PepGen (NASDAQ: PEPG) details PGN-EDODM1 DM1 data and 2026 milestones
Rhea-AI Filing Summary
PepGen Inc. updated its corporate presentation to spotlight PGN-EDODM1, an investigational therapy for myotonic dystrophy type 1 (DM1) built on its EDO oligonucleotide delivery platform. The company reports dose-dependent, single-dose splicing correction in a Phase 1 study, with mean improvements of 12.3% at 5 mg/kg, 29.1% at 10 mg/kg, and 53.7% at 15 mg/kg, alongside generally well-tolerated safety with mainly mild to moderate adverse events. A multinational Phase 2 multiple-ascending-dose FREEDOM2-DM1 trial is under way, though a partial clinical hold has recently been placed by the U.S. FDA. PepGen highlights upcoming clinical readouts in Q1 2026 for the 5 mg/kg cohort and in the second half of 2026 for the 10 mg/kg cohort, and states it has cash runway into the second half of 2027.
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Insights
PepGen shows promising DM1 biomarker data but faces an FDA hold on its Phase 2 study.
PepGen emphasizes PGN-EDODM1 for myotonic dystrophy type 1, showing strong biomarker signals in its Phase 1 single-ascending-dose trial. Mean splicing correction rose to
The program has entered the FREEDOM2 Phase 2 multiple-ascending-dose trial across several countries, targeting functional endpoints such as hand strength and walking tests. However, the U.S. FDA has placed a partial clinical hold on FREEDOM2-DM1, and one drug-related serious adverse event plus renal biomarker changes at higher doses underline residual safety questions.
PepGen guides to key milestones, including 5 mg/kg clinical results in
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
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Item 7.01 Regulation FD Disclosure.
On March 4, 2026, PepGen Inc. (the “Company”) updated its Corporate Presentation, a copy of which is being furnished as Exhibit 99.1 and incorporated herein by reference.
The information in this Current Report on Form 8-K (including Exhibit 99.1 attached hereto) is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing. This Current Report on Form 8-K will not be deemed an admission as to the materiality of any information in this Item 7.01 (including Exhibit 99.1).
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit Number |
Description |
99.1 |
Corporate Presentation updated as of March 2026 |
104 |
Cover Page Interactive Data File (embedded within Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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PepGen Inc. |
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March 4, 2026 |
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/s/ Noel Donnelly |
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Noel Donnelly, Chief Financial Officer |
March 2026 Company Presentation
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this presentation that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements include, without limitation, statements regarding the potential of our EDO platform to deliver high levels of oligonucleotide to the nuclei, the therapeutic potential and safety profile of PGN-EDODM1 based on data from the 5, 10 and 15 mg/kg cohorts of the FREEDOM-DM1 study, our expectations regarding the potential for significant correction of mis-splicing with more doses of PGN-EDODM1 over a longer treatment period to potentially provide improved functional benefit for patients with DM1, the design, initiation and conduct of clinical trials, including expected timelines for initial data report from our FREEDOM2-DM1 trial and the potential to extend dosing to the 12.5 mg/kg dose level, the potential for any functional improvements that may result from robust splicing correction with PGN-EDODM1, dose-dependent increases in splicing suggesting that PGN-EDODM1 is getting into the muscle and effectively binding to the target, the potential for PGN-EDODM1 to offer a best-in-class treatment option, ongoing and planned regulatory interactions and our financial resources and expected cash runway. Any forward-looking statements in this presentation are based on current expectations, estimates and projections only as of the date of this presentation and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: delays or failure to successfully initiate or complete our ongoing and planned development activities for our product candidates, including PGN-EDODM1; our ability to enroll patients in our clinical trials, including FREEDOM2, that our interpretation of clinical and preclinical study results may be incorrect, or that we may not observe the levels of therapeutic activity in clinical testing that we anticipate based on prior clinical or preclinical results, including for PGN-EDODM1; our product candidates, including PGN-EDODM1, may not be safe and effective or otherwise demonstrate safety and efficacy in our clinical trials; adverse outcomes from our regulatory interactions, including delays in regulatory review, clearance to proceed or approval by regulatory authorities with respect to our programs, including clearance to commence planned clinical studies of our product candidates, including release of the partial clinical hold placed by FDA on the FREEDOM2 study, or other regulatory feedback requiring modifications to our development programs, including with respect to the FREEDOM2 program; changes in regulatory framework that are out of our control; our ability to obtain, maintain and protect our intellectual property; our ability to enforce our patents against infringers and defend our patent portfolio against challenges from third parties; competition from others developing therapies for the indications we are pursuing; unexpected increases in the expenses associated with our development activities or other events that adversely impact our financial resources and cash runway; and our dependence on third parties for some or all aspects of our product manufacturing, research and preclinical and clinical testing. Additional risks concerning PepGen's programs and operations are described in our most recent filings with the SEC. PepGen explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. This presentation discusses PGN-EDODM1, an investigational therapy, that has not been approved for use in any country,and is not intended to convey conclusions about their efficacy or safety. There is no guarantee that PGN-EDODM1 or any other investigational therapy will successfully complete clinical development or gain regulatory authority approval.
Leveraging EDO Platform to Drive Meaningful Impact for Patients PGN-EDODM1: Myotonic Dystrophy Type 1 Best-in-class potential; selectively targets only pathogenic DMPK RNA Favorable emerging safety profile and highest splicing correction ever reported in patients Regulatory clearance received in South Korea, Australia, and New Zealand; enrollment now open across Canada, UK, and South Korea Orphan Drug & Fast Track Designation (U.S.); Orphan Drug Designation (EU) Developing research pipeline that applies platform differentiators to address underlying neuromuscular disease drivers Exploring EDO's potential in genetic conditions, including Charcot-Marie-Tooth disease Research Pipeline EDO PLATFORM Achieving superior nuclear delivery and uptake of therapeutic oligonucleotides, overcoming key limitations of prior approaches Backed by a team of leading neuromuscular researchers with deep expertise in genetic disease biology and oligonucleotide drug development OUR VISION Develop therapies that address the root cause of serious genetic neuromuscular and neurological diseases—driving meaningful, functional improvement Q1 2026: FREEDOM2 5 mg/kg clinical results H2 2026: FREEDOM2 10 mg/kg clinical results Anticipated Upcoming Milestones Cash runway into 2H 2027
The Challenge of Oligonucleotides PGN-PMODM1 (Naked Oligo at 20 µM) Red = oligo Naked oligonucleotides do not efficiently penetrate muscle cells and nucleus Immortalized myoblasts from a healthy individual or a DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotubes and then treated with fluorescently tagged PGN-PMODM1 (PMO) or PGN-EDODM1 (PPMO) at concentrations detailed above. Cells were visualized by confocal microscopy 24h after treatment.
PGN-EDODM1 (10 µM) Red = oligo PepGen’s EDO Platform Has Been Designed and Developed to Solve this Decades Long Problem EDO platform results in nuclear delivery of oligonucleotide therapeutics Immortalized myoblasts from a healthy individual or a DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotubes and then treated with fluorescently tagged PGN-PMODM1 (PMO) or PGN-EDODM1 (PPMO) at concentrations detailed above. Cells were visualized by confocal microscopy 24h after treatment.
15x 20x 19x 22x 55x 98x 73x PMO Delivery in DM1 Cells EDO Technology Can Improve Endosomal Escape and Has Been Shown to Increase Nuclear Uptake up to 98-Fold CELLULAR UPTAKE NUCLEAR UPTAKE Immortalized myoblasts from a healthy individual or a DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotubes and then treated with fluorescently tagged PGN-PMODM1 (PMO) or PGN-EDODM1 (PPMO) at concentrations detailed above. Cells were visualized by confocal microscopy 24h after treatment. Graphs are presented as mean ± SD.
1. FREEDOM 15 mg/kg data readout when compared with prior published data. Differentiated Delivery Technology Receptor-independent EDO peptide delivery Designed to escape the endosome – unlike TfnR targeting 1 Differentiated Target Selectively targets pathogenic RNA (CUG repeat in DMPK) Demonstrated highest rate of splicing correction ever reported in DM1 after only a single dose1 2 Cost Effective Manufacturing EDO peptide is a short linear peptide – not cell culture product 3 PGN-EDODM1: A Differentiated Drug with Best-in-Class Potential
PGN-EDODM1 – Myotonic Dystrophy Type 1 (DM1)
Myotonic Dystrophy Type 1 Overview and Unmet Medical Need Sources: Neuroepidemiology (2022) 56 (3): 163–173., Neurology 2021 Feb 16;96(7):e1045-e1053 CUG: cytosine-uracil-guanine; DMPK: dystrophia myotonica protein kinase Overview Market Opportunity CUG expansion in the DMPK gene Onset of symptoms variable- childhood to adulthood Myotonia Muscle weakness Cardiac arrythmias Loss of lung function Fatigue Average life expectancy is 50-60 years for non-congenital forms of DM1 U.S. and EU over 115,000 patients No approved therapies that address underlying cause of the disease Jubal, retired professor living with DM1
PGN-EDODM1 Blocking Approach Targets the Pathogenic CUGexp Repeats DMPK RNA Wojciechowska, et al., Quantitative Methods to Monitor RNA Biomarkers in Myotonic Dystrophy, Nature, April 12, 2018 DM1 is caused by pathogenic DMPK transcripts PGN-EDODM1 binds selectively to the pathogenic DMPK transcript Bound MBNL1 (inactive) DMPK transcript Free MBNL1 (active) PGN-EDODM1 PGN-EDODM1 binds selectively to the pathogenic DMPK transcript This reduces the ability of the CUGexp repeats to form hairpin loops and sequester RNA splicing proteins DM1 is caused by pathogenic DMPK transcripts containing CUGexp repeat sequences that form hairpin loops These hairpin loops trap MBNL1 proteins that are needed for correct splicing of mRNAs Trapped MBNL1 is inactive and results in mis-splicing Liberated MBNL1 restores correct splicing
MBNL1 Liberation Foci Reduction PGN-EDODM1 Reduced Pathogenic Nuclear Foci, Liberated MBNL1 and Corrected Mis-Splicing in Patient Cells with Long CUG Repeats Immortalized myoblasts from healthy individual or DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotubes. Treatment with peptide-PMO conjugates at concentrations given. Cells were harvested for analysis 24h after treatment. RNA isolation, RT-PCR and capillary electrophoresis (QIAxcel) analysis were performed. Visualization with FISH and immunofluorescence microscopy. Mean ± SD; n = 5 per group. Not Treated PGN-EDODM1 Treated Not Treated PGN-EDODM1 Treated 54% reduction in toxic foci Across multiple transcripts Mis-Splicing Correction 69% correction
Multiple Doses of PGN-EDODM1 Led to Greater Improvement in Splicing Correction and Myotonia vs Single Dose in Preclinical Studies Protocol: HSALR mice received 1 or 4 doses of PGN-EDODM1, with 4-week intervals between doses. Skeletal muscle tissues were collected 4 weeks post-final dose. Skeletal muscle tissue concentration was measured by fluorescent based HPLC method. Graph is presented as mean ± SD; n = 8-12 per cohort. Mis-splicing analysis considers multiple transcripts. Graph is presented as mean ± SD; n = 8-12 per cohort per transcript. Action myotonia evaluation (pinch test) was performed 4 weeks post-final dose. Grade 3 = Clear sign of myotonia strong AND reproducible, Grade 2 = Clear sign of myotonia, strong OR reproducible, Grade 1 = Clear sign of myotonia but non reproducible, Grade 0 = No sign of myotonia. Graphs are presented as mean ± SD; n = 12-43 per cohort. Skeletal muscle Tissue Concentration Across multiple transcripts Mis-Splicing Correction Correction of Myotonia Pinch test 56 120 0 68% 99% 0% 76% 99% Correction of myotonia
FREEDOM: Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design DSMB: data safety monitoring board; IV: intravenous; PBO: placebo; SAD: single-ascending dose; PK: pharmacokinetics PGN-EDODM1 dose FREEDOM Phase 1 Study Overview Multinational, randomized, double-blind, placebo-controlled SAD study in patients Single IV administration of PGN-EDODM1 Muscle biopsies in tibialis anterior at Baseline, Day 28, Week 16 Safety, PK, correction of mis-splicing, initial functional assessments Single Dose PGN-EDODM1 or Placebo (randomized 3:1) 15 mg/kg or PBO Baseline DSMB Wk 16* D28 Biopsy Biopsy Biopsy 10 mg/kg or PBO Baseline DSMB Wk 16 D28 Biopsy Biopsy Biopsy Dosed n=8 n=8 5 mg/kg or PBO Baseline DSMB Wk 16 D28 Biopsy Biopsy Biopsy n=8
PGN-EDODM1 Produced Dose-Dependent Best-in-Class Splicing Correction Following Single Dose Splicing Index Changes: 22-Gene Panel* at D28 Improvement -53.7% -29.1% 3.3% -12.3% 87.5% of participants across all doses showed improved splicing % Mean change from baseline Placebo1 (n=5) 5 mg/kg (n=6) 10 mg/kg2 (n=4) 15 mg/kg3 (n=6) 1.Missing samples due to unavailability of biopsy tissue or sample outside of assay window. 2. One subject at 10 mg/kg biopsy was not collected at day 28 due to pseudoaneurysm in connection with biopsy and one participant’s splicing index fell below the pre-specified assay range at baseline and at day 28 (indicating no detectable mis-splicing) 3.One subject at 15mg/kg received 77% of the dose and was still included in the splicing index change analysis for the cohort *Provenzano et al., The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1,J Clin. Invest. 2025
1.Missing samples due to unavailability of biopsy tissue 2.One subject at 15mg/kg received 77% of the dose and was still included in the muscle tissue concentration analysis for the cohort * Robust, Greater Than Dose-Proportional Increase in Muscle Tissue Concentration Following Single Dose 5 mg/kg (n=6) 10 mg/kg1 (n=5) 15 mg/kg1,2 (n=5) Concentration (ng/g) Mean ± SE 160.6 44.1 13.7 Muscle Tissue Concentration at D28 Mean TA Muscle
PGN-EDODM1 Was Generally Well Tolerated, with TEAEs Primarily Mild to Moderate Across Dose Cohorts *As of database lock on December 23, 2025. Unblinded FREEDOM safety data TEAE: treatment-emergent adverse event, SAE: serious adverse event, DLT: Dose limiting toxicity, eGFR(cys): estimated glomerular filtration rate (cystatin equation) Placebo (n=6) N (events) Cohort 1 5 mg/kg (n=6) Cohort 2 10 mg/kg (n=6) Cohort 3 15 mg/kg (n=6) Total (n=24) Any TEAE, n (events) 5 (16) 3 (20) 4 (16) 5 (18) 17 ( 70) Any TEAE by Max Severity Mild/Moderate Severe 5 0 2 1 2 2 5 0 14 3 Any related TEAE, n (events) 1 (3) 1 (1) 2 (4) 4 (14) 8 ( 22) Any SAE (event) 1(2) 1 (1) 2 (2) 0 (0) 4 (5) Any related SAE 0 0 1 (1) 0 1(1) Any TEAE leading to study withdrawal 0 0 0 0 0 Any TEAE leading to death 0 0 0 0 0 Most frequent TEAEs: nausea, nasopharyngitis, and headache No electrolyte-related TEAEs or hypomagnesemia observed across dose cohorts No renal-related TEAEs observed at 5 and 10 mg/kg; DLT at 15 mg/kg involving a transient decrease in eGFR(cys), resolving without intervention Transient moderate albuminuria observed at 15 mg/kg and mild albuminuria at 10 mg/kg; Normalized within 2-7 days without intervention One drug-related hypersensitivity reaction (rash) during infusion at 15 mg/kg, resolving within 2 hours with oral antihistamines One drug-related SAE of severe abdominal pain at 10 mg/kg, confounded by off-label medication use on the day of dosing
FREEDOM2 Phase 2 MAD Study Underway DSMB: data safety monitoring board; FU: follow-up; IV: intravenous; MAD: multiple-ascending dose; PBO: placebo; PK: pharmacokinetics; vHOT: video hand opening test; OLE: open label extension * Dose dependent on recommendations of DSMB **The U.S. FDA recently placed a partial clinical hold on FREEDOM2-DM1 FREEDOM2 Study Overview Multinational, randomized, double-blind, placebo-controlled, MAD study open in Canada, UK, NZ, Australia and South Korea** IV administration of PGN-EDODM1 or placebo every 4 weeks for a period of 12 weeks OLE open in CA and UK 4 Doses of PGN-EDODM1 or Placebo (randomized 3:1) n=8 Safety FU Biopsy Biopsy 12.5 mg/kg* or PBO DSMB Safety FU Biopsy Biopsy 10 mg/kg or PBO DSMB Biopsy Biopsy 5 mg/kg or PBO DSMB n=8 n=8 Safety FU Dosing complete PGN-EDODM1 dose Key endpoints: Safety, PK, correction of splicing, functional assessments: vHOT, hand grip, 10-meter walk run test Enrolling
Summary: PGN-EDODM1 Designed to Address the Underlying Cause of DM1 87.5% of participants across all doses showed improved splicing More than dose-proportionate increases in splicing correction observed across doses at Day 28 Unprecedented splicing provides a window of pharmacodynamically active doses that can be assessed in the MAD study Highest Ever Reported Mean Splicing Correction in DM1 12.3% at 5 mg/kg 29.1% at 10 mg/kg 53.7% at 15 mg/kg Robust Single-Dose Splicing Correction Supports Evaluation of Optimized Dose Regimens in MAD Study Safety & Tolerability: Splicing correction comparison is based on cross trial comparisons for exploratory purposes. FREEDOM2 dosing at 10 mg/kg is ongoing, with the 5 mg/kg readout anticipated in Q1 2026 and 10 mg/kg readout in H2 2026 PGN-EDODM1 was generally well-tolerated across all doses. One drug-related SAE (at 10 mg/kg), possibly confounded by concomitant medication Asymptomatic transient changes in renal biomarkers resolved without intervention No kidney-related TEAEs observed at 5 and 10 mg/kg
Summary of PGN-EDODM1 and FREEDOM Program Favorable emerging safety profile Unprecedented splicing correction achieved with single dose FREEDOM STUDY : EXPLORATORY: PD (SPLICING) PRIMARY: SAFETY Fully enrolled 5 mg/kg cohort; All patients have completed dosing Dosing patients in 10 mg/kg cohort; 50% (4/8) of patients have received up to two doses PHASE 2 FREEDOM2 (MAD) UPCOMING PLANNED READOUTS: Q1 2026: FREEDOM2 5 mg/kg clinical results H2 2026: FREEDOM2 10 mg/kg clinical results Splicing correction comparison is based on cross trial comparisons for exploratory purposes Differentiated Delivery Technology 1 Differentiated Target 2 Cash runway into 2H 2027
FAQ
What did PepGen (PEPG) highlight about PGN-EDODM1 in its updated presentation?
What were the key Phase 1 PGN-EDODM1 results PepGen (PEPG) presented for DM1?
How is PepGen’s (PEPG) FREEDOM2 Phase 2 study for PGN-EDODM1 designed?
What regulatory updates did PepGen (PEPG) disclose about FREEDOM2-DM1?
What future milestones did PepGen (PEPG) outline for the PGN-EDODM1 program?
How long is PepGen’s (PEPG) cash runway according to the presentation?
What is the unmet medical need in myotonic dystrophy type 1 that PepGen (PEPG) targets?
Filing Exhibits & Attachments
2 documentsPress Releases
