program, EDO51, targets exon 51, a validated genetic target in approximately 13% of DMD patients. By blocking the inclusion of exon 51 , the proper dystrophin-producing reading frame is restored, and a shortened, but functional, dystrophin is produced.
In clinical and preclinical studies to date, PGN-EDO51 has demonstrated:
- PGN-EDO51 treatment resulted in the highest levels of oligo delivery & exon 51 skipping in humans following a single dose*
- Highest level of exon 51 skipping in NHP skeletal muscle at tolerable target dose levels, and highest level of dystrophin production in mdx mouse skeletal muscle**
- Generally well-tolerated
* Comparative statements are based on cross-trial comparisons with publicly-available data for other exon skipping approaches that have been assessed following a single dose in humans, and following single and multiple doses in NHP.
** Of clinical-stage DMD therapies.
Indication
Discovery
Preclinical
Phase 1
Phase 2
Phase 3
Milestones
Myotonic dystrophy type 1, or DM1, is a genetic disorder that affects many parts of the body. DM1 (also known as Steinert’s disease) is the most prevalent form of the condition and generally the most severe. DM1 affects an estimated 40,000 people in the U.S. With an average life expectancy of 45-60 years, patients typically present with myotonia (stiff or contracted muscles), muscle weakness, and cardiac and respiratory abnormalities. Many patients also experience excessive daytime sleepiness, fatigue, and issues with gastrointestinal or cognitive dysfunction that greatly affect their quality of life. The congenital form of DM1 is the most severe version and can be life-threatening.
Our most advanced candidate in the DM1 program, EDODM1, delivers a peptide conjugated antisense oligonucleotide (ASO) to restore cellular function. DM1 is caused by CUG repeats that form hairpin loops in the DMPK RNA that cause sequestering of the MBNL1 protein, a key RNA processing factor protein. This results in downstream mis-splicing events and aberrant expression of myotonic dystrophy protein kinase, a protein that plays a critical role in muscle contraction and relaxation. By blocking the toxic CUG repeats, functional downstream splicing and muscle function are restored.
In preclinical studies to date, EDODM1 has demonstrated:
- Broad biodistribution and delivery to key tissue types,
- Complete amelioration of the DM1 myotonia phenotype following a single dose,
- Sustained correction of mRNA mis-splicing for up to six months following a single dose, and
- Good tolerability.
Future opportunities
We are also advancing discovery programs in additional neuromuscular and neurologic indications to continue to leverage the broad potential of PepGen’s Enhanced Delivery Oligonucleotide (EDO) technology.