PepGen trial shows 16.2% hand-grip strength improvement
The 12.5 mg/kg cohort is fully enrolled, with results expected in the first half of 2027; interim extension data are expected in January 2027.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Filing Summary
PepGen Inc. reported topline results from the 10 mg/kg cohort of its Phase 2 FREEDOM2-DM1 trial: mean muscle splicing correction was 46.5% at Week 13, with five of six participants showing more than 20% and four showing more than 50%. At Week 16, video Hand Opening Time improved 3.9 seconds (52.7%), hand-grip strength improved 16.2%, Timed Up and Go improved 8.5%, and the 10-Meter Walk/Run Test improved 6.8%.
At 10 mg/kg, no serious or severe adverse events, dose-limiting toxicities, or treatment discontinuations were reported; patient-reported outcomes were inconclusive. The fully enrolled 12.5 mg/kg cohort has received up to three doses, with results expected in the first half of 2027; interim open-label-extension safety and clinical data are expected in January 2027. The FDA issued a partial clinical hold on FREEDOM2 in March 2026, citing nonclinical findings in mice.
Cash, cash equivalents and marketable securities were $104.805 million as of September 30, 2026; PepGen believes this will fund planned operations into 2028. Quarterly net loss was $19.391 million, compared with $18.026 million for the three months ended September 30, 2025. Research and development expense was $14.476 million, versus $13.423 million.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Positive
- Major point46.5% mean splicing correction in the 10 mg/kg cohort at Week 13.
Negative
- Major pointFREEDOM2 is under a partial U.S. clinical hold issued in March 2026.
- Moderate pointQuarterly net loss was $19.391 million, versus $18.026 million a year earlier.
Filing Explained
The FDA selected PGN-EDODM1 for its manufacturing-readiness pilot, which provides structured regulatory engagement on manufacturing strategy; FREEDOM2 remains under a partial U.S. clinical hold, so this is not a hold release.
8-K Event Classification
Key Figures
Key Terms
splicing correction medical
multiple ascending dose medical
partial clinical hold regulatory
open-label extension medical
dose-limiting toxicities medical
Earnings Snapshot
PepGen believes its existing cash, cash equivalents and marketable securities will be sufficient to fund operations into 2028, based on currently planned operations.
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What did PEPG report from the 10 mg/kg DM1 trial cohort?
When are PEPG's next FREEDOM2-DM1 and open-label extension results expected?
Why is PEPG's FREEDOM2 study under a partial clinical hold?
What were PEPG's third-quarter 2026 net loss and cash balance?
AI-generated analysis. How Rhea-AI works. Not financial advice.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
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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
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 2.02 Results of Operations and Financial Condition.
On November 10, 2026, PepGen Inc. (the “Company”) announced its financial results for the quarter ended September 30, 2026 and other business updates and issued a press release titled “PepGen Reports Third Quarter 2026 Financial Results and Recent Corporate Highlights.” A copy of the press release is furnished as Exhibit 99.1.
The information in Item 2.02 of this Current Report on Form 8-K (this “Form 8-K”), including Exhibit 99.1, 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 into any of the Company’s filings under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 7.01 Regulation FD Disclosure.
On November 10, 2026, the Company issued a press release titled “PepGen Announces Positive Phase 2 FREEDOM2-DM1 10mg/kg Results Demonstrating Highest Reported Splicing Correction and Improvements Across Multiple Functional Measures.” A copy of the press release in connection with the announcement is being furnished as Exhibit 99.2 to this Form 8-K.
The information in Item 7.01 of this Form 8-K, including Exhibit 99.2, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of 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 or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
A copy of the Company’s presentation titled “FREEDOM2-DM1, 10 mg/kg MAD Cohort Data Update,” is filed hereto as Exhibit 99.3 to this Form 8-K and is incorporated herein by reference. Representatives of the Company will use the presentation in various meetings with investors from time to time.
Item 9.01 Financial Statements and Exhibits.
d) Exhibits
Exhibit Number |
Description |
99.1 |
Press release issued by PepGen Inc. on November 10, 2026 titled “PepGen Reports Third Quarter 2026 Financial Results and Recent Corporate Highlights” |
99.2 |
Press release issued by PepGen Inc. on November 10, 2026 titled “PepGen Announces Positive Phase 2 FREEDOM2-DM1 10mg/kg Results Demonstrating Highest Reported Splicing Correction and Improvements Across Multiple Functional Measures” |
99.3 |
FREEDOM2-DM1, 10 mg/kg MAD Cohort Data Update Presentation, as of November 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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November 10, 2026 |
By: |
/s/ Noel Donnelly |
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Noel Donnelly, Chief Financial Officer |
PepGen Reports Third Quarter 2026 Financial Results
and Recent Corporate Highlights
– 12.5 mg/kg FREEDOM2-DM1 cohort fully enrolled, with participants having received up to three doses; results expected in 1H 2027 –
– FREEDOM-OLE 10 mg/kg safety and 5 mg/kg clinical data expected in January 2027 –
– Well-funded with $104.8M of cash as of September 30, 2026, sufficient to fund operations into 2028 –
BOSTON— November 10, 2026-- PepGen Inc. (Nasdaq: PEPG), a clinical-stage biotechnology company pioneering oligonucleotide therapies with the potential to transform the treatment of rare genetic diseases, today reported financial results and recent corporate highlights for the quarter ended September 30, 2026. PepGen also released today positive topline results from the 10 mg/kg multiple ascending dose cohort of the ongoing Phase 2 FREEDOM2-DM1 trial (NCT06667453) evaluating PGN-EDODM1 in patients with myotonic dystrophy type 1 (DM1), a rare, progressive, and multisystemic genetic disease.
