Is Highly Volatile Pepgen Worth a Closer Look?

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Written By Kevin MacDonald

Shares of PepGen Inc. (NASDAQ: PEPG) have experienced significant volatility, with the stock cratering 80% from its peak, rebounding 370%, and then falling back slightly within a span of 14 months.

This fluctuation occurred as the company advanced two clinical candidates. The rebound was driven by news that Sarepta’s (SRPT) second-generation DMD exon 51 clinical candidate demonstrated significantly lower skipping output compared to PepGen’s PGN-EDO51.

With data from its two programs expected in 2024 and an increasingly competitive neuromuscular clinical landscape, the extreme volatility in PepGen’s stock warrants further investigation.

Company Overview

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PepGen Inc. is a Boston-based clinical-stage biopharmaceutical company focused on developing oligonucleotide therapies for severe neuromuscular and neurologic diseases.

The company is advancing two programs in human trials, targeting Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). PepGen commenced operations in 2018 and went public in 2022, raising net proceeds of $110.2 million at $12 per share.

Its stock trades around $13.50 a share, translating to an approximate market cap of $440 million.


Oligonucleotide therapies are a growing focus in the biotech industry, with FDA approvals for multiple indications.

These treatments fall under two categories based on their bioactive moieties: antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs).

PepGen’s enhanced delivery oligonucleotide (EDO) platform conjugates cell-penetrating peptides (CPPs) to PMOs, designed to improve cellular uptake and evade the cell’s transportation and sorting mechanism, enhancing nuclear delivery of its PMOs significantly over unconjugated counterparts.


PepGen’s pipeline includes two peptide-conjugated PMO (PPMO) clinical programs:

PGN-EDO51: This lead product candidate is designed to treat DMD in patients amenable to exon 51 skipping, representing approximately 13% of all DMD cases in the U.S. and EU. DMD is a severe genetic disorder characterized by muscle weakness and wasting, with most patients becoming wheelchair-bound by their teenage years and facing life-threatening complications by their 30s.

PGN-EDO51 is undergoing evaluation in a three-cohort Canadian Phase 2 trial (CONNECT1-EDO51) and a Phase 1 study has shown promising results, achieving significantly higher exon skipping compared to Sarepta’s Exondys 51 and its second-generation candidate SRP-5051.

PGN-EDODM1: This clinical asset targets DM1, a monogenic, autosomal dominant disease with manifestations including muscle weakness and cardiac arrhythmias.

DM1 affects more than 40,000 individuals in the U.S. and approximately 74,000 in Europe. PGN-EDODM1’s Phase 1 study (FREEDOM-DM1) began in December 2023, with data expected in the second half of 2024.

The IND for PGN-EDODM1 received orphan and fast track designations and was lifted from a clinical hold in October 2023.

Financials and Market Position

PepGen conducted a secondary offering in early February 2024, raising net proceeds of $76.9 million. The company ended the first quarter with over $175 million in cash and marketable securities, sufficient to advance its programs into 2026.

Additional Risk Factors

PepGen faces several risks typical for developmental firms, including dependency on trial results and low trading volume, which can lead to stock volatility. Institutions own over 90% of the float, and significant insider buying was noted in the February secondary offering.

There have been no insider sales since August of the previous year.

All Eyes on Ongoing Trials

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PepGen’s stock has been highly volatile since its IPO. The company’s lead candidates, PGN-EDO51 and PGN-EDODM1, show promise in their respective indications, with the potential for significant market impact.

The competitive landscape for DMD and DM1 is evolving, and upcoming data from ongoing trials will be crucial in determining PepGen’s future success. The company’s strong financial position and positive analyst outlook suggest a robust foundation for advancing its pipeline.


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