Pipeline

Therapies with the
potential to halt disease
progression

PepGen is advancing a pipeline of disease-modifying, peptide-conjugated oligonucleotide candidates to treat neuromuscular and neurological diseases, beginning with Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). These treatments have the potential to halt, slow or potentially reverse the progression of these diseases.

PepGen’s clinical candidates for DMD and DM1 have demonstrated early signs of activity as well as being generally well tolerated. We are focused on continuing to advance these therapies through clinical trials.

INDICATION

RESEARCH

PRECLINICAL

PHASE 1

PHASE 2

Indication: DMD

Target: Exon 51 Progress Phase 2

PGN-EDO51

Target: Exon 53 Progress Preclinical

PGN-EDO53

Target: Exon 45 Progress Discovery

PGN-EDO45

Target: Exon 44 Progress Discovery

PGN-EDO44

PGN-EDO51 targets exon 51, a validated genetic target in approximately 13% of DMD patients. By skipping over the inclusion of exon 51, the proper dystrophin-producing reading frame is restored, and a shortened, functional dystrophin is produced.

In clinical and preclinical studies to date, PGN-EDO51 has demonstrated:

The highest levels of exon 51 skipping in humans following a single dose*
The 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

We are also advancing additional candidates targeting additional validated genetic targets including exon 53, exon 45, and exon 44.

_{* 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: DM1

Target: DMPK Progress Phase 2

PGN-EDODM1

PGN-EDODM1 is designed to liberate MBNL1 from toxic DMPK-CUG expansion foci without degrading DMPK. DM1 is caused by the expansion of CUG repeats forming hairpin loops in the DMPK RNA that cause sequestration of the MBNL1 protein, a key RNA processing factor protein. Sequestration of MBNL1 results in multiple downstream mis-splicing events, including aberrant expression of CLCN1, which plays a critical role in muscle contraction and relaxation. By blocking the toxic CUG repeats and liberating MBNL1, functional downstream splicing and muscle function are restored.

Clinical data from our FREEDOM 5 mg/kg and 10 mg/kg cohorts (as of a February 24, 2025 press release) showed that:

PGN-EDODM1 was observed to have a favorable emerging safety profile
Mean splicing correction from evaluable participants was 12.3% and 29.1% at 5 mg/kg and 10 mg/kg, respectively, at 28 days post-dosing
Dose dependent increase in muscle tissue concentrations was observed at 5 mg/kg and 10 mg/kg at Day 28

FUTURE

We are also advancing discovery programs in additional neuromuscular and neurological indications to continue to leverage the broad potential of PepGen’s Enhanced Delivery Oligonucleotide (EDO) technology.

Clinical Trials

PepGen is committed to changing the lives of people living with neuromuscular and neurological diseases. Our clinical trials are conducted with participant safety and wellbeing at the forefront. We work side by side with people living with these diseases, their families, advocacy groups, clinicians, regulators, and industry experts. At PepGen, we recognize the time and effort that is devoted to clinical trials by not only participants, but also their loved ones, and we are grateful to them for supporting our mission at PepGen. This information is available in Spanish, French and Italian.

See our active clinical trials below:

Duchenne Muscular Dystrophy (DMD)

CONNECT1-EDO51
CONNECT1-EDO51

Official Title: A Phase 2, Open-Label, Multiple Ascending Dose Study of PGN-EDO51 With a Long-Term Extension in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment (CONNECT1-EDO51)

Summary: The primary purpose of the multiple ascending dose (MAD) period is to evaluate the safety, tolerability, and dystrophin levels after multiple ascending intravenous doses of PGN-EDO51 are administered to participants with Duchenne muscular dystrophy (DMD). The primary purpose of the long-term extension period is to evaluate the long-term safety and tolerability of PGN-EDO51 in participants who have completed the MAD period. The study consists of 3 periods: A screening period (up to 45 days), a treatment and observation period (16 weeks), and an extension period (108 weeks).