“The positive 10 mg/kg cohort results we announced today were made possible by our team’s focused execution,” said James McArthur, Ph.D., President and Chief Executive Officer of PepGen. “We are very confident in PGN-EDODM1’s potential to deliver meaningful benefit to the DM1 community, and our company ended the quarter in a strong position to advance the program to the third and highest dose cohort, which is fully enrolled.”
Recent Program Updates
PGN-EDODM1: Myotonic Dystrophy Type 1 (DM1)
Corporate Updates
Financial Results for the Three Months Ended September 30, 2026
About Myotonic Dystrophy Type 1 (DM1)
Myotonic dystrophy type 1 (DM1) is a rare, progressive genetic disease that affects muscles and multiple systems throughout the body. DM1 is caused by an abnormal expansion of cytosine-thymine-guanine (CTG) repeats in the dystrophia myotonica protein kinase (DMPK) gene, resulting in pathogenic RNA that interferes with normal RNA splicing and drives the disease. Symptoms can begin in childhood or adulthood and vary widely in type, severity, and progression. DM1 has a world-wide distribution and is estimated to affect more than 110,000 people across the United States and the European Union, and average life expectancy for people with non-congenital DM1 is approximately 50 to 60 years. No approved therapies currently address the underlying cause of DM1.
About PGN-EDODM1
PGN-EDODM1 is an investigational Enhanced Delivery Oligonucleotide (EDO) designed to address the underlying molecular mechanism of DM1. Using PepGen’s proprietary EDO technology designed to enhance cellular uptake and nuclear delivery of a therapeutic oligonucleotide, PGN-EDODM1 selectively binds to expanded CUG repeats in pathogenic dystrophia myotonica protein kinase (DMPK) RNA. This binding releases MBNL1, a key regulator of RNA splicing, to restore correct splicing. Unlike approaches that degrade DMPK RNA, PGN-EDODM1 is designed to disrupt pathogenic DMPK hairpin structures while preserving normal DMPK function. The U.S. Food and Drug Administration has granted PGN-EDODM1 Orphan Drug and Fast Track designations, and the European Medicines Agency has granted it Orphan Designation.
About FREEDOM2-DM1
FREEDOM2-DM1 (NCT06667453) is a multinational, randomized, double-blind, placebo-controlled Phase 2 multiple ascending dose study evaluating PGN-EDODM1 in people living with
DM1. The study enrolled three cohorts of eight participants each, randomized 3:1 to receive PGN-EDODM1 or placebo at doses of 5, 10, or 12.5 mg/kg. Participants receive four intravenous doses every four weeks over 12 weeks. Key endpoints include safety and tolerability, pharmacokinetics, correction of RNA mis-splicing in muscle tissue, and functional measures of myotonia, strength, and mobility. FREEDOM2 is being conducted in Canada, the United Kingdom, New Zealand, Australia, and South Korea and is subject to a partial clinical hold in the United States. Eligible participants may continue treatment in the FREEDOM-OLE study.
About PepGen
PepGen Inc. is a clinical-stage biotechnology company pioneering oligonucleotide therapies with the potential to transform the treatment of rare genetic diseases. Founded on more than a decade of research and development, PepGen’s Enhanced Delivery Oligonucleotide (EDO) technology leverages cell-penetrating peptides to improve the uptake and activity of conjugated oligonucleotide therapeutics. Using this EDO technology, PepGen is advancing PGN-EDODM1, a clinical candidate for the treatment of myotonic dystrophy type 1.
For more information, please visit PepGen.com. Follow PepGen on LinkedIn and X.
Forward-Looking Statements
This press release 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 press release 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 therapeutic potential and safety profile of PGN-EDODM1, statements regarding PGN-EDODM1’s potential to deliver meaningful benefit to the DM1 community, expectations regarding the timing of data for the 12.5 mg/kg cohort of the FREEDOM2-DM1 trial, the FREEDOM-OLE 10 mg/kg safety and 5 mg/kg clinical results, our plans to initiate an expansion cohort running in parallel to cohort 3, timing regarding the end-of-Phase 2 (EOP2) meeting for FREEDOM2 and FREEDOM-OLE studies, the potential for the CDRP program to accelerate alignment on critical manufacturing development strategies ahead of Phase 3 and NDA submission, forecasts relating to PepGen’s cash runway, and ongoing and planned regulatory interactions, including the potential timing and successful resolution of questions from the FDA relating to the partial clinical hold.
Any forward-looking statements in this press release are based on current expectations, estimates and projections only as of the date of this release 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 risks related 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 or cross-trial comparisons, including for PGN-EDODM1 and cross-trial comparisons; 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 the lifting of the partial clinical hold on PGN-EDODM1, or other regulatory feedback requiring modifications to our development programs, including in each case with respect to our PGN-EDODM1 program; changes in regulatory framework that are out of our control; 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 reports filed with the SEC. PepGen explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
This release discusses PGN-EDODM1, an investigational therapy that has not been approved for use in any country, and is not intended to convey conclusions about its efficacy or safety. There is no guarantee that PGN-EDODM1 or any other investigational therapy will successfully complete clinical development or gain approval from regulatory authorities.
Condensed Consolidated Statements of Operations
(unaudited, in thousands)
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Three Months Ended |
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2026 |
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2025 |
Operating expenses: |
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Research and development |
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$ 14,476 |
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$ 13,423 |
General and administrative |
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5,907 |
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5,231 |
Total operating expenses |
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$ 20,383 |
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$ 18,654 |
Operating loss |
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$ (20,383) |
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$ (18,654) |
Other income (expense) |
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Interest income |
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1,005 |
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634 |
Other (expense) income, net |
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— |
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(6) |
Total other income, net |
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1,005 |
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628 |
Net loss before income tax |
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$ (19,378) |
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$ (18,026) |
Income tax expense |
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(13) |
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— |
Net loss |
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$ (19,391) |
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$ (18,026) |
Net loss per share, basic and diluted |
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$ (0.28) |
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$ (0.52) |
Weighted-average common stock outstanding, basic and diluted |
69,260,353 |
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34,362,876 |
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Condensed Consolidated Balance Sheets
(unaudited, in thousands)
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September 30, |
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December 31, |
Assets |
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Cash, cash equivalents and marketable securities |
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$ 104,805 |
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$ 148,456 |
Other assets |
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22,972 |
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25,451 |
Total assets |
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$ 127,777 |
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$ 173,907 |
Liabilities and stockholders’ equity |
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Liabilities |
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$ 24,711 |
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$ 26,463 |
Stockholders’ equity |
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103,066 |
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147,444 |
Total liabilities and stockholders’ equity |
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$ 127,777 |
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$ 173,907 |
Investor Contact
Laurence Watts
New Street Investor Relations
laurence@newstreetir.com
Media Contact
Amir Khan
Chamberlain Healthcare PR
Amir.Khan@syneoshealth.com
PepGen Announces Positive Phase 2 FREEDOM2-DM1 10 mg/kg Results Demonstrating Highest Reported Splicing Correction and Improvements Across Multiple Functional Measures
- Mean splicing correction of 46.5% following four monthly doses of PGN-EDODM1, five of six participants having more than 20% splicing correction and four participants exceeding 50% splicing correction –
- Video Hand Opening Time (vHOT), a measure of myotonia, improved by 3.9 seconds (52.7%) from baseline at Week 16 -
- Meaningful functional improvements observed across measures of strength, ambulation, and mobility, supporting the potential for broad clinical benefit in DM1 -
- PGN-EDODM1 was generally well tolerated, with no serious or severe adverse events or dose-limiting toxicities reported -
- Conference call scheduled today at 8:00 a.m. ET -
BOSTON-- November 10, 2026-- PepGen Inc. (Nasdaq: PEPG), a clinical-stage biotechnology company pioneering oligonucleotide therapies with the potential to transform the treatment of rare genetic diseases, today announced positive topline results from the 10 mg/kg multiple ascending dose cohort of the ongoing Phase 2 FREEDOM2-DM1 trial (NCT06667453) evaluating PGN-EDODM1 in patients with myotonic dystrophy type 1 (DM1), a rare, progressive, and multisystemic genetic disease.
The results demonstrated the highest level of splicing correction ever reported in a multiple dose study for DM1 as well as notable improvements across multiple functional measures including myotonia, strength, ambulation, and mobility following four monthly doses of PGN-EDODM1. Mean splicing correction in muscle reached 46.5%, with five of six participants having more than 20% splicing correction and four participants showing more than 50% splicing correction, as measured by the 22-gene panel at Week 131. These findings were accompanied by sustained improvements in video Hand Opening Time (vHOT), hand grip strength, 10-Meter Walk/Run Test (10MWRT), and Timed Up and Go (TUG) assessments, providing compelling evidence of PGN-EDODM1’s potential to address multiple clinical manifestations of DM1 and supporting continued development.
“Our ambition is to fundamentally change how DM1 is treated through greater targeting of the underlying molecular mechanism of the disease,” said James McArthur, Ph.D.,
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President and Chief Executive Officer of PepGen. “The 10 mg/kg results mark an important milestone in that pursuit, with robust splicing correction accompanied by encouraging improvements across multiple measures of muscle function. Importantly, these findings strengthen our confidence not only in PGN-EDODM1’s potential, but in our broader development strategy. With our 12.5 mg/kg cohort fully enrolled and the ongoing FREEDOM-OLE study exceeding 135 doses administered, we believe we are well positioned to continue building the evidence needed to advance toward pivotal studies.”
“DM1 is a multisystemic disease, placing a major burden on patients and their families,” said Hanns Lochmüller, M.D., Ph.D., FAAN, Professor of Neurology at the University of Ottawa, Senior Scientist at the CHEO Research Institute and Neurologist at The Ottawa Hospital, and a FREEDOM2 study investigator. “The improvements observed across myotonia, mobility and grip strength are encouraging because they reflect functions that affect patients’ daily lives. The relationship between splicing correction and improvements in myotonia is particularly interesting, and longer-term follow-up will be important to better understand the durability and clinical relevance of these findings.”
FREEDOM2-DM1 10 mg/kg Cohort Results
FREEDOM2-DM1 is an ongoing, randomized, double-blind, placebo-controlled Phase 2 multiple ascending dose study evaluating PGN-EDODM1 in patients with DM1. The 10 mg/kg cohort enrolled eight participants, randomized 3:1 to receive four doses of PGN-EDODM1 (n=6) or placebo (n=2) administered intravenously every four weeks. All eight participants completed the Week 16 assessment.
Splicing Correction and Functional Results:
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Safety and Tolerability Results:
“For people living with DM1, the impact extends far beyond any single symptom, underscoring the need for treatments that target the root cause of the disease,” said Paul Streck, M.D., MBA, Executive Vice President, Head of Research and Development of PepGen. “We are extremely encouraged by the magnitude of splicing correction observed at 10 mg/kg and the dose-dependent improvements across multiple measures of muscle function. Together, these findings strengthen our confidence in PGN-EDODM1’s potential to deliver meaningful benefit for patients. We are deeply grateful to the FREEDOM2 investigators, study teams, participants, and their families for their dedication and commitment to this study.”
The 12.5 mg/kg cohort of FREEDOM2 is fully enrolled, with participants having received up to three doses and clinical results expected in the first half of 2027. PepGen also expects to report interim clinical data at 5 mg/kg and safety data at 10 mg/kg from the open-label extension study in January 2027.
Conference Call Details
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PepGen will host a conference call and webcast today at 8:00 a.m. ET to discuss the FREEDOM2-DM1 10 mg/kg results. To access the live webcast, please visit the Events & Presentations section of PepGen’s investor website here. An archived replay will be available following the event.
About Myotonic Dystrophy Type 1 (DM1)
Myotonic dystrophy type 1 (DM1) is a rare, progressive genetic disease that affects muscles and multiple systems throughout the body. DM1 is caused by an abnormal expansion of cytosine-thymine-guanine (CTG) repeats in the dystrophia myotonica protein kinase (DMPK) gene, resulting in pathogenic RNA that interferes with normal RNA splicing and drives the disease. Symptoms can begin in childhood or adulthood and vary widely in type, severity, and progression. DM1 has a world-wide distribution and is estimated to affect more than 110,000 people across the United States and the European Union, and average life expectancy for people with non-congenital DM1 is approximately 50 to 60 years. No approved therapies currently address the underlying cause of DM1.
About PGN-EDODM1
PGN-EDODM1 is an investigational Enhanced Delivery Oligonucleotide (EDO) designed to address the underlying molecular mechanism of DM1. Using PepGen’s proprietary EDO technology designed to enhance cellular uptake and nuclear delivery of a therapeutic oligonucleotide, PGN-EDODM1 selectively binds to expanded CUG repeats in pathogenic dystrophia myotonica protein kinase (DMPK) RNA. This binding releases MBNL1, a key regulator of RNA splicing, to restore correct splicing. Unlike approaches that degrade DMPK RNA, PGN-EDODM1 is designed to disrupt pathogenic DMPK hairpin structures while preserving normal DMPK function. The U.S. Food and Drug Administration has granted PGN-EDODM1 Orphan Drug and Fast Track designations, and the European Medicines Agency has granted it Orphan Designation.
About FREEDOM2-DM1
FREEDOM2-DM1 (NCT06667453) is a multinational, randomized, double-blind, placebo-controlled Phase 2 multiple ascending dose study evaluating PGN-EDODM1 in people living with DM1. The study enrolled three cohorts of eight participants each, randomized 3:1 to receive PGN-EDODM1 or placebo at doses of 5, 10, or 12.5 mg/kg. Participants receive four intravenous doses every four weeks over 12 weeks. Key endpoints include safety and tolerability, pharmacokinetics, correction of RNA mis-splicing in muscle tissue, and functional measures of myotonia, strength, and mobility. FREEDOM2 is being conducted in Canada, the United Kingdom, New Zealand, Australia, and South Korea and
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is subject to a partial clinical hold in the United States. Eligible participants may continue treatment in the FREEDOM-OLE study.
About PepGen
PepGen Inc. is a clinical-stage biotechnology company pioneering oligonucleotide therapies with the potential to transform the treatment of rare genetic diseases. Founded on more than a decade of research and development, PepGen’s Enhanced Delivery Oligonucleotide (EDO) technology leverages cell-penetrating peptides to improve the uptake and activity of conjugated oligonucleotide therapeutics. Using this EDO technology, PepGen is advancing PGN-EDODM1, a clinical candidate for the treatment of myotonic dystrophy type 1.
For more information, please visit www.pepgen.com. Follow PepGen on LinkedIn and X.
Forward-Looking Statements
This press release 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 press release 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 therapeutic potential and safety profile of PGN-EDODM1, statements regarding PGN-EDODM1’s potential to deliver meaningful benefit to the DM1 community, evidence of PGN-EDODM1’s potential to address multiple clinical manifestations of DM1 including PepGen’s ambition to change how DM1 is treated, the topline results from the 10 mg/kg multiple ascending dose cohort of the ongoing Phase 2 FREEDOM2-DM1 trial, expectations regarding the timing of data for the 12.5 mg/kg cohort of the FREEDOM2-DM1 trial, the FREEDOM-OLE 10mg/kg safety and 5 mg/kg clinical results, the potential for any functional improvements that may result from 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, and ongoing and planned regulatory interactions.
Any forward-looking statements in this press release are based on current expectations, estimates and projections only as of the date of this release 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
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uncertainties include, but are not limited to risks related 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 or cross-trial comparisons, including for PGN-EDODM1 and cross-trial comparisons; 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, or other regulatory feedback requiring modifications to our development programs, including in each case with respect to our FREEDOM2 program; changes in regulatory framework that are out of our control; 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 reports filed with the SEC. PepGen explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
This release discusses PGN-EDODM1, an investigational therapy that has not been approved for use in any country, and is not intended to convey conclusions about its 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.
Investor Contact
Laurence Watts
New Street Investor Relations
laurence@newstreetir.com
Media Contact
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Amir Khan
Chamberlain Healthcare Public Relations
Amir.Khan@syneoshealth.com
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November 10, 2026 FREEDOM2-DM1 10 mg/kg MAD Cohort Data Update
Forward-Looking Statements This presentation is being made by PepGen Inc. (“PepGen,” “we,” “our,” “us”) and 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 and to deliver to a broad range of tissues, the promising trends and therapeutic potential and safety profile of PGN-EDODM1 based on data from the 5, 10 and 15 mg/kg cohorts of the FREEDOM study and 5 and 10 mg/kg cohorts of the FREEDOM2 trial, PGN-EDODM1's potential to deliver meaningful benefit to the DM1 community, our expectations regarding the timing of data from the 12.5 mg/kg cohort of the FREEDOM2 trial, our expectations on the timing of the 5 mg/kg clinical and 10 mg/kg safety data from the FREEDOM-OLE trial, our plans to initiate an expansion cohort running in parallel to cohort 3, the design, initiation and conduct of clinical trials, including expected timelines for data readouts from our FREEDOM2 and OLE trials, the potential for any functional improvements that may result from 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. These 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. Many actual events and circumstances are beyond PepGen’s control 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 and OLE trials, 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 or cross-trial comparisons, including for PGN-EDODM1 and cross-trial comparisons; 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. These forward-looking statements should not be relied upon as representing our assessments as of any date subsequent to the date of this presentation. Additional risks concerning our programs and operations are described in our most recent filings with the U.S. Securities and Exchange Commission. 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.