Requirements:

Male by birth and 6 to 16 years old

Diagnosed with DMD amenable to exon 51 skipping (genetic testing will be required to join)

Weigh at least 18 kg/40 lbs

Willing to have a total of two open muscle biopsies (to collect muscle tissue samples)

Note: Other study requirements will apply

Ages: 6-16
CONNECT2-EDO51
CONNECT2-EDO51

Official Title:A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study of PGN-EDO51 with a Long-Term Extension in Participants with Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment (CONNECT2-EDO51)

Summary: The primary purpose of the multiple ascending dose (MAD) period is to evaluate safety and tolerability, as well as levels of dystrophin in skeletal muscle, following monthly intravenous doses of PGN-EDO51 administered to participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The MAD period is double-blind, placebo controlled where patients will be assigned randomly in a 3:1 ratio to either active PGN-EDO51 or placebo. The placebo looks like PGN-EDO51 but contains no active medicine. The MAD period is followed by an open-label extension period, where patients who complete the MAD period will receive active PGN-EDO51, regardless of assignment previously.

Overall, the study consists of a screening period (up to 45 days) and MAD period (28 weeks), followed by the open-label extension period (108 weeks).

Requirements:

Male by birth and between 6 and 16 years old

Diagnosed with DMD amenable to exon 51 skipping (genetic testing will be required to join)

Weigh at least 25 kg/55 lbs

Willing to have a total of two open muscle biopsies (to collect muscle tissue samples)

Note: Other study requirements will apply

Ages: 6 and older

Myotonic Dystrophy 1 (DM1)

FREEDOM-DM1
FREEDOM-DM1

Official Title: A Phase 1 Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of PGN-EDODM1 in Adult Participants With Myotonic Dystrophy Type 1 (FREEDOM-DM1)

Summary: The primary purpose of the study is to evaluate the safety and tolerability of single intravenous doses of PGN-EDODM1 administered to participants with myotonic dystrophy type 1 (DM1). The study consists of 2 periods: a screening period (up to 30 days) and a treatment and observation period (16 weeks).

Requirements:

Age 18-50

Have DM1

Willing to have a total of 3 needle muscle biopsies (a sample of your leg tissue will be collected) over several months

Note: Other inclusion and exclusion criteria may apply.

recruiting

Ages: 18-50

For more information click here or view on clinicaltrials.gov
(NCT06204809)
FREEDOM2-DM1
FREEDOM2-DM1

Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multiple‑Ascending Dose Study of PGN-EDODM1 in Adult Participants with Myotonic Dystrophy Type 1 (FREEDOM2-DM1)

Summary: The primary purpose of this study is to evaluate the safety and tolerability of multiple intravenous doses of PGN-EDODM1 administered to participants with myotonic dystrophy type 1 (DM1). The study consists of a screening period of up to 45 days, and a treatment period of 12 weeks.

Requirements:

Age 16-60

Have DM1

Willing to have a total of 2 needle muscle biopsies (a sample of your leg tissue will be collected) over several months

Note: Other inclusion and exclusion criteria may apply.

recruiting

Ages: 16-60

For more information click here or view on clinicaltrials.gov
(NCT06667453)

If you have questions about our clinical trials, email us at clinicaltrials@pepgen.com

Expanded Access

PepGen is developing Enhanced Delivery Oligonucleotides (EDOs) for the potential treatment of neuromuscular diseases. We are currently conducting clinical trials to assess the potential of our investigational EDOs. These clinical trials have specific inclusion and exclusion criteria designed to best interpret data at this early stage of development. The data generated from these trials may allow PepGen, in the future, to apply for necessary marketing approvals from regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

When a person is unable to participate in a clinical trial, there is a specific set of criteria that can allow the person to have access to the investigational drug. These situations are often called expanded access programs (EAPs), compassionate use, or early access. To qualify, the person must have a serious or immediately life-threatening disease or condition, there is no comparable or satisfactory therapy available to the person, and the potential benefits justify the potential risks of the treatment. In this situation, a person’s physician may seek access to investigational therapies outside of the clinical trial setting.

Currently, PepGen does not offer expanded access to any of its investigational EDOs outside of clinical trials as the company is still obtaining preclinical and clinical data to better understand the risks and potential benefits of its investigational EDOs. As a result, access to our investigational EDOs is only available through participation in clinical trials. As we continue to develop our investigational EDOs, our goal is to provide access to these therapies at the appropriate time and with the best interests of the community in mind. Should PepGen decide to make expanded access available in the future, this policy will be updated, including the criteria PepGen will apply in evaluating requests for expanded access.

If you are a healthcare provider who is interested in learning more about one of our investigational EDOs, or a physician with questions about this expanded access policy or participation by your patients in one of our clinical trials, please submit a request to clinicaltrials@pepgen.com. The company will acknowledge questions as soon as possible and generally within seven (7) business days of receipt.