Agenda Paul Streck, MD, MBA Executive Vice President, Head of R&D FREEDOM2 Clinical Trial Design, Safety, Splicing, and Q&A James McArthur, PhD President and Chief Executive Officer Key Takeaways, Closing Remarks, and Q&A Noel Donnelly, MBA Chief Financial Officer Q&A Johanna Hamel, MD Associate Professor of Neurology, Pathology and Laboratory Medicine University of Rochester FREEDOM2 Clinical Data and Q&A
PGN-EDODM1 MAD 10 mg/kg Cohort Reported Best-In-Class Splicing with Improvements Across Myotonia, Mobility, and Grip Strength 1 2 3 4 Highest level of splicing correction reported in a multiple dose study 46.5% mean change in splicing at week 13 5 of 6 patients improved more than 20% natural variability range1; 4 of 6 patients above 50% splicing correction 1PepGen’s analysis of natural history data of 114 patients from C Thornton et al., Lancet Neurology 2023; 22: 218–28. Supplement MAD: Multiple ascending dose; vHOT: video Hand Opening Time; TUG: Timed Up and Go; 10MWRT: 10-Meter Walk/Run Test; SAE: Serious adverse event; AESI: Adverse event of special interest; DLT: Dose limiting toxicity; AE: Adverse event 5 Mechanism linked to function vHOT improved 4.3 seconds at Week 13 and 3.9 seconds at Week 16, highest improvement reported at 3 or 6 months Associated with splicing correction of CLCN1, a muscle chloride channel driving myotonia in DM1 Benefit across proximal and distal muscle groups Improvement in mobility and balance as measured by TUG, with the highest improvement reported at 3 or 6 months Encouraging improvement in hand grip strength and 10MWRT Clear dose response Large improvement in splicing correction and functional endpoints at 10 mg/kg relative to 5 mg/kg Favorable safety No SAEs, AESIs, DLTs, or discontinuations; all AEs mild or moderate
PGN-EDODM1 Introduction, Study Design, Splicing, and PK Paul Streck, MD, MBA Head of R&D
Sources: Neuroepidemiology (2022) 56 (3): 163–173., Neurology 2021 Feb 16;96(7):e1045-e1053 1Some estimates are as much as 5-fold higher prevalence of DM1: Brain (10 Oct 2026), awag250 CTG: cytosine-thymine-guanine; DMPK: dystrophia myotonica protein kinase Tara and Rhys, Living with DM1 Jubal and Family, Living with DM1 Caused by CTG expansion in the DMPK gene, resulting in pathogenic DMPK transcripts driving disease pathology More than 110,000 people1 affected in the U.S. and EU Symptoms can develop from childhood through adulthood with greater severity in each successive generation Average life expectancy is 50–60 years in patients with non-congenital DM1 No approved therapies currently address the underlying cause of the disease Myotonic Dystrophy Type 1 (DM1)
PGN-EDODM1 is Designed to Target Pathogenic DMPK RNA to Restore Splicing Using EDO Technology to Deliver to a Broad Range of Tissues EDO technology improves endosomal escape, resulting in a 98-fold increase in nuclear delivery EDO technology uses receptor independent peptide delivery for broad, multisystemic reach1 PGN-EDODM1 binds selectively to the pathogenic DMPK transcript to restore splicing Liberated MBNL1 restores correct splicing Bound MBNL1 (inactive) DMPK transcript Free MBNL1 (active) PGN-EDODM1 Enhanced Delivery Oligo (EDO) 1EDO technology reached all tissues in non-human primate studies
FREEDOM2: Phase 2 MAD Study Design 1The U.S. FDA placed a partial clinical hold on FREEDOM2-DM1, with no U.S. participants dosed in the FREEDOM2-DM1 study to date DSMB: data safety monitoring board; FU: follow-up; IV: intravenous; MAD: multiple-ascending dose; PBO: placebo; PK: pharmacokinetics; vHOT: video Hand Opening Time; OLE: open label extension; 10MWRT: 10-Meter Walk Run Test Multinational, randomized, double-blind, placebo-controlled, MAD study open in Canada, UK, New Zealand, Australia, and South Korea1 IV administration of PGN-EDODM1 or placebo every 4 weeks for a period of 12 weeks FREEDOM-OLE open for participants from FREEDOM & FREEDOM2 Complete Key endpoints: Safety, PK, correction of splicing, vHOT, hand grip, 10MWRT Complete Biopsy Biopsy 5 mg/kg or PBO n=8 DSMB Safety FU PGN-EDODM1 dose 7d post final dose Safety FU Biopsy Biopsy 10 mg/kg or PBO n=8 DSMB 7d post final dose Safety FU Biopsy Biopsy 12.5 mg/kg or PBO n=8 DSMB 7d post final dose 4 Doses of PGN-EDODM1 or Placebo (randomized 3:1) Fully Enrolled
Baseline Demographics of FREEDOM2 Study Participants 1Splicing index is measured on a scale of 0 to 1: mild = 0–0.40, moderate = 0.41–0.75, and severe = 0.76–1.00 (Provenzano M, et al. J Clin Invest. 2025;135:e185426) BMI, body mass index; Q4W, once every 4 weeks; SD, standard deviation Characteristic Cohort 1: 5 mg/kg Q4W and Placebo (n = 8) Cohort 2: 10 mg/kg Q4W and Placebo (n = 8) Age, years, mean (SD) 32.5 (6.0) 38.5 (8.7) Age of symptom onset, mean (SD) 14.5 (7.6) 23.6 (12.1) Sex, female, n (%) 2 (25.0) 6 (75.0) Race, White, n (%) 6 (75.0) 7 (87.5) Weight, kg, mean (SD) 71.3 (12.0) 60.9 (14.1) BMI, kg/m2, mean (SD) 24.8 (5.0) 22.5 (4.9) Splicing index, %1, mean (SD) 69.2 (17.3) 66.7 (18.4) CTG repeats, mean (SD) 602.9 (301.1) 562.0 (316.7)
Any TEAE 7 (87.5) 8 (100) Mild Moderate Severe 4 (50.0) 3 (37.5) 0 (0.0) 4 (50.0) 4 (50.0) 0 (0.0) Any SAE 0 0 Any related SAE 0 0 Any AESI or dose-limiting toxicities 0 0 Any TEAE leading to study withdrawal 0 0 Any TEAE leading to death 0 0 Consistent, Favorable Safety Profile of PGN-EDODM1 at 5 and 10 mg/kg Summary of Treatment Emergent Adverse Events (TEAEs)1 1Data cutoff date: 17 Sept 2026 AE: Adverse event; AESI: Adverse event of special interest; DLT: Dose limiting toxicities; SAE: Serious adverse event; TEAE: Treatment emergent adverse event; eGFR: estimated Glomerular Filtration Rate 5 mg/kg (n=8) n (%) PGN-EDODM1 was Generally Well Tolerated, with All AEs Mild or Moderate in Severity1 All participants completed all 4 doses Nausea was the most common AE No SAEs, AESIs, or DLTs Four renal TEAEs reported, all were mild eGFR and creatinine measurements remained stable Transient albuminuria improved with subsequent doses No notable changes in liver or hematological values and no cardiovascular events No anti-drug antibodies detected 10 mg/kg (n=8) n (%)
Renal Biomarker Analysis Supports Favorable Safety Profile 1Magnesium: One participant showed a decrease in serum magnesium at a single timepoint at 10mg/kg 2Serum Creatinine: One participant at 10mg/kg at a single timepoint went above the upper limit of normal and returned to normal 24 hours later Horizontal dotted and dashed lines represent the laboratory-defined upper or lower limit of normal for adult males and females, respectively UACR: Urine albumin-to-creatinine ratio; eGFR: estimated Glomerular Filtration Rate; SE: standard error UACR Magnesium1 Serum Creatinine2 eGFR (Cystatin C)
PGN-EDODM1: Highest Splicing Correction Reported in a Multiple Dose Study Demonstrates Robust Target Engagement 1 DM1 Splicing index at day 28 analysis from the single ascending dose (SAD) study 2 DM1 Splicing index at day 7 following the fourth dose from the multiple ascending dose (MAD) study 3Missing samples due to unavailability of biopsy tissue. Improvement FREEDOM SAD Study1 FREEDOM2 MAD Study2 4One subject at 10 mg/kg biopsy was not collected at day 28 due to pseudoaneurysm in connection with biopsy; one participant’s splicing index fell below pre-specified assay range at baseline and day 28 (indicating no detectable mis-splicing) 5One subject at 15mg/kg received 77% of the dose, was still included in the splicing index change analysis for the cohort Q4W: One dose every 4 weeks; SE: standard error
Splicing Index Changes: 22-Gene Panel2 4 of 6 participants at 10 mg/kg showed improved splicing greater than 50% PGN-EDODM1 Splicing Correction Exceeds Natural Splicing Variability1 in 5 of 6 Participants at 10 mg/kg DM1 Splicing index at day 7 following the fourth dose from FREEDOM2-DM1 clinical study; Q4W: One dose every 4 weeks 1PepGen’s analysis of natural history data of 114 patients from C Thornton et al., Lancet Neurology 2023; 22: 218–28. Supplement; such natural splicing variability represented by +/-20% dotted lines on graph 2Provenzano et al., The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1, J Clin. Invest. 2025 Improvement
Repeated Dosing of PGN-EDODM1 Increased Muscle Tissue Levels 28d or 7d indicates days following the only dose (SAD) or last dose (MAD 4 dose study) 1SAD 5mg/kg group reflects n=4 above the lower limit of quantification (LLOQ) and SAD 10 mg/kg group reflects n=5 due to unavailability of biopsy tissue SEM: standard error of the mean; TA: Tibialis Anterior TA Muscle Tissue Concentration
FREEDOM2 Key Functional Outcomes Johanna Hamel, MD University of Rochester
In DM1, Muscle Dysfunction Drives Multisystemic Impact for Patients DM1 Most Prevalent Symptoms1 1Christopher Project Reference Group. The myotonic dystrophy experience: a North American cross-sectional study. Muscle Nerve. 2019;59(4):457-464. doi:10.1002/mus.26420. Tara and Rhys, Living with DM1
Early and Sustained Improvement in Myotonia at 10 mg/kg Myotonia measured by video Hand Opening Time (vHOT) FREEDOM2 10 mg/kg data plotted two ways: Left panel shows change from baseline over time; Right panel shows change from baseline as a bar graph with mean and standard error of the mean vHOT analysis is with the middle finger; SE: standard error; Q4W: One dose every 4 weeks; BL: baseline vHOT Analysis Improvement vHOT Change From Baseline (sec) BL: 5.1s BL: 12.1s BL: 7.4s Administration of PGN-EDODM1 (Q4W)
vHOT vs CLCN1 Splicing at 13 Weeks Splicing Correction of CLCN1, a Muscle Chloride Channel, was Associated with Improved Myotonia at 10 mg/kg Data illustrate direction only and do not represent a statistical correlation 1Charlet-B. et al. Mol. Cell, 2002, Vol. 10, 35-44 DSI: DM1 splicing index; Q4W: once every 4 weeks; s: seconds; vHOT: video Hand Opening Time; SE: standard error Mechanism CLCN1 encodes the skeletal muscle chloride channel Mis-splicing of CLCN1 is believed to be a primary driver of myotonia in DM11 Dose-Dependent Improvements Greater CLCN1 splicing correction was associated with greater vHOT improvement in a dose-dependent manner Improvement Improvement
Hand Grip Strength Analysis Hand Grip Change From Baseline (max PPN) FREEDOM2 10 mg/kg data plotted two ways: Left panel shows change from baseline over time; Right panel shows change from baseline as a bar graph with mean and standard error of the mean PPN: percent predicted normal; SE: standard error; Q4W: One dose every 4 weeks; BL: baseline Continued Improvement in Hand Grip Strength Through Week 16 Improvement BL: 36.8 BL: 20.5 BL: 38.8 Administration of PGN-EDODM1 (Q4W)
Timed Up and Go Analysis TUG Change From Baseline (sec) FREEDOM2 10 mg/kg data plotted two ways: Left panel shows change from baseline over time; Right panel shows change from baseline as a bar graph with mean and SEM Week 12 was not collected for this endpoint; SE: standard error Q4W: One dose every 4 weeks; BL: baseline Improvement Sustained Improvement in Transitional Balance and Mobility Mobility measured by Timed Up and Go (TUG) BL: 6.6s BL: 6.8s BL: 6.7s TUG measures how long it takes someone to stand up from a chair, walk 3 meters, turn around, walk back, and sit down again Administration of PGN-EDODM1 (Q4W)
10-Meter Walk/Run Test Analysis 10MWRT Change From Baseline (sec) FREEDOM2 10 mg/kg data plotted two ways: Left panel shows change from baseline over time; Right panel shows change from baseline as a bar graph with mean and SEM Week 12 was not collected for this endpoint; SE: standard error Q4W: One dose every 4 weeks; BL: baseline Consistent Gains in 10MWRT at 10 mg/kg at All Timepoints Ambulation measured by 10-Meter Walk/Run Test (10MWRT) Improvement BL: 4.7s BL: 4.9s BL: 5.9s Administration of PGN-EDODM1 (Q4W) 10MWRT measures the time it takes a person to walk or run 10 meters
Conclusion James McArthur, PhD CEO
Highest Reported Splicing Correction in a Multidose Study and Improvement in Mobility, Myotonia, and Strength, with Favorable Safety Profile Observed at 10 mg/kg 10 mg/kg n=6, placebo pooled n=4; Percent improvement values are shown as week 13 for splicing, and week 16 for all other endpoints. Percentage improvement was calculated by dividing mean change at 16-week by mean baseline for all functional endpoints. PBO, Placebo; vHOT, video Hand Opening Time; wks, weeks; PPN, percent predicted normal; CFB, Change from Baseline 46.5% Improved Splicing Correction 5 of 6 patients improved >20% 4 of 6 patients improved >50% PBO improved 6.8% at 13 weeks 52.7% Reduced Myotonia (vHOT) 3.9s improvement at 16 weeks 4.3s improvement at 13 weeks PBO improved 0.2s at 16 weeks 8.5% Improved Timed Up and Go 0.6s improvement at 16 weeks 0.6s improvement at 13 weeks PBO worsened 0.5s at 16 weeks 6.8% Improved 10m Walk/Run Test 0.4s improvement at 16 weeks 0.6s improvement at 13 weeks PBO improved 0.2s at 16 weeks 0 Serious, severe, or dose limiting TEAEs No discontinuations No SAEs 16.2% Improved Hand Grip Strength 6.3 max PPN CFB at 16 weeks 5.3 max PPN CFB at 13 weeks PBO improved 0.9 PPN CFB at 16 wks
Next Steps for PGN-EDODM1 Development DLT: Dose limiting toxicities; SAE: Serious adverse event FREEDOM2 AND FREEDOM-OLE Cohort 3 (12.5 mg/kg) is fully enrolled, participants have received up to 3 doses FREEDOM2 and OLE studies are expected to support End of Phase 2 meeting in H2 2027 H1 2027: FREEDOM2 Cohort 3 (12.5 mg/kg) clinical results expected Open-label extension (OLE): >35 doses at 10 mg/kg and 100 doses at 5 mg/kg have been delivered 19 total participants enrolled to date No SAEs, no DLTs, one discontinuation due to hypersensitivity reaction Jan 2027: Interim FREEDOM-OLE 5 mg/kg clinical and 10 mg/kg safety data expected Building upon the positive results seen at 10 mg/kg, PepGen plans to initiate an expansion cohort, running in parallel to Cohort 3, to generate longer term (up to 9 months) data and evaluate PGN-EDODM1 in additional participants
Question and Answer Session Paul Streck, MD, MBA Executive Vice President, Head of R&D James McArthur, PhD President and Chief Executive Officer Noel Donnelly, MBA Chief Financial Officer Johanna Hamel, MD Associate Professor of Neurology, Pathology and Laboratory Medicine University of Rochester